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12,700 | 11,790,064 | In the big picture , use of health decision aids should result in better decisions .
If the choice of a screening or treatment strategy is to be truly informed , patient knowledge about the decision seems a straightforward outcome measure .
Another logical end point for choice of strategy is whether decision aids result in selection s that are more consistent with a patient 's assessed outcome preferences , risk attitudes , and time preferences .
Finally , improved decision making may lead to better health status in some situations , which can be measured by using a host of disease-specific or generic health status measurements . | In the day-to-day practice of medicine , patients and their physicians face an increasing number of complex choices regarding prevention , diagnosis , and treatment .
The options usually have different profiles of potential benefits and risks ( not to mention costs ) .
Deber and colleagues ( 1 , 2 ) have thoughtfully distinguished problem solving tasks in medicine , which involve one right course of action and provide little room for patient involvement , and decision-making tasks , in which there are several reasonable courses of action and patient involvement is important ( 1 , 2 ) .
The optimal choice for a decision-making task depends not only on the probabilities of various outcomes with each strategy but also on the patient 's relative preferences for the possible outcome states ( and their timing ) and his or her attitudes toward risk ( 3 , 4 ) .
Health Decision Aids Health decision aids are design ed to facilitate shared decision making by helping patients and their physicians choose among reasonable clinical options ( 5 , 6 ) .
The most common are combinations of written and oral information ( including audiotapes ) ; personal counseling , sometimes supplemented by decision boards ; linear videotapes ; and interactive , computer-driven multimedia programs .
R and omized trials have examined the effectiveness of each of these types of decision aids , addressing a variety of medical decisions .
Of interest , although simple written brochures are probably the most widely used decision aids in office practice , they are the least well studied .
Measuring a Good Decision Later in this paper I discuss the evidence on the impact of health decision aids .
First , however , it is important to be clear about how one would expect such programs to affect patients and the process and outcomes of medical decision making .
Participation in decision making is commonly assessed by using a single-item ( 13 ) or multi-item scale ( 14 ) , the Autonomy Preference Index ( 14 ) .
The degree of conflict a patient feels about a decision is often measured by using the Decisional Conflict Scale ( 5 ) .
Choice of treatment is also decision specific , but changes in what patients elect to do alone do not indicate whether the therapeutic choices are better with a decision aid .
Of note , older research with coaching interventions used to encourage patient participation at their office visits has suggested that increasing patients ' participation in their care appears to improve health status , independent of effects on their diseases ( 15 , 16 ) .
More recently , we found similar results in a trial of a decision aid for men facing a decision about treatment for benign prostatic hyperplasia ( 12 ) .
However , ratings of balance by viewers can be tricky . | Abstrac Objective : To test the effect of extra non-directive information about prenatal testing , given individually or in a class . Setting : Antenatal clinics in a district general hospital and a university hospital . Design : R and omised controlled trial ; participants allocated to control group or offer of extra information individually or in class . Subjects : 1691 women booking antenatal care before 15 weeks ' gestation . Interventions : All participants received the usual information about prenatal tests from hospital staff . Individual participants were offered a separate session with a research midwife in which prenatal screening was described in detail . Class participants were offered the same extra information in an early prenatal class . Main outcome measures : Attendance at extra information sessions ; uptake rates of prenatal tests ; levels of anxiety , underst and ing , and satisfaction with decisions . Results : Attendance at classes was lower than at individual sessions ( adjusted odds ratio 0.45 ; 95 % confidence interval 0.35 to 0.58 ) . Ultrasonography was almost universally accepted ( 99 % ) and was not affected by either intervention . Uptake of cystic fibrosis testing , high in controls ( 79 % ) , was lowered in the individual group ( 0.44 ; 0.20 to 0.97 ) and classes ( 0.39 ; 0.18 to 0.86 ) . Uptake of screening for Down 's syndrome , already low ( 34 % ) in controls , was not further depressed by extra information in classes ( 0.99 ; 0.70 to 1.39 ) and was slightly higher in the individual group ( 1.45 ; 1.04 to 2.02 ) . Women offered extra information had improved underst and ing and were more satisfied with information received ; satisfaction with decisions about prenatal testing was unchanged . The offer of individual information reduced anxiety later in pregnancy . Conclusions : Ultrasonography is valued for non-medical reasons and chosen even by fully informed people who eschew prenatal diagnosis . The offer of extra information has no overall adverse effects on anxiety and reduces uptake of blood tests when background uptake rate is high ( but not when it is already low ) . High uptake of prenatal blood tests suggests compliant behaviour and need for more information The purpose of this study was to determine if providing men with information about screening for prostate cancer would enable them to assume a more active role in decision making with their family physician , and lower levels of anxiety and decisional conflict . Men were recruited from one family medical clinic in Winnipeg , Manitoba . One hundred men scheduled for a periodic health examination ( PHE ) were r and omly assigned to receive verbal and written information either prior to the PHE , or following the second interview . Men completed measures of preferred decisional role and anxiety prior to the PHE ; and assumed decisional role , decisional conflict , and anxiety post PHE . Results demonstrated that men who received the information prior to the PHE assumed a significantly more active role in making a screening decision , and had lower levels of decisional conflict post PHE . The two groups did not differ with regard to levels of state anxiety . Providing men with information enables them to make informed screening decisions with their family physicians The purpose of this study was to develop and test a decision support intervention ( DSI ) to assist women to make and act on informed decisions that are consistent with their values in the area of menopause and hormone replacement therapy ( HRT ) . Mode and intensity of intervention were tested in midlife women ( N = 248 ) , r and omly assigned to one of three intervention formats : written information only , guided discussion , or personalized decision exercise . Data were collected over 12 months . Knowledge , decisional conflict , satisfaction with health care provider , and self-efficacy improved following intervention and were maintained for 12 months for all groups . Women 's adherence to their own plans over 12 months was 59 % ( exercise ) , 76 % ( calcium intake ) , and 89 % ( HRT ) . Carefully written information is effective in promoting knowledge , adherence , and satisfaction among well-educated , interested women . It was concluded that women can underst and complex information , including tradeoffs regarding treatment options . Women will adhere to their own plans , suggesting that consumer rather than provider plans may be the more appropriate gold st and ard for measuring adherence Patient satisfaction measures have previously addressed satisfaction with medical care , satisfaction with providers , and satisfaction with outcomes , but not satisfaction with the health care decision itself . As patients become more involved in health care decisions , it is important to underst and specific dynamics of the decision itself The Satisfaction with Decision ( SWD ) scale measures satisfaction with health care decisions . It was developed in the context of postmenopausal hormone-replacement therapy decisions The six-item scale has excellent reliability ( Cronbach 's alpha = 0.86 ) . Discriminant validity , tested by performing principal- components analysis of items pooled from the SWD scale and two conceptually related measures , was good . Correlation of the SWD scale with measures of satisfaction with other aspects of the decision-making process showed the SWD scale was correlated most highly ( 0.64 ) with " decisional confidence , " and least with " desire to participate in health care de cisions " and " satisfaction with provider " The SWD scale predicts decision certainty in this study . Use in an independent study showed that the SWD scale was correlated with the likelihood of patients ' intentions to get a flu shot . Further investigation in relation to other health decisions will establish the utility of the SWD scale as an outcome measure Key words : patient satisfaction ; medical decision making ; decision support ( Med Decis Making 1996;16:58 - 64 OBJECTIVE : To assess the impact of providing an educational videotape , ' Treatment Choices for Ischaemic Heart Disease : a Shared Decision-Making Program Videotape , ' to patients referred for coronary angiography compared with st and ard patient-physician decision making ( usual care ) . STUDY DESIGN : R and omized controlled clinical trial . SETTING : University Hospital and Veterans Affairs Hospital . PATIENTS : A consecutive sample of 217 patients referred for coronary angiography were r and omized to receive ' usual care ' or to receive the videotape in addition to st and ard patient physician decision making ( videotape ) : 109 completed the study ( 50 % completion rate ) . MAIN OUTCOME MEASURES : Knowledge of coronary artery disease , satisfaction , self-reported physical and mental health functioning , and the proportion of patients who were referred for coronary revascularization . RESULTS : Compared with patients who received ' usual care , ' those who received the videotape were more knowledgeable ( mean score 83 vs. 58 % ; P < 0.0001 ) but less satisfied with their treatment ( 79 vs. 88 % ; P = 0.038 ) . There were no significant differences between the videotape and ' usual care ' groups with respect to satisfaction with the decision making process ( mean score 73 vs. 77 % ; P = 0.37 ) , satisfaction with the decision made ( mean score 73 vs. 78 % ; P = 0.28 ) , physical functioning ( 38 vs. 38 % ; P = 0.76 ) , mental health functioning ( 49 vs. 49 % ; P = 0.94 ) , or in referral for coronary revascularization ( OR 0.60 ; 95 % CI 0.22 - 1.65 ; P = 0.33 ) . CONCLUSION : Although the educational videotape increased patients ' knowledge level , it was associated with a decrease in their level of satisfaction with treatment . Before there is wide-spread dissemination of this technology , advocates should demonstrate its effectiveness in everyday practice In early 1983 , all 1,280 faculty and resident physicians at one hospital who were eligible to be vaccinated against hepatitis B were divided r and omly into three groups : Group 1 physicians received general information about the risks and benefits of alternative vaccine decisions ; Group 2 physicians were additionally invited to provide personal information for an individualized decision analysis ( 12.6 percent responded ) ; and Group 3 physicians , who served as controls , were not contacted . In one year 's follow-up , 20 percent of physicians were screened for hepatitis B antibody or vaccinated . More Group 2 physicians whose decision analyses recommended screening or vaccination took these actions ( 39 percent ) than any other group . Group assignment remained significantly associated with vaccine decisions after analyzing results by the " intention to treat " principle , and after adjusting for training status , exposure to blood and blood products , and pre- study intentions about the vaccine . Despite the low overall vaccine acceptance rate , it is concluded that individualized decision analysis can influence the clinical decisions taken by knowledgeable and interested patients Background . This investigation examined factors affecting patient involvement in consultations to decide local treatment for early breast cancer and the effectiveness of two methods of preconsultation education aim ed at increasing patient participation in these discussion OBJECTIVE : To determine the effect of the Ischemic Heart Disease Shared Decision-Making Program ( IHD SDP ) an interactive videodisc design ed to assist patients in the decision-making process involving treatment choices for ischemic heart disease , on patient decision-making . DESIGN : R and omized , controlled trial . SETTING : The Toronto Hospital , University of Toronto , Toronto , Ontario , Canada . PARTICIPANTS : Two hundred forty ambulatory patients with ischemic heart disease amenable to elective revascularization and ongoing medical therapy . MEASUREMENTS AND MAIN RESULTS : The primary outcome was patient satisfaction with the decision-making process . This was measured using the 12-item Decision-Making Process Question naire that was developed and vali date d in a r and omized trial of the benign prostatic hyperplasia SDP . Secondary outcomes included patient knowledge ( measured using 20 questions about knowledge deemed necessary for an informed treatment decision ) , treatment decision , patient-angiographer agreement on decision , and general health scores . Outcomes were measured at the time of treatment decision and /or at 6 months follow-up . Shared decision-making program scores were similar for the intervention and control group ( 71 % and 70 % , respectively ; 95 % confidence interval [ CI ] for 1 % difference , −3 % to 7 % ) . The intervention group had higher knowledge scores ( 75 % vs 62 % ; 95 % CI for 13 % difference , 8 % to 18 % ) . The intervention group chose to pursue revascularization less often ( 58 % vs 75 % for the controls ; 95 % CI for 17 % difference , 4 % to 31 % ) . At 6 months , 52 % of the intervention group and 66 % of the controls had undergone revascularization ( 95 % CI for 14 % difference , 0 % to 28 % ) . General health and angina scores were not different between the groups at 6 months . Exposure to the IHD SDP result ed in more patient-angiographer disagreement about treatment decisions . CONCLUSIONS : There was no significant difference in satisfaction with decision-making process scores between the IHD SDP and usual practice groups . The IHD SDP patients were more knowledgeable , underwent less revascularization ( interventional therapies ) , and demonstrated increased patient decision-making autonomy without apparent impact on quality of life BACKGROUND In response to the isolation of the BRCA1 gene , a breast-ovarian cancer-susceptibility gene , biotechnology companies are already marketing genetic tests to health care providers and to the public . Initial studies indicate interest in BRCA1 testing in the general public and in population s at high risk . However , the optimal strategies for educating and counseling individuals have yet to be determined . PURPOSE Our goal was to evaluate the impact of alternate strategies for pretest education and counseling on decision-making regarding BRCA1 testing among women at low to moderate risk who have a family history of breast and /or ovarian cancer . METHODS A r and omized trial design was used to evaluate the effects of education only ( educational approach ) and education plus counseling ( counseling approach ) , as compared with a waiting-list ( control ) condition ( n = 400 for all groups combined ) . The educational approach review ed information about personal risk factors , inheritance of cancer susceptibility , the benefits , limitations , and risks of BRCA1 testing , and cancer screening and prevention options . The counseling approach included this information , as well as a personalized discussion of experiences with cancer in the family and the potential psychological and social impact of testing . Data on knowledge of inherited cancer and BRCA1 test characteristics , perceived risk , perceived benefits , limitations and risks of BRCA1 testing , and testing intentions were collected by use of structured telephone interviews at baseline and at 1-month follow-up . Provision of a blood sample for future testing served as a proxy measure of intention to be tested ( in the education and counseling arms of the study ) . The effects of intervention group on study outcomes were evaluated by use of hierarchical linear regression modeling and logistic regression modeling ( for the blood sample outcome ) . All P values are for two-sided tests . RESULTS The educational and counseling approaches both led to significant increases in knowledge , relative to the control condition ( P < .001 for both ) . The counseling approach , but not the educational approach , was superior to the control condition in producing significant increases in perceived limitations and risks of BRCA1 testing ( P < .01 ) and decreases in perceived benefits ( P < .05 ) . However , neither approach produced changes in intentions to have BRCA1 testing . Prior to and following both education only and education plus counseling , approximately one half of the participants stated that they intended to be tested ; after the session , 52 % provided a blood sample . CONCLUSIONS St and ard educational approaches may be equally effective as exp and ed counseling approaches in enhancing knowledge . Since knowledge is a key aspect of medical decision-making , st and ard education may be adequate in situations where genetic testing must be streamlined . On the other h and , it has been argued that optimal decision-making requires not only knowledge , but also a reasoned evaluation of the positive and negative consequences of alternate decisions . Although the counseling approach is more likely to achieve this goal , it may not diminish interest in testing , even among women at low to moderate risk . Future research should focus on the merits of these alternate approaches for subgroups of individuals with different background s who are being counseled in the variety of setting s where BRCA1 testing is likely to be offered Background . In 1990 , a pilot study was begun that evaluated benign prostatic hyperplasia ( BPH ) at five clinical institutions . Data management and coordination of this study was performed at the Medical Practice s Evaluation Center at Massachusetts General Hospital . Because of decreased patient enrollment , one institution was dropped . This was a r and omized , prospect i ve , clinical study that provided an initial overview of the trial and a rationale for the project An intervention was developed to increase patient involvement in care . Using a treatment algorithm as a guide , patients were helped to read their medical record and coached to ask questions and negotiate medical decisions with their physicians during a 20-minute session before their regularly scheduled visit . In a r and omized controlled trial we compared this intervention with a st and ard educational session of equal length in a clinic for patients with ulcer disease . Six to eight weeks after the trial , patients in the experimental group reported fewer limitations in physical and role-related activities ( p less than 0.05 ) , preferred a more active role in medical decision-making , and were as satisfied with their care as the control group . Analysis of audiotapes of physician-patient interactions showed that patients in the experimental group were twice as effective as control patients in obtaining information from physicians ( p less than 0.05 ) . Results of the intervention included increased involvement in the interaction with the physician , fewer limitations imposed by the disease on patients ' functional ability , and increased preference for active involvement in medical decision-making Seventy-four patients , ranging in age from 15 to 50 and presenting with a moderate to severe dentofacial deformity requiring orthognathic surgery , were r and omly assigned to a video imaging or a st and ard case presentation ( CP ) group . Motives for treatment did not differ significantly between the video image and st and ard CP groups . Two weeks after the case presentation , 60 % of the st and ard CP group and 74 % of the video image group ranked the anticipated change in facial appearance as an important factor in making a treatment decision . Seventy percent of the st and ard CP group and 83 % of the video image group agreed with the statement that surgery would be necessary to correct their problem . In the st and ard CP group , 47 % of the patients ranked dental casts as the most helpful physical record in making a treatment decision , and 46 % said the acetate profile tracing was the most helpful tool for underst and ing what to expect from treatment . In the video imaging group , 42 % of the patients said the video imaging presentation was the most helpful tool in making a treatment decision , and 39 % of the patients said it was the most helpful tool for underst and ing treatment expectations . The proportion of patients in the video image case presentation group with elevated self-image expectations following treatment was significantly higher ( P = .045 ) than in the st and ard case presentation group . The presentation of video images appears to be a valuable information source for conveying treatment options to patients , but caution may be needed to prevent elevated or possibly unrealistic treatment expectations Abstract OBJECTIVE : Routine screening for prostate cancer is controversial because of frequent false-positive results , the potential for slow , non-life-threatening growth of untreated cancer , the uncertainty regarding whether treatment can extend life , and the potential for treatment complications . This study examines how information about prostate-specific antigen ( PSA ) testing and the uncertain benefits of treating prostate cancer affects patients ’ desire for PSA testing . DESIGN : An educational videotape design ed to inform men about the uncertainty surrounding PSA screening and the treatment of early-stage prostate cancer was presented to two groups of male patients 50 years of age or older . SETTING : Dartmouth-Hitchcock Medical Center . PATIENTS / PARTICIPANTS : For study 1 , men seeking a free prostate cancer screening were preassigned to view the educational videotape ( N=184 ) or another videotape ( N=188 ) . For study 2 , men scheduled to visit a general internal medicine clinic viewed either the educational videotape ( N=103 ) or no videotape ( N=93 ) . MEASUREMENTS AND MAIN RESULTS : The men ’s information and preferences about prostate cancer screening and treatment and actual choice of PSA test at the next test opportunity were measured . Men who viewed the educational videotape were : better informed about PSA tests , prostate cancer , and its treatment ; preferred no active treatment if cancer were found ; and preferred not to be screened ( all significant atp≤.002 in both studies ) . Men viewing the educational video were less likely to have a PSA test ( p=.041 , study 2 ) . This tendency was not significant at the free-PSA clinic ( p=.079 ) . CONCLUSIONS : Preference regarding cancer screening and treatment is greatly affected by information about medical uncertainties . Because informed patient choices vary , PSA screening decisions should incorporate individual preferences Although practice guidelines suggest that postmenopausal women learn about the benefits and nsks and consider their values when deciding about hormone therapy , the optimal decision-support method has not been established . In a r and omized controlled trial , the authors compared the efficacy of a general educational pamphlet with that of a tailored decision aid . The pamphlet briefly summarized benefits , risks , and likely beneficiaries in general terms . The decision aid , delivered via booklet and audiotape , provided : detailed benefits and risks using functional terms and probabilities tailored to clinical risk ; and steps for considering the issue in a woman 's own situation , including a value-clarification exercise . Compared with the pamphlet group , the decision-aid group had statistically significant ( p < 0.05 ) improvements in terms of realistic personal expectations of the benefits and nsks , decisional conflict , and perceived acceptability of the intervention . Levels of general knowledge about the main benefits and nsks were comparable for the two interventions It is concluded that tailored decision aids prepare women for decision making better than do general pamphlets . Key words : decision making ; choice behavior ; informed consent ; decision-support techniques ; woman education ; woman participation ; health education ; consumer satisfaction ; hormone replacement therapy ; menopause . ( Med Decis Making 1998;18:295 - 303 BACKGROUND Prostate cancer screening with serum prostate-specific antigen ( PSA ) and digital rectal examination ( DRE ) continues to increase . Our goal was to test the effect of a prostate cancer screening decision-aid on patients ' knowledge , beliefs , and use of prostate cancer screening tests . METHODS Our study was a r and omized controlled trial of a prostate cancer screening decision-aid consisting of an illustrated pamphlet as opposed to a comparison intervention . We included 257 men aged 50 to 80 years who were receiving primary care at a Department of Veterans Affairs Hospital in Milwaukee , Wisconsin . The decision-aid provided quantitative outcomes of prostate cancer screening with DRE and PSA . We subsequently evaluated prostate cancer screening knowledge , beliefs , and test use . RESULTS The illustrated pamphlet decision-aid was effective in improving knowledge of prostate cancer screening tests : 95 % of the experimental group were aware of the possibility of false-negative test results compared with 85 % of the comparison group ( P < .01 ) . Ninety-one percent of the experimental group were aware of the possibility of a false-positive screening test result compared with 65 % of the comparison group ( P < .01 ) . However , there was no difference in the use of prostate cancer screening between the experimental ( 82 % ) and comparison ( 84 % ) groups , ( P > .05 ) . CONCLUSIONS When used in a primary care setting , an illustrated pamphlet decision-aid was effective in increasing knowledge of prostate cancer screening tests but did not change the use of these tests To maximize disease control , patients must participate effectively in their medical care . The authors developed an intervention design ed to increase the involvement of patients in medical decision making . In a 20-minute session just before the regular visit to a physician , a clinic assistant review ed the medical record of each experimental patient with him/her , guided by a diabetes algorithm . Using systematic prompts , the assistant encouraged patients to use the information gained to negotiate medical decisions with the doctor . A r and omized trial was conducted in two university hospital clinics to compare this intervention with st and ard educational material s in sessions of equal length . The mean pre-intervention glycosylated hemoglobin ( HbA1 ) values were 10.6 + /- 2.1 % for 33 experimental patients and 10.3 + /- 2.0 % for 26 controls . After the intervention the mean levels were 9.1 + /- 1.9 % in the experimental group ( p less than 0.01 ) and 10.6 + /- 2.22 % for controls . Analysis of audiotapes of the visits to the physician showed the experimental patients were twice as effective as controls in eliciting information from the physician . Experimental patients reported significantly fewer function limitations . The authors conclude that the intervention is feasible and that it changes patient behavior , improves blood sugar control , and decreases functional limitations OBJECTIVE To evaluate a patient-educational approach to shared decision making for prostate cancer screening . DESIGN R and omized controlled trial with preoffice visit assessment and 2-week follow-up . SETTING University-based family practice center . PATIENTS Men aged 45 through 70 years with no history of prostate cancer or treatment for prostate disease ( N = 160 ) . Two patients were unavailable for follow-up . INTERVENTION Twenty-minute educational videotape on advantages and disadvantages of prostate-specific antigen ( PSA ) screening for prostate cancer . MAIN OUTCOME MEASURES A measure of patients ' core knowledge of prostate cancer developed for this study , reported preferences for PSA testing , and ratings of the videotape . RESULTS Patients ' core knowledge at baseline was poor . At 2-week follow-up , subjects undergoing videotape intervention showed a 78 % improvement in the number of knowledge questions answered correctly ( P = .001 ) , and knowledge increased about mortality due to early-stage prostate cancer , PSA screening performance , treatment-related complications , and disadvantages of screening . No overall change was observed for control subjects . At follow-up , 48 ( 62 % ) of 78 intervention patients planned to have the PSA test compared with 64 ( 80 % ) of 80 control patients ( 18.5 % absolute reduction ; 95 % confidence interval , 4.6%-32.4 % ; P = .009 ) . Intervention subjects rated favorably the amount of information provided and the clarity , balance , and length of the videotape and would recommend the videotape to others . CONCLUSIONS Patient education regarding the potential benefits and harms of early detection of prostate cancer can lead to more informed decision making . Incorporating the PSA videotape into the periodic health examination for asymptomatic men aged 50 years and older is recommended Patients often want considerable information about their conditions , and enhanced patient participation might reduce unwanted practice variation and improve medical decisions . The authors assessed how men with benign prostatic hyperplasia reacted to an educational program design ed to facilitate participation in decisionmaking , and how strongly ratings of their symptom state and the prospect of complications predicted their treatment choice . A prospect i ve cohort study was conducted in three hospital-based urology practice s : two in prepaid group practice s , and one Veterans Administration clinic . Four hundred twenty-one men with symptomatic benign prostatic hyperplasia without prior prostatectomy or benign prostatic hyperplasia complications were enrolled , and 373 provided usable ratings . Subjects participated in an interactive videodisc-based shared decisionmaking program about benign prostatic hyperplasia and its treatment options , prostatectomy , and “ watchful waiting . ” They rated the length , clarity , balance , and value of the program and were followed for 3 months to determine if they underwent surgery . Patients rated the program as generally clear , informative , and balanced . Across all three sites , 77 % of patients were very positive and 16 % were generally positive about the program 's usefulness in making a treatment decision . Logistic models predicting choice of surgical treatment documented the independent importance of negative ratings of the current symptom state ( odds ratio 7.0 , 95 % confidence interval 2.9–16.6 ) , as well as the prospect of postoperative sexual dysfunction ( odds ratio 0.20 , 95 % confidence interval 0.08–0.48 ) in decisionmaking . Patients rated the Shared Decisionmaking Program very positively and made decisions consistent with their assessed preferences . These results suggest that patients can be helped to participate in treatment decisions , and support a r and omized trial of the Shared Decisionmaking Program The national health care debate reflects the fervent and sometimes disparate views that patients and physicians have on what is important in health care . Research has found that patient satisfaction is clearly composed of many elements . Such diverse issues as technical skill , communication , accessibility , physical qualities of the facility , and coordination of care all seem to play a role in satisfying patients [ 1 - 4 ] . However , few research ers have attempted to determine the priorities that patients assign to attributes of care . In the early 1980s , Fletcher and colleagues [ 5 ] studied the priorities of 225 patients attending an academic medical clinic and found that continuity of care was the highest priority for these patients and that issues of cost and convenience were lowest . Robbins and colleagues [ 6 ] studied 100 patient visits to an academic primary care practice and found that overall satisfaction with the visit appeared to be related to aspects of the physical examination , time spent on health education , and discussion of the effects of treatment . We know of no published attempts to establish patient priorities in nonacademic setting s , and no empirical comparisons of patients ' and physicians ' opinions on the importance of various elements of health care are readily available . Thus , we surveyed patients and physicians for their opinions on the importance of various specific attributes of care to the overall quality of outpatient care . Methods Study Sample s Physicians Governors of the American College of Physicians from Arizona , Michigan , Oklahoma , Tennessee , Georgia , Maine , and Connecticut helped recruit a total of 74 members of the College from their respective states . These states were selected because they represented a wide geographic area . Only physicians who spent at least 60 % of their time practicing general internal medicine were eligible to participate . Full-time academicians , full-time specialists , full-time research ers , and trainees were excluded . The seven College governors each provided the names of 10 to 15 physicians from their own states who met these eligibility criteria and were thought to be exemplary clinicians . Research personnel sent these physicians ( n = 81 ) a letter explaining that the College governor had recommended them for participation in this project . Telephone follow-up was used to describe the project in detail . Of the 81 physicians recruited , 74 ( 91 % ) agreed to participate ; these 74 physicians make up our physician sample . Patients After participating physicians notified the patients they saw during a specified 2-week period that the patients might be contacted to participate in a voluntary , confidential study of quality of care , the physicians gave study personnel copies of their appointment logs for this period . Research staff r and omly selected 11 patients listed in each office 's log to participate in the study ( n = 814 ) according to the following procedure , which was devised by the firm that administered the surveys . Research staff divided the total number of patients listed on the log by 11 ( the target sample size for each practice ) to obtain a number , A. They rounded A up to the next highest integer and went to the Ath number on the r and om-number table . That r and om number was divided by 10 to obtain a number , B. The number B was rounded to the next highest integer , and the Bth patient on the log became the first patient in the sample . The second patient was selected by adding A and B to get a number , C. The Cth number on the r and om-number table was then divided by 10 and rounded to the next highest integer to obtain a number , D. The Dth patient listed on the physician 's log became the second patient in the sample . The third patient was selected by adding A and D and repeating the same process . The physicians and their staffs had no role in selecting patients from the logs and were not aware of subsequent patient participation . Question naire Using the literature on patient perceptions of care and separate focus groups with patients and physicians , we identified a comprehensive list of elements of medical office practice thought to be associated with quality of care in that setting . The 125 elements thought to be important in the delivery of high- quality office-based care covered the following nine domains , which were defined a priori : physician clinical skill , physician interpersonal skill , office support staff , office environment , provision of health-related information , patient involvement in care , nonfinancial access , finances , and coordination of care . The domains are defined in Table 3 . In this report , we refer to the 125 elements of care as elements , attributes , or items . Table 3 . Appendix : Definition of Domains We then constructed a question naire that asked both physician and patient respondents to rate , from their own perspectives , the importance of each of the 125 elements to the quality of care delivered in a physician 's office ( Table 4 ) . Respondents rated each item using a 4-point scale : 1 signified that the respondent considered the item not important ; 2 indicated that the item was of medium importance ; 3 meant that the item was of high importance ; and 4 indicated that the item was essential . Patients and physicians were asked to rate the importance of each item to office-based care in general , not to the performance of the patient 's individual physician or to the physician 's own practice . Table 4 . Appendix : Summary of Question naire : Instructions , Domains , and Sample Items Data Collection and Analysis An independent survey firm mailed the question naire to participants within 1 month of the index visit . Data collection remained open for 5 weeks , and reminders were sent 1 week after the initial mailing . We used group consensus to cluster items into the domains on the basis of qualitative assessment . When agreement about which domain an item belonged to was not unanimous , we discussed the item as a group until we reached a consensus . During a separate phase of our research that examined patients ' reports on the performance of their physicians , we also did a factor analysis that loosely guided the assignment of items to domains . The factor analysis identified two factors . The first was related to the specific skills and style of the physician and thus encompassed the domains of physician clinical skill , physician interpersonal skill , provision of health-related information , and patient involvement in care . The second factor was less directly related to physician skill or style and was thought to encompass the domains of office support staff , office environment , nonfinancial access , coordination of care , and finances . The assignment of items to the nine domains was guided by whether the item belonged to a domain related to the first factor or to the second factor . We examined the median importance ratings and interquartile ranges of physicians ' and patients ' ratings for each element of care and then analyzed items aggregated into the nine domains . For each respondent , we determined a domain-specific importance rating by calculating the average rating that the respondent assigned to items in each of the nine domains that the question naire addressed . For example , if a respondent assigned importance ratings of 2 , 3 , 3 , 3 , 4 , and 4 to the six items in the domain of office environment , that person 's rating of the importance of the office environment domain would be 3.17 ( [ 2 + 3 + 3 + 3 + 4 + 4]/6 ) . We then determined the median importance ratings assigned to each domain by the patients and by the physicians and used the Mann-Whitney U test to compare the two groups . We also ranked the perceived importance of the domains for patients and physicians by ordering the domains from those with the highest importance score to those with the lowest . We then compared the rank orders of physicians ' and patients ' ratings of the nine domains using the Spearman rank-order correlation coefficient . All reported P values are two sided . Results Physician and Patient Characteristics All 74 physicians who supplied appointment logs were in solo or small-group practice . The mean age was 44 years , 14.9 % were women , and 8 % belonged to an ethnic minority group . Nine physicians were from Arizona , 9 were from Michigan , 15 were from Oklahoma , 11 were from Tennessee , 12 were from Georgia , 9 were from Maine , and 9 were from Connecticut . Of the 74 physicians , 69 ( 93 % ) completed the study question naire . Of these 69 physicians , the mean age was 45.5 years , 16 ( 22 % ) were women , 5 ( 7 % ) belonged to an ethnic minority group , and all were in solo or small-group practice . The patient response rate was 60 % ( 485 of 815 patients ) . The characteristics of these patients are shown in Table 1 . Table 1 . Patient Characteristics Patients ' and Physicians ' Ratings of the Importance of Individual Elements Physicians and patients differed substantially in an element-by-element comparison of ratings . Disagreement about the level of importance was statistically significant for 58 % of the elements ( 72 of 125 ) . Table 2 shows data for the 15 elements on which patients ' and physicians ' ratings greatly differed . Of note , 9 of the 15 largest differences concerned the provision of information to the patient . Table 2 . Elements of Care for Which Patients ' and Physicians ' Importance Ratings Differed Most Patients ' and Physicians ' Ratings of the Importance of the Domains Patients and physicians agreed strongly about the rank order of the nine domains ( Spearman r , 0.80 ) . For example , both groups ranked clinical skills highest and office environment lowest . Provision of information was the only domain for which the rank order substantially differed between groups . Physicians ranked office support staff , physician interpersonal skill , patient involvement , and coordination of care higher than patients did , but these differences were not statistically significant . Although agreement on rank order ( that is , relative importance ) was BACKGROUND Because of the many uncertainties surrounding screening for prostate cancer , authorities recommend that patients be involved in the screening decision . OBJECTIVE To determine the impact of informed consent on patient interest in undergoing prostate-specific antigen ( PSA ) screening . METHODS Men 50 years or older with no prior PSA testing and no history of prostate cancer presenting to 1 of 4 university-affiliated primary care practice s were eligible for enrollment . Patients were r and omized to receive either a scripted informational intervention simulating an informed consent presentation ( intervention group , n = 103 ) or a single sentence about the PSA ( control group , n = 102 ) . The main outcome measure was patient interest in undergoing PSA screening measured on a 5-point Likert scale . RESULTS Patients who received the informational intervention were significantly less interested in undergoing PSA screening than controls ( mean difference in interest , 0.8 on 5-point scale , P < .001 ) . Informed patients were much less likely to indicate high interest in screening ( odds ratio , 0.34 ; 95 % confidence interval , 0.19 - 0.60 ; P < .001 ) . In a multivariate model , family history of prostate cancer was associated with increased interest and advancing age with decreased interest in PSA screening , but the informational intervention remained the strongest predictor of interest . CONCLUSIONS Among primary care patients of predominantly lower socioeconomic status , those who received informed consent were significantly less interested in PSA screening than those who did not . For physicians who offer the PSA as a screening test , this finding highlights the importance of apprising patients of the associated benefits , burdens , and uncertainties and allowing them to participate in the screening decision |
12,701 | 17,505,249 | There are no definitive studies illustrating that incidence of UTIs is affected by sterile single-use or coated catheters compared to clean reused catheters . | PURPOSE Intermittent catheterization is a commonly prescribed procedure for people with incomplete bladder emptying not managed by other methods .
The most frequent complication of intermittent catheterization is urinary tract infection ( UTI ) .
It is unclear what strategies , including sterile vs clean catheters or coated vs uncoated PVC catheters , affect the incidence of UTIs .
This systematic review summarizes current evidence on the relationship between sterile single-use catheters or clean reused catheters and the incidence of UTIs . | Objective To evaluate the current range of hydrophilic‐coated catheters for intermittent self‐catheterization , focusing on the adherence of the catheter to the urethral mucosa at the end of catheterization OBJECTIVE The frequency of bacteriuria is high in children with neurogenic bladder on intermittent catheterization for bladder emptying . In an effort to decrease bacteriuria , we examined whether the method of catheter care was responsible for the high rate of bacteriuria . For this , the frequency of bacteriuria was examined in the same patient on single-use sterile catheters and on reused clean catheters . METHODS A prospect i ve , r and omized , crossover trial was conducted with 10 patients who were r and omized to 4 months of a new , sterile catheter for intermittent catheterization and 4 months of reuse of a clean catheter for intermittent catheterization . Each week , a urine sample was collected and symptoms of infection and medication use were recorded . RESULTS A total of 158 urine sample s were collected during 164 patient-weeks on the new catheter method for each void ; 115 ( 73 % ) were positive for a pathogen . Of the 161 sample s collected during 169 patient-weeks on the st and ard , reuse method for voiding , 123 ( 76 % ) were positive ( 115 [ 73 % ] of 158 vs 123 [ 76 % ] of 161 ) . Escherichia coli was the most common pathogen detected during both method periods . CONCLUSION A new , sterile catheter for each void did not decrease the high frequency of bacteriuria in patients with neurogenic bladder on intermittent catheterization PURPOSE We compared a recently developed hydrophilic catheter to the st and ard polyethylene catheter in regard to hematuria , infection and patient satisfaction . MATERIAL S AND METHODS A hydrophilic LoFric or st and ard Mentor catheter was assigned at r and om to 17 and 16 boys , respectively , who were skilled in intermittent self-catheterization . They were evaluated by weekly urinalysis and a question naire . RESULTS Significantly fewer episodes of microscopic hematuria occurred in the LoFric than Mentor catheter group ( 9 episodes in 6 subjects versus 19 episodes in 11 , p < 0.05 ) . There were also fewer episodes of bacteriuria in the LoFric group but the difference was not statistically significant . Mean scores plus or minus st and ard deviation on a visual analogue scale with 0 equal to most and 10 equal to least favorable were LoFric 3.3 + /- 2.8 versus Mentor 4.9 + /- 2.7 for catheter convenience and 2.7 + /- 2.4 versus 4.2 + /- 2.6 for insertion comfort , significantly favoring the LoFric group ( p < 0.05 for both ) . Of the 16 LoFric subjects 13 preferred to continue its use , particularly those with a history of urethral trauma or sphincteric spasm . CONCLUSIONS In boys the LoFric catheter appears to cause less trauma . Although it is not reusable and is more expensive than the st and ard catheter , satisfaction is higher with the LoFric device and for select patients it has significant advantages OBJECTIVES To compare the safety and cost of clean versus sterile intermittent bladder catheterization in male nursing home residents . To provide evidence to support the hypothesis that intermittent catheterization is a valid , alternative method of bladder management in male residents of long-term care in whom urinary retention is a documented problem . DESIGN R and omized clinical trial . SETTING Three long-term care sites having predominantly male population s. PARTICIPANTS Eighty male veterans , residents of three long-term care facilities , ranging in age from 36 to 96 years with a mean age of 72 . INTERVENTIONS St and ardized procedures for clean and sterile intermittent catheterization ( IC ) were implemented by staff nurses at each site . Patients were r and omized into clean and sterile IC groups . Nursing time and catheterization equipment usage were recorded using bar code readers . Clinical data were collected from the medical chart . Treatment of urinary tract infection was prescribed by the medical personnel responsible for each individual resident . MEASUREMENTS We compared the number of treatment episodes for symptomatic bacteriuria between groups r and omized to receive either clean or sterile intermittent catheterization . Laboratory analysis of blood and urine was done on predetermined days . Control variables were research site and patient history of urinary tract infection within the last 6 months . A cost comparison of nursing time and equipment usage for the two catheterization techniques was also performed . RESULTS No significant differences were found between clean and sterile groups with regard to number of treatment episodes , time to first infection , type of organism cultured , or cost of antibiotic treatment . The cost of sterile technique was considerably higher both in terms of nursing time and supplies . CONCLUSIONS Findings from this study demonstrate that clean technique intermittent catheterization is a safe and cost-effective bladder management technique with male , nursing home residents , despite the frailty of this high risk population . An annual savings of approximately $ 1460 per patient in nursing time and catheterization supplies could be anticipated if a patient were catheterized an average of four times per day substituting clean IC technique for sterile IC technique Monthly urine cultures were analyzed at the University of Alberta Department of Medical Microbiology and Infectious Diseases to determine whether single-use sterile catheters and clean technique reduced the incidence of bacterial colonization in those using long-term intermittent self-catheterization . Thirty subjects with spina bifida , ages 3 years to 16 years , entered a crossover study with r and om assignment to 6 months of sterile single-use catheters or clean reused catheters . Seventeen subjects were catheterized by a parent or caregiver ; 13 were responsible for self-catheterization and cleaning of the catheters . Six months of descriptive data were also collected at Alberta Children 's Hospital from a similar group of subjects with spina bifida who used sterile catheters only . In the crossover group , 38 % of all urine cultures were positive regardless of whether sterile single-use or clean reused catheters were employed . The other group using only sterile catheters had a 36 % positive culture rate . No difference in positive cultures was found between males and females or between children who catheterized themselves and children whose parents catheterized them . The authors concluded that plastic urethral catheters may be reused OBJECTIVES To compare the performance of SpeediCath hydrophilic-coated catheters versus uncoated polyvinyl chloride ( PVC ) catheters , in traumatic spinal cord injured patients presenting with functional neurogenic bladder-sphincter disorders . METHODS A 1-year , prospect i ve , open , parallel , comparative , r and omised , multi centre study included 123 male patients , > or = 16 y and injured within the last 6 months . Primary endpoints were occurrence of symptomatic urinary tract infection ( UTI ) and hematuria . Secondary endpoints were development of urethral strictures and convenience of use . The main hypothesis was that coated catheters cause fewer complications in terms of symptomatic UTIs and hematuria . RESULTS 57 out of 123 patients completed the 12-month study . Fewer patients using the SpeediCath hydrophilic-coated catheter ( 64 % ) experienced 1 or more UTIs compared to the uncoated PVC catheter group ( 82 % ) ( p = 0.02 ) . Thus , twice as many patients in the SpeediCath group were free of UTI . There was no significant difference in the number of patients experiencing bleeding episodes ( 38/55 SpeediCath ; 32/59 PVC ) and no overall difference in the occurrence of hematuria , leukocyturia and bacteriuria . CONCLUSIONS The results indicate that there is a beneficial effect regarding UTI when using hydrophilic-coated catheters Local reactions of the urethral wall are known to occur by repeated introduction of a catheter in the urethra . Urethritis was found in 2 - 19 % of patients practising intermittent catheterisation . Although the use of catheters of smaller size and the liberal use of lubricants may prevent urethral irritation and trauma , it was postulated that hydrophilic catheters ( LoFric , Astra Tech Ltd , Stroud , Engl and ) induce significantly less trauma than PVC catheters because of the binding of the water molecules to the catheter surface which consists of polyvinylpyrrolidone and sodium chloride . Although urethritis and urethral stricture may represent one end of the spectrum of repeated urethral trauma , minor degrees of inflammation need to be quantitatively determined while assessing two different catheters for intermittent catheterisation . The degree of urethral inflammation in patients practising intermittent catheterisation was studied by urethral cytology and staining the smear by Papanicolaou 's method . The number of neutrophil polymorphs and epithelial cells in three r and om high power fields in the urethral smear was counted and the percentage ratio of polymorphs to epithelial cells was calculated . Group 1 comprised 14 patients practising intermittent catheterisation with a PVC catheter and group 2 comprised 17 patients performing intermittent catheterisation with a LoFric catheter . There was no significant difference between the two groups as regards the age , diagnosis , size of the catheter used for intermittent catheterisation and the number of times that they performed catheterisation during a 24 hour period . Urethral cytology revealed a percentage ( mean ratio ) ratio of polymorphs to epithelial cells of 66 in group 1 and 0.04 in group 2 . ( < 0.0005 ) . Urethral cytology also revealed a significantly greater number of bacteria in group 1 as compared to group 2 ( p < 0.01 ) . In conclusion , use of a LoFric catheter for intermittent catheterisation was associated with significantly lesser degree of urethral inflammatory response when compared to the use of a PVC catheter This study was design ed to determine the effect of sterile and nonsterile intermittent catheterization on the incidence of urinary tract infection ( UTI ) in patients after spinal cord injury . The study included 29 patients with neurogenic bladder dysfunction treated with intermittent catheterization . One group of 14 patients was on sterile catheterization ; another group of 15 patients was on nonsterile catheterization . On a weekly basis , urine sample s were obtained and analyzed . A total of 122 urine sample s were analyzed . The patients on sterile catheterization had a 28.6 % UTI incidence ; the group using a nonsterile catheterization technique had a UTI incidence of 42.4 % . The most common urinary pathogen in both groups was E. coli ( 65 % ) . The cost of antibiotics for patients on the sterile catheterization program was only 43 % of the cost of antibiotics for those on the nonsterile program . However , the sterile kits cost 371 % of the cost of the catheterization kits for the patients in the nonsterile program , so the total cost of managing neurogenic bladder on the sterile program was 277 % of the cost of the nonsterile program To evaluate whether patients performing clean intermittent self‐catheterization ( CISC ) for a short period preferred a prelubricated , hydrophilic , disposable polyvinyl chloride ( PVC ) catheter or a non‐hydrophilic PVC catheter which could be used several times and that had to be lubricated by the patient PURPOSE We compared the safety and patient acceptance of a conventional Nélaton and a prelubricated nonhydrophilic catheter in 18 spinal cord injured patients on intermittent catheterization . MATERIAL S AND METHODS In a prospect i ve crossover study each catheter was used for 7 weeks and the initial course was r and omized . Urinalysis and urine culture were performed at 2 , 4 and 7 weeks . Urethral trauma was evaluated by urethral cell count on the surface of each catheter used on the last day of each study period . Patient satisfaction was assessed at the end of the study by a question naire using multiple visual analog scales . RESULTS Urinary tract infection was identified in 12 and 4 patients on a Nélaton and a prelubricated nonhydrophilic catheter ( p = 0.03 ) , while asymptomatic bacteruria was identified in 18 and 8 ( p = 0.0244 ) , respectively . The mean urethral cell count plus or minus st and ard deviation on the catheter surface was 6.7 + /- 2.8 x 10(4 ) and 15.1 + /- 8.9 x 10(4 ) for the prelubricated nonhydrophilic and the Néelaton catheter , respectively ( p = 0.01 ) . The prelubricated nonhydrophilic catheter result ed in a better mean satisfaction score than the Nélaton catheter ( 2.33 + /- 1.06 versus 4.72 + /- 2.13 , p = 0.022 ) . Urethral bleeding was reported in 2 patients during the study period while using the Nélaton catheter . CONCLUSIONS The prelubricated nonhydrophilic catheter is a safe , effective and comfortable option in spinal cord injured patients on intermittent self-catheterization The purpose of this study was to compare the incidence of urinary infection using clean intermittent catheterization with the incidence of infection using sterile intermittent catheterization in patients hospitalized with spinal cord injury who were not receiving prophylactic antibiotics . Forty-six patients were assigned r and omly to a clean ( n = 23 ) or sterile ( n = 23 ) study group . Catheterizations were done at least every six hours . Infection was defined as bacteriuria greater than or equal to 100,000 organisms/mL or greater than or equal to 10,000 organisms per mL with fever of 100 degrees F or greater . Results of urinary dipslides were recorded daily . Twenty-eight subjects ( 60.9 % ) converted to greater than or equal to 100,000 organisms per mL. Method of catheterization was neither associated significantly with development of greater than or equal to 100,000 organisms per mL. ( X2[1,46 ] = .36 , p = .55 ) nor with symptomatic infections ( X2[1,46 ] = .15 , p = .70 ) . Data support the use of clean intermittent catheterization under the conditions used in this study , including the use of a sterile catheter each day and careful monitoring of infection and technique . Before using this method with other diagnostic groups or in different clinical setting s , further investigation is needed Objective : To compare the onset of symptomatic urinary tract infection in individuals with spinal cord injury in a rehabilitation setting who are r and omized to clean or sterile intermittent catheterization technique . Design : R and omized controlled design . Setting : Spinal cord rehabilitation units in western Canada . Subjects : Thirty-six patients with cervical spinal cord injuries requiring intermittent catheterization by nursing staff were recruited . None had a previous history of voiding dysfunction or urinary tract infections . Interventions : Subjects were r and omized to either clean or sterile intermittent catheterization technique . Protocol s for both clean and sterile techniques were st and ardized and followed by nursing staff and caregivers . Main measures : Primary outcome measure was symptomatic urinary tract infection as diagnosed by urine culture ≥ 105 colony-forming units/mL , pyuria ( ≥ 10 leukocytes on high-power field ) , and accompanying symptoms . Results : A total of 189 urine specimens from 36 subjects were cultured . Of the 36 subjects , 15 ( 43 % ) developed a symptomatic urinary tract infection : 6/16 ( 37 % ) from the clean group ; 9/20 ( 45 % ) from the sterile group ( P>0.05 ) . Mean time to onset for symptomatic urinary tract infection for the clean group was 3.0 ( st and ard deviation ( SD ) 2.4 ) weeks and for the sterile group , 3.6 ( SD 1.3 ) weeks ( P>0.05 ) . The most common urinary organisms at onset of symptomatic urinary tract infection were Enterococcus species followed by Klebsiella . Conclusion : Clean intermittent catheterization in the rehabilitation setting does not appear to place the patient with spinal cord injury at increased risk for developing symptomatic urinary tract infection , and has significant cost and time saving benefits for the health care system , as well as enhancing the transition for the patient from rehabilitation to community PURPOSE We compared the incidence of hematuria , pyuria and clinical urinary tract infection in patients who performed intermittent self-catheterization using a hydrophilic coated LoFric ( Astra Tech AB , Mölndal , Sweden ) or st and ard plastic catheter . MATERIAL S AND METHODS A total of 62 male patients who performed intermittent self-catheterization to manage neurogenic bladder were r and omized into 2 treatment groups at 3 American study sites . Outcome measures included urinary tract infection , microhematuria , pyuria and satisfaction rates . RESULTS Of the 62 enrolled patients 49 completed the 12-month study . The withdrawal rate was not different in the 2 groups . At the end of the study there was statistically significantly less hematuria in the hydrophilic coated catheter group compared with controls . In addition , there was a significant decrease in the urinary tract infection rate from baseline in the hydrophilic coated catheter group but not in controls . CONCLUSIONS Use of the hydrophilic coated catheter by patients on intermittent self-catheterization is associated with less hematuria and a significant decrease in the incidence of urinary tract infections . Therefore , it may be preferable for some patients , especially those with a history of difficult catheterization , urethral trauma or a high rate of urinary tract infection |
12,702 | 23,891,267 | In studies comparing tamoxifen with aromatase inhibitors , the latter were superior in terms of tumor response and rates of breast-conserving surgery ( BCS ) . | In recent years , studies investigating neoadjuvant therapies have been emerging , because of the additional benefits it provides in terms of facilitating less extensive surgery and the possibility of investigating tumor biological features and response .
Neoadjuvant hormonal therapy ( NHT ) is , in general , considered to be a suitable option for hormone receptor (HR)-positive patients who are unfit for chemotherapy or surgery , and is increasingly being utilized to achieve tumor downsizing before surgery in postmenopausal women . | Several studies evaluating the clinical effectiveness of endocrine therapy alone in breast cancer patients aged 70 years or older reported comparable survival rates to conventional surgical therapy , although the incidence of local recurrences was higher . Primary endocrine therapy is therefore only recommended as an alternative approach in elderly woman with estrogen receptor positive tumors who are deemed inoperable or who refuse surgery . We report our experience with aromatase inhibitors as primary endocrine therapy for estrogen receptor positive breast cancer in postmenopausal woman who are impaired by other diseases , refuse surgery or are of old age . Fifty-six patients with fifty-seven ER+ operable breast cancers who refused surgery , were judged ineligible for surgery because of comorbidity , or were of old age were treated with endocrine therapy using aromatase inhibitors only . Digital mammography and high-end breast ultrasound were used to assess tumor sizes . The mean age of the patients was 74 years ( range 52 - 102 years ) . All patients suffered from breast cancer . The mean follow-up interval was 40 months ( range 5 - 92 months ) . Seven patients ( 12 % ) achieved complete clinical remission , 31 ( 57 % ) partial response giving an overall objective response rate of 69 % . In addition , seven ( 12 % ) patients showed stable disease , giving a clinical benefit rate ( complete remission + partial response + stable disease rate ) of 81 % . Eleven patients ( 19 % ) progressed after an initial partial response or stable disease . Only one patient ( 2 % ) progressed on endocrine therapy within the first months . Eventually , 22 ( 39 % ) patients underwent surgery after informed consent to achieve better local tumor control . Primary endocrine therapy with aromatase inhibitors may offer an effective and safe alternative to surgery giving a high local control rate in postmenopausal women who refuse surgery , who are judged ineligible for surgery , or are of old age Invasive lobular cancer ( ILC ) responds poorly to neoadjuvant chemotherapy but appears to respond well to endocrine therapy . We examined the effectiveness of neoadjuvant letrozole in postmenopausal women ( PMW ) with estrogen receptor (ER)-rich ILC . PMW were considered for treatment with neoadjuvant letrozole if they had ER-rich , large operable , or locally advanced cancers , or were unfit for surgical therapy . Tumor volume was estimated at diagnosis and at 3 months using calipers ( clinical ) , ultrasound , and mammography . At 3 months , if physically fit , women were assessed for surgery . Responsive women with cancers too large for breast-conserving surgery continued with letrozole . Patients had surgery or were switched to alternative therapy if tumor volume was increasing . Sixty-one patients ( mean age , 76.2 years ) with 63 ILCs were treated with letrozole for ≥3 months . The mean reduction in tumor volume at 3 months was 66 % ( median , 76 % ) measured clinical ly , 61 % ( median , 73 % ) measured by ultrasound , and 54 % ( median , 60 % ) measured by mammography . Surgery was possible at 3 months in 24 cancers in 24 patients , and all but two of the remaining patients continued with letrozole therapy for a median duration of 9 months . At the time of this publication , 40 patients with a total of 41 cancers have undergone surgery . The rate of successful breast conservation was 81 % ( 25/31 ) . Twenty-one patients have continued with letrozole monotherapy , and 19 remain controlled on letrozole at a median of 2.8 years . There is a high rate of response to letrozole in PMW with ER-rich ILC Eighty-eight patients presenting with operable breast cancer of 4 cm or greater in diameter ( T2 , T3 , N0 , N1 , M0 ) have received primary systemic therapy . Response was assessed following 12 weeks of systemic therapy by linear regression analysis of changes in tumour volume . Definitive locoregional surgery ( mastectomy n = 82 , wide local excision n = 6 ) was performed on completion of systemic therapy ( 3 - 6 months ) . Response was observed in 24 ( 39 % ) of the 61 patients who received endocrine therapy ; all 24 had tumours with an oestrogen receptor ( ER ) concentration of greater than or equal to 20 fmol mb-1 cytosol protein . Cytotoxic therapy was reserved for patients with tumours of ER concentration less than 20 fmol mg-1 cytosol protein ( n = 27 ) or when endocrine therapy had failed ( n = 20 ) . Response was observed in 34 patients ( 72 % ) . The overall survival rate at 3 years was 86 % , with 81 % remaining free from local relapse . We propose that the treatment policy outlined in this paper should now be tested against orthodox management by controlled r and omised trial Background In recent years , preoperative volume reduction of locally advanced breast cancers , result ing in higher rates of breast-conserving surgery ( BCS ) , has become increasingly important also in postmenopausal women . Clinical interest has come to center on the third-generation nonsteroidal aromatase inhibitors ( AIs ) , including letrozole , for such neoadjuvant endocrine treatment . This usually lasts 3–4 months and has been extended to up to 12 months , but optimal treatment duration has not been fully established . Methods This study was design ed as a multicenter , open-label , single-arm , exploratory phase IIb/III clinical trial of letrozole 2.5 mg , one tablet daily , for 4–8 months . The primary objective was to investigate the effect of neoadjuvant treatment duration on tumor regression and BCS eligibility to identify optimal treatment duration . Tumor regression ( by clinical examination , mammography , and ultrasound ) , shift towards BCS eligibility , and safety assessment s were the main outcome measures . St and ard parametric and nonparametric descriptive statistics were performed . Results Letrozole treatment was received by 32 of the enrolled 33 postmenopausal women ( median ( range ) : 67.0 ( 56–85 ) years ) with unilateral , initially BCS-ineligible primary breast cancer ( clinical stage ≥ T2 , N0 , M0 ) . Letrozole treatment duration in the modified intent-to-treat ( ITT ; required 4 months ' letrozole treatment ) analysis population ( 29 patients ) was 4 months in 14 patients and > 4 months in 15 patients . The respective per- protocol ( PP ) subgroup sizes were 14 and 11 . The majority of partial or complete responses were observed at 4 months , though some beneficial responses occurred during prolonged letrozole treatment . Compared with baseline , median tumor size in the ITT population was reduced by 62.5 % at Month 4 and by 70.0 % at final study visit ( Individual End ) . Similarly , in the PP population , respective reductions were 64.0 % and 67.0 % . Whereas initially all patients were mastectomy c and i date s , letrozole treatment enabled BCS ( lumpectomy ) in 22 ITT ( 75.9 % ) and 18 PP ( 72.0 % ) patients . Conclusion Over half of patients become BCS-eligible within 4 months of preoperative letrozole treatment . While prolonged treatment for up to 8 months can result in further tumor volume reduction in some patients , there is no clear optimum for treatment duration . Letrozole has a favorable overall safety and tolerability profile . Trial registration Clinical Trials.gov identifier NCT00535418 BACKGROUND Neoadjuvant aromatase inhibitor therapy has been reported to improve surgical outcomes for postmenopausal women with clinical stage II or III hormone receptor-positive breast cancer . A multicenter phase II clinical trial was conducted to investigate the value of this approach for US surgical practice . STUDY DESIGN One hundred fifteen postmenopausal women with > 2 cm , estrogen receptor ( ER ) or progesterone receptor (PgR)-positive breast cancer were enrolled in a trial of 16 to 24 weeks of letrozole 2.5 mg daily before operation . RESULTS One hundred six patients were eligible for primary analysis , 96 underwent operations , 7 received chemotherapy after progressive disease , and 3 did not undergo an operation . Baseline surgical status was marginal for breast-conserving surgery ( BCS ) in 48 ( 45 % ) , 47 were definitely ineligible for BCS ( 44 % ) , and 11 were inoperable by st and ard mastectomy ( 10 % ) . Overall Response Evaluation Criteria In Solid Tumors clinical response rate in the breast was 62 % , with 12 % experiencing progressive disease . Fifty percent underwent BCS , including 30 of 46 ( 65 % ) patients who were initially marginal for BCS and 15 of 39 ( 38 % ) patients who were initially ineligible for BCS . All 11 inoperable patients successfully underwent operations , including 3 ( 27 % ) who had BCS . Nineteen percent of patients undergoing mastectomy had a pathologic T1 tumor , suggesting that some highly responsive tumors were overtreated surgically . CONCLUSIONS Neoadjuvant aromatase inhibitor improves operability and facilitates BCS , but there was considerable variability in responsiveness . Better techniques to predict response , determine residual tumor burden before operation , and greater willingness to attempt BCS in responsive patients could additionally improve the rate of successful BCS It has been proposed that knowledge of estrogen receptor beta ( ER-beta ) expression may refine estrogen receptor alpha ( ER-alpha ) predictivity of response to endocrine therapy . We challenged this hypothesis in ER-alpha-positive breast cancers subjected to preoperative antiestrogen treatment . Forty-seven elderly ( > or = 65 years old ) women with nonmetastatic , ER-alpha-positive ( by immunohistochemistry ) primary breast cancers ( > 2 cm in diameter ) entered a neoadjuvant hormone therapy protocol ( 60 mg/day toremifene for 3 months ) . ER-alpha and ER-beta ( ERs ) mRNA was determined by semiquantitative RT-PCR , before ( on core needle biopsy ) and after ( on surgical specimens ) neoadjuvant treatment . Study end points included : ( 1 ) relation between treatment response and ER mRNA expression ; and ( 2 ) changes in ER expression after treatment . The response was clinical ly assessed as tumor size change at the end of the preoperative treatment . ER mRNA expression was assessable before and after treatment in 38 and 20 cases respectively . ER-beta was co-expressed with ER-alpha at variable levels and significantly correlated only with progesterone receptor ( P = 0.0285 ) . Objective clinical response , including patients with minor change ( > or = 25-<50 % tumor shrinkage after treatment ) , was documented in 68.4 % of cases and was independent of ER-beta levels or changes . ER-alpha levels were higher in tumors from patients in complete remission than in those from women achieving partial response or minor change compared with non-responsive patients ( median expression values : 801 versus 516 versus 320 arbitrary units ) and were consistently down-regulated by preoperative treatment . We conclude that in this elderly patient population with ER-alpha-positive tumors , ER-beta mRNA was neither predictive of response to preoperative toremifene nor provided additional information to the knowledge of ER-alpha mRNA levels , which , conversely , were directly correlated with likelihood of response OBJECTIVES To evaluate the efficacy and safety of combing aromatase inhibitor ( AI ) and cyclooxygenase-2 ( COX-2 ) inhibitor neoadjuvantly in postmenopausal patients with invasive hormone-sensitive breast cancer . METHODS Eighty-two patients were r and omly assigned to receive exemestane 25 mg daily and celecoxib 400 mg twice daily ( group A , n=30 ) , exemestane 25 mg daily ( group B , n=24 ) and letrozole 2.5 mg daily ( group C , n=28 ) . RESULTS All groups showed clinical responses ( 58.6 % for group A , 54.5 % for group B and 62.0 % for group C ) and decrease in tumor area ( 61.8 % for group A , 58.1 % for group B and 55.7 % for group C ) . 3 out of 5 patients with complete clinical response were observed from group A and 2 out of 69 patients operated with pathologic complete response were observed in group C. The mean microscopic tumor size was 2.53 cm for group A , 3.05 cm for group B and 2.10 cm for group C. The differences were only statistically significant when group C was compared with group B ( P=0.025 ) . The toxicity profiles among groups were satisfactory . CONCLUSION AI is effective in treating breast cancer and may be safely used preoperatively . The addition of COX-2 inhibitor may provide additional benefit In 1973 , the European Institute of Oncology performed the first prospect i ve neoadjuvant chemotherapy study in locally advanced , inoperable breast cancer . The original purpose was to downstage the primary tumor in order to achieve surgical resection . This approach has subsequently increased in popularity , and in the last 10 years , r and omized controlled trials of neoadjuvant chemotherapy have been performed with a view to further downstage the primary tumor and lymph nodes in order to achieve greater rates of breast-conserving surgery and to test whether systemic therapy given earlier would confer a survival benefit . Although the net result of these trials did demonstrate a higher rate of breast conservation , no overall survival benefit was seen . However , in subgroup analysis , there was a significant survival benefit in patients in whom a complete pathologic response ( pCR ) was achieved . In the National Surgical Adjuvant Breast and Bowel Project B-18 trial of neoadjuvant chemotherapy , at 9 years median follow-up , the overall survival rate for patients achieving a pCR was 85 % compared with 73 % in those in whom residual cancer was detected on histopathologic examination . For disease-free survival , the respective rates were 75 % and 58 % . After adjustment for other prognostic factors , achievement of a pCR was associated with a 50 % reduction in deaths compared with the group as a whole . Mauri et al evaluated nine r and omized studies , with a total of 3,946 patients with breast cancer in whom neoadjuvant therapy was compared with adjuvant systemic therapy . They found no statistically or clinical ly significant difference between neoadjuvant therapy and adjuvant therapy arms with regard to overall survival , disease progression , or distant disease recurrence . However , they observed that neoadjuvant therapy was associated with an increased risk of locoregional disease recurrence compared with adjuvant therapy , especially in trials where more patients in the neoadjuvant arm received radiation therapy without surgery . In several retrospective studies , the pCR rates in invasive ductal breast carcinoma ( no special type ) have been shown to be approximately 15 % or less , whereas the pCR rates in invasive lobular carcinoma have been shown to be 2 % or less . Katz et al review ed r and omized trials of neoadjuvant chemotherapy and noted that the pCR rate was 1.7 % in invasive lobular carcinoma and 11.6 % in invasive ductal breast carcinoma ( no special type ) . Regarding invasive lobular carcinoma , they concluded : “ the benefit from systemic chemotherapy for individuals with this form of breast disease is unclear . ” Similarly , two retrospective studies have demonstrated low rates of successful breast conservation for patients with lobular carcinoma who underwent neoadjuvant chemotherapy . In patients who received breast-conserving surgery after neoadjuvant therapy , Soucy et al found surgical margin involvement in 43 % of patients with lobular carcinoma compared with 16 % of patients with invasive ductal carcinoma ( no special type ) . Another study , from the M. D. And erson Cancer Center , of 284 consecutive patients diagnosed with pure invasive lobular carcinoma between 1998 and 2006 compared patients who received neoadjuvant chemotherapy with those who received primary surgery as first-line treatment and concluded that neoadjuvant chemotherapy did not increase the rates of breast conservation in this morphologic subtype . It should be noted that the above studies are retrospective , not r and omized , trials . In the three r and omized trials of neoadjuvant endocrine therapy ( P024 conducted by the Letrozole Neoadjuvant Breast Cancer Study Group , IMPACT [ Immediate Preoperative Anastrozole , Tamoxifen , or Combined with Tamoxifen ] , and PROACT [ Pre-Operative “ Arimidex ” Compared to Tamoxifen ] ) for women with estrogen receptor ( ER ) –positive disease , none of which carried out analysis of histological tumor type ( ie , lobular v ductal [ no special type ] ) , a higher rate of breast conservation was observed in women who received preoperative endocrine treatment . The lack of subgroup analysis in these three studies does not allow one to draw conclusions regarding histologic type-specific effectiveness of neoadjuvant endocrine treatment , although classical lobular carcinoma is well recognized as more often being ER positive than ductal tumors ( no special type ) . JOURNAL OF CLINICAL ONCOLOGY COMMENTS AND CONTROVERSIES VOLUME 28 NUMBER 22 AUGUST 1 Sixty-three postmenopausal women with large primary breast cancers were treated with neoadjuvant letrozole ( 2.5 mg daily ) for 3 months . Tumour sample s were taken at diagnosis and after 10–14 days and 3 months treatment . Immunohistochemical staining for Ki67 , oestrogen receptor ( ER ) and progesterone receptor ( PgR ) was performed and related to clinical ( ClinR ) and pathological responses ( PathR ) after 3 months treatment . ClinR was observed in 48 of 63 cases ( 76.2 % ) and PathR in 47 of 62 ( 75.8 % ) . Pretreatment Ki67 scores were similar in responders ( R ) and non-responders ( NR ) . Highly significant Ki67 decreases occurred in all tumour subgroups at 10–14 days ( P<0.005 ) . A significant difference in Ki67 scores at 10–14 days ( P<0.007 ) was found between PathR and PathNR but not between ClinR and ClinNR . At 3 months , decreases from pretreatment Ki67 scores were highly significant in all tumour subgroups irrespective of response status . However , whereas Ki67 scores were significantly different between pathological R and NR ( P=0.009 ) , the corresponding comparison of ClinR status was not . Significant decreases between 10–14 days and 3 months were found only in ClinR and PathR ( P=0.02 and 0.045 , respectively ) . Treatment significantly reduced PgR expression at 14 days and 3 months ( both P<0.0001 ) , but the level of changes was not different between response status groups . In summary , letrozole produces rapid and profound decreases in expression of Ki67 and PgR but changes do not always correlate with clinical and pathological responses Preoperative endocrine therapy is effective in postmenopausal patients with breast cancers expressing oestrogen receptor . We investigated the activity of primary therapy with letrozole in combination with GnRH analogue in premenopausal women with T2–T4 N0–N2 breast cancer , whose tumours expressed oestrogen and progesterone receptors . We measured the expression of molecular factors involved in responsiveness to endocrine agents including ERα , EGFR , HER2 , MAP kinases ( and phosphorylated forms ) ER-β1 , both at initial biopsy and at the time of surgery . Thirty-five patients were included and 32 patients were evaluable for response . Sixteen patients ( 50 % , 95 % CI 32–68 % ) obtained a partial response , 16 patients were stable . One patient showed pathological complete response ( 3 % , 95 % CI 0–16 % ) . Response was significantly associated with younger age ( P<0.05 ) and a longer duration of treatment ( P<0.05 ) . Treatment significantly decreased ERα-p-Ser118 and upregulated ER-β1 , independently of response . No or negligible overexpression of EGFR was observed at baseline or after treatment in this population . Preoperative letrozole and GnRH analogue are effective in premenopausal women . A biological response in terms of downregulation of phosphorylated ERα was observed in all patients . Future investigations might focus on treatments of longer duration Sixty patients with locally advanced breast cancer , but with no evidence of distant metastases were r and omised to receive primary endocrine therapy or chemotherapy after assessment and ' Trucut ' biopsy of the primary tumour . After 12 weeks all patients were assessed . Eight out of 30 ( 27 % ) of the patients who received chemotherapy showed complete clinical regression of the primary cancer , eight patients ' tumours had regressed by more than 50 % , and ten showed a 25 - 50 % reduction in bi-dimensional diameter . Only four ( 13 % ) patients ' tumours failed to reduce in size . Seven patients were judged to require mastectomy at the end of the 12 week period of treatment with chemotherapy . In contrast , only three out of 30 ( 10 % ) patients receiving endocrine therapy showed a greater than 50 % reduction in tumour size , and four patients had a 25 - 50 % reduction at 12 weeks . The remaining patients ' tumours either stabilised ( 12 patients ) or enlarged ( 11 patients ) . We conclude that primary chemotherapy in patients with primary breast cancer is more effective in rapidly reducing the size of the primary breast cancer than endocrine therapy ( P = 0.001 ) and alters significantly the future management of these patients . However , at 65 weeks on completion of the follow-up , there is no significant difference in the number of patients ' disease-free , locally or distant recurrent , or dead Anastrozole , an orally active , nonsteroidal aromatase inhibitor , was evaluated in a r and omized , double-blind , single-center study to determine its efficacy as neoadjuvant therapy in postmenopausal women with newly diagnosed , estrogen receptor-rich , locally advanced or large ( > 3 cm ) , operable breast cancers . Twenty-four eligible patients were recruited into the study and received either 1 mg ( n = 12 ) or 10 mg ( n = 12 ) of anastrozole daily over a 3-month period . Tumor volumes were estimated clinical ly , by using caliper measurements and ultrasound ( at baseline and after 1 , 2 , and 3 months ' treatment ) and by mammography ( at baseline and after 3 months ) . Tumor volume was also measured in surgical specimens . Twenty-one patients were classified as T2 , two patients as T3 , and one patient as T4B at baseline . Three patients had clinical evidence of lymph node involvement . When considering the difference between the volume as measured by each assessment and the actual pathological volume , the interquartile range and the difference between the maximum and minimum values were smaller for ultrasound when compared with those measured with calipers and mammography . Therefore , of the three clinical assessment s of tumor volume used in this study , the data suggest that ultrasound may be the most accurate . The median reductions in tumor volumes as measured by ultrasound for those patients with a measurable 12-week assessment were 80.5 and 69.6 % for anastrozole ( 1 and 10 mg , respectively ) after 12 weeks of treatment and 75.5 % when both doses were grouped together . Moreover , of these patients , 11 of 12 given 1 mg and 7 of 11 given 10 mg of anastrozole were found on ultrasound to have a > 50 % reduction in tumor volume after 12 weeks of treatment . Of the 17 patients who would have required a mastectomy at initiation of treatment , 15 were suitable for breast conservation after anastrozole treatment . These results suggest that anastrozole is highly effective as neoadjuvant therapy in postmenopausal women with estrogen receptor-rich , large , operable breast cancer . Future studies comparing anastrozole with tamoxifen as a neoadjuvant treatment should be considered Abstract Aims . To investigate the efficacy of letrozole 2.5 mg and 10 mg used as primary neoadjuvant therapy for patients with locally advanced and large operable breast cancer . Patients and Methods . Twenty-four postmenopausal patients with locally advanced or large operable breast cancer were treated in two consecutive series with letrozole 2.5 mg ( n=12 ) or letrozole 10 mg ( n=12 ) . Response at three months was measured by change in tumor volume according to WHO criteria ( partial response was defined as a reduction in tumor volume ≥65 % ) . Tumor volumes were assessed clinical ly , by ultrasound and mammography , and pathologically . Results . All 24 patients were estrogen receptor-positive , were considered ‘ receptor-rich ’ , and mean age was 77.6 years and 71.6 years in the letrozole 2.5 mg and 10 mg treatment groups , respectively . There were five complete clinical responses and seven partial clinical responses in the patients treated with 2.5 mg letrozole , and nine partial responses and three patients with stable disease in patients treated with 10 mg letrozole . Assessed by ultrasound and mammography , the 12 patients treated with 2.5 mg had one complete response , nine partial responses and two with no change . In the 12 patients treated with 10 mg letrozole , imaging gave eight partial responses and four with no change . One patient treated with the 2.5 mg dose had a complete clinical and pathological response . There was no significant difference between the two doses in effect on tumor volume , and no recordable side effects associated with either dose . Conclusion . Letrozole used in a neoadjuvant setting is highly effective , producing clinical ly beneficial reductions in tumor volume allowing all patients to have breast conserving surgery , and has an acceptable safety profile BACKGROUND Luminal breast cancer is a highly endocrine responsive disease . However , the therapeutic benefit of chemotherapy ( CT ) in this population is not fully characterized . This study investigates the value of CT and hormone therapy ( HT ) in luminal breast cancer patients in the neoadjuvant setting . PATIENTS AND METHODS Patients with operable breast cancer and immunophenotypically defined luminal disease ( ER+/PR+/HER2-/cytokeratin 8/18 + ) were recruited . Patients were r and omized to CT ( epirubicin 90 mg/m(2 ) plus cyclophosphamide 600 mg/m(2 ) 4 cycles followed by docetaxel 100 mg/m(2 ) 4 cycles [ EC-T ] ) or HT ( exemestane 25 mg daily 24 weeks [ combined with goserelin in premenopausal patients ] ) . The primary end point was the clinical response measured by magnetic resonance imaging . RESULTS Ninety-five patients were r and omized ( 47 CT , 48 HT ) . The clinical response rate was 66 % for CT and 48 % for HT ( P = 0.075 ) . We performed an unplanned analysis based on Ki67 levels ( cut-off of 10 % ) . Similar clinical response was seen between arms in patients with low Ki67 ( CT : 63 % , HT : 58 % ; P = 0.74 ) ; patients with high Ki67 had a better response with CT ( 67 versus 42 % ; P = 0.075 ) . Grade 3/4 toxicity was more frequent with CT . CONCLUSIONS Luminal immunophenotype is not enough to identify patients who do not benefit from neoadjuvant CT . Luminal patients with low proliferation index could potentially avoid CT The predictive role of the degree of endocrine responsiveness to preoperative chemotherapy ( PCT ) is unclear . We review ed pretreatment biopsies of 553 patients with locally advanced breast cancer who were treated with PCT . The incidence of pathological complete remission ( pCR ) and outcome were assessed with respect to the degree of estrogen ( ER ) and progesterone receptor ( PgR ) expression ( ER and PgR absent , vs. ER or PgR 0–49 % , vs. ER and PgR ≥50 % of the cells positive ) . A statistically significant higher pCR rate was observed at the multivariate analysis for patients with ER and PgR absent tumors ( 17.7 % ) versus patients with tumors expressing high ER and PgR ( 0 % ) ( OR 14.4 P < 0.001 ) . Despite the higher incidence of pCR , a statistically significant worse disease-free survival ( DFS ) , and overall survival ( OS ) was observed for patients with ER and PgR absent tumors versus patients with tumors expressing high ER and PgR ( HR 6.4 , 95 % CI 3.5–11.6 , for DFS ; HR 3.6 95 % CI 2.4–5.6 for OS ) . Response and outcome after PCT are correlated with the degree of expression of steroid hormone receptors . Studies on tailored preoperative therapies are needed Abstract Purpose The aim of this study was to investigate the potential benefits of prolonged treatment with neoadjuvant letrozole . Patients and Methods About 182 consecutive patients have been treated in Edinburgh with neoadjuvant letrozole for 3 months or longer and 63 patients have continued on letrozole beyond 3 months . Outcomes are reported . Results Of the 63 patients who continued on letrozole , 38 patients took letrozole for more than 1 year and 23 took letrozole for more than 24 months . The median reduction in clinical volume in the first 3 months in these 63 patients was 52 % . Similar reductions in median clinical volume were seen between three to 6 months ( 50 % ) , 6–12 months and 12–24 months ( medians 37 and 33 % , respectively ) . At 3 months 69.8 % of the 182 patients had a partial or complete response . The response rate increased to 83.5 % with prolonged letrozole treatment . Continuing letrozole beyond 3 months increased the number of women who initially required mastectomy or had locally advanced breast cancer who were subsequently suitable for breast conserving surgery from 60 % ( 81/134 ) at 3 months to 72 % ( 96/134 ) . Thirty-three women remain on letrozole alone ( man age at diagnosis 83 years ) and at 3 years the median time to treatment failure has not been reached . Conclusion Continuing letrozole in responding patients beyond 3–4 months achieves further clinical reduction in tumour size . For elderly women with a short life expectancy letrozole alone may provide long-term disease control PURPOSE Cross-talk between the estrogen receptor ( ER ) and the phosphoinositide-3-kinase (PI3K)/Akt/mammalian target of rapamycin ( mTOR ) pathways is a mechanism of resistance to endocrine therapy , and blockade of both pathways enhances antitumor activity in pre clinical models . This study explored whether sensitivity to letrozole was enhanced with the oral mTOR inhibitor , everolimus ( RAD001 ) . PATIENTS AND METHODS Two hundred seventy postmenopausal women with operable ER-positive breast cancer were r and omly assigned to receive 4 months of neoadjuvant treatment with letrozole ( 2.5 mg/day ) and either everolimus ( 10 mg/day ) or placebo . The primary end point was clinical response by palpation . M and atory biopsies were obtained at baseline and after 2 weeks of treatment ( ie , day 15 ) . Sample s were assessed for PI3 K mutation status ( PIK3CA ) and for pharmacodynamic changes of Ki67 , phospho-S6 , cyclin D1 , and progesterone receptor ( PgR ) by immunohistochemistry . RESULTS Response rate by clinical palpation in the everolimus arm was higher than that with letrozole alone ( ie , placebo ; 68.1 % v 59.1 % ) , which was statistically significant at the preplanned , one-sided , alpha = 0.1 level ( P = .062 ) . Marked reductions in progesterone receptor and cyclin D1 expression occurred in both treatment arms , and dramatic downregulation of phospho-S6 occurred only in the everolimus arm . An antiproliferative response , as defined by a reduction in Ki67 expression to natural logarithm of percentage positive Ki67 of less than 1 at day 15 , occurred in 52 ( 57 % ) of 91 patients in the everolimus arm and in 25 ( 30 % ) of 82 patients in the placebo arm ( P < .01 ) . The safety profile was consistent with historical results of everolimus monotherapy ; grade s 3 to 4 adverse events occurred in 22.6 % of patients who received everolimus and in 3.8 % of patients who received placebo . CONCLUSION Everolimus significantly increased letrozole efficacy in neoadjuvant therapy of patients with ER-positive breast cancer BACKGROUND A r and omized , double-blind , multicenter study was conducted to compare the anti-tumor activity of letrozole vs. tamoxifen in postmenopausal women with ER and /or PgR positive primary untreated breast cancer . PATIENTS AND METHODS Three hundred thirty-seven postmenopausal women with ER and /or PgR positive primary untreated breast cancer were r and omly assigned once daily treatment with either letrozole 2.5 mg or tamoxifen 20 mg for four months . At baseline none of the patients were considered to be c and i date s for breast-conserving surgery ( BCS ) and 14 % of the patients were considered inoperable . The primary endpoint was to compare overall objective response ( CR + PR ) determined by clinical palpation . Secondary endpoints included overall objective response on ultrasound and mammography and the number of patients who qualified for BCS . RESULTS Overall objective response rate ( clinical palpation ) was statistically significantly superior in the letrozole group , 55 % compared to tamoxifen , 36 % ( P < 0.001 ) . Secondary endpoints of ultrasound response , 35 % vs. 25 % ( P = 0.042 ) , mammographic response , 34 % vs. 16 % ( P < 0.001 ) , and BCS , 45 % vs. 35 % ( P = 0.022 ) between the letrozole and tamoxifen groups , respectively , showed letrozole to be significantly superior . Both treatments were well tolerated . CONCLUSIONS This study shows that letrozole is more effective than tamoxifen as preoperative therapy in postmenopausal patients with ER and /or PgR positive primary untreated breast cancer and is at least as well tolerated BACKGROUND Multiple studies suggest better efficacy of chemotherapy in invasive ductal breast carcinomas ( IDC ) than invasive lobular breast carcinomas ( ILC ) . However , data on efficacy of adjuvant endocrine therapy regimens and histological subtypes are sparse . This study assessed endocrine therapy efficacy in IDC and ILC . The influence of semi-quantitative oestrogen receptor ( ER ) expression by Allred score was also investigated . METHODS Dutch and Belgian patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational ( TEAM ) trial were r and omized to exemestane ( 25 mg daily ) alone or following tamoxifen ( 20 mg daily ) for 5 years . Inclusion was restricted to IDC and ILC patients . Histological subtype was assessed locally ; ER expression was central ly review ed according to Allred score ( ER-poor ( < 7 ; n=235 ) ; ER-rich ( 7 ; n=1789 ) ) . Primary end-point was relapse-free survival ( RFS ) , which was the time from r and omization to disease relapse . FINDINGS Overall , 2140 ( 82 % ) IDC and 463 ( 18 % ) ILC patients were included . RFS was similar for both endocrine treatment regimens in IDC ( hazard ratio ( HR ) for exemestane was 0.83 ( 95%confidence interval ( CI ) 0.67 - 1.03 ) ) , and ILC ( HR 0.69 ( 95%CI 0.45 - 1.06 ) ) . Irrespective of histological subtype , patients with ER-rich Allred scores allocated to exemestane alone had an improved RFS ( multivariable HR 0.71 ( 95%CI 0.56 - 0.89 ) ) . In contrast , patients with ER-poor Allred scores allocated to exemestane had a worse RFS ( multivariable HR 2.33 ( 95%CI 1.32 - 4.11 ) ) . Significant effect modification by ER-Allred score was confirmed ( multivariable p=0.003 ) . INTERPRETATION Efficacy of endocrine therapy regimens was similar for IDC and ILC . However , ER-rich patients showed superior efficacy to upfront exemestane , while ER-poor patients had better outcomes with sequential therapy , irrespective of histological subtype , emphasising the relevance of quantification of ER expression PURPOSE Expression of ErbB-1 and ErbB-2 ( epidermal growth factor receptor and HER2/neu ) in breast cancer may cause tamoxifen resistance , but not all studies concur . Additionally , the relationship between ErbB-1 and ErbB-2 expression and response to selective aromatase inhibitors is unknown . A neoadjuvant study for primary breast cancer that r and omized treatment between letrozole and tamoxifen provided a context within which these issues could be addressed prospect ively . PATIENTS AND METHODS Postmenopausal patients with estrogen- and /or progesterone receptor-positive ( ER+ and /or PgR+ ) primary breast cancer ineligible for breast-conserving surgery were r and omly assigned to 4 months of neoadjuvant letrozole 2.5 mg daily or tamoxifen 20 mg daily in a double-blinded study . Immunohistochemistry ( IHC ) for ER and PgR was conducted on pretreatment biopsies and assessed by the Allred score . ErbB-1 and ErbB-2 IHC were assessed by intensity and completeness of membranous staining according to published criteria . RESULTS For study biopsy-confirmed ER+ and /or PgR+ cases that received letrozole , 60 % responded and 48 % underwent successful breast-conserving surgery . The response to tamoxifen was inferior ( 41 % , P = .004 ) , and fewer patients underwent breast conservation ( 36 % , P = .036 ) . Differences in response rates between letrozole and tamoxifen were most marked for tumors that were positive for ErbB-1 and /or ErbB-2 and ER ( 88 % v 21 % , P = .0004 ) . CONCLUSION ER+ , ErbB-1 + , and /or ErbB-2 + primary breast cancer responded well to letrozole , but responses to tamoxifen were infrequent . This suggests that ErbB-1 and ErbB-2 signaling through ER is lig and -dependent and that the growth-promoting effects of these receptor tyrosine kinases on ER+ breast cancer can be inhibited by potent estrogen deprivation therapy Fifty eight ( 58 ) patients with early breast cancer ( mean age 78.3 years ) and 37 patients with advanced breast cancer ( mean age 65.9 years ) were treated with tamoxifen orally 20 mg daily or twice daily . The mean follow-up time was 19.1 months in the early group and 18.4 months in the late group . The drug was extremely well tolerated . All patients had cytological or histological evidence of breast cancer . A complete or partial response was found in only 36 % of the patients with early breast cancer and only 13 % in the advanced group . We conclude that tamoxifen was disappointing as a primary therapy in our patients . Although because of its lack of toxicity it can be seen as initial therapy for patients with breast cancer , it may have to be supplanted rapidly by other forms of therapy in the substantial proportion of patients in whom a response will not occur PURPOSE We aim ed to identify signaling pathways involved in the response and resistance to aromatase inhibitor therapy in patients with breast cancer . PATIENTS AND METHODS One hundred fourteen women with T2 - 4 N0 - 1 , estrogen receptor ( ER ) alpha-positive tumors were r and omly assigned to neoadjuvant letrozole or letrozole plus metronomic cyclophosphamide . Twenty-four tumor proteins involved in apoptosis , cell survival , hypoxia , angiogenesis , growth factor , and hormone signaling were assessed by immunohistochemistry in pretreatment sample s ( eg , caspase 3 , phospho- mammalian target of rapamycin , hypoxia-inducible factor 1alpha [ HIF-1alpha ] , vascular endothelial growth factor , mitogen-activated protein kinase [ MAPK ] , phosphorylated epidermal growth factor receptor , phosphorylated ERalpha [ pERalpha ] ) . A multivariate generalized linear regression approach was applied using a penalized least-square minimization to perform variable selection and regularization . Ten-fold cross-validation and iterative leave-one-out were employed to vali date and test the model , respectively . Tumor size , nodal status , age , tumor grade , histological type , and treatment were included in the analysis . RESULTS Ninety-one patients ( 81 % ) attained a disease response , 48 achieved a complete clinical response ( 43 % ) whereas 22 did not respond ( 19 % ) . Increased pERalpha and decreased p44/42 MAPK were significant factors for complete response to treatment in all leave-one-out iterations . Increased p44/42 MAPK and HIF-1alpha were significant factors for treatment resistance in all leave-one-out iterations . There was no significant interaction between these variables and treatment . CONCLUSION Activated ERalpha form was an independent factor for sensitivity to chemoendocrine treatment , whereas HIF-1alpha and p44/42 MAPK were independent factors for resistance . Although further confirmatory analyses are needed , these findings have clear potential implication s for future strategies in the management of clinical trials with aromatase inhibitors in the breast cancer PURPOSE The Immediate Preoperative Anastrozole , Tamoxifen , or Combined With Tamoxifen ( IMPACT ) trial was design ed to test the hypothesis that the clinical and /or biologic effects of neoadjuvant tamoxifen compared with anastrozole and with the combination of tamoxifen and anastrozole before surgery in postmenopausal women with estrogen receptor ( ER ) -positive , invasive , nonmetastatic breast cancer might predict for outcome in the Arimidex , Tamoxifen Alone or in Combination ( ATAC ) adjuvant therapy trial . PATIENTS AND METHODS Postmenopausal women with ER-positive , invasive , nonmetastatic , and operable or locally advanced potentially operable breast cancer were r and omly assigned to neoadjuvant tamoxifen ( 20 mg daily ) , anastrozole ( 1 mg daily ) , or a combination of tamoxifen and anastrozole for 3 months . The tumor objective response ( OR ) was assessed by both caliper and ultrasound . Comparisons were also made of clinical response with ultrasound response , actual and feasible surgery with feasible surgery at baseline , OR in human epidermal growth factor receptor 2 (HER2)-positive cancers , and tolerability . RESULTS There were no significant differences in OR in the intent-to-treat population between patients receiving tamoxifen , anastrozole , or the combination . In patients who were assessed as requiring mastectomy at baseline ( n = 124 ) , 44 % of patients received breast-conserving surgery ( BCS ) after anastrozole compared with 31 % of patients after tamoxifen ( P = .23 ) ; this difference became significant for patients who were deemed feasible for BCS by their surgeon ( 46 % v 22 % , respectively ; P = .03 ) . The OR for patients with HER2-positive cancer ( n = 34 ) was 58 % for anastrozole compared with 22 % for tamoxifen ( P = .18 ) . All treatments were well tolerated . CONCLUSION Neoadjuvant anastrozole is as effective and well tolerated as tamoxifen in ER-positive operable breast cancer in postmenopausal women , but the hypothesis that clinical outcome might predict for long-term outcome in adjuvant therapy was not fulfilled Purpose Letrozole is superior to tamoxifen in terms of response and breast preservation rates as primary systemic therapy ( PST ) in postmenopausal women with ER-positive early breast cancer . However , the optimum duration of endocrine PST remains uncertain . Methods A phase 2 multicentre , open-label trial was conducted to evaluate the efficacy of letrozole over a preoperative period of 4 months to 1 year . Seventy postmenopausal patients ( over 65 years ) were recruited in four centers . The primary endpoint was to establish the optimal duration of treatment defined as the time required to attain the maximum response by clinical palpation . Results The median age of the group was 79 years ( 66–91 ) and the median tumour size 35 mm ( range 25–100 mm ) . No severe adverse events were reported . Fifty-six patients were evaluable for the primary objective . A total of 43 patients ( 76.8 % ) achieved an objective response ; 29 ( 51.8 % ) being partial and 14 ( 25.0 % ) complete . The median time to objective response was 3.9 months ( 95 % CI , 3.3–4.5 ) and the median time to maximum response was 4.2 months ( 95 % CI , 4.0–4.5 ) , although 20 ( 37.1 % ) patients achieved the maximal response within 6–12 months . Conclusions Letrozole shows a high activity and excellent tolerability as neoadjuvant therapy in elderly patients with endocrine-dependent breast cancer . Four to six months of letrozole as PST is an optimum duration with modest benefits thereafter PURPOSE Preoperative aromatase inhibitor ( AI ) treatment promotes breast-conserving surgery ( BCS ) for estrogen receptor (ER)-positive breast cancer . To study this treatment option , responses to three AIs were compared in a r and omized phase II neoadjuvant trial design ed to select agents for phase III investigations . PATIENTS AND METHODS Three hundred seventy-seven postmenopausal women with clinical stage II to III ER-positive ( Allred score 6 - 8 ) breast cancer were r and omly assigned to receive neoadjuvant exemestane , letrozole , or anastrozole . The primary end point was clinical response . Secondary end points included BCS , Ki67 proliferation marker changes , the Preoperative Endocrine Prognostic Index ( PEPI ) , and PAM50-based intrinsic subtype analysis . RESULTS On the basis of clinical response rates , letrozole and anastrozole were selected for further investigation ; however , no other differences in surgical outcome , PEPI score , or Ki67 suppression were detected . The BCS rate for mastectomy-only patients at presentation was 51 % . PAM50 analysis identified AI-unresponsive nonluminal subtypes ( human epidermal growth factor receptor 2 enriched or basal-like ) in 3.3 % of patients . Clinical response and surgical outcomes were similar in luminal A ( LumA ) versus luminal B tumors ; however , a PEPI of 0 ( best prognostic group ) was highest in the LumA subset ( 27.1 % v 10.7 % ; P = .004 ) . CONCLUSION Neoadjuvant AI treatment markedly improved surgical outcomes . Ki67 and PEPI data demonstrated that the three agents tested are biologically equivalent and therefore likely to have similar adjuvant activities . LumA tumors were more likely to have favorable biomarker characteristics after treatment ; however , occasional paradoxical increases in Ki67 ( 12 % of tumors with > 5 % increase after therapy ) suggest treatment-resistant cells , present in some LumA tumors , can be detected by post-treatment profiling In France , 20 % of breast cancers occur in women over the age of 70 and 10 % in women over the age of 80 . As these women are not included in screening programs , breast cancer is often diagnosed later , at the stage of a large tumor . Purpose : To analyze clinical response , possibilities of conservative treatment and course of hormonal receptors in patients receiving neoadjuvant aromatase inhibitor ( AI ) therapy for at least 6 months . Patients and Methods : There were 75 patients , with a mean age of 75 ± 8 years ( range , 58–91 years ) received AI for 6 months after the diagnosis of invasive breast cancer with positive hormonal receptors . Clinical and radiologic tumor reduction , the number of conservative treatments and the course of estrogens receptor-labeled cells were determined for each patient . Results : All but 1 of these patients obtained clinical reduction of their tumor . Of these , 86 % patients received conservative treatment . In the majority of patients , estrogen receptor ( ER ) level did not vary between the initial assay and analysis of the operative specimen . Discussion and Conclusion : Aromatase inhibitors are effective as neoadjuvant therapy in ER positive elderly patients with large tumors , as is tamoxifen . Changes in hormone receptor expression during treatment do not predict clinical response . In our experience , neo6adjuvant AI therapy should be administered for at least 6 months to optimize clinical response before deciding upon surgery . Discrepancy observed in the literature could be explained by the duration of the treatment BACKGROUND Aromatase inhibitors have shown increased efficacy compared with tamoxifen in postmenopausal early breast cancer . We aim ed to assess the efficacy and safety of anastrozole versus tamoxifen in premenopausal women receiving goserelin for early breast cancer in the neoadjuvant setting . METHODS In this phase 3 , r and omised , double-blind , parallel-group , multicentre study , we enrolled premenopausal women with oestrogen receptor (ER)-positive , HER2-negative , operable breast cancer with WHO performance status of 2 or lower . Patients were r and omly assigned ( 1:1 ) to receive goserelin 3·6 mg/month plus either anastrozole 1 mg per day and tamoxifen placebo or tamoxifen 20 mg per day and anastrozole placebo for 24 weeks before surgery . Patients were r and omised sequentially , stratified by centre , with r and omisation codes . All study personnel were masked to study treatment . The primary endpoint was best overall tumour response ( complete response or partial response ) , assessed by callipers , during the 24-week neoadjuvant treatment period for the intention-to-treat population . The primary endpoint was analysed for non-inferiority ( with non-inferiority defined as the lower limit of the 95 % CI for the difference in overall response rates between groups being 10 % or less ) ; in the event of non-inferiority , we assessed the superiority of the anastrozole group versus the tamoxifen group . We included all patients who received study medication at least once in the safety analysis set . We report the primary analysis ; treatment will also continue in the adjuvant setting for 5 years . This trial is registered with Clinical Trials.gov , number NCT00605267 . FINDINGS Between Oct 2 , 2007 , and May 29 , 2009 , 204 patients were enrolled . 197 patients were r and omly assigned to anastrozole ( n=98 ) or tamoxifen ( n=99 ) , and 185 patients completed the 24-week neoadjuvant treatment period and had breast surgery ( 95 in the anastrazole group , 90 in the tamoxifen group ) . More patients in the anastrozole group had a complete or partial response than did those in the tamoxifen group during 24 weeks of neoadjuvant treatment ( anastrozole 70·4 % [ 69 of 98 patients ] vs tamoxifen 50·5 % [ 50 of 99 patients ] ; estimated difference between groups 19·9 % , 95 % CI 6·5 - 33·3 ; p=0·004 ) . Two patients in the anastrozole group had treatment-related grade 3 adverse events ( arthralgia and syncope ) and so did one patient in the tamoxifen group ( depression ) . One serious adverse event was reported in the anastrozole group ( benign neoplasm , not related to treatment ) , compared with none in the tamoxifen group . INTERPRETATION Given its favourable risk-benefit profile , the combination of anastrozole plus goserelin could represent an alternative neoadjuvant treatment option for premenopausal women with early-stage breast cancer . FUNDING AstraZeneca Few studies have compared primary neoadjuvant endocrine therapy with neoadjuvant chemotherapy in breast cancer patients . The need for preoperative chemotherapy with doxorubicin or taxanes may be reduced in postmenopausal patients with estrogen receptor (ER)‐positive and /or progesterone receptor (PgR)‐positive tumors . This r and omized , controlled , phase 2 study evaluated the efficacy of neoadjuvant chemotherapy compared with endocrine treatment with aromatase inhibitors in postmenopausal women with ER‐positive and /or PgR‐positive breast cancer The authors report on a series of 120 elderly ( age over 69 ) women with primary breast treated with tamoxifen alone . Treatment schedule was 160 mg on day 1 followed by a daily maintenance dose of 20 mg . Compliance to treatment was optimal and side effects were minimal . The best results achieved after at least six months of treatments were complete response in 12 , a partial response in 46 and minor response in 10 patients , whereas stable disease or progression was observed in 43 or 9 patients , respectively . Response duration was limited and progression was increasingly observed over time . After 6 , 12 , 24 , 36 , 48 and 60 months the proportion of subjects still showing response to treatment was 43 % , 57 % , 56 % , 46 % , 32 % and 31 % , whereas progression rate was 7 % , 12 % , 25 % , 39 % , 55 % and 60 % , respectively , the difference being accounted for by patients with stable disease . As determined in a subset of 27 subjects , treatment response was strongly associated with immunocytochemically assessed tumor estrogen receptor content , progression being 100 % , 43 % or 6 % in subjects with 0 % , 30 - 60 % or > 60 % immunostained cells , respectively . These results do not support primary hormone therapy as a current alternative to surgery , which should be the st and ard treatment in otherwise healthy elderly patients with operable breast cancer . When surgery is specifically contraindicated , hormone treatment should be proposed as an alternative only in subjects with high tumor estrogen receptor content BACKGROUND We investigated the efficacy and safety of anastrozole as neoadjuvant therapy in a group of postmenopausal patients with locally-advanced breast cancer . PATIENTS AND METHODS This was an open-label trial , which recruited patients with histopathologically-confirmed unilateral , locally-advanced , estrogen-receptor-positive breast cancer ( stage IIIA/B ) . All patients received anastrozole 1 mg/day for 3 months , after which the clinical response was evaluated . All patients with a complete or partial clinical response ( cCR or cPR ) underwent surgery ( radical modified mastectomy ) , after which patients continued with the same therapy for two years or until progression . Primary end points were clinical response rate ( cCR + cPR ) , surgery rate , pathological complete response rate and tolerability profile . RESULTS cCR and cPR were seen in 61/112 ( 54.5 % ) and 32/112 ( 28.6 % ) patients ( n=112 ) , respectively , giving an objective response rate of 93/112 ( 83 % ) patients . Following surgery in responding patients , 14/61 patients ( 23 % ) had a pathological CR and 47/61 ( 77 % ) patients had a pathological PR . CONCLUSION Neoadjuvant anastrozole treatment was highly effective and well-tolerated in postmenopausal women with hormone-dependent locally-advanced breast cancer The Pre‐Operative “ Arimidex ” Compared to Tamoxifen ( PROACT ) study was a r and omized , multicenter study comparing anastrozole with tamoxifen as a preoperative treatment of postmenopausal women with large , operable ( T2/3 , N0‐2 , M0 ) , or potentially operable ( T4b , N0‐2 , M0 ) breast cancer . The effect of preoperative endocrine therapy in patients scheduled for mastectomy or with inoperable tumors at baseline was also investigated AIMS Neoadjuvant systemic therapy of large and locally advanced breast cancers may , through shrinkage , enable breast conservation surgery . Letrozole , an aromatase inhibitor , is used frequently in the treatment of oestrogen receptor-positive breast cancer . The aim was to examine the response patterns in a letrozole-treated group compared with a chemotherapy-treated group . MATERIAL S AND METHODS Fifty patients with primary breast cancer were treated with 3 months of chemotherapy and 53 with 3 months of neoadjuvant letrozole . Excised tumours were compared with preoperative core biopsy specimens . Volume calculations before and after therapy were used to calculate clinical response in the letrozole group . RESULTS Response patterns were significantly different between the two therapies ( P < 0.0005 ) . Chemotherapy produced more complete pathological responses ( P = 0.008 ) and a scattered cell pattern was also seen more frequently ( P = 0.035 ) . Letrozole produced substantially more central scars - 31 cases as opposed to two cases in the chemotherapy group ( P = 0.0001 ) - and there was a statistically significant correlation with central scarring and clinical tumour volume reduction ( P = 0.034 ) . CONCLUSIONS There are significantly different histological responses between cancers treated with chemotherapy and endocrine therapy , particularly central scarring . This has not been documented previously and may be an important factor in down-sizing tumours with letrozole , enabling subsequent conservation surgery |
12,703 | 27,433,992 | The findings indicate a grade d dose-response relationship whereby increases in RT volume produce greater gains in muscle hypertrophy | ABSTRACT The purpose of this paper was to systematic ally review the current literature and eluci date the effects of total weekly resistance training ( RT ) volume on changes in measures of muscle mass via meta-regression . | The strength training has been shown to be effective for attenuating the age-related physiological decline . However , the adequate volume of strength training volume adequate to promote improvements , mainly during the initial period of training , still remains controversial . Thus , the purpose of this study was to compare the effects of a short-term strength training program with single or multiple sets in elderly women . Maximal dynamic ( 1-RM ) and isometric strength , muscle activation , muscle thickness ( MT ) , and muscle quality ( MQ = 1-RM and MT quadriceps quotient ) of the knee extensors were assessed . Subjects were r and omly assigned into one of two groups : single set ( SS ; n = 14 ) that performed one set per exercise or multiple sets ( MS ; n = 13 ) that performed three-sets per exercise , twice weekly for 6 weeks . Following training , there were significant increases ( p ≤ 0.05 ) in knee extension 1-RM ( 16.1 ± 12 % for SS group and 21.7 ± 7.7 % for MS group ) , in all MT ( p ≤ 0.05 ; vastus lateralis , rectus femoris , vastus medialis , and vastus intermedius ) , and in MQ ( p ≤ 0.05 ) ; 15.0 ± 12.2 % for SS group and 12.6 ± 7.2 % for MS group ) , with no differences between groups . These results suggest that during the initial stages of strength training , single- and multiple-set training demonstrate similar capacity for increasing dynamic strength , MT , and MQ of the knee extensors in elderly women The purpose of this study was to compare single and multiple sets of weight training for strength gains in recreation-ally trained individuals . Sixteen men ( age = 21 ± 2.0 ) were r and omly assigned to 1 set ( S-1 ; n = 8) or 3 set ( S-3 ; n = 8) groups and trained 3 days per week for 12 weeks . One repetition maximum ( 1RM ) was recorded for bench press and leg press at pre- , mid- , and posttest . Subjects trained according to daily undulating periodization ( DUP ) , involving the bench press and leg press exercises between 4RM and 8RM . Training intensity was equated for both groups . Analysis of variance with repeated measures revealed statistically significant differences favoring S-3 in the leg press ( p < 0.05 , effect size [ ES ] = 6.5 ) and differences approaching significance in the bench press ( p = 0.07 , ES = 2.3 ) . The results demonstrate that for recreationally trained individuals using DUP training , 3 sets of training are superior to 1 set for eliciting maximal strength gains A polymorphic variant of the human angiotensin converting enzyme ( ACE ) gene was identified . The ’ D ’ ( rather than ‘ I ’ ) variant was associated with improvements in strength related to physical training . We set out to determine whether the response to different patterns of strength training might also differ . Ninty-nine Caucasian male non-elite athletes were r and omly allocated into one of three groups : 31 non-training/control ( CG : 31 ) , single-set ( SSG : 35 ) and multiple-set ( MSG : 33 ) . SSG and MSG trained three times a week for 6 weeks . Both training groups were underwent a strength-training program with two mesocycles ( 12–15 repetition maximum ( RM ) and 8–12 RM mesocycles ) . One RM loads in half squat and bench press were assessed before training and after the first and second mesocycles . ACE polymorphisms analysed by polymerase chain reaction ( PCR ) methods . Subjects with ACE II genotype in the MST group had improved strength development in 12–15 RM , while SST and MST groups had similar gains in 8–12 RM . Subjects with ACE DD genotype in both the SSG and the MSG had similar benefits from both 12–15 RM and 8–12 RM . Strength gains for subjects with ACE ID genotype in the SSG were similar to MSG gains in response to 8–12 RM loads but not with 12–15 RM loads . Additionally , subjects with DD genotype had superior strength gains in both strength training groups . Tailoring strength training programmes ( single-set vs. multiple set ) according to the athlete ’s ACE genotype may be advantageous We have reported that the acute postexercise increases in muscle protein synthesis rates , with differing nutritional support , are predictive of longer-term training-induced muscle hypertrophy . Here , we aim ed to test whether the same was true with acute exercise-mediated changes in muscle protein synthesis . Eighteen men ( 21 ± 1 yr , 22.6 ± 2.1 kg/m(2 ) ; means ± SE ) had their legs r and omly assigned to two of three training conditions that differed in contraction intensity [ % of maximal strength ( 1 repetition maximum ) ] or contraction volume ( 1 or 3 sets of repetitions ) : 30%-3 , 80%-1 , and 80%-3 . Subjects trained each leg with their assigned regime for a period of 10 wk , 3 times/wk . We made pre- and posttraining measures of strength , muscle volume by magnetic resonance ( MR ) scans , as well as pre- and posttraining biopsies of the vastus lateralis , and a single postexercise ( 1 h ) biopsy following the first bout of exercise , to measure signaling proteins . Training-induced increases in MR-measured muscle volume were significant ( P < 0.01 ) , with no difference between groups : 30%-3 = 6.8 ± 1.8 % , 80%-1 = 3.2 ± 0.8 % , and 80%-3= 7.2 ± 1.9 % , P = 0.18 . Isotonic maximal strength gains were not different between 80%-1 and 80%-3 , but were greater than 30%-3 ( P = 0.04 ) , whereas training-induced isometric strength gains were significant but not different between conditions ( P = 0.92 ) . Biopsies taken 1 h following the initial resistance exercise bout showed increased phosphorylation ( P < 0.05 ) of p70S6 K only in the 80%-1 and 80%-3 conditions . There was no correlation between phosphorylation of any signaling protein and hypertrophy . In accordance with our previous acute measurements of muscle protein synthetic rates a lower load lifted to failure result ed in similar hypertrophy as a heavy load lifted to failure The aim of this study was to compare the effects of low- and high-volume strength training on strength , muscle activation and muscle thickness ( MT ) of the lower- and upper-body , and on muscle quality ( MQ ) of the lower-body in older women . Twenty apparently healthy elderly women were r and omly assigned into two groups : low-volume ( LV , n=11 ) and high-volume ( HV , n=9 ) . The LV group performed one-set of each exercise , while the HV group performed three-sets of each exercise , twice weekly for 13 weeks . MQ was measured by echo intensity obtained by ultrasonography ( MQEI ) , strength per unit of muscle mass ( MQST ) , and strength per unit of muscle mass adjusted with an allometric scale ( MQAS ) . Following training , there was a significant increase ( p≤0.001 ) in knee extension 1-RM ( 31.8±20.5 % for LV and 38.3±7.3 % for HV ) and in elbow flexion 1-RM ( 25.1±9.5 % for LV and 26.6±8.9 % for HV ) and in isometric maximal strength of the lower-body ( p≤0.05 ) and upper-body ( p≤0.001 ) , with no difference between groups . The maximal electromyographic activation for both groups increased significantly ( p≤0.05 ) in the vastus medialis and biceps brachii , with no difference between groups . All MT measurements of the lower- and upper-body increased similarly in both groups ( p≤0.001 ) . Similar improvements were also observed in MQEI ( p≤0.01 ) , MQST , and MQAS ( p≤0.001 ) for both groups . These results demonstrate that low- and high-volume strength training promote similar increases in neuromuscular adaptations of the lower- and upper-body , and in MQ of the lower-body in elderly women Dual-energy X-ray absorptiometry ( DEXA ) is reported to be inferior to computed tomography ( CT ) to measure changes in appendicular soft tissue composition . We compared CT- and DEXA-measured thigh muscle and fat mass to evaluate the r and om and systematic discrepancies between these two methods . Thigh skeletal muscle area ( single-slice CT ) was suboptimally ( r(2 ) = 0.74 , P < 0.0001 ) related to DEXA-measured thigh fat-free mass ( FFM ) . In contrast , thigh muscle and adipose tissue volumes ( multislice CT ) were highly related to DEXA-measured thigh FFM and fat ( both r(2 ) = 0.96 , P < 0.0001 ) . DEXA-measured leg fat was significantly less than multislice-CT-measured leg adipose tissue volume , whereas multislice-CT-measured leg muscle mass was less ( P < 0.0001 ) than DEXA-measured leg FFM . The systematic discrepancies between the two approaches were consistent with the 10 - 15 % nonfat components of adipose tissue . In conclusion , CT and DEXA measures of appendicular soft tissue are highly related . Systematic differences between DEXA and CT likely relate to the underlying principles of the techniques The purpose of this study was to compare serum growth hormone ( GH ) , testosterone ( T ) , cortisol ( C ) , and whole blood lactate ( L ) responses to single set ( 1S ) versus multiple set ( 3S ) heavy-resistance exercise protocol s. Eight recreationally weight-trained men completed two identical resistance exercise workouts ( 1S vs. 3S ) . Blood was obtained preexercise ( PRE ) , immediately postexercise ( OP ) , and 5 min ( 5P ) , 15 min ( 15P ) , 30 min ( 30P ) and 60 min ( 60P ) postexercise and was analyzed for GH , T , C , and L levels . For 1S and 3S , GH , L , and T significantly increased from PRE to OP and remained significantly elevated to 60P , except for 1S . For GH , T , and L , 3S showed significantly greater increases compared to 1S . For C , 3S and 1S were increased significantly from resting at OP , 5P , and 15P ; 3S increased compared to 1S at 5P , 15P and 30P . Higher volumes of total work produce significantly greater increases in circulating anabolic hormones during the recovery phase following exercise Regular performance of resistance exercise induces an increase in skeletal muscle mass , however , the molecular mechanisms underlying this effect are not yet fully understood . The purpose of the present investigation was to examine acute changes in molecular signalling in response to resistance exercise involving different training volumes . Eight untrained male subjects carried out one , three and five sets of 6 repetition maximum ( RM ) in leg press exercise in a r and om order . Muscle biopsies were taken from the vastus lateralis both prior to and 30 min after each training session and the effect on protein signalling was studied . Phosphorylation of Akt was not altered significantly after any of the training protocol s , whereas that of the mammalian target of rapamycin was enhanced to a similar extent by training at all three volumes . The phosphorylation of p70S6 kinase ( p70S6k ) was elevated threefold after 3 × 6 RM and sixfold after 5 × 6 RM , while the phosphorylation of S6 was increased 30- and 55-fold following the 3 × 6 RM and 5 × 6 RM exercises , respectively . Moreover , the level of the phosphorylated form of the gamma isoform of p38 MAPK was enhanced three to fourfold following each of the three protocol s , whereas phosphorylation of ERK1/2 was unchanged 30 min following exercise . These findings indicate that when exercise is performed in a fasted state , the increase in phosphorylation of signalling molecules such as p70S6k and the S6 ribosomal protein in human muscle depends on the exercise volume Abstract Radaelli , R , Fleck , SJ , Leite , T , Leite , RD , Pinto , RS , Fern and es , L , and Simão , R. Dose-response of 1 , 3 , and 5 sets of resistance exercise on strength , local muscular endurance , and hypertrophy . J Strength Cond Res 29(5 ) : 1349–1358 , 2015—The study 's purpose was to compare the response of performing 1 , 3 , and 5 sets on measures of performance and muscle hypertrophy . Forty-eight men , with no weight training experience , were r and omly assigned to one of the 3 training groups , 1 SET , 3 SETS , 5 SETS , or control group . All training groups performed 3 resistance training sessions per week for 6 months . The 5 repetition maximum ( RM ) for all training groups increased in the bench press ( BP ) , front lat pull down ( LPD ) , shoulder press ( SP ) , and leg press ( LP ) ( p ⩽ 0.05 ) , with the 5RM increases in the BP and LPD being significantly greater for 5 SETS compared with the other training groups ( p ⩽ 0.05 ) . Bench press 20RM in the 3-SET and 5-SET groups significantly increased with the increase being significantly greater than the 1-SET group and the 5-SET group increase being significantly greater than the 3-SET group ( p ⩽ 0.05 ) . LP 20RM increased in all training groups ( p ⩽ 0.05 ) , with the 5-SETS group showing a significantly greater increase than the 1-SET group ( p ⩽ 0.05 ) . The 3-SET and 5-SET groups significantly increased elbow flexor muscle thickness ( MT ) with the 5-SET increase being significantly greater than the other 2 training groups ( p ⩽ 0.05 ) . The 5-SET group significantly increased elbow extensor MT with the increase being significantly greater than the other training groups ( p ⩽ 0.05 ) . All training groups decreased percent body fat , increased fat-free mass , and vertical jump ability ( p ⩽ 0.05 ) , with no differences between groups . The results demonstrate a dose-response for the number of sets per exercise and a superiority of multiple sets compared with a single set per exercise for strength gains , muscle endurance , and upper arm muscle hypertrophy This study was design ed to examine the effects of a 12-week resistance training program using single versus multiple sets of a complex versus simple exercise on EMG , strength and regional body composition . Twenty-eight untrained men ( n=15 ) and women ( n=13 ) performed resistance training twice per week . Group 1 ( S-1 , n=9 ) performed one set of a leg press ( LP ) and bicep curl ( BC ) exercise , group 2 ( M-6 , n=9 ) performed six sets of a LP and BC exercise , and group 3 ( C , n=10 ) was the control group . One-repetition maximums ( 1RMs ) and EMG were measured in the LP and BC during pre- , mid- , and post-training . Lean body mass of the legs and arms were measured pre- and post-training by dual energy X-ray absorptiometry . Results of the study indicated that both S-1 and M-6 groups significantly increased percentage strength pre- to post-training in both the LP and BC [ S-1 pre-/post-LP=41.2 (23.7)% , BC=8.5 (6.71)% ; M-6 pre-/post-LP=52.6 (12.6)% , BC=22.8 (15.6)% ; mean ( SD ) ] . However , compared to S-1 , M-6 showed a significantly greater increase in percentage strength in the BC ( P≤0.05 ) from pre- to post-testing . Results also showed that M-6 produced a significant increase in biceps ( single-joint ) muscle EMG values pre- to mid-testing compared to S-1 . There were no significant differences found in lean muscle mass gains for the legs or arms in either training group . The data from this study suggest that multiple sets produce a greater increase in percentage strength gain for a simple exercise . It is possible that some type of neural mechanism is responsible for the observed difference OBJECTIVES To determine whether variation in resistance exercise volume affects muscle function and physical performance response in older adults . DESIGN A r and omized trial with subjects assigned to a single-set ( 1-SET ) or three-set ( 3-SET ) exercise group . SETTING An exercise facility at the University of Queensl and . PARTICIPANTS Twenty-eight community-dwelling men and women aged 65 to 78 . INTERVENTION Progressive resistance training consisting of seven exercises targeting the major muscle groups of the upper and lower body performed on exercise machines twice weekly for 20 weeks at eight-repetition maximum ( RM ) intensity . MEASUREMENTS Muscle function included isotonic muscle strength ( 1-RM ) of the seven exercises , isokinetic and isometric knee extensor strength , and muscle endurance for the chest press and leg press exercises . Physical performance included timed chair rise , usual and fast 6-m walk , 6-m backwards walk , 400-m walk , floor rise to st and ing , and stair climbing ability . In addition , body composition was determined using dual energy x-ray absorptiometry . RESULTS Isotonic muscle strength increased in both exercise groups for all seven exercises ( P<.01 ) , with the gain in the 3-SET group greater ( P<.05 ) for the seated row , triceps extension , and knee extension ( analysis of covariance ) . Similarly , muscle endurance gains were greater for the 3-SET than the 1-SET group ( P<.01 ) , with no significant difference between groups for isokinetic and isometric knee extensor strength . Both groups improved ( P<.05 ) in the chair rise ( 1-SET , 10.1 % ; 3-SET , 13.6 % ) , 6-m backwards walk ( 1-SET , 14.3 % ; 3-SET , 14.8 % ) , 400-m walk ( 1-SET , 3.8 % ; 3-SET , 7.4 % ) , and stair climbing test ( 1-SET , 7.7 % ; 3-SET , 6.4 % ) , with the only difference between groups for the 400-m walk ( P<.05 ) . There was no difference between groups for change in body composition . CONCLUSION Resistance training consisting of only single-set exercises is sufficient to significantly enhance muscle function and physical performance , although muscle strength and endurance gains are greater with higher-volume work . These findings have application in design ing time-efficient exercise regimens to enhance neuromuscular function in older adults Abstract We compared early-phase effects between high- and low-volume moderate-intensity resistance training on lean muscle volume , maximal bilateral leg extension strength , maximal isometric torque , normalized maximal bilateral leg extension strength , normalized maximal isometric torque , and muscle recruitment of the right knee extensors in previously untrained young ( 23.8 ± 3.7 years , range 20–30 years ; n = 16 ) and older women ( 67.6 ± 6.3 years , range 60–78 years ; n = 15 ) . Participants performed either one set or three sets of 10 repetitions for the bilateral leg extension and bilateral leg curl at an intensity of 50–75 % of maximal strength 3 days per week for 10 weeks . Main effects were observed over time for all variables ( P < 0.05 ) with increases ranging from 7.1 % to 27.8 % and effect sizes ( Cohen 's d ) ranging from 0.45 to 1.38 . No interactions between age and training volume over time were observed for any variable ( P > 0.05 ) . Our results provide a novel contribution to the literature demonstrating that additional neuromuscular adaptation during early-phase moderate-intensity resistance training in previously untrained young and older women may not be elicited through higher-volume training when training loads are matched provided that a minimal volume threshold is attained . These findings may have practical applications for the prescription of short- duration resistance training programmes to enhance muscle strength and achieve hypertrophic and non-hypertrophic adaptations in untrained women We aim ed to determine if any mechanistic differences exist between a single set ( 1SET ) and multiple sets ( i.e. 3 sets ; 3SET ) of resistance exercise by utilizing a primed constant infusion of [ring-13C6]phenylalanine to determine myofibrillar protein synthesis ( MPS ) and Western blot analysis to examine anabolic signalling molecule phosphorylation following an acute bout of resistance exercise . Eight resistance-trained men ( 24+/-5 years , BMI = 25+/-4 kg m2 ) were r and omly assigned to perform unilateral leg extension exercise at 70 % concentric one repetition maximum ( 1RM ) until volitional fatigue for 1SET or 3SET . Biopsies from the vastus lateralis were taken in the fasted state ( Fast ) and fed state ( Fed ; 20 g of whey protein isolate ) at rest , 5 h Fed , 24 h Fast and 29 h Fed post-exercise . Fed-state MPS was transiently elevated above rest at 5 h for 1SET ( 2.3-fold ) and returned to resting levels by 29 h post-exercise . However , the exercise induced increase in MPS following 3SET was superior in amplitude and duration as compared to 1SET at both 5 h ( 3.1-fold above rest ) and 29 h post-exercise ( 2.3-fold above rest ) . Phosphorylation of 70 kDa S6 protein kinase ( p70S6 K ) demonstrated a coordinated increase with MPS at 5 h and 29 h post-exercise such that the extent of p70S6 K phosphorylation was related to the MPS response ( r=0.338 , P=0.033 ) . Phosphorylation of 90 kDa ribosomal S6 protein kinase ( p90RSK ) and ribosomal protein S6 ( rps6 ) was similar for 1SET and 3SET at 24 h Fast and 29 h Fed , respectively . However , 3SET induced a greater activation of eukaryotic translation initiation factor 2B ( eIF2B ) and rpS6 at 5 h Fed . These data suggest that 3SET of resistance exercise is more anabolic than 1SET and may lead to greater increases in myofibrillar protein accretion over time The purpose of this study was to compare the effects of single- and multiple-set strength training on hypertrophy and strength gains in untrained men . Twenty-one young men were r and omly assigned to either the 3L-1UB group ( trained 3 sets in leg exercises and 1 set in upper-body exercises ; n = 11 ) , or the 1L-3UB ( trained 1 set in leg exercises and 3 sets in upper-body exercises ; n = 10 ) . Subjects trained 3 days per week for 11 weeks and each workout consisted of 3 leg exercises and 5 upper-body exercises . Training intensity varied between 10 repetition maximum ( RM ) and 7RM . Strength ( 1RM ) was tested in all leg and upper-body exercises and in 2 isokinetic tests before training , and after 3 , 6 , 9 , and 11 weeks of training . Cross sectional area ( CSA ) of thigh muscles and the trapezius muscle and body composition measures were performed before training , and after 5 and 11 weeks of training . The increase in 1RM from week 0 to 11 in the lower-body exercises was significantly higher in the 3L-1UB group than in the 1L-3UB group ( 41 vs. 21 % ; p < 0.001 ) , while no difference existed between groups in upper-body exercises . Peak torque in maximal isokinetic knee-extension and thigh CSA increased more in the 3L- 1UB group than in the 1L-3UB group ( 16 vs. 8 % ; p = 0.03 and 11 vs. 7 % ; p = 0.01 , respectively ) , while there was no significant difference between groups in upper trapezius muscle CSA . The results demonstrate that 3-set strength training is superior to 1-set strength training with regard to strength and muscle mass gains in the leg muscles , while no difference exists between 1- and 3-set training in upper-body muscles in untrained men Abstract Sooneste , H , Tanimoto , M , Kakigi , R , Saga , N , and Katamoto , S. Effects of training volume on strength and hypertrophy in young men . J Strength Cond Res 27(1 ) : 8–13 , 2013—Knowledge of the effects of training volume on upper limb muscular strength and hypertrophy is rather limited . In this study , both arms of the same subject were trained in a crossover-like design with different training volumes ( 1 or 3 sets ) to eliminate the effects of genetic variation and other individual differences . The purpose of this study was to investigate the effects of training volume on muscular strength and hypertrophy in sedentary , untrained young Japanese men . Eight subjects ( age , 25.0 ± 2.1 years ; body mass , 64.2 ± 7.9 kg ; height , 171.7 ± 5.1 cm ) were recruited . The subjects trained their elbow flexor muscles twice per week for 12 consecutive weeks using a seated dumbbell preacher curl . The arms were r and omly assigned to training with 1 or 3 sets . The training weight was set at 80 % of 1 repetition maximum for all sets . The 3-set protocol increased cross-sectional area significantly more than did 1 set ( 1 set , 8.0 ± 3.7 % ; 3 sets , 13.3 ± 3.6 % , p < 0.05 ) . Furthermore , gains in strength with the 3-set protocol tended to be greater than those with 1 set ( 1 set , 20.4 ± 21.6 % ; 3 sets , 31.7 ± 22.0 % , p = 0.076 ) . Based on the results , the authors recommend 3 sets for sedentary untrained individuals . However , this population should incorporate light training days of 1 set into their training program to prevent overtraining and ensure adherence . The findings are relevant for the sedentary , untrained young male population and must be interpreted within the context of this study |
12,704 | 27,832,642 | Conclusions : The counts of TMPs , PMPs , MMPs and EMPs elevated in patients with T2DM .
And cell-derived MPs may play a role in the pathogenesis of T2DM | Background / Aims : The aim of this study was to assess the association between circulating cell-derived microparticles ( MPs ) and type 2 diabetes mellitus ( T2DM ) . | Diabetes is a risk factor for the development of atherothrombosis and venous thromboembolism ( VTE ) . We investigated whether plasma from patients with type 2 diabetes has an imbalance of pro- versus anti-coagulation result ing in hypercoagulability despite normal conventional coagulation tests . We analyzed blood sample s from 60 patients with type 2 diabetes and 60 gender- and age-matched healthy subjects ( controls ) for the levels of pro- and anti-coagulant factors , for thrombin generation and for the numbers of cell-derived circulating microparticles bearing such pro-coagulant triggers as tissue factor and negatively charged phospholipids . The levels of pro- or anti-coagulants as measured with conventional coagulation tests or single factor measurements were similar to those of the control population . In contrast , the median ( range ) of the height of the thrombin peak ( taken as an index of thrombin generation ) was higher in patients [ 205 nM ( 126–352 ) ] than controls [ 151 nM ( 41−289 ) ] , P < 0.001 . The median numbers of circulating microparticles were higher for patients [ 5,041/μl ( 1,821–13,132 ) ] than for controls [ 1,753/μl ( 554–13,308 ) ] , P < 0.001 and their values were correlated with the height of the thrombin peak ( ρ = 0.66 , P < 0.001 ) . In conclusion , plasma from patients with type 2 diabetes possesses an imbalance of pro- versus anti-coagulation result ing in hypercoagulability that can be detected by thrombin generation tests , but not by the measurement of the single pro- or anti-coagulant factors . This hypercoagulability is associated with increased numbers of circulating microparticles bearing endogenous pro-coagulant triggers . These findings might explain the relatively high risk of atherothrombosis and VTE described in these patients Abstract Background : Diabetic patients also show hypercoagulability and platelet hyperaggregability , with increased levels of platelet activation-markers such as P-selectin ( CD62P ) and platelet-derived microparticles . We investigated the effects of losartan and simvastatin on circulating levels of platelet activation markers , microparticles , soluble selectins , and soluble cell adhesion molecules in hypertensive and hyperlipidemic patients with or without Type 2 diabetes . Methods : The subjects included 25 normotensive healthy controls and 41 hypertensive patients . The 41 hypertensive patients were divided into three groups : group A had hypertension and hyperlipidemia ( n = 11 ) , group B had hypertension and Type 2 diabetes ( n = 14 ) , and group C had hypertension , hyperlipidemia , and diabetes ( n = 16 ) . Losartan was administered to all of the patients at a dose of 50 mg/day for 24 weeks . In addition , simvastatin was administered to the hyperlipidemic patients at a dose of 10 mg/day for 24 weeks . Results : There were significant differences in the levels of CD62P , CD63 , PAC-1 , platelet microparticles , endothelial microparticles , sE-selectin , and sVCAM-1 between the hypertensive patients and healthy controls . These markers were all significantly increased in hypertensive and hyperlipidemic patients with Type 2 diabetes . In hypertensive patients with diabetes , CD62P , CD63 , PAC-1 , platelet and endothelial microparticles , and soluble adhesion markers were all decreased by losartan monotherapy . The decrease of each marker in hypertensive and hyperlipidemic patients given combined therapy with losartan plus simvastatin was greater among those with than without Type 2 diabetes . Low-density lipoprotein was decreased significantly by simvastatin and was correlated with CD62P or platelet microparticles in all of the patients . Conclusion : Administration of losartan plus simvastatin to hypertensive and hyperlipidemic patients with Type 2 diabetes may prevent the development of cardiovascular complications caused by activated platelets and microparticles via another mechanism in addition to reduction of the blood pressure or lipid levels This study investigated the impact of either type 2 diabetes or obesity , separately or in combination , on the absolute amounts of microparticles ( MP ) and the pathways by which these are associated with either condition . The concentrations of circulating MP derived from platelets ( PMP ) , leukocytes ( LMP ) and monocytes ( MMP ) , together with their specific activation markers , were compared in 30 subjects who were characterised across 4 cohorts as obese or type 2 diabetes . The subjects with type 2 diabetes had elevated concentrations of total PMP ( P = 0.003 ) , and PMP that were fibrinogen-positive ( P = 0.04 ) , tissue factor-positive ( P < 0.001 ) , P-selectin-positive ( P = 0.03 ) . Type 2 diabetes did not alter either total or activated LMP or MMP . Obesity per se did not impact on any MP measurement . Elevated concentrations of plasma PMP occurred in subjects with type 2 diabetes , whether they were obese or non-obese . In contrast , obesity in the absence of type 2 diabetes had no effect . The increased concentrations of specific marker-positive PMP in the subjects with diabetes might reflect potential pathways by which PMP may contribute to the pathogenesis of atherosclerosis and type 2 diabetes We investigated the effects of probucol and ticlopidine on circulating levels of platelet activation markers , microparticles , soluble selectins , and malondialdehyde-low density lipoprotein ( MDA-LDL ) in hyperlipidemic patients with or without type 2 diabetes . There were significant differences in the levels of CD62P , PAC-1 , annexin V , PDMP , MDMP , sP-selectin , sE-selectin and MDA-LDL between the hyperlipidemic patients and the controls . In particular , these markers were significantly increased in hyperlipidemic patients who had type 2 diabetes . In the hyperlipidemic patients with diabetes , MDA-LDL was decreased by both monotherapy with probucol and combination therapy ( probucol and ticlopidine ) . In these patients , CD62P , PAC-1 , annexin V , MDMP , PDMP , sP-selectin , and sE-selectin were also significantly decreased after treatment . The decreases of CD62P , PAC-1 , annexin V , PDMP and sP-selectin were greater combination therapy than with monotherapy . These findings suggest that administration of probucol and ticlopidine to hyperlipidemic patients with type 2 diabetes may help to prevent the development of cardiovascular complications caused by modified LDL , selectins , or activated platelets and monocytes We compared the levels of microparticles , platelet activation markers , soluble cell adhesion molecules , and soluble selectins between hypertensive patients with and without type 2 diabetes and control subjects . Binding of anti-glycoprotein IIb/IIIa and anti-glycoprotein Ib monoclonal antibodies to platelets did not differ significantly between the hypertensive patients and controls , but platelet expression of activation markers ( CD62P , CD63 , PAC-1 , and annexin V ) was higher in the hypertensive patients . Platelet-derived microparticle ( PDMP ) and monocyte-derived microparticle ( MDMP ) levels were significantly higher in the hypertensive patients than in the controls . Soluble ICAM-1 , VCAM-1 , P-selectin , and E-selectin levels were also higher in the hypertensive patients , and they were significantly higher in the hypertensive patients with diabetes . After treatment with efonidipine , the levels of PDMPs , CD62P- , CD63- , PAC-1- , and annexin V-positive platelets , sICAM-1 , sVCAM-1 , sP-selectin , and sE-selectin all decreased significantly . The MDMP levels decreased , and the decrease was significant in the hypertensive patients with diabetes . These findings suggest that administration of efonidipine to hypertension patients with diabetes may prevent the development of cardiovascular complications caused by cell adhesion molecules or activated platelets and monocytes AIM The aim of this study was to evaluate the significance of endothelial cell-derived microparticles ( EDMP ) , angiopoietin-2 ( Ang-2 ) and adiponectin in hyperlipidemic patients with and without type 2 diabetes mellitus , and to compare the two for the effects of eicosapentaenoic acid ( EPA ) on these markers . METHODS One hundred and twenty-six hyperlipidemic patients with and without type 2 diabetes mellitus received EPA 1,800 mg daily , and 50 of the patients were non-diabetic . RESULTS EDMP and Ang-2 levels prior to treatment were higher in diabetic patients than in non-diabetic patients , whereas adiponectin levels were lower in diabetics . When diabetic patients were classified into two groups on the basis of Ang-2 levels , the levels of all markers remained unchanged in those without a high Ang-2 level after EPA treatment . In contrast , all markers except for adiponectin were decreased significantly in diabetic patients with high Ang-2 levels after 6 months of EPA treatment . These diabetic patients with high Ang-2 levels displayed a more significant increase in adiponectin levels after EPA treatment than those who did not . CONCLUSION These results suggest that EPA possesses an adiponectin-dependent anti-atherosclerotic effect and may be beneficial for the prevention of vascular complications in diabetic patients with high Ang-2 levels Monocyte-derived microparticles play an important role in the pathogenesis of diabetic vasculopathy , and angiotensin II receptor blocker and statin have been shown to have a beneficial effect on the angiopathies of hypertension and hyperglycemia in patients with type 2 diabetes mellitus . However , the interaction between angiotensin II receptor blocker and statin , and monocyte-derived microparticles in atherosclerosis is poorly understood . The effects of losartan and simvastatin on circulating concentrations of monocyte-derived microparticles , chemokines , and soluble adhesion markers were studied in hypertensive patients with or without type 2 diabetes mellitus . Monocyte-derived microparticles were measured by flow cytometry , and levels of serum chemokines ( MCP-1 and RANTES ) and soluble adhesion markers ( sP-selectin and sVCAM-1 ) were measured by enzyme-linked immunosorbent assay . Losartan decreased both the systolic and diastolic blood pressure in hypertensive patients with and without type 2 diabetes mellitus . The concentrations of monocyte-derived microparticles , chemokines , and soluble adhesion molecules were higher in hypertensive patients who also had type 2 diabetes mellitus vs. those who did not . The administration of angiotensin II receptor blocker decreased the circulating concentration of all these markers . In addition , all markers were decreased by combination therapy , and monocyte-derived microparticles were decreased more with combination therapy with losartan and simvastatin than monotherapy with losartan . The administration of angiotensin II receptor blocker inhibited monocyte-derived microparticle generation and suggests that angiotensin II is intimately related to vascular changes that occur in type 2 diabetes mellitus . Combination therapy with a statin and angiotensin II receptor blocker might be valuable as anti-atherosclerotic therapy in patients with type 2 diabetes mellitus and nephropathy Platelet-derived microparticles , activated platelets , and monocyte-derived microparticles were measured in 73 patients with diabetes mellitus . A comparative study of these parameters was performed before and after administration of ticlopidine . The number of platelet-derived microparticles and activated platelets was increased significantly in diabetic patients . Monocyte-derived microparticles were also increased significantly . After administration of ticlopidine , platelet-derived microparticles and activated platelets corrected positively , not only CD62P- and CD63-positive platelets , but also platelet-derived microparticles and monocyte-derived microparticles showed a significant decrease . These data suggest that in patients with diabetes , platelet-derived microparticles and activated platelets stimulate the activation of monocytes and promote the production of monocyte-derived microparticles , and that ticlopidine is useful for hypercoagulabillity in diabetic patients * Laboratory for Experimental Internal Medicine , Academic Medical Center , University of Amsterdam , Amsterdam ; Department of InternalMedicine , Slotervaart Hospital , Amsterdam ; Laboratory of Haematology and Clinical Chemistry , Onze Lieve Vrouwe Gasthuis , Amsterdam ; and § Department of Internal Medicine and Cardiovascular Research Institute Maastricht , Academic Hospital and University of Maastricht , Maastricht , The Netherl and sTo cite this article : Sommeijer DW , Joop K , Leyte A , Reitsma PH , ten Cate H. Pravastatin reduces fibrinogen receptor gpIIIa on platelet-derivedmicroparticles in patients with type 2 diabetes . J Thromb Haemost 2005 ; 3 : 1168–71.See also Davi ` G , Ferroni P. Microparticles in type 2 diabetes mellitus . This issue , pp 1166–7 The effects of treatment with pitavastatin on inflammatory and platelet activation markers and adiponectin in 117 patients with hyperlipidemia were investigated to determine whether pitavastatin may prevent the progression of atherosclerotic changes in hyperlipidemic patients . Adiponectin levels prior to pitavastatin treatment in hyperlipidemic patients with and without diabetes were lower than levels in normolipidemic controls . Both total cholesterol and the low-density lipoprotein cholesterol decreased significantly after pitavastatin administration . Additionally , hyperlipidemic patients with or without type 2 diabetes exhibited a significant increase in adiponectin levels 6 months after pitavastatin treatment ( diabetes : 3.52 ± 0.80 vs. 4.52 ± 0.71 µg/ml , p < 0.001 ; no diabetes : 3.48 ± 0.71 vs. 4.23 ± 0.82 µg/ml , p < 0.05 ) . However , high-sensitivity C-reactive protein , platelet-derived microparticle and soluble P-selectin did not exhibit any differences before or after pitavastatin administration . Levels of adiponectin significantly increased after pitavastatin administration in the group of lower soluble P-selectin ( soluble P-selectin before pitavastatin treatment < 200 ng/ml ) . These results suggest that pitavastatin possesses an adiponectin-increasing effect in patients with hyperlipidemia and this effect is influenced by intensive platelet activation Angiotensin II receptor blockade has been shown to have a beneficial effect on the angiopathies of hypertension and hyperglycemia in patients with type 2 diabetes . However , the effect of angiotensin II receptor blockade on monocyte and endothelial cell adhesion markers in type 2 diabetes is poorly understood . We investigated the effects of valsartan on these markers in 53 hypertensive patients with and without type 2 diabetes mellitus . Levels of monocyte activation markers ( soluble CD14 : 2.1+/-0.9 vs. 3.3+/-1.4 microg/ml , p<0.01 ; monocyte chemotactic peptide : 392+/-94 vs. 489+/-114 pg/ml , p<0.05 ; and monocyte-derived microparticles : 264+/-98 vs. 511+/-128/microL , p<0.01 ) and endothelial cell activation markers ( soluble E-selectin : 41+/-11 vs. 61+/-20 ng/ml , p<0.001 ; and soluble vascular cell adhesion molecule-1 : 478+/-82 vs. 584+/-101 ng/ml , p<0.01 ) were significantly increased in hypertensive patients with type 2 diabetes compared to normotensive controls . In addition , the concentrations of adiponectin were significantly decreased in patients with type 2 diabetes ( 8.1+/-3.1 vs. 5.2+/-2.5 microg/ml , p<0.01 ) . Regardless of the presence of diabetic complications , both systolic and diastolic blood pressures significantly decreased after valsartan administration ( valsartan 80 mg/day for 8 weeks ) . Monocyte and endothelial cell activation markers were decreased significantly in patients with type 2 diabetes after valsartan treatment , but not in non-type 2 diabetic patients . In addition , valsartan alleviated hypoadiponectinemia in hypertensive patients with diabetes ( before vs. after : 5.2+/-2.5 vs. 7.6+/-2.7 microg/ml , p<0.001 ) but did not increase adiponectin levels in the non-diabetic hypertensive group , for which the average adiponectin level was normal prior to treatment . These results suggest angiotensin II receptor blockade ( valsartan ) may be beneficial as an anti-atherosclerotic therapy in patients with type 2 diabetes in addition to its anti-hypertensive action |
12,705 | 28,873,092 | We also found that invitation letters alone ( or with a follow up phone contact ) , making an appointment , and sending reminders to patients who are due or overdue for screening had a significant effect on improving participation and CCS rates in population s at risk .
Our findings supports the implementation of theory-based cervical cancer educational interventions to increase women 's participation in cervical cancer screening programs , particularly when targeting communities with low literacy levels . | BACKGROUND Although cervical cancer is largely preventable through screening , detection and treatment of precancerous abnormalities , it remains one of the top causes of cancer-related morbidity and mortality globally .
OBJECTIVES The objective of this systematic review is to underst and the evidence of the effect of cervical cancer education compared to control conditions on cervical cancer screening rates in eligible women population at risk of cervical cancer .
We also sought to underst and the effect of provider recommendations for screening to eligible women on cervical cancer screening ( CCS ) rates compared to control conditions in eligible women population at risk of cervical cancer . | Our objective was to assess the efficiency of a home-visit invitation aim ed to increase uptake of cervical cancer screening in women between 35 and 60 years of age . From May , 2006 , we conducted a quasi-r and omized trial to determine if an in-home education and invitation intervention would increase uptake of cervical cancer screening . We r and omly recruited 304 women from the Samliem inner-city community , Khon Kaen , Northeast Thail and , and assigned participants to either the intervention or control zone . Baseline screening coverage interviews were then performed : 58 of 158 women in the intervention zone and 46 of 146 in the control zone were excluded from the study because of having had a Pap smear within 5 years , but these were included in the final analysis . First , 100 women in the intervention group were visited in their homes by one of the research ers , who provided culturally-sensitive health education that emphasized the need for screening . Four months later , post-intervention , screening-coverage interviews were again performed in both groups , in combination with the same health education for 100 women in the control group for a comparison . There was no difference in the baseline Pap smear screening-coverage rate in the intervention vs. control zones ( 36.7 vs. 31.5 % , p=0.339 ) . One hundred women in the intervention group completed the intervention interviews and after four months , 100 women in the intervention group and 100 in the control group also completed the post-intervention interviews . The increased screening-coverage rate in the intervention zone was similar to that of the control zone ( 43.6 vs. 34.9 % , p=0.119 ) ; however , there was a borderline significant increase in the intervention zone compared with baseline ( 36.7 to 43.6 % , p=0.070 ) . Therefore , home visit education and invitation intervention produced only a nominal effect on increasing Pap smear coverage within a 4-month study period BACKGROUND Few Iranian women take the Papanicolaou test despite its important role in preventing cervical cancer . This study aim ed to determine the effectiveness of an educational intervention based on the protection motivation theory ( PMT ) variables and implementation intentions in the first and second Pap test practice among Iranian women . MATERIAL S AND METHODS In this quasi-r and omized controlled trial , 200 women who were referred to 30 primary health care clinics in Tehran were r and omly selected . PMT variables and Pap test practice were measured at baseline and again after 3 and 15 months . The 4-week educational intervention program was conducted for the intervention group . RESULTS Following the intervention , the mean scores of self-efficacy , perceived vulnerability , and behavior intention variables were significantly higher in the intervention group when compared to the control group ( p<0.05 ) . No significant differences were found in the perceived severity , response efficacy , response cost , and fear between the two groups following the intervention . Higher percent of women in the intervention group had obtained first and second Pap test compared to the controls . CONCLUSIONS The PMT and implementation intentions provide a suitable theory-based framework for developing educational interventions regarding Pap test practice in Iran BACKGROUND The North Carolina Native American Cervical Cancer Prevention Project was a 5-year , National Cancer Institute-funded trial of health education design ed to increase screening for cervical cancer among Native-American women in North Carolina . PURPOSE This study was conducted to evaluate the effectiveness of this education program in the Eastern-B and Cherokee target population . METHODS Cherokee tribal l and s were mapped and all households ( N = 2223 ) were listed to ensure maximum coverage of the eligible population ( women , aged 18 years and older , who were enrolled tribal members ) . Eligible women were identified by the use of a brief question naire administered to an adult member of the household . Of the 1279 households with eligible women , 1020 ( 79.8 % ) agreed to participate . The intervention was an individualized health education program delivered by female Cherokee lay health educators . The participants were r and omly assigned to receive or not to receive the intervention ( i.e. , to program and control groups , respectively ) by use of the Solomon Four-Group design . Data were collected in face-to-face interviews conducted in the participant 's home . Of the 996 women who were ultimately enrolled , 540 were r and omly assigned to receive a pretest ( preintervention ) interview that involved administration of a 96-item question naire design ed to collect data on knowledge , intentions , and behaviors related to cervical cancer ; of these 540 women , 263 were r and omly assigned to receive the education program . The remaining 456 women did not receive the pretest , but 218 were r and omly assigned to receive the education program . Six months after receiving the education program , the women in all four groups were administered a post-test that was identical to the pretest . Logistic regression was used to assess the effects of the pretest and the educational program . All P values result ed from two-sided statistical tests . RESULTS Eight hundred and fifteen ( 81.8 % ) of the 996 participants completed the post-test interview . The remaining 181 women who were lost to follow-up were evenly distributed among the four study groups . At the post-test , 282 ( 73.2 % ) of the 385 women who received the education program reported having had a Pap smear following the intervention , compared with 275 ( 64 % ) of the 430 control subjects . Women who received the education program were more likely to answer all knowledge items correctly on the post-test ( odds ratio [ OR ] = 2.18 , 95 % confidence interval [ CI ] = 1.08 - 4.39 ) and to report having obtained a Pap smear in the past year ( OR = 2.06 , 95 % CI = 1.14 - 3.72 ) than women in the control groups . CONCLUSION Women who received the education program exhibited a greater knowledge about cervical cancer prevention and were more likely to have reported having had a Pap smear within the past year than women who did not receive the program Objective Human papillomavirus ( HPV ) self-sampling ( Self-HPV ) may be used as a primary cervical cancer screening method in a low re source setting . Our aim was to evaluate whether an educational intervention would improve women 's knowledge and confidence in the Self-HPV method . Method Women aged between 25 and 65 years old , eligible for cervical cancer screening , were r and omly chosen to receive st and ard information ( control group ) or st and ard information followed by educational intervention ( interventional group ) . St and ard information included explanations about what the test detects ( HPV ) , the link between HPV and cervical cancer and how to perform HPV self-sampling . The educational intervention consisted of a culturally tailored video about HPV , cervical cancer , Self-HPV and its relevancy as a screening test . All participants completed a question naire that assessed sociodemographic data , women 's knowledge about cervical cancer and acceptability of Self-HPV . Results A total of 302 women were enrolled in 4 health care centers in Yaoundé and the surrounding countryside . 301 women ( 149 in the “ control group ” and 152 in the “ intervention group ” ) completed the full process and were included into the analysis . Participants who received the educational intervention had a significantly higher knowledge about HPV and cervical cancer than the control group ( p<0.05 ) , but no significant difference on Self-HPV acceptability and confidence in the method was noticed between the two groups . Conclusion Educational intervention promotes an increase in knowledge about HPV and cervical cancer . Further investigation should be conducted to determine if this intervention can be sustained beyond the short term and influences screening behavior . Trials Registration International St and ard R and omised Controlled Trial Number ( IS RCT N ) Register IS RCT Background Cervical cancer is the second most common form of cancer observed among women in Turkey . The participation of women in cervical cancer screening programs is strongly affected by Turkish attitudes , beliefs , and sociocultural structure . Aim This study was conducted to assess the effectiveness of health education that aim ed to raise awareness about Papanicolaou testing and to emphasize the importance of the early diagnosis of cervical cancer . Material s and Methods The study was conducted as a prospect i ve , r and omized , controlled trial and was carried out in 148 women . Seventy-five women in the control group were asked to fill out question naire forms . A 45-minute conference-style training was given to 73 women in the study group , and all of the subjects were asked to fill out the forms after the training . The sociodemographic characteristics of the 2 groups and the mean “ Health Belief Model Scale for Cervical Cancer and Pap Smear Test ” scores of the 2 groups were statistically analyzed by Statistical Package of Social Sciences ( SPSS ) , version 15 . Results There was no statistically significant difference noticed between the sociodemographic characteristics of the 2 groups ( P > 0.05 ) . The difference in test scores , which represented knowledge about cervical cancer and Papanicolaou testing , was statistically significant between the control group and the study group ( t = 10.122 , P < 0.05 ) . In the Health Belief Model Scale for Cervical Cancer and Pap Smear Test , there were statistically significant differences in the following measures : lower levels of susceptibility to cervical cancer score ( t = −2.035 , P < 0.05 ) , lower levels of perceived benefit from a Papanicolaou test score ( t = 3.278 , P < 0.05 ) and lower levels of perceived barriers to Papanicolaou test score ( t = −3.182 , P < 0.05 ) . Conclusion Nurses should be involved in educating women about cervical cancer and Papanicolaou testing . By doing so , they can change the attitudes , knowledge , and beliefs of the women Background Cervical cancer is a disease of public health importance affecting many women and contributing to avoidably high levels of cancer deaths in Nigeria . In spite of the relative ease of prevention , the incidence is on the increase . This study aim ed to determine the effect of health education on the awareness , knowledge and perception of cervical cancer and screening among women in rural Nigerian communities . Methods The study design was quasi-experimental . The study was carried out among adult women in Odogbolu ( intervention ) and Ikenne ( control ) local government areas ( LGA ) of Ogun state . Three hundred and fifty ( 350 ) women were selected per group by multistage r and om sampling technique . Data was collected by semi structured interviews with the aid of question naire . The intervention consisted of structured health education based on a movie . Result The intervention raised the level of awareness of cervical cancer and screening to 100 % ( p < 0.0001 ) . The proportion of women with very good knowledge of cervical cancer and screening rose from 2 % to 70.5 % ( χ2 = 503.7 , p < 0.0001 ) while the proportion of those with good perception rose from 5.1 % to 95.1 % ( p < 0.0001 ) . The mean knowledge and mean perception scores were also increased ( p < 0.0001 ) . There was increase in the proportion of women who had undertaken cervical screening from 4.3 % to 8.3 % ( p = 0.038 ) . The major reason stated by the women for not having had cervical screening done was lack of awareness about cervical cancer and screening . There was statistically significant difference between the intervention and control groups concerning their knowledge attitude and practice towards cervical and screening ( p < 0.05 ) after the intervention . Conclusion Multiple media health education based on a movie is effective in creating awareness for and improving the knowledge and perception of adult women about cervical cancer and screening . It also improves the uptake of cervical cancer screening . The creation of awareness is very crucial to the success of a cervical cancer prevention programme Background Countries must decide whether or not to replace primary cytology-based screening with primary human papillomavirus (HPV)-based screening . We aim ed to assess how primary screening for an HPV infection , a sexually transmitted infection ( STI ) , and the type of information included in the invitation letter , will affect screening intention . Methods We r and omized a representative sample of Norwegian women to one of three invitation letters : 1 ) Pap smear , 2 ) HPV testing or 3 ) HPV testing with additional information about the nature of the infection . Intention to participate , anxiety level and whether women intend to follow-up abnormal results were measured between groups using chi-squared and nonparametric Kruskal-Wallis tests . Determinants of intention were explored using logistic regression . Results Responses from 3540 women were representative of the Norwegian population with respect to age , civil status and geographic location . No significant difference across invitation letters was found in women ’s stated intention to participate ( range : 91.8 - 92.3 % ) , anxiety ( 39 - 42 % were either quite or very worried ) or to follow-up after an abnormal result ( range : 97.1 - 97.6 % ) . Strength of intention to participate was only marginally lower for HPV-based invitation letters , albeit significant ( p-value = 0.008 ) , when measured on a scale . Only 36–40 % of respondents given the HPV invitations correctly understood that they likely had an STI . Conclusions We found that switching to primary HPV screening , independent of additional information about HPV infections , is not likely to reduce screening participation rates or increase anxiety ; however , women lacked the ability to interpret the meaning of an HPV-test result BACKGROUND Our aim was to determine if cervical cancer screening uptake would increase among under-screened women living in rural Ontario , Canada , if at-home self-collected sampling for human papillomavirus ( HPV ) testing was offered as a primary cervical cancer screening modality , compared to invited papanicolaou ( Pap ) testing or routine opportunistic screening . METHODS Women 30 - 70 years of age who were overdue for cervical cancer screening were r and omized to receive ( 1 ) an at-home self-collected HPV kit , ( 2 ) a reminder invitation for Pap testing , or ( 3 ) st and ard of care opportunistic screening . The first two arms were also asked demographic and screening history questions . Women r and omized to arm 1 were asked about acceptability . RESULTS In total , 818 eligible women were identified in a small rural community in Southwestern Ontario : 335 received a self-collected HPV testing kit , 331 received a reminder letter , and 152 received st and ard of care . In the HPV self- collection arm , 21 % ( 70/335 ) returned the sample and question naire and 11 % ( 37/335 ) opted to undergo Pap testing . In total , 32 % from the HPV self- collection arm , 15 % ( 51/331 ) from the Pap invitation arm , and 8.5 % ( 13/152 ) with st and ard of care were screened . Women receiving the self-collected HPV kit were 3.7 ( 95 % confidence interval 2.2 - 6.4 ) times more likely to undergo screening compared to the st and ard of care arm . In the HPV self-sampling arm , 80 % ( 56/70 ) said they would be very likely to choose self-collected sampling in the future . CONCLUSIONS Providing self-collected sampling for HPV testing was more effective than sending reminder letters to increase screening coverage in under-screened women Objective : Despite the proven survival benefits associated with cervical cancer screening , use of the Pap test continues to be suboptimal in some population subgroups , such as among Korean-American women who face considerable barriers to screening . Therefore , we evaluated a multifaceted intervention that combined psychoeducational counseling with patient navigation to address both psychosocial and access barriers to screening . Method : Women ( n = 102 ) were recruited from Korean community centers and assigned to the intervention or control condition . The intervention group received cervical cancer education and patient navigation delivered by bilingual Korean health educators . The control group received general health education , including information about cervical cancer and screening . Assessment s were obtained at baseline and postintervention . Screening behavior was assessed at 6 months postintervention . Results : At baseline , 17 % of participants reported having had a Pap test in the previous year . At 6 months postintervention , 83 % of women in the intervention group had obtained screening compared with 22 % in the control group , χ2(1 ) = 41.22 , P < 0.001 . Multivariate logistic regression analyses indicated that participation in the intervention was associated with screening ( P < 0.001 ) . Fewer psychosocial barriers ( e.g. , discomfort at having a stranger perform Pap ) and greater self-efficacy were also associated with screening ( P < 0.05 ) . Conclusion : A combined modality intervention that delivers education with patient navigation training and assistance result ed in increased screening rates . Multifaceted approaches may be effective in reducing the psychosocial , access , and language barriers that contribute to cancer health disparities in underserved population s. ( Cancer Epidemiol Biomarkers Prev 2007;16(6):1–5 Although age-adjusted mortality rates from cancer among Native-Americans are generally lower than for the US population as a whole , cervical cancer mortality rates are higher . This report presents results from a National Cancer Institute-funded health education program conducted among the Lumbee tribe in North Carolina that was design ed to increase the proportion of women , age 18 and older , who receive Pap smears to screen for cervical cancer . The Solomon Four Group research design was used for this project . Participants were selected at r and om from the enrollment records of the Lumbee tribe and data collection was carried out during face-to-face interviews . The health education program was provided one-on-one in women 's homes by a trained lay health educator and included verbal , print and videotape information . A total of 979 women were enrolled in the study , and 125 were lost to follow-up between the pre-test and post-test . Women who received the education program were found to be more likely to have knowledge of the Pap smear and to report a Pap smear in the past year at the post-test than those in the control group , regardless of whether they received the pre-test interview , P < 0.05 . Women most likely to respond to the education program were also likely to have reported that they receive an annual physical examination . Women with better knowledge of the Pap smear tended to have more education , higher income and greater identification with Native-American culture than those with less knowledge . We conclude that the health education program was associated with greater knowledge about cervical cancer prevention and higher proportions of Lumbee women obtaining Pap smears in the past year A r and omized trial was conducted to evaluate the combined impact of a physician reminder letter and a telephone contact on the use of Pap tests and mammograms in a low-income managed care program . Women 40 to 79 years of age who were past due for cancer screening were r and omly assigned to an intervention or control group . Medical cl aims were review ed after 6 months to determine intervention effectiveness . The odds of receiving all needed cancer screening tests during follow-up were four times higher in the intervention group . Women who reported having to take time off from work to see a doctor had lower odds of getting screened Background In the United States certain minority groups , such as racial/ethnic immigrant women , are less likely than non-Hispanic White women to be screened for cervical cancer . Barriers to such care include health insurance , cost , knowledge , attitudes , health literacy , and cultural norms and practice s. Among the most promising approaches to increase screening in these groups are patient navigators that can link women to sources of appropriate care . Another recent promising approach is using human papilloma virus ( HPV ) self-sampling . In this manuscript , we describe our National Cancer Institute-sponsored study testing such approaches among immigrant minority women . Design The South Florida Center for the Reduction of Cancer Health Disparities ( SUCCESS ) is conducting a three-arm r and omized trial among Hispanic , Haitian , and African American women in Miami-Dade County . Community health workers ( CHW ) based in each of three communities are recruiting 200 women at each site ( 600 total ) . Eligibility criteria include women aged 30–65 years who have not had a Pap smear test in the last 3 years . Prior to r and omization , all women undergo a st and ardized structured interview . Women r and omized to public health outreach , Group 1 , receive culturally tailored educational material s. Women in Group 2 receive an individualized comprehensive cervical cancer CHW-led education session followed by patient navigation to obtain the Pap smear test at community-based facilities . Women in Group 3 have the option of navigation to a Pap smear test or performing HPV self-sampling . The primary outcome is self-report of completed screening through a Pap smear test or HPV self-sampling within 6 months after enrollment . Discussion SUCCESS is one of the first trials testing HPV self-sampling as a screening strategy among underserved minority women . If successful , HPV self-sampling may be an important option in community outreach programs aim ed at reducing disparities in cervical cancer . Trial registration Clinical Trials.gov # NCT02121548 , registered April 21 , 2014 Background : Attendance in screening is an important determinant of cervical cancer . Previous experience on high-risk human papillomavirus ( hrHPV ) DNA testing on patient-obtained sample s suggests a good effect among nonattendees of screening . We assessed the effects of self-sampling on attendance in the Finnish screening program . Methods : Nonattendees after the primary invitation in one municipality ( Espoo ) were r and omized to receive either a self-sampling kit ( 2,397 women ) or an extra invitation ( 6,302 women ) . One fourth ( 1,315 women ) of reminder letter arm nonattendees also received a self-sampling kit as a third intervention . Main outcomes were increases in screening attendance and coverage . Results : The adjusted relative risk for participation by self-sampling as a second intervention in comparison to a reminder letter arm was 1.21 ( 95 % CI : 1.13–1.30 ) . Total attendance increased from 65 % to 76 % by self-sampling and from 65 % to 74 % with a reminder letter . Combining the interventions ( reminder letter and then self-sampling ) increased total attendance from 63 % to 78 % . One fifth of the participants in all three groups increased screening coverage ( previous Pap smear ≥5 years ago or never ) . Self-obtained sample s were more often HPV positive than provider-obtained ones ( participants after primary invitation and reminder letter ) , 12 % to 13 % versus 7 % . Conclusions : Self-sampling is a feasible option in enhancing the attendance at organized screening , particularly as an addition to a reminder letter . Impact : If self-sampling is used as a third intervention after two written invitations , the overall attendance in Finl and could most likely reach the desired 80 % to 85 % . Cancer Epidemiol Biomarkers Prev ; 20(9 ) ; 1960–9 . © 2011 AACR Background In the US , Hispanic women have a higher incidence of , and mortality from , cervical cancer than non-Hispanic white women . The reason for this disparity may be attributable to both low rates of screening and poor adherence to recommended diagnostic follow-up after an abnormal Pap test . The ' Cervical Cancer Screening and Adherence to Follow-up Among Hispanic Women ' study is a collaboration between a research institution and community partners made up of members from community based organizations , the Yakima Valley Farm Workers Clinic and the Breast , Cervical , and Colon Health Program of the Yakima District . The study will assess the efficacy of two culturally-appropriate , tailored educational programs design ed to increase cervical cancer screening among Hispanic women , based in the Yakima Valley , Washington , US . Methods / design A parallel r and omized-controlled trial of 600 Hispanic women aged 21–64 , who are non-compliant with Papanicolau ( Pap ) test screening guidelines . Participants will be r and omized using block r and omization to ( 1 ) a control arm ( usual care ) ; ( 2 ) a low-intensity information program , consisting of a Spanish- language video that educates women on the importance of cervical cancer screening ; or ( 3 ) a high-intensity program consisting of the video plus a ‘ promotora ’ or lay-community health educator-led , home based intervention to encourage cervical cancer screening . Participants who attend cervical cancer screening , and receive a diagnosis of an abnormal Pap test will be assigned to a patient navigator who will provide support and information to promote adherence to follow-up tests , and any necessary surgery or treatment . Primary endpoint : Participants will be tracked via medical record review at community-based clinics , to identify women who have had a Pap test within 7 months of baseline assessment . Medical record review ers will be blinded to r and omization arm . Secondary endpoint : An evaluation of the patient navigator program as a method to improve adherence and reduce time to follow-up among participants who receive an abnormal Pap test result . An additional secondary endpoint is the cost-effectiveness of the two different intensity intervention programs . Discussion This culturally sensitive intervention aims to increase compliance and adherence to cervical screening in a Hispanic population . If effective , such interventions may reduce incidence of cervical cancer . Trial registration Background : Most women with cervical cancer have not participated in Pap-smear screening . Self-sampling of vaginal fluid in combination with high-risk HPV testing may be a method to increase the attendance rate . Methods : A total of 4060 women , 39–60 years old , who had not attended the organised Pap-smear screening for 6 years or more were r and omised into two equal groups . A study group was offered to self- sample vaginal fluid ( Qvintip ) at home and /or recommended to attend the Pap-smear screening . The collected fluid after self-sampling was examined for the presence of high-risk HPV ( Hybrid Capture 2 method ) . Controls were only recommended to attend the Pap-smear screening . The end point was a histological identification of CIN2–3 . Results : The participation rate was 39 % ( 771 out of 2000 ) in the self-sampling group and 9 % ( 188 out of 2060 ) in the conventional cytology ( P<0.001 ) . The number of histological CIN2–3 alterations detected was 0.4 % ( 8 out of 2000 ) among women offered self-sampling of vaginal fluid and 0.07 % ( 3 out of 4060 ) in women offered Pap-smears . The odds ratio ( OR ) for offering self-sampling and HPV testing instead of Pap-smear screening for detection of CIN2–3 was OR=5.42 ( 95 % CI : 1.30–31.8 ) . Conclusion : Offering self-sampling of vaginal fluid followed by a high-risk HPV test was considerably more effective for detection of histological CIN2–3 lesions in comparison with offering Pap-test in a midwife reception in women not regularly attending organised screening Context Minority and low-income women have low screening rates for cancer . Contribution In this trial from 11 community and migrant health centers in New York City , 1413 women overdue for cancer screening were r and omly assigned to receive a telephone-based intervention ( delivered by 8 prevention care managers ) or usual care . The intervention included information about breast , cervical , and colorectal cancer and motivational and logistical support for obtaining screening . Within 18 months , the screening rates for all 3 forms of cancer increased more with telephone support than through usual care . Implication s Telephone support delivered by trained personnel can improve cancer screening rates among some minority , low-income women . The Editors Higher screening rates for breast , cervical , and colorectal cancer could reduce cancer mortality rates substantially ( 1 - 4 ) . Current cancer screening rates are particularly disappointing among ethnic minorities and individuals with low socioeconomic status ( 5 , 6 ) who often present with late-stage diagnoses ( 7 ) and have high mortality rates ( 8 , 9 ) . Interventions to increase cancer screening have shown limited sustainability and effect on health care disparities . A previous study showed that an office systems approach , which used a medical record flowsheet and practice teamwork , increased screening rates by 20 % to 33 % in small rural community practice s ( 10 ) ; however , a similar intervention was less effective in larger urban practice s ( 11 ) . An office intervention in low-income setting s in Florida increased mammography use and home fecal occult blood testing at 12 months ( 12 ) , but rates decreased substantially after research support ended ( 13 ) . Use of the telephone to support cancer screening is well documented ( 14 - 18 ) , but interventions have typically addressed a single form of cancer screening . In some setting s , telephone infrastructures to support childhood immunization ( 19 ) and patients with chronic illnesses ( 20 - 23 ) already exist . These infrastructures could add screening support for patients who are already enrolled , or they could exp and services to others while making minimal additional dem and s on primary care practice s ( 24 ) . This paper reports the results of a r and omized , controlled trial that tested the effect of central ized telephone care management on cancer screening rates among women 50 to 69 years of age who obtained care at community and migrant health centers in New York City . Methods Setting s Federally qualified community and migrant health centers provide comprehensive community-oriented primary care to over 12 million patients nationally ( 25 ) and are uniquely positioned to deliver cancer screenings to underserved and minority population s. We sought participation from 15 of the 21 community and migrant health centers in New York City because of their anticipated ability to provide sufficient patients for the study and their affiliations with tertiary care facilities that conduct mammography and colorectal screening and provide follow-up services for abnormal test results . Of these 15 sites , 2 were involved in competing research projects , 2 had few patients who were likely to be eligible and therefore served as pilot sites , and the remaining 11 participated . Clinical Directors Network , a practice -based research network in New York City , was responsible for recruiting clinicians , practice s , and women and for implementing the intervention and evaluation . The project was approved by the Committee for the Protection of Human Subjects at Dartmouth College , by the institutional review board at Clinical Directors Network , and by all relevant bodies responsible for review ing research at participating community and migrant health centers . Patients Recruitment Women were approached by research assistants during routine visits to the centers or were referred by a clinician . Research assistants explained the study and obtained written informed consent from women who agreed to participate . Women were compensated $ 15 for participating in an interview whether or not they met eligibility criteria . Eligibility Eligible women were 50 to 69 years of age , were overdue for at least 1 cancer screening according to their medical records , were patients of the center for at least 6 months , and had no plans to move or change health centers within 15 months . We excluded women whose primary language was not English , Spanish , or Haitian Creole and those who were acutely ill or currently receiving cancer treatment . After we obtained consent , a research assistant review ed patient medical records to confirm eligibility . Mammography and Papanicolaou tests that were performed within the past year were seen as evidence of breast and cervical cancer screening , respectively , whereas reports of home fecal occult blood testing within the past year , sigmoidoscopy within the past 5 years , or colonoscopy within the past 10 years were seen as evidence of colorectal cancer screening . Women whose charts indicated that they were up to date on all 3 cancer screenings were excluded . We also excluded women with unresolved abnormal screening results ( for example , positive results on home fecal occult blood testing ; mammography results that were categorized as American College of Radiology level 0 , 4 , or 5 ; and certain Papanicolaou test results ) and notified their physicians of these findings . Design Eligible , consenting women were grouped by center , duration of enrollment at their center ( 12 months or > 12 months ) , and the number of cancer screenings that they had received at recommended intervals ( 0 or 1 screening or 2 screenings ) . The New Yorkbased research assistant assigned women in each group to receive the intervention or usual care by using sealed r and omization forms that were produced by Dartmouth College staff with a computer-based r and om-number generator . Patients were informed of their group assignment individually by telephone . At time of consent , all women received the publication titled Put Prevention into Practice Personal Health Guide ( 26 ) , which contained information regarding recommended preventive services . Women who were assigned to the usual care group received a single telephone call during which trial staff answered questions about preventive care , informed women of their usual care status , advised them to obtain needed preventive care from their primary care clinician , and thanked them for their participation . Women who were assigned to the intervention group received a series of telephone support calls from a trained prevention care manager who was monitored to ensure quality and consistency . In much the same way that patient navigators guide women through the health care system during cancer treatment ( 27 ) , prevention care managers facilitated the screening process for each woman by addressing barriers that prevent or delay receipt of cancer screenings . Prevention care managers received 7 hours of training , including an overview of the U.S. Preventive Services Task Force guidelines ( 28 - 30 ) ; a review of barriers to breast , cervical , and colorectal cancer screenings ; and detailed explanations of the targeted screenings . Additional training included role-playing telephone calls during which the managers used the intervention scripts . Thereafter , logs were review ed in monthly meetings to ensure fidelity to the intervention . The 8 prevention care managers were women , and most were college graduates . Their assignments were determined by patient language needs . Each care manager focused most of her work on patients from 1 or 2 sites while supporting smaller numbers of patients from other sites ; contact with clinicians was limited . During the first call with a patient in the intervention group , the prevention care manager answered questions about the health guide and confirmed or up date d screening date s found in the woman 's medical record . She next determined how ready the woman was to act on each screening ( 31 ) and worked with the woman to prioritize overdue screenings . The prevention care manager then provided motivational support , responding to each participant 's specific barriers to screening by using a structured script that was developed through an earlier series of interviews with women ( 32 ) . Some participants had been advised during office visits with their clinicians to undergo screening ; those who had not received such recommendations were sent a written recommendation from their clinician . Women who reported that they had difficulty communicating with their physician were sent brightly colored patient activation cards that listed overdue screenings , which they could share with their clinician at their next appointment . Care managers also scheduled appointments , provided accurate information about screenings over the telephone and by mail , prompted women with appointment reminder calls and letters , provided directions to screening facilities , and helped women to find a means of transportation to appointments . During subsequent calls , which continued for 18 months or until the patient was up to date for all screenings , the prevention care manager asked about future appointments and screenings the patient had received since the last call . The manager then responded to new and ongoing barriers for remaining overdue screenings . Only clinicians , not care managers , were responsible for ordering screenings at all but 2 centers , which permitted care managers to mail home fecal occult blood test kits directly to women who were willing to perform this test . Evaluation Descriptive data on the centers were gathered from surveys that were completed by clinicians and clinical directors . Outcome data were based on review s of patient medical records , which were conducted at least 3 months after the intervention period to allow for the time lag between receipt of a service and the availability of documentation . Data included patient demographic characteristics , screening date s and results , chronic Abstract OBJECTIVE : To determine if women would have higher breast and cervical cancer screening rates if lay health advisers recommended screening and offered a convenient screening opportunity . DESIGN : Controlled trial . SETTING : Urban county teaching hospital . PARTICIPANTS : Women aged 40 years and over attending appointements in several non- primary -care outpatient clinics . INTERVENTIONS : Lay health advisers assessed the participants ’ breast and cervical cancer screening status and offered women in the intervention group who were due for screening an appointment with a female nurse practitioner . MEASUREMENTS AND MAIN RESULTS : Screening rates at base-line and at follow-up 1 year after the intervention were determined . At follow-up , the mammography rate was 69 % in the intervention group versus 63 % in the usual care group ( p=.009 ) , and the Pap smear rate was 70 % in the intervention group versus 63 % in the usual care group ( p=.02 ) . In women who were due for screening at baseline , the mammography rate was 60 % in the intervention group versus 50 % in the usual care group ( p=.006 ) , and the Pap smear rate was 63 % in the intervention group versus 50 % in the usual care group ( p=.002 ) . The intervention was effective across age and insurance payer strata , and was particularly effective in Native American women . CONCLUSIONS : Breast and cervical cancer screening rates were improved in women attending non- primary -care outpatient clinics by using lay health advisers and a nurse practitioner to perform screening . The effect was strongest in women in greatest need of screening INTRODUCTION We conducted a r and omized controlled trial to determine if an in-home educational intervention conducted by lay health workers ( LHWs ) could increase adherence among low-income , inner-city , African-American women to breast and cervical cancer screening schedules . METHODS We recruited 321 African-American women from diverse inner-city sources . After baseline interviews , they were r and omly assigned to either the intervention ( n = 163 ) or the control ( n = 158 ) group . Those in the intervention group were visited in their homes up to three times by LHWs who provided a culturally sensitive educational program that emphasized the need for screening . RESULTS Ninety-three ( 93 ) women in the intervention group and 102 in the control group completed the postintervention interview . For Pap smears , the increase in screening was similar in both groups . For clinical breast exams ( CBEs ) , however , there was a modest increase in the intervention group . The improvement was greatest for mammography , for which there was a 10 % to 12 % increase . Among women who were not on recommended schedules at baseline , the improvement was substantial and greater in the intervention group . CONCLUSIONS LHWs ' intervention appeared to improve the rate at which inner-city women obtained CBEs and mammograms , but had no effect on Pap smears . A high attrition rate weakened our ability to make conclusive statements about the exact impact of the intervention BACKGROUND Human papillomavirus ( HPV ) testing is known to be more sensitive , but less specific than cytology for detecting cervical intraepithelial neoplasia ( CIN ) . We assessed the efficacy of cervical-cancer screening policies that are based on HPV testing . METHODS Between March , 2004 , and December , 2004 , in two separate recruitment phases , women aged 25 - 60 years were r and omly assigned to conventional cytology or to HPV testing in combination with liquid-based cytology ( first phase ) or alone ( second phase ) . R and omisation was done by computer in two screening centres and by sequential opening of numbered sealed envelopes in the remaining seven centres . During phase one , women who were HPV-positive and aged 35 - 60 years were referred to colposcopy , whereas women aged 25 - 34 years were referred to colposcopy only if cytology was also abnormal or HPV testing was persistently positive . During phase two , women in the HPV group were referred for colposcopy if the HPV test was positive . Two rounds of screening occurred in each phase , and all women had cytology testing only at the second round . The primary endpoint was the detection of grade 2 and 3 CIN , and of invasive cervical cancers during the first and second screening rounds . Analysis was done by intention to screen . This trial is registered , number IS RCT N81678807 . FINDINGS In total for both phases , 47,001 women were r and omly assigned to the cytology group and 47,369 to HPV testing . 33,851 women from the cytology group and 32,998 from the HPV-testing group had a second round of screening . We also retrieved the histological diagnoses from screening done elsewhere . The detection of invasive cervical cancers was similar for the two groups in the first round of screening ( nine in the cytology group vs seven in the HPV group , p=0.62 ) ; no cases were detected in the HPV group during round two , compared with nine in the cytology group ( p=0.004 ) . Overall , in the two rounds of screening , 18 invasive cancers were detected in the cytology group versus seven in the HPV group ( p=0.028 ) . Among women aged 35 - 60 years , at round one the relative detection ( HPV vs cytology ) was 2.00 ( 95 % CI 1.44 - 2.77 ) for CIN2 , 2.08 ( 1.47 - 2.95 ) for CIN3 , and 2.03 ( 1.60 - 2.57 ) for CIN2 and 3 together . At round two the relative detection was 0.54 ( 0.23 - 1.28 ) for CIN2 , 0.48 ( 0.21 - 1.11 ) for CIN3 , and 0.51 ( 0.28 - 0.93 ) for CIN2 and 3 together . Among women aged 25 - 34 years , there was significant heterogeneity between phases in the relative detection of CIN3 . At round one the relative detection was 0.93 ( 0.52 - 1.64 ) in phase one and 3.91 ( 2.02 - 7.57 ) in phase two . At round two the relative detection was 1.34 ( 0.46 - 3.84 ) in phase one and 0.20 ( 0.04 - 0.93 ) in phase two . Pooling both phases , the detection ratio of CIN2 for women aged 25 - 34 years was 4.09 ( 2.24 - 7.48 ) at round one and 0.64 ( 0.23 - 1.27 ) at round two . INTERPRETATION HPV-based screening is more effective than cytology in preventing invasive cervical cancer , by detecting persistent high- grade lesions earlier and providing a longer low-risk period . However , in younger women , HPV screening leads to over-diagnosis of regressive CIN2 . FUNDING European Union , Italian Ministry of Health , Regional Health Administrations of Piemonte , Tuscany , Veneto and Emilia-Romagna , and Public Health Agency of Lazio BACKGROUND A disproportionate number of women diagnosed with cervical cancer are from low-income and /or ethnically diverse groups . This study was design ed to evaluate the effectiveness of an outreach and counseling intervention at improving the rate of follow-up of abnormal Pap smears among women at Alameda County Medical Center , Oakl and , CA . METHODS Between September 1 , 1999 and August 31 , 2001 , 348 women with abnormal Pap test results were r and omly assigned to intervention or usual care . The main outcome was rate of follow-up . RESULTS The intervention produced a significant increase in the rate of follow-up visits within 6 months . Women in the intervention group were much more likely to obtain timely follow-up at Highl and Hospital than were those in the control group ( 61 % vs. 32 % , P = 0.001 ) . The intervention was equally effective when delivered to women in the control group who had no follow-up by 6 months . Overall , we were able to contact 90 % of women in the intervention group . CONCLUSIONS An outreach intervention is highly effective at increasing follow-up of abnormal Pap smears in a public hospital setting . Institutions offering cervical cancer screening to low-income , high-risk women should consider the use of outreach workers to reduce loss to follow-up BACKGROUND Computers that collect data from patients and provide both patients and practitioners with printed feedback on a range of health risks are a tool for assisting general practitioners with preventive care . This study assessed the impact of computer-generated printed feedback on cervical screening among women who were underscreened for cervical cancer . METHOD Female attenders at two Australian general practice s were r and omly allocated to Experimental or Control groups . Women in both groups completed a health risk survey on a touch screen computer prior to their consultation . Those in the Experimental group received printed pages summarizing their results , including their eligibility for cervical screening and last Pap test , for themselves and their doctor . The number and proportion of underscreened women who had a Pap test in the 6 months after completing the computer survey , as determined by pathology records , were examined . RESULTS Of the 679 participants , 139 were classified as underscreened on the basis of self-report ( 74 Experimental , 65 Control ) and 272 on the basis of their pathology records ( 148 Experimental , 124 Control ) . Overall about one-third of women had a test in the 6-month period , and the differences between the groups were not significant for women overall ( 18 - 70 years ) or for women 18 - 49 years . Among women 50 - 70 who were underscreened based on self-report , those receiving the printout were more likely to have a Pap test in the next 6 months ( P < 0.05 ) . This pattern was also evident , but did not reach statistical significance , for older women who were underscreened based on pathology records . CONCLUSIONS We are unable to draw conclusions regarding the effectiveness of the computer system due to the modest proportions of women screened , the small numbers , and the fact that the computer survey may have created an intervention effect in the Control group . As the study suggests the computer system is acceptable to women and may be effective for encouraging screening among older women , further exploration of the system is desirable OBJECTIVES To test the effectiveness of a community intervention program to promote breast and cervical cancer screening . METHOD Low-income Mexican American neighborhoods located in 2 Texas cities were assigned to intervention or comparison conditions . A 2-year community intervention was delivered via local mass media and reinforced by indigenous volunteers . RESULTS There were higher Pap smear completion rates for women under 40 years of age in the intervention community . CONCLUSION Although it is important to address the cultural needs of all Mexican American women , it is also important to underst and the tangible environmental barriers faced by the older women BACKGROUND Previous research has shown that breast and cervical cancer screening rates are low among Vietnamese women . METHODS Over a 24-month period , we implemented a media-led community education campaign to promote recognition , intention , receipt , and currency of routine checkups , clinical breast examinations , mammograms , and Pap tests among Vietnamese-American women in Alameda and Santa Clara Counties in northern California . Women in Los Angeles and Orange Counties in southern California served as controls . To evaluate its impact , pretest telephone interviews were conducted of 451 r and omly selected women in the intervention area and 482 women in the control area and posttest interviews with 454 and 422 women , respectively . RESULTS At posttest , after controlling for demographic differences in the surveyed population s , the odds ratios for the intervention effect were statistically significant for having heard of a general checkup , Paptest , and clinical breast examination ( CBE ) ; planning to have a checkup , Pap test , CBE , and mammogram ; and having had a checkup and Pap test . The intervention had no effect on being up to date for any of the tests . CONCLUSIONS A media-led education intervention succeeded in increasing recognition of and intention to undertake screening tests more than receipt of or currency with the tests A r and omised field trial was used to assess Mexican women 's response to a mailed invitation for a Papanicolaou test . A sample of 4,802 women , 20 to 64 years old , chosen at r and om from the Mexican Social Security Institute Register were r and omly assigned to an intervention and to a control group . A letter of invitation and a reminder were sent to the intervention group . A letter was also sent to the control group at the end of the follow-up period ( 8.5 weeks ) in order to compare the response among women who received a letter in both groups . Cumulative incidence and incidence rates were used to determine the response and the speed of response , respectively . The response among women who had received the letter was 33.5 % ( efficacy ) in the intervention group , while 5.9 % ( p<0.001 ) in the control group attended a Papanicolaou test . For the total of women invited , the response was 20.1 % ( effectiveness ) and 3.3 % ( p<0.001 ) , respectively . The response was greater in rural areas ( rural vs. urban/suburban ; p = 0.002 ) and eldest women ( 50 - 64 vs. 20 - 49 ; p = 0 . 02 ) . The response rate was 7 times grater in the intervention than in the control group ( RR = 7.1 ; 95 % CI 5.4 - 9.4 ; p < 0.001 ) . A mailed invitation to have a Papanicolaou test substantially increases attendance by women who receive it . A mailed reminder improves results . This strategy could be implemented in addition to the ones already in use , mainly among rural and elderly women In Australia , Vietnamese women are at greater risk of cervical cancer than other Australian women . To increase their participation in cervical screening , the Vietnamese community was exposed to a media campaign about the advantages of cervical smear screening which was delivered in Vietnamese through Vietnamese newspapers and radio . In addition , 689 Vietnamese ( 18–67 years ) were selected from the electoral roll . They were r and omly assigned to either receive a personal letter written in Vietnamese promoting cervical screening , or not . We report on the effect of the letter on smear rates Aims and background Attendance level has been identified as a major determinant of cost-effectiveness of organized screening programs . We tested the effectiveness of 4 different invitation systems in the context of an organized population screening program for cervical and breast cancer . Methods Women eligible for invitation - 8385 for cervical and 8069 for breast cancer screening - listed in the rosters of 43 and 105 general practitioners ( GP ) , respectively , who had accepted to collaborate in the program , were r and omized to 4 invitation groups : Group A - letter signed by the GP , with a prefixed appointment ; Group B - open-ended invitation , signed by the GP , prompting women to contact the screening center to arrange an appointment ; Group C - letter ( same as for group A ) , signed by the program coordinator , with a prefixed appointment ; Group D - extended letter ( highlighting the benefits of early cancer detection ) signed by the GP , with a prefixed appointment . Assignment to the interventions was based on a r and omized block design ( block = GP ) . Results Assuming Group A as the reference , the overall compliance with cervical cancer screening was reduced by 39 % in Group B ( RR=0.61 ; 95 % CI , 0.56 - 0.68 ) and by 14 % in Group C ( RR=0.86 ; 95 % CI , 0.78 - 0.93 ) ; no difference was observed for Group D ( RR=1.03 ; 95 % CI , 0.95 - 1.1 ) . The response pattern was similar for breast screening ( Group B : RR=0.71 ; 95 % CI , 0.65 - 0.76 ; Group C : RR=0.87 ; 95 % CI , 0.81 - 0.94 ; Group D : RR=1.01 ; 95 % CI , 0.94 - 1.08 ) . Conclusions Personal invitation letters signed by the woman 's GP , with preallocated appointments , induce a significant increase in compliance with screening . Efficiency can be ensured through the adoption of overbooking , provided that attendance levels are regularly monitored BACKGROUND Regular screening has the potential to reduce breast and cervical cancer mortality , but despite health plan programs to encourage screening , many women remain unscreened . Tailored communications have been identified as a promising approach to promote mammography and Pap test screening . METHODS The study used a four-group r and omized design to compare with Usual Care the separate and combined effects of two tailored , motivational interventions to increase screening-a clinical office In-reach intervention and a sequential letter/telephone Outreach intervention . Subjects were 510 female HMO members ages 52 - 69 who had had no mammogram in the past 2 years and no Pap smear in the past 3 years . Primary outcomes were the percentage of women in each condition who received a mammogram , a Pap smear , or both screening tests during the 14-month study period . RESULTS Thirty-two percent of the Combined group , 39 % of the Outreach group , and 26 % of the In-reach group obtained both services versus 19 % of Usual Care participants . Overall , compared with Usual Care , both Outreach ( P = 0.006 ) and Combined ( P = 0.05 ) screened significantly more women . For subjects ages 65 - 69 , Outreach rates were lower than those of Usual Care . CONCLUSION A tailored letter-telephone Outreach appears to be more effective at screening women ages 52 - 64 than a tailored office-based intervention , in large part because most In-reach women did not have clinic visits at which to receive the intervention Please cite this paper as : de Bie R , Massuger L , Lenselink C , Derksen Y , Prins J , Bekkers R. The role of individually targeted information to reduce anxiety before colposcopy : a r and omised controlled trial . BJOG 2011;118:945–950 |
12,706 | 10,796,409 | The one trial that specifically addressed the question of lower versus higher PaO2 found no effect on death , but did not report ( in sufficient detail to warrant inclusion ) the effect of this intervention on eye or other outcomes .
REVIEW ER 'S CONCLUSIONS The results of this meta- analysis confirm the commonly held view of today 's clinicians that a policy of unrestricted , unmonitored oxygen therapy has potential harms , without clear benefits . | OBJECTIVES In preterm or low birth weight infants , does targeting ambient oxygen concentration to achieve a lower versus higher blood oxygen range , or administering restricted versus liberal supplemental oxygen , influence mortality , retinopathy of prematurity , lung function , growth or development ? | Aminophylline and caffeine are commonly used for prophylaxis of apnea in premature infants . Previous studies have indicated different effects of the drugs on cerebral circulation . Therefore , we have compared the acute effects of bolus administration of caffeine citrate or aminophylline on left ventricular output , heart rate , blood pressure and global cerebral blood flow . The study group consisted of 33 newborn , spontaneously breathing , preterm infants r and omly assigned to receive either aminophylline 5mg/kg ( n= 19 ) or caffeine citrate 20mg/kg ( n= 14 ) . Two hours after iv drug administration , global cerebral blood flow measured by the Xe‐clearance technique was significantly lower after aminophylline than after caffeine ( mean(SD ) ) : 13.2 ( + 2.9/ ‐ 2.3 ) versus 17.2 ( + 7.1/ ‐ 5.1 ) ml/100 g/min ) ( p= 0.01 ) . There were no other statistically significant differences in circulatory or ventilatory parameters between the groups . Further studies are needed to clarify the clinical relevance of these results To determine if the use of oxygen in the delivery room influences subsequent global cerebral blood flow ( CBF ) , 70 infants of gestational age of less than 33 completed weeks were r and omly assigned to receive room air ( group I ) or 80 % oxygen ( group II ) during the initial stabilisation at birth . In group I supplemental oxygen was administered on clinical indications , when required . After being admitted to the neonatal intensive care unit all infants were treated according to our normal practice . At a postnatal age of 2 hours CBF was measured by xenon clearance . Seventy four per cent of the infants in group I were successfully stabilised without the need for supplemental oxygen . CBF was significantly higher in group I than in group II ( CBF median ( interquartile range ) : 15.9 ( 13.6 - 21.9 ) v 12.2 ( 10.7 - 13.8 ) ml/100 g/minute ) . Differences in oxygen exposure seemed to be the only explanation for the differences in CBF . No differences in short term outcome were found between the groups OBJECTIVE To investigate the effects on oxygenation of targeting the higher versus the lower end of the currently recommended range for pulse oximetry ( Spo2 ) . DESIGN Nonr and omized crossover trial with the use of within-subject comparisons ( two-tailed paired t test ) . SETTING Level III neonatal intensive care unit of a university hospital . PATIENTS Twenty infants whose lungs were mechanically ventilated ( mean + /- SD : birth weight , 1192 + /- 396 gm ; gestational age , 28.7 + /- 2.7 weeks ; age at time of study , 42 + /- 26 hours ) . INTERVENTIONS The inspired oxygen concentration was adjusted to achieve Spo2 readings of 93 % to 96 % versus 89 % to 92 % ( Ohmeda pulse oximeter ) or 95 % to 98 % versus 91 % to 94 % ( Nellcor oximeter ) . MEASUREMENTS Cardiac output was measured by echocardiography , oxygen content of arterial blood sample s by cooximetry , and oxygen consumption by indirect calorimetry . RESULTS The inspired oxygen concentrations required to achieve the Spo2 target ranges were 39.8 % + /- 8.3 % versus 28.7 % + /- 6.1 % ( p < 0.001 ) . The respective arterial oxygen contents were 18.0 + /- 2.6 ml/dl versus 16.9 + /- 2.5 ml/dl ( p < 0.001 ) . Oxygen consumption was unchanged . In the lower-oxygen condition no compensatory increase in cardiac output was detected ; thus the estimated mixed venous oxygen tension decreased and the oxygen extraction ratio increased . Venous admixture increased from 15 % + /- 6 % to 31 % + /- 9 % in the lower-oxygen condition ( p < 0.001 ) . CONCLUSIONS The " low normal " Spo2 target range allowed for less oxygen exposure . No signs of mismatch between systemic oxygen delivery and dem and could be detected Sleep fragmentation , decreased rapid eye movement ( REM ) sleep time , and REM sleep hypoxemia have been reported in infants with chronic neonatal lung disease ( CNLD ) in early infancy despite an awake hemoglobin oxygen saturation ( SaO2 ) > 93 % . Interestingly , higher inspired O2 concentrations have been demonstrated to reduce REM sleep fragmentation in CNLD patients in middle infancy . However , the effect of increased SaO2 on sleep architecture in infants with CNLD near the time of discharge from neonatal intensive care has not been reported . We performed paired overnight polysomnography in a sleep laboratory on 16 infants with CNLD ( 4 weeks median corrected age ) in air or their usual inspired oxygen ( SaO2 > 93 % ) and again when receiving 0.25 L/min higher than baseline inspired oxygen via nasal catheters ( SaO2 > 97 % ) . A control group of seven healthy preterm infants was similarly studied . For CNLD infants on supplemented O2 , sleep duration decreased by 15 % ( 422+/-66 min vs. 359+/-89 min ; P < 0.005 ) , and sleep efficiency decreased by 7 % ( 73.2+/-10.6 % vs. 66.4+/-14.0 % ; P < 0.005 ) but percentage of time in REM sleep ( REM% ) ( 31.5+/-8.9 % vs. 29.8+/-8.6 % ; P=0.560 ) , REM epoch duration ( 12.4+/-2.8 min vs. 13.4+/-4.3 min ; P=0.420 ) , and REM arousal index ( 18.6+/-6.5 vs. 18.8+/-7.2 ; P=0.990 ) were not significantly affected . Conversely , higher O2 did not alter sleep architecture in the control group . The mean non-REM ( NREM ) respiratory rate decreased ( CNLD : P=0.003 ; controls : P=0.02 ) , NREM SaO2 increased ( P < 0.05 ) , although the mean transcutaneous CO2 was unaltered in both CNLD and control groups . This study confirmed low REM% in CNLD infants in early infancy and demonstrated that a higher SaO2 adversely affected sleep time but did not influence REM sleep duration or arousal frequency . A target SaO2 > 93 % is , therefore , as efficacious as an SaO2 > 97 % in optimizing sleep architecture in CNLD infants A previous report has shown no difference between the clinical outcome of infants exposed to a high oxygen ( O2 ) regimen and those exposed to a low O2 regimen for the treatment of respiratory distress syndrome ( RDS ) . Mechanical ventilation was not used in either group . In the present study , pulmonary function tests were performed on 14 survivors receiving the low O2 regimen ( low O2 group ) and on nine receiving the high O2 regimen ( high O2 group ) ten years after their initial illness . Similar evidence of abnormalities of large airways was found in both groups of prematurely born children that was comparable with that previously reported for normal prematurely born children . There was evidence in the high O2 group similar to that reported for ventilated survivors with RDS exposed to a high concentration of O2 . From these data , it was concluded that neonatal exposure to high O2 concentrations in the absence of mechanical ventilation is capable of causing long-term change in small airways This study was performed to determine whether the use of continuous transcutaneous oxygen tension ( tcPO2 ) monitoring could reduce the incidence of retinopathy of prematurity in preterm infants receiving oxygen therapy . A total of 296 infants with birth weights less than or equal to 1,300 g were r and omly assigned to a continuous monitoring or a st and ard care group . Infants in the continuous monitoring group had tcPO2 monitored continuously as long as they required supplemental oxygen , and infants in the st and ard care group had tcPO2 monitored only during the more acute state of their illness . Management of both groups was otherwise identical . Of 148 infants in the continuous monitoring group , 101 survived ; of the 148 patients in the st and ard care group , 113 survived . Mean birth weights and gestational ages were similar for both groups . Duration of mechanical ventilation and oxygen therapy was also similar . The overall incidence of retinopathy of prematurity was 51 % in the continuous monitoring group and 59 % in the st and ard care group . As birth weight for infants greater than or equal to 1,000 g increased , a higher risk of retinopathy of prematurity developing was noted in the st and ard care group . Cicatricial retinopathy of prematurity developed in four infants in the continuous monitoring group and five in the st and ard care group . These results suggest that continuous tcPO2 monitoring may reduce the incidence of retinopathy of prematurity in infants with birth weights greater than 1,000 g but not in the smaller infants in whom this complication occurs more frequently and is more severe Between 1966 and 1970 , infants with birthweights between 1000 and 1500 g entered a r and omized controlled trial to determine the short‐term and long‐term results of neonatal intensive care . Of 158 long‐term survivors , five were lost to follow‐up , but the multidisciplinary research team prospect ively followed 143 children up to the age of eight years . Useful data were available for the other 10 children . Of the long‐term survivors 74 had received routine , and 84 had received intensive nursery care Oxygen saturation determined by pulse oximetry was monitored in 152 pediatric surgical patients divided into two groups . In one group , the oximeter data and alarms were available ( N = 76 ) to the anesthesia team , and , in the other group , these data were unavailable ( N = 76 ) . A trained observer recorded all intraoperative hypoxic episodes and informed the anesthesia team of all major events ( i.e. , oxygen saturation less than or equal to 85 % for greater than or equal to 30 s ) ( PaO2 approximately 52 mmHg ) . Thirty-five major events occurred : 24 in the unavailable group , and 11 in the available group ( P = 0.021 ) . A greater number of major events occurred in children less than or equal to 2 yr of age ( P = 0.013 ) . Hypoxic events diagnosed by the oximeter , but not by the anesthesiologist , were more frequent in the unavailable group ( 13 ) than in the available group ( 5 ) ( P = 0.0495 ) . ASA Physical Status 3 and 4 patients were more likely to suffer a major event ( P = 0.009 available , 0.006 unavailable ) . The pulse oximeter diagnosed hypoxemia before the signs and symptoms of hypoxemia were apparent ( i.e. , prior to observed cyanosis or bradycardia ) . Major hypoxic events were unrelated to duration of anesthesia . Major events were evenly distributed among induction , maintenance , and awakening from anesthesia ; a greater number of hypoxic events occurred during induction in the unavailable group ( P = 0.031 ) . No morbidity was documented in any patient who suffered an hypoxic event . ( ABSTRACT TRUNCATED AT 250 WORDS The relation between PaO2 and retrolental fibroplasia ( RLF ) was studied prospect ively in 719 premature infants born in or treated in the intensive care units of a group of university hospitals . Blood gas studies were performed on 589 of these infants , 66 of whom had a diagnosis of RLF ; in 27 of these 66 , some grade of mostly nonblinding cicatricial disease developed . The frequency of RLF was highest among infants of lowest birth weight . A multivariate statistical method was used to analyze simultaneously the effect of possible etiologic factors associated with RLF . The occurrence of RLF was found to be unrelated to PaO2 , as determined by the limited information available from intermittent sampling . RLF is associated with concentration of oxygen administered in the lightest birth weight group , but the strongest association , aside from birth weight , was with time in oxygen . None of the other variables involving blood chemical values appeared to be associated with RLF . The severity of cicatricial RLF is clearly greater in infants weighing less than 1,200 g at birth . Conservative administration of oxygen may have been responsible for failure to demonstrate quantitative association between PaO2 levels and disease . Agreement between the observed and predicted numbers of infants with RLF demonstrate the strength of the multivariate technique employed in making the statistical analyses AIMS : To determine if decreasing arterial blood saturation from 95 % to 90 % could cause vasoconstriction of the pulmonary vasculature and dilatation of a patent ductus arteriosus in preterm newborn infants with respiratory distress syndrome ( RDS ) . METHODS : Doppler echocardiographic studies were compared at 95 % and 90 % pulse oxygen saturation ( SpO2 ) in 13 preterm infants aged 61.7 ( 4.3 ) hours with RDS and Doppler echocardiographic evidence of tricuspid regurgitation . RESULTS : The mean (SD)Doppler echocardiographic indices determined at 95 % were heart rate ( 146 ( 3.60 ) beats per minute ) , acceleration time of the velocity wave forms of the pulmonary artery ( PAAT ) ( 51.8 ( 2.5 ) milliseconds ) , ratio of PAAT to right ventricular ejection time ( ET ) ( 0.26 ( 0.02 ) ) , diameter of the ductus arteriosus ( 2.6 ( 0.6 ) mm ) , pulmonary blood flow ( 0.33 ( 0.03 ) l/minute ) and the left ventricular shortening fraction (SF)(0.4 (0.02)% ) . The ascending aorta flow velocity wave form was used for the calculation of pulmonary blood flow . The right ventricular to right atrial systolic pressure gradient calculated using the peak velocity of the tricuspid regurgitation jet was 26.7 ( 7.4 ) mm Hg . CONCLUSIONS : A decrease from 95 % to 90 % SpO2 did not have any effect on the pulmonary circulatory haemodynamics nor the ductus arteriosus To determine whether the use of continuous transcutaneous oxygen monitoring ( tcPO2 ) could reduce the incidence of retinopathy of prematurity ( ROP ) in pre-term infants receiving oxygen therapy , a r and omized , prospect i ve trial of constant monitoring using the transcutaneous oxygen monitor versus intermittent monitoring of oxygen was performed on a population of premature infants at very high risk for the development of ROP . Two hundred ninety-six infants were r and omly assigned to either a constantly monitored ( CM ) or st and ard care ( SC ) group . CM infants had tcPO2 monitored continuously as long as they required supplemental oxygen , whereas SC infants had tcPO2 monitored only during the more acute state of their illness . Management of both groups was otherwise identical . One hundred one of 148 infants in the CM group and 113 of 148 in the SC group survived . The overall incidence of ROP was 51 % in the CM group and 59 % in the SC group ( no significant difference ) . In infants over 1000 g birthweight , as the weight increased there was increasing risk of developing ROP in the SC group . The odds ratio for the ROPsc : ROPcm reached 7.6 in infants between 1200 and 1300 g in infants with Apgar scores greater than or equal to 8 at 5 minutes . The incidence of cicatricial ROP was similar in both groups : four in the CM and five in the SC group Retinopathy of prematurity ( ROP ) is a potentially blinding disease of preterm infants . 21 days of computer-recorded transcutaneous oxygen ( TcPO2 ) data were compared in 31 infants with stage 3 or greater ROP and 38 infants with no ROP or stage 1 or 2 . In a multiple logistic regression adjusted for significant perinatal factors ( birthweight , gestation , and intraventricular haemorrhage ) , babies with stage 3 or higher ROP showed an increased variability of TcPO2 in week 1 ( p < 0.01 ) and 2 ( p = 0.012 ) but not week 3 . Variability of TcPO2 in the first 2 weeks of life is a significant predictor of severe ROP Retrolental fibroplasia ( RLF ) was first recognized as a disease of premature infants in 1942 ; it is now first among the causes of blindness in children in the United States and is the foremost problem other than death itself in the care of premature infants . Several physicians 1 have noted an association of RLF with intensive oxygen therapy . Adequate controls are needed , however , to establish such a relationship beyond question . The present study was design ed to test this relationship under controlled conditions . We found a high incidence of blindness among infants given liberal oxygen treatment and none among those receiving little or none . The infants were not harmed by limited oxygen therapy . PLAN OF THE STUDY All patients between 1,000 and 1,850 gm . ( 2.2 and 4.1 lb . ) birth weight and less than 12 hours old on admission to the Bellevue Hospital Premature Nursery were assigned in the order of admission by r and |
12,707 | 24,942,321 | For children , insufficient evidence is available to corroborate the effectiveness of play opportunities , media distractions , and music for mitigating anxiety in children awaiting medical procedures .
CONCLUSIONS : Music is a well-established means of decreasing anxiety in adult patients awaiting medical interventions .
The effect of music on children ’s anxiety is not known . | BACKGROUND : Reducing waiting anxiety is an important objective of patient-centered care .
Anxiety is linked to negative health outcomes , including longer recovery periods , lowered pain thresholds , and for children in particular , resistance to treatment , nightmares , and separation anxiety .
The goals of this study were ( 1 ) to systematic ally review published research aim ed at reducing preprocedural waiting anxiety , and ( 2 ) to provide directions for future research and development of strategies to manage preprocedural waiting anxiety in health care environments . | Pre‐operative anxiety is common and often significant . Ambulatory surgery challenges our pre‐operative goal of an anxiety‐free patient by requiring people to be ‘ street ready ’ within a brief period of time after surgery . Recently , it has been demonstrated that music can be used successfully to relieve patient anxiety before operations , and that audio embedded with tones that create binaural beats within the brain of the listener decreases subjective levels of anxiety in patients with chronic anxiety states . We measured anxiety with the State‐Trait Anxiety Inventory question naire and compared binaural beat audio ( Binaural Group ) with an identical soundtrack but without these added tones ( Audio Group ) and with a third group who received no specific intervention ( No Intervention Group ) . Mean [ 95 % confidence intervals ] decreases in anxiety scores were 26.3%[19–33 % ] in the Binaural Group ( p = 0.001 vs. Audio Group , p < 0.0001 vs. No Intervention Group ) , 11.1%[6–16 % ] in the Audio Group ( p = 0.15 vs. No Intervention Group ) and 3.8%[0–7 % ] in the No Intervention Group . Binaural beat audio has the potential to decrease acute pre‐operative anxiety significantly Many patients in the Surgical Holding Area become stressed and anxious . In a hospital setting music reduces patients ' anxiety . This study determined that music can reduce the anxiety and stress of patients in the Surgical Holding Area . In this study , one group of subjects listed to music while a second group did not . Subjects who listened to music while in the Surgical Holding Area had significantly less stress and anxiety than did those who did not listen to music . Both groups spent similar lengths of time in the Surgical Holding Area . The results strongly suggest that if music were available to all patients in the Surgical Holding Area , most would select this option , and they would experience less anxiety OBJECTIVE To compare the effects of two pediatric venipuncture distress-management distraction strategies that differed in the degree to which they required children 's interaction . METHODS Eighty-eight 1- to 7-year-old children receiving venipuncture were r and omly assigned to one of three treatment conditions : interactive toy distraction , passive movie distraction , or st and ard care . Distress was examined via parent , nurse , self-report ( children over 4 years ) , and observational coding . Engagement in distraction was assessed via observational coding . RESULTS Children in the passive condition were more distracted and less distressed than children in the interactive condition . Although children in the interactive condition were more distracted than st and ard care children , there were no differences in distress between these groups . CONCLUSIONS Despite literature that suggests that interactive distraction should lower distress more than passive distraction , results indicate that a passive strategy might be most effective for children 's venipuncture . It is possible that children 's distress interfered with their ability to interact with the distractor The anticipation of surgery has been recognized as a stressful event that produces anxiety for most patients ( Kapnoullas 1988 ) . Even minor surgical procedures can produce anxiety in patients ; this in turn can affect their postoperative recovery and lead to a risk of physiological complications ( Swindale 1989 ) . Thus , preoperative anxiety is identified as one of the common nursing diagnoses or problems for surgical patients OBJECTIVES Dental anxiety is common in children . This study sought to determine the impact of viewing positive images of dentistry prior to a dental appointment on the anticipatory dental anxiety levels of children attending for dental treatment . METHODS Controlled trial . Assessment of anxiety and analysis of data were conducted blind to experimental condition . Assessment of anxiety was carried out in the waiting room postintervention but before the patient entered the dental surgery for treatment . PARTICIPANTS Thirty-eight children and young adults attending a dental clinic in South West Engl and . INTERVENTION Participants were r and omly assigned to one of two conditions . In both conditions the participant was asked to look at photographs for 2 min in the waiting area prior to their appointment . The intervention consisted of viewing positive images of dentistry and dental treatment , the control condition consisted of dentally neutral images . Positive and neutral images were vali date d independently by four paediatric dentists . The assessment of anticipatory dental anxiety was made blind to experimental condition and statistical analysis was conducted blind to group membership . OUTCOME MEASURE Anticipatory anxiety assessed by the Venham Picture Test . FINDINGS A significant difference in anticipatory dental anxiety was found between the two groups ( median-positive images = 0 , median-neutral images = 3 ; P < 0.001 ) . Anticipatory anxiety was not correlated to age ( rho = 0.04 P > 0.05 ) , there was no difference between male and female participants in their level of anticipatory anxiety ( median-males = 0.5 , median-females = 1 P > 0.05 ) . CONCLUSIONS Viewing positive images of dentistry and dentists results in short-term reductions in anticipatory anxiety in children The aim of this study was to test how distraction influences pain , distress and anxiety in children during wound care . Sixty participants aged 5 - 12 years were r and omized to three groups : serious gaming , the use of lollipops and a control group . Self-reported pain , distress , anxiety and observed pain behaviour were recorded in conjunction with wound care . Serious gaming , an active distraction , reduced the observed pain behaviour and self-reported distress compared with the other groups . A sense of control and engagement in the distraction , together , may be the explanation for the different pain behaviours when children use serious gaming AIMS AND OBJECTIVES To identify the effect of music on preprocedure anxiety levels of Hong Kong Chinese patients undergoing day procedures in a local community based hospital . DESIGN Pre and post-test quasi experimental design with non-r and om assignment . METHOD A total of 113 participants were assigned to the control group or intervention group depending on the day of their procedure . Participants ' anxiety levels were measured objective ly by comparing their vital signs and subjectively by the Spielberger State Trait Anxiety Scale . Participants ' physiological parameters ( blood pressure , pulse and respiration ) and State Trait Anxiety Scale were measured at two time periods . The control group undertook the usual relaxing activities provided in the waiting room compared with the intervention group who listened to music of their own choice in reclining chairs while waiting for the procedure . RESULTS The physiological parameters for both the control and intervention groups dropped significantly during the waiting period , however , only the intervention group had a significant reduction in reported anxiety levels . CONCLUSIONS These results suggest that providing self-selected music to day procedure patients in the preprocedure period assists in the reduction of physiological parameters and anxiety , yet , a relaxing environment can assist in the reduction of physiological parameters . RELEVANCE TO CLINICAL PRACTICE The administration of self-selected music to day procedure patients in the preprocedure period can be effective in the reduction of physiological parameters and anxiety Background . The induction of anesthesia is one of the most stressful moments for a child who must undergo surgery : it is estimated that 60 % of children suffer anxiety in the preoperative period . Preoperative anxiety is characterized by subjective feelings of tension , apprehension , nervousness , and worry . These reactions reflect the child ’s fear of separation from parents and home environment , as well as of loss of control , unfamiliar routines , surgical instruments , and hospital procedures . High levels of anxiety have been identified as predictors of postoperative troubles that can persist for 6 months after the procedure . Both behavioral and pharmacologic interventions are available to treat preoperative anxiety in children . Objective . The aim of this study was to investigate the effects of the presence of clowns on a child ’s preoperative anxiety during the induction of anesthesia and on the parent who accompanies him/her until he/she is asleep . Methods . The sample was composed of 40 subjects ( 5–12 years of age ) who had to undergo minor day surgery and were assigned r and omly to the clown group ( N = 20 ) , in which the children were accompanied in the preoperative room by the clowns and a parent , or the control group ( N = 20 ) , in which the children were accompanied by only 1 of his/her parents . The anxiety of the children in the preoperative period was measured through the Modified Yale Preoperative Anxiety Scale instrument ( observational behavioral checklist to measure the state anxiety of young children ) , and the anxiety of the parents was measured with the State-Trait Anxiety Inventory ( Y-1/Y-2 ) instrument ( self-report anxiety behavioral instrument that measures trait/baseline and state/situational anxiety in adults ) . In addition , a question naire for health professionals was developed to obtain their opinion about the presence of clowns during the induction of anesthesia , and a self-evaluation form was developed to be filled out by the clowns themselves about their interactions with the child . Results . The clown group was significantly less anxious during the induction of anesthesia compared with the control group . In the control group there was an increased level of anxiety in the induction room in comparison to in the waiting room ; in the clown group anxiety was not significantly different in the 2 locations . The question naire for health professionals indicated that the clowns were a benefit to the child , but the majority of the staff was opposed to continuing the program because of perceived interference with the procedures of the operating room . The correlation between the scores of the form to self-evaluate the effectiveness of the clowns and of the Modified Yale Preoperative Anxiety Scale is significant for both the waiting room and induction room . Conclusions . This study shows that the presence of clowns during the induction of anesthesia , together with the child ’s parents , was an effective intervention for managing children ’s and parents ’ anxiety during the preoperative period . We would encourage the promotion of this form of distraction therapy in the treatment of children requiring surgery , but the resistance of medical personnel make it very difficult to insert this program in the activity of the operating room It is common clinical experience that anxiety about pain can exacerbate the pain sensation . Using event-related functional magnetic resonance imaging ( FMRI ) , we compared activation responses to noxious thermal stimulation while perceived pain intensity was manipulated by changes in either physical intensity or induced anxiety . One visual signal , which reliably predicted noxious stimulation of moderate intensity , came to evoke low anxiety about the impending pain . Another visual signal was followed by the same , moderate-intensity stimulation on most of the trials , but occasionally by discriminably stronger noxious stimuli , and came to evoke higher anxiety . We found that the entorhinal cortex of the hippocampal formation responded differentially to identical noxious stimuli , dependent on whether the perceived pain intensity was enhanced by pain-relevant anxiety . During this emotional pain modulation , entorhinal responses predicted activity in closely connected , affective ( perigenual cingulate ) , and intensity coding ( mid-insula ) areas . Our finding suggests that accurate preparatory information during medical and dental procedures alleviates pain by disengaging the hippocampus . It supports the proposal that during anxiety , the hippocampal formation amplifies aversive events to prime behavioral responses that are adaptive to the worst possible outcome OBJECTIVES To review the effect of lavender scent on anticipatory anxiety in dental participants . METHODS In a cluster r and omized-controlled trial , patients ' ( N = 340 ) anxiety was assessed while waiting for a scheduled dental appointment , either under the odor of lavender or with no odor . Current anxiety , assessed by the brief State Trait Anxiety Indicator ( STAI-6 ) , and generalized dental anxiety , assessed by the Modified Dental Anxiety Scale ( MDAS ) were examined . RESULTS Analyses of variance ( anovas ) showed that although both groups showed similar , moderate levels of generalized dental anxiety ( MDAS F((1,338 ) ) = 2.17 , P > 0.05 ) the lavender group reported significantly lower current anxiety ( STAI : F((1,338 ) ) = 74.69 , P < 0.001 ) than the control group . CONCLUSIONS Although anxiety about future dental visits seems to be unaffected , lavender scent reduces state anxiety in dental patients CONTEXT Interest in the use of alternative therapies to reduce anxiety in patients undergoing medical interventions is increasing . We sought to assess the effectiveness of aromatherapy involving essential oils in reducing preoperative anxiety in women undergoing abortions . SETTING An urban , free-st and ing abortion clinic in Vancouver , BC . PATIENTS 66 women waiting for surgical abortions . DESIGN A double blind , r and omized trial . INTERVENTION Ten minutes spent sniffing a numbered container with either a mixture of the essential oils vetivert , bergamot , and geranium ( treatment arm ) or a hair conditioner ( placebo ) . OUTCOME MEASURES Anxiety was measured before and after the intervention by using a verbal anxiety scale from 0 to 10 . RESULTS The anxiety score was reduced by 1.0 point ( 5.0 to 4.0 ) in the aromatherapy group and by 1.1 points ( 6.1 to 5.0 ) in the placebo group ( P = 0.71 ) . The 95 % CI on the 0.1 greater decrease in anxiety for the placebo group extends from 0.55 less ( favors aromatherapy ) to 0.75 greater ( favors placebo ) . CONCLUSION Aromatherapy involving essential oils is no more effective than having patients sniff other pleasant odors in reducing preprocedure anxiety BACKGROUND Stress and anxiety during pregnancy have been associated with premature and low birth weight babies , presumably through fetus over exposion to glucocorticoids . Antenatal stress also seems to have long-term effects upon infant development and adult health . However , medication for stress may carry risks to the expectant mother , therefore the efficacy of non-pharmacological interventions should be investigated . METHODS Pregnant women ( n=154 ) awaiting amniocentesis , were r and omly assigned in the morning and the afternoon to three groups for 30 min : ( 1 ) listening to relaxing music , ( 2 ) sitting and reading magazines , and ( 3 ) sitting in the waiting-room . Before and after that period , they completed the Spielberger 's State and Trait anxiety inventory and provided blood sample s for cortisol . The groups were then compared regarding change in cortisol levels and anxiety . RESULTS Maternal cortisol and state anxiety were correlated ( r=0.25 , p=0.04 ) in the afternoon , but not in the morning . The larger decreases in cortisol occurred in the music group ( -61.8 nmol/L , ANOVA : p=0.01 ) , followed by magazine , being differences among groups more pronounced in the morning . Women in the music group also exhibited the greater decreases in state anxiety ( p<0.001 ) . Younger mothers with less gestational age were on average the most anxious , and also the ones with greater decreases in cortisol and anxiety levels after relaxation . CONCLUSION A relaxing intervention as short as 30 min , especially listening to music , decreases plasma cortisol and self-reported state anxiety score . Pregnant women might benefit from the routine practice of relaxation in the imminence of clinical stressful events BACKGROUND While waiting for surgery , patients often exhibit fear and anxiety . Music is thought to be an alternative to medication to relieve anxiety . However , due to concerns about infection control , devices other than headphones may be considered for this purpose . OBJECTIVES The purpose of this study was to determine the anxiety-relieving effect of broadcast versus headphone music playing for patients awaiting surgery . DESIGN A r and omized controlled clinical study . SETTING The waiting area of an operating theater of a metropolitan teach hospital in Taiwan . PARTICIPANTS Alert adult with age between 20 and 65 years old waiting for surgery without premedications . METHODS A total of 167 patients were r and omly assigned to the headphone , broadcast and control groups . Both the headphone and the broadcast groups were provided with the same instrumental music , while the control group did not listen to any music . The tools for measuring anxiety were visual analogue scale ( VAS ) ranging from " not anxious at all " to " extremely anxious " and heart rate variability ( HRV ) . RESULTS The VAS score exhibited a significant decrease for both the headphone and broadcast groups . The low frequency and low-to-high frequency LF/HF ratio of the broadcast and headphone groups were significantly lower than those of the control group . None of the heart rate variables showed significant differences between the broadcast group and the headphone group . CONCLUSION Both headphone and broadcast music are effective for reducing the preoperative patient 's anxiety in the waiting room . RELEVANCE TO CLINICAL PRACTICE In order to take infection control into account , broadcast speakers can substitute for headphones for playing music to lower the anxiety level of patients waiting for surgery Patients scheduled for gastrointestinal procedures such as colonoscopy or esophagogastroduodenoscopy are often anxious and frightened . High levels of anxiety may result in more difficult and painful procedures . Past research has reported education , coping skills , relaxation techniques , and combinations of these including music , have decreased anxiety in patients across many setting s. Self-selected music therapy for preprocedural anxiety has not been studied . A r and omized controlled trial of 198 patients was undertaken to determine whether 15 minutes of self-selected music reduced preprocedure anxiety . The State Trait Anxiety Inventory was used to measure patients ’ anxiety . One-hundred ninety-three men and 5 women comprised the sample with an average age of 61 ( SD 10.5 ) . Patients who listened to music ( n = 100 ) reduced their anxiety score from 36.7 ( SD 9.1 ) to 32.3 ( SD 10.4 ) , while those who did not listen to music ( n = 98 ) reduced their anxiety score from 36.1 ( SD 8.3 ) to 34.6 ( SD 11.5 ) . These differences were statistically significant ( F = 7.5 , p = .007 ) after controlling for trait anxiety . There were no significant vital sign changes premusic and postmusic . Music is a noninvasive nursing intervention that can significantly reduce patients ’ anxiety prior to gastrointestinal procedures . Further research should address using music to reduce anxiety in other procedure areas and testing effectiveness of self-selected versus investigator-selected music in reducing anxiety AIMS AND OBJECTIVES The objective of this study was to evaluate the effects of musical intervention on preoperative anxiety and vital signs in patients undergoing day surgery . BACKGROUND Studies and systematic meta-analyses have shown inconclusive results of the efficacy of music in reducing preoperative anxiety . We design ed a study to provide additional evidence for its use in preoperative nursing care . DESIGN R and omised , controlled study . METHOD Patients ( n = 183 ) aged 18 - 65 admitted to our outpatient surgery department were r and omly assigned to either the experimental group ( music delivered by earphones ) or control group ( no music ) for 20 minutes before surgery . Anxiety , measured by the State-Trait Anxiety Inventory , and vital signs were measured before and after the experimental protocol . RESULTS A total of 172 patients ( 60 men and 112 women ) with a mean age of 40·90 ( SD 11·80 ) completed the study . The largest number ( 35·7 % ) was undergoing elective plastic surgery and 76·7 % of the total reported previous experience with surgery . Even though there was only a low-moderate level of anxiety at the beginning of the study , both groups showed reduced anxiety and improved vital signs compared with baseline values ; however , the intervention group reported significantly lower anxiety [ mean change : -5·83 ( SD 0·75 ) vs. -1·72 ( SD 0·65 ) , p < 0·001 ] on the State-Trait Anxiety Inventory compared with the control group . CONCLUSIONS Patients undergoing day surgery may benefit significantly from musical intervention to reduce preoperative anxiety and improve physiological parameters . RELEVANCE TO CLINICAL PRACTICE Finding multimodal approaches to ease discomfort and anxiety from unfamiliar unit surroundings and perceived risks of morbidity ( e.g. disfigurement and long-term sequelae ) is necessary to reduce preoperative anxiety and subsequent physiological complications . This is especially true in the day surgery setting , where surgical admission times are often subject to change and patients may have to accommo date on short notice or too long a wait that may provoke anxiety . Our results provide additional evidence that musical intervention may be incorporated into routine nursing care for patients undergoing minor surgery AIM This paper reports a study to test the hypothesis that day surgery patients who listen to music during their preoperative wait will have statistically significantly lower levels of anxiety than patients who receive routine care . BACKGROUND Although previous day surgery research suggests that music effectively reduces preoperative anxiety , method ological issues limit the generalizability of results . METHODS In early 2004 , a r and omized controlled trial design was conducted to assess anxiety before and after listening to patient preferred music . Participants were allocated to an intervention ( n=60 ) , placebo ( n=60 ) or control group ( n=60 ) . Pre- and post-test measures of anxiety were carried out using the State-Trait Anxiety Inventory . RESULTS Music statistically significantly reduced the state anxiety level of the music ( intervention ) group . No relationships were found between socio-demographic or clinical variables such as gender or type of surgery . CONCLUSION The findings support the use of music as an independent nursing intervention for preoperative anxiety in patients having day surgery Background : Patients often exhibit preoperative fear and anxiety that may influence the process of induction and recovery from anesthesia . Music is thought to be an alternative to medication for relief of fear and anxiety . Objectives : The purpose of the present study was to explore the feasibility of using heart rate ( HR ) variability ( HRV ) for evaluating the efficacy of music listening to relieve the patients ’ anxiety during their stay in the operation room waiting area and to compare the HRV measures with subjective Visual Analogue Scale ( VAS ) scores . Methods : In total , 140 patients were r and omly assigned to the experimental ( n = 64 ) or control group ( n = 76 ) . The intervention consisted of a 10-min period of exposure to relaxing music delivered through headphones . Anxiety levels were measured by VAS ( a 10-point scale ) and 5 min of HRV monitoring before and after the music intervention . Results : The music group demonstrated significant reductions in VAS scores , mean HR , low-frequency HRV , and low- to high-frequency ratio and an increase in high-frequency HRV , while patients in the control group showed no changes . The subjective results of patients ’ VAS anxiety scores were consistent with the objective results of HRV parameters . Conclusions : Listening to music can significantly lower the anxiety levels of patients before surgery . The frequency-domain parameters of HRV can be indicators for monitoring the change in anxiety level of preoperative patients Patients scheduled for vascular angiography are often anxious and frightened . High levels of anxiety may result in more difficult and painful procedures . Past research has reported mixed results for anxiety reduction techniques in other procedures setting s , such as education , cognitive-behavioral skills , coping and relaxation skills , combinations of techniques , and music . Music as an intervention for pre-procedural anxiety prior to vascular angiography has not been studied . A r and omized controlled trial of 170 patients was undertaken to determine whether 15 minutes of self-selected music reduced pre-procedure anxiety . The State Trait Anxiety Inventory was used to measure patients ' anxiety . One-hundred sixty-six men and 4 women comprised the sample with an average age of 66.8 years ( SD 9.95 , range 37 to 85 years ) . Patients who listened to music ( n=89 ) reduced their anxiety score from 38.57 ( SD 10.46 ) to 35.2 ( SD 9.7 ) , while those who did not listen to music ( n=81 ) reduced their anxiety score from 36.23 ( SD 10.54 ) to 35.1 ( SD 10.59 ) ; the difference between the groups was statistically significant ( t=1.95 , df 161 , p=0.05 ) . Pulse achieved a statistically significant reduction in the music group ( t=2.45 , df 167 , p=0.02 ) . Music is a noninvasive nursing intervention that patients enjoy and reduces their anxiety and their pulse rate . Further research should address using music to reduce anxiety in other interventional vascular angiography setting s with equal numbers of men and women and comparing self-selected versus investigator-selected music 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 . Introduction : Patients who await surgery often suffer from fear and anxiety , which can be prevented by anxiolytic drugs . Relaxing music may be an alternative treatment with fewer adverse effects . This r and omised clinical trial compared pre‐operative midazolam with relaxing music We assessed the effect of music on the level of sedation and the electroencephalograph bispectral index ( BIS ) during the preoperative period . Fifty-four ASA physical status I – II patients , scheduled for elective septo-rhinoplastic surgery , were included in the study . Subjects were assigned to receive either music ( music group ; n = 28 ) or no music ( control group ; n = 26 ) during the preoperative period . Sedative premedication was provided with midazolam 0.08 mg/kg IM . Observer ’s Assessment of Alertness/Sedation Scales ( OAAS ) scores and BIS values were recorded at specific time intervals . In the control group , there were more patients with an OAAS score of 1 than in the music group at 30 min after midazolam injection . In addition , there were more patients with an OAAS score of 2 in the control group than in the music group at 30–50 min . However , there were significantly more patients with an OAAS score of 3 in the music group than in the control group at 20–50 min . BIS values of the music group were also smaller than the control group at 30 and 40 min . BIS values were significantly decreased from baseline values at 10–50 min in the music group , whereas BIS values decreased at 30–50 min in the control group . In conclusion , listening to music during midazolam premedication is associated with an increase in sedation level in the preoperative period as reflected by a lower BIS value Abstract The authors investigated the effect of music on the state anxiety of a sample of 20 patients awaiting breast biopsy at a suburban medical facility . The patients were assigned alternately to either the control or experimental group . The individuals in the experimental group were given a 20-minute music-based intervention in a preoperative holding area , whereas the patients in the control group received the customary preoperative care . Clinicians measured blood pressure , heart rate , and respiration in both groups of patients , and the participants completed the State portion of the self-administered State-Trait Anxiety Inventory ( STAI ) . After the patients completed the 20 minutes of music or of preoperative care without music , clinicians again measured the participants ' vital signs and the patients completed the STAI . The authors ' findings indicated that the posttest state anxiety and respiratory rates of the patients in the experimental group were significantly lower than those of the patients in the control group The authors investigated music as a method to reduce ambulatory surgery patients ' preoperative anxiety . They assigned 42 patients to either an experimental or a control group and compared the patients ' vital signs and self-reports of anxiety , which were measured using the state portion of the State-Trait Anxiety Inventory . The study results indicate that music can be more beneficial than preoperative instruction alone in reducing ambulatory surgery patients ' anxiety . Patients who listened to their choice of music before surgery in addition to receiving preoperative instruction had significantly lower heart rates than patients in the control group who received only preoperative instruction . Differences in experimental and control group patients ' blood pressure measurements and respiratory rates approached significance . The authors suggest that perioperative nurses offer music as a viable option to reduce anxiety in ambulatory surgery patients who believe music is a method of relaxation Objective : To examine the influence of positive distraction on the behavior and activity of children in two clinic waiting areas . Background : People spend a considerable proportion of time waiting in hospitals . Studies show that the quality of waiting environments influences the perception of quality of care and caregivers , that perception of waiting time is a better indicator of patient satisfaction than actual waiting time , and that the waiting environment contributes to the perception of wait time . In fact , the attractiveness of the physical environment in waiting areas has been shown to be significantly associated with higher perceived quality of care , less anxiety , and higher reported positive interaction with staff . Can positive distractions in waiting areas improve the waiting experience , as indicated by the behavior and activities of children waiting for treatment ? Method : Five distraction conditions were r and omly introduced in the waiting area of the dental and cardiac clinics of a major pediatric tertiary care center through a single plasma screen intervention . The attention , behavior , and activities of waiting children were recorded . Data on 158 pediatric patients were collected over 12 days during December 2008 and January 2009 . Results : Data analysis shows that the introduction of distraction conditions was associated with more calm behavior and less fine and gross movement , suggesting significant calming effects associated with the distraction conditions . Data also suggest that positive distraction conditions are significant attention grabbers and could be an important contributor to improving the waiting experience for children in hospitals by improving environmental attractiveness The purpose of this study was to evaluate the use of aromatherapy to reduce anxiety prior to a scheduled colonoscopy or esophagogastroduodenoscopy . A controlled , prospect i ve study was done on a convenience sample of 118 patients . The “ state ” component of the State Trait Anxiety Inventory ( STAI ) was used to evaluate patients ' anxiety levels pre- and postaromatherapy . The control group was given an inert oil ( placebo ) for inhalation , and the experimental group was given the essential oil , lavender , for inhalation . The STAI state anxiety raw score revealed that patients were at the 99th ( women ) and 96th ( men ) percentiles for anxiety . The intervention group and the control group had similar levels of state anxiety prior to the beginning of the study ( t[116 ] = .47 , p = .64 ) . There was no difference in state anxiety levels between pre- and postplacebo inhalation in the control group ( t[112 ] = .48 , p = .63 ) . There was no statistical difference in state anxiety levels between pre- and postlavender inhalation in the experimental group ( t[120 ] = .73 , p = .47 ) . Although this study did not show aromatherapy to be effective based on statistical analysis , patients did generally report the lavender scent to be pleasant . Lavender is an inexpensive and popular technique for relaxation that can be offered to patients as an opportunity to promote preprocedural stress reduction in a hospital setting Background : Cast room procedures , such as cast application and removal , pin removal , and suture removal can cause significant anxiety in young children . The use of music therapy in the cast room to decrease anxiety has not been previously reported . Methods : We performed a r and omized , prospect i ve study of soft lullaby music compared with no music in 69 children 10 years or younger undergoing cast room procedures . Heart rates ( beats per minute ) were recorded in the waiting room and cast room using a pulse oximeter . Results : A total of 28 children were r and omized to music and 41 children to no music . The mean rise in heart rate between the waiting room and entering the cast room was −2.7 beats/min in the music group and 4.7 beats/min in the no music group ( P = 0.001 ) . The mean difference in heart rate between the waiting room and during the procedure was 15.3 beats/min in the music group and 22.5 beats/min in the no music group ( P = 0.05 ) . There were 7 patients in the no music group with heart rate increases of greater than 40 beats/min . No patient in the music group had an increase of this magnitude . Conclusions : Playing soft music in the cast room is a simple and inexpensive option for decreasing anxiety in young children during cast room procedures . Level of Evidence : R and omized Clinical Trial , Level II BACKGROUND Listening to music has a stress-reducing effect in surgical procedures . The effects of listening to music immediately before a cesarean section have not been studied . The objective of this study was to assess the effects of listening to selected music while waiting for a cesarean section on emotional reactions , on cognitive appraisal of the threat of surgery , and on stress-related physiological reactions . METHODS A total of 60 healthy women waiting alone to undergo an elective cesarean section for medical reasons only were r and omly assigned either to an experimental or a control group . An hour before surgery they reported mood , and threat perception . Vital signs were assessed by a nurse . The experimental group listened to preselected favorite music for 40 minutes , and the control group waited for the operation without music . At the end of this period , all participants responded to a question naire assessing mood and threat perception , and the nurse measured vital signs . RESULTS Women who listened to music before a cesarean section had a significant increase in positive emotions and a significant decline in negative emotions and perceived threat of the situation when compared with women in the control group , who exhibited a decline in positive emotions , an increase in the perceived threat of the situation , and had no change in negative emotions . Women who listened to music also exhibited a significant reduction in systolic blood pressure compared with a significant increase in diastolic blood pressure and respiratory rate in the control group . CONCLUSION Listening to favorite music immediately before a cesarean section may be a cost-effective , emotion-focused coping strategy . ( BIRTH 39:2 June 2012 ) 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 OBJECTIVE The aim of this study was to evaluate the efficacy of a playroom next to the operating room to reduce preoperative anxiety in children . METHODS AND MATERIAL S In 2009 , we design ed a playroom in a preoperative waiting room in our hospital . The playroom had colored toys and cars appropriate for different ages and a TV and video to show cartoons . Patients were r and omly assigned into a case or a control group . Control group patients were admitted to the preoperative waiting room 30 min prior to operation . Case group patients were admitted to the playroom for the same period of time . The anxiety levels of the children were compared using the modified Yale Preoperative Anxiety Scale ( m-YPAS ) . RESULTS In this study 200 children were evaluated ( 100 patients in the case group , 100 patients in the control group ) . There were 20 female and 80 male patients in the case group with a mean age of 4.33 ± 1.5 years and 26 female and 74 male patients in the control group with a mean age of 3.87 ± 1.2 years ( p = NS ) . Inguinal herniorraphy was the most common procedure in both groups . Preoperative anxiety was significantly decreased for all categories of the anxiety score as assessed by m-YPAS question naire . CONCLUSION A preoperative playroom is a very effective method to reduce preoperative anxiety in children Music may decrease the anxiety experienced by patients before surgery . Previous studies of this issue were hindered with multiple method ological problems . In this investigation , we examined this hypothesis while using a rigorous study design and objective outcome measures . Adult patients undergoing anesthesia and surgery were r and omly assigned to two study groups . Subjects in Group 1 ( n = 48 ) listened to a 30-min patient-selected music session , and subjects in Group 2 ( n = 45 ) received no intervention . By using self-report vali date d behavioral ( State-Trait Anxiety Inventory ) and physiological measures of anxiety ( heart rate , blood pressure , and electrodermal activity and serum cortisol , epinephrine , and norepinephrine ) , patients were evaluated before , during , and after administration of the intervention . We found that after intervention , subjects in the Music group reported significantly lower anxiety levels as compared with the Control group ( F1,91 = 15.4 , P = 0.001 ) . That is , the postintervention anxiety level of subjects in the Music group decreased by 16 % as compared with the preintervention level , whereas the anxiety level of the Control group did not change significantly . Two-way repeated- measures analysis of variance performed for the electrodermal activity , blood pressure , heart rate , cortisol , and catecholamine data demonstrated no group difference and no time × group interaction ( P = not significant ) . In conclusion , under the conditions of this study , patients who listened to music before surgery reported lower levels of state anxiety . Physiological outcomes did not differ , however , between the two study groups BACKGROUND : We performed this study to determine the beneficial effects of viewing an animated cartoon and playing with a favorite toy on preoperative anxiety in children aged 3 to 7 years in the operating room before anesthesia induction . METHODS : One hundred thirty children aged 3 to 7 years with ASA physical status I or II were enrolled . Subjects were r and omly assigned to 1 of 3 groups : group 1 ( control ) , group 2 ( toy ) , and group 3 ( animated cartoon ) . The children in group 2 were asked to bring their favorite toy and were allowed to play with it until anesthesia induction . The children in group 3 watched their selected animated cartoon until anesthesia induction . Children ’s preoperative anxiety was determined by the modified Yale Preoperative Anxiety Scale ( mYPAS ) and parent-recorded anxiety Visual Analog Scale ( VAS ) the night before surgery , in the preanesthetic holding room , and just before anesthesia induction . RESULTS : In the preanesthetic holding room , the group 2 mYPAS and parent-recorded anxiety VAS scores were significantly lower than those of groups 1 and 3 ( mYPAS : P = 0.007 ; parent-recorded anxiety VAS : P = 0.02 ) . In the operating room , the children in group 3 had the lowest mYPAS and parent-recorded anxiety VAS scores among the 3 groups ( mYPAS : P < 0.001 ; parent-recorded anxiety VAS : P < 0.001 ) . In group 3 , the mYPAS and parent-recorded anxiety VAS scores of only 3 and 5 children were increased in the operating room compared with their scores in the preanesthetic holding room , whereas the anxiety scores of 32 and 34 children in group 1 and 25 and 32 children in group 2 had increased ( P < 0.001 ) . The number of children whose scores indicated no anxiety ( mYPAS score < 30 ) in the operating room was 3 ( 7 % ) , 9 ( 23 % ) , and 18 ( 43 % ) in groups 1 , 2 , and 3 , respectively ( P < 0.001 ) . CONCLUSIONS : Allowing the viewing of animated cartoons by pediatric surgical patients is a very effective method to alleviate preoperative anxiety . Our study suggests that this intervention is an inexpensive , easy to administer , and comprehensive method for anxiety reduction in the pediatric surgical population Patients develop anxiety before undergoing gastroscopy . By removing such distressing feelings , patients are more likely to experience gastroscopy more smoothly . This study was design ed to examine changes in anxiety levels in patients undergoing gastroscopy and the effect of an optimal soothing environment ( OSE ) as a new nonpharmacological intervention to reduce patient anxiety prior to gastroscopy . During a 6-month period , 50 out patients referred for gastroscopy were r and omly assigned to two groups ( control group , n = 24 patients ; OSE group , n = 26 patients ) . This study was performed at the digestive endoscopy service of a 150-bed acute care hospital in Japan . The patient anxiety was assessed using the Face Scale score . Pre- and postprocedural systolic blood pressures were measured and values were compared with blood pressure upon arrival at the hospital . The tools for an OSE , including a safe essential oil burner with lavender essential oil and a digital video disk program entitled “ Flow ” manufactured by NHK ( Japan Broadcasting Corporation ) software , were provided to patients in the waiting room before gastroscopy . The score for self-assessed anxiety level just before gastroscopy was significantly higher than that on arrival at the hospital but returned to baseline after gastroscopy in the control group , whereas the score did not increase before starting gastroscopy in the OSE group . Systolic blood pressure measurements just before and after gastroscopy were significantly higher than those on arrival at the hospital and the baseline values in the control group , whereas it was not increased before starting gastroscopy in the OSE group . Providing an OSE before and during gastroscopy is useful to minimize patient anxiety regarding experiencing a gastroscopy . This nonpharmacological method is a simple , inexpensive , and safe method of minimizing anxiety before and during gastroscopy Children have increased anxiety during the preoperative period . The administration of oral premedication to children is often met with apprehension , reluctance , or refusal . We sought to determine whether giving a small toy to the children would decrease the anxiety associated with taking oral premedication . This was a prospect i ve study involving 100 children 3–6 yr of age r and omized into two equal groups . The anxiety of each child was assessed using the Modified Yale Preoperative Anxiety Scale . The results showed significantly less anxiety in children who received a toy before oral administration of midazolam AIM OF THE STUDY To test the effects of music intervention on pre-operative anxiety in Chinese males undergoing transurethral resection of the prostate . RATIONALE No studies have measured the effects of music intervention in reducing pre-operative anxiety for patients with transurethral resection of the prostate ( TURP ) . Previous studies have examined the effects of music on pre-operative anxiety but have not examined the possible effects of the presence of a carer as an independent variable in pre-operative anxiety levels of patients in addition to the music intervention . The cultural validity of applying a music intervention to the reduction of pre-operative anxiety was also investigated . DESIGN A quasi-experimental design with three groups : music intervention , nurse presence and control group . METHOD Thirty patients having TURP were r and omly assigned ( n = 10 each group ) to one of the three groups . Pre- and post-test measures of systolic and diastolic blood pressure , heart rate and state anxiety using the Chinese State-Trait Anxiety Inventory ( C-STAI ) were obtained for the three groups . RESULTS The findings showed that the music intervention significantly reduced all blood pressure levels for the patients . A reduction in state anxiety level was also found for the music intervention group . No significant reductions in blood pressure , heart rate and state anxiety level were found in the nurse presence and control groups . CONCLUSION The results support the cross-cultural validity of using a music intervention in pre-operative anxiety reduction , in this case for TURP patients waiting in the theatre holding area BACKGROUND Hospitalization causes anxiety for many patients . It increases when patients anticipate their turn for cardiac catheterization . Music therapy reduces the psychophysiologic effects of anxiety and stress through the relaxation response . AIM To determine the effects of music therapy an anxiety , heart rate and arterial blood pressure in patients waiting for their scheduled cardiac catheterization . METHODS In a quasi-experimental , pretest-posttest design , 101 subjects were r and omly assigned to either the test group : those who listened to 20 minutes of preselected music , or the control group : those who received treatment as usual . Subject anxiety levels and physiological values were measured while waiting their turn for cardiac catheterization and just prior to departure to the cardiac lab . RESULTS 63 males and 38 females participated in the study . There was a statistically significant reduction in anxiety in the test group alone ( P = 0.003 ) and in comparing the test to the control group ( P = 0.004 ) . In comparing the initial and departure physiologic values , it was noted that both heart rate and systolic blood pressure dropped in the test group , but increased in the control group . Within gender groups , there were no statistically significant differences in hemodynamics or STAI scores , but between gender groups there were significantly higher diastolic blood pressure in males and STAI initial and departure scores for females . DISCUSSION Patients waiting for their cardiac catheterization benefit from music therapy . Anxiety and the heightened physiological values elicited by the stress response are reduced . Results also suggest that women waiting for cardiac catheterization experience a higher level of anxiety than males |
12,708 | 29,996,668 | Furthermore , training seems to improve postural sway and joint position sense .
Conclusion : Balance training reduces the incidence of ankle sprains and increases dynamic neuromuscular control , postural sway , and the joint position sense in athletes | Objective : To investigate how dynamic neuromuscular control , postural sway , joint position sense , and incidence of ankle sprain are influenced by balance training in athletes compared with the control group in r and omized clinical trials . | Preventive effect of proprioceptive training is proven by decreasing injury incidence , but its proprioceptive mechanism is not . Major hypothesis : the training has a positive long-term effect on ankle joint position sense in athletes of a high-risk sport ( h and ball ) . Ten elite-level female h and ball-players represented the intervention group ( training-group ) , 10 healthy athletes of other sports formed the control-group . Proprioceptive training was incorporated into the regular training regimen of the training-group . Ankle joint position sense function was measured with the " slope-box " test , first described by Robbins et al. Testing was performed one day before the intervention and 20 months later . Mean absolute estimate errors were processed for statistical analysis . Proprioceptive sensory function improved regarding all four directions with a high significance ( p<0.0001 ; avg . mean estimate error improvement : 1.77 degrees ) . This was also highly significant ( p < or = 0.0002 ) in each single directions , with avg . mean estimate error improvement between 1.59 degrees ( posterior ) and 2.03 degrees ( anterior ) . Mean absolute estimate errors at follow-up ( 2.24 degrees + /-0.88 degrees ) were significantly lower than in uninjured controls ( 3.29 degrees + /-1.15 degrees ) ( p<0.0001 ) . Long-term neuromuscular training has improved ankle joint position sense function in the investigated athletes . This joint position sense improvement can be one of the explanations for injury rate reduction effect of neuromuscular training Objective : To compare the effectiveness of a combination of vibration and wobble board training against wobble board training alone in footballers suffering from functional ankle instability ( FAI ) . Design : A 2 × 3 prefactorial – postfactorial design . Setting : University research laboratory . Participants : Thirty-three male semiprofessional footballers with self-reported unilateral FAI were r and omly assigned in 3 groups : vibration and wobble board ( mean age 22.2 years ) , wobble board ( mean age 22.7 years ) , and control ( mean age 23.1 years ) . Interventions : Participants in each intervention group performed a 6-week progressive rehabilitation program using a wobble board , either with or without the addition of vibration stimulus . Main Outcome Measures : Absolute center of mass ( COM ) distribution during single-leg stance , modified star excursion balance test ( SEBT ) reach distances , and single-leg triple hop for distance ( SLTHD ) were measured before and after 6-week intervention . Results : Combined vibration and wobble board training result ed in reduced COM distribution [ P ⩽ 0.001 , effect size ( ES ) = 0.66 ] , increased SEBT reach distances ( P ⩽ 0.01 and P ⩽ 0.002 , ES = 0.19 and 0.29 , respectively ) , and increased SLTHD ( P ⩽ 0.001 , ES = 0.33 ) compared with wobble board training alone during the course of the 6-week training intervention . Conclusions : Combined vibration and wobble board training improves COM distribution , modified SEBT scores , and SLTHD among footballers suffering FAI compared with wobble board training alone Abstract . This prospect i ve r and omized intervention investigated whether training on a balance board could reduce the amount of traumatic injuries of the lower extremities in female soccer players . A total of 221 female soccer players from 13 different teams playing in the second and third Swedish divisions volunteered to participate in the study . Seven teams ( n=121 ) were r and omized to an intervention group and six teams ( n=100 ) to a control group and were followed during one outdoor season ( April – October ) . Before and after the season muscle flexibility and balance/postural sway of the lower extremities were measured in the players . There were no significant differences in age , height , weight , muscle flexibility and balance/postural sway of the lower extremities between the intervention and the control group . During the season the players in the intervention group performed a special training program consisting of 10–15 min of balance board training in addition to their st and ard soccer practice and games . After a 37 % drop-out the intervention group consisted of 62 players and the control group of 78 players . The results showed no significant differences between the groups with respect either to the number , incidence , or type of traumatic injuries of the lower extremities . The incidence rate of " major " injuries was higher in the intervention group than in the control group . Four of five anterior cruciate ligament injuries occurred in the intervention group , which means that we could not prevent severe knee injuries in female soccer players with balance board training . However , among the players who had been injured during the 3-month period prior to this investigation there were significantly more players from the control group than from the intervention group who sustained new injuries during the study period Eisen , TC , Danoff , JV , Leone , JE , and Miller , TA . The effects of multiaxial and uniaxial unstable surface balance training in college athletes . J Strength Cond Res 24(7 ) : 1740 - 1745 , 2010-The purpose of this study was to compare the effects of 2 different types of unstable surface balance training ( uniaxial on a rocker board [ RB ] and multiaxial on a dynadisc [ DD ] ) on balance in division 1 collegiate athletes in sports that are at high risk for ankle sprains . Subjects ( n = 36 ) consisted of male soccer players and female volleyball and soccer players who were equally and r and omly assigned to 1 of 3 groups ( CON , DD , and RB ) . Balance training consisting of balancing on 1 leg on either the RB or DD , while repeatedly catching a 1-kg ball was performed 3 times per week for 4 weeks . Balance was tested with the Star Excursion Balance Test ( SEBT ) before , halfway through , and at the completion of the balance training . Control ( CON ) subjects also were given the balance test but did not participate in the training . A 3-way repeated analysis of variance revealed that no group individually changed SEBT scores from pre ( CON , 0.98 ± 0.086 ; DD , 0.98 ± 0.083 ; RB , 0.97 ± 0.085 ) to post ( CON , 1.00 ± 0.090 ; DD , 1.01 ± 0.088 ; RB , 1.02 ± 0.068 ) after balance training . When the 2 treatment groups were combined ( DD and RB ) , the p value decreased and came closer to significance ( p = 0.136 ) . When all 3 groups were combined , there was a significant difference in SEBT scores from pretraining ( CON + DD + RB ; 0.98 ± 0.085 ) to posttraining ( CON + DD + RB ; 1.01 ± 0.082 ) , which likely indicates low statistical power . The increase in physical activity the subjects experienced during the return to in-season activity , may have contributed to the significant differences in SEBT scores over time but not between DD or RB training . Therefore , a threshold level of physical activity may exist that is necessary to maintain balance during the off-season BACKGROUND Balance training is widely used in the rehabilitation after an ankle sprain and is thought to have a decreasing effect on postural sway . The present study investigated whether a 5.5-week balance training programme leads to a decreased postural sway showing in a reduced range of centre of pressure excursion . METHODS Thirty university students participated in this study . Twenty-two untrained subjects were r and omly assigned to either an intervention group ( n=11 ) or a control group ( n=11 ) . The remaining eight subjects were participants in an organized volleyball competition and were assigned to an additional volleyball group ( n=8 ) . All subjects of the intervention group and the volleyball group received a 5.5-week balance training programme , while subjects of the control group received no training . Centre of pressure of the ground reaction force was measured as a proxy measure of postural sway , using a force platform . Measurements took place before and after the 5.5-week training programme for st and ing on one leg ( both for right and for left leg ) of single leg stance , both for the eyes-open and eyes-closed situation . From these measurements centre of pressure excursion in the anterior-posterior and the medial-lateral direction was calculated . A linear regression analysis was performed to check for differences in centre of pressure excursion between any of the groups over the training period . FINDINGS No differences in changes of centre of pressure excursion were found between any of the groups over the 5.5-week training period . INTERPRETATION Balance training does not lead to a reduction in centre of pressure excursion in a general population consisting of non-injured and previously injured subjects STUDY DESIGN Controlled cohort repeated- measures experimental design . OBJECTIVES To determine if a neuromuscular training program ( NMTP ) focused on core stability and lower extremity strength would affect performance on the star excursion balance test ( SEBT ) . We hypothesized that NMTP would improve SEBT performance in the experimental group and there would be no side-to-side differences in either group . BACKGROUND The SEBT is a functional screening tool that is used to assess dynamic stability , monitor rehabilitation progress , assess deficits following an injury , and identify athletes at high risk for lower extremity injury . The SEBT requires lower extremity coordination , balance , flexibility , and strength . METHODS Twenty uninjured female soccer players ( 13 experimental , 7 control ) participated . Players trained together as a team , so group allocation was not r and omized . The SEBT was administered prior to and following 8 weeks of NMTP in the experimental group and 8 weeks of no NMTP in the control group . A 3-way mixed-model ANOVA was used to determine the effect of group ( experimental versus control ) , training ( pretraining versus posttraining ) , and limb ( right versus left ) . RESULTS After participation in a NMTP , subjects demonstrated a significant improvement in the SEBT composite score ( mean ± SD ) on the right limb ( pretraining , 96.4 % ± 11.7 % ; posttraining , 104.6 % ± 6.1 % ; P = .03 ) and the left limb ( pretraining , 96.9 % ± 10.1 % ; posttraining , 103.4 % ± 8.0 % ; P = .04 ) . The control group had no change on the SEBT composite score for the right ( pretraining , 95.7 % ± 5.2 % ; posttraining , 94.4 % ± 5.2 % ; P = .15 ) or the left ( 97.4 % ± 7.2 % ; 93.6 % ± 5.0 % ; P = .09 ) limb . Further analysis identified significant improvement for the SEBT in the posterolateral direction on both the right ( P = .008 ) and left ( P = .040 ) limb and the posteromedial direction of the left limb ( P = .028 ) in the experimental group . CONCLUSION Female soccer players demonstrated an improved performance on the SEBT after NMTP that focused on core stability and lower extremity strength Background Ankle sprains are the most common injuries in a variety of sports . Hypothesis A proprioceptive balance board program is effective for prevention of ankle sprains in volleyball players . Study Design Prospect i ve controlled study . Methods There were 116 male and female volleyball teams followed prospect ively during the 2001 - 2002 season . Teams were r and omized by 4 geographical regions to an intervention group ( 66 teams , 641 players ) and control group ( 50 teams , 486 players ) . Intervention teams followed a prescribed balance board training program ; control teams followed their normal training routine . The coaches recorded exposure on a weekly basis for each player . Injuries were registered by the players within 1 week after onset . Results Significantly fewer ankle sprains in the intervention group were found compared to the control group ( risk difference = 0.4/1000 playing hours ; 95 % confidence interval , 0.1 - 0.7 ) . A significant reduction in ankle sprain risk was found only for players with a history of ankle sprains . The incidence of overuse knee injuries for players with history of knee injury was increased in the intervention group . History of knee injury may be a contraindication for proprioceptive balance board training . Conclusions Use of proprioceptive balance board program is effective for prevention of ankle sprain recurrences PURPOSE To investigate the effectiveness of a multistation proprioceptive exercise program for the prevention of ankle injuries in basketball players using a prospect i ve r and omized controlled trial in combination with biomechanical tests of neuromuscular performance . METHODS A total of 232 players participated in the study and were r and omly assigned to a training or control group following the CONSORT statement . The training group performed a multistation proprioceptive exercise program , and the control group continued with their normal workout routines . During one competitive basketball season , the number of ankle injuries was counted and related to the number of sports participation sessions using logistic regression . Additional biomechanical pre – post tests ( angle reproduction and postural sway ) were performed in both groups to investigate the effects on neuromuscular performance . RESULTS In the control group , 21 injuries occurred , whereas in the training group , 7 injuries occurred . The risk for sustaining an ankle injury was significantly reduced in the training group by approximately 65 % . [ corrected ] The corresponding number needed to treat was 7 . Additional biomechanical tests revealed significant improvements in joint position sense and single-limb stance in the training group . CONCLUSIONS The multistation proprioceptive exercise program effectively prevented ankle injuries in basketball players . Analysis of number needed to treat clearly showed the relatively low prevention effort that is necessary to avoid an ankle injury . Additional biomechanical tests confirmed the neuromuscular effect and confirmed a relationship between injury prevention and altered neuromuscular performance . With this knowledge , proprioceptive training may be optimized to specifically address the dem and s in various athletic activities Background Ankle sprains are frequent injuries in soccer . Several strategies can be used to prevent further ankle sprains in athletes : the most common are proprioceptive training , strength training , and orthoses . Objective To investigate which of these 3 interventions is the most effective in preventing ankle sprains in athletes with previous ankle inversion sprain . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods and Measures Eighty male soccer players ( age , 24.6 ± 2.63 years ; height , 175.60 ± 4.36 cm ; weight , 64.26 ± 8.37 kg ) in the first division of a men 's league who had experienced previous ankle inversion sprain were r and omly selected from an original population of 120 players . The subjects were individually and r and omly assigned to 4 study groups : group 1 ( n = 20 ) followed the proprioceptive program , group 2 ( n = 20 ) followed the strength program , group 3 ( n = 20 ) used orthoses , and group 4 ( n = 20 ) was the control group . Data on the frequency of ankle sprain reinjury were collected at the end of the session . Results There were no significant differences among the groups in the number of exposures . The incidence of ankle sprains in players in the proprioception training group was significantly lower than in the control group ( relative risk of injury , 0.13 ; 95 % confidence interval , 0.003 - 0.93 ; P = .02 ) . The findings with respect to the strength and orthotic groups in comparison with the control group were not significant ( relative risk of injury , 0.5 ; 95 % confidence interval , 0.11 - 1.87 ; P = .27 for strength ; relative risk of injury , 0.25 ; 95 % confidence interval , 0.03 - 1.25 ; P = .06 for orthotic group ) . Conclusion Proprioceptive training , compared with no intervention , was an effective strategy to reduce the rate of ankle sprains among male soccer players who suffered ankle sprain Background Very little objective data are available regarding medial ankle instability . Hypothesis Several structures contribute to the stabilization of the medial ankle , and , in the case of injury , they are not involved in a uniform way . Study Design Explorative , prospect i ve case series . Methods Fifty-one patients ( 52 ankles ; males 27 , females 25 ; age 36.4 [ 16 to 60 ] years ) were surgically treated because of medial ankle instability . All clinical findings and structural changes , as found by arthroscopy and surgical exploration , were compared with the clinical diagnosis and then addressed for surgical reconstruction . Results Pain in the medial gutter was noted in all ankles ( 100 % ) . Arthroscopy verified a clinical ly expected additional lateral instability in 40 ankles ( 77 % ) . At 4.43 years ( 2 to 6.5 years ) after surgical reconstruction , the clinical result was considered to be good/excellent in 46 cases ( 90 % ) , fair in 4 cases ( 8 % ) , and poor in 1 case ( 2 % ) . Conclusion The clinical characteristics of medial ankle instability are a feeling of giving way , pain on the medial gutter of the ankle , and a valgus and pronation deformity of the foot that can typically be actively corrected by the posterior tibial muscle . Arthroscopy was shown to be a very helpful diagnostic tool in verifying medial instability Objective To evaluate the effectiveness of an unsupervised proprioceptive training programme on recurrences of ankle sprain after usual care in athletes who had sustained an acute sports related injury to the lateral ankle ligament . Design R and omised controlled trial , with one year follow-up . Setting Primary care . Participants 522 athletes , aged 12 - 70 , who had sustained a lateral ankle sprain up to two months before inclusion ; 256 ( 120 female and 136 male ) in the intervention group ; 266 ( 128 female and 138 male ) in the control group . Intervention Both groups received treatment according to usual care . Athletes allocated to the intervention group additionally received an eight week home based proprioceptive training programme . Main outcome measure Self reported recurrence of ankle sprain . Results During the one year follow-up , 145 athletes reported a recurrent ankle sprain : 56 ( 22 % ) in the intervention group and 89 ( 33 % ) in the control group . Nine athletes needed to be treated to prevent one recurrence ( number needed to treat ) . The intervention programme was associated with a 35 % reduction in risk of recurrence . Cox regression analysis showed significantly fewer recurrent ankle sprains in the intervention than in the control group . This effect was found for self reported recurrent ankle sprains ( relative risk 0.63 , 95 % confidence interval 0.45 to 0.88 ) , recurrent ankle sprains leading to loss of sports time ( 0.53 , 0.32 to 0.88 ) , and recurrent ankle sprains result ing in healthcare costs or lost productivity costs ( 0.25 , 0.12 to 0.50 ) . No significant differences were found between medically treated athletes in the intervention group and medically treated controls . Athletes in the intervention group who were not medically treated had a significantly lower risk of recurrence than controls who were not medically treated . Conclusions The use of a proprioceptive training programme after usual care of an ankle sprain is effective for the prevention of self reported recurrences . This proprioceptive training was specifically beneficial in athletes whose original sprain was not medically treated . Trial registration Lateral ankle sprain ( LAS ) is one of the most common injuries incurred during sporting activities , and effective rehabilitation programs for this condition are challenging to develop . The purpose of this research was to compare the effect of 6 weeks of balance training on either a mini-trampoline or a dura disc on postural sway and to determine if the mini-trampoline or the dura disc is more effective in improving postural sway . Twenty subjects ( 11 men , 9 women ) with a mean age of 25.4 ± 4.2 years were r and omly allocated into a control group , a dura disc training ( DT ) group , or a mini-trampoline ( MT ) group . Subjects completed 6 weeks of balance training . Postural sway was measured by subjects performing a single limb stance on a force plate . The disbursement of the center of pressure was obtained from the force plate in the medial-lateral and the anterior-posterior sway path and was subsequently used for pretest and posttest analysis . After the 6-week training intervention , there was a significant ( p < 0.05 ) difference in postural sway between pre- and posttesting for both the MT ( pretest = 56.8 ± 20.5 mm , posttest = 33.3 ± 8.5 mm ) and DT ( pretest = 41.3 ± 2.6 mm , posttest = 27.2 ± 4.8 mm ) groups . There was no significant ( p > 0.05 ) difference detected for improvements between the MT and DT groups . These results indicate that not only is the mini-trampoline an effective tool for improving balance after LAS , but it is equally as effective as the dura disc Background Ankle sprains are the most common musculoskeletal injuries that occur in athletes , and they have a profound impact on health care costs and re sources . Hypothesis A balance training program can reduce the risk of ankle sprains in high school athletes . Study Design R and omized controlled clinical trial ; Level of evidence , 1 . Methods Seven hundred and sixty-five high school soccer and basketball players ( 523 girls and 242 boys ) were r and omly assigned to either an intervention group ( 27 teams , 373 subjects ) that participated in a balance training program or to a control group ( 28 teams , 392 subjects ) that performed only st and ard conditioning exercises . On-site athletic trainers recorded athlete exposures and sprains . Results The rate of ankle sprains was significantly lower for subjects in the intervention group ( 6.1 % , 1.13 of 1000 exposures vs 9.9 % , 1.87 of 1000 exposures ; P = .04 ) . Athletes with a history of an ankle sprain had a 2-fold increased risk of sustaining a sprain ( risk ratio , 2.14 ) , whereas athletes who performed the intervention program decreased their risk of a sprain by one half ( risk ratio , 0.56 ) . The ankle sprain rate for athletes without previous sprains was 4.3 % in the intervention group and 7.7 % in the control group , but this difference was not significant ( P = .059 ) . Conclusion A balance training program will significantly reduce the risk of ankle sprains in high school soccer and basketball players The objective of the present study was to determine the effectiveness of a 6-week balance training program on patients with Chronic Ankle Instability ( CAI ) in relation to the results obtained in Dynamic Balance , subjective feeling of instability and pain using a single-blind r and omized controlled trial . 70 athletes were r and omly assigned to control or intervention group . The control group performed their usual training , and the intervention group was administered the same usual activity in addition to a balance program . The paired t-test was performed to evaluate the change scores in each group . The t-test for independent sample s was performed to evaluate between-group differences in change scores . Significance level was assigned for p-values less than 0.05 for all analyses . There were significant differences between groups in change scores in CAIT and all of the SEBTs reach distances ( p<0.001 ) but not in Pain ( p=0.586 ) . The effect sizes were larger for the outcomes measures that showed significant differences . In the within-group change , the experimental groups showed larger effect sizes in CAIT , SEBT posteromedial and SEBT posterolateral , and moderate effect sizes in SEBT anterior . Exercise therapy training based on multi-station balance tasks led to significant improvements in dynamic balance and self-reported sensation of instability in patients with CAI PURPOSE The purpose of this r and omized controlled trial was to determine the effect of a 4-wk balance training program on static and dynamic postural control and self-reported functional outcomes in those with chronic ankle instability ( CAI ) . METHODS Thirty-one young adults with self-reported CAI were r and omly assigned to an intervention group ( six males and 10 females ) or a control group ( six males and nine females ) . The intervention consisted of a 4-wk supervised balance training program that emphasized dynamic stabilization in single-limb stance . Main outcome measures included the following : self-reported disability on the Foot and Ankle Disability Index ( FADI ) and the FADI Sport scales ; summary center of pressure ( COP ) excursion measures including area of a 95 % confidence ellipse , velocity , range , and SD ; time-to-boundary ( TTB ) measures of postural control in single-limb stance including the absolute minimum TTB , mean of TTB minima , and SD of TTB minima in the anteroposterior and mediolateral directions with eyes open and closed ; and reach distance in the anterior , posteromedial , and posterolateral directions of the Star Excursion Balance Test ( SEBT ) . RESULTS The balance training group had significant improvements in the FADI and the FADI Sport scores , in the magnitude and the variability of TTB measures with eyes closed , and in reach distances with the posteromedial and the posterolateral directions of the SEBT . Only one of the summary COP-based measures significantly changed after balance training . CONCLUSIONS Four weeks of balance training significantly improved self-reported function , static postural control as detected by TTB measures , and dynamic postural control as assessed with the SEBT . TTB measures were more sensitive at detecting improvements in static postural control compared with summary COP-based measures CONTEXT Plyometric exercise has been recommended to prevent lower limb injury , but its feasibility in and effects on those with functional ankle instability ( FAI ) are unclear . OBJECTIVE To investigate the effect of integrated plyometric and balance training in participants with FAI during a single-legged drop l and ing and single-legged st and ing position . DESIGN R and omized controlled clinical trial . SETTING University motion- analysis laboratory . PATIENTS OR OTHER PARTICIPANTS Thirty athletes with FAI were divided into 3 groups : plyometric group ( 8 men , 2 women , age = 23.20 ± 2.82 years ; 10 unstable ankles ) , plyometric-balance (integrated)-training group ( 8 men , 2 women , age = 23.80 ± 4.13 years ; 10 unstable ankles ) , and control group ( 7 men , 3 women , age = 23.50 ± 3.00 years ; 10 unstable ankles ) . INTERVENTION(S ) A 6-week plyometric-training program versus a 6-week integrated-training program . MAIN OUTCOME MEASURE(S ) Postural sway during single-legged st and ing with eyes open and closed was measured before and after training . Kinematic data were recorded during medial and lateral single-legged drop l and ings after a 5-second single-legged stance . RESULTS Reduced postural sway in the medial-lateral direction and reduced sway area occurred in the plyometric- and integrated-training groups . Generally , the plyometric training and integrated training increased the maximum angles at the hip and knee in the sagittal plane , reduced the maximum angles at the hip and ankle in the frontal and transverse planes in the lateral drop l and ing , and reduced the time to stabilization for knee flexion in the medial drop l and ing . CONCLUSIONS After 6 weeks of plyometric training or integrated training , individuals with FAI used a softer l and ing strategy during drop l and ings and decreased their postural sway during the single-legged stance . Plyometric training improved static and dynamic postural control and should be incorporated into rehabilitation programs for those with FAI OBJECTIVES Despite the health benefits of organized sports , high school athletes are at risk for lower extremity sports-related injuries ( LESRIs ) . The authors documented the epidemiology of LESRIs among U.S. high school athletes . METHODS Via two-stage sampling , 100 U.S. high schools were r and omly selected . During the 2005 school year , LESRIs in nine sports were reported : boys ' baseball , football , and wrestling ; girls ' softball and volleyball ; and boys ' and girls ' basketball and soccer . The authors calculated rates as the ratio of LESRIs to the number of athlete exposures . National estimates were generated by assigning injuries a sample weight based on the inverse probability of the school 's selection into the study . RESULTS Among high school athletes in 2005 , 2,298 of 4,350 injuries ( 52.8 % ) were LESRIs . This represents an estimated 807,222 LESRIs in U.S. high school athletes in nine sports ( 1.33/1,000 athlete exposures ) . Football had the highest LESRI rate for boys ( 2.01/1,000 ) and soccer the highest for girls ( 1.59/1,000 ) . Leading diagnoses were sprains ( 50 % ) , strains ( 17 % ) , contusions ( 12 % ) , and fractures ( 5 % ) . The ankle ( 40 % ) , knee ( 25 % ) , and thigh ( 14 % ) were most frequently injured . Fractures occurred most often in the ankle ( 42 % ) , lower leg ( 29 % ) , or foot ( 18 % ) . Girls with ligamentous knee injuries required surgery twice as often as boys ( 67 % vs. 35 % ; p < 0.01 ) . Girls had 1.5 times the proportion of season-ending LESRIs of boys ( 12.5 % vs. 8 % ; p < 0.01 ) . CONCLUSIONS While LESRIs occur commonly in high school athletes , team- and gender-specific patterns exist . Emergency department staff will likely encounter such injuries . To optimize prevention strategies , ongoing surveillance is needed |
12,709 | 25,040,541 | We conclude that good conditions for tracheal intubation are more likely by delaying laryngoscopy after injecting a higher dose of mivacurium with an opioid , particularly in older people | null | null |
12,710 | 25,883,410 | Investigators could do more to help participants achieve a complete underst and ing | Abstract Objective To estimate the proportion of participants in clinical trials who underst and different components of informed consent . | Summary Objective Several reports have shown that despite the informed consent process , enrolled patients misunderst and the modalities and goals of r and omized clinical trials ( RCTs ) . We believe that this may be linked to a priori misconceptions in the main population . The purpose of this study is to compare the knowledge about cancer RCTs in enrolled participants ( cases ) versus patients treated under cancer st and ard care who have never taken part in RCTs ( controls ) . Methods We su bmi tted a vali date d question naire ( ICEC-R ) to both population s to explore their knowledge about RCTs . A total of 75 cases and 107 controls were included . Results Globally , the cases ’ knowledge was significantly better , especially about ( i ) the r and omization process , ( ii ) the uncertain potential benefits , and ( iii ) the right to withdraw consent . Both population s presented the lowest scores for items exploring the r and omization process and uncertain treatment benefits . Conclusion Enrolled patients ’ comprehension of the goals and means of RCTs is actually better than controls ’ . Nevertheless , additional efforts should be made to enhance information about clinical research to patients as well as to the main population . Practice Implication s Having better knowledge about patients ’ difficulties in underst and ing RCTs would allow physicians to adjust the information they give and then to enhance patients ’ well-being We attempted to characterize the motivation , comprehension and expectations of patients who had given informed consent to participate in phase I trials of anti-cancer agents at the National Cancer Center of Japan . Thirty-three patients were given a simple multiple-choice question naire and asked to return it at a later date . The completed survey was returned by 32 patients . The patients were surveyed before they had received any investigational phase I agents . Nineteen per cent of patients were motivated to participate in the phase I trials by the possibility of therapeutic benefit , 9 % because participation seemed a better choice than no treatment and only 6 % for altruistic reasons . Most patients comprehended the major features of a phase I trial , namely its investigational nature , the unknown effects of the agent investigated and the unclear benefit to the patients themselves . Fifty-nine per cent of the patients anticipated that they might suffer severe or life-threatening side-effects if they participated in the phase I trial , and 43 % were able to indicate accurately the purpose of the phase I trial as a dose determination study . Although only a minority of the patients indicated that their motivation to participate was possible treatment benefit to themselves , when answering questions regarding expectations , more than half indicated that there might be personal benefits of varying degrees by participation Background and aim : As non-r and omised studies have suggested that surgical decompression may reduce mortality in patients with space occupying hemispheric infa rct ion , r and omisation may be considered unethical in controlled trials testing this treatment strategy . We studied differences in recall of information and in appreciation of the informed consent procedure between representatives included in the Hemicraniectomy After Middle cerebral artery infa rct ion with Life-threatening Edema Trial ( HAMLET ) and representatives of patients participating in the r and omised trial of Paracetamol ( Acetaminophen ) In Stroke ( PAIS ) . Methods : 1 year after study inclusion , we contacted 30 consecutive representatives who had given informed consent for participation of their relative in HAMLET , and 30 for PAIS . Recall of trial details and appreciation of the informed consent procedure were investigated using st and ardised question naires and compared between the two groups . Results : All 30 PAIS representatives and 28 HAMLET representatives were interviewed . Participation of their relative in a clinical trial was remembered by 86 % of HAMLET and 40 % of PAIS representatives ( p<0.001 ) . HAMLET representatives remembered more trial details ( effect of the treatment under study ( 61 % vs 3 % , p<0.001 ) ; r and omised treatment allocation ( 71 % vs 0 % , p<0.001 ) ) . With respect to appreciation of the informed consent procedure , we found no differences between the groups : in each trial , four representatives ( 14 % vs 13 % ) had considered the question of r and omisation unacceptable . Conclusions : Participation of patients in a r and omised controlled trial of surgical decompression for space occupying infa rct ion is generally considered acceptable by their representatives , and recall of trial details is better than in a trial in which less vital issues are at stake Background : R and omised controlled trials of interventions in critical situations are necessary to establish safety and evaluate outcomes . Pregnant women have been identified as a potentially vulnerable population . Objective : To explore women ’s experiences of being recruited to ORACLE , a r and omised controlled trial of antibiotics in pre-term labour . Methods : Twenty qualitative interviews were conducted with women who had participated in ORACLE . Analysis was based on the constant comparative method . Results : Women gave prominence to the socioemotional aspects of their interactions with healthcare professionals in making decisions on trial participation . Comments on the quality of written and spoken information were generally favourable , but women ’s accounts suggest that the stressful nature of the situation affected their ability to absorb the information . Women generally had poor underst and ing of trial design and practice s. The main motivation for trial participation was the possibility of an improved outcome for the baby . The second and less prominent motivation was the opportunity to help others , but this was conditional on there being no risks associated with trial participation . In judging the risks of participation , women seemed to draw on “ common sense ” underst and ings including a perception that antibiotics were risk free . Discussion : Recruitment to trials in critical situations raises important questions . Future studies should explore how rigorous governance arrangements for trials , particularly in critical situations , can protect participants rather than relying on ideals of informed consent that may be impossible to achieve . Future research should include a focus on interactions between research c and i date s and professionals involved in recruitment BACKGROUND : Consent for participation in clinical research is considered valid if it is informed , understood , and voluntary . In the case of minors , parents give permission for their child to participate in research studies after being presented with all information needed to make an informed decision . Although informed consent is a vital component of clinical research , there is little information evaluating its validity in neonatal intensive-care population s. The objective of this project was to determine the validity of informed consent obtained from parents of infants enrolled in the multicenter r and omized research study , neurologic outcomes and pre-emptive analgesia in the neonate ( NEOPAIN ) . DESIGN / METHODS : Parents of infants who survived to discharge and had signed consent for their newborn to participate in the NEOPAIN study at the University of Kentucky were asked 20 open-ended questions to determine their level of underst and ing about the NEOPAIN study . The NEOPAIN consent form , which had been approved by the University of Kentucky Medical Institutional Review Board ( IRB ) , was used to formulate these questions . Questions addressed the timing of consent , parental underst and ing of the purpose , benefits , and risks of the study , the voluntary nature of the project , and their willingness to enroll in future studies if the opportunity presented . Answers were scored on a Likert scale , with 1 for no underst and ing and 5 for complete underst and ing . RESULTS : Five of 64 parents ( 7.8 % ) had no re collection of the NEOPAIN study or of signing consent . Of those who remembered the study , only 67.8 % understood the purpose of the study , with a higher proportion of the mothers than fathers knowing the purpose of the study ( 73.3 % vs 57.1 % ) , ( p=0.029 ) . Of those who understood the purpose of the study 95 % were able to verbalize the benefits , but only 5 % understood any potential risks . No parents reported feeling pressured or coerced to sign consent for the project and all parents reported they would enroll their child in additional studies if asked . CONCLUSIONS : Valid consent in the antenatal/perinatal population is difficult , if not impossible , to obtain . To maximize validity of consent in the antenatal/perinatal population every effort should be made to include mothers in the consent process . Additional attention during the consent process should be given to possible risks of the study Background Informed consent ( IC ) has been an international st and ard for decades for the ethical conduct of clinical trials . Yet frequently study participants have incomplete underst and ing of key issues , a problem exacerbated by language barriers or lack of familiarity with research concepts . Few investigators measure participant comprehension of IC , while even fewer conduct interim assessment s once a trial is underway . Methods and Findings We assessed comprehension of IC using a 20- question true/false quiz administered in 6-month intervals in the context of a placebo-controlled , r and omized trial for the prevention of tuberculosis among HIV-infected adults in Botswana ( 2004–2009 ) . Quizzes were offered in both Setswana and English . To enroll in the TB trial , participants were required to have ≥16/20 correct responses . We examined concepts understood and the degree to which underst and ing changed over three-years . We analyzed 5,555 quizzes from 1,835 participants . The participants ' highest education levels were : 28 % primary , 59 % secondary , 9 % tertiary and 7 % no formal education . Eighty percent of participants passed the enrollment quiz ( Quiz1 ) on their first attempt and the remainder passed on their second attempt . Those having higher than primary education and those who took the quiz in English were more likely to receive a passing score on their first attempt ( adjusted odds ratios and 95 % confidence intervals , 3.1 ( 2.4–4.0 ) and 1.5 ( 1.2 , 1.9 ) , respectively ) . The trial 's purpose or procedures were understood by 90–100 % of participants , while 44–77 % understood r and omization , placebos , or risks . Participants who failed Quiz1 on their initial attempt were more likely to fail quizzes later in the trial . Pass rates improved with quiz re-administration in subsequent years . Conclusions Administration of a comprehension quiz at enrollment and during follow-up was feasible in a large , international collaboration and efficiently determined IC comprehension by trial participants . Strategies to improve underst and ing of concepts like placebos and r and omization are needed . Comprehension assessment s throughout a study may reinforce key concepts In the Beta-blocker Heart Attack Trial ( BHAT ) a number of strategies were implemented to increase the probability of informed voluntary consent among survivors of an acute myocardial infa rct ion . To evaluate the subjects ' comprehension of the study , a bioethicist conducted in-depth home interviews with a r and om sample of 64 participants from 11 geographic areas . The great majority of respondents proved to be well informed about the study design , its scientific logic , and possible risks of the experimental drug . However , five subjects ( 8 % of the sample ) appeared to believe they were involved in a therapeutic program rather than a research project . The analysis of predictor variables indicates that education , race , and age were associated with the degree of respondent awareness of fundamental aspects of the trial Background : In patients with acute life threatening diseases , and in their relatives , the ability to make a balanced decision on participation in a clinical trial may be impaired . Objectives : To assess what relevant information could be recalled by patients who were living independently after a subarachnoid haemorrhage , and by their relatives ; and to determine how these patients and relatives had reacted to the informed consent encounter . Methods : Twenty months ( range 7 to 31 ) after treatment for subarachnoid haemorrhage , 49 patients and 47 relatives who had participated in one of two r and omised trials on medical management were interviewed . The interview consisted of items on : spontaneous recall and knowledge of trial design ; underst and ing of the trial design and the informed consent procedure ; the amount and clarity of the information given ; and reasons for participating . Finally patients and relatives were asked whether they would participate again in similar circumstances . Results : One third of the patients recalled having participated in a clinical trial . Thirteen per cent of the patients and 20 % of the relatives felt that the information supplied had not been sufficient . Nine per cent of the patients and half the relatives had read the written information . None of the patients and one relative thought that participation had been obligatory . Twenty eight per cent of the patients and 94 % of the relatives felt in retrospect that they had been capable of making an adequate decision . Virtually all patients and relatives would participate again in similar circumstances . Conclusions : Many patients and their relatives have little recall of the informed consent procedure and the essentials of acute subarachnoid haemorrhage trials . However , most were satisfied with the overall procedure and would participate again Background and objectives : There are few insights from sub-Saharan Africa on research participants ’ experiences of the informed consent process , particularly in the context of r and omised controlled trials , where issues of r and omisation and the use of placebos may be confusing concepts for participants . This study investigated the knowledge and perceptions of the informed consent process among individuals participating in influenza vaccine trials in two disadvantaged communities in South Africa . Method : Four to 12 months after completion of the trials , participants were contacted to return to participate in the informed consent study . The semistructured question naire administered to assess recall of trial procedures and the informed consent process covered key issues including : purpose of the study ; awareness that the study was not part of routine treatment ; voluntary nature of participation and freedom to withdraw ; r and omisation ; placebos ; and remuneration . Results : A total of 334 participants ( 93 % of the original vaccine trial sample ; mean age 68 years , median level of education grade 8 , 69 % women ) completed the question naire . Only 21 % were able to recall that they were allocated r and omly to the different treatment arms . Only 19 % of those involved in the placebo controlled study had interpreted the concept of placebo as an inactive medication . Conclusion : Although a good general recall of trial concepts was demonstrated , only a small proportion of the participants correctly interpreted and recalled the concepts of r and omisation and placebos . Informed consent in this and similarly disadvantaged communities may often be inadequate and new ways to improve underst and ing of the research process should be explored This paper reports on the reasons why patients agreed to or declined entry into r and omized trials of cancer following discussion s conducted by clinicians in both District General and University Hospitals . Two hundred and four patients completed a 16-item question naire following the consultation , of these 112 ( 55 % ) were women with breast cancer . Overall results showed that 147 ( 72.1 % ) patients accepted entry to a r and omized clinical trial ( RCT ) . The main reasons nominated for participating in a trial were that ‘ others will benefit ’ ( 23.1 % ) and ‘ trust in the doctor ’ ( 21.1 % ) . One of the main reasons for declining trial entry was that patients were ‘ worried about r and omization ’ ( 19.6 % ) . There was a significantly higher acceptance rate for trials providing active treatment in every arm 98 ( 80.6 % ) compared with those trials with a no treatment arm 46 ( 60.5 % ) , χ2test P = 0.003 . The study outlines a number of factors that appear to influence a patient ’s decision to accept or decline entry into an RCT of cancer therapy . An important factor is whether or not the trial offers active treatment in all arms of the study . Communication that promotes trust and confidence in the doctor is also a powerful motivating influence . © 2000 Cancer Research R and omized controlled trials ( RCTs ) are widely accepted by the scientific community as the most rigorous way of evaluating interventions in health care . Although their central feature , r and om allocation of treatment , is generally seen as method ologically appropriate , its application has caused much debate amongst health professionals and ethicists . This paper describes the views of parents who consented that their critically ill newborn baby should be enrolled in a neonatal trial . In-depth interviews were used to determine their response to the trial and r and omization . The nature of the trial was often poorly understood . The r and om basis of the allocation of treatment and the rationale behind this approach were also problematic issues . Some parents did not perceive a r and om element in the process at all . These findings advance underst and ing of the perceptions of trial participants and raise important issues for those concerned with RCTs . Greater underst and ing of participants ' views provides the potential to improve the management of future trials and so the experience of those agreeing to take part PURPOSE To examine both the use of the consent document during the informed consent process for pediatric leukemia clinical trials , as well as relationships between the use of the document and parental underst and ing of essential elements of informed consent . METHODS Participants included 140 parents of children diagnosed with pediatric leukemia . Informed consent conferences in which r and omized clinical trials were discussed were observed , audiotaped , and coded for specific behaviors . Parents were also interviewed within 48 h of their participation in informed consent conferences . RESULTS Observations revealed that 74 % of cases included explanation of consent documents during consent conferences . Parents who reported that they read the consent document were more likely to underst and differences between the clinical trial and off study therapy and were more likely to underst and the right to withdraw . Reading of the consent document was not associated with underst and ing of voluntariness . In comparison to racial/ethnic majority parents , racial/ethnic minority parents were less likely to report that they read the consent document , underst and voluntariness or the right to withdraw , and were less likely to be able to distinguish between the clinical trial and off study therapy . Low SES was associated with a lower probability of reading the consent document and being able to distinguish between clinical trials and off study therapy . CONCLUSIONS Attention to the importance of reading the consent document and improving communication during consent conferences is likely to enhance underst and ing of essential elements of informed consent Objectives : To explore how subjects in a placebo-controlled vitamin A supplementation trial among Ghanaian women aged 15–45 years perceive the trial and whether they know that not all trial capsules are the same , and to identify factors associated with this knowledge . Methods : 60 semistructured interviews and 12 focus groups were conducted to explore subjects ’ perceptions of the trial . Steps were taken to address areas of low comprehension , including retraining fieldworkers . 1971 trial subjects were r and omly selected for a survey measuring their knowledge that not all trial capsules are the same . The subjects ’ fieldworkers were also interviewed about their characteristics and trial knowledge . Factors associated with knowledge were explored using multi-level modeling . Results : Although subjects knew they were taking part in research , most thought they were receiving an active and beneficial medication . Variables associated with knowledge were education and district of residence . Radio broadcasts benefited those with some schooling . Fieldworkers ’ characteristics were not associated with subjects ’ knowledge . Conclusions : Research and debate on new or improved consent procedures are urgently required , particularly for subjects with little education OBJECTIVE The HIV vaccine attempts in developing countries have underlined many ethical questions on the informed consent of the participants . These problems have already been encountered in the context of studies on the prevention of mother-child transmission ( MCT ) of HIV in Africa . This study is aim ed at describing the level of underst and ing and interpretations that these women have of the clinical trial , r and omisation and placebo , as well as their motivations for participating in the study . METHODS This was a qualitative study conducted in 1997 by a sociologist in the form of in-depth , structured interviews among 57 women participating in a clinical trial on the prevention of MCT of HIV . The interview included a section on the representation of MCT then questions on the eventual sharing of information concerning the HIV-infection status , the motivations for participating in the study and the underst and ing of the r and omIsation and the placebo . RESULTS Nearly half of the women had not shared the result of their blood test with anyone . Their isolation enhanced the difficulties in getting information on the study . The notion of a probability of transmission was not easy to explain in terms adapted to the level of education of the women . The r and omisation was understood as a number pulled out of a hat during a lucky draw . The women did not really underst and the pictures used to describe the placebo . They cl aim ed that they wanted to participate in the study essentially to protect their child and to have access to treatment . CONCLUSION The correct information of patients participating in clinical trials requires repeated interventions throughout the research period . When there is no social protection , the notion of freedom of choice itself , including the idea of informed consent , is relative and the pragmatic choices made by the women clearly show this . These elements must be taken into consideration in the projects of vaccination trials Recruitment to trials is known to be difficult . Previous research suggests that a crucial factor may be participants ' difficulty with the concept of r and omization . This study explored patients ' perceptions of r and omization and reasons for consent or refusal to participate in the ProtecT study ( a r and omized trial of surgery , radiotherapy , and monitoring for localized prostate cancer ) . In-depth interviews were conducted with 21 men diagnosed with localized prostate cancer who were invited to participate in the ProtecT treatment trial . Interviewees were selected purpose fully from three U.K. clinical centers to ensure the inclusion of similar proportions of those agreeing or refusing r and om treatment allocation in each of the treatment groups . Interviews explored men 's recall and underst and ing of chance , comparison , and equipoise , and reasons for consent/refusal of r and omization and acceptance/rejection of treatment allocation . Data were analyzed method ically using the techniques of constant comparison . Checking of coding and interpretation was assured by four experienced qualitative research ers . Recall and underst and ing of the major principles of the r and omized design were good and were similar for " chance " and " comparison " between those who consented to and refused r and omization . Clinical equipoise , however , caused difficulty . Almost all recalled and understood it , but those who found it acceptable tended to consent to r and omization and those who could not accept it tended to refuse to participate . Belief in clinical equipoise was key to participants ' consent to r and omization . Ensuring patients underst and and accept equipoise may thus increase their readiness to consent to participate in trials . A priority for future research is to focus on the provision and presentation of suitable and effective trial information , concentrating in particular on the neglected concept of clinical equipoise PURPOSE To compare the informed consent processes for phase III pediatric and adult oncology clinical trials in view of the critical importance of human subjects protection in both pediatric and adult cancer care . Findings are discussed in terms of the opportunities for improving pediatric and adult oncology informed consent . PATIENTS AND METHODS A total of 219 subjects are reported on . Adult oncology patients made up 36.1 % ( n = 79 ) of the sample . Pediatric surrogates made up the remaining 63.9 % ( n = 140 ) . Subjects in both studies were observed and audiotaped in conversation with their oncologists , and interviewed afterwards . Comparisons between the adult and pediatric subjects were done using chi(2 ) statistics and t tests . RESULTS Differences between the pediatric and adult informed consent processes were found . Adult oncology decision makers were , on average , more fully informed and more actively engaged by their oncologists . Pediatric decision makers were , however , given more information about survival/cure , r and omization , and voluntariness . Comprehension difficulties were more frequent among pediatric decision makers . Suggestions for improvement are made in view of the differences between adult and pediatric oncology research environments . CONCLUSION Ongoing efforts to improve the ethical framework of clinical cancer research need to take into account the key differences between pediatric and adult oncology informed consent . More research needs to be done to explore the differences between adult and pediatric informed consent processes in oncology OBJECTIVE To identify the determinants of patients ' decision-making for participation in a cataract surgery clinical trial in a tertiary care hospital . DESIGN Prospect i ve observational study . PARTICIPANTS We interviewed by question naire 40 patients scheduled to have cataract surgery . METHODS The data collected from patients included attitudes about informed consent , evaluation of the provision of information , and sociodemographic variables . RESULTS Overall , 20 ( 50 % ) patients consented to enter the trial . All patients ( n = 20;100 % ) in the consenting group expected positive implication s compared to 6 ( 30 % ) in the nonconsenting group , who expected negative implication s ( p = 0.008 ) . The majority of patients ( 90 % ) in the nonconsenting group felt that the degree of risk incurred by undergoing trial treatment was moderate to high . The perceived burden imposed on daily life by participating was seen by the nonconsenting group to be moderately higher in 11 patients ( 55 % ) compared to 3 patients ( 15 % ) in the consenting group ( p = 0.026 ) . Of the nonconsenting patients , 50 % were dissatisfied with the attitudes of medical experiments as compared to 2 % of those who did consent ( p = 0.023 ) . CONCLUSION The major reasons for participation in a cataract surgery trial were ( i ) expected positive implication s result ing from involvement ; and ( ii ) satisfaction with the attitudes of medical experiments . Patients who refused to enter the trial felt that the degree of risk as well as the burden imposed on daily life by participating were high . Demographic variables did not have any impact on a patients ' decisions to accept or decline entry into the trial BACKGROUND The informed consent procedure plays a central role in r and omised controlled trials but has only been explored in a few studies on children . AIM To assess the quality of the informed consent process in a paediatric setting . METHODS A question naire was sent to parents who volunteered their child ( 230 children ) for a r and omised , double blind , placebo controlled trial of ibuprofen syrup to prevent recurrent febrile seizures . RESULTS 181 ( 79 % ) parents responded . On average , 73 % of parents were aware of the major study characteristics . A few had difficulty underst and ing the information provided . Major factors in parents granting approval were the contribution to clinical science ( 51 % ) and benefit to the child ( 32 % ) . Sociodemographic status did not influence initial participation but west European origin of the father was associated with willingness to participate in future trials . 89 % of participants felt positive about the informed consent procedure ; however , 25 % stated that they felt obliged to participate . Although their reasons for granting approval and their evaluation of the informed consent procedure did not differ , relatively more were hesitant about participating in future . Parents appreciated the investigator being on call 24 hours a day ( 38 % ) and the extra medical care and information provided ( 37 % ) as advantages of participation . Disadvantages were mainly the time consuming aspects and the work involved ( 23 % ) . CONCLUSIONS Parents ’ underst and ing of trial characteristics might be improved by design ing less difficult informed consent forms and by the investigator giving extra attention and information to non-west European parents . Adequate measures should be taken to avoid parents feeling obliged to participate , rather than giving true informed consent Background HIV prevention trials conducted among disadvantaged vulnerable at-risk population s in developing countries present unique ethical dilemmas . A key concern in bioethics is the validity of informed consent for trial participation obtained from research subjects in such setting s. The purpose of this study was to investigate the effectiveness of a continuous informed consent process adopted during the MDP301 phase III vaginal microbicide trial in Mwanza , Tanzania . Methods A total of 1146 women at increased risk of HIV acquisition working as alcohol and food vendors or in bars , restaurants , hotels and guesthouses have been recruited into the MDP301 phase III efficacy and safety trial in Mwanza . During preparations for the trial , participatory community research methods were used to develop a locally-appropriate pictorial flipchart in order to convey key messages about the trial to potential participants . Pre-recorded audio tapes were also developed to facilitate underst and ing and compliance with gel-use instructions . A comprehension checklist is administered by clinical staff to all participants at screening , enrolment , 12 , 24 , 40 and 50 week follow-up visits during the trial . To investigate women 's perceptions and experiences of the trial , including how well participants internalize and retain key messages provided through a continuous informed consent process , a r and om sub- sample of 102 women were invited to participate in in-depth interviews ( IDIs ) conducted immediately after their 4 , 24 and 52 week follow-up visits . Results 99 women completed interviews at 4-weeks , 83 at 24-weeks , and 74 at 52 weeks ( a total of 256 interviews ) . In all interviews there was evidence of good comprehension and retention of key trial messages including that the gel is not currently know to be effective against HIV ; that this is the key reason for conducting the trial ; and that women should stop using gel in the event of pregnancy . Conclusions Providing information to trial participants in a focussed , locally-appropriate manner , using methods developed in consultation with the community , and within a continuous informed-consent framework result ed in high levels of comprehension and message retention in this setting . This approach may represent a model for research ers conducting HIV prevention trials among other vulnerable population s in re source -poor setting s . Trial registration Current Controlled Trials IS RCT Abstract Objectives To explore trial participants ' underst and ings of r and omisation . Design In this exploratory study , which used qualitative research methods , in-depth , semistructured interviews were carried out with 20 participants from the CLasP r and omised controlled trial . Interviews were recorded on audio tape and fully transcribed . Data were analysed by comparing transcripts and describing emergent themes , using a grounded theory approach . Setting The CLasP study comprises three linked multicentre , pragmatic r and omised controlled trials evaluating the effectiveness and cost effectiveness of laser therapy , st and ard surgery , and conservative management for men with lower urinary tract symptoms or urinary retention , or both , related to benign prostatic disease . Subjects 20 participants in the CLasP study were interviewed . Sampling was purpose ful : men were included from each of the treatment arms , the two major centres , and at different points in the trial . Interventions and outcome measures Interviews used a checklist of topics to encourage participants to describe their experiences . Narratives concerning r and omisation were compared to identify common themes , retaining the context of the discussion to allow detailed interpretation . Results Most participants recalled and described aspects of r and omisation , such as the involvement of chance , comparison , and concealed allocation . Many found the concept of r and omisation difficult , however , and developed alternative lay explanations to make sense of their experiences . Inaccurate patient information and lay interpretations of common trial terms caused confusion . Conclusions The provision of clear and accurate patient information is important , but this alone will not ensure consistent interpretation of concepts such as r and omisation . Patients may need to discuss the purpose s of r and omisation in order to underst and them fully enough to give truly informed consent Objectives To analyse the parental underst and ing of informed consent information in first-line r and omised clinical trials ( RCTs ) including children with malignant solid tumours and to assess parents ’ needs for decision-making . Design Observational prospect i ve study . Setting 3 paediatric oncology centres in the Parisian region in France . Participants 53 parents were approached to participate in a RCT for their child with malignant solid tumour , over a 1-year period . 40 parents have been interviewed in our study . Primary and secondary outcome measures Parental underst and ing of information in RCTs , parents ’ needs for decision-making . Parents were question ed by a psychologist , independent of the paediatric oncology teams , using a semidirected interview , 1 ( M1 ) and 6 months ( M6 ) after the consent was sought . Results 18 parents ( 45 % ) did not underst and the concept of r and omisation . Half of the parents could explain neither the aim of the clinical trial nor the potential benefit to their child of inclusion . 35 parents ( 87.5 % ) expressed very few specific risks related to the trial . Being mostly French-speaking ( p=0.03 ) and the reading of the information sheet by the parents ( p=0.0025 ) improved their underst and ing . The parental comprehension did not differ between M1 and M6 . The principal factors underlying their decision were confidence in the medical team ( 39 % ) , wish to access to the best treatment ( 37 % ) and the best quality of life ( 37 % ) . Conclusions Despite medical explanations , parents have limited knowledge in some areas in first-line RCTs and improvements of information process are required . The risks specific to the r and omised trial are underestimated by parents and the unproven nature of the treatment is not well-known or understood Background The process of obtaining informed consent continues to be a contentious issue in clinical and public health research carried out in re source -limited setting s. We sought to evaluate this process among human research participants in r and omly selected active research studies approved by the School of Medicine Research and Ethics Committee at the College of Health Sciences , Makerere University . Methods Data were collected using semi-structured interviewer-administered question naires on clinic days after initial or repeat informed consent procedures for the respective clinical studies had been administered to each study participant . Results Of the 600 participants interviewed , two thirds ( 64.2 % , 385/600 ) were female . Overall mean age of study participants was 37.6 ( SD = 7.7 ) years . Amongst all participants , less than a tenth ( 5.9 % , 35/598 ) reported that they were not given enough information before making a decision to participate . A similar proportion ( 5.7 % , 34/597 ) reported that they had not signed a consent form prior to making a decision to participate in the study . A third ( 33.7 % , 201/596 ) of the participants were not aware that they could , at any time , voluntarily withdraw participation from these studies . Participants in clinical trials were 50 % less likely than those in observational studies [ clinical trial vs. observational ; ( odds ratio , OR = 0.5 ; 95 % CI : 0.35 - 0.78 ) ] to perceive that refusal to participate in the parent research project would affect their regular medical care . Conclusions Most of the participants signed informed consent forms and a vast majority felt that they received enough information before deciding to participate . On the contrary , several were not aware that they could voluntarily withdraw their participation . Participants in observational studies were more likely than those in clinical trials to perceive that refusal to participate in the parent study would affect their regular medical care Studies repeatedly have shown that clinical research subjects have trouble appreciating the implication s for their clinical care of participating in a clinical trial . When this failure is based on a lack of appreciation of the impact on individualized clinical care of elements of the research design , it has been called the " therapeutic misconception " . Failure to distinguish the consequences of research participation from receiving ordinary treatment may seriously undermine the informed consent of research subjects . This article reports results concerning appreciation of the risks of trial participation from intensive interviews with 155 subjects from 40 different clinical trials at two different medical centers in the USA . Working from transcripts of the interviews , every statement of a risk or disadvantage of trial participation was identified and coded into one of 5 different categories . Totally , 23.9 % of subjects reported no risks or disadvantages in spite of being explicitly asked about them . Another 2.6 % reported only incidental disadvantages such as having to drive a long way to get to the experimental site . In all 14.2 % reported only disadvantages associated with the st and ard treatment ( usually side effects ) . Another 45.8 % told the interviewer about disadvantages and risks associated with the experimental intervention ( usually side effects ) . Only 13.5 % could report any risks or disadvantages result ing from the research design itself , such as r and omization , placebos , double-blind design s and restrictive protocol s. The results of this research suggest that subjects often sign consents to participate in clinical trials with only the most modest appreciation of the risks and disadvantages of participation The aim of this study was to explore the fulfilment of the requirements of informed consent in patients participating in cancer clinical trials . All patients consenting to a phase II or III clinical trial during one year were included ( n=325 , 176 women , 54 % ) . Data were collected by a question naire , Quality of Informed Consent . The response rate was 87 % . High levels of knowledge ( > 80 % ) were found for items concerning voluntariness , r and omisation , benefits for future patients , participation in a research trial , and the right to withdraw . Less than 50 % responded correctly to items about risks associated with the trial , the unproven nature of the trial and issues about insurances . High levels of perceived underst and ing were reported . Despite high levels of knowledge and perceived underst and ing in the majority of elements of informed consent , improvements are warranted regarding knowledge about risks , the unproven nature of the treatment and the duration of treatment Objectives : To investigate the re collection s of parents consenting for their infants to be research subjects and determine their views about the need for consent . Subjects : Parents of 154 sick newborn infants enrolled in a r and omised trial in the early neonatal period . All parents had given written consent and received printed information . Methods : A question naire and accompanying letter was sent to the parental home 18 months later . Non-responders were sent a further question naire and letter . Results : Response rate was 64 % ( 99/154 ) . Some respondents ( 12 % ) did not remember being asked to consent to their baby joining a study , and a further 6 % were unsure . Most of the respondents ( 79 % ) were happy , 13 % neutral , and 8 % unhappy with their decision to give consent . None felt heavy pressure to agree . Entering the trial caused 24 % of respondents to feel more anxious , 56 % neutral , and 20 % less anxious about their baby . Most of the respondents ( 83 % ) would be unhappy to forgo the consent process for trials passed by the institutional ethics committee . Conclusions : A significant proportion of parents who give written consent for a trial in the early neonatal period do not later remember having done so . Parents who have had experience of neonatal research would be unhappy for their baby to be enrolled in a study that had ethics committee approval without their consent being obtained OBJECTIVES Survival rates for childhood cancer have improved substantially partly as a result of national and international r and omized clinical trials ( RCT ) . However , the decision for families is complex and emotional . Our aim was to describe the views of mothers of children newly diagnosed with ALL regarding consent to r and omized controlled trials . DESIGN Qualitative interview to explore mothers knowledge , and reasons for involving their child in RCTs . Interviews took place in mothers ' homes . PARTICIPANTS Fifty mothers of children with newly diagnosed ALL ( age 4 - 16 years ; mean = 7.4 ) recruited through research nurses at outpatient appointments . RESULTS All but three families had consented for their child to be treated in the RCT , although there was wide variation in their underst and ing of the aims , costs and benefits . Most mothers reported the aim of the trial to compare ' old ' and ' new ' treatments . CONCLUSION Despite detailed verbal and written information , mothers were poorly informed about the purpose of the trial , and possibility of side effects . Individual preferences for either st and ard or new treatment were routinely reported . The data raise questions about the extent to which families give truly informed consent to recruitment of their child to an RCT Injection drug users ( IDUs ) at high risk for human immunodeficiency virus ( HIV ) infection are being identified as a population for HIV vaccine trials . We studied willingness of drug users to enroll and their comprehension of consent procedures in the context of a Phase II trial at one site . Of 175 people screened for enrollment and whose data sets were complete , 119 ( 68 % ) were IDUs . Of the 71 who were eligible , 39 ( 55 % ) were IDUs . Exclusion of IDUs was usually for medical reasons . Using a 17-item true/false test , comprehension of the informed consent procedure was high ( median score , 16 of 17 for IDUs and non-IDUs ) ; only three subjects ( all of whom were IDUs ) were excluded from enrollment due to lack of comprehension . Follow-up rates were similar for IDUs and non-IDUs . These data suggest that recruitment of IDUs into HIV vaccine trials is feasible , that IDUs can comprehend and complete the informed consent procedures , and that they return for follow-up visits Objective To evaluate the extent to which parents are satisfied with and underst and the information they are given when their consent is sought for their child to participate in a phase III r and omised clinical trial and the reasons for their decision . Patients and method The authors carried out a prospect i ve study . The authors included all parents whose consent was sought for their child to participate in the FRALLE 2000A protocol ( acute lymphoblastic leukaemia ) at two centres . The parents were question ed twice by a qualified psychologist using a semidirected interview , 1 and 6 months after consent was sought . Results 43 first interviews were carried out . All the parents declared they were satisfied with the explanations provided by the physician . 35 ( 81 % ) parents felt that the information provided with the request for consent was appropriate . Eight ( 19 % ) parents did not realise that their child had been included in a research protocol . 16 ( 39 % ) parents did not underst and the concept of r and omisation . Half the parents could explain neither the aim of the clinical trial nor the potential benefit of inclusion to their child . Only one third of the parents were aware that they had an alternative . The principal factor underlying their decision , as stated by 29 parents ( 67 % ) , was confidence in the medical team . Conclusions The parents signed consent forms without having fully understood all the elements specific to the experimental protocol . Rather , the parents based their decision on their confidence in the medical team , even when their child 's life was at risk OBJECTIVE To assess participants ' knowledge of key aspects about the clinical trials in which they are enrolled , describe the consent process , and assess the importance that investigators give to various aspects of trial information when verbally informing c and i date s. DESIGN Prospect i ve study based on a structured question naire interview of participants within 3 months after trial enrollment and an anonymous question naire sent to clinical trial investigators . SUBJECTS A total of 140 participants included in 40 clinical trials were interviewed , and 51 investigators answered the question naire . RESULTS The formal steps to obtain informed consent were usually carried out . Participants were aware of the purpose of the trial and the right to discontinue participation , but only 23 % knew that treatment was r and omly allocated , 57 % knew they might receive a placebo , and 42 % was aware that adverse effects could occur . Patients who had read the information sheet had better knowledge of most aspects , except for the risk of adverse effects . The investigators considered that compensation , insurance coverage , possibility of receiving a placebo , and treatment allocation were the least important aspects of the trial when informing c and i date s for participation . CONCLUSIONS Although the formal steps for obtaining informed consent were usually carried out , a relevant percentage of patients included in clinical trials were unaware of important aspects of their participation . Patients showed more limited knowledge about the same points that investigators considered less important when informing potential participants . Deferring signature on the consent form and encouraging reading of the information sheet may improve participants ' knowledge about clinical trials Previous research has found that cancer patients often overestimate the likelihood that they will achieve a positive response in Phase I trials . However , maintaining optimistic expectations may help patients cope with a poor prognosis and uncertain outcome . The authors prospect ively examined the association between treatment‐specific optimism and mental health among patients participating in a Phase I/b trial OBJECTIVE To examine the level of children 's underst and ing of informed consent in clinical trials and factors that may influence these processes . DESIGN Twenty nine children who were included in clinical trials for treatment of cancer or HIV , were offered the possibility to complete a semidirective interview , with parental permission . METHODS Children 's underst and ing was measured by a score of 0 - 9 including items required to obtain a valid consent according to French and European legislations . RESULTS Children were 8.5 - 18 years old ( 13.6 + /- 2.8 years ) . The higher percentage of underst and ing was obtained for the study objectives ( n = 18 , 62 % ) , the risks ( n = 17 , 58 % ) , the potential self- benefits ( n = 18 , 62 % ) and the potential benefits to other children ( n = 17 , 58 % ) . The lower percentage of underst and ing was obtained for the procedures ( n = 5 , 17 % ) , the possibility of alternative treatments ( n = 9 , 31 % ) , the duration of participation ( n = 6 , 21 % ) , their right to withdraw ( n = 6 , 21 % ) , and the voluntary participation ( n = 6 , 21 % ) . Sixteen children ( 55 % ) thought that the given information was adequate . Underst and ing was significantly correlated with child 's age ( r = 0.65 ; P = 0.0001 ) and the mean score was higher in patients over 14 years old compared to patients under the age of 14 ( 4.4 + /- 2.4 , n = 14 vs. 2.6 + /- 2.6 , n = 15 , P < 0.05 ) . The mean score was also higher in children when informed consent was sought some time after the diagnosis ( > 7 days ) rather than at the same time ( < 7 days ) ( score : 4.14 + /- 2.59 n = 21 vs. 1.87 + /- 2.03 n = 8 ; P = 0.03 ) . The clarity of information perceived by children did not influence their underst and ing ( score : 3.6 + /- 2.6 n = 14 vs. 3.5 + /- 2.7 n = 15 ; P = 0.91 ) . CONCLUSION Children have an incomplete underst and ing of the elements included in the informed consent forms . Underst and ing is related to age and timing of informed consent BACKGROUND AND OBJECTIVE To develop and evaluate an Informed Consent Question naire ( ICQ ) for measuring self-reported perceived underst and ing of informed consent in a r and omized clinical trial . METHODS The study was embedded in a Department of Veterans Affairs r and omized clinical trial of Gulf War veterans ' illnesses ( CSP#470 ) . The trial was initiated in May 1999 at 20 hospitals and concluded in September 2001 ; 1,092 participants were enrolled and followed for 12 months . The reliability and validity sample included 1,086 participants evaluated at baseline , 906 at 3 months , 929 at 6 months , and 910 at 12 months . The psychometric evaluations included tests of acceptability ( based on missing data , endorsement frequencies , and floor/ceiling effects ) , item reduction , internal consistency , and construct validity ( based on Cronbach 's alpha coefficients , item-total correlations , and principal components analysis ) . RESULTS The ICQ had > 5 % missing information on some questions at baseline , indicating poor acceptability prior to the initiation of the trial ; however , the scale had good acceptability at each of the follow-up visits . Psychometric evaluation following st and ard item reduction techniques confirmed the reliability and validity of a four-item subscale of the ICQ ( ICQ-4 ) . CONCLUSIONS The ICQ-4 is a simple and psychometrically sound self-report measure of perceived underst and ing of informed consent Background : Recruitment into research studies in the neonatal intensive care unit has been problematic . Therefore suggestions have been made to take decision making about enrolment out of the h and s of the parents . Objective : To underst and parental perceptions of the process of recruitment and enrolment for research in the neonatal intensive care unit . Method : A question naire was developed and used in both a retrospective survey and a prospect i ve study of parents whose newborns were enrolled in trials in a neonatal intensive care unit . Closed ended and open ended questions were included , as well as demographic questions . Results : The retrospective survey had a 79 % response rate ( 29 of 38 ) . Overall , 90 % of parents felt that they had made informed decisions , and 93 % were against the option that a doctor decide if the newborn should be enrolled into a study , rather than the parent . Although some parents ( 38 % ) found that recruitment did add “ stress to an already stressful situation ” , 90 % felt that they had made informed decisions and understood the elements of the study . Most parents had been requested to enrol their newborn into more than one trial , and , on average , they thought that they would be comfortable with enrolment into two studies ( range 0–6 ) . When asked how the process could be improved , parents suggested that information be made available before delivery . The responses of parents in the prospect i ve study were mostly consistent with those from the retrospective survey . Conclusions : Overall the parents did not support the suggestion that decision making about enrolment be taken away from parents and put into the h and s of doctors . The healthcare team should support parents in their role of decision maker , enhance availability of the research staff , and provide more information about the research OBJECTIVE We sought to evaluate the application of the French law for the protection of persons participating in research studies in biology and medicine . Specifically , we examined comprehension and consequences of informed consent procedures in the field of stroke , characterized by an emergency setting , cognitive impairment and poor prognosis . PATIENTS AND METHODS Patients ( or proxies ) included in recent years in clinical studies conducted in our Neurology Department for evaluating treatment of acute phase cerebral ischemia were interviewed to determine their knowledge of the disease , its treatment , the study protocol and the legal regulations , and the affective and psychological consequences of the informed consent procedure . RESULTS Among 72 patients included in 7 studies ( [ fibrinolytic agent : 3 ( n = 43 ) , anticoagulant agent : 1 ( n = 4 ) , neuroprotective drugs ( n = 25 ) ] , [ 7 r and omized studies , 6 double-blind versus placebo , 5 with a 6-hour inclusion time interval ] ) , 15 died during the acute phase , 5 were lost to follow-up , 4 refused to participate and 7 gave very partial answers . Consent was signed by the patient in 15 % of cases , the spouse in 50 % , a descendant in 23 % . These persons were aware of the spontaneous risk of death ( 85 % ) or definitive functional impairment ( 95 % ) . Half of them thought a specific treatment existed , 11 % had some idea of the mechanism of action of the proposed treatment while 67 % learned about this mechanism from the information provided . Although they had received information , only 25 % of the patients had knowledge of placebo and 7 % of therapeutic risk . 37 % expected complete recovery from the treatment , 44 % partial recovery , and 13 % were very disappointed by the outcome . 81 % felt they were free to make their own decision . Although 86 % did not know there was a law protecting them , 82 % were in agreement with the requirement for their consent while 17 % would have preferred to delay consent . Most wished to be given the opportunity to discuss the study again , after the acute phase , and to receive the results of the study . CONCLUSION This study shows that most French stroke victims and their closest relatives are unaware of the law protecting persons in biomedical research and have poor knowledge of medical data after being given appropriate information . Even so , the quality of information increases the quality of the patient-physician relationship . Patients want to be free to make their own decision to consent to biomedical research , but their desire was more for good information than for the power to make their decision alone . Being asked to give informed consent in order to participate in a clinical study accentuates the affective and psychological consequences of stroke , a factor which should be taken into consideration during follow-up Background : Informed consent is regarded as a contract between autonomous and equal parties and requires the elements of information disclosure , underst and ing , voluntariness and consent . The validity of informed consent for critically ill patients has been question ed . Little is known about how these patients experience the process of consent . Objective : The aim of this study was to explore critically ill patients ’ experience with the principle of informed consent in a clinical trial and their ability to give valid informed consent . Design : 11 stroke patients who had been informed about thrombolytic treatment and had been through the process of deciding whether or not to participate in a thrombolysis trial went through repeated qualitative semistructured interviews . Results : None of the patients had any clear underst and ing of the purpose of the trial . Neither did they underst and the principles of r and omisation and voluntariness . Reasons for giving or not giving consent were trust , conceptions of benefits and risks and altruism . Several patients found it immoral to involve patients in the consent procedure and argued that this was the doctors ’ responsibility . Others argued that it is a duty to question patients and perceived it as a sign of being treated with respect and dignity . A majority of the patients found the consent process vague and ambiguous . Conclusions : The results indicate that the principle of informed consent from critically ill patients can not be seen as a contract between equal and autonomous parties . Further studies are needed to explore critically ill patients ’ experiences with the process of informed consent To better underst and parental perceptions of the informed consent process in pediatric oncology clinical trials , 20 parents of newly diagnosed children at two pediatric cancer centers described their perceptions in a semi-structured interview . They recalled well the diagnosis , the general treatment plan , and the statistics of survival and /or cure , but the research nature of the clinical trials , particularly r and omization , was not well understood . However , despite the need to assimilate a great deal of information , time pressure to make decisions , and reportedly high levels of distress during the discussion s , parents expressed general satisfaction with the informed consent discussion s with their pediatric oncology providers . However , half to two thirds of parents felt there had been inadequate discussion of alternatives to the proposed treatment and of the research nature of the protocol . While further study of the informed consent process should be conducted in larger , representative sample s , the findings from this pilot study suggest that a goal of future informed consent interventions should be to improve parents ' underst and ing of the research aspects of treatment . It is critical to parents ' ability to provide informed consent that they feel satisfied that they know alternatives to proposed treatment and that they underst and the r and omization of treatments , which is the gold st and ard of clinical trials in pediatric oncology Recall and underst and ing of information provided to contraceptive study participants in four sites were assessed . Analysis was completed of data for 70 women who were asked about their re collection of information and underst and ing of participation . Most women understood the purpose of the study . Their reasons for agreeing to participate varied by site and included wanting to try a new method wanting to help others and wishing to avoid pregnancy . Most women recalled correctly the burden of participation — number and frequency of visits tests and examinations . Most understood that they could withdraw from the study without jeopardizing their care . The women were also asked to recall the risks and benefits of the contraceptive they were testing . Only 23 % recalled the pregnancy risk correctly ; 40 % underestimated and 19 % overestimated it . Few women interpreted rates of risk correctly ; some perceived high rates as low ones and the rates of the spermicide being studied as better than those of other contraceptives . This study confirms that risk is better recalled than understood . The participants surveyed remembered the information they were question ed about better than did participants in some other studies a finding that supports earlier research results showing that younger healthier patients ( such as contraceptive users ) recall better than older less healthy ones . ( authors Previous studies report mixed results about how much information study participants actually can read , underst and and retain after completing the informed consent process ; fewer studies have examined disparities in the retention and recall of information by patient factors , such as age , education , and race . Not retaining or being able to recall information from the informed consent process has potentially important ethical and legal implication s and consequences for research quality and integrity , especially when found in population s that commonly are underserved or underrepresented in clinical trials . To determine how much basic knowledge participants finishing a five-year , multi-center , double-blinded r and omized , placebo-controlled clinical trial had about the study , participants ( n=1,789 ) were asked at their final follow-up visit three multiple-choice questions : ( 1 ) the study 's purpose ; ( 2 ) the name of the medication under investigation ; ( 3 ) the main side effect of the medication . The associations between knowledge of these fundamental details and participant social and demographic factors were investigated . A majority of participants correctly recalled the study 's purpose ( 64.7 % ) and medication ( 79.6 % ) , but few correctly reported the main side effect ( 31.1 % ) . In spite of relatively high recall for study purpose and medication , disparities by age , education and race exist . Increasing age was significantly associated with higher odds of incorrectly recalling both the study purpose and the name of the study medication . Likewise those with less than a high school education were more likely to incorrectly identify the study 's purpose and the name of the study medication . Black and other non-white race or ethnic groups were more than two and a half times as likely to incorrectly identify the study 's purpose . These findings suggest that even the most basic information may not be understood or retained by important subgroups of patients enrolled in clinical trials . Implementing effective strategies , such as additional time and effort for consent or repetition of study information , may be necessary in order to assure ethical and valid consent PURPOSE To describe prospect i ve participants ' initial source of information about , underst and ing of , and motivation to participate in a phase I clinical trial of the antiangiogenesis agent human recombinant endostatin . PATIENTS AND METHODS We surveyed 100 of 130 persons referred to the endostatin trial between October 1999 and November 2000 and analyzed media coverage of the agent from 1997 to 2000 . RESULTS Forty-seven percent of survey respondents first heard about the trial from media reports . Fifty-one percent of these subsequently contacted their physicians . Thirty-three percent of respondents correctly understood the purpose of the trial . Seventy-nine respondents were interviewed before they met trial investigators to discuss the trial . Of these , those who first heard about endostatin from the media were five times more likely to underst and correctly the trial 's purpose than those who first heard from other sources . Seventy-four percent ( 70 of 95 ) of respondents cited hope for personal benefit as the main reason for their willingness to enroll . Those who first heard about endostatin from the media were no more motivated by hope of personal benefit ( 77 % ) than those who first heard from other sources ( 71 % ) ( P = .46 ) . Ninety-nine percent of all respondents cited " joining the study gives me hope " as a contributing factor in their decision making about the trial . CONCLUSION Media coverage prompted prospect i ve participants to contact their physicians but did not seem to hinder underst and ing nor could it be shown to heighten their hope for personal benefit Objective : To study the quality of the information provided to and the procedure for obtaining the consent of chronically ill patients participating in a clinical trial . All patients included in a clinical trial concerning a lipid‐lowering treatment over a 1‐year period were asked to participate in the present research ethical study . Material and Methods : Patients ( n=55 ) on hemodialysis or in a prerenal state were selected . About 2 weeks after being recruited , the patients received a question naire concerning different aspects of the information provided . None of those responsible for providing information and obtaining consent were aware of the research ethical study in advance . Results : A total of 44 patients answered the question naire ( response rate 80 % ) . All but one participant perceived the information provided as being very good or fairly good . None felt that they had been forced to participate in the trial . A total of 12 patients stated that they had delegated the decision making to their doctor . Compared to the younger patients , elderly participants more often stated that they had only been informed orally ( p=0.027 ) . Those who stated that they were only informed orally tended to let the doctor decide whether or not they should participate in the trial . Conclusions : The study indicates that , compared to younger patients , elderly patients tended to be informed about the trial only orally and were also inclined to let the doctor decide whether or not they should participate . Providing information both orally and in writing and providing sufficient time for consideration may improve the informed consent process for severely ill patients To illuminate the process of obtaining informed consent to research in a medically dependent population , we interviewed 156 patients and 37 physicians involved in research projects at four Veterans Administration hospitals . Most patients knew they were research subjects , had voluntarily consented , and knew the details of their medical treatment , but few understood the research well . Readability analysis indicated that consent forms required college-level education . Twenty-eight percent of patients were not aware of their participation in research although they had signed consent forms . No single act , omission , or personal attribute completely explains this unawareness , but it is associated with incomplete consent forms , the identity of the person explaining the research , the manner of the explanation , and , in some cases , grave illness BACKGROUND In clinical tests , the Informed Consent is critical to preserve the ethics , but due to its high complexity level , it can not be fully understood . This study assesses the Informed Consent as viewed by patients . OBJECTIVE We addressed the issue of what do patients underst and about the studies based on the IC . METHODS We invited participants of outpatient clinical drug trials phase II , III and IV to answer a question naire with 29 questions , such as : why have you accepted to participate ? Did you read the Informed Consent before signing it ? By signing it , were you sure you have fully understood it ? Eighty individuals ( 20 women and 60 men ) showed up , from 106 patients . The variables of each question were considered as often as they appeared . The comparison of the averages among the groups was made by t tests of Student or Wilcoxon ; and for associations , Chi-square or Likelihood Ratio , or Fisher 's exact test . RESULTS Ages averaged 58.7 + /- 9.3 years . Concerning their reasons to taking part in the survey , 66.2 % pointed out their own benefit ; 42.5 % , for science 's sake ; 25.0 % cl aim ed they were doing so at their doctor 's request ; 50 % did not underst and the Informed Consent properly ; and 32.9 % did not read it , but signed it . Among those who were administered placebo after r and omization ( n = 47 ) , 66.7 % did not underst and the meaning of the informed consent . A strong correlation between failure to underst and the meaning of placebo with literacy level ( p = 0,02 ) was verified , which is an evidence that the smaller is the literacy level , the smaller is the underst and ing level . CONCLUSION The Informed Consent is poorly understood by patients and for some of them , trusting a doctor affected their decision in taking part in the clinical trial with drugs . Their literacy level also influenced their underst and ing of the term ' placebo ' The aim of this study was to determine the communicative needs of the patients in the context of being invited to participate in a clinical trial . A question naire was sent to 299 patients with breast cancer r and omised in a trial of adjuvant therapy . It was returned by 261 ( 87 % ) of them . Ninety-one per cent ( 231/255 ) of the patients regarded the information provided as easy or quite easy to underst and . However , the method of treatment allocation was unclear to most patients : 51 % ( 128/251 ) thought that the doctor had chosen the treatment while only 23 % ( 57/251 ) knew that they had been r and omised . Younger and better educated patients had a better underst and ing . For 55 % ( 125/226 ) of the patients written information had been helpful in decision making . This correlated highly with the education of the patient . Sixty-eight per cent ( 174/255 ) of the patients thought that they had enough time for decision-making . Less educated patients and older patients had needed more time . Eighty-seven per cent ( 218/251 ) were happy with their decision to participate . While most patients are satisfied with the information received , there is a poor underst and ing of how treatment is allocated . Information should be modified for older and less-educated patients . The needs of the patients when offered participation in a clinical trial are clear information , enough time to consider the options and psychological support CONTEXT Most children diagnosed as having leukemia become research subjects in r and omized clinical trials ( RCTs ) , but little is known about how r and omization is explained to or understood by parents . OBJECTIVE To investigate physicians ' explanation and parental underst and ing of r and omization in childhood leukemia RCTs . DESIGN AND SETTING A multisite study of the informed consent communication process for RCTs of childhood leukemia . Consecutive cases were recruited from pediatric oncology inpatient wards at 6 US children 's hospitals associated with major academic medical centers from July 1 , 1999 , until December 31 , 2001 . The informed consent conferences were observed and audiotaped , and the information obtained was coded and analyzed . Parents were interviewed shortly after the conference to ascertain their underst and ing . PARTICIPANTS Parents and members of the health care team who participated in 137 informed consent conferences for children with newly diagnosed acute leukemia . MAIN OUTCOME MEASURES Observed explanations of r and omization and parental underst and ing of r and omization after the consent conference . RESULTS R and omization was explained by physicians in 83 % of cases and a consent document was presented during the conference in 95 % of cases . Interviews after the conference demonstrated that 68 ( 50 % ) of 137 parents did not underst and r and omization . Parents of racial minority and lower socioeconomic status were less likely to underst and r and omization ( P<.001 for each ) . Discussion of specific clinical trial details and the presence of a nurse during the conference were associated with underst and ing . Eighty-four percent of children were enrolled in a leukemia trial . CONCLUSIONS Despite oral and written explanation , half of the parents in this study did not underst and r and omization for childhood leukemia trials . To make informed consent more effective , future research must seek to improve communication during this critical interchange Patients , aged 36 to 78 years , who had participated in two studies that included the ventilatory effects of postoperative analgesia , returned a question naire canvassing their views of the procedure for obtaining consent and the conduct of the study . Fourteen of 18 patients from one study , and all 18 from the second , returned their question naires . Thirty of the 32 patients were satisfied with the pre‐operative explanation . Eleven patients felt obliged to take part , not because of coercion , but from a sense of duty to others . The breathing tests caused discomfort to eight patients but only one of them found this more than expected from the pre‐operative explanation . Only two patients , both in the second study , said that they would not volunteer again for a similar study . There was no suggestion that the age of the patient or the fact that they were undergoing major surgery had any influence on their attitudes or comprehension . It may be prudent to use this type of question naire to evaluate the response of patients to some research projects Recent reports in the media about the NHS inquiry at a North Staffordshire hospital have highlighted concerns about clinical trials involving children , especially about informed consent and the information given to parents . An inquiry led by Professor Griffiths has recommended that the Department of Health produce guidelines for the conduct of clinical trials ( Boseley 2000 , Rumbelow and Johnstone 2000 ) . The UKCC Code of Professional Conduct ( 1992 ) requires that nurses must ‘ act always in such a manner to promote and safeguard the interests and well being of patients and clients ’ . Polit and Hungler ( 1991 ) summarise informed consent as meaning ‘ subjects have adequate information regarding the research ; are capable of comprehending the information and have the power of free choice , enabling them to voluntarily consent to participate in the research or decline participation ’ . While actively recruiting pre-school children for a r and omised controlled trial , the research team became aware that despite adhering to the consent procedure and regular contacts with parents , 14 of the 54 participants failed to complete the trial as requested . Albert and Chadwick ( 1992 ) suggest that effective communication can only take place if a message is successfully and completely transferred from one person to another . It was important that the research team ( two nurses , a registrar and a consultant ) were able to identify and underst and any potential communication problems with the information given about the trial . A retrospective postal audit of all 54 participants was carried out to address the question of why some parents failed to complete the trial and if information given to parents should be adapted . The results of this audit will be presented in this article OBJECTIVE To evaluate the informed consent process for a clinical trial of intravenous doxycycline for rheumatoid arthritis . METHODS Participants completed a self-administered question naire about the consent process at baseline and 16 weeks following enrollment in a clinical trial . RESULTS Respondents ( n = 30 ) affirmed voluntary participation in the parent trial . Participants acknowledged hope and altruism as reasons for entering the trial more than expectation of personal benefit or outside influences . Many respondents did not underst and r and omization ( 14/30 ) , placebos ( 15/30 ) , or risks of study medications ; 11/30 respondents believed that the study drug was completely safe . CONCLUSION Respondents generally understood the experimental nature of the trial and confirmed their participation was voluntary . However , gaps existed in participants underst and ing of trial design , raising the question of whether they were adequately informed about the research study prior to enrollment . Further education of potential participants in clinical trials may be required to achieve valid informed consent We interviewed 64 parents by question naire after completion of a clinical trial involving their children for their perceptions and attitudes about informed consent . The results show that only a small minority realized that drug trials are design ed to assess not only efficacy but safety as well . More worrisome was the majority of parents who felt that drug trials conducted by hospitals are of no or low risks . Moreover , a significant minority offered the view that the strict informed consent procedures we followed were unnecessary because they would do what the doctor advised . Even more worrisome was the small percentage of parents who realized that a signed consent form was primarily meant to protect their rights , and only one-third of the parents knew of their right to withdraw their child unconditionally from the trial at any time . These findings suggest that there may be significant attitudinal barriers to parental underst and ing of the informed consent process Comprehension and recall of the information contained in the informed consent statement was tested in clinical ly hypertensive patients entering a controlled trial comparing hydrochlorothiazide and propranolol . The consent statement was the primary vehicle for conveying the information to the patient . The average of correct answers to a multiple‐choice quiz was 71.6 % at 2 hr and 61.2 % at 3 mo after the consent procedure . The effectiveness of recall did not correlate with level of education . Patients exhibited greater comprehension of the action of the drugs than of their side effects . Nearly all patients indicated their belief that they would receive the best possible care . While 95 % wanted to be informed about the trial , 75 % stated they would have given their consent even without this information According to international regulatory authorities1 and local institutional guidelines , 2 informed consent is a prerequisite for participation in every clinical trial . Consent implies that participation is voluntary . Furthermore , the participant must know the implication s of participation.3 Even if a participant has signed an informed consent form , the participant does not necessarily underst and what the participation will entail , and consent thus may not be informed.4 On the other h and , a study conducted in a South African hospital found that patient consent for HIV testing was informed but not truly voluntary.5 The aim of this study was to investigate whether the consent for HIV testing and subsequent participation in a r and omized , double-blind , placebo-controlled trial investigating the effect of vitamin A on mother-to-child transmission of HIV6 was informed and voluntary . Participants ’ knowledge about HIV and AIDS and the trial was used to measure how informed their consent was , and participants ’ perceptions about their willingness to participate , about their ability to withdraw , and about whether they would no longer receive good medical care if they withdrew were used to measure how voluntary their consent was . The trial was conducted from September 1997 to December 2000 in Bloemfontein , Free State , South Africa . In 1997 , in the annual survey of the South African Department of Health of women attending public health antenatal clinics , 20 % of the Free State women were found to be HIV positive , with the national figure being 17%.7 Despite these figures , no routine intervention has been aim ed at preventing vertical transmission in South Africa OBJECTIVES We surveyed Ug and an parents who enrolled their children in a r and omized pediatric malaria treatment trial to evaluate the parents ' levels of underst and ing about the treatment trial and the quality of the parents ' consents to allow their children to participate in the study . METHODS We conducted 347 interviews immediately following enrollment at 4 Ug and an sites . RESULTS A majority ( 78 % ) of the parents , most of whom where mothers ( 86 % ) had at most a primary school education . Of the participating mothers , a substantial percentage reported that they remembered being told about the study 's purpose ( 77 % ) , the required number of visits ( 88 % ) , the risks involved ( 61 % ) , treatment allocation ( 84 % ) , and their ability to discontinue their children 's participation ( 64 % ) . In addition , most reported knowing the trial 's purpose ( 80 % ) and the required number of visits ( 78 % ) ; however , only 18 % could name possible side effects from the drugs being administered , and only 19 % knew that children would not all be administered identical treatments . Ninety-four percent reported that they made the enrollment decision themselves , but 58 % said they felt pressure to participate because of their child 's illness , and 15 % said they felt some type of pressure to participate from others ; 41 % reported knowing that they did not have to participate . CONCLUSIONS The consent Ug and an parents provided to allow their children to participate in the malaria study was of mixed quality . Parents understood many of the study details , but they were not very aware of the risks involved or of r and omization . Many parents felt that they could not have refused to participate because their child was sick and they either did not know or did not believe that their child would receive treatment outside of the study . Our results indicate that further debate is needed about informed consent in treatment studies of emergent illnesses in children PURPOSE Some patients may be at greater risk than others of enrolling on a r and omized clinical trial ( RCT ) without fully underst and ing the implication s. To investigate this possibility , this study poses the question , Do non-English-speaking Latino parents of children with leukemia show differences in their discussion of and underst and ing of an RCT when compared with English-speaking minority parents and with English-speaking majority ( ie , white ) parents ? This research hypothesizes that factors such as social and educational status and the role of language interpreters may account for significant differences in the discussion and underst and ing of an RCT among the three groups . PATIENTS AND METHODS A total of 108 parents are reported on , all of whom were observed , interviewed , and audiotaped during informed-consent discussion s about participation in an RCT with their child 's oncologist . Comparisons among the groups were performed using chi2 tests and a one-way analysis of variance . RESULTS Problems of consent-related communication and underst and ing were more frequent among parents of low social status who spoke little or no English than they were in the two other groups . Several factors may have contributed to this disparity , including language interpretation , social status , and prevailing cultural norms . CONCLUSION Some patients may be at greater risk than others of enrolling on an RCT without fully underst and ing the implication s of their decision to do so . Numerous factors may contribute to this disparity , including language interpretation , social status , and prevailing cultural norms . Some specific strategies are suggested to help address this disparity btaining the informed consent of participants in clinical studies is a fundamental requirement for ethical research . ' Based on the principle of respect for persons , potential research subjects are provided with relevant information about a study so that they can make an informed and voluntary decision about participation . Skepticism and controversy exists , however , about informed consent from research participants in developing countries . In addition to concepts about research and individual choice that might be unfamiliar , developing country participants may be plagued by poverty , illiteracy , and limited access to health care services that make it difficult for them to give valid informed consent.2 Most agree that following the provision of adequate and accurate information about a study , valid informed consent requires at least some knowledge of the study details and a voluntary decision to enroll.3 Evaluation of the quality of informed consent therefore should attempt to measure what participants underst and and how freely they made the enrollment decision . A small yet increasing number of studies using quantitative or qualitative methods to evaluate participants ' informed consent or to test informed consent interventions have been reported . Yet , only a few published studies from Thail and , 4 South Africa , s The Gambia,6 Bangladesh,7 and Haiti,8 have used quantitative methods to survey research participants in developing countries about the informed consent process . Although the results of these studies show mixed comprehension , the paucity and small size of these studies make it difficult to say much about the quality of informed consent in developing countries or to compare it to the quality of informed consent in developed countries . This difficulty is compounded by method ological limitations in the studies that have been conducted in both setting s. For example , in some studies the time period between the informed consent process and the administration of the informed consent question naire varied from respondent to respondent , even extending to several months.9 In other studies , crucial domains , such as the degree to which subjects felt pressured to participate in the clinical research , were excluded . 10 To assess the quality of informed consent in a developing country while avoiding some of these method ological limitations , we interviewed 141 individuals immediately after they consented to participate in a r and omized HIV study in Bangkok , Thail and . In Thai culture , individuals often defer to the authority of the health care professional . However , because there has been a considerable volume of clinical research in Thail and including HIV research , Thai citizens may be more familiar with and experienced in research overall than people in other re source poor countries . Very little is known , however , about the quality of informed consent given by Thai subjects in HIV studies . In this study , individuals were surveyed about their experience with the informed consent process , their underst and ing of the information they were given about the trial , and the voluntary nature of their decision to join OBJECTIVES To address participants ' knowledge of informed consent and to explore whether knowledge level is related to clinical trial satisfaction . METHODS One hundred and fourteen patients enrolled in three ongoing r and omized controlled trials of osteoarthritis and rheumatoid arthritis were asked to complete a mailed form . The survey was related to aspects of the informed consent process : quality of information given during the informed consent process , participants ' self perception of knowledge , objective evaluation of participants ' knowledge and participants ' overall trial satisfaction . These four aspects were categorized as high , intermediate or low . Correlation between participants ' knowledge and satisfaction was measured using the Spearman 's Rho test and variables associated with knowledge by st and ard univariable analyses . A p value < or = 0.05 was considered significant . RESULTS One hundred and five participants answered the question naire . The quality of information given during the informed consent process was rated as being high by 81 % participants , intermediate by 15.2 % and low by 3.8 % . Fifty-one percent of the participants believed they had a good level of knowledge , but , objective evaluation qualified as high in only 14.3 % of them . Overall trial satisfaction was high in 95 % of the participants . No significant correlation was found between knowledge and satisfaction ( r=0.16 ; p=0.086 ) . Age was negatively associated with a higher level of knowledge ( 48 vs. 58 years old , p=0.008 ) . CONCLUSIONS We found a lack of correlation between satisfaction and knowledge in clinical trials participants . During a r and omized controlled trial the investigator should consider encouraging activities to improve not only participants ' satisfaction , but also their level of knowledge Background : Informed consent in clinical research is m and ated throughout the world . Both patient subjects and investigators are required to underst and and accept the distinction between research and treatment . Aim : To document the extent and to identify factors associated with therapeutic misconception in a population of patient subjects or parent proxies recruited from a variety of multicentre trials ( parent studies ) . Patients and methods : The study comprised two phases : the development of a question naire to assess the quality of informed consent and a survey of patient subjects based on this question naire . Results : A total of 303 patient subjects or parent proxies were contacted and 279 question naires were analysed . The median age was 49.5 years , sex ratio was 1 and 61 % of respondents were professionally active . Overall memorisation of the oral or written communication of informed consent was good ( 69–97 % ) , and satisfaction with the process was around 70 % . Therapeutic misconception was present in 70 % of respondents , who expected to receive better care and ignored the consequence of r and omisation and treatment comparisons . This was positively associated with the acuteness and severity of the disease . Conclusion : The authors suggest that the risk of therapeutic misconception be specifically addressed in consent forms as an educational tool for both patients and investigators |
12,711 | 29,608,708 | Conclusions There is insufficient evidence demonstrating whether cycling exercise during HD improves patient outcomes . | Background Intradialytic cycling ( IDC ) , delivered during haemodialysis ( HD ) , has the potential to improve many health issues .
This systematic review and meta- analysis examine the evidence on the effects of IDC on exercise capacity , quality of life ( QoL ) , physical function and cardiovascular health . | INTRODUCTION Cardiovascular disease is the major cause of death in hemodialysis patients . Regular aerobic or intradialytic exercise may play a role in reducing cardiovascular mortality in these patients . The aim of this study was to evaluate the relationship between intradialytic exercise and echocardiographic findings . METHODS AND MATERIAL S Forty patients were enrolled in the study from Shahrekord Hemodialysis Center . They were r and omly assigned into the exercise and control groups . In the exercise group , the patients had a 30-minute exercise program per dialysis session , 3 times a week , for 3 months . Electrocardiography and echocardiography were done at the beginning of the study and 3 months later . RESULTS The mean age and body mass index of the patients were 43.2 + /- 10.5 years and 21.7 + /- 5.4 kg/m2 , respectively . Left ventricular ejection fraction increased and systolic pulmonary artery pressure and right ventricular size decreased significantly after the study in the exercise group patients . CONCLUSIONS Our results showed the improvement of cardiac systolic and diastolic function in patients who had physical exercise during dialysis sessions . Regular intradialysis exercise can be suggested for hemodialysis patients without cardiac disease Objective To examine how poor reporting and inadequate methods for key method ological features in r and omised controlled trials ( RCTs ) have changed over the past three decades . Design Mapping of trials included in Cochrane review s. Data sources Data from RCTs included in all Cochrane review s published between March 2011 and September 2014 reporting an evaluation of the Cochrane risk of bias items : sequence generation , allocation concealment , blinding , and incomplete outcome data . Data extraction For each RCT , we extracted consensus on risk of bias made by the review authors and identified the primary reference to extract publication year and journal . We matched journal names with Journal Citation Reports to get 2014 impact factors . Main outcomes measures We considered the proportions of trials rated by review authors at unclear and high risk of bias as surrogates for poor reporting and inadequate methods , respectively . Results We analysed 20 920 RCTs ( from 2001 review s ) published in 3136 journals . The proportion of trials with unclear risk of bias was 48.7 % for sequence generation and 57.5 % for allocation concealment ; the proportion of those with high risk of bias was 4.0 % and 7.2 % , respectively . For blinding and incomplete outcome data , 30.6 % and 24.7 % of trials were at unclear risk and 33.1 % and 17.1 % were at high risk , respectively . Higher journal impact factor was associated with a lower proportion of trials at unclear or high risk of bias . The proportion of trials at unclear risk of bias decreased over time , especially for sequence generation , which fell from 69.1 % in 1986 - 1990 to 31.2 % in 2011 - 14 and for allocation concealment ( 70.1 % to 44.6 % ) . After excluding trials at unclear risk of bias , use of inadequate methods also decreased over time : from 14.8 % to 4.6 % for sequence generation and from 32.7 % to 11.6 % for allocation concealment . Conclusions Poor reporting and inadequate methods have decreased over time , especially for sequence generation and allocation concealment . But more could be done , especially in lower impact factor journals Background There is emerging evidence that exercise training could positively impact several of the cardiovascular risk factors associated with sudden cardiac death amongst patients on haemodialysis . The primary aim of this study is to evaluate the effect of an intradialytic exercise programme on left ventricular mass . Method and design Prospect i ve , r and omised cluster open-label blinded endpoint clinical trial in 130 patients with end stage renal disease on haemodialysis . Patients will be r and omised 1:1 to either 1 ) minimum of 30 min continuous cycling thrice weekly during dialysis or 2 ) st and ard care . The primary outcome is change in left ventricular mass at 6 months , assessed by cardiac MRI ( CMR ) . In order to detect a difference in LV mass of 15 g between groups at 80 % power , a sample size of 65 patients per group is required . Secondary outcome measures include abnormalities of cardiac rhythm , left ventricular volumes and ejection fraction , physical function measures , anthropometric measures , quality of life and markers of inflammation , with interim assessment for some measures at 3 months . Discussion This study will test the hypothesis that an intradialytic programme of exercise leads to a regression in left ventricular mass , an important non-traditional cardiovascular risk factor in end stage renal disease . For the first time this will be assessed using CMR . We will also evaluate the efficacy , feasibility and safety of an intradialytic exercise programme using a number of secondary end-points . We anticipate that a positive outcome will lead to both an increased patient uptake into established intradialytic programmes and the development of new programmes nationally and internationally . Trial registration numberIS RCT N11299707 ( registration date 5th March 2015 ) BACKGROUND Cardiovascular disease ( CVD ) mortality rates are greatly elevated in chronic kidney disease patients receiving maintenance haemodialysis therapy . The purpose of this study was to evaluate the efficacy of intradialytic endurance exercise training on novel risk factors that may contribute to this excessive CVD risk . METHODS Seventeen haemodialysis patients were r and omized to either an intradialytic exercise training ( cycling ) group ( EX ; n = 8) or a non-exercising control group ( CON ; n = 9 ) for 4 months . At baseline and following the intervention , we measured serum parameters related to CVD risk and renal function , used echocardiography to measure variables related to cardiac structure and function and assessed physical performance by a vali date d shuttle walk test . RESULTS Performance on the shuttle walk test increased by 17 % in EX ( P < 0.05 ) , but did not change in CON . There was no change in serum lipids or inflammatory markers ( C-reactive protein , interleukin-6 ) in either group . Serum thiobarbituric acid reactive substances , a marker of oxidative stress , were reduced by 38 % in EX ( P < 0.05 ) , but did not change in CON . In addition , serum alkaline phosphatase ( ALP ) , a putative risk factor for vascular calcification , was reduced by 27 % in EX ( P < 0.05 ) , but did not change in CON . There was no change in left atrial volume , left ventricular mass or myocardial performance index in either group . However , the thickness of the epicardial fat layer was reduced by 11 % in EX ( P < 0.05 ) , but did not change in CON . Furthermore , the change in physical performance was inversely correlated to the change in epicardial fat ( r = -0.63 ; P = 0.03 ) . CONCLUSIONS These results suggest that endurance exercise training may improve CVD risk in haemodialysis patients by decreasing novel risk factors including serum oxidative stress , ALP and epicardial fat BACKGROUND Sedentary behavior is associated with an increased risk for death in the general population . However , the association between inactivity and mortality has not been studied in a large cohort of dialysis patients despite the high prevalence of sedentary behavior in this group . METHODS We used the Dialysis Morbidity and Mortality Study Wave 2 , a prospect i ve study of a national sample of 4,024 incident peritoneal dialysis and hemodialysis patients from 1996 to 1997 , to determine whether sedentary behavior is associated with increased mortality during a 1-year period in this group after adjusting for confounding variables . RESULTS The study population consisted of the 2,837 patients with accurate survival data who were able to ambulate and transfer . Eleven percent of the sedentary patients died during the study period compared with 5 % of nonsedentary patients . In a survival analysis , sedentary behavior ( hazard ratio , 1.62 ; 95 % confidence interval , 1.16 to 2.27 ) was associated with an increased risk for death at 1 year after adjusting for all variables that we postulated might be associated with survival and for differences between sedentary and nonsedentary patients . CONCLUSION Sedentary behavior is associated with an increased risk for mortality among dialysis patients similar in magnitude to that of other well-established risk factors , such as a one-point reduction in serum albumin concentration . More attention should be given to exercise behavior in dialysis patients , and controlled clinical trials are needed to further define the association of sedentary behavior with mortality 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 Background / Aims : Patients requiring haemodialysis have cardiovascular and immune dysfunction . Little is known about the acute effects of exercise during haemodialysis . Exercise has numerous health benefits but in other population s has a profound impact upon blood pressure , inflammation and immune function ; therefore having the potential to exacerbate cardiovascular and immune dysfunction in this vulnerable population . Methods : Fifteen patients took part in a r and omised-crossover study investigating the effect of a 30-min bout of exercise during haemodialysis compared to resting haemodialysis . We assessed blood pressure , plasma markers of cardiac injury and systemic inflammation and neutrophil degranulation . Results : Exercise increased blood pressure immediately post-exercise ; however , 1 hour after exercise blood pressure was lower than resting levels ( 106±22 vs. 117±25 mm Hg ) . No differences in h-FABP , cTnI , myoglobin or CKMB were observed between trial arms . Exercise did not alter circulating concentrations of IL-6 , TNF-α or IL-1ra nor clearly suppress neutrophil function . Conclusions : This study demonstrates fluctuations in blood pressure during haemodialysis in response to exercise . However , since the fall in blood pressure occurred without evidence of cardiac injury , we regard it as a normal response to exercise superimposed onto the haemodynamic response to haemodialysis . Importantly , exercise did not exacerbate systemic inflammation or immune dysfunction ; intradialytic exercise was well tolerated Abstract Inflammation , endothelial dysfunction , and mineral bone disease are critical factors contributing to morbidity and mortality in hemodialysis ( HD ) patients . Physical exercise alleviates inflammation and increases bone density . Here , we investigated the effects of intradialytic aerobic cycling exercise on HD patients . Forty end-stage renal disease patients undergoing HD were r and omly assigned to either an exercise or control group . The patients in the exercise group performed a cycling program consisting of a 5-minute warm-up , 20 minutes of cycling at the desired workload , and a 5-minute cool down during 3 HD sessions per week for 3 months . Biochemical markers , inflammatory cytokines , nutritional status , the serum endothelial progenitor cell ( EPC ) count , bone mineral density , and functional capacity were analyzed . After 3 months of exercise , the patients in the exercise group showed significant improvements in serum albumin levels , the body mass index , inflammatory cytokine levels , and the number of cells positive for CD133 , CD34 , and kinase insert domain-conjugating receptor . Compared with the exercise group , the patients in the control group showed a loss of bone density at the femoral neck and no increases in EPCs . The patients in the exercise group also had a significantly greater 6-minute walk distance after completing the exercise program . Furthermore , the number of EPCs significantly correlated with the 6-minute walk distance both before and after the 3-month program . Intradialytic aerobic cycling exercise programs can effectively alleviate inflammation and improve nutrition , bone mineral density , and exercise tolerance in HD patients Cardiovascular ( CV ) disease is the most common cause of mortality in end‐stage kidney disease ( ESKD ) , and arterial stiffness , measured by pulse wave velocity ( PWV ) , is an independent predictor of all‐cause and CV mortality . B‐type natriuretic peptide ( BNP ) levels are high in patients with CV disease and ESKD , and increases in BNP may also be a marker of CV risk . Regular exercise has many benefits on quality of life and physical strength and may also improve CV risk , but few studies have addressed the impact of exercise on CV risk in ESKD . We performed a prospect i ve cross‐over trial in 19 hemodialysis ( HD ) patients to assess the impact of regular exercise on surrogate markers of CV risk‐arterial compliance and BNP levels . Exercise involved the use of a bicycle ergometer for minimum 30 min at each HD session for 3 months , with a 1‐month washout period . Group A ( n=9 ) exercised for the first 3 months only , while group B ( n=10 ) performed no intradialytic exercise initially and exercised for 3 months at cross‐over ( month 4 ) . Pulse wave velocity was performed using a SphygmoCor device , with concurrent measurements of BNP and other serum markers , at the commencement of the study , at 3 months , and on completion . The mean PWV ( A : 10.4±3.1 m/s , B : 9.8±3.8 at baseline ) showed a trend toward improvement with exercise ( A : 8.7±2.7 , p=0.07 ) , and no significant change without ( B : 10.5±3.6 , p=0.31 ) . After cross‐over , there was an increase in PWV in group A with cessation of exercise ( 9.75±2.4 , p=0.01 vs. 3 months ) and an improvement in group B with exercise ( 9.33±2.3 , p=0.11 vs. 3 months ) . When comparing PWV after 3 months of exercise vs. 3 months of no exercise ( paired t test ) , there was a significant difference in favor of exercise ( 9.04±0.59 vs. 10.16±0.74 , p=0.008 ) . The mean BNP levels following 3 months of exercise were also lower than those after 3 months of no exercise ( 504.4±101.2 vs. 809.4±196.1[N<100 ] , p=0.047 ) . There was an overall improvement in PWV , and to a lesser extent BNP levels , with 3 months of intradialytic exercise compared with no exercise , suggesting that regular exercise in ESKD may be associated with improvements in arterial compliance and a reduction in CV risk Rational : Patients under regular dialysis can also present alterations in the cardiovascular , musculoskeletal , and metabolic systems . Objectives : The aim of this study is to compare the effects of strength and aerobic exercises performed during hemodialysis ( HD ) in individuals with chronic renal disease . Material s and Methods : R and omized clinical trial . It was developed as a program of exercises three times a week , in the first 2 h of HD for 8 weeks . The patients were divided into three groups : control ( Group 1 , n : 11 ) , strength ( Group 2 , n : 11 ) , and aerobic ( Group 3 , n : 10 ) . G1 has not developed any type of physical training ; G2 utilized a training load of 40 % of one repetition maximum ( 1RM ) with anklets , and developed three series of 15 repetitions . G3 pedaled seated in the dialysis seat , during 20 min , in an ergometric bicycle , with intensity regulated by the perceived effort scale . Before and after 8 weeks , the following variables were evaluated : respiratory muscular strength , pulmonary function , functional capacity , blood biochemistry , and quality of life . Main Findings : In the pre- and post-training comparison , there was statistically significant improvement ( p < 0.05 ) in the maximal inspiratory pressure ( MIP ) , number of steps achieved ( NSA ) , and quality of life ( QoL ) in the trained groups , as compared to the non-exercised group ( G1 ) . Conclusions : The strength and aerobic exercises developed during HD can improve the respiratory muscular strength , functional performance , and quality of life , when compared to individuals presenting the disease who have not developed any type of physical training Fast breath-hold cardiovascular magnetic resonance ( CMR ) shows excellent results for inter study reproducibility of left ventricular ( LV ) volumes , ejection fraction , and mass , which are thought to be superior to results of 2-dimensional echocardiography . However , there is no direct comparison of the inter study reproducibility of both methods in the same subjects . A total of 60 subjects ( normal volunteers [ n = 20 ] , or patients with heart failure [ n = 20 ] or LV hypertrophy [ n = 20 ] ) underwent 2 CMRs and 2 echocardiographic studies for assessment of LV volumes , function , and mass . The inter study reproducibility coefficient of variability was superior for CMR in all groups for all parameters . Statistical significance was reached for end-systolic volume ( 4.4 % to 9.2 % vs 13.7 % to 20.3 % , p < 0.001 ) , ejection fraction ( 2.4 % to 7.3 % vs 8.6 % to 19.4 % , p < 0.001 ) , and mass ( 2.8 % to 4.8 % vs 11.6 % to 15.7 % p < 0.001 ) , with a trend for end-diastolic volume ( 2.9 % to 4.9 % vs 5.5 % to 10.5 % , p = 0.17 ) . The superior inter study reproducibility result ed in considerably lower calculated sample sizes ( reductions of 55 % to 93 % ) required by CMR compared with echocardiography to show clinical ly relevant changes in LV dimensions and function . Thus , CMR has excellent inter study reproducibility in normal , dilated , and hypertrophic hearts , and is superior to 2-dimensional echocardiography Background Restless Legs Syndrome is very common in hemodialysis patients however there are no comparative studies assessing the effectiveness of a non-pharmacological treatment to a classical treatment on parameters related to syndromes ’ severity and quality of life . Methods In this r and omized , partially double blind , placebo controlled trial , thirty two hemodialysis patients with restless legs syndrome were r and omly assigned into three groups : 1 ) the exercise training group ( N = 16 ) , 2 ) the dopamine agonists group ( ropinirole 0.25 mg/d ) ( N = 8) and 3 ) the placebo group ( N = 8) . The intervention programs lasted 6 months . Restless Legs Syndrome severity was assessed using the international severity scale , physical performance by a battery of tests , muscle size and composition by computed tomography , body composition by Dual Energy X Ray Absorptiometry , while depression score , sleep quality , daily sleepiness and quality of life were assessed through question naires . Results Exercise training and dopamine agonists were effective in reducing syndrome ’s symptoms by 46 % ( P = 0.009 ) and 54 % ( P = 0.001 ) respectively . Within group changes revealed that both approaches significantly improved quality of life ( P < 0.05 ) , however , only the dopamine agonists significantly improved sleep quality ( P = 0.009 ) . Within group changes showed a tendency for lean body mass improvements with dopamine agonists , this reached statistical significance only with the exercise training ( P = 0.014 ) , which also reduced fat infiltration in muscles ( P = 0.044 ) and improved physical performance ( P > 0.05 ) in various tests . Between group changes detect significant improvements with both exercise and dopamine agonists in depression score ( P = 0.003 ) , while only the dopamine agonist treatment was able to significantly improve sleep quality , compared to exercise and placebo ( P = 0.016 ) . Conclusions A 6-month exercise training regime was as effective as a 6-month low dosage dopamine agonist treatment in reducing restless legs syndrome symptoms and improving depression score in uremic patients . Further research is needed in order to show whether a combination treatment could be more beneficial for the amelioration of RLS.Trial registration In chronic kidney disease ( CKD ) , oxidative stress ( OS ) plays a central role in the development of cardiovascular diseases . This pilot program aim ed to determine whether an intradialytic aerobic cycling training protocol , by increasing physical fitness , could reduce OS and improve other CKD-related disorders such as altered body composition and lipid profile . Eighteen hemodialysis patients were r and omly assigned to either an intradialytic training ( cycling : 30 min , 55%-60 % peak power , 3 days/week ) group ( EX ; n = 8) or a control group ( CON ; n = 10 ) for 3 months . Body composition ( from dual-energy X-ray absorptiometry ) , physical fitness ( peak oxygen uptake and the 6-minute walk test ( 6MWT ) ) , lipid profile ( triglycerides ( TG ) , total cholesterol , high-density lipoprotein , and low-density lipoprotein ( LDL ) ) , and pro/antioxidant status ( 15-F2α-isoprostanes ( F2-IsoP ) and oxidized LDL in plasma ; superoxide dismutase , glutathione peroxidase , and reduced/oxidized glutathione in erythrocytes ) were determined at baseline and 3 months later . The intradialytic training protocol did not modify body composition but had significant effects on physical fitness , lipid profile , and pro/antioxidant status . Indeed , at 3 months : ( i ) performance on the 6MWT was increased in EX ( + 23.4 % , p < 0.001 ) but did not change in CON , ( ii ) plasma TG were reduced in EX ( -23 % , p < 0.03 ) but were not modified in CON , and ( iii ) plasma F2-IsoP concentrations were lower in EX than in CON ( -35.7 % , p = 0.02 ) . In conclusion , our results show that 30 min of intradialytic training , 3 times per week for 3 months , are enough to exert beneficial effects on the most sensitive and reliable marker of lipid peroxidation ( IsoP ) while improving CKD-associated disorders ( lipid profile and physical fitness ) . Intradialytic aerobic cycling training represents a useful and easy strategy to reduce CKD-associated disorders . These results need to be confirmed with a larger r and omized study Incomplete and inadequate reporting is an avoidable waste that reduces the usefulness of research . The CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement is an evidence -based reporting guideline that aims to improve research transparency and reduce waste . In 2008 , the CONSORT Group developed an extension to the original statement that addressed method ological issues specific to trials of nonpharmacologic treatments ( NPTs ) , such as surgery , rehabilitation , or psychotherapy . This article describes an up date of that extension and presents an extension for reporting abstract s of NPT trials . To develop these material s , the authors review ed pertinent literature published up to July 2016 ; surveyed authors of NPT trials ; and conducted a consensus meeting with editors , trialists , and method ologists . Changes to the CONSORT Statement extension for NPT trials include wording modifications to improve readers ' underst and ing and the addition of 3 new items . These items address whether and how adherence of participants to interventions is assessed or enhanced , description of attempts to limit bias if blinding is not possible , and specification of the delay between r and omization and initiation of the intervention . The CONSORT extension for abstract s of NPT trials includes 2 new items that were not specified in the original CONSORT Statement for abstract s. The first addresses reporting of eligibility criteria for centers where the intervention is performed and for care providers . The second addresses reporting of important changes to the intervention versus what was planned . Both the up date d CONSORT extension for NPT trials and the CONSORT extension for NPT trial abstract s should help authors , editors , and peer review ers improve the transparency of NPT trial reports BACKGROUND Hemodialysis patients show reduced physical function and greater risk of increased arterial stiffness because of hypertension , metabolic disturbances , and vascular calcification . Exercise interventions potentially could improve their vascular risk profile . STUDY DESIGN R and omized controlled pilot clinical study comparing the effects of 6 months of supervised intradialytic exercise training versus home-based exercise training or usual care on physical function and arterial stiffness in hemodialysis patients . SETTING & PARTICIPANTS 70 hemodialysis patients from 3 renal units . INTERVENTION Intradialytic-exercise patients trained 3 times/wk for 6 months on a cycle ergometer and home-based-exercise patients followed a walking program to achieve the same weekly physical activity . Usual-care patients received no specific intervention . OUTCOMES & MEASUREMENTS Primary outcome measures were distance traveled during a 6-minute walk test and aortic pulse wave velocity . Secondary outcome measures included augmentation index ( augmentation pressure as a percentage of central pulse pressure ) , peripheral ( brachial ) and central blood pressures ( measured noninvasively using radial tonometry ) , physical activity , and self-reported physical functioning . Measurements were made at baseline and 6 months . RESULTS At 6 months , there were no significant differences between changes in 6-minute walk test distance ( intradialytic exercise , + 14 % ; home-based exercise , + 11 % ; usual care , + 5 % ) , pulse wave velocity ( intradialytic exercise , -4 % ; home-based exercise , -2 % ; usual care , + 5 % ) , or any secondary outcome measure . LIMITATIONS Lack of medication data limited the analysis of vascular parameters in this study . CONCLUSION There were no differences between intradialytic or home-based exercise training and usual care for either physical function or vascular parameters OBJECTIVE To investigate if high-intensity constant work rate ( CWR ) would constitute a more appropriate testing strategy compared with incremental work rate ( IWR ) to assess the effectiveness of intradialytic aerobic training in patients with end-stage renal disease ( ESRD ) . DESIGN R and omized controlled trial . SETTING Nephrology unit at the university hospital . PARTICIPANTS Patients ( N=28 ; 47.0±11.9y ) under hemodialysis ( 4.4±4.3y ) were r and omly assigned to exercise and control groups . INTERVENTION Patients included in the exercise group underwent a moderate-intensity intradialytic aerobic training program 3 times per week for 12 weeks . MAIN OUTCOME MEASURES Cardiopulmonary and perceptual responses were obtained during an IWR and a high-intensity CWR test to the limit of tolerance on a cycle ergometer . RESULTS Training-induced increases in peak oxygen uptake ( Vo(2)peak ) and time to exercise intolerance ( Tlim ) . Mean improvement in Tlim ( 97.4%±75.6 % ) was significantly higher than increases in Vo(2)peak ( 12%±11.3 % ) ( P<.01 ) ; in fact , while Tlim improved 50 % to 200 % in 9 of 12 patients , Vo(2)peak increases were typically in the 15 % to 20 % range . CWR test revealed lower metabolic , ventilatory , cardiovascular , and subjective stresses at isotime ; in contrast , submaximal responses during the incremental work rate ( at the gas exchange threshold ) remained unaltered after training . CONCLUSIONS A laboratory-based measure of endurance exercise capacity ( high-intensity CWR test to Tlim ) was substantially more sensitive than oxygen uptake at the peak IWR test to unravel the physiologic benefits of an intradialytic aerobic training program in mildly impaired patients with ESRD BACKGROUND Arterial baroreflex sensitivity ( BRS ) evaluation has been increasingly used as an index of cardiac autonomic control . Cardiac autonomic dysfunction leading to depressed BRS has been associated with an increased risk of ventricular arrhythmias and sudden death in patients with chronic kidney disease ( CKD ) on hemodialysis ( HD ) . AIM The purpose of this study was to investigate the effects of an exercise training program during hemodialysis on BRS in CKD patients . PATIENTS AND METHODS 43 HD patients participated in the study . They were r and omly assigned into either a 7-month exercise training program during HD ( Group A : n=22 patients ) or a sedentary control group ( Group B : n=21 patients ) . Additionally , 20 sex- and age-matched sedentary individuals comprised a healthy control group ( Group C ) . All patients at the beginning and the end of the study underwent a tilt test for evaluation of BRS and an exercise testing with spiroergometric study for cardiorespiratory capacity estimation . The level of Hb , medications and the HD procedure remained stable during the study . RESULTS At baseline BRS was found to be reduced by 51.5 % ( p<0.05 ) and baroreflex effectiveness index ( BEI ) by 36.4 % ( p<0.05 ) in Group A compared with Group C. Initially , all HD patients had also significantly lower exercise time and VO2 peak than the healthy subjects . After training , Group A showed a significant improvement in BRS by 23.0 % ( p<0.05 ) , in BEI by 27.0 % ( p<0.05 ) , in event and ramp count by 35.0 % ( p<0.05 ) and 29.0 % ( p<0.05 ) , respectively as well as in VO2 peak by 22.4 % ( p<0.05 ) and in exercise time by 40.9 % ( p<0.05 ) . Significant correlations were found between BRS and METs ( r=0.476 , p<0.05 ) , BRS and VO2 peak ( r=0.443 , p<0.05 ) , BEI and METs ( r = 0.492 , p<0.05 ) , BEI and VO2 peak ( r=0.467 , p<0.05 ) , event count and VO2 peak ( r=0.715 , p<0.01 ) , event count and exercise time ( r=0.799 , p<0.01 ) , in Group A at the end of the study . CONCLUSIONS Our results indicate that HD patients had considerably reduced cardiorespiratory capacity and impaired cardiac BRS compared to healthy sedentary individuals . Importantly , exercise training during HD yielded a marked increase of the indices representing baroreflex activity in association to the improvement of their functional capacity Functional capacity of end-stage renal disease patients is dramatically impaired . Although exercise training programs appear to have beneficial morphological , functional and psychosocial effects in end-stage renal disease patients on hemodialysis ( HD ) , the adherence rate is high . The purpose of this study was to compare the effects of three modes of exercise training on aerobic capacity and to identify the most favourable , efficient and preferable to patients on HD with regard to functional improvements and participation rate in the programs . Fifty-eight volunteer patients were screened for low-risk status and selected from the dialysis population . The 48 patients who completed the study protocol were r and omly assigned either to one of the three training groups or to a control group . Sixteen of them ( Group A - mean age 46.4+/-13.9 years ) completed a 6-month supervised outpatient exercise renal rehabilitation program consisting of three weekly sessions of aerobic and strengthening training on the non-dialysis days ; 10 ( Group B - mean age 48.3+/-12.1 years ) completed a 6-month exercise program during HD ; 10 ( Group C - mean age 51.4+/-12.5 years ) followed an unsupervised moderate exercise program at home , and 12 patients ( Group D-mean age 50.2+/-7.9 years ) were used as patient controls . The level of anemia , the medications and the HD prescription remained stable during the study . Fifteen sex- and age-matched sedentary individuals ( Group E - mean age 46.9+/-6.4 years ) comprised a healthy control group for baseline data . All subjects at the beginning and end of the study underwent clinical examination , laboratory tests and a treadmill exercise test to fatigue endpoints with direct measurement of aerobic capacity . Group A had a higher dropout rate ( 24 % ) compared to groups B ( 17 % ) and C ( 17 % ) . Peak oxygen consumption ( VO2 peak ) increased by 43 % ( p < 0.05 ) , anaerobic threshold ( VO2AT ) by 37 % ( p < 0.05 ) and exercise time by 33 % ( p < 0.05 ) after training in Group A ; by 24 % ( p < 0.05 ) , 18 % ( p < 0.05 ) and 22 % ( p < 0.05 ) , respectively , in B ; and by 17 % ( p < 0.05 ) , 8 % ( p < 0.05 ) and 14 % ( p < 0.05 ) , respectively , in C ; while both remained almost unchanged in Group D. These results demonstrate that intense exercise training on non-dialysis days is the most effective way of training , whereas exercise during HD is also effective and preferable 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 INTRODUCTION Decreased heart rate variability ( HRV ) in patients with end stage renal disease ( ESRD ) undergoing hemodialysis is predictive of cardiac death , especially due to sudden death . OBJECTIVE To evaluate the effects of aerobic training during hemodialysis on HRV and left ventricular function in ESRD patients . METHODS Twenty two patients were r and omized into two groups : exercise ( n = 11 ; 49.6 ± 10.6 years ; 4 men ) and control ( n = 11 ; 43.5 ± 12.8 ; 4 men ) . Patients assigned to the exercise group were su bmi tted to aerobic training , performed during the first two hours of hemodialysis , three times weekly , for 12 weeks . HRV and left ventricular function were assessed by 24 hours Holter monitoring and echocardiography , respectively . RESULTS After 12 weeks of protocol , no significant differences were observed in time and frequency domains measures of HRV in both groups . The ejection fraction improved non-significantly in exercise group ( 67.5 ± 12.6 % vs. 70.4 ± 12 % ) and decreased non-significantly in control group ( 73.6 ± 8.4 % vs. 71.4 ± 7.6 % ) . CONCLUSION A 12-week aerobic training program performed during hemodialysis did not modify HRV and did not significantly improve the left ventricular function AIM We wished to determine if an 8-week program of exercise during dialysis in end-stage renal disease ( ESRD ) patients would increase urea removal ( enhance dialysis efficacy ) with subsequent improvements in work performance and perception of quality of life , and /or alterations in cardiovascular status . METHODS Self-care hemodialysis patients ( EX , n = 6 ) performed cycle ergometry exercise 3 times per week during their dialysis session at 40 - 50 % maximal work capacity for 15 min during each of the first 3 hours of dialysis and were matched for age , protein catabolism rate , and WLmax with a CON group ( n = 7 ) . Dialysis efficacy was measured using serum urea clearance ( Kt/V ) and dialysate urea clearance ( DUC ) during the first 2 hours of dialysis . Resting blood pressure was monitored on a sessional basis , pre- and postdialysis and during exercise in the EX group . QOL , measured using the SF-36 question naire , and WLmax were determined prior to and at 4 and 8 weeks of the exercise program . RESULTS DUC was significantly elevated in the EX group at the end of the exercise program , but was of insufficient magnitude to result in an overall increase in Kt/V. DUC decreased in the CON group but Kt/V remained unchanged . No changes in resting blood pressure occurred in either group over the course of the study , however , pulse pressure tended to increase in the CON group but decrease in the EX group , indicating a potential beneficial adaptation of the cardiovascular system in patients undergoing an exercise program . The exercise program had no effect on QOL scores and this was most likely due to the short duration of the exercise program and high-functioning level of the population studied as compared to normative data for this patient population . We also found that 33 % of the exercise sessions in the 3rd hour of dialysis were not performed due to hypotensive events . CONCLUSION Exercise during dialysis enhanced dialysate urea removal but not serum urea clearance . Alterations in the modality and the timing of exercise during dialysis may be required to elicit increases in serum urea clearance . It is also recommended that exercise during dialysis be performed during the first 2 hours of dialysis Background : Exercise during dialysis ( EDD ) in End-Stage Renal Disease ( ESRD ) has been documented as an effective intervention to improving a patient 's aerobic capacity . Aims : This pilot study aim ed to confirm physiological improvements , to establish its safety and practicality and to form guidelines for a long-term study , leading to the integration of EDD in ESRD therapy . Methods : A total of 17 patients on hospital haemodialysis were recruited : ten exercisers ( age 42.4 ± 12.6 ) and six controls ( age 41.0 ± 8.3 ) . Both groups were initially tested for estimated VO2max , heart rate , blood pressure , leg extension peak torque , anxiety and depression levels , as well as biochemical and haematological values . The exercisers then underwent cycling ergometer exercise sessions during dialysis , twice weekly , for a total of 12 sessions . Both groups were re-tested after this period . Results : All test and exercise sessions were completed without complication . Compliance was high with only 1 exerciser failing to complete all 12 sessions . The exercisers showed a statistically significant increase ( p < 0.05 ) in EDD workrates ( 44.3 to 52.1 watts ) during the 12 sessions and a reduction in anxiety ( p < 0.05 ) . Statistical analysis showed no other significant changes in either group after the 6-week period . Conclusion : This pilot study has confirmed that aerobic EDD is feasible and well accepted by patients on hospital haemodialysis . EDD reduced anxiety scores and showed a trend for an improved level of aerobic fitness |
12,712 | 29,063,728 | There is no evidence to inform the comparative effectiveness of LRP or RARP compared with ORP for oncological outcomes .
Urinary and sexual quality of life appear similar .
Overall and serious postoperative complication rates appear similar .
The difference in postoperative pain may be minimal .
Men undergoing LRP or RARP may have a shorter hospital stay and receive fewer blood transfusions | OBJECTIVE To determine the effects of laparoscopic radical prostatectomy ( LRP ) , or robot-assisted radical prostatectomy ( RARP ) compared with open radical prostatectomy ( ORP ) in men with localized prostate cancer . | BACKGROUND The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen ( PSA ) testing remains uncertain . METHODS We compared active monitoring , radical prostatectomy , and external-beam radiotherapy for the treatment of clinical ly localized prostate cancer . Between 1999 and 2009 , a total of 82,429 men 50 to 69 years of age received a PSA test ; 2664 received a diagnosis of localized prostate cancer , and 1643 agreed to undergo r and omization to active monitoring ( 545 men ) , surgery ( 553 ) , or radiotherapy ( 545 ) . The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up . Secondary outcomes included the rates of disease progression , metastases , and all-cause deaths . RESULTS There were 17 prostate-cancer-specific deaths overall : 8 in the active-monitoring group ( 1.5 deaths per 1000 person-years ; 95 % confidence interval [ CI ] , 0.7 to 3.0 ) , 5 in the surgery group ( 0.9 per 1000 person-years ; 95 % CI , 0.4 to 2.2 ) , and 4 in the radiotherapy group ( 0.7 per 1000 person-years ; 95 % CI , 0.3 to 2.0 ) ; the difference among the groups was not significant ( P=0.48 for the overall comparison ) . In addition , no significant difference was seen among the groups in the number of deaths from any cause ( 169 deaths overall ; P=0.87 for the comparison among the three groups ) . Metastases developed in more men in the active-monitoring group ( 33 men ; 6.3 events per 1000 person-years ; 95 % CI , 4.5 to 8.8 ) than in the surgery group ( 13 men ; 2.4 per 1000 person-years ; 95 % CI , 1.4 to 4.2 ) or the radiotherapy group ( 16 men ; 3.0 per 1000 person-years ; 95 % CI , 1.9 to 4.9 ) ( P=0.004 for the overall comparison ) . Higher rates of disease progression were seen in the active-monitoring group ( 112 men ; 22.9 events per 1000 person-years ; 95 % CI , 19.0 to 27.5 ) than in the surgery group ( 46 men ; 8.9 events per 1000 person-years ; 95 % CI , 6.7 to 11.9 ) or the radiotherapy group ( 46 men ; 9.0 events per 1000 person-years ; 95 % CI , 6.7 to 12.0 ) ( P<0.001 for the overall comparison ) . CONCLUSIONS At a median of 10 years , prostate-cancer-specific mortality was low irrespective of the treatment assigned , with no significant difference among treatments . Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring . ( Funded by the National Institute for Health Research ; ProtecT Current Controlled Trials number , IS RCT N20141297 ; Clinical Trials.gov number , NCT02044172 . ) BACKGROUND The absence of trial data comparing robot-assisted laparoscopic prostatectomy and open radical retropubic prostatectomy is a crucial knowledge gap in uro-oncology . We aim ed to compare these two approaches in terms of functional and oncological outcomes and report the early postoperative outcomes at 12 weeks . METHOD In this r and omised controlled phase 3 study , men who had newly diagnosed clinical ly localised prostate cancer and who had chosen surgery as their treatment approach , were able to read and speak English , had no previous history of head injury , dementia , or psychiatric illness or no other concurrent cancer , had an estimated life expectancy of 10 years or more , and were aged between 35 years and 70 years were eligible and recruited from the Royal Brisbane and Women 's Hospital ( Brisbane , QLD ) . Participants were r and omly assigned ( 1:1 ) to receive either robot-assisted laparoscopic prostatectomy or radical retropubic prostatectomy . R and omisation was computer generated and occurred in blocks of ten . This was an open trial ; however , study investigators involved in data analysis were masked to each patient 's condition . Further , a masked central pathologist review ed the biopsy and radical prostatectomy specimens . Primary outcomes were urinary function ( urinary domain of EPIC ) and sexual function ( sexual domain of EPIC and IIEF ) at 6 weeks , 12 weeks , and 24 months and oncological outcome ( positive surgical margin status and biochemical and imaging evidence of progression at 24 months ) . The trial was powered to assess health-related and domain-specific quality of life outcomes over 24 months . We report here the early outcomes at 6 weeks and 12 weeks . The per- protocol population s were included in the primary and safety analyses . This trial was registered with the Australian New Zeal and Clinical Trials Registry ( ANZCTR ) , number ACTRN12611000661976 . FINDINGS Between Aug 23 , 2010 , and Nov 25 , 2014 , 326 men were enrolled , of whom 163 were r and omly assigned to radical retropubic prostatectomy and 163 to robot-assisted laparoscopic prostatectomy . 18 withdrew ( 12 assigned to radical retropubic prostatectomy and six assigned to robot-assisted laparoscopic prostatectomy ) ; thus , 151 in the radical retropubic prostatectomy group proceeded to surgery and 157 in the robot-assisted laparoscopic prostatectomy group . 121 assigned to radical retropubic prostatectomy completed the 12 week question naire versus 131 assigned to robot-assisted laparoscopic prostatectomy . Urinary function scores did not differ significantly between the radical retropubic prostatectomy group and robot-assisted laparoscopic prostatectomy group at 6 weeks post-surgery ( 74·50 vs 71·10 ; p=0·09 ) or 12 weeks post-surgery ( 83·80 vs 82·50 ; p=0·48 ) . Sexual function scores did not differ significantly between the radical retropubic prostatectomy group and robot-assisted laparoscopic prostatectomy group at 6 weeks post-surgery ( 30·70 vs 32·70 ; p=0·45 ) or 12 weeks post-surgery ( 35·00 vs 38·90 ; p=0·18 ) . Equivalence testing on the difference between the proportion of positive surgical margins between the two groups ( 15 [ 10 % ] in the radical retropubic prostatectomy group vs 23 [ 15 % ] in the robot-assisted laparoscopic prostatectomy group ) showed that e quality between the two techniques could not be established based on a 90 % CI with a Δ of 10 % . However , a superiority test showed that the two proportions were not significantly different ( p=0·21 ) . 14 patients ( 9 % ) in the radical retropubic prostatectomy group versus six ( 4 % ) in the robot-assisted laparoscopic prostatectomy group had postoperative complications ( p=0·052 ) . 12 ( 8 % ) men receiving radical retropubic prostatectomy and three ( 2 % ) men receiving robot-assisted laparoscopic prostatectomy experienced intraoperative adverse events . INTERPRETATION These two techniques yield similar functional outcomes at 12 weeks . Longer term follow-up is needed . In the interim , we encourage patients to choose an experienced surgeon they trust and with whom they have rapport , rather than a specific surgical approach . FUNDING Cancer Council Queensl and Background Few studies to date have directly compared outcomes of retropubic ( RRP ) and laparoscopic ( LRP ) radical prostatectomy . We investigated a single institution experience with RRP and LRP with respect to functional and pathological outcomes . Methods 168 patients who underwent RRP were compared to 171 patients who underwent LRP at our institution . Pathological and functional outcomes including postoperative urinary incontinence and erectile dysfunction ( ED ) of the two cohorts were examined . Results Patients had bilateral , unilateral and no nerve sparing technique performed in 83.3 % , 1.8 % and 14.9 % of cases for RRP and 23.4 % , 22.8 % and 53.8 % of cases for LRP , respectively ( p < 0.001 ) . Overall positive surgical margin rates were 22.2 % among patients who underwent RRP compared to 26.5 % of patients who underwent LRP ( p = 0.435 ) . Based upon pads/day , urinary continence postoperatively was achieved in 83.2 % and 82.8 % for RRP and LRP , respectively ( p = 0.872 ) . Analysis on postoperative ED was limited due to lack of information on the preoperative erectile status . However , postoperatively there were no differences with respect to ED between the two cohorts ( p = 0.151 ) . Based on ICIQ-scores , surgeons with more experience had lower rates of postoperative incontinence irrespective of surgical technique ( p = 0.001 and p < 0.001 for continuous and stratified data , respectively ) . Conclusions RRP and LRP represent effective surgical approaches for the treatment of clinical ly localized prostate cancer . Pathological outcomes are excellent for both surgical techniques . Functional outcomes including postoperative urinary incontinence and ED are comparable between the cohorts . Surgeon experience is more relevant than surgical technique applied PURPOSE We prospect ively evaluated the morbidity , and minor and major complications of laparoscopic radical prostatectomy performed by a single surgical team . MATERIAL S AND METHODS Between January 28 , 1998 and February 28 , 2001 , 567 patients 42 to 77 years old ( mean age plus or minus st and ard deviation 63.5 + /- 6 ) with clinical ly localized prostate cancer underwent laparoscopic radical prostatectomy , including 458 ( 80.6 % ) , without lymphadenectomy . Mean body mass index was 25.3 + /- 2.9 ( range 17.3 to 37.5 ) . American Society of Anesthesiologists score was 1 to 3 in 65 % , 27 % and 8 % of cases , respectively . A total of 12 patients ( 2.1 % ) had undergone intra-abdominal surgery below the mesocolon and 40 had undergone urological surgery . Intraoperative and postoperative data were recorded as well as all complications and their severity score within the initial 30 days postoperatively . RESULTS A total of 105 complications were observed in 97 patients ( 17.1 % ) , including 21 major ( 3.7 % ) and 83 minor ( 14.6 % ) complications . Of the patients 21 ( 3.7 % ) underwent reoperation for a postoperative complication , including 10 ( 1.76 % ) who required an intensive care unit stay . Seven cases ( 1.2 % ) were converted to conventional retropubic radical prostatectomy . Mean blood loss was 380 + /- 195 ml . and the overall transfusion rate was 4.9 % . In 2 patients ( 0.3 % ) deep vein thrombosis was associated with another surgical complication but not with pulmonary embolism . Urological , bowel and hemorrhagic complications represented 66.6 % , 16.2 % and 7.6 % ( total 89.4 % ) of all complications , and 20 % , 33.3 % and 33.3 % of all repeat interventions , respectively . CONCLUSIONS Laparoscopic radical prostatectomy was performed according to the defined protocol with no complications in 82.9 % of patients . The morbidity of this approach compares favorably with that of retropubic surgery . Growing experience and knowledge sharing concerning the prevention and early management of these complications would make possible a further decrease in the morbidity of laparoscopic radical prostatectomy PURPOSE Given the lack of r and omized trials comparing robot-assisted radical prostatectomy ( RARP ) and open radical prostatectomy ( ORP ) , we sought to re-examine the outcomes of these techniques using a cohort of patients treated in the postdissemination era . PATIENTS AND METHODS Overall , data from 5,915 patients with prostate cancer treated with RARP or ORP within the SEER-Medicare linked data base diagnosed between October 2008 and December 2009 were abstract ed . Postoperative complications , blood transfusions , prolonged length of stay ( pLOS ) , readmission , additional cancer therapies , and costs of care within the first year after surgery were compared between the two surgical approaches . To decrease the effect of unmeasured confounders , instrumental variable analysis was performed . Multivariable logistic regression analyses were then performed . RESULTS Overall , 2,439 patients ( 41.2 % ) and 3,476 patients ( 58.8 % ) underwent ORP and RARP , respectively . In multivariable analyses , patients undergoing RARP had similar odds of overall complications , readmission , and additional cancer therapies compared with patients undergoing ORP . However , RARP was associated with a higher probability of experiencing 30- and 90-day genitourinary and miscellaneous medical complications ( all P ≤ .02 ) . Additionally , RARP led to a lower risk of experiencing blood transfusion and of having a pLOS ( all P < .001 ) . Finally , first-year reimbursements were greater for patients undergoing RARP compared with ORP ( P < .001 ) . CONCLUSION RARP and ORP have comparable rates of complications and additional cancer therapies , even in the postdissemination era . Although RARP was associated with lower risk of blood transfusions and a slightly shorter length of stay , these benefits do not translate to a decrease in expenditures OBJECTIVES To prospect ively compare intra- and peri-operative outcomes of open radical retropubic prostatectomy ( RRP ) and laparoscopic prostatectomy ( LRP ) by a single surgeon . PATIENTS AND METHODS One-hundred-twenty , consecutive , age-matched patients diagnosed with clinical ly localized prostate cancer were eligible for surgery . Sixty patients underwent RRP and 60 , LRP . Intra- and peri-operative parameters , pathologic findings and early complications were recorded . A vali date d visual analogue scale was used to assess pain in the recovery room , 3 h after the operation and on post-operative days 1 , 2 and 3 . A cystogram was performed on post-operative day 5 . RESULTS Operating time was significantly shorter in the RRP group versus the LRP group ( mean+/-SD , 170+/-34 . 2 vs 235+/-49.9 min , p<0.001 ) . Blood loss was significantly less in the LRP group versus the RRP group ( mean+/-SD , 853.3+/-485 vs 257.3+/-177 ml , p<0.001 ) , but no patient in either group underwent early re-intervention for bleeding . The RRP group showed a trend for higher use of analgesia . A watertight anastomosis was shown at cystourethrography and the catheter removed in 86 % and 66 % of LRP and RRP patients , respectively . The overall percentage of post-operative complications and positive margins were comparable . CONCLUSION Laparoscopic prostatectomy is an attractive alternative to open prostatectomy , offering the advantages of reduced blood loss and safe early catheter removal . Furthermore , the laparoscopic procedure proved to be safe oncologically . Long-term follow-up is required to compare functional results in terms of continence and potency Holmberg L , Bill-Axelson A , Helgesen F , Salo JO , Folmerz P , Haggman M , et al. A r and omized trial comparing radical prostatectomy with watchful waiting in early prostate cancer . N Engl J Med 2002;347 : 781 - 9 . Background : The clinical importance and disease burden of prostate cancer — the PURPOSE To cure localized prostate cancer , the entire prostate must be eliminated , which is what all forms of treatment must achieve . Although there is no better way to cure localized disease than total surgical removal , the challenge is whether this can be accomplished with acceptable morbidity . MATERIAL S AND METHODS To evaluate quality of life following radical retropubic prostatectomy , patient reported outcomes of 62 men who underwent radical retropubic prostatectomy at this institution were recorded during the first 18 months of followup . By 18 months 93 % of the patients were dry ( wearing no pads ) and 93 % to 98 % characterized urinary bothersomeness as none or small . Potency , defined as the ability to achieve unassisted intercourse with or without the use of sildenafil , improved gradually and by 18 months 86 % of the patients were potent and 84 % considered sexual bothersomeness as none or small . In an effort to improve the outcome of radical prostatectomy , the surgical procedures on these 62 patients were videotaped prospect ively . The videotapes were review ed 18 months after the study was initiated and 4 specific steps in the surgical procedure were correlated with patient reported outcomes . Surgeons who wish to improve their outcomes should consider using this technique to identify in their own h and s other important arbitrary variations that may improve results . RESULTS The probability of maintaining an undetectable prostate specific antigen was evaluated in men with similar pathological stages of disease who were or were not potent following surgery . Men who were potent had the same outcome as those who were impotent , supporting the premise that preservation of sexual function does not compromise cancer control . Cancer control and quality of life following brachytherapy were analyzed and the following conclusions were made : 1 ) high dose intensification is necessary if radiation therapy is expected to cure prostate cancer but I doubt that any form of radiotherapy will produce durable cancer control for 20 to 30 years ; 2 ) although brachytherapy is rarely adequate as monotherapy , I am not certain that brachytherapy combined with external beam radiotherapy is any better than 3-dimensional conformal therapy alone and the side effects are uncertain , and 3 ) I believe that a prostate specific antigen nadir of less than 0.2 ng./ml . is necessary to confirm an adequate response to radiation . CONCLUSIONS I believe that there is no better way to cure organ confined cancer than total surgical removal . Today continence and potency rates should be high . If not , a review of intraoperative videotapes of successful and unsuccessful cases can improve results . In men treated with radiotherapy stringent criteria for treatment response and quality of life outcomes are needed The terms applicability , generalizability , external validity and transferability are related , sometimes used interchangeably and have in common that they lack a clear and consistent definition in the classic epidemiological literature . However , all of these terms generally describe one overarching theme : whether or not available research evidence can be directly utilized to answer the healthcare questions at h and , ideally supported by a judgment about the degree of confidence for this utilization . This concept has been called directness . The objectives of this paper were to delineate how non-r and omized studies ( NRS ) inform judgments in relation to directness and the concepts that it encompasses in the context of systematic review s. We will briefly review what is known and describe the theoretical and practical issues as well as offer guidance to those tackling the challenges of judging directness and using research evidence to answer healthcare questions with evidence from NRS . In particular , we suggest a framework in which authors can use NRS as a complement , sequence or replacement for r and omized controlled trials ( RCTs ) by focusing on judgments about the population , intervention , comparison and outcomes . Authors of systematic review s will use NRS to complement judgments about the inconsistencies , the rationale and credibility of subgroup analysis , the baseline risk estimates for the determination of absolute benefits and downsides , and the directness of surrogate outcomes . This evidence includes context ual or supplementary evidence . Authors of systematic review and other summaries of the evidence use NRS as sequential evidence to provide evidence when insufficient evidence is available for an outcome from RCTs , but NRS evidence is available ( e.g. , long-term harms ) . Use of evidence from NRS may also serve to replace RCT evidence when NRS provide equivalent ( or potentially higher ) confidence in the evidence ( i.e. quality ) compared to indirect evidence from RCTs . These judgments will be made in the context of other domains that influence the overall quality of the body of evidence , including the risk of bias , publication bias ( i.e. limitations in the detailed study design and execution ) , inconsistency , imprecision and factors that increase our confidence in effects . This article will support systematic review ers in their interaction with decision makers , that is , those who use the systematic review to develop guidelines , address health policy makers , and make clinical decisions , by making these judgments transparent . Copyright © 2013 John Wiley & Sons , BACKGROUND We previously found no significant differences in mortality between men who underwent surgery for localized prostate cancer and those who were treated with observation only . Uncertainty persists regarding nonfatal health outcomes and long‐term mortality . METHODS From November 1994 through January 2002 , we r and omly assigned 731 men with localized prostate cancer to radical prostatectomy or observation . We extended follow‐up through August 2014 for our primary outcome , all‐cause mortality , and the main secondary outcome , prostate‐cancer mortality . We describe disease progression , treatments received , and patient‐reported outcomes through January 2010 ( original follow‐up ) . RESULTS During 19.5 years of follow‐up ( median , 12.7 years ) , death occurred in 223 of 364 men ( 61.3 % ) assigned to surgery and in 245 of 367 ( 66.8 % ) assigned to observation ( absolute difference in risk , 5.5 percentage points ; 95 % confidence interval [ CI ] , ‐1.5 to 12.4 ; hazard ratio , 0.84 ; 95 % CI , 0.70 to 1.01 ; P=0.06 ) . Death attributed to prostate cancer or treatment occurred in 27 men ( 7.4 % ) assigned to surgery and in 42 men ( 11.4 % ) assigned to observation ( absolute difference in risk , 4.0 percentage points ; 95 % CI , ‐0.2 to 8.3 ; hazard ratio , 0.63 ; 95 % CI , 0.39 to 1.02 ; P=0.06 ) . Surgery may have been associated with lower all‐cause mortality than observation among men with intermediate‐risk disease ( absolute difference , 14.5 percentage points ; 95 % CI , 2.8 to 25.6 ) but not among those with low‐risk disease ( absolute difference , 0.7 percentage points ; 95 % CI , ‐10.5 to 11.8 ) or high‐risk disease ( absolute difference , 2.3 percentage points ; 95 % CI , ‐11.5 to 16.1 ) ( P=0.08 for interaction ) . Treatment for disease progression was less frequent with surgery than with observation ( absolute difference , 26.2 percentage points ; 95 % CI , 19.0 to 32.9 ) ; treatment was primarily for asymptomatic , local , or biochemical ( prostate‐specific antigen ) progression . Urinary incontinence and erectile and sexual dysfunction were each greater with surgery than with observation through 10 years . Disease‐related or treatment‐related limitations in activities of daily living were greater with surgery than with observation through 2 years . CONCLUSIONS After nearly 20 years of follow‐up among men with localized prostate cancer , surgery was not associated with significantly lower all‐cause or prostate‐cancer mortality than observation . Surgery was associated with a higher frequency of adverse events than observation but a lower frequency of treatment for disease progression , mostly for asymptomatic , local , or biochemical progression . ( Funded by the Department of Veterans Affairs and others ; PIVOT Clinical Trials.gov number , NCT00007644 . |
12,713 | 21,708,850 | All treatment strategies result ed in acceptable pain control and were well tolerated . | The European Association for Palliative Care recommendation for starting morphine for cancer pain is dose titration with immediate release ( IR ) oral morphine given every 4 h with additionally doses for breakthrough pain .
As part of a EU 6th framework programme to revise the guidelines we review the evidence regarding starting treatment and dose titration of opioids in adult patients with moderate to severe cancer pain . | Objectives To evaluate whether the current European Association for Palliative Care recommendation regarding the starting dose of 5 mg of normal-release morphine ( NRM ) sulfate oral solution every 4 hours in opioid naive patients or 10 mg in patients already being treated with “ weak ” opioids is effective and could be proposed as starting routine dose in clinical practice . Secondary aims were to estimate the percentage of patients who were high responders to NRM and to study the association of baseline patient characteristics with both high analgesic responsivity and the need of opioid dose escalation . Methods Consecutive strong opioid-naive patients with cancer pain were enrolled in a multicenter uncontrolled phase 4 clinical trial . Oral NRM was administered at 2 different dosages : 5 and 10 mg every 4 hours , respectively , for opioids-naive ( group A ) and nonopioids-naive ( group B ) patients as starting therapy . Average daily dosages of NRM and opioid escalation index ( OEI ) were calculated and the reduction in pain score was tested through Student t test both in group A and in group B patients . Results One hundred fifty-nine consecutive patients were enrolled and data analysis was conducted on 151 ( 95 % ) patients . On an average the OEIs were : 3.2 in group A and 6.5 in group B and a significant reduction in pain score both after 3 and 5 days from baseline ( P<0.001 ) was shown in both groups . In multivariate analysis both Karnofsky Performance Status and episodic pain showed to be independent prognostic factors of a high analgesic response . The presence of neuropathic pain showed to be associated with a higher OEI . Discussion These data show that empiric st and ard doses of NRM during titration , recommended by European Association for Palliative Care , are effective in clinical practice To treat cancer pain , physicians often decide to jump directly from step 1 of the World Health Organization ( WHO ) analgesic ladder to step 3 . The use of transdermal fentanyl in patients with cancer pain who had either used no opioid before , or only codeine , is evaluated in the present trial . Both opioid-naive ( N = 14 ) and codeine-using ( N = 14 ) patients started with transdermal fentanyl in the lowest available delivery rate ( 25 microg/hr ) . Immediate-release oral morphine was present as " rescue " medication . Transdermal fentanyl provided good to excellent pain relief in the majority ( 68 % ) of these patients . During the study , 5 patients continued with 25 microg/hr , and the others used a higher dose . Clinical ly relevant respiratory depression was not observed . The common side effects of opioids were found ; constipation was mentioned by 3 patients ( 11 % ) . Transdermal fentanyl appeared a safe analgesic in these opioid-naive cancer pain patients . In this study , WHO step 2 could be skipped without untoward complications BACKGROUND In a multicenter study , 28 patients with cancer pain and insufficient pain relief with analgesic treatment according to step II of the guidelines of the World Health Organization ( WHO ) were switched to oral slow-release morphine . METHODS Patients received intravenous morphine through a patient-controlled pump ( PCA ) for the first 24 hours ( bolus = 1 mg , lockout interval = 5 minutes , maximum dose = 12 mg/hour ) . From day 2 patients were treated with oral slow-release morphine . Daily doses were calculated from the requirements of the day before . Breakthrough pain was treated with PCA until stable doses were reached ( < 2 boluses/day ) and then with oral immediate-release morphine solution . Pain intensity was reported in a diary four times a day , in addition to mood , activity , and quality of sleep once daily . RESULTS Mean duration until adequate pain relief reported ( < 30 on a 101-step numerical scale ; NRS ) was 5 hours ( range = 80 - 620 minutes ) . Mean pain intensity was reduced from 67 NRS to 22 NRS . Mean doses of oral morphine were 133 mg/day initially and then 154 mg/day on day 14 . Serious adverse events such as respiratory depression were not observed . Two patients terminated the study due to progressive symptoms of gastrointestinal obstruction . Seventy-five percent of the patients evaluated the effectiveness of the analgesic regime as good . CONCLUSIONS Dose finding with intravenous PCA may be appropriate for a small minority of patients with severe pain . Higher treatment costs and the risk of complications are drawbacks of this method compared with conventional oral titration & NA ; A titration procedure using immediate‐release morphine given 4‐hourly is recommended during start of oral morphine for cancer pain . This recommendation is not based on evidence from controlled studies , and many physicians start morphine treatment with controlled‐release morphine . We included 40 patients with malignant disease and pain despite treatment with opioids for mild to moderate pain in a r and omized , double‐blind , double‐dummy , parallel‐group study comparing titration with immediate‐release morphine given 4‐hourly with titration with sustained‐release morphine given once daily . The primary end point was the time needed to achieve adequate pain relief Secondary end points were other symptoms ( nausea , tiredness , lack of sleep , vertigo , appetite and constipation ) , health related quality of life and patient satisfaction . The mean times needed for titration were 2.1 ( 95 % CI ; 1.4–2.7 ) days using immediate‐release morphine and 1.7 ( 95 % CI ; 1.1–2.3 ) days using sustained‐release morphine . Patients titrated with immediate‐release reported statistically significant more tiredness at the end of titration . We observed no other differences in adverse effects or health related quality of life functions between the two treatments . Similar global satisfactions with the morphine treatments were reported . In conclusion , a simplified titration using sustained‐release morphine once daily is equally effective as immediate‐release morphine given 4‐hourly SUMMARY Objective : To determine the safety and efficacy of transdermal fentanyl for pain relief in cancer patients and to compare the effects on patients according to whether they had previously received strong opioids , weak opioids or non-opioid analgesia . Methods : Cancer patients requiring strong analgesia were recruited into an open-label , multicentre study , conducted in eight countries . Patients received transdermal fentanyl treatment for 28days . Pain severity , overall satisfaction with pain control , convenience of use of patches and treatment preferences were recorded daily . Results : Of the 292 participants , 135 had previously received a strong opioid , 84 had previously received a weak opioid and 73 had received no regular opioids . Thirty-eight patients did not complete the study , mainly due to adverse events . For all groups the proportion of patients with ‘ good to excellent ’ pain control increased after transdermal fentanyl treatment . Transdermal fentanyl was well tolerated , with the most common treatment-related adverse events being nausea , vomiting and constipation . The percentage of strong-opioid-tolerant patients with constipation decreased following transdermal fentanyl treatment and increased slightly in the strong-opioid-naïve groups . Most patients rated the convenience of the patches as ‘ good to excellent ’ , and most preferred transdermal fentanyl to their previous therapy . Conclusions : Transdermal fentanyl is an effective and well-tolerated treatment for cancer-related pain for patients regardless of whether they have previously received opioids . Previous guidelines have often advocated initial dose finding with short-acting opioids but this study demonstrates that such a complex titration and conversion schedule may not be necessary , and that treatment may be initiated directly with long-acting formulations such as transdermal fentanyl when previous analgesic therapy fails to provide adequate relief BACKGROUND Considerable dose variations and frequent initial side effects have been postulated during start of morphine treatment to patients with pain caused by malignant disease . However , to our knowledge , only one previous study has reported effective doses in morphine naive cancer patients and no prospect i ve evaluation has compared symptoms before with symptoms during morphine titration . METHODS We recruited 40 cancer patients with uncontrolled pain despite receiving codeine or dextropropoxyphen . Baseline data were obtained for two days before start of morphine titration using a fixed scheduled escalation of immediate-release ( IR ) morphine . When a stable morphine dose was achieved , IR morphine was replaced with slow-release ( SR ) morphine in equivalent doses . Intensity of pain and side effects were assessed daily . The daily consumption of morphine , rescue analgesics and rescue antiemetics were registered . RESULTS The mean titration time to achieve adequate analgesia was 2.3 days ( range : 1 - 6 ) using a mean daily morphine dose of 97 mg ( range : 60 - 180 ) . Nausea was unaltered after start with morphine but an increased incidence of vomiting occurred ( premorphine period 5 % , IR morphine period 29 % ) . Transient sedation delayed dose increment in 9 of the 40 patients but mean sedation scores were unaltered . Constipation scores increased while other side effect scores were unaltered . Eighty-two percent of the patients were satisfied or very satisfied with the pain treatment during introduction of morphine . CONCLUSION In cancer patients with uncontrolled pain on weak opioids , successful titration of morphine is achieved fast , with a three-fold morphine dose variation and with little increase in side effects This report is a prospect i ve study of 223 patients with intractable cancer pain who were offered continuing care during the year 1988 at the Pain Relief Unit , Kidwai Memorial Institute of Oncology , Bangalore , India , with a minimum follow‐up of 4 months and a maximum follow‐up of 16 months . A high percentage of pain relief was attained within a mean duration of 4 days , which on follow‐up was maintained at a steady level in most patients ( 91.1 % ) . Oral morphine could not be continued in three patients because of vomiting . The main side effects noticed were nausea and vomiting , itching , and constipation . At any time during the first 140 days , only 30 % of patients had side effects and appropriate medication successfully managed these side effects . During the rest of the study period , the side effects were minimal . Oral morphine used with proper adjuncts offers the best pain palliation in most patients , with minimal side effects Initial dose finding in patients with cancer pain who are started on TTS fentanyl ( Duragesic , TTS-F ) is often unsatisfactory with currently recommended doses and intervals . Acknowledging that studies reveal a " psuedo steady state " 15 to 20 hr after application of TTS-F , we prospect ively investigated an increased initial dose and day-to-day titration of TTS-F in 39 ( evaluable ) patients with uncontrolled cancer pain . Significant pain reduction ( P = 0.001 ) was seen after 24 hr , and satisfactory analgesia was achieved within 48 h and maintained for the rest of the study . Significant increases in TTS-F were necessary during weeks 1 through 4 to maintain pain control . Forty-nine percent of the patients needed one or more early dose increases . Only one patient had side effects partially due to the specific properties of the TTS . Other side effects seemed to be less common compared with usual morphine treatment . TTS-F can be titrated effectively and safely on a day-to-day basis with an increased initial dose and adequate patient monitoring , thus avoiding more complicated approaches . TTS-F seemed to induce less constipation than might be expected This r and omized controlled trial compared intravenous route with oral route for initial dose titration of morphine in 62 patients with end-stage cancer and severe pain . Patients in the intravenous group received 1.5 mg intravenous bolus doses of morphine every ten minutes till pain relief was total or until they became drowsy . After that they got oral morphine at a dose equal to the total initial intravenous requirement four-hourly . Patients in the oral group got oral morphine 5 mg doses ( if opioid-naÖve ) or 10 mg ( if already on weak opioid ) four hourly . Patients in both groups had the option to receive rescue doses of their regular oral dose as and when needed , if necessary hourly . Twenty-seven of 31 in the intravenous group had either total or satisfactory pain relief by the end of one hour , whereas only eight of 31 in the oral group had a similar result . After 24 hours and later both groups had similar results . There was no immediate serious side effect in any of the patients . The late side effects were similar in the two groups . In the intravenous group , the ratio of initial intravenous dose requirement to the subsequent regular single oral dose after two days centred around 1:1 ( range 1:0.5 - 1:3.3 ) . This study found the intravenous method to be safe , effective and superior to the traditional method in providing immediate relief to severe cancer pain Abstract Objective : Moderate to severe pain is commonly experienced by cancer and non-cancer patients . Although opioids are generally the most important drugs in chronic pain management , their use in Italy remains low . We design ed a prospect i ve open trial to assess the efficacy and safety of a st and ard therapy clinical ly available for a large range of patients . Methods : A total of 172 consecutive patients ( 89 women and 83 men ) with chronic pain ( daily mean visual analogue scale ( VAS ) score > 4 ) that was not adequately managed by their existing pain regimen were enrolled to receive an immediate release ( IR ) dose of morphine : 30 mg/day ( opioid-naive patients ) or 60 mg/day ( non-naive patients ) for 5 days . After this period ( start therapy ) , all patients were switched to slow release ( SR ) opioid therapy for 30 days ( steady therapy ) . Each breakthrough pain ( BTP ) episode was treated with a single dose of IR morphine ( 20 % of the daily dose ) during all study periods . Results : Daily VAS score was reduced from 7.4 ± 1.3 at baseline to 3.8 ± 1.5 ( p < 0.0001 ) after 30 days of steady therapy in cancer and non-cancer patients . Fewer patients reported BTP events by study end ( 55 % of patients with BTP at basal time had no BTP at last follow up ) , and the number of daily BTP events experienced by patients was reduced by therapy to 1–2 per day in 75 % of patients reporting BTP . Further , the time delay to reach pain relief following administration of a rescue dose of IR morphine was 15 minutes or less in 52.1 % of patients at study end . The st and ard therapy was well tolerated and fewer adverse effects were recorded at the end of the study period compared with baseline , with the exception of constipation , which showed a moderate increase ( from 18.2 % to 25.0 % ) . Conclusion : Start therapy with IR morphine followed by conversion to SR opioid therapy could be implemented as a st and ard therapy to manage moderate to severe chronic pain in patients with cancer or non-cancer pain . ORamorph ® in TIBER study ( ORTIBER ) & NA ; Forty patients with cancer pain receiving intermittent narcotics were admitted to a prospect i ve study design ed to assess the cognitive effects of narcotics . Twenty patients had undergone no change in narcotic dose or type ⩾ 7 days ( stable dose , SD , group ) , and 20 patients had undergone an increase of ⩾ 30 % in dose ⩽ 3 days before ( increased dose , ID , group ) . Age , primary tumor , type , dose and route of narcotic were not different between the SD and ID group . Cognitive tests ( finger tapping , FT , 10 and 30 sec , arithmetics , A , reverse memory of digits , RM , and visual memory , VM ) were performed in all patients before and 45 min after their morning dose of narcotics for 2 consecutive days . Mean percentual change in FT 10 sec , FT 30 sec , A , RM , and VM after the narcotic dose were 97 ± 9 % , 100 ± 14 % , 100 ± 13 % , 100 ± 15 % , 98 ± 19 % , in the SD group , vs. 77 ± 14 % ( P < 0.001 ) , 83 ± 13 % ( P < 0.001 ) , 124 ± 21 % ( P < 0.001),60 ± 21 % ( P < 0.001 ) and 68 ± 21 % ( P < 0.001 ) in the ID group , respectively . Our results suggest that patients who undergo a significant increase in the dose of intermittent narcotics experience significant cognitive impairment , that disappears after 1 week of the increase . More research is needed to better characterize the cognitive toxicity of intermittent narcotics , and to determine the cognitive effects of long acting narcotics , continuous infusions , or of the addition of amphetamines BACKGROUND Fentanyl is a synthetic opioid , suitable for transdermal delivery , offering an interesting solution as a step 3 opioid in cancer pain treatment . The purpose of the study was to carefully investigate : 1 ) the feasibility of the direct conversion from codeine to TTS fentanyl , in patients already receiving codeine and requiring strong opioids for their analgesia ; 2 ) the safety of 25 microg/hour incremental steps and at shorter than 72-hour intervals , if clinical ly required . PATIENTS AND METHODS 130 patients were judged eligible for the study . All the patients were receiving 280 - 360 mg or more of codeine and required strong opioid for their analgesia . The study lasted 56 days . The initial dose was 25 microg/hour . TTS fentanyl for all patients . Data assessment s were made on baseline , day 1 , day 2 , day 3 , in the hospital and thereafter on days 7 , 14 , 21 , 28 , 42 and 56 . After the patch application , all the patients were given an immediate release oral morphine ( 5 mg ) every 4 - 6 hours for the first 12 hours and then if needed only as rescue doses . The patients remained in the hospital for the first three days of the study where follow-up ( pain score , satisfaction , side effects etc . ) . was recorded by the palliative care team and by daily cards . RESULTS The itnitial dose of fentanyl was 25 microg/hour while the mean dose on day 3 was 45.9 microg/hour . All the patients required upward titration of the study medication during follow-up visits . On day 56 the mean dose of fentanyl was 87.4 microg/hour . Mean pain intensity decreased from an initial 5.96 on the baseline to 0.83 on day 3 . Karnofsky scale measurements between treatment phases revealed non-significant changes . The rate of overall satisfaction was quite high . Nine patients discontinued the study due to inadequate pain relief or side effects between day 7 and day 28 , while five patients died between day 28 and day 56 . Constipation , nausea and vomiting were the most common side effects . Skin reaction was relatively mild and acceptable during the study . CONCLUSION Under controlled conditions , TTS fentanyl seems to be feasible for direct conversion from mild to strong opioids and additionally , 25 microg/hour incremental steps day by day can be made by palliative care specialists , if clinical ly required for cancer pain management Cancer pain can be managed in most patients through the use of the analgesic ladder proposed by the World Health Organization . Recent studies have proposed to skip the second " rung " of the ladder by using a so-called " strong " opioid for moderate pain . However , usual doses of strong opioids commonly prescribed for the third rung of the analgesic ladder may pose several problems in terms of tolerability in opioid-naive patients . The aim of this multicenter study was to evaluate the efficacy and tolerability of very low doses of morphine in advanced cancer patients no longer responsive to nonopioid analgesics . A sample of 110 consecutive opioid-naive patients with moderate-to-severe pain were given oral morphine at a starting dose of 15 mg/day ( 10 mg in those older than 70 years ) . Doses were then titrated according to the clinical situation . Pain intensity , morphine doses , symptom intensity , quality of life , and the requirement for dose escalation were monitored for a period of 4 weeks . The treatment was effective and well tolerated by most patients , who were able to maintain relatively low doses for the subsequent weeks ( mean dose 45 mg at Week 4 ) . Only 12 patients dropped out due to poor response or other reasons . The use of very low doses of morphine proved to be a reliable method in titrating opioid-naive advanced cancer patients who were also able to maintain their dose , in a 4-week period , below the dose level commonly used when prescribing strong opioids Adequate and rapid pain control is one of the main goals of cancer pain treatment . The objective of this study was to assess the effect and tolerability of oral normal-release morphine during the initial phase of treatment in patients with moderate-to-severe cancer pain . Consecutive patients naïve to strong opioids received normal-release morphine 5 or 10 mg every 4 h during the titration phase ( first 5 days ) , depending on previous analgesic therapy . Pain intensity was assessed using an 11-point Numerical Rating Scale ( 0–10 ) , and data were recorded in a patient-compiled diary . The primary endpoint was the proportion of time with pain control ( a reduction of at least 50 % with respect to the baseline pain score ) during the titration phase . A total of 159 consecutive patients ( 102 men ; mean age 65 years ) with cancer-related pain were enrolled . Pain control was observed for 75 % ( 95 % CI 70–80 ) of the follow-up period in the intent-to-treat population . Overall , 50 % and 75 % of patients achieved pain control within 8 and 24 h after starting normal-release morphine therapy respectively . The mean pain score was 7.63 points at baseline , and decreased to 2.43 and 1.67 points ( both P < 0.001 ) at days 3 and 5 respectively . The most commonly reported adverse events were somnolence ( 24 % of patients ) , constipation ( 22 % ) , vomiting ( 13 % ) , nausea ( 10 % ) and confusion ( 7 % ) . Normal-release morphine results in rapid and satisfactory pain control , and is well tolerated , during the strong-opioid titration phase in patients with moderate-to-severe cancer pain |
12,714 | 27,022,114 | Antipseudomonal penicillin and fourth-generation cephalosporin monotherapy were associated with similar failure and mortality rates .
Outpatient management and oral antibiotics were safe in low-risk FN with no infection-related mortality observed in any patient and no significant differences in outcomes compared with inpatient management and intravenous therapy .
Monotherapy for high-risk FN and outpatient and oral management for low-risk FN are effective strategies . | PURPOSE To describe treatment failure and mortality rates with different antibiotic regimens and different management strategies for empirical treatment of fever and neutropenia ( FN ) in pediatric patients with cancer and hematopoietic stem-cell transplantation ( HSCT ) recipients . | Recent reports and previous r and omized trials conducted at the authors ' institution suggested that children with lower risk febrile neutropenic ( LRFN ) may benefit from substitution of oral antibiotic therapy for parenteral therapy . The objective of this study was to determine the efficacy of parenteral‐oral outpatient therapy in the management of children with LRFN who were receiving treatment for malignant disease A prospect i ve , r and omized clinical trial was conducted to compare the efficacy of piperacillin/tazobactam and amikacin combination with carbapenem monotherapy for the empirical treatment of febrile neutropenic episodes of children with acute lymphoblastic leukemia or acute myeloblastic leukemia . Patients aged 2–16 years with hematological malignancies who had febrile neutropenia were r and omly assigned to receive piperacillin/tazobactam ( 80 mg/kg piperacillin/10 mg/kg tazobactam , q6h ) combined with amikacin ( PTA ) ( 7.5 mg/kg , q12h ) or meropenem or imipenem ( 20 mg/kg , q8h ) ( C ) . Response to antimicrobial therapy , evaluated for etiological agents , was measured . Duration of fever , neutropenia , and hospitalization , mortality , and the need for additional antibiotics or antifungal drugs were compared for the treatment success between the two groups . Out of 87 febrile neutropenic episodes that were evaluable for comparison , 46 patients received PTA and 41 patients were treated with carbapenems ( imipenem or meropenem ) . Overall , the microbiologically documented infection rate was 21.9 % , with Staphylococcus epidermidis as the most common cause of bacteremia . The rate of treatment modification was 56.5 % in the PTA group and 53.6 % in the carbapenem group with no statistical difference ( p > . 05 ) . There was no infection-related mortality during the study period . There was no difference between the two regimens for duration s of fever , neutropenia , and hospitalization ( p > . 05 for all categories ) . PTA was as effective as carbapenem monotherapy as an initial empirical regimen in febrile neutropenic episodes of pediatric hematological malignancies BACKGROUND The aim of this study was to evaluate the efficacy and safety of piperacillin/tazobactam ( PIP/TAZO ) and cefozopran ( CZOP ) monotherapy in pediatric cancer patients with febrile neutropenia ( FN ) . PROCEDURE A total of 119 febrile episodes in 49 neutropenic pediatric cancer patients ( 20 females and 29 males ) with a median age of 6.8 years ( range , 0.3 - 18.4 years ) received r and omized treatment either with PIP/TAZO 125 mg/kg every 8 hr or CZOP 25 mg/kg every 6 hr . Clinical response was determined at completion of therapy . Duration s of fever and neutropenia , the need for modification of the therapy , and mortality rates were compared between the two groups . RESULTS The frequency of success without modification of treatment was not significantly different between PIP/TAZO ( 59.6 % ) and CZOP ( 53.2 % ) . Duration s of fever and antibiotic therapy did not differ between the treatment groups , and no major side effects were observed in either group . CONCLUSIONS PIP/TAZO and CZOP monotherapy were both effective and safe for the initial empirical treatment of pediatric cancer patients with FN PURPOSE To compare outcome and cost of ambulatory versus hospitalized management among febrile neutropenic children at low risk for invasive bacterial infection ( IBI ) . PATIENTS AND METHODS Children presenting with febrile neutropenia at six hospitals in Santiago , Chile , were categorized as high or low risk for IBI . Low-risk children were r and omly assigned after 24 to 36 hours of hospitalization to receive ambulatory or hospitalized treatment and monitored until episode resolution . Outcome and cost were determined for each episode and compared between both groups using predefined definitions and question naires . RESULTS A total of 161 ( 41 % ) of 390 febrile neutropenic episodes evaluated from June 2000 to February 2003 were classified as low risk , of which 149 were r and omly assigned to ambulatory ( n = 78 ) or hospital-based ( n = 71 ) treatment . In both groups , mean age ( ambulatory management , 55 months ; hospital-based management , 66 months ) , sex , and type of cancer were similar . Outcome was favorable in 74 ( 95 % ) of 78 ambulatory-treated children and 67 ( 94 % ) of 71 hospital-treated children ( P = NS ) . Mean cost of an episode was US 638 dollars ( 95 % CI , 572 dollars to 703 dollars ) and US 903 dollars ( 95 % CI , 781 dollars to 1,025 dollars ) for the ambulatory and hospital-based groups , respectively ( P = .003 ) . CONCLUSION For children with febrile neutropenia at low risk for IBI , ambulatory management is safe and significantly cost saving compared with st and ard hospitalized therapy A prospect i ve , open-label , r and omized , comparative study in pediatric cancer patients was conducted to evaluate the efficacy and safety of cefepime and meropenem in the empiric therapy of febrile neutropenic patients . Febrile episodes were classified as microbiologically documented infection , clinical documented infection , or fever of unknown origin . Clinical response to therapy was classified as success or failure . In this period 37 children with solid tumors including lymphoma , 25 males , 12 females , had neutropenia on 65 occasions . Microbiologically documented infections occurred in 21 episodes ( 32.31 % ) . Frequency of positive bacteria isolated was higher than gram-negative bacteria . There was no infection-related death . There were no statistical differences between the cefepime and meropenem groups for duration of fever or neutropenia , response rate , and necessity for modification . Cefepime appears to be as effective and safe as meropenem for empiric treatment of febrile episodes in neutropenic pediatric cancer patients BACKGROUND AND PURPOSE The empirical use of antibiotic therapy is widely accepted for patients with fever and neutropenia during cancer chemotherapy . The use of intravenous monotherapy with broad-spectrum antibiotics in patients at high risk for complications is an appropriate alternative . However , few data are available for pediatric patients . The aim of this study was to compare the efficacy and safety of cefepime ( CFP ) monotherapy with ceftriaxone plus amikacin ( CFT+AK ) in children and adolescents with febrile neutropenia ( FN ) . METHODS A prospect i ve r and omized open study of patients with lymphoma or leukemia who had fever and neutropenia during chemotherapy was conducted . Patients were r and omized to receive CFP or CFT+AK . The r and omization was based on number lists . RESULTS Fifty seven patients with 125 episodes of fever and neutropenia were evaluated ( CFP , 62 episodes ; CFT+AK , 63 episodes ) . The mean neutrophil count at admission to hospital was 118.6 cells/mm(3 ) for patients in the CFP group and 107 cells/mm(3 ) for patients in the CFT+AK group . The mean duration of neutropenia was 9 days for the CFP group and 8 days for the CFT+AK group . Analysis of only the first episodes for each patient showed that CFP treatment was successful for 65.5 % of episodes and CFT+AK was successful for 64.3 % of episodes . The overall rates of success with modification were 90 % for the CFP group and 89 % for the CFT+AK group . No major treatment-emergent toxicity was reported . CONCLUSION Monotherapy with CFP seems to be as effective and safe as CFT+AK for initial empirical therapy in children and adolescents with FN BACKGROUND Febrile neutropenia ( FN ) is a frequent , serious complication of intensive pediatric chemotherapy regimens . The aim of this trial was to compare quality of life ( QOL ) between inpatient and outpatient intravenous antibiotic management of children and adolescents with low risk febrile neutropenia ( LRFN ) . PROCEDURE In this r and omised non-blinded trial , patients between 1 and 21 years old , receiving low/moderate intensity chemotherapy were pre-consented and , on presentation to emergency ( ED ) with FN satisfying low risk criteria , r and omised to either outpatient or inpatient care with intravenous cefepime 50 mg/kg ( 12 hourly ) . All patients continued antibiotics for at least 48 hours , until afebrile for 24 hours and demonstrating a rising absolute neutrophil count ≥200/mm(3 ) . Several domains of QOL were examined by daily question naire . RESULTS Eighty-one patients presented to ED with 159 episodes of fever . Thirty-seven FN presentations involving 27 patients were r and omised to inpatient ( 18 ) and outpatient ( 19 ) management . Combined QOL mean scores for parents were higher for the outpatient group and scores for three specific parent variables ( keeping up with household tasks/time spent with partner/time spent with other children ) were higher among out patients . There was no difference in parent confidence/satisfaction in care between groups . Patients scored better in the outpatient group overall and for sleep and appetite . The mean length of fever was equivalent between groups and there were no serious adverse events attributable to cefepime or outpatient care . CONCLUSION Outpatient cefepime management of LRFN provided significant benefit to parents and patients across several QOL domains and appeared both feasible and safe PURPOSE To determine if granulocyte colony-stimulating factor ( G-CSF ) with empirical antibiotics accelerates febrile neutropenia resolution compared with antibiotics without it . PATIENTS AND METHODS Eligible children were treated without prophylactic G-CSF and presented with fever ( temperature > 38.3 degrees C ) and neutropenia afterward . Patients with acute myelogenous leukemia and myelodysplastic syndrome were excluded . Assignments were r and omized between G-CSF ( 5 microg/kg/day ) or none beginning within 24 hr of antibiotics . Subcutaneous administration was recommended , but intravenous G-CSF was allowed . Patients remained on study until absolute neutrophil count ( ANC ) > 500/microl and > or = 48 hr without fever . RESULTS One of 67 patients enrolled was ineligible , 59 had acute lymphoblastic leukemia ( ALL ) . Thirty-four were assigned to antibiotics , 32 to G-CSF plus antibiotics . Adding G-CSF significantly reduced neutropenia and febrile neutropenia recovery times . Median days to febrile neutropenia resolution was nine earlier with G-CSF ( 4 vs. 13 days ) ( P < 0.0001 ) . However , there was no difference in the resolution of fever between arms . Hospitalization median was shorter by 1 day with G-CSF ( 4 vs. 5 days ) ( P = 0.04 ) . There was no difference in the duration of IV and oral antibiotic treatment , addition of antifungal therapy , and shock incidence . A trend for decreased incidence of late fever with G-CSF was noted ( 6.3 vs. 23.5 % ) ( P = 0.08 ) . CONCLUSIONS Adding G-CSF to empiric antibiotic coverage accelerates chemotherapy-induced febrile neutropenia resolution by 9 days in pediatric patients , mainly with ALL , which results in a small but significant difference in the median length of hospitalization The purpose of this study is to compare the efficacy and safety of piperacillin/tazobactam ( PIP/TAZO ) versus PIP/TAZO plus amikacin in febrile neutropenic children with acute leukemia ( AL ) . Children with AL who had febrile neutropenic episodes were r and omized to treatment with PIP/TAZO versus PIP/TAZO plus amikacin . Modification was defined as addition of other antimicrobials and /or antifungal agents to the empirical therapy . Protocol failure was defined as withdrawal of the empirical regimen and introduction of other antimicrobials due to failure in controlling infection . Seventy-two febrile episodes of 42 patients with a median age of 4.5 years ( 3.5 months to 19 years ) were evaluated . There were 37 and 35 episodes in PIP/TAZO and combination arms , respectively . Success without modification , with modification , protocol failure , duration of treatment were 45.9 % , 35.1 % , 18.9 % , and 10 days in PIP/TAZO arm and 42.9 % , 37.1 % , 20 % , and 12 days in combination arm , respectively ( P > .05 ) . There was no significant difference between the empirical therapy arms regarding median duration of neutropenia and defervescence of fever . Empirical therapy was substituted by other drugs in 6 and 5 episodes in PIP/TAZO and combination arms , respectively . There was no infection-related death . There was reversible increase in serum creatinine in 1 episode on the combination arm . Monotherapy with PIP/TAZO was effective and safe for initial empirical treatment of febrile neutropenic episodes in children with AL . However , local bacterial resistance patterns should be considered in daily practice . Combination of amikacin with PIP/TAZO did not improve treatment success , but it may increase nephrotoxicity During a 2-year period , all children with cancer , neutropenia , and fever who were admitted to Hospital de Niños Luis Calvo Mackenna ( Santiago , Chile ) were enrolled in a study of the safety of stopping antibiotic therapy on day 3 of treatment . Children who met predefined criteria for nonbacterial fever were r and omized on day 3 to stop ( group A ) or continue ( group B ) antibiotic therapy . A total of 220 children with cancer had 238 episodes of fever and neutropenia ; 68 children with 75 episodes met entry criteria for nonbacterial fever ( group A , 36 ; group B , 39 ) . Both groups were comparable in terms of age , gender , oncological disease , chemotherapy status , and initial neutrophil count . Resolution of symptoms occurred in 34 of 36 episodes in group A and 36 of 39 episodes in group B ( P > .05 ) . No deaths occurred , and bacterial superinfections were uncommon . For children with cancer as well as episodes of fever and neutropenia without an identifiable bacterial etiology at admission , stopping antibiotic therapy on day 3 was safe and not associated with a higher risk of bacterial superinfections Purpose Fever combined with neutropenia in pediatric oncology patients has traditionally been managed in the hospital with broad-spectrum intravenous antibiotics until there is documented neutrophil recovery . Recent evidence has suggested that patients at “ low-risk ” can be discharged from the hospital before neutrophil recovery . Whether oral antibiotics are required at the time of discharge is not known . Patients and Methods Using a r and omized , double-blind , placebo-controlled study design , 73 patients at low-risk with episodes of fever and neutropenia were discharged home while still neutropenic : 37 administered with oral cloxacillin and cefixime and 36 administered with corresponding placebos . Low-risk criteria included : afebrile for more than 24 hours , negative blood culture results at 48 hours , absence of clinical sepsis , cancer in bone marrow remission , and absence of comorbid conditions . Results Five patients ( 14 % ; 95 % confidence interval [ CI ] ; 2%–25 % ) in the antibiotic arm and two patients ( 6 % ; 95 % CI ; 0%–13 % ) in the placebo arm were readmitted to the hospital with recurrent fever while still neutropenic ( P = 0.43 ) . One patient r and omized to the placebo arm had a positive blood culture result on readmission , which responded to appropriate intravenous antibiotics . All of the readmissions were uneventful and there were no fatalities . The average cost per episode of fever and neutropenia was $ 1,821 Canadian dollars with only minimal incremental cost to the antibiotic arm . Conclusion This study supports the discontinuation of antibiotics in pediatric oncology patients at low-risk who still have neutropenia at the time of discharge from the hospital Fifty-four pediatric cancer patients with a total of 100 febrile neutropenic episodes treated at China Medical College Hospital were r and omized to receive meropenem or ceftazidime plus amikacin from January 2001 to April 2002 . The characteristics of 76 assessable febrile episodes ( 39 with meropenem and 37 with ceftazidime plus amikacin ) were compared between the 2 groups . The success rate with unmodified therapy was not significantly different between the meropenem group ( 72 % ) and the ceftazidime-plus-amikacin group ( 57 % ) . The incidence of side effects was similar between the 2 groups and these side effects were reversible . Microbiologically documented infection , clinical ly documented infection , and unexplained fever accounted for 35 % , 37 % , and 28 % of episodes , respectively . The clinical response rates in subgroups of documented infection and unexplained fever did not significantly differ between the 2 treatment groups . Meropenem was significantly more effective than ceftazidime plus amikacin in children at high risks of developing severe infection who had profound neutropenia ( absolute neutrophil count [ ANC ] < 100/mm3 ) , prolonged neutropenia ( ANC < 500/mm3 lasting for > 10 days ) , or clinical ly deteriorating shock ( p=0.045 ) . As an empirical treatment , meropenem seems to be as effective and safe as ceftazidime plus amikacin for febrile episodes in children with cancer and neutropenia . Meropenem is more effective for pediatric cancer patients at the high risk of severe infection Febrile neutropenia is a heterogeneous condition . Recently , several risk factors have been defined , permitting the definition of a lower risk group of patients who may benefit form less aggressive therapy . The use of an oral antibiotic approach was tested in the current trial In a double blind study of 58 episodes of fever and profound neutropenia , children with cancer received either recombinant human granulocyte-macrophage colony-stimulating factor ( rhGM-CSF ) or placebo , combined with identical antimicrobial therapy , i.e. imipenem , on admission . The criteria for discontinuation of therapy were identical . A difference was demonstrated both in the number of hospital days , totaling 252 days in the rhGM-CSF group and 354 in the placebo group , days receiving antibiotics ( 220 vs. 322 ) , and in the resolution of neutropenia ( 4.5 days vs. 6.0 days ; P < 0.05 ) . The number of episodes requiring antimicrobial therapy for longer than 10 days was 5 of 28 ( 12 % ) in the rhGM-CSF group as opposed to 15 of 30 ( 50 % ) in the placebo group ( P = 0.01 ) . rhGM-CSF was well-tolerated . We conclude that rhGM-CSF was efficacious in accelerating myeloid recovery and reducing the length of hospitalization in febrile neutropenia BACKGROUND The st and ard treatment of fever in chemotherapy-induced neutropenia ( FN ) includes emergency hospitalization and empirical intravenous antimicrobial therapy . This study determined if first-day step-down to oral outpatient treatment is not inferior to continued st and ard regarding safety and efficacy in children with low-risk FN . PROCEDURE In a r and omized controlled non-blinded multicenter study , pediatric patients with FN after non-myeloablative chemotherapy were reassessed after 8 - 22 hours of inpatient intravenous antimicrobial therapy . Low-risk patients were r and omized to first-day step-down to experimental ( outpatient , oral amoxicillin plus ciprofloxacin ) versus continued st and ard treatment . Exact non-inferiority tests were used for safety ( no serious medical complication ; non-inferiority margin of difference , 3.5 % ) and efficacy ( resolution of infection without recurrence , no modification of antimicrobial therapy , no adverse event ; 10 % ) . RESULTS In 93 ( 26 % ) of 355 potentially eligible FN episodes low-risk criteria were fulfilled , and 62 were r and omized , 28 to experimental ( 1 lost to follow-up ) and 34 to st and ard treatment . In intention-to-treat analyses , non-inferiority was not proven for safety [ 27 of 27 ( 100 % ) vs. 33 of 34 ( 97 % ; 1 death ) episodes ; 95 % upper confidence border , 6.7 % ; P = 0.11 ] , but non-inferiority was proven for efficacy [ 23 of 27 ( 85 % ) vs. 26 of 34 ( 76 % ) episodes ; 95 % upper confidence border , 9.4 % ; P = 0.045 ] . Per- protocol analyses confirmed these results . CONCLUSIONS In children with low-risk FN , the efficacy of first-day step-down to oral antimicrobial therapy with amoxicillin and ciprofloxacin in an outpatient setting was non-inferior to continued hospitalization and intravenous antimicrobial therapy . The safety of this procedure , however , was not assessable with sufficient power BACKGROUND Hospitalization with single or multi-agent antibiotic therapy has been the st and ard of care for treatment of febrile neutropenia in cancer patients . We hypothesized that an empiric antibiotic regimen that is effective and that can be administered once-daily will allow for improved hospital utilization by early transition to outpatient care . PROCEDURE Febrile pediatric cancer patients with anticipated prolonged neutropenia were r and omized between a regimen of once-daily ceftriaxone plus amikacin ( C + A ) and imipenem monotherapy ( control ) . Afebrile patients on C + A satisfying " Early Discharge Criteria " at 72 hr continued treatment as out patients . We compared the outcome , adverse events , duration of hospitalization , and cost between both groups . RESULTS A prospect i ve r and omized controlled clinical trial was conducted on 129 febrile episodes in pediatric cancer patients with prolonged neutropenia . No adverse events were seen in 32 children ( 84 % of study arm ) treated on an outpatient basis . We found a statistically significant difference between the duration of hospitalization of the C + A group [ median 5 days ] and control [ median 9 days](P < 0.001 ) , per episode antibiotic cost ( P < 0.001 ) and total episode cost ( P < 0.001 ) . There was no statistically significant difference in the response to treatment at 72 hr or after necessary antimicrobial modifications . CONCLUSIONS We conclude that pediatric febrile cancer patients initially considered at risk for sepsis due to prolonged neutropenia can be re-evaluated at 72 hr for outpatient therapy . The convenience , low incidence of adverse effects , and cost benefit of the once-daily regimen of C + A may be particularly useful to reduce the overall treatment costs and duration of hospitalization PURPOSE Infection in neutropenic patients is potentially life-threatening and carries important implication s for hospital re source use . Prophylactic administration of cytokines may reduce the severity of neutropenia , but involves the treatment of all patients for the possible benefit of a minority . This study evaluates whether treatment with cytokines in the setting of established febrile neutropenia will influence outcome and be potentially more cost-effective . PATIENTS AND METHODS In a double-blind study , pediatric patients with fever and severe neutropenia were r and omized to receive granulocyte colony-stimulating factor ( [ G-CSF ] filgrastim ; 5 microg/kg/d ) or placebo , in addition to antibiotics . The study protocol required a resolution of fever and a neutrophil count > or = 0.2 x 10(9)/L for hospital discharge . Patients could be r and omized for up to four independent febrile episodes . A total of 186 episodes of febrile neutropenia were investigated . RESULTS Patients r and omized to G-CSF had a shorter hospital stay ( median , 5 v 7 days ; P = .04 ) and fewer days of antibiotic use ( median , 5 v 6 days ; P = .02 ) . G-CSF-treated patients also had more rapid neutrophil recovery and higher neutrophil levels at discharge . The 2-day reduction in hospital stay reduced the median bed cost by 29 % per patient admission ( P = .04 ) . CONCLUSION Under the clinical guidelines of our institution , the use of G-CSF in the treatment of established febrile neutropenia produced a small but significant reduction in the time that children required antibiotics and hospital admission , with possible cost savings The purpose of this study was to compare the efficacy , safety , and cost of piperacillin/tazobactam with cefepime monotherapy in children with febrile neutropenia . A prospect i ve r and omized study in children and adolescent with cancer was conducted . Patients were r and omly assigned to receive either 80 mg/kg piperacillin/10 mg/kg tazobactam every 6 h ( maximum 4.5 g/dose ) or cefepime 50 mg/kg every 8 h ( maximum 2 g/dose ) . Treatment modification was defined as all the changes in the empirical antimicrobials after the first 96 h. Overall treatment success was defined as cure of febrile episode with or without modification . Cost of hospitalization , antimicrobial drugs , and supportive therapy were calculated . Fifty febrile netropenic episodes ( 25 in the piperacillin/tazobactam group , 25 in the cefepime group ) in 27 pediatric cancer patients were evaluated . The groups were comparable in terms of age , gender , body weight , primary diagnosis , disease status , initial neutrophil count , and duration of neutropenia . Microbiologically and clinical ly documented infection rate was 46 % . There was no infection-related mortality in the study period . The treatment success of initial empirical therapy without modification was not different in the 2 groups ( 56 % in piperacillin/tazobactam group and 48 % in cefepime group ) . Anti-anaerobic drugs were added more frequently in the cefepime group . Duration of fever , neutropenia , treatment , and cost of therapy were not different in the treatment groups . Piperacillin/tazobactam monoterapy is as effective as cefepime monotherapy in febril neutropenia of pediatric cancer patients Fever and neutropenia ( F&N ) is a common complication of cancer chemotherapy . It is conveniently managed by hospitalization and empiric administration of parenteral antibiotics . This study attempted to determine whether pediatric cancer patients with F&N identified as low risk for morbidity and mortality by clinical criteria at the time of presentation could be treated safely as out patients The efficacy , safety , and cost of cefepime and ceftazidime + amikacin as empirical therapy in children with febrile neutropenia is compared . A prospect i ve r and omized study in children with cancer was conducted . Patients were r and omly assigned to receive either cefepime 150 mg/kg/day or ceftazidime 150 mg/kg/day combined with amikacin 15 mg/kg/day . Treatment modification was defined as all the changes in the empirical antimicrobials after the first 72 h. Overall treatment success was defined as cure of febrile episode with or without modification . Costs of hospitalization , antimicrobial drugs , and supportive therapy were calculated . Fifty febrile netropenic episodes were evaluated . Infectious agents were microbiologically identified in 28 % of episodes . The incidence of gram-negative and gram-positive isolates was equal . Overall treatment success was 100 % and success of initial empirical therapy without modification was 52 and 40 % in the cefepime and cefepime + amikacin groups , respectively . The response rate after glycopeptides were added to the regimen was 64 and 52 % in the cefepime and cefepime + amikacin arms , respectively . Glycopeptide and antifungal drugs were added more frequently in the ceftazidime + amikacin group . Duration of fever , hospitalization , and antimicrobial drug administration were longer in the ceftazidime + amikacin arm . The costs of the antimicrobial drugs , hospitalization , and total cost were lower in the cefepime arm . Cefepime monotherapy is as effective as ceftazidime + amikacin combination in febrile neutropenia of pediatric cancer patients and must be preferred due to shorter defervescence of fever , shorter hospitalization , and lower therapy cost OBJECTIVES This is a prospect i ve , r and omized , and open-label clinical trial that examines the efficiency and safety of PIP/TAZO monotherapy in comparison to cefepime ( CEF ) , for the empirical treatment of pediatric cancer patients with neutropenia and fever . METHODS One hundred thirty-one consecutive febrile episodes in 70 neutropenic pediatric cancer patients received r and omized treatment either with piperacillin/tazobactam ( PIP/TAZO ) 80 mg/kg piperacillin/10 mg/kg tazobactam every 6 hr or CEF 50 mg/kg every 8 hr . Clinical response was determined at completion of therapy . Duration of fever , neutropenia , hospitalization , the need for modification of the therapy , and mortality rates were compared between the two groups . RESULTS One hundred twenty-seven episodes in 69 patients ( 35 females , 34 males ) with a median age of 4.2 years were assessed for efficiency ( 65 PIP/TAZO , 62 CEF ) . The frequency of success without modification of treatment was nearly identical for both PIP/TAZO ( 60.0 % ) and CEF ( 61.3 % ) ( P > 0.05 ) . The overall response rate , with or without modification of assigned treatment , was 96.9 % for PIP/TAZO and 98.4 % for CEP ( P > 0.05 ) . Infection-related mortality at the end of the febrile episode was 2.4 % . Duration of fever and hospitalization were not different between the treatment groups . No major side effects were observed in neither of the groups . CONCLUSIONS PIP/TAZO treatment was as effective and safe as CEF monotherapy as an initial empirical regimen in pediatric cancer patients with fever and neutropenia OBJECTIVE To compare the use of intravenous vs. oral antibiotic therapy . METHODS All febrile neutropenic patients younger than 18 years old with low risk of complications and receiving chemotherapy were selected . The study was conducted from 2002 to 2005 at the Pediatric Oncology Unit of Hospital de Clínicas de Porto Alegre , Porto Alegre , Brazil . Patients were divided into group A and group B and were r and omly assigned to receive oral or intravenous therapy . The empirical antimicrobial treatment used for group A consisted in oral ciprofloxacin plus amoxicillin-clavulanate and intravenous placebo , and group B received cefepime and oral placebo . RESULTS A total of 91 consecutive episodes of febrile neutropenia in 58 children were included in the study . For patients of group A , treatment failure rate was 51.2 % ; the mean length of hospital stay was 8 days ( range 2 - 10 days ) . For patients treated with intravenous antibiotic therapy , treatment failure rate was 45.8 % ; the mean length of hospital stay was 7 days ( range 3 - 10 days ) . CONCLUSION There was no difference in the outcome in oral vs. intravenous therapy . There is need of larger r and omized trials before oral empirical therapy administered to this population should be considered the new st and ard of treatment Abstract Infection remains the major cause of morbidity and mortality in immuno-compromised children with malignancy . In addition , the economic impact of antibiotic treatment should always be evaluated , especially in developing countries . In our center between January 1998 and January 1999 , 73 children with hematological malignancies [ acute lymphoblastic leukemia ( ALL ) , acute myeloid leukemia ( AML ) ] ; 9 children with solid tumors ( rhabdomyosarcoma , neuroblas-toma ) had 87 febrile neutropenic episodes ( related to chemotherapy ) . These children were r and omized prospect ively into three treatment groups . The first group ( n : 28 ) received cefepime plus netilmicin , while the second group ( n : 29 ) was treated with ceftazidime plus amikacin and the third ( n : 30 ) with meropenem as monotherapy . The aim of the study was to compare the success rates and cost of fourth generation cephalosporin plus aminoglycoside and monotherapy of meropenem with ceftazidime plus amikacin , which is the st and ard therapy for febrile neutropenia . Microbiologically documented infections were 29.9 % , clinical ly documented infections were 9.2 % and 60.9 % of the febrile neutropenic episodes were considered to be FUO . Gram-positive microorganisms were the most commonly isolated agents from blood cultures [ MRSA ( Methicillin Resistant Staphylococcus aureus ) in 6 patients and MSSA ( Methicillin Sensitive Staphylococcus aureus ) in 4 patients ] . The success rates were 78.5 % , 79.3 % and 73.3 % for the 1st , 2nd and 3rd groups respectively . In 4 patients ( 4.5 % ) fever responded only to amphotericin-B therapy . There was no statistically significant difference between the three treatment regimens with respect to efficacy , safety and tolerance ( x2 test , p>0.05 ) , but while the third and fourth generation cephalosporins + aminoglycosides were comparable for cost , the monotherapy regimen was the most expensive . The main determining factors for the choice of treatment of febrile neutropenic children , especially in a developing country , are cost , presence of indwelling catheter and the bacterial flora of the unit , as well as efficacy Chemotherapy associated febrile neutropenia is an important cause of morbidity and mortality in pediatric patients with cancer . The use of granulocyte-colony stimulating factor ( G-CSF ) post chemotherapy decreases the risk of infectious complications but its efficacy during the febrile neutropenic episode remains controversial . Thirty five episodes of high-risk febrile neutropenia were r and omized into two treatment arms , 18 received antibiotics and G-CSF ( group A ) and 17 received antibiotics only upon admission ( group B ) . Both groups were comparable in terms of demographic and clinical characteristics . No significant differences between groups were found in duration of hospitalization ( mean group A 7 vs group B 8 days ) , antibiotic treatment ( mean 7 vs 8 days ) , fever ( 3 vs 2 days ) , nor of neutropenia ( 4 vs 3 days ) . One patient in group A died after RSV infection . Considering these results and a literature review , we propose that G-CSF should not be recommended in children during the course of their febrile neutropenic episode BACKGROUND The empirical use of antibiotic treatments is widely accepted as a means to treat cancer patients in chemotherapy who have fever and neutropenia . Intravenous monotherapy , with broad spectrum antibiotics , of patients with a high risk of complications is a possible alternative . METHODS We conducted a prospect i ve open-label , r and omized study of patients with lymphoma or leukemia who had fever and neutropenia during chemotherapy . Patients received either monotherapy with ticarcillin/clavulanic acid ( T ) or ceftriaxone plus amikacin ( C+A ) . RESULTS Seventy patients who presented 136 episodes were evaluated , 68 in each arm of the study . The mean neutrophil counts at admission were 217cells/mm(3 ) ( T ) and 201cells/mm(3 ) ( C+A ) . The mean duration of neutropenia was 8.7 days ( T ) and 7.6 days ( C+A ) . Treatment was successful without the need for modifications in 71 % of the episodes in the T group and 81 % in the C+A group ( p=0.23 ) . Treatment was considered to have failed because of death in two episodes ( 3 % ) in the T group and three episodes ( 4 % ) in the C+A group , and because of a change in the drug applied in one episode in the T group and two episodes in the C+A group . Overall success was 96 % ( T ) and 93 % ( C+A ) . Adverse events that occurred in group T were not related to the drugs used in this study . CONCLUSION In pediatric and adolescent patients with leukemia or lymphoma , who presented with fever and neutropenia , during chemotherapy , ticarcillin/clavulanic acid was as successful as the combination of ceftriaxone plus amikacin . It should be considered an appropriate option for this group of patients at high risk for infections Recent reports and a previous r and omized trial conducted at the authors ' institution suggested that a lower risk subset of children with febrile neutropenia under chemotherapy might benefit of an oral antibiotic outpatient approach Background Outpatient oral therapy is infrequently used in pediatric low-risk febrile neutropenia ( LRFN ) as there is insufficient data regarding its equivalence as compared with parenteral therapy . Methods This is a single institutional , r and omized control trial in pediatric LRFN aged 2 to 15 years , in which 123 episodes in 88 patients were r and omized to outpatient oral ofloxacin 7.5 mg/kg 12 hourly and amoxycillin-clavulanate 12.5 mg/kg 8 hourly or outpatient intravenous ( IV ) ceftriaxone 75 mg/kg and amikacin 15 mg/kg once daily after blood cultures . Results Out of 119 evaluable episodes , one-third were leukemia patients in maintenance and rest were solid tumors . Success was achieved in 55/61 ( 90.16 % ) and 54/58 ( 93.1 % ) in oral and IV arms , respectively , ( P=0.56 ) . There were 3 hospitalizations but no mortality . Median days to resolution of fever , absolute neutrophil count > 500/mm3 and antibiotic use were 3 , 5 , and 6 days in both arms . There were 5 blood culture isolates ( 3 gram-positive and 2 gram-negative bacteria ) . Failure of outpatient therapy was associated with perianal infections , bacteremia , febrile neutropenia onset before day 9 of chemotherapy in solid tumors and Vincristine , actinomycin-D , and cyclophosphamide chemotherapy for rhabdomyosarcoma . All gram-positive isolates were successes , whereas both gram-negative isolates were failures . Diarrhea in IV arm and Vincristine , actinomycin-D , and cyclophosphamide chemotherapy in the oral arm predicted failure in subgroup analysis . Conclusions Outpatient therapy is efficacious and safe in pediatric LRFN . There was no difference in outcome in oral versus IV outpatient therapy . Amoxycillin-clavulanate and ofloxacin may be the oral regimen of choice Empiric oral antibiotic therapy for febrile neutropenic cancer patients has been suggested as a means to decrease hospitalization , but the safety of this approach has not been adequately studied in children . We compared continued iv antibiotic therapy with switching treatment to orally administered cefixime in a group of selected febrile neutropenic children for whom blood cultures were sterile after 48 h of incubation . Two hundred episodes of febrile neutropenia were studied ( 156 patients ) , and 100 episodes were r and omized to receive each treatment . Failure to respond to therapy was defined by documented or suspected bacterial infection , recurrent fever , or discontinuation of assigned therapy for any reason before neutropenia resolved . Rates of treatment failure were similar in the oral cefixime group ( 28 % ) and in the iv antibiotic group ( 27 % ; P=1.0 ) . Results support the safety of oral cefixime therapy for low-risk febrile neutropenic children , a therapeutic approach that would facilitate earlier outpatient management and decrease the costs of treatment BACKGROUND Infections are one of the major complications in children undergoing chemotherapy . Monotherapy with either ciprofloxacin or ceftriaxone is safe and efficient in low-risk patients ( solid tumors and stage I/II lymphomas ) . The same drugs may be used in an outpatient setting , decreasing costs and the risk of nosocomial infections . PROCEDURE Low-risk patients ( N = 70 ) with episodes of fever and neutropenia ( N = 116 ) were r and omized to receive either oral ciprofloxacin or intravenous ceftriaxone as out patients . Only one patient had a central venous catheter . RESULTS Episodes of fever and neutropenia were classified as fever of unknown origin ( 41 % vs. 32 % ) or clinical ly documented infection ( 56 % vs. 63 % ) in the ciprofloxacin and ceftriaxone groups , respectively . Most of these infections were of upper respiratory tract , skin , or gastrointestinal origin . The mean duration of neutropenia was 5 vs. 6 days . Fever persisted for 1 - 9 days ( mean 2 vs. 3 days ) . Therapy was successful with no modifications in 83 % vs. 75 % of the episodes . Patients were admitted in 7 % vs. 4 % of the episodes . No bone or joint side effects were seen in either group . All patients survived . CONCLUSIONS Outpatient therapy with either oral ciprofloxacin or intravenous ceftriaxone for fever and neutropenia is effective and safe in pediatric patients with solid tumors and stage I/II non-Hodgkin lymphoma ( low-risk patients ) To evaluate the efficacy and safety of piperacillin/tazobactam ( PIPC/TAZ ) or cefepime ( CFPM ) monotherapy for febrile neutropenia ( FN ) in children , a total of 53 patients with 213 febrile episodes were r and omly treated with either PIPC/TAZ 337.5 mg/kg/day , or CFPM 100 mg/kg/day . No significant differences were observed in the success rates of the PIPC/TAZ and CFPM treatments ( 62.1 % vs. 59.1 % , P = 0.650 ) . Furthermore , no differences were noted in the rates of new infection and mortality , and no serious adverse effects occurred in either of groups . Both PIPC/TAZ and CFPM were effective and safe as an empirical therapy for FN in children . Pediatr Blood Cancer 2015;62:356 - 358 . © 2014 Wiley Periodicals , |
12,715 | 12,804,399 | REVIEW ER 'S CONCLUSIONS Treatment does not improve clinical outcome because the benefit is offset by an increase in poor outcome caused by cerebral ischemia as a result of treatment with antifibrinolytics .
These data do not support the routine use of antifibrinolytic drugs in the treatment of patients with aneurysmal subarachnoid haemorrhage | BACKGROUND Rebleeding is an important cause of death and disability in people with aneurysmal subarachnoid haemorrhage .
Rebleeding is probably due to dissolution of the clot by natural fibrinolytic activity .
OBJECTIVES The objective of this review was to assess the effect of antifibrinolytic treatment in patients with aneurysmal subarachnoid haemorrhage . | Antifibrinolytic treatment for 4 weeks after a subarachnoid hemorrhage has been shown to have no effect on outcome since a reduction in the rate of rebleeding was offset by an increase in ischemic events . To determine if a shorter course ( 4 days ) of antifibrinolytic treatment before the expected onset of ischemic complications might reduce the rate of rebleeding yet avoid ischemic complications , we prospect ively studied a series of 119 patients with subarachnoid hemorrhage ; 479 patients with subarachnoid hemorrhage from our previous r and omized double-blind study ( 238 treated with placebo , 241 with long-term tranexamic acid ) served as historical control groups . At 3 months ' follow-up , the outcome of patients treated with short-term tranexamic acid was not different from that of patients treated with long-term tranexamic acid . The rate of rebleeding ( 24 of 119 , 20 % ) was near that with placebo ( 56 of 238 , 24 % ) . In contrast , the rate of cerebral infa rct ion ( 33 of 119 , 28 % ) was almost identical to that after long-term tranexamic acid ( 59 of 241 , 24 % ) , although mortality from cerebral infa rct ion was reduced . Compared with historical control groups , treatment with tranexamic acid for 4 days fails to reduce the incidence of rebleeding but still increases the rate of cerebral infa rct ion OBJECTIVE The aim of this study was to investigate prospect ively in an unselected series of patients with an aneurysmal subarachnoid haemorrhage what at present the complications are , what the outcome is , how many of these patients have “ modern treatment”—that is , early obliteration of the aneurysm and treatment with calcium antagonists — what factors cause a delay in surgical or endovascular treatment , and what the estimated effect on outcome will be of improved treatment . METHODS A prospect i ve , observational cohort study of all patients with aneurysmal subarachnoid haemorrhage in the hospitals of a specified region in The Netherl and s. The condition on admission , diagnostic procedures , and treatments were recorded . If a patient had a clinical deterioration , the change in Glasgow coma score ( GCS ) , the presence of focal neurological signs , the results of additional investigations , and the final diagnosed cause of the deterioration were recorded . Clinical outcome was assessed with the Glasgow outcome scale ( GOS ) at 3 month follow up . In patients with poor outcome at follow up , the cause was diagnosed . RESULTS Of the 110 patients , 47 ( 43 % ) had a poor outcome . Cerebral ischaemia , 31 patients ( 28 % ) , was the most often occurring complication . Major causes of poor outcome were the effects of the initial haemorrhage and rebleeding in 34 % and 30 % of the patients with poor outcome respectively . Of all patients 102 ( 93 % ) were treated with calcium antagonists and 45 ( 41 % ) patients had early treatment to obliterate the aneurysm . The major causes of delay of treatment were a poor condition on admission or deterioration shortly after admission , in 31 % and 23 % respectively . CONCLUSIONS In two thirds of the patients with poor outcome the causes of poor outcome are the effects of the initial bleeding and rebleeding . Improved treatment of delayed or postoperative ischaemia will have only minor effects on the outcome of patients with subarachnoid haemorrhage Summary Tranexamic acid as an antifibrinolytic agent has been investigated in a controlled study in patients with recent subarachnoid haemorrhage . It is concluded that tranexamic acid improves neither rebleeding rates , nor mortality . Predominantly thrombotic complications have been noted as a more serious side effect of tranexamic acid Summary Seventy-four patients with recent subarachnoid haemorrhage were r and omly allocated to placebo or tranexamic acid treatment . Fibrinolytic activity in the blood and cerebrospinal fluid was assessed before treatment , one week later and two weeks later . The natural history of fibrinolysis following subarachnoid haemorrhage was obtained from analysis of the placebo group . Following subarachnoid haemorrhage , fibrin degradation products and plasminogen activity in the cerebrospinal fluid were elevated . Subsequently , fibrin degradation products in the cerebrospinal fluid fell progressively over the following 2 weeks . Changes in cerebrospinal fluid plasminogen activity correlated with those of blood plasminogen activity . Complications such as rebleeding , hydrocephalus or cerebral thrombosis could not be predicted from analysis of fibrinolytic activity . Tranexamic acid treatment result ed in a reduction in cerebrospinal fluid and blood plasminogen activity . The relevance of fibrinolysis in cerebrospinal fluid and blood to the management of subarachnoid haemorrhage is discussed The outcome of treatment with an antifibrinolytic agent ( tranexamic acid ) for six weeks after rupture of an intracranial aneurysm was assessed in a r and omised controlled trial . Twenty-two out of 25 ( 88 % ) treated patients survived at follow-up of three to 33 months compared with 14 out of 25 ( 56 % ) control patients . Among the patients who did not undergo operation the survival rate was 81 % ( 13 out of 16 ) in treated patients and 42 % ( 8 out of 19 ) in controls . Antifibrinolytic treatment has so far been assumed merely to postpone rebleeding and has been used to enable surgery to be deferred . These findings suggest that tranexamic acid may actually prevent rebleeding without operation . Prolonged antifibrinolysis may therefore prove useful in those patients in good condition whose aneurysms do not lend themselves to surgical obliteration Objective : To investigate whether antifibrinolytics in combination with treatment to prevent cerebral ischemia improve outcome in patients with subarachnoid hemorrhage ( SAH ) in whom occlusion of the aneurysm is delayed . Background : Antifibrinolytic treatment reduces rebleeding , but outcome does not improve because of a concurrent increase in the occurrence of cerebral ischemia . Because treatment of ischemia has improved , antifibrinolytics might now have a beneficial effect . Methods : A prospect i ve , double-blind , placebo-controlled multicenter clinical trial was performed . R and omized were 462 patients ( 229 received tranexamic acid , 233 placebo ) admitted within 96 hours after onset of SAH , in whom treatment of the aneurysm was delayed beyond 48 hours after SAH . All patients were treated with calcium antagonists and hypervolemia . At 3 months , outcome was assessed with the Glasgow Outcome Scale . The occurrence of cerebral ischemia and other complications were recorded , and the effects of treatment were related to the clinical condition on admission . Results : Antifibrinolytic treatment had no beneficial effect on outcome ( relative risk [ RR ] , 1.10 ; 95 % confidence limits [ CL ] , 0.91–1.34 ) . Antifibrinolytics significantly reduced the occurrence of rebleeding ( RR , 0.58 ; 95 % CL , 0.42–0.80 ) ; the occurrence of ischemic and other complications was the same in the two groups . Conclusion : Antifibrinolytic treatment combined with treatment to prevent cerebral ischemia does not improve outcome Summary One hundred patients with a verified subarachnoid haemorrhage were studied in a double blind , placebo-controlled trial at a single centre to determine the value and relative risks of tranexamic acid ( TXA ) in the management of ruptured intracranial aneurysms . The incidence of recurrent haemorrhage between active and placebo groups was identical ( 12 % ) and the mortality from recurrent haemorrhage was 7 % and 5 % , respectively . The overall incidence of cerebral infa rct ion before surgery , at discharge and at 6 months follow-up was greater in the TXA group ( 27 % ) than in the control group ( 11 % ) . Post-operative cerebral ischaemia was significantly more frequent in the active , 18 of 29 as compared to 6 of 32 patients , in the placebo group . In a fifth of the patients in whom cerebral blood flow was estimated there was a significant reduction of cerebral blood flow ( CBF ) on the side of the ruptured aneurysm in the TXA treated group . It is suggested that this may be the cause of the increased incidence of cerebral ischaemia in this group . There was no significant difference in the incidence of cerebral vasospasm , hydrocephalus , visual disturbances and gastrointestinal disturbances . More fatalities were encountered from ischaemia and recurrent haemorrhage in the TXA group but these differences did not reach statistical significance at the 5 % level . Given that disability was due to either vasospasm or recurrent haemorrhage then a patient under TXA treatment was significantly more likely to have disability due to vasospasm ( p<0.04 ) ; the reverse was true for the placebo patient ( p<0.05 ) In a series of 176 prospect ively studied patients who survived for at least 24 hours after aneurysmal subarachnoid hemorrhage , 39 had at least one computerized tomography (CT)-proven rebleed within 4 weeks after the first rupture . There were peaks in the incidence of rebleeding at the end of the 2nd and 3rd weeks . Sudden loss of consciousness occurred in 35 patients , preceded in one-third of them by headache . A sudden increase in headache was a symptom of rebleeding in only one patient . Loss of brain-stem reflexes was recorded in 13 patients , respiratory arrest in six , and both symptoms in eight patients . Apnea was temporary in 11 patients . Rebleeding occurred as gross intraventricular hemorrhage in 20 patients , as a space-occupying hematoma in four , as both types of hemorrhage in three , and as a purely subarachnoid hemorrhage in 12 . The location of the rebleed could not be inferred from the clinical features . Rebleeding was fatal in 51 % of cases ( two of 12 patients with a purely subarachnoid hemorrhage , and 18 of the other 27 patients ( p less than 0.005 ) ) . The risk of rebleeding could not be predicted from the patients ' clinical condition on admission or from the amount of subarachnoid blood identified on the initial CT scan . The risk of further rebleeding was significantly increased in survivors of a first rebleed ( 47 % : p less than 0.01 ) . Only seven ( 18 % ) of the 39 patients with rebleeding had survived at 3 months after the initial hemorrhage A r and omized controlled clinical trial was carried out to study the effect of tranexamic acid ( AMCA , Cyklokapron ; AB Kabi , Stockholm , Sweden ) in the prevention of early rebleeding after the rupture of an intracranial aneurysm . The incidence of vasospasm , hydrocephalus , cerebral ischemic and thromboembolic complications , morbidity , and mortality was also evaluated . The series comprises 59 patients , 30 treated with tranexamic acid and 29 controls . The treatment was stopped if there was rebleeding , operation , or discharge from the hospital . There were 6 recurrent hemorrhages in 6 patients in the tranexamic acid-treated group and 11 recurrences in 7 patients in the control group . Recurrent hemorrhages occurred later in tranexamic acid-treated patients than in controls . Five patients in each group died from rebleeding . Five additional treated patients and 2 controls died from cerebral ischemic dysfunction . The results suggest that tranexamic acid may protect patients with ruptured aneurysms from rebleeding for 1 or 2 weeks , but that it also may produce cerebral ischemic complications A double‐blind clinical trial of tranexamic acid was carried out on 39 patients with fresh subarachnoid hemorrhage from a ruptured aneurysm . Twenty patients received tranexamic acid , 6 gm daily for 14 to 21 days , while 19 patients received conventional therapy of bedrest and dexamethasone when cerebral edema developed , plus isotonic saline . Rebleeding and mortality were reduced by one‐fourth and one‐fifth , respectively ( p < 0.001 ) . No side‐effects were observed . Tranexamic acid is valuable in the treatment of subarachnoid hemorrhage caused by ruptured intracranial aneurysms MODIFICATION of the blood-clotting mechanisms as an adjunct to , or a substitute for , surgery in intracranial aneurysms has interested several workers ( Uihlein et al. , 1966 ; Gibbs & O'Gorman , 1967 ; Mullan & Dawley , 1968 ; Uttley & Buckell , 1968 ; Mullan , 1969 , personal communication ) . Uihlein et al. ( 1966 ) used the anti-fibrinolytic agent epsilonamino caproic acid ( EACA ) with hypothermia in the surgery of aneurysms , and Mullan & Dawley ( 1968 ) reported two recurrent haemorrhages only among thirty cases of angiographically proved aneurysms treated with EACA but no surgery . Since then , Mullan ( personal communication ) has combined this treatment with lowering of the systemic blood pressure by hypotensive drugs . Gibbs & O'Gorman ( 1967 ) studied fibrinolysis in 109 cases of proved intracranial aneurysms , not treated by definitive surgery , between 1963 and 1965 . Sixty-four of these patients were given EACA , either alone or with reversible proximal arterial closure . They concluded that the likelihood of recurrent haemorrhage within the first few weeks might be reduced if the whole blood-clot lysis time could be prolonged over a period to 40 hr or longer . Though no serious complications were attributed to the oral administration of EACA in doses of 36 g daily , nausea and diarrhoea were frequently troublesome . The development of amino-methyl cyclohexane carboxylic acid ( AMCA , tranexamic acid ) , more powerful than EACA both in vitro ( Maki & Beller , 1966 ) and in vivo ( Dubber , McNicol & Douglas , 1965 ) in inhibiting fibrinolysis , prompted the following clinical trial at the South-East Metropolitan Regional Neurosurgical Centre In a prospect i ve consecutive non-r and omised study including 1076 patients with ruptured intracranial aneurysms 205 patients received epsilon aminocraproic acid ( EACA ) and 871 did not . No significant differences between the two groups concerning clinical condition on admission , sex , age , localisation and size of the aneurysms were seen . No cases of rebleeding ( RB ) were observed within the first 4 days in the EACA treated patients , but within the first 48 hours , which is the optimal period recommended for operation of patients in good clinical condition , this difference of the rates of RB between EACA treated and not treated patients is not significant . A significantly lower rate of RB was observed in the EACA group within the first 2 weeks , but no significant differences in morbidity and mortality were found at the 2-year follow-up examination In a double‐blind controlled clinical trial on 51 patients with subarachnoid hemorrhage , tranexamic acid , 4 gm per day for ten consecutive days , did not favorably affect the outcome . Neither mortality nor rebleeding rates were improved after a follow‐up of three months OBJECT By pursuing a policy of very early aneurysm treatment in neurosurgical centers , in-hospital rebleeds can be virtually eliminated . Nonetheless , as many as 15 % of patients with aneurysm rupture suffer ultraearly rebleeding with high mortality rates , and these individuals are beyond the reach of even the most ambitious protocol for diagnosis and referral . Only drugs given immediately after the diagnosis of subarachnoid hemorrhage ( SAH ) has been established at the local hospital level can , in theory , contribute to the minimization of such ultraearly rebleeding . The object of this r and omized , prospect i ve , multicenter study was to assess the efficacy of short-term antifibrinolytic treatment with tranexamic acid in preventing rebleeding . METHODS Only patients suffering SAH verified on computerized tomography ( CT ) scans within 48 hours prior to the first hospital admission were included . A 1-g dose of tranexamic acid was given intravenously as soon as diagnosis of SAH had been verified in the local hospitals ( before the patients were transported ) , followed by doses of 1 g every 6 hours until the aneurysm was occluded ; this treatment did not exceed 72 hours . In this study , 254 patients received tranexamic acid and 251 patients were r and omized as controls . Age , sex , Hunt and Hess and Fisher grade distributions , as well as aneurysm locations , were congruent between the groups . Outcome was assessed at 6 months post-SAH by using the Glasgow Outcome Scale ( GOS ) . Vasospasm and delayed ischemic neurological deficits were classified according to clinical findings as well as by transcranial Doppler ( TCD ) studies . All events classified as rebleeding were verified on CT scans or during surgery . CONCLUSIONS More than 90 % of patients reached the neurosurgical center within 12 hours of their first hospital admission after SAH ; 70 % of all aneurysms were clipped or coils were inserted within 24 hours of the first hospital admission . Given the protocol , only one rebleed occurred later than 24 hours after the first hospital admission . Despite this strong emphasis on early intervention , however , a cluster of 27 very early rebleeds still occurred in the control group within hours of r and omization into the study , and 13 of these patients died . In the tranexamic acid group , six patients rebled and two died . A reduction in the rebleeding rate from 10.8 to 2.4 % and an 80 % reduction in the mortality rate from early rebleeding with tranexamic acid treatment can therefore be inferred . Favorable outcome according to the GOS increased from 70.5 to 74.8 % . According to TCD measurements and clinical findings , there were no indications of increased risk of either ischemic clinical manifestations or vasospasm that could be linked to tranexamic acid treatment . Neurosurgical guidelines for aneurysm rupture should extend also into the preneurosurgical phase to guarantee protection from ultraearly rebleeds . Currently available antifibrinolytic drugs can provide such protection , and at low cost . The number of potentially saved lives exceeds those lost to vasospasm We enrolled 479 patients with subarachnoid hemorrhage in a multicenter , r and omized , double-blind , placebo-controlled trial to determine whether treatment with the antifibrinolytic agent tranexamic acid improves outcome by preventing rebleeding . At three months there was no statistical difference between the outcomes in the tranexamic acid group and the control group . Of the 173 patients who died , 84 had received tranexamic acid and 89 placebo ( 95 per cent confidence interval for the difference in mortality rate , -6 to 11 per cent ) . Similarly , when analysis was restricted to patients with an angiographically demonstrated aneurysm , there was no significant difference between the groups . This absence of effect was not due to a lack of antifibrinolytic action , since the rate of rebleeding was reduced from 24 per cent in the control group to 9 per cent in the tranexamic acid-treated group ( chi-square = 18.07 , P less than 0.001 ) , but result ed from a concurrent increase in the incidence of ischemic complications ( 15 per cent in the control group and 24 per cent in the tranexamic acid group ; chi-square = 8.07 , P less than 0.01 ) . We conclude that until some method can be found to minimize ischemic complications , tranexamic acid is of no benefit in patients with subarachnoid hemorrhage A r and omized , controlled clinical trial was carried out to study the effect of tranexamic acid ( AMCA , trans-AMCHA ) in prevention of early rebleeding after proven rupture of an intracranial aneurysm . The series comprises 46 patients admitted to the hospital within three days after the first bleeding . Twenty-three were treated with tranexamic acid and 23 were controls . Nine patients in the control group and one in the group treated with tranexamic acid had confirmed rebleeding . The incidence of vasospasm , cerebral ischemia and hydrocephalus as well as mortality and morbidity is discussed A comparative controlled clinical trial of epsilon aminocaproic acid ( EACA ) , 36 g/day and tranexamic acid ( TEA ) , 6 g/day , was undertaken to assess their effectiveness in reducing early recurrence of subarachnoid haemorrhage ( SAH ) . Of 90 patients treated with EACA recurrent haemorrhage was seen in 8 % of these patients and 7 % of the patients developed delayed ischaemic deficit . The total pre-operative mortality in EACA-group was 11 % . Of 61 patients treated with TEA , 10 % had recurrent haemorrhage and delayed ischaemic deficit occurred in 5 % of the patients . The total pre-operative mortality in TEA-group was 11 % . No difference was found between the effectiveness and side-effects of these drugs The effects of intravenous tranexamic acid were compared with placebo in 64 patients with subarachnoid hemorrhage . A double-blind procedure was used . One gram of tranexamic acid was given intravenously every 4 hours up to the time of operation on an intracranial arterial aneurysm or for up to 21 days after the first bleeding if operative treatment was not feasible . There were no differences in re-bleeds , morbidity or mortality between the tranexamic and placebo-treated groups . No thromboemboiic complications were noted in either group . Our results do not support the use of tranexamic acid in subarachnoid hemorrhage in daily doses of 6 The value of the antifibrinolytic treatment was assessed in two groups od patients treated after subarachnoid haemorrhage from ruptured aneurysm . One group of 449 patients received EACA before the operation , and 308 were not given EACA . The effectiveness of this treatment was analysed considering the frequency of recurrent haemorrhages , site of aneurysm and sequelae of recurrent haemorrhage as well as ischaemic complications of subarachnoid haemorrhage . The frequency of recurrent haemorrhages was significantly lower in the group not treated with EACA , and the frequency of ischaemic complications of subarachnoid haemorrhage was significantly higher in those treated with EACA |
12,716 | 29,774,010 | Conclusion V and etanib should be considered as a promising treatment in advanced MTC .
However , data based on RECIST endpoints do not currently provide high-level evidence on its efficacy | Background V and etanib is the most largely used tyrosine kinase inhibitor ( TKI ) in patients with locally advanced and /or metastatic medullary thyroid cancer ( MTC ) .
Here , we conducted a systematic review on its efficacy and attempted to perform a meta- analysis adopting st and ardized RECIST criteria as end-points . | BACKGROUND Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics : both tumour shrinkage ( objective response ) and disease progression are useful endpoints in clinical trials . Since RECIST was published in 2000 , many investigators , cooperative groups , industry and government authorities have adopted these criteria in the assessment of treatment outcomes . However , a number of questions and issues have arisen which have led to the development of a revised RECIST guideline ( version 1.1 ) . Evidence for changes , summarised in separate papers in this special issue , has come from assessment of a large data warehouse ( > 6500 patients ) , simulation studies and literature review s. HIGHLIGHTS OF REVISED RECIST 1.1 : Major changes include : Number of lesions to be assessed : based on evidence from numerous trial data bases merged into a data warehouse for analysis purpose s , the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total ( and from five to two per organ , maximum ) . Assessment of pathological lymph nodes is now incorporated : nodes with a short axis of 15 mm are considered measurable and assessable as target lesions . The short axis measurement should be included in the sum of lesions in calculation of tumour response . Nodes that shrink to < 10 mm short axis are considered normal . Confirmation of response is required for trials with response primary endpoint but is no longer required in r and omised studies since the control arm serves as appropriate means of interpretation of data . Disease progression is clarified in several aspects : in addition to the previous definition of progression in target disease of 20 % increase in sum , a 5 mm absolute increase is now required as well to guard against over calling PD when the total sum is very small . Furthermore , there is guidance offered on what constitutes ' unequivocal progression ' of non-measurable/non-target disease , a source of confusion in the original RECIST guideline . Finally , a section on detection of new lesions , including the interpretation of FDG-PET scan assessment is included . Imaging guidance : the revised RECIST includes a new imaging appendix with up date d recommendations on the optimal anatomical assessment of lesions . FUTURE WORK A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI . It was concluded that , at present , there is not sufficient st and ardisation or evidence to ab and on anatomical assessment of tumour burden . The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression . As is detailed in the final paper in this special issue , the use of these promising newer approaches requires appropriate clinical validation studies Purpose : Medullary thyroid carcinoma ( MTC ) is a manifestation of multiple endocrine neoplasia type 2 ( MEN2 ) syndromes caused by germline , activating mutations in the RET ( REarranged during Transfection ) proto-oncogene . V and etanib , a VEGF and EGF receptor inhibitor , blocks RET tyrosine kinase activity and is active in adults with hereditary MTC . Experimental Design : We conducted a phase I/II trial of v and etanib for children ( 5–12 years ) and adolescents ( 13–18 years ) with MTC to define a recommended dose and assess antitumor activity . The starting dose was 100 mg/m2 administered orally , once daily , continuously for 28-day treatment cycles . The dose could be escalated to 150 mg/m2/d after two cycles . Radiographic response to v and etanib was quantified using RECIST ( v1.0 ) , biomarker response was measured by comparing posttreatment serum calcitonin and carcinoembryonic antigen ( CEA ) levels to baseline , and a patient-reported outcome was used to assess clinical benefit . Results : Sixteen patients with locally advanced or metastatic MTC received v and etanib for a median ( range ) 27 ( 2–52 ) cycles . Eleven patients remain on protocol therapy . Diarrhea was the primary dose-limiting toxicity . In subjects with M918 T RET germline mutations ( n = 15 ) the confirmed objective partial response rate was 47 % ( exact 95 % confidence intervals , 21%–75 % ) . Biomarker partial response was confirmed for calcitonin in 12 subjects and for CEA in 8 subjects . Conclusion : Using an innovative trial design and selecting patients based on target gene expression , we conclude that v and etanib 100 mg/m2/d is a well-tolerated and highly active new treatment for children and adolescents with MEN2B and locally advanced or metastatic MTC . Clin Cancer Res ; 19(15 ) ; 4239–48 . © 2013 AACR BACKGROUND A r and omized phase III trial demonstrated that v and etanib treatment is effective in patients with metastatic medullary thyroid cancer ( MTC ) , leading to regulatory approval , but its use may be associated with toxicities that require specific monitoring and management . The objective of the present study performed in France was to describe the toxicity profile and efficacy of v and etanib treatment when given outside any trial . METHODS Sixty-eight patients were treated with v and etanib in the frame of a temporary use authorization ( ATU ) in France from August 2010 to February 2012 , when the drug was available on request for patients with locally advanced or metastatic MTC . Patients were registered by the French health authorities , and characteristics , treatment parameters , toxicity profile , and efficacy were retrospectively review ed . Eight patients were excluded from the analysis because v and etanib treatment was not administered ( n=3 ) , had been given in a trial before ATU ( n=3 ) , or was given for a non-MTC cancer ( n=2 ) . RESULTS Data from the 60 MTC patients were analyzed . Mean age was 58 years ( range 11 - 83 years ) , 39 patients were male , and six had hereditary MTC . Fifty-six ( 93 % ) had metastatic disease in the mediastinum ( 82 % ) , bones ( 65 % ) , liver ( 53 % ) , or lung ( 53 % ) , and four had only locally advanced disease . At the time of study evaluation , with a median follow-up of 20 months and a median duration of treatment of 9.7 months ( range 0.3 - 36 months ) , 15 patients were continuing v and etanib treatment ( range 18 - 36 months ) . Median progression-free survival was 16.1 months . Twenty-five patients discontinued treatment for disease progression ( range 0.3 - 29 months ) . Best tumor response was a complete response in one patient , a partial response in 12 ( 20 % ) , stable disease in 33 ( 55 % ) , and progression in seven patients ( 12 % ) . All patients had at least one adverse event ( AE ) during treatment . The main AEs were skin toxicity , diarrhea , and asthenia . Sixteen patients ( 27 % ) discontinued treatment for toxicity , and one patient died from v and etanib-induced cardiac toxicity . CONCLUSIONS V and etanib is an effective option for patients with advanced MTC . AEs should be monitored carefully and should be minimized by educating both patients and care providers and by applying symptomatic treatment and dose reduction OBJECTIVE In a phase III trial , Western patients with medullary thyroid cancer ( MTC ) treated with the oral multikinase inhibitor v and etanib showed significantly improved progression-free survival ( PFS ) and objective response rate ( ORR ) compared with placebo . The biology of MTC and pharmacokinetics ( PK ) are similar for Japanese and Western patients ; therefore , similar clinical benefit is anticipated in the Japanese population . This study evaluated the safety and tolerability of v and etanib in Japanese patients with unresectable locally advanced or metastatic MTC . METHODS This was a phase I/II , open-label , nonr and omized study . Patients received v and etanib ( 300 mg daily ) until objective disease progression . The primary endpoints were safety and tolerability . Secondary endpoints included efficacy and PK . Final data analysis was conducted once all patients with measurable baseline disease had been followed to progression , or for 56 weeks . RESULTS Fourteen patients received v and etanib . All patients experienced at least one adverse event ( AE ) , and 7 patients ( 50 % ) experienced grade ≥3 AEs . Common AEs included diarrhea ( 79 % ) , hypertension ( 64 % ) , and rash ( 43 % ) . Four patients reported a total of five serious AEs ( SAEs ) . Eleven patients ( 79 % ) had dose interruptions , and 8 patients ( 57 % ) had dose reductions . One patient discontinued treatment because of an SAE ( interstitial lung disease ) . No patients met the prespecified criterion for QTc prolongation . The ORR was 38 % and PFS at 12 months was 85 % . CONCLUSION Safety and efficacy data were comparable to those previously reported , and AEs were generally manageable by st and ard clinical practice or dose modifications . Overall , v and etanib was considered to be beneficial for Japanese MTC patients . ABBREVIATIONS AE = adverse event CI = confidence interval Css , max = maximum steady-state plasma concentration DCR = disease control rate EGFR = epidermal growth factor receptor ILD = interstitial lung disease MTC = medullary thyroid cancer ORR = objective response rate PFS = progression-free survival PK = pharmacokinetics RECIST = Response Evaluation Criteria in Solid Tumors RET = re-arranged during transfection SAE = serious adverse event VEGFR = vascular endothelial growth factor receptor |
12,717 | 29,733,373 | Results suggest therapeutic communities are effective in reducing recidivism and , to a lesser extent substance use after release .
There is also evidence to suggest that opioid maintenance treatment is effective in reducing the risk of drug use after release from prison for opioid users .
Furthermore , care after release from prison appears to enhance treatment effects for both types of interventions . | We conducted a systematic review to examine the substance use and recidivism outcomes of prison-based substance use interventions . | BACKGROUND Despite its effectiveness , methadone maintenance is rarely provided in American correctional facilities . This study is the first r and omized clinical trial in the US to examine the effectiveness of methadone maintenance treatment provided to prisoners with pre-incarceration heroin addiction . METHODS A three-group r and omized controlled trial was conducted between September 2003 and June 2005 . Two hundred eleven Baltimore pre-release inmates who were heroin dependent during the year prior to incarceration were enrolled in this study . Participants were r and omly assigned to the following : counseling only : counseling in prison , with passive referral to treatment upon release ( n=70 ) ; counseling+transfer : counseling in prison with transfer to methadone maintenance treatment upon release ( n=70 ) ; and counseling+methadone : methadone maintenance and counseling in prison , continued in a community-based methadone maintenance program upon release ( n=71 ) . RESULTS Two hundred participants were located for follow-up interviews and included in the current analysis . The percentages of participants in each condition that entered community-based treatment were , respectively , counseling only 7.8 % , counseling+transfer 50.0 % , and counseling+methadone 68.6 % , p<.05 . All pairwise comparisons were statistically significant ( all ps<.05 ) . The percentage of participants in each condition that tested positive for opioids at 1-month post-release were , respectively , counseling only 62.9 % , counseling+transfer 41.0 % , and counseling+methadone 27.6 % , p<.05 , with the counseling only group significantly more likely to test positive than the counseling+methadone group . CONCLUSIONS Methadone maintenance initiated prior to or immediately after release from prison appears to have beneficial short-term impact on community treatment entry and heroin use . This intervention may be able to fill an urgent treatment need for prisoners with heroin addiction histories Aim To test the efficacy and safety of osmotic release oral system ( OROS ) methylpheni date ( MPH ) in doses up to 180 mg/day to treat attention deficit hyperactivity disorder ( ADHD ) and prevent any drug relapse in individuals with a co-diagnosis of ADHD and amphetamine dependence . Design R and omized placebo-controlled 24-week double-blind trial with parallel groups design . Setting Participants were recruited from medium security prisons in Sweden . The medication started within 2 weeks before release from prison and continued in out-patient care with twice-weekly visits , including once-weekly cognitive behavioural therapy . Participants Fifty-four men with a mean age of 42 years , currently incarcerated , meeting DSM-IV criteria for ADHD and amphetamine dependence . Measurements Change in self-reported ADHD symptoms , relapse to any drug use ( amphetamine and other drugs ) measured by urine toxicology , retention to treatment , craving and time to relapse . Findings The MPH-treated group reduced their ADHD symptoms during the trial ( P = 0.011 ) and had a significantly higher proportion of drug-negative urines compared with the placebo group ( P = 0.047 ) , including more amphetamine-negative urines ( P = 0.019 ) and better retention to treatment ( P = 0.032 ) . Conclusions Methylpheni date treatment reduces attention deficit hyperactivity disorder symptoms and the risk for relapse to substance use in criminal offenders with attention deficit hyperactivity disorder and substance dependence BACKGROUND Screening , brief intervention , and referral to treatment ( SBIRT ) is an evidence -based practice that has been shown to reduce alcohol and drug use in healthcare , educational , and other setting s , but research on the effectiveness of SBIRT with population s involved in the criminal justice system is limited . These population s have high rates of substance use but have limited access to interventions . METHODS The study r and omized 732 jail inmates from a large urban jail to the SBIRT intervention or to the control group . Using the Alcohol , Smoking , and Substance Involvement Screening Test ( ASSIST ) , the intervention assessed the risk level for drug and alcohol misuse by inmates and provided those who were at low or medium risk with a brief intervention in jail and referred those at high risk to community treatment following release , including the opportunity to participate in a brief treatment ( eight sessions ) protocol . Using interview and records data from a 12-month follow-up , analyses compared the two groups with respect to the primary study outcomes of reductions in drug and alcohol use and the secondary outcomes of participation in treatment , rearrest , reduction in HIV risk behaviors , and quality of life . In addition , the costs of delivering the SBIRT intervention were calculated . RESULTS When baseline differences were controlled , the groups did not differ at follow-up on any of the primary or secondary outcomes . CONCLUSIONS Future research should develop and evaluate SBIRT models that are specifically adapted to the characteristics and needs of the jail population . Until more favorable results emerge , attempts to use SBIRT with jail inmates should be implemented with caution , if at all . TRIAL REGISTRATION NUMBER NCT01683643 This r and omized controlled pilot study compared a cognitive-behavioral therapy ( Seeking Safety ; SS ) plus treatment-as-usual ( TAU ) to TAU-alone in 49 incarcerated women with substance use disorder ( SUD ) and posttraumatic stress disorder ( PTSD ; full or subthreshold ) . Seeking Safety consisted of a voluntary group treatment during incarceration and individual treatment after prison release . TAU was required in the prison and comprised 180 to 240 hours of individual and group treatment over 6 to 8 weeks . Assessment s occurred at intake , 12 weeks after intake , and 3 and 6 months after release from prison . There were no significant differences between conditions on all key domains ( PTSD , SUD , psychopathology , and legal problems ) ; but both conditions showed significant improvements from intake to later time points on all of these outcomes across time . Secondary analyses at follow-up found trends for SS participants improving on clinician-rated PTSD symptoms and TAU participants worsening on self-reported PTSD symptoms . Also , SS demonstrated continued improvement on psychopathology at 3 and 6 months , whereas TAU did not . However , alcohol use improved more for TAU during follow-up . Satisfaction with SS was high , and a greater number of SS sessions was associated with greater improvement on PTSD and drug use . Six months after release from prison , 53 % of the women in both conditions reported a remission in PTSD . Study limitations include lack of assessment of SS outcomes at end of group treatment ; lack of blind assessment ; omission of the SS case management component ; and possible contamination between the two conditions . The complex needs of this population are discussed OBJECTIVES To describe and evaluate a pilot methadone maintenance program for heroin-dependent inmates of Las Malvinas men 's prison in San Juan , Puerto Rico . METHODS Data from self-report of inmates ' drug use before and during incarceration , attitudes about drug treatment in general and methadone maintenance in particular , and expectations about behaviors upon release from prison and from testing inmates ' urine were analyzed comparing program patients ( n=20 ) and inmates selected at r and om from the prison population ( n=40 ) . Qualitative data obtained by interviewing program staff , the correctional officers and superintendent , and commonwealth officials responsible for establishing and operating the program were analyzed to identify attitudes about methadone and program effectiveness . RESULTS Heroin use among prisoners not in treatment was common ; 58 % reported any use while incarcerated and 38 % reported use in past 30 days . All patients in the treatment program had used heroin in prison in the 30 days prior to enrolling in treatment . While in treatment , the percentage of patients not using heroin was reduced , according to both self-report and urine testing , to one in 18 ( 94 % reduction ) and one in 20 ( 95 % reduction ) , respectively . Participation in treatment was associated with an increased acceptance of methadone maintenance . Prison personnel and commonwealth officials were supportive of the program . CONCLUSIONS The program appears to be a success , and prison officials have begun an expansion from the current ceiling of 24 inmates to treat 300 or more inmates AIMS To examine the long-term impact of methadone maintenance treatment ( MMT ) on mortality , re-incarceration and hepatitis C seroconversion in imprisoned male heroin users . DESIGN , SETTING AND PARTICIPANTS The study cohort comprised 382 imprisoned male heroin users who had participated in a r and omized controlled trial of prison-based MMT in 1997/98 . Subjects were followed-up between 1998 and 2002 either in the general community or in prison . MEASUREMENTS All-cause mortality , re-incarceration , hepatitis C and HIV serostatus and MMT retention . FINDINGS There were no deaths recorded while subjects were enrolled in MMT . Seventeen subjects died while out of MMT , representing an untreated mortality rate of 2.0 per 100 person-years ( 95 % CI , 1.2 - 3.2 ) . Re-incarceration risk was lowest during MMT episodes of 8 months or longer ( adjusted hazard ratio 0.3 ( 95 % CI , 0.2 - 0.5 ; P < 0.001 ) , although MMT periods 2 months or less were associated with greatest risk of re-incarceration ( P < 0.001 ) . Increased risk of hepatitis C seroconversion was significantly associated with prison sentences of less than 2 months [ adjusted hazard ratio 20 ( 95 % CI , 5 - 76 ; < P = 0.001 ) ] and MMT episodes less than 5 months [ adjusted hazard ratio 4.2 ( 95 % CI , 1.4 - 12.6 ; P = 0.01 ) ] . Subjects were at greatest risk of MMT dropout during short prison sentences of 1 month or less ( adjusted hazard ratio 10.4 ( 95 % CI , 7.0 - 15.7 ; P < 0.001 ) . HIV incidence was 0.3 per 100 person-years ( 95 % CI , 0.03 - 0.99 ) . CONCLUSIONS Retention in MMT was associated with reduced mortality , re-incarceration rates and hepatitis C infection . Prison-based MMT programmes are integral to the continuity of treatment needed to ensure optimal outcomes for individual and public health This study examined benefits of methadone maintenance among prerelease prison inmates . Incarcerated males with preincarceration heroin dependence ( n = 197 ) were r and omly assigned to ( a ) group educational counseling ( counseling only ) ; ( b ) counseling , with opportunity to begin methadone maintenance on release ( counseling + transfer ) ; or ( c ) counseling and methadone maintenance in prison , with opportunity to continue methadone maintenance on release ( counseling + methadone ) . At 90-day follow-up , counseling + methadone participants were significantly more likely than counseling-only and counseling + transfer participants to attend drug treatment ( p = .0001 ) and less likely to be reincarcerated ( p = .019 ) . Counseling + methadone and counseling + transfer participants were significantly less likely ( all ps < .05 ) to report heroin use , cocaine use , and criminal involvement than counseling-only participants . Follow-up is needed to determine whether these findings hold over a longer period AIMS Recent studies have demonstrated the efficacy of both methadone and buprenorphine when used with opioid dependent men transitioning from prison to the community , but no studies have been conducted with women in the criminal justice ( CJ ) system . The aim of this study was to determine the efficacy of buprenorphine for relapse prevention among opioid dependent women in the CJ system transitioning back to the community . METHODS 36 women under CJ supervision were recruited from an inpatient drug treatment facility that treats CJ individuals returning back to the community . Nine were enrolled in an open label buprenorphine arm then 27 were r and omized to buprenorphine ( n=15 ) or placebo ( n=12 ; double-blind ) . All women completed baseline measures and started study medication prior to release . Participants were followed weekly , provided urine drug screens ( UDS ) , received study medication for 12 weeks , and returned for a 3-month follow-up . Intent-to-treat analyses were performed for all time points through 3 month follow-up . RESULTS The majority of participants were Caucasian ( 88.9 % ) , young ( M±SD=31.8±8.4 years ) , divorced/separated ( 59.2 % ) women with at least a high school/GED education ( M±SD=12±1.7 years ) . GEE analyses showed that buprenorphine was efficacious in maintaining abstinence across time compared to placebo . At end of treatment , 92 % of placebo and 33 % of active medication participants were positive for opiates on urine drug screen ( Chi-Square=10.9 , df=1 ; p<0.001 ) . However , by the three month follow-up point , no differences were found between the two groups , with 83 % of participants at follow-up positive for opiates . CONCLUSIONS Women in the CJ system who received buprenorphine prior to release from a treatment facility had fewer opiate positive UDS through the 12 weeks of treatment compared to women receiving placebo . Initiating buprenorphine in a controlled environment prior to release appears to be a viable strategy to reduce opiate use when transitioning back to the community OBJECTIVE To test the hypothesis that among hazardously drinking incarcerated women who are returning to the community , a brief alcohol intervention will result in less alcohol use at follow-up relative to st and ard of care . METHODS Eligible participants endorsed hazardous alcohol consumption-four or more drinks at a time on at least 3 separate days in the previous 3 months or a score of 8 or above on the Alcohol Use Disorders Identification Test . Participants were r and omized to either an assessment -only condition or to two brief motivationally focused sessions , the first delivered during incarceration , the second 1 month later after community re-entry . Participants recalled drinking behaviors at 3 and 6 months after the baseline interview using a 90-day time-line follow-back method . RESULTS The 245 female participants averaged 34 years of age , and were 71 % Caucasian . The mean percentage of alcohol use days in the 3 months prior to incarceration was 51.7 % and heavy alcohol use days was 43.9 % . Intervention effects on abstinent days were statistically significant at 3 months ( odds ratio = 1.96 , 95 % confidence interval 1.17 , 3.30 ) ; the percentage of days abstinent was 68 % for those r and omized to intervention and 57 % for controls . At 6 months the effect of the intervention was attenuated and no longer statistically significant . CONCLUSIONS Among incarcerated women who reported hazardous drinking , a two-session brief alcohol intervention increased abstinent days at 3 months , but this effect decayed by 6 months . Study participants continued to drink heavily after return to the community . More intensive intervention pre-release and after re-entry may benefit hazardously drinking incarcerated women Correctional systems nationwide have increasingly turned to therapeutic community ( TC ) programs for the treatment of addiction in prisons . TC treatment , with modifications , has shown considerable promise in treating offenders who have co-occurring mental and substance use disorders , a group that has a mounting prevalence in prison population s. This article reports data from a study that r and omly assigned male inmates with mental illness and chemical abuse ( MICA ) disorders ( n = 139 ) to either a Modified TC ( MTC ) or a comparison group . Analyses revealed that the MTC group had significantly greater declines in alcohol and drug use at 12-months post-prison release . Additional analysis related positive substance use outcomes to reduced contact with the justice system and self-reported criminal activity . Implication s for treatment and policy are discussed Background In the United Kingdom ( UK ) , there is an extensive market for the class ' A ' drug heroin and many heroin users spend time in prison . People addicted to heroin often require prescribed medication when attempting to cease their drug use . The most commonly used detoxification agents in UK prisons are currently buprenorphine and methadone , both are recommended by national clinical guidelines . However , these agents have never been compared for opiate detoxification in the prison estate and there is a general paucity of research evaluating the most effective treatment for opiate detoxification in prisons . This study seeks to address this paucity by evaluating the most routinely used interventions amongst drug users within UK prisons . Methods / Design This study uses r and omised controlled trial methodology to compare the open use of buprenorphine and methadone for opiate detoxification , given in the context of routine care , within three UK prisons . Prisoners who are eligible and give informed consent will be entered into the trial . The primary outcome will be abstinence status eight days after detoxification , as determined by a urine test . Secondary outcomes will be recorded during the detoxification and then at one , three and six months post-detoxification . Trial registration Current Controlled Trials IS RCT This study , the largest r and omized controlled trial of treatment for major depressive disorder ( MDD ) in an incarcerated population to date , wave-r and omized 38 incarcerated women ( 6 waves ) with MDD who were attending prison substance use treatment to adjunctive group interpersonal psychotherapy ( IPT ) for MDD or to an attention-matched control condition . Intent-to-treat analyses found that IPT participants had significantly lower depressive symptoms at the end of 8 weeks of in-prison treatment than did control participants . Control participants improved later , after prison release . IPT 's rapid effect on MDD within prison may reduce serious in-prison consequences of MDD China faces the challenge of dual epidemics of drug use and HIV/AIDS . Despite the high relapse rate among heroin addicts released from compulsory rehabilitation facilities , there are few programs available in China to assist these addicts in the community . We pilot-tested in China a Recovery Management Intervention ( RMI ) program design ed to facilitate early detection of relapse and prompt linkage from compulsory rehabilitation to the community and , if participants relapse , to community-based methadone maintenance treatment ( MMT ) programs . One hundred heroin addicts were r and omly assigned to either the St and ard Care group ( n = 50 ) or the RMI group ( n = 50 ) . At the end of the 3-month trial , participants in the RMI group , relative to the st and ard care group , demonstrated positive outcomes in recidivism due to relapse ( 0 vs. 6 % , p = .08 ; d = 0.354 ) , MMT participation ( 8 % vs. 0 , p = 0.06 ; d = 0.417 ) , and employment ( 33 % vs. 2 % , p < .001 ; d = 0.876 ) , although no difference was found in urine testing results ( 8.5 % vs. 8.7 % ; d = 0.013 ) among interviewed participants . These pilot study results were based on a small sample size and short-term observation , suggesting the need for more research to further improve and test RMI effectiveness with larger sample s over a longer period of time in order to provide evidence in support of RMI as an effective strategy for community reintegration among addicts released from rehabilitation facilities in China AIMS To evaluate the effects of a jail-based continuation of methadone maintenance therapy ( MMT ) on subsequent inmate recidivism risks . DESIGN Prospect i ve , longitudinal , observational study . SETTING A large , Southwestern United States jail that continues MMT for heroin-addicted inmates on MMT at the time of booking . PARTICIPANTS A total of 589 inmates booked between 22 November 2005 ( the start date for the MMT program ) and 31 October 2006 . MEASUREMENTS The outcome measure was time from release to subsequent re-booking in the jail . Predictors included binary dosing with methadone in the jail , final dose received ( mg ) , age , gender , race/ethnicity , previous bookings and days in jail . FINDINGS AND CONCLUSIONS R and om effects Weibull proportional hazards models were fit to the recidivism times to estimate the impact of treatment with MMT in the jail on re-booking risks . There was no statistically significant effect of receiving methadone in the jail or dosage on subsequent recidivism risks ( hazard ratio = 1.16 ; 95 % confidence interval = 0.8 - 1.68 ) . Offering jail-based MMT does not increase recidivism risks by eliminating the deterrent effect of imposed withdrawal , nor does it reduce recidivism in this high-risk population This study tested the viability of auricular acupuncture in prisons for alleviating inmates ' symptoms of psychological and physical discomfort and reducing their drug use . The experimental NADA-Acudetox protocol was compared with a non-specific helix control protocol in a r and omized trial . Over a period of 18 months , a 4-week , 14-session auricular acupuncture treatment program was offered in two prisons to 163 men and women with self-reported drug use . Among treatment completers , no differences by method were found in self-reported symptoms of discomfort . Drug use occurred in the NADA group but not in the helix group . In contrast , confidence in the NADA treatment increased over time while it decreased for the helix treatment . No significant negative side effects were observed for either method . Participants in both groups reported reduced symptoms of discomfort and improved nighttime sleep . Future research should compare auricular acupuncture to a non-invasive control in order to attempt to disentangle active effects from placebo OBJECTIVES The aim was to determine whether methadone maintenance treatment reduced heroin use , syringe sharing and HIV or hepatitis C incidence among prisoners . METHODS All eligible prisoners seeking drug treatment were r and omised to methadone or a waitlist control group from 1997 to 1998 and followed up after 4 months . Heroin use was measured by hair analysis and self report ; drugs used and injected and syringe sharing were measured by self report . Hepatitis C and HIV incidence was measured by serology . RESULTS Of 593 eligible prisoners , 382 ( 64 % ) were r and omised to MMT ( n=191 ) or control ( n=191 ) . 129 treated and 124 control subjects were followed up at 5 months . Heroin use was significantly lower among treated than control subjects at follow up . Treated subjects reported lower levels of drug injection and syringe sharing at follow up . There was no difference in HIV or hepatitis C incidence . CONCLUSIONS Consideration should be given to the introduction of prison methadone programs particular where community based programs exist Individuals who use heroin and illicit opioids are at high risk for infection with human immunodeficiency virus ( HIV ) and other blood-borne pathogens , as well as incarceration . The purpose of the r and omized trial reported here is to compare outcomes between participants who initiated methadone maintenance treatment ( MMT ) prior to release from incarceration , with those who were referred to treatment at the time of release . Participants who initiated MMT prior to release were significantly more likely to enter treatment postrelease ( P < .001 ) and for participants who did enter treatment , those who received MMT prerelease did so within fewer days ( P = .03 ) . They also reported less heroin use ( P = .008 ) , other opiate use ( P = .09 ) , and injection drug use ( P = .06 ) at 6 months . Initiating MMT in the weeks prior to release from incarceration is a feasible and effective way to improve MMT access postrelease and to decrease relapse to opioid use AIMS To describe the profile of imprisoned opioid-dependent patients , prescriptions of maintenance therapy at imprisonment and 3-year outcome in terms of re-incarceration and mortality . DESIGN Prospect i ve , observational study ( France , 2003 - 06 ) . SETTING Health units of 47 rem and prisons . PARTICIPANTS A total of 507 opioid-dependent patients included within the first week of imprisonment between June 2003 and September 2004 , inclusive . MEASUREMENTS Physicians collected socio-demographic data , penal history , history of addiction , maintenance therapy and psychoactive agent use , general health status and comorbidities . Prescriptions at imprisonment were recorded by the prison pharmacist . Re-incarceration data were retrieved from the National Register of Inmates , survival data and causes of death from the National Registers of vital status and death causes . FINDINGS Prison maintenance therapy was delivered at imprisonment to 394/507 ( 77.7 % ) patients . These patients had poorer health status , heavier opioid use and prison history and were less socially integrated than the remaining 113 patients . Over 3 years , 238/478 patients were re-incarcerated [ 51.3 re-incarcerations per 100 patient-years , 95 % confidence interval ( CI ) 46.4 - 56.2 ] . Factors associated independently with re-incarceration were prior imprisonment and benzodiazepine use . After adjustment for confounders , maintenance therapy was not associated with a reduced rate of re-incarceration ( adjusted relative risk 1.28 , 95 % CI 0.89 - 1.85 ) . The all-cause mortality rate was eight per 1000 patient-years ( n = 10 , 95 % CI 4 - 13 ) . CONCLUSIONS Prescription of maintenance therapy has increased sharply in French prisons since its introduction in the mid-1990s . However , the risk of re-imprisonment or death remains high among opioid-dependent prisoners . Substantial efforts are needed to implement more effective preventive policies A sample of 296 drug-using inmates in 14 Swedish prisons was r and omized during 2004–2006 into three intervention groups ; Motivational Interviewing delivered by counselors with workshop-only training , or by counselors with workshop training followed by peer group supervision , and controls . Drug and alcohol use was measured by the Addiction Severity Index ( ASI ) at intake and at 10 months after release . Complete data from 114 clients were analyzed by a stepwise regression analysis . All three groups reduced alcohol and drug use . Limitations in the study are discussed and future research is suggested . The study is financed by grants from the Research Committee of the National Prison and Probation Administration The study r and omly assigned male inmates with co-occurring serious mental illness and chemical abuse ( MICA ) disorders to either modified therapeutic community ( MTC ) or mental health ( MH ) treatment programs . On their release from prison , MICA inmates who completed the prison MTC program could enter the MTC aftercare program . The results , obtained from an intent-to-treat analysis of all study entries , showed that inmates r and omized into the MTC group had significantly lower rates of reincarceration compared with those in the MH group . The results also show that differences between the MTC + aftercare and comparison group across a variety of crime outcomes ( i.e. any criminal activity , and alcohol or drug related criminal activity ) are consistent and significant , and persist after an examination of various threats to validity ( e.g. initial motivation , duration of treatment , exposure to risk ) . This study provides some support for the effectiveness of the prison TC only condition . The findings are encouraging and consonant with other studies of integrated prison and aftercare TC programs for substance abusing non-MICA offenders , although qualified by the possibility that selection bias ( i.e. differences in motivation on entry into aftercare ) may be operating . Nevertheless , given the available evidence and the need for effective programming for MICA offenders , program and policy makers should strongly consider developing integrated prison and aftercare modified TC programs for MICA offenders Buprenorphine has rarely been administered as an opioid agonist maintenance therapy in a correctional setting . This study introduced buprenorphine maintenance in a large urban jail , Rikers Isl and in New York City . Heroin-dependent men not enrolled in community methadone treatment and sentenced to 10 - 90 days in jail ( N=116 ) were voluntarily r and omly assigned either to buprenorphine or methadone maintenance , the latter being the st and ard of care for eligible inmates at Rikers . Buprenorphine and methadone maintenance completion rates in jail were equally high , but the buprenorphine group reported for their design ated post-release treatment in the community significantly more often than did the methadone group ( 48 % vs. 14 % , p<.001 ) . Consistent with this result , prior to release from Rikers , buprenorphine patients stated an intention to continue treatment after release more often than did methadone patients ( 93 % vs. 44 % , p<.001 ) . Buprenorphine patients were also less likely than methadone patients to withdraw voluntarily from medication while in jail ( 3 % vs. 16 % , p<.05 ) . There were no post-release differences between the buprenorphine and methadone groups in self-reported relapse to illicit opioid use , self-reported re-arrests , self-reported severity of crime or re-incarceration in jail . After initiating opioid agonist treatment in jail , continuing buprenorphine maintenance in the community appears to be more acceptable to offenders than continuing methadone maintenance This study examined the impact of prison-initiated methadone maintenance at 12 months postrelease . Males with pre-incarceration heroin dependence ( N = 204 ) were r and omly assigned to ( a ) Counseling Only : counseling in prison , with passive referral to treatment upon release ; ( b ) Counseling + Transfer : counseling in prison with transfer to methadone maintenance treatment upon release ; and ( c ) Counseling + Methadone : counseling and methadone maintenance in prison , continued in the community upon release . The mean number of days in community-based drug abuse treatment were , respectively , Counseling Only , 23.1 ; Counseling + Transfer , 91.3 ; and Counseling + Methadone , 166.0 ( p < .01 ) ; all pairwise comparisons were statistically significant ( all ps < .01 ) . Counseling + Methadone participants were also significantly less likely than participants in each of the other two groups to be opioid-positive or cocaine-positive according to urine drug testing . These results support the effectiveness of prison-initiated methadone for males in the United States . Further study is required to confirm the findings for women OBJECTIVES This r and omized controlled study compared acceptance and commitment therapy ( ACT ) , cognitive-behavioral therapy ( CBT ) , and a control group . METHOD The participants were 50 incarcerated women diagnosed with current substance use disorder . Two psychologists carried out pre- and posttreatment assessment and a 6-month follow-up assessment using the following instruments : Anxiety Sensitivity Index , Addiction Severity Index-6 , Mini International Neuropsychiatric Interview , and Acceptance and Action Question naire . RESULTS The study shows that the women who received treatment benefited differentially from the interventions . At posttreatment , CBT was more effective than ACT in reducing anxiety sensitivity ; however , at follow-up , ACT was more effective than CBT in reducing drug use ( 43.8 vs. 26.7 % , respectively ) and improving mental health ( 26.4 % vs. 19.4 % , respectively ) . CONCLUSION ACT may be an alternative to CBT for treatment of drug abuse and associated mental disorders . In fact , at long-term , ACT may be more appropriate than CBT for incarcerated women who present serious problems AIMS This study examined the effectiveness of methadone maintenance initiated prior to or just after release from prison at 6 months post-release . DESIGN A three-group r and omized controlled trial was conducted between September 2003 and June 2005 . SETTING A Baltimore pre-release prison . PARTICIPANTS Two hundred and eleven adult pre-release inmates who were heroin-dependent during the year prior to incarceration . INTERVENTION Participants were assigned r and omly to the following : counseling only : counseling in prison , with passive referral to treatment upon release ( n = 70 ) ; counseling + transfer : counseling in prison with transfer to methadone maintenance treatment upon release ( n = 70 ) ; and counseling + methadone : methadone maintenance and counseling in prison , continued in a community-based methadone maintenance program upon release ( n = 71 ) . MEASUREMENTS Addiction Severity Index at study entry and follow-up . Additional assessment s at 6 months post-release were treatment record review ; urine drug testing for opioids , cocaine and other illicit drugs . FINDINGS Counseling + methadone participants were significantly more likely than both counseling only and counseling + transfer participants to be retained in drug abuse treatment ( P = 0.0001 ) and significantly less likely to have an opioid-positive urine specimen compared to counseling only ( P = 0.002 ) . Furthermore , counseling + methadone participants reported significantly fewer days of involvement in self-reported heroin use and criminal activity than counseling only participants . CONCLUSIONS Methadone maintenance , initiated prior to or immediately after release from prison , increases treatment entry and reduces heroin use at 6 months post-release compared to counseling only . This intervention may be able to fill an urgent treatment need for prisoners with heroin addiction histories Addiction is serious problem that requires effective treatment . Previous studies support personalized feedback interventions ( PFIs ) as an effective treatment for drinking ; however , the potential beneficial effects of this treatment on illegal drug use have not been explored . The present study examined the effects of PFIs in a sample of repetitive drug-related offenders . Participants were 50 repetitive drug-related offenders incarcerated in a Japanese prison . They were r and omly assigned to the PFIs ( n = 20 ) or control ( n = 30 ) group . The PFIs group received six letters for 3 months , whereas the control group did not undergo any interventions . We defined relapse and recidivism as drug-related reoffending and reentering prison after release , respectively . In the 3.6-year follow-up analysis ( range , 0.1–5.8 years ) , participants ’ criminal records were examined , and results indicated a decreased risk of relapse and recidivism for the PFIs group relative to the control group , even when controlling for age , educational level , number of prison terms , and sentence length . Thus , our findings suggest that PFIs reduce the likelihood of relapse and recidivism in drug-related offenders This r and om assignment study compared female offenders ( n = 468 ) with substance use disorders in a prison therapeutic community program with those in a cognitive-behavioral intervention . The study demonstrates that all women benefitted from gender-sensitive prison treatment , but the therapeutic community was more effective in reducing drug use , criminal activity , and exposure to trauma and increasing mental health functioning and time until reincarceration during the year after prison . In addition , the ability to sustain and even improve behavior change after the women leave prison highlights the importance of providing accessible community-based continuity of mental health and substance abuse services during reentry BACKGROUND AND AIMS Relapse to addiction following incarceration is common . We estimated the feasibility and effectiveness of extended-release naltrexone ( XR-NTX ) as relapse prevention among opioid-dependent male adults leaving a large urban jail . DESIGN Eight-week , proof-of-concept , open-label , non-blinded r and omized effectiveness trial . SETTING New York City jails and Bellevue Hospital Center Adult Primary Care clinics , USA . PARTICIPANTS From January 2010 to July 2013 , 34 opioid-dependent adult males with no stated interest in agonist treatments ( methadone , buprenorphine ) received a counseling and referral intervention and were r and omized to XR-NTX ( n = 17 ) versus no medication ( n = 17 ) within one week prior to jail release . INTERVENTION XR-NTX ( Vivitrol ( ® ) ; Alkermes Inc. ) , a long-acting injectable mu opioid receptor antagonist . MEASURES The primary intent-to-treat outcome was post-release opioid relapse at week 4 , defined as ≥10 days of opioid misuse by self-report and urine toxicologies . Secondary outcomes were proportion of urine sample s negative for opioids and rates of opioid abstinence , intravenous drug use ( IVDU ) , cocaine use , community treatment participation , re-incarceration and overdose . FINDINGS Acceptance of XR-NTX was high ; 15 of 17 initiated treatment . Rates of the primary outcome of week 4 opioid relapse were lower among XR-NTX participants : 38 versus 88 % [ P<0.004 ; odds ratio ( OR ) = 0.08 , 95 % confidence interval ( CI ) = 0.01 - 0.48 ] ; more XR-NTX urine sample s were negative for opioids , 59 versus 29 % ( P<0.009 ; OR = 3.5 , 95 % CI = 1.4 - 8.5 ) . There were no significant differences in the remaining secondary outcomes , including rates of IVDU , cocaine use , re-incarceration and overdose . CONCLUSION Extended-release naltrexone is associated with significantly lower rates of opioid relapse among men in the United States following release from jail when compared with a no medication treatment-as-usual condition BACKGROUND R and omized trial evidence on the effectiveness of incarceration and treatment of first-time driving while intoxicated ( DWI ) offenders who are primarily American Indian has yet to be reported in the literature on DWI prevention . Further , research has confirmed the association of antisocial personality disorder ( ASPD ) with problems with alcohol including DWI . METHODS A r and omized clinical trial was conducted , in conjunction with 28 days of incarceration , of a treatment program incorporating motivational interviewing principles for first-time DWI offenders . The sample of 305 offenders including 52 diagnosed as ASPD by the Diagnostic Interview Schedule were assessed before assignment to conditions and at 6 , 12 , and 24 months after discharge . Self-reported frequency of drinking and driving as well as various measures of drinking over the preceding 90 days were available at all assessment s for 244 participants . Further , DWI rearrest data for 274 participants were available for analysis . RESULTS Participants r and omized to receive the first offender incarceration and treatment program reported greater reductions in alcohol consumption from baseline levels when compared with participants who were only incarcerated . Antisocial personality disorder participants reported heavier and more frequent drinking but showed significantly greater declines in drinking from intake to posttreatment assessment s. Further , the treatment result ed in larger effects relative to the control on ASPD than non-ASPD participants . CONCLUSIONS Nonconfrontational treatment may significantly enhance outcomes for DWI offenders with ASPD when delivered in an incarcerated setting , and in the present study , such effects were found in a primarily American-Indian sample BACKGROUND Extended-release naltrexone , a sustained-release monthly injectable formulation of the full mu-opioid receptor antagonist , is effective for the prevention of relapse to opioid dependence . Data supporting its effectiveness in U.S. criminal justice population s are limited . METHODS In this five-site , open-label , r and omized trial , we compared a 24-week course of extended-release naltrexone ( Vivitrol ) with usual treatment , consisting of brief counseling and referrals for community treatment programs , for the prevention of opioid relapse among adult criminal justice offenders ( i.e. , persons involved in the U.S. criminal justice system ) who had a history of opioid dependence and a preference for opioid-free rather than opioid maintenance treatments and who were abstinent from opioids at the time of r and omization . The primary outcome was the time to an opioid-relapse event , which was defined as 10 or more days of opioid use in a 28-day period as assessed by self-report or by testing of urine sample s obtained every 2 weeks ; a positive or missing sample was computed as 5 days of opioid use . Post-treatment follow-up occurred at weeks 27 , 52 , and 78 . RESULTS A total of 153 participants were assigned to extended-release naltrexone and 155 to usual treatment . During the 24-week treatment phase , participants assigned to extended-release naltrexone had a longer median time to relapse than did those assigned to usual treatment ( 10.5 vs. 5.0 weeks , P<0.001 ; hazard ratio , 0.49 ; 95 % confidence interval [ CI ] , 0.36 to 0.68 ) , a lower rate of relapse ( 43 % vs. 64 % of participants , P<0.001 ; odds ratio , 0.43 ; 95 % CI , 0.28 to 0.65 ) , and a higher rate of opioid-negative urine sample s ( 74 % vs. 56 % , P<0.001 ; odds ratio , 2.30 ; 95 % CI , 1.48 to 3.54 ) . At week 78 ( approximately 1 year after the end of the treatment phase ) , rates of opioid-negative urine sample s were equal ( 46 % in each group , P=0.91 ) . The rates of other prespecified secondary outcome measures --self-reported cocaine , alcohol , and intravenous drug use , unsafe sex , and reincarceration -- were not significantly lower with extended-release naltrexone than with usual treatment . Over the total 78 weeks observed , there were no overdose events in the extended-release naltrexone group and seven in the usual-treatment group ( P=0.02 ) . CONCLUSIONS In this trial involving criminal justice offenders , extended-release naltrexone was associated with a rate of opioid relapse that was lower than that with usual treatment . Opioid-use prevention effects waned after treatment discontinuation . ( Funded by the National Institute on Drug Abuse ; Clinical Trials.gov number , NCT00781898 . ) This article describes a r and omized study to determine the effectiveness of a reentry modified therapeutic community ( RMTC ) for offenders with co-occurring substance use and mental disorders ( co-occurring disorders or COD ) . Men with COD , approved for community corrections placement postrelease , were recruited from nine Colorado prisons and stratified according to the type of treatment received while incarcerated ( i.e. , a prison modified therapeutic community [ MTC ] program or st and ard care ) . When released , each offender was r and omly assigned either to the experimental RMTC ( E-RMTC ) condition ( n = 71 ) or to the control parole supervision and case management ( PSCM ) condition ( n = 56 ) . An intent-to-treat analysis 12 months postprison release showed that the E-RMTC participants were significantly less likely to be reincarcerated ( 19 % vs. 38 % ) , with the greatest reduction in recidivism found for participants who received MTC treatment in both setting s. These findings support the RMTC as a st and -alone intervention and provide initial evidence for integrated MTC programs in prison and in aftercare for offenders with COD Almost half of convicted jail inmates have an alcohol use disorder and many are released to environments that put them in contact with network members and cues that make them more likely to relapse on alcohol or drugs . Given the high-risk period immediately following release , the purpose of this study was to examine the efficacy of a brief motivational intervention administered just prior to release to increase substance use treatment entry and attendance , decrease alcohol and drug use , and change social networks for inmates with alcohol use disorders . Forty adult male inmates with AUDs were consented into the study and r and omized to a motivational intervention or the control condition ( an educational intervention ) , and then were contacted to do a 1-month follow-up interview ( 62.5 % completed this interview ) . Results indicated that conducting these interventions was feasible and considered extremely helpful by participants . Although there were no significant group differences , medium to large effect sizes suggest possible benefits from the motivational intervention in decreasing days of alcohol and drug use and increasing abstinence , and reducing the proportion of heavy drug users or users of any kind in the social network . Future studies should replicate these findings in larger sample sizes and over longer follow-up time periods . Results may have implication s for the use of brief intervention strategies at jails for inmates with AUDs |
12,718 | 16,088,113 | Conclusion : Data on novel risk factors for stroke are lacking compared with the equivalent data for acute coronary events , and there are very few data on specific subtypes of ischaemic stroke | Background : To identify new treatments to prevent stroke , it is important that we have reliable data on potential novel risk factors . | An elevated level of C-reactive protein is a strong predictor of cardiovascular events in elderly persons . Whether C-reactive protein has direct adverse vascular effects or is a marker of aspecific systemic inflammation remains to be determined . The aim of this study was to investigate the relation between C-reactive protein and the occurrence of fatal strokes in elderly persons . In the Leiden 85-Plus Study , a population -based prospect i ve follow-up study , we studied the levels of C-reactive protein in 80 participants who died from stroke within the first 5 years of follow-up . Levels of C-reactive protein were determined in serum sample s at baseline . Levels of C-reactive protein were also determined in 82 control subjects who survived for the first 5 years of follow-up and in 83 participants who died from noncardiovascular causes . Mortality risks were estimated with logistic regression and adjusted for differences in age , sex , smoking , medication , total cholesterol , history of diabetes or hypertension , and previous cardiovascular events . Levels of C-reactive protein at baseline were 2-fold higher in subjects who died from stroke than in control subjects ( median 5.7 versus 2.7 mg/L , P<0.005 ) . The levels of C-reactive protein in subjects who died from stroke or from noncardiovascular causes were similar ( median 5.7 versus 4.9 mg/L , P=0.7 ) . The risk of death from stroke as well as from noncardiovascular causes increased linearly up to 10-fold in subjects with the highest levels of C-reactive protein at baseline ( P<0.001 ) . The levels of C-reactive protein were lower when more time had elapsed between blood sampling and time of death during follow-up ( P=0.01 ) . C-reactive protein is a strong but nonspecific risk factor of fatal stroke in old persons . The data do not support the idea that C-reactive protein has direct vascular effects that underlie fatal cerebrovascular disease Little is known about the prospect i ve associations of fibrinogen , factor VII , or factor VIII with cardiovascular disease ( CVD ) and mortality in the elderly . At baseline in the Cardiovascular Health Study ( 5888 white and African American men and women ; aged > /=65 years ) , we measured fibrinogen , factor VIII , and factor VII . We used sex-stratified stepwise Cox survival analysis to determine relative risks ( RRs ) for CVD events and all-cause mortality ( up to 5 years of follow-up ) , both unadjusted and adjusted for CVD risk factors and sub clinical CVD . After adjustment , comparing the fifth quintile to the first , fibrinogen was significantly associated in men with coronary heart disease events ( RR=2.1 ) and stroke or transient ischemic attack ( RR=1.3 ) , and also with mortality within 2.5 years of follow-up ( RR=5.8 ) and later ( RR=1.7 ) . Factor VIII was significantly associated in men with coronary heart disease events ( RR=1.5 ) and mortality ( RR=1.8 ) , and in women with stroke/transient ischemic attack ( RR=1.4 ) . For both factors , values were higher in those who died , whether causes were CVD-related or non-CVD-related , but highest in CVD death . Factor VII exhibited associations with incident angina ( RR=1.44 ) in men and with death in women ( RR , middle quintile compared with first=0.66 ) . However , in general , factor VII was not consistently associated with CVD events in this population . We conclude that , if confirmed in other studies , the measurement of fibrinogen and /or factor VIII may help identify older individuals at higher risk for CVD events and mortality 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 BACKGROUND AND PURPOSE Several cross-sectional and prospect i ve studies have indicated that high titers of antibodies to Chlamydia pneumoniae and cytomegalovirus ( CMV ) are associated with coronary heart disease . The aim of the present study was to examine whether elevated titers of antibodies to these pathogens are predictive of not only coronary but also cerebrovascular disease . METHODS Serum titers of antibodies to C pneumoniae ( IgM , IgG , IgA , IgG immune complex ) and CMV ( IgG ) were determined at baseline ( n=130 ) and after 3.5 years ( n=111 ) in a total sample of 152 men . All individuals had treated hypertension and at least 1 additional risk factor for cardiovascular disease ( hypercholesterolemia , smoking , or diabetes mellitus ) and constituted 93 % of a r and omly selected subgroup ( n=164 ) of patients participating in a multiple risk factor intervention study . RESULTS Elevations of any or both of the IgA or IgG titers to C pneumoniae at entry or after 3.5 years were found in 84 cases ( 55 % ) . Of those with high titers at entry , 97 % remained high at the 3.5 year reexamination . After 6.5 years of follow-up , high titers to C pneumoniae at entry were associated with an increased risk for future stroke ( relative risk [ RR ] , 8.58 ; P=0.043 ; 95 % CI , 1.07 to 68.82 ) and for any cardiovascular event ( RR , 2.69 ; P=0.042 ; 95 % CI , 1.04 to 6.97 ) . A high serum titer of antibodies to CMV was found in 125 cases ( 85 % ) , and this was not associated with an increased risk of future cardiovascular events . CONCLUSIONS Seropositivity for C pneumoniae , but not for CMV , was associated with an increased risk for future cardiovascular disease and , in particular , stroke OBJECTIVE : To determine whether Helicobacter pylori , a chronic bacterial infection often acquired in childhood , is associated with increased risk of coronary heart disease and stroke later in life . DESIGN : Nested case-control study . SETTING : Prospect i ve study of cardiovascular disease in men aged 40 - 59 years at entry ( 1978 - 1980 ) in 24 British towns . SUBJECTS : 135 cases of myocardial infa rct ion and 137 cases of stroke occurring before December 1991 ; 136 controls were identified , frequency matched to cases by town and age group . METHODS : Serum sample s stored at entry were analysed by an enzyme linked immunosorbent assay for the presence of H pylori specific IgG antibodies . RESULTS : 95 of the myocardial infa rct ion cases ( 70 % ) and 93 ( 68 % ) of the stroke cases were seropositive for H pylori compared with 78 ( 57 % ) of the controls ( odds ratio for myocardial infa rct ion 1.77 , 95 % confidence interval ( CI ) 1.06 to 2.95 , P = 0.03 ; odds ratio for stroke 1.57 , 95 % CI 0.95 to 2.60 , P = 0.07 ) . Helicobacter pylori infection was associated with manual social class , residence in Northern Engl and or Scotl and , cigarette smoking , higher systolic pressure and blood glucose , and a lower height-st and ardised forced expiratory volume in one second . Adjustment for these factors attenuated the relation between H pylori and myocardial infa rct ion ( odds ratio = 1.31 , 95 % CI 0.70 to 2.43 , P = 0.40 ) and effectively abolished the relation with stroke ( odds ratio = 0.96 , 0.46 to 2.02 , P = 0.92 ) . The relation between helicobacter infection and fatal myocardial infa rct ion was slightly stronger ( odds ratio 2.41 , 95 % CI 1.13 to 5.12 ) but was also markedly attenuated after adjustment ( 1.56 , 95 % CI 0.68 to 3.61 ) . CONCLUSION : In this prospect i ve study the association between Helicobacter pylori infection and increased risk of myocardial infa rct ion and stroke was substantially confounded by the relation between this infection , adult social class , and major cardiovascular risk factors BACKGROUND Sinking prebeta lipoprotein is a putative marker for elevated levels of lipoprotein ( a ) . Although prospect i ve data suggest that increased plasma lipoprotein ( a ) is an independent risk factor for coronary heart disease in men , no prospect i ve studies are available in women . METHODS AND RESULTS From 1968 through 1975 , sinking prebeta lipoprotein was determined by paper electrophoresis in 3103 women Framingham Heart Study participants who were free of prevalent cardiovascular disease . A sinking prebeta lipoprotein b and was detectable in 434 of the women ( 14 % ) studied . The median follow-up interval was approximately 12 years . Incident cardiovascular disease was associated with b and presence using a proportional hazards model that included age , smoking , body mass index , systolic blood pressure , glucose intolerance , low- and high-density lipoprotein cholesterol , and ECG left ventricular hypertrophy . Multivariable adjusted relative risk estimates ( with 95 % confidence intervals ) for outcomes in the b and present versus absent groups were as follows : myocardial infa rct ion ( 82 events ) , 2.37 ( 1.48 to 3.81 ) ; intermittent claudication ( 62 events ) , 1.94 ( 1.07 to 3.50 ) ; cerebrovascular disease ( 83 events ) , 1.88 ( 1.12 to 3.15 ) ; total coronary heart disease ( 174 events ) , 1.61 ( 1.13 to 2.29 ) ; and total cardiovascular disease ( 305 events ) , 1.44 ( 1.09 to 1.91 ) . A subset analysis indicated that b and presence was 50.9 % sensitive and 95.4 % specific for detecting plasma lipoprotein ( a ) levels of > 30 mg/dL , the threshold value linked to increased cardiovascular disease risk in men . CONCLUSIONS Sinking prebeta lipoprotein was a valid surrogate for elevated lipoprotein ( a ) levels in Framingham Heart Study women . B and presence and , equivalently , elevated plasma lipoprotein ( a ) , was a strong , independent predictor of myocardial infa rct ion , intermittent claudication , and cerebrovascular disease . Confirmation of these findings in other longitudinal studies of women is needed Background : To decide whether a person with certain characteristics should be given any kind of intervention to prevent a cardiovascular event , it would be helpful to classify subjects in low , medium and high risk categories . The study evaluated which well known cerebrovascular and cardiovascular correlates , in particular fibrinogen level and ECG characteristics , are able to predict the occurrence of stroke in men of the general population using data from three European cohorts participating in EUROSTROKE . Methods : EUROSTROKE is a collaborative project among ongoing European population based cohort studies and design ed as a prospect i ve nested case-control study . For each stroke case two controls were sample d. Strokes were classified according to MONICA criteria or review ed by a panel of four neurologists . Complete data were available of 698 men ( 219 stroke events ) from cohorts in Cardiff ( 84 cases/200 controls ) , Kuopio ( 74/148 ) and Rotterdam ( 61/131 ) . Multivariable logistic regression modeling was used to evaluate which information from history , physical examination ( for example , blood pressure ) , blood lipids , and fibrinogen and ECG measurements independently contributed to the prediction of stroke . The area under receiver operating characteristic curve ( ROC area ) was used to estimate the predictive ability of models . Results : Independent predictors from medical history and physical examination were age , stroke history , medically treated hypertension , smoking , diabetes mellitus and diastolic blood pressure . The ROC area of this model was 0.69 . After validating and transforming this model to an easy applicable rule , 40 % of all future stroke cases could be predicted . Adding pulse rate , body mass index , blood lipids , fibrinogen level and ECG parameters did not improve the classification of subjects in low , medium and high risk . Results were similar when fibrinogen was dichotomised at the upper tertile or quintile . Conclusion : In the general male population the future occurrence of stroke may be predicted using easy obtainable information from medical history and physical examination . Measurement of pulse rate , body mass index , blood lipids , fibrinogen level and ECG characteristics do not contribute to the risk stratification of stroke and have no value in the screening for stroke in the general male population BACKGROUND Experimental studies have suggested both atherogenic and thrombogenic properties of lipoprotein(a ) [ Lp(a ) ] , depending on Lp(a ) plasma concentrations and varying antifibrinolytic capacity of apolipoprotein(a ) [ apo(a ) ] isoforms . Epidemiological studies may contribute to assessment of the relevance of these findings in the general population . METHODS AND RESULTS This study prospect ively investigated the association between Lp(a ) plasma concentrations , apo(a ) phenotypes , and the 5-year progression of carotid atherosclerosis assessed by high-resolution duplex ultrasound in a r and om sample population of 826 individuals . We differentiated early atherogenesis ( incident nonstenotic atherosclerosis ) from advanced ( stenotic ) stages in atherosclerosis that originate mainly from atherothrombotic mechanisms . Lp(a ) plasma concentrations predicted the risk of early atherogenesis in a dose-dependent fashion , with this association being confined to subjects with LDL cholesterol levels above the population median ( 3.3 mmol/L ) . Apo(a ) phenotypes were distributed similarly in subjects with and without early carotid atherosclerosis . In contrast , apo(a ) phenotypes of low molecular weight emerged as one of the strongest risk predictors of advanced stenotic atherosclerosis , especially when associated with high Lp(a ) plasma concentrations ( odds ratio , 6.4 ; 95 % CI , 2.8 to 14 . 9 ) . CONCLUSIONS Lp(a ) is one of the few risk factors capable of promoting both early and advanced stages of atherogenesis . Lp(a ) plasma concentrations predicted the risk of early atherogenesis synergistically with high LDL cholesterol . Low-molecular-weight apo(a ) phenotypes with a putatively high antifibrinolytic capacity in turn emerged as one of the leading risk conditions of advanced stenotic stages of atherosclerosis Serum lipoproteins including lipoprotein(a ) , Lp(a ) , are emerging as possible biological markers for cerebrovascular disease . Existing data on Lp(a ) and serum lipids levels following acute ischemic stroke ( AIS ) are however equivocal . To determine whether serum Lp(a ) and other lipid levels obtained within 24 h of acute ischemic stroke onset changed over the ensuing 4 weeks and whether these levels are related to an acute phase response , acquired nutritional deficiency , and neurovascular data , we conducted repeated measurement analyses among 19 subjects ( mean age 65.0 + /- 12.1 years ; 32 % women ) presenting with AIS ( evaluated within 9.7 + /- 12.7 h ) . Eleven of the subjects had a moderate-to-severe stroke , defined by NIH stroke severity scale , and seven patients had a large cerebral infa rct ion . Seven serial measurements of Lp(a ) , total cholesterol , high density lipoprotein cholesterol , low density lipoprotein cholesterol , and other lipoproteins , major acute phase reactants and albumin levels were collected for each subject over 4 weeks . The mean initial levels , ( mg/dl ) , of total cholesterol , LDL cholesterol , HDL cholesterol , triglycerides , Lp(a ) , apolipoproteins A-I and B were : 225 + /- 57.6 , 154 + /- 56.0 , 40 + /- 10.4 , 181 + /- 93.7 , 52 + /- 28.6 , 130 + /- 24.6 , and 141 + /- 46.1 , respectively . There were no significant changes in mean serum lipid , apolipoprotein or Lp(a ) levels over the 4-week study period , analyzed by a r and om effects model to test for time trend . In addition , there were no significant changes in established acute phase or nutritional markers ( C-reactive protein , alpha 1-glycoprotein , haptoglobin or serum albumin ) . Our findings suggest that serum lipid , apolipoprotein and Lp(a ) levels remain stable following AIS , consistent with the absence of acute phase response or nutritional deficiency Background and Purpose — The mechanisms of immune reaction involved in the pathogenesis and clinical course of acute vascular incidents are still not completely understood . The aim of this study was to examine the presence of immune complexes ( IC ) in the acute stroke setting and the first month thereafter and to characterize IC by analyzing the contents of chlamydial lipopolysaccharide and anti-cytomegalovirus ( CMV ) antibodies in IC . Methods — Serum concentration of IC was investigated in 179 stroke patients , 122 “ old ” controls and 112 “ young ” controls , by the precipitation method . The presence of chlamydial lipopolisaccharyde and anti-CMV antibodies was investigated in some IC preparations by the ELISA method after earlier dissociation of IC into components by high pH treatment . Results — Significantly increased serum IC concentration in stroke patients was noticed . Increased serum IC concentration was revealed as an independent strong stroke risk factor and was connected with significantly worse neurological status and increased 30-day mortality rate . A significantly larger proportion of stroke patients than controls had Chlamydia pneumoniae antigen and anti-CMV antibodies in IC . Conclusions — This study provides the first evidence of an association between increased serum level of IC and the clinical course of cerebral ischemia and identifies a potentially important association of C pneumoniae and CMV-specific IC with stroke incidence BACKGROUND Elevated lipoprotein(a ) [ Lp(a ) ] levels have been associated with the presence of atherosclerotic disease . However , the results of prospect i ve studies of Lp(a ) and cardiovascular disease have been contradictory . METHODS AND RESULTS From 1968 through 1982 , lipoprotein analysis was performed in 11,335 Olmsted County residents . Quantitative cholesterol and triglycerides were obtained along with semiquantitative Lp(a ) levels based on electrophoretic pattern . Lp(a ) b and s were scored from 0 ( absent ) to 3 ( increased ) . A cohort of 4967 men and 4968 women with no prior history of atherosclerotic disease who had baseline Lp(a ) determinations were followed up for 14 years for development of coronary artery disease ( CAD ) and cerebrovascular disease ( CVD ) . During 131,330 person-years of follow-up , there were 1848 CAD events and 841 CVD events . Age , diabetes , hypertension , cholesterol , and triglycerides were significantly and independently associated with an increased risk of CAD and CVD in men and women . There was a significant increase in the adjusted hazards ratio for CAD with increasing Lp(a ) levels for men and women . For Lp(a ) level 3 , the hazard ratio was 1.9 ( range , 1.3 to 2.9 ) in women and 1.6 ( range , 1.0 to 2.5 ) in men . The adjusted hazard ratio for CVD showed an irregular association with Lp(a ) levels in men and no association in women . CONCLUSIONS In this cohort of 9936 men and women initially free of cardiovascular disease who were followed up for 14 years , Lp(a ) was a significant predictor of risk of future CAD . Lp(a ) was a weak risk factor for CVD in men and was not a significant predictor of CVD risk in women OBJECTIVES --To determine whether fibrinogen and lipid concentrations are risk factors for ischaemic stroke . DESIGN --Case-control study with a population based comparison within the overall study . SETTING --Oxfordshire community stroke project and a neurology clinic . SUBJECTS--105 patients who had a transient ischaemic attack or minor ischaemic stroke and 352 r and omly chosen controls matched for age and sex from the same general practitioners as the incident cases . 52 controls were ineligible or refused interview . 104 cases and 241 controls gave blood sample s for analysis . MAIN OUTCOME MEASURES --Response to structured question naire , height , weight , blood pressure , and serum concentrations of fibrinogen and lipids . RESULTS --Adjusted for other variables , odds ratios of ischaemic stroke were 1.78 ( 95 % confidence interval 0.91 to 3.48 ; p = 0.09 ) [ corrected ] for fibrinogen concentrations greater than 3.6 g/l ; 1.73 ( 0.90 to 3.29 ; p = 0.09 ) [ corrected ] for total cholesterol concentrations greater than 6.0 mmol/l ; 1.34 ( 0.69 to 2.61 ; p greater than 0.4 ) for low density lipoprotein cholesterol concentrations greater than 3.5 mmol/l ; and 0.32 ( 0.15 to 0.69 ; p = 0.002 ) for high density lipoprotein cholesterol concentration greater than 1.2 mmol/l . Similar results emerged comparing only community derived cases with transient ischaemic attacks and controls . The effects of fibrinogen , total cholesterol , and high density lipoprotein cholesterol were significant in a test of trend after adjusting for all other variables in the study ( chi 2 = 4.14 , p less than 0.05 ; chi 2 = 4.31 , p less than 0.05 , and chi 2 = 12.15 , p greater than 0.001 , respectively ) . History of ischaemic heart disease and hypertension were the only other variables that showed significance , though both lost significance after adjustment ( 2.06 , p = 0.08 and 1.53 , p = 0.2 , respectively ) . CONCLUSIONS --Fibrinogen and lipids are important risk factors for ischaemic stroke . The pattern of changes mirrors that found in ischaemic heart disease Background and Purpose The present multicenter case-control study was prospect ively design ed to assess the extent to which single and combined clotting factor abnormalities influence the onset of symptomatic ischemic stroke in full-term neonates . Methods Lipoprotein (Lp)(a ) ; the factor V ( FV ) G1691A mutation ; the prothrombin ( PT ) G20210A variant ; the methylenetetrahydrofolate reductase ( MTHFR ) T677 T genotype ; antithrombin ; protein C ; protein S ; and anticardiolipin antibodies ( ACAs ) were investigated in 91 consecutively recruited neonatal stroke patients and 182 age- and sex-matched healthy controls . Results Sixty-two of 91 stroke patients ( 68.1 % ) had at least 1 prothrombotic risk factor compared with 44 control subjects ( 24.2 % ) ( odds ratio [OR]/95 % confidence interval [ CI ] , 6.70/3.84 to 11.67 ) . An increased Lp(a ) level ( > 30 mg/dL ) was found in 20 patients and 10 controls ( OR/95 % CI , 4.84/2.16 to 10.86 ) ; FV G1691A was present in 17 patients and 10 controls ( OR/95 % CI , 3.95/1.72 to 9.0 ) ; the PT G20210A variant was detected in 4 patients and 4 controls ( OR/95 % CI , 2.04/0.49 to 8.3 ) ; the MTHFR TT677 genotype was found in 15 patients and 20 controls ( OR/95 % CI , 1.59/0.77 to 3.29 ) ; and protein C type I deficiency was found in 6 neonates . Neither antithrombin deficiency nor protein S deficiency was found in the neonatal patients studied . Acquired IgG ACAs were found in 3 cases . Additional triggering factors , ie , asphyxia , septicemia , maternal diabetes , and perinatally acquired renal venous thrombosis , were reported in 54.0 % of patients . Conclusions Besides acquired triggering factors , the data presented here suggest that genetic prothrombotic risk factors play a role in symptomatic neonatal stroke We examined the relationships of whole blood viscosity and its major determinants to incident cardiovascular events ( ischaemic heart disease and stroke ) in a prospect i ve study of a r and om population sample of 1592 men and women aged 55–74 years ( the Edinburgh Artery Study ) . 272 fatal and non‐fatal cardiovascular events occurred during 5 years of follow‐up ( cumulative incidence 17.1 % ) . Age and sex adjusted mean levels of blood viscosity ( 3.70 v 3.55 mPa.s ) , haematocrit ( 46.2 v 45.7 % ) , haematocrit‐corrected blood viscosity ( 3.57 v 3.48 mPa.s ) , plasma viscosity ( 1.35 v 1.33 mPa.s ) and fibrinogen ( 2.88 v 2.67 g/l ) were significantly higher in subjects who experienced events than in subjects who did not . The relationships of these rheological variables to cardiovascular events were at least as strong as those of conventional risk factors ( smoking habit , diastolic blood pressure , and low‐density lipoprotein cholesterol ) . After adjustment for these conventional risk factors , the associations of blood viscosity and haematocrit remained significant for stroke , but not for total events ; whereas the associations of plasma viscosity and fibrinogen remained significant for total events and for stroke OBJECTIVES We sought to determine prospect ively whether lipoprotein-associated phospholipase A(2 ) ( Lp-PLA(2 ) ) was a predictor of future cardiovascular risk in women . BACKGROUND Inflammatory markers may help predict cardiovascular risk . Lp-PLA(2 ) levels have recently been hypothesized to be an independent predictor of cardiovascular risk in hypercholesterolemic men . METHODS We conducted a prospect i ve , nested case-control study among 28,263 apparently healthy middle-aged women to assess the risk of death from coronary heart disease , non-fatal myocardial infa rct ion , and stroke associated with baseline levels of Lp-PLA(2 ) over a mean follow-up of three years . RESULTS In univariate analysis , mean levels of Lp-PLA(2 ) correlated strongly with low-density lipoprotein cholesterol ( r = 0.51 ; p = 0.0001 ) , were lower among women currently using hormone replacement therapy ( mean 0.98 mg/l vs. 1.23 mg/l ; p = 0.0001 ) and were significantly higher at baseline among cases ( n = 123 ) than controls ( n = 123 ) ( mean 1.20 mg/l vs. 1.05 mg/l ; p = 0.016 ) . However , the predictive value of Lp-PLA(2 ) was markedly attenuated after adjustment for these and other cardiovascular risk factors . Specifically , the multivariate relative risks of future cardiovascular events for women in the lowest ( referent ) to highest quartiles of Lp-PLA(2 ) were 1.00 , 0.75 , 0.64 and 1.17 , respectively ( all p values non-significant ) . In contrast , the adjusted relative risks of future cardiovascular events for each increasing quartile of C-reactive protein ( another marker of low- grade inflammation ) were 1.00 , 1.78 , 2.02 and 4.66 , respectively ( p-value for trend = 0.002 ) . Inclusion of Lp-PLA(2 ) levels did not significantly attenuate this latter observation . CONCLUSIONS In contrast to prior data among hyperlipidemic men , the current data suggest that Lp-PLA(2 ) is not a strong predictor of future cardiovascular risk among unselected women In vitro studies provide mechanisms by which elevated lipoprotein(a ) [ Lp(a ) ] concentrations may promote both thrombosis and atherogenesis . Case-control studies have reported raised Lp(a ) concentrations in patients with stroke , but prospect i ve studies have failed to confirm the association . A potential confounding factor is that Lp(a ) may rise acutely after stroke . We determined Lp(a ) concentrations in 164 patients studied at least 21 days after stroke or transient ischaemic attack , and in 91 controls . In the patient group we correlated Lp(a ) concentrations with both the degree of carotid stenosis estimated on duplex ultrasonography , and with stroke subtype ( large vessel disease , lacunar infa rct ion , and cardioembolic and unknown pathogenesis ) . There was no difference between Lp(a ) concentration in cases and controls [ median ( quartiles ) 0·10 ( 0·04 , 0·39 ) versus 0·12 ( 0·04 , 0·30 ) g/L , P = 0·34 ] . There was no difference in the proportion of cases compared with controls with a markedly elevated Lp(a ) of > 0·4g/L ( 21·3 versus 16·5 % , P = 0·34 ) . There was non-significant trend towards higher median Lp(a ) concentrations in women [ median ( quartiles ) 0·16 ( 0·04 , 0·32)g/L versus 0·12 ( 0·04 , 0·28 ) g/L , P = 0·3 ] . In view of this trend we analysed the differences between cases and controls for each sex separately . Lp(a ) concentrations in men were median ( quartiles ) 0·08 ( 0·04 , 0·26)g/L in the 101 cases and 0·12 ( 0·04 , 0·28 ) g/L in the 43 controls ( P = 0·6 ) . Lp(a ) concentrations in women were median ( quartiles ) 0·25 ( 0·04 , 0·44 ) g/L in the 63 cases , and 0·16 ( 0·04 , 0·32 ) g/L in the 48 controls ( P = 0·16 ) . Within the patient group there was no difference between Lp(a ) concentrations in the different stroke subgroups . There was no relationship between Lp(a ) concentrations and mean percentage carotid stenosis ( r s = 0·14 , P = 0·07 ) . Our results suggest that in an unselected population of men studied more than 3 weeks post event there is no relationship between lipoprotein(a ) concentrations and either stroke/transient ischaemic attack , or carotid atheroma . The relationship in women requires further study Over an 18-month period , all incident cases of neurological disorders were ascertained prospect ively in an unselected urban population based in 13 general practice s in the London area by a General Practice Linkage Scheme with the National Hospital for Neurology and Neurosurgery . In three of these practice s , the lifetime prevalence of neurological disorders was also assessed . A population of 100 230 patients registered with participating general practice s was followed prospect ively for the onset of neurological disorders . Multiple methods of case finding were used to maintain accuracy . The age- and sex-adjusted incidence rates of neurological disorders were calculated . The lifetime prevalence of neurological disorders was surveyed in 27 658 of the patients . The age- and sex-adjusted incidence rates were calculated for major neurological conditions . [ These are expressed as rates per 100 000 persons per annum , with 95 % confidence intervals ( CI ) in parentheses ] . The commonest of these were first cerebrovascular events , 205 ( CI : 183 , 230 ) ; shingles , 140 ( CI : 104 , 184 ) ; diabetic polyneuropathy , 54 ( CI : 33 , 83 ) ; compressive neuropathies , 49 ( CI : 39 , 61 ) ; epilepsy , 46 ( CI : 36 , 60 ) ; Parkinson 's disease , 19 ( CI : 12 , 27 ) ; peripheral neuropathies , 15 ( CI : 9 , 23 ) ; CNS infections , 12 ( CI : 5 , 13 ) ; post-herpetic neuralgia , 11 ( CI : 6 , 17 ) ; and major neurological injuries , 10 ( CI : 4 , 11 ) . Lifetime prevalence rates are also reported ( expressed as rate per 1000 persons with 95 % CI ) . The most prevalent conditions were : completed stroke , 9 ( CI : 8 , 11 ) ; transient ischaemic attacks , 5 ( CI : 4 , 6 ) ; active epilepsy , 4 ( CI : 4 , 5 ) ; congenital neurological deficit , 3 ( CI : 3 , 4 ) ; Parkinson 's disease , 2 ( CI : 1 , 3 ) ; multiple sclerosis , 2 ( CI : 2 , 3 ) ; diabetic polyneuropathy , 2 ( CI : 1 , 3 ) ; compressive mononeuropathies , 2 ( CI : 2 , 3 ) ; and sub-arachnoid haemorrhage , 1 ( CI : 0.8 , 2 ) . Overall , the onset of 625 neurological disorders was observed per 100 000 population annually . Six percent of the population had at some time had a neurological disorder . This is the first study of the incidence and lifetime prevalence of neurological disorders in recent times ; we found that these disorders give rise to significant morbidity in the community PURPOSE Plasma fibrinogen has emerged as an important predictor of cardiovascular disease , but few data are available on its association with stroke . We sought to determine if plasma fibrinogen is a marker of increased risk or a direct causative risk factor for stroke . SUBJECTS AND METHODS Patients from the Bezafibrate Infa rct ion Prevention Study , a placebo-controlled , r and omized clinical trial of secondary prevention of coronary heart disease by lipid modification with bezafibrate retard ( 400 mg daily ) , were studied . Plasma fibrinogen levels were measured at baseline and yearly thereafter . Stroke , a prospect ively monitored endpoint , was systematic ally assessed regarding stroke type , subtype , and functional outcome . RESULTS Mean baseline fibrinogen levels were significantly higher in patients subsequently having a cerebrovascular event ( 140 strokes , 36 transient ischemic attacks ; mean follow-up , 6.2 years ) than in patients who did not ( 375 vs. 349 mg/dL , P < 0.0001 ) . Fibrinogen levels did not differ significantly by the type , subtype , or severity of the cerebrovascular event . Risk of ischemic stroke increased from 3.3 % in the lowest tertile ( baseline fibrinogen < 314 mg/dL ) to 7.% in the middle tertile ( fibrinogen 314 to 373 mg/dL ) to 10 % in the upper tertile ( fibrinogen > 373 mg/dL , P < 0.001 ) . Adjusting for age , blood pressure , and other covariates , fibrinogen levels in the upper tertile were associated with more than a twofold increase in risk of ischemic stroke compared with in the lowest tertile ( hazard ratio = 2.6 ; 95 % confidence interval : 1.5 to 4.3 ) . We did not find fibrinogen change from baseline to be related to subsequent ischemic stroke events . CONCLUSION Plasma fibrinogen is a strong predictor of , rather than a direct causative factor for , subsequent stroke among patients at increased risk owing to manifest coronary heart disease OBJECTIVE To assess prospect ively the risk of future stroke associated with baseline concentration of lipoprotein(a ) , abbreviated Lp(a ) . DESIGN Nested case-control study using baseline plasma sample s. SETTING Men in the Physicians ' Health Study . PARTICIPANTS A cohort of 14,916 male physicians with no prior history of stroke , transient ischemic attack , or myocardial infa rct ion provided plasma sample s at baseline and were followed prospect ively for 7.5 years . Sample s from 198 physicians who subsequently developed stroke ( 155 thromboembolic , 35 hemorrhagic , eight indeterminate ) were analyzed for Lp(a ) concentration together with paired controls , matched for age and smoking habit . MAIN OUTCOME MEASURE Fatal and nonfatal stroke . RESULTS Median Lp(a ) concentration ( 8.88 mg/dL [ 0.23 mmol/L ] vs 8.55 mg/dL [ 0.22 mmol/L ] ) , P = .69 ) and overall distributions of Lp(a ) ( P = .54 ) were similar at baseline in men who did and did not develop future stroke . In analyses controlling for age , smoking status , blood pressure , obesity , and the presence of diabetes , the relative risks ( RRs ) associated with baseline Lp(a ) concentration exceeding the 25th , 50th , 75th , 90th , and 95th percentiles of the control distribution were 1.26 , 0.99 , 1.06 , 0.90 , and 1.03 ( all P values nonsignificant ) . There was likewise no association in analyses limited to thromboembolic events . For example , among subjects with baseline Lp(a ) values exceeding the 95th percentile of the control distribution , the RR of future thromboembolic stroke was 1.01 ( P = .9 ) . No evidence of association between Lp(a ) and stroke risk was found in analyses limited to individuals with hypercholesterolemia . CONCLUSIONS Among nearly 15,000 predominantly white , healthy , middle-aged men followed in the Physicians ' Health Study for a period of 7.5 years , we found no evidence of association between baseline plasma concentration of Lp(a ) and future risk of total or thromboembolic stroke BACKGROUND Inflammation may be important in the pathogenesis of atherothrombosis . We studied whether inflammation increases the risk of a first thrombotic event and whether treatment with aspirin decreases the risk . METHODS We measured plasma C-reactive protein , a marker for systemic inflammation , in 543 apparently healthy men participating in the Physicians ' Health Study in whom myocardial infa rct ion , stroke , or venous thrombosis subsequently developed , and in 543 study participants who did not report vascular disease during a follow-up period exceeding eight years . Subjects were r and omly assigned to receive aspirin or placebo at the beginning of the trial . RESULTS Base-line plasma C-reactive protein concentrations were higher among men who went on to have myocardial infa rct ion ( 1.51 vs. 1.13 mg per liter , P<0.001 ) or ischemic stroke ( 1.38 vs. 1.13 mg per liter , P=0.02 ) , but not venous thrombosis ( 1.26 vs. 1.13 mg per liter , P=0.34 ) , than among men without vascular events . The men in the quartile with the highest levels of C-reactive protein values had three times the risk of myocardial infa rct ion ( relative risk , 2.9 ; P<0.001 ) and two times the risk of ischemic stroke ( relative risk , 1.9 ; P=0.02 ) of the men in the lowest quartile . Risks were stable over long periods , were not modified by smoking , and were independent of other lipid-related and non-lipid-related risk factors . The use of aspirin was associated with significant reductions in the risk of myocardial infa rct ion ( 55.7 percent reduction , P=0.02 ) among men in the highest quartile but with only small , nonsignificant reductions among those in the lowest quartile ( 13.9 percent , P=0.77 ) . CONCLUSIONS The base-line plasma concentration of C-reactive protein predicts the risk of future myocardial infa rct ion and stroke . Moreover , the reduction associated with the use of aspirin in the risk of a first myocardial infa rct ion appears to be directly related to the level of C-reactive protein , raising the possibility that antiinflammatory agents may have clinical benefits in preventing cardiovascular disease Data from several studies have suggested that persons with coronary heart disease have an increased prevalence of chronic infection with such agents as Chlamydia pneumoniae , Helicobacter pylori , herpes simplex virus , and cytomegalovirus ( 1 ) . In addition , it has been hypothesized that infection may be a risk factor for acute coronary events ( 2 ) . However , chronic infection is also more prevalent among smokers , elderly persons , and persons of lower socioeconomic status , and persons with a history of coronary disease may be more susceptible to subsequent infection . Therefore , it is uncertain whether the associations between infection and coronary heart disease that have been observed in retrospective and cross-sectional studies were caused by confounding or represent a result of ischemic heart disease rather than a cause ( 3 ) . To resolve these issues , investigators have used prospect i ve , controlled setting sin which exposure status can be ascertained before the onset of thrombosisto evaluate the theory that previous infection is related to atherosclerosis . The few reported prospect i ve studies of C. pneumoniae ( 4 - 7 ) , H. pylori ( 8 - 12 ) , herpes simplex virus ( 13 ) , and cytomegalovirus ( 13 ) have not provided strong evidence of an association ; however , none of these studies evaluated multiple infectious exposures simultaneously . This is a potentially important issue because it has been hypothesized that a person 's total burden of pathogens may be a critical factor in determining atherogenesis ( 14 ) . In addition , the available prospect i ve data were derived from studies that predominantly or exclusively evaluated men . To further investigate the theory that previous infection is related to atherothrombosis , we measured IgG antibody titers against C. pneumoniae , H. pylori , herpes simplex virus , and cytomegalovirus in baseline blood sample s obtained from a large cohort of apparently healthy postmenopausal women who were followed prospect ively for the occurrence of first cardiovascular events . We also related these antibody titers to plasma concentrations of high-sensitivity C-reactive protein , a marker of chronic inflammation that has previously been shown to predict coronary risk in this cohort ( 15 ) . Methods We performed a nested casecontrol study among participants in the Women 's Health Study , an ongoing primary prevention trial that enrolled 39 876 postmenopausal female health professionals with no history of myocardial infa rct ion , stroke , or transient ischemic attack ( 16 ) . Of women enrolled in the study , 28 311 ( 71 % ) provided baseline blood sample s , which were frozen in liquid nitrogen until analysis . Case- patients were initially healthy Women 's Health Study participants who provided a baseline blood sample and who subsequently reported a first cardiovascular event ( myocardial infa rct ion , stroke , cardiovascular death , or coronary revascularization procedure ) during follow-up . Reported myocardial infa rct ion was confirmed if review of hospital records met World Health Organization criteria and if the event was associated with characteristic electrocardiographic changes or elevated levels of cardiac enzymes . Reported stroke was confirmed if records showed a new neurologic deficit persisting for more than 24 hours ; such records almost always included evidence from computed tomography or magnetic resonance imaging . Reported coronary angioplasty or coronary bypass surgery was confirmed by record review . Cardiovascular death was confirmed by autopsy reports , death certificates , and circumstances at the time of death . Controls were r and omly selected from the pool of initially healthy Women 's Health Study participants who remained free of cardiovascular disease during study follow-up and also provided a baseline blood sample . Two controls , matched for age ( 1 year ) and smoking status ( never , past , or current ) , were selected for each case-patient . Baseline plasma sample s from case- patients and controls were thawed and assayed for IgG antibody titers against C. pneumoniae by using microimmunofluorescence techniques ( 6 , 17 ) . Similarly , enzyme-linked immunosorbent assays were used to qualitatively detect IgG antibodies to herpes simplex virus ( Wampole Laboratories , Cranbury , New Jersey ) , cytomegalovirus ( Gull Laboratories , Salt Lake City , Utah ) , and H. pylori ( Wampole Laboratories ) in baseline plasma sample s. For each variable , sample s from a case-patient and two matched controls were assayed as a group ; sample s from the case-patient were positioned r and omly within the group to reduce interassay variability and to avoid systematic bias . All laboratory investigators were unaware of case-patient or control status at the time of IgG analysis . C-reactive protein levels were evaluated by using a high-sensitivity assay ( Abbott Laboratories , Abbott Park , Illinois ) , as described elsewhere ( 15 ) . We used conditional logistic regression analyses to test for evidence of an association between the presence of IgG antibodies at baseline and subsequent risk for cardiovascular events . A priori , we chose to evaluate the association between C. pneumoniae and subsequent risk across a series of IgG antibody titers ( range,>1:16 to>1:128 ) . The presence or absence of IgG seropositivity for herpes simplex virus , cytomegalovirus , and H. pylori was determined according to cut-points established by the assay manufacturers . Adjusted estimates of risk were computed after we controlled for baseline differences between case- patients and controls . To evaluate the theory that total infectious burden rather than any single IgG titer may be associated with risk , we further classified study participants as having zero , one , two , three , or four positive antibody titers . Because the number of study participants with zero positive titers at baseline was small ( n=15 ) , data from these participants and from participants with one positive titer were combined for analysis . Where applicable , tests for trend were used to evaluate evidence of increasing risk across increasing antibody titers ( 18 ) . We also compared the distribution of C-reactive protein values for participants with two or more positive IgG antibody titers with the distribution of values for participants with zero or one positive IgG antibody titer . All P values are two-tailed . Results Among 122 case- patients , 85 myocardial infa rct ions or strokes occurred and 37 coronary revascularizations were performed . As is expected in a study of incident coronary events , case- patients were more likely than controls to have a history of hyperlipidemia ( 45.9 % compared with 28.3 % ; P=0.001 ) , hypertension ( 55.5 % compared with 31.3 % ; P=0.001 ) , and diabetes ( 9.8 % compared with 2.1 % ; P=0.001 ) and to have a family history of premature coronary disease ( 21.3 % compared with 12.7 % ; P=0.04 ) . Case- patients also had a greater mean body mass index than controls ( 27.1 compared with 26.0 kg/m2 ; P=0.05 ) . Because of matching , mean age ( 59.3 8.3 years ) and smoking status ( 27.9 % of participants currently smoked , 42.6 % had never smoked , and 29.5 % had smoked in the past ) were identical in the case-patient and control groups . Exposure rates among controls were similar to those reported in previous studies ; for example , 60 % of controls had C. pneumoniae titers greater than 1:8 ( 1 , 2 ) . However , as shown in Table 1 , the proportion of study participants with positive IgG titers was similar regardless of case-patient or control status . For example , the crude rate ratios for future cardiovascular events in women with C. pneumoniae titers 1:16 , 1:32 , 1:64 , and 1:128 were 1.1 , 1.1 , 1.1 , and 1.0 , respectively ( P>0.2 overall ) ( Table 1 ) . Similarly , the crude rate ratios for future cardiovascular events associated with baseline seropositivity to H. pylori , herpes simplex virus , and cytomegalovirus were 0.9 , 1.2 , and 0.9 , respectively ( P>0.2 overall ) . As shown in Figure 1 , these point estimates did not change after adjustment for baseline differences in hyperlipidemia , hypertension , exercise frequency , body mass index , diabetes , and family history of premature coronary artery disease . Table 1 . Rate Ratios for Future Cardiovascular Events among Apparently Healthy Women , according to Baseline IgG Antibody Status Figure 1 . Adjusted rate ratios for future cardiovascular events among apparently healthy women , according to the presence of baseline IgG antibody titers against Chlamydia pneumoniae , herpes simplex virus , cytomegalovirus , and Helicobacter pylori ( top ) and the number of positive baseline IgG titers present ( bottom ) . To evaluate the theory that total pathogen burden might be associated with increased risk , we stratified patients into four groups according to the total number of positive titers observed in a given case-patient or control . As shown in Table 2 , the rate ratios for future cardiovascular events in women with zero or one , two , three , or four positive IgG titers were 0.9 , 1.1 , 1.0 , and 1.0 , respectively ( P>0.2 overall ) . Similarly , in analyses that evaluated evidence of trend across these four groups , little evidence supported an association ( P>0.2 for trend ) . As shown in Figure 1 , adjustment for baseline differences between case- patients and controls had little or no effect on these results . Table 2 . Rate Ratios for Future Cardiovascular Events among Apparently Healthy Women , according to the Total Number of IgG Antibody Titers Present in a Given Study Participant Previously obtained data from this cohort indicate that median C-reactive protein levels are significantly higher in participants who subsequently reported coronary events than in controls ( 6.45 compared with 3.75 mg/L ; P<0.001 ) ; this suggests that chronic low- grade inflammation is a marker of risk in this group of women ( 15 ) . However , when we compared participants with and those without positive IgG antibody titers , the distribution of C-reactive protein levels was similar in isolated analyses limited to each pathogen , in analyses evaluating total pathogen burden ( Figure 2 ) , and in OBJECTIVES This prospect i ve population study was conducted to assess the role of elevated lipoprotein(a ) [ Lp(a ) ] as a coronary risk factor . BACKGROUND The role of elevated Lp(a ) as a risk factor for coronary heart disease is controversial . In addition , little attention has been paid to the interaction of Lp(a ) with other risk factors . METHODS A total of 788 male participants of the Prospect i ve Cardiovascular Münster ( PROCAM ) study aged 35 to 65 years were followed for 10 years . Both Lp(a ) and traditional cardiovascular risk factors ( e.g. , age , low density lipoprotein [ LDL ] cholesterol , high density lipoprotein [ HDL ] cholesterol , triglycerides , systolic blood pressure , cigarette smoking , diabetes mellitus , angina pectoris , and family history of myocardial infa rct ion ) were evaluated in 44 men who suffered from myocardial infa rct ion , and in 744 men who survived without major coronary events or stroke . A multiple logistic function algorithm was used to estimate global cardiovascular risk by the combined effects of traditional risk factors . RESULTS Overall , the risk of a coronary event in men with an Lp(a ) > or = 0.2 g/liter was 2.7 times that of men with lower levels ( 95 % confidence interval [ CI ] : 1.4 to 5.2 ) . This increase in risk was most prominent in men with LDL cholesterol level > or = 4.1 mmol/liter ( relative risk [ RR ] : 2.6 ; 95 % CI : 1.2 to 5.7 ) , with HDL cholesterol < or = 0.9 mmol/liter ( RR 8.3 ; 95 % CI : 2.0 to 35.5 ) , with hypertension ( RR 3.2 ; 95 % CI : 1.4 to 7.2 ) , or within the two highest global risk quintiles ( relative risk : 2.7 ; 95 % CI : 1.3 to 5.7 ) . CONCLUSIONS Lp(a ) increases the coronary risk , especially in men with high LDL cholesterol , low HDL cholesterol , hypertension and /or high global cardiovascular risk BACKGROUND AND PURPOSE In several cross-sectional studies , a high serum lipoprotein(a ) [ Lp(a ) ] level was found to be an independent risk factor for cerebral infa rct ion . In a recent prospect i ve study , however , no association was found between Lp(a ) levels at baseline and future risk of stroke . Whether Lp(a ) is a prognostic factor in a high-risk population of patients with acute ischemic stroke remains unclear . METHODS We assessed Lp(a ) level on admission to study its relationship with cardiovascular risk profile , stroke severity , and prognosis in 151 consecutive patients with acute cerebral ischemia . The mean follow-up period was 2.5 + /- 1.2 years . Lp(a ) was measured by means of a solid-phase two-site immunoradiometric assay . RESULTS Increased Lp(a ) levels were found in 53 ( 35 % ) of the patients with cerebral ischemia . Median ( 5th and 95th percentile ) values of Lp(a ) were 191 ( 12 and 1539 ) mg/L and 197 ( 10 and 1255 ) mg/L for patients with transient ischemic attack and patients with ischemic stroke , respectively . No relationship was found between Lp(a ) levels and stroke severity ( P=.68 ) or the occurrence of vascular events during follow-up ( P log rank=0.81 ) . CONCLUSIONS We conclude that Lp(a ) is increased in about one third of patients with acute cerebral ischemia , but it does not appear to be associated with the cardiovascular risk profile , stroke characteristics , or the prognosis of such patients OBJECTIVES We sought to determine whether seropositivity to Helicobacter pylori , Chlamydia pneumoniae , and cytomegalovirus ( CMV ) is an independent predictor of incident cardiovascular disease . BACKGROUND Recent reports have suggested that infections may contribute to risk of cardiovascular disease . However , prospect i ve studies of these associations in a free-living population are lacking . METHODS We measured serum H. pylori IgG , C. pneumoniae IgG and IgA , and CMV IgG levels in Framingham Heart Study cohort participants . Blood sample s were drawn during the 16th biennial examination cycle ( 1979 to 1982 ) from 1,187 participants free of cardiovascular disease ( mean age 69 years ) and stored at -20 degrees C. A pooled primary end point of myocardial infa rct ion , atherothrombotic stroke , and coronary heart disease deaths was studied in relation to serology . Using a Cox model , hazard ratios ( HR ) and 95 % confidence intervals ( CI ) were calculated , adjusting for age , gender , and established risk factors . RESULTS Seropositivity to H. pylori IgG , C. pneumoniae IgG , C. pneumoniae IgA , and CMV IgG was 60 % , 45 % , 11 % , and 69 % , respectively . During 10 years of follow-up , incident cardiovascular disease occurred in 199 participants ( 16.8 % ) . In age- and gender-adjusted models , H. pylori IgG ( HR 1.09 , 95 % CI 0.81 to 1.46 ) , C. pneumoniae IgG ( HR 0.91 , 95 % CI 0.68 to 1.20 ) , C. pneumoniae IgA ( HR 0.65 , 95 % CI 0.39 to 1.07 ) , and CMV IgG ( HR 0.84 , 95 % CI 0.62 to 1.12 ) were not associated with incident cardiovascular disease . These associations were further attenuated after adjustment for risk factors including body mass index , total and high-density lipoprotein cholesterol , diabetes mellitus , smoking , and hypertension . These estimates did not change for the individual components of cardiovascular disease , and seropositivity to more than one organism did not alter these risk estimates substantially . CONCLUSIONS In this elderly cohort , chronic H. pylori , C. pneumoniae , and CMV infections , as evidence d by seropositivity , were not associated with increased risk for cardiovascular disease . Additional studies are needed to determine the relations of chronic infections to cardiovascular disease risk in younger persons To clarify the sequence of alterations in the thrombotic and fibrinolytic systems after acute brain infa rct ion , we prospect ively examined sequential changes in coagulatory markers in 38 patients suffering from cardioembolic infa rcts ( CEI ) , 41 patients with atherothrombotic infa rcts ( ATI ) , 58 patients with lacunar infa rcts ( LI ) , and 32 age-matched controls . The plasma level of thrombin-antithrombin III complex ( TAT ) , fibrinopeptide A ( FpA ) , D-dimer , fibrin degradation products-E ( FDP-E ) , fibrinogen , alpha2-plasmin inhibitor-plasmin complex ( PIC ) , and percent activity of antithrombin III ( AT-III ) were measured within 48 h , at 1 week , and at 3 weeks after the stroke onset . Significantly elevated levels of TAT and FpA , which are both markers of thrombin formation , were observed in CEI patients , and these elevated levels were associated with increasing D-dimer levels for 3 weeks ( P<0.0001 ) . D-Dimer in CEI patients was significantly elevated compared to control , LI and ATI levels within 48 h ( P<0.001 ) . Percent activity of AT-III was significantly decreased in CEI patients for 3 weeks compared to this activity in controls , LI and ATI ( P<0.001 ) . TAT and FpA also increased significantly within 48 h in ATI subjects and declined thereafter . A significant elevation of FDP-E ( P<0.001 ) and D-dimer ( P<0.05 , P<0.01 ) was detected in parallel with increasing fibrinogen for 3 weeks . However , there was no significant depletion of percent activity of AT-III in ATI . In LI subjects , no significant elevation of TAT , D-dimer or FDP-E were observed within 1 week . PIC increased significantly in three subtypes of brain infa rcts , but did not differ significantly among the three subtypes for 3 weeks . An accurate assessment of sequential alterations in thrombotic and fibrinolytic markers in the acute stage of brain infa rct should contribute to the clinical diagnosis of brain infa rct subtype . Alterations in these markers in response to activation of the coagulatory system are attributable to the different pathogenesis of ischemic stroke To study the possible risk factors for cardiovascular disease , we collected data on plasma levels of coagulation factors , blood pressure , serum cholesterol , and smoking in a r and om sample of 792 men 54 years of age . During 13.5 years of follow-up , myocardial infa rct ion occurred in 92 men , stroke in 37 , and death from causes other than myocardial infa rct ion or stroke in 60 . The blood pressure , degree of smoking , serum cholesterol , and fibrinogen level measured at the base-line examination proved to be significant risk factors for infa rct ion by univariate analyses during follow-up , and blood pressure and fibrinogen were risk factors for stroke . Fibrinogen and smoking were strongly related to each other . The relation between fibrinogen and infa rct ion , and between fibrinogen and stroke , became weaker when blood pressure , serum cholesterol , and smoking habits were taken into account , but was still significant for stroke . Although causality can not be inferred from these data , it is possible that the fibrinogen level plays an important part in the development of stroke and myocardial infa rct ion Plasma fibrinogen is a consistent predictor of ischemic heart disease ( IHD ) in prospect i ve studies , but there are fewer data relating other hemostatic variables to IHD and also to stroke . We therefore studied the relationships of plasma fibrinogen , von Willebr and factor antigen , tissue plasminogen activator ( TPA ) antigen , factor VII , and fibrin D-dimer to incidence of IHD and stroke and determined whether any associations could be explained by conventional risk factors and baseline heart disease . In the Edinburgh Artery study , 1592 men and women aged 55 to 74 years , r and omly sample d from the general population , were followed prospect ively over 5 years to detect fatal and nonfatal IHD and stroke events . During the 5 years , 268 new vascular events were identified . Baseline plasma fibrinogen was independently related to risk of stroke in multivariate analysis that adjusted for cigarette smoking , LDL-cholesterol , systolic blood pressure , and preexisting IHD ( relative risk [ RR ] 1.52 , 95 % confidence interval [ CI ] 1.17 , 1.98 ) . TPA antigen , and fibrin D-dimer were also independently associated with risk of stroke ( RR 1.69,95 % CI 1.22,2.35 and RR 1.96 , 95 % CI 1.12,3.41 , respectively ) . Significant relationships were found between TPA antigen and myocardial infa rct ion ( P < or = .05 ) . In older men and women , increased coagulation activity and disturbed fibrinolysis are predictors of future vascular events ( both IHD and stroke ) |
12,719 | 17,054,211 | There appeared to be a short-term effect of approximately 50 % hair reduction with alex and rite and diode lasers up to six months after treatment , whereas little evidence was obtained for an effect of intense pulsed light , neodymium : YAG or ruby lasers .
Long-term hair removal was not documented with any treatment .
Pain , skin redness , swelling , burned hairs and pigmentary changes were infrequently reported adverse effects .
Some treatments lead to temporary short-term hair removal . | BACKGROUND Unwanted hair growth is a therapeutic challenge and considerable re sources are spent to achieve a hair-free appearance .
Epilation with laser devices ( alex and rite , diode , neodymium : YAG , and ruby lasers ) and intense pulsed light are commonly used although the long-term effect is uncertain .
OBJECTIVES To assess the effects of epilation with lasers and light sources . | Background . Multiple laser systems are available for the purpose of hair removal . Objective . The purpose of this study was to determine the safety and long‐term efficacy of the 800 nm , pulsed diode laser at reducing hair count . Methods . Fifty volunteers , primarily Fitzpatrick skin types II and III , with dark brown or black hair , were treated with a diode laser ( 800 nm , 10–40 J/cm2 , 5–30 msec , 9 mm 9 mm , 5 ° C chilled h and piece ) . Each subject had eight treatment sites at varying fluences and pulse duration s , as well as a varying number of treatments and pulses . Hair counts were obtained at each site at baseline , 1 , 3 , 6 , 9 , and an average of 20 months after treatment . Results . After one treatment , hair regrowths ranged from 22 to 31 % at the 1‐month follow‐up visit , then remained stable between 65 and 75 % from the 3‐month to the averaged 20‐month follow‐up . After two treatments there were relatively longer growth delays , with hair regrowths plateauing beginning at 6 months after treatment and ranging from 47 to 66 % for the remainder of the follow‐up evaluations . Side effects were limited to pigmentary changes , transient in subjects with skin types II and III . Conclusions . This 800 nm diode laser with a chilled sapphire tip and variable pulse duration is safe and effective for long‐term hair reduction in individuals with skin types II and III Background . The C and ela alex and rite and the Coherent diode laser systems come equipped with built‐in skin cooling systems that are design ed to both protect the epidermis , allowing higher fluences , and to alleviate discomfort . Nevertheless , pain can be a significant problem especially with treatment of larger areas . Scatter of the laser beam is reportedly affected by the spot size . It is cl aim ed that larger spot sizes are more effective at identical fluences . Objective . This study evaluated the effectiveness of a topical 5 % lidocaine cream ( ELA‐Max ) to control pain and compared pain levels at identical fluences between the 8 mm and 12 mm spot size of the alex and rite laser and between the alex and rite and diode laser with its 9 mm spot size . Methods . The study was conducted in the axillae of 12 patients . Each axilla was divided in half for side‐by‐side comparison . Half of the right axilla was treated with the alex and rite 8 mm and the other half with the 12 mm spot size at identical fluences . The left axilla was treated at the maximum tolerated fluences with the alex and rite 12 mm spot size and the diode 9 mm spot size . Results . At identical fluences and other parameters , there was significantly more pain with the alex and rite 12 mm spot size than with the alex and rite 8 mm spot size , both with or without topical anesthesia . The alex and rite laser was significantly less painful than the diode laser both with and without topical anesthetic . The difference was most noticeable between the alex and rite 8 mm spot size and the diode 9 mm spot size . Topical 5 % lidocaine anesthesia was effective in reducing pain , though not completely , for both the alex and rite and the diode lasers . Conclusion . Topical 5 % lidocaine cream is a simple and effective method for reducing patient discomfort during laser hair removal procedures , even when a skin cooling device is being used . A larger spot size causes more pain than a smaller spot size at identical fluences . The 800 nm diode laser causes greater discomfort than the 755 nm alex and rite laser Promising clinical results have been obtained with the normal mode ruby laser for removal of unwanted hair . Melanin within the hair follicles is thought to act as target for the ruby laser pulses , whereas epidermal melanin is thought to be a competitive chromophore , responsible for potential side effects . This study aim ed ( i ) to objectify postoperative changes in skin pigmentation and texture and ( ii ) to evaluate the importance of variations in preoperative skin pigmentation for the development of side effects 12 weeks after 1 treatment with the normal-mode ruby laser . A total of 17 volunteers ( skin types I-IV ) were laser-treated in the hairy pubic region ( n = 51 test areas ) . A shaved test area served as control . Skin reflectance spectroscopical measurements , 3-dimensional surface contour analysis and ultrasonography objectified postoperative changes in skin pigmentation and texture . Blinded clinical assessment s revealed postoperative hyperpigmentation ( 2 % of test areas ) and hypopigmentation ( 10 % ) , whereas no textural changes were seen . Reflectance spectroscopically-determined pigmentary changes depended on the degree of preoperative skin pigmentation , fairly pigmented skin types experiencing sub clinical hyperpigmentation and darkly pigmented skin types experiencing sub clinical hypopigmentation . Three-dimensional surface profilometry documented similar pre- and postoperative surface contour parameters , indicating that the skin surface texture is preserved after laser exposure . Ultrasonography revealed similar skin thicknesses in laser-exposed and untreated control areas . It is concluded that normal-mode ruby laser treatment is safe for hair removal in skin types I-IV BACKGROUND AND OBJECTIVES The aim was to study hair removal efficacy , and possible side effects of two commercially available long pulsed diode lasers . The radiant exposure was selected to a value of 35 J/cm2 , which is frequently used in the clinic in accordance with manufacturer 's recommendations . STUDY DESIGN / MATERIAL S AND METHODS A prospect i ve clinical study was performed on twenty-nine patients with hair color ranging from light brown to black on the upper lip . One half of the upper lip was r and omly selected for treatment with the MedioStar laser ; the contralateral half of the lip was treated with the LightSheer laser . Three treatments were performed at 6 - 8 week intervals . Percent hair reduction and acute- and long-term side effects were evaluated after treatment . RESULTS The average hair reductions 6 months after the first treatment were 49 % with the MedioStar laser and 48 % with the LightSheer laser . No scarring or pigmentary change of the skin was observed after any of the treatments with either laser . However , differences in acute side effects such as degree of erythema and burned hairs were observed . CONCLUSIONS No statistically significant differences in hair removal efficacy were observed . These results agree with mathematical modeling , which also offers a method to estimate hair removal efficacy and adverse effects for a range of hair characteristics and laser parameters BACKGROUND AND OBJECTIVE The aim was to investigate the efficacy , side effects , and the long-term results of a long pulsed Nd : YAG-Laser for hair removal in different hair colors and skin types . STUDY DESIGN / MATERIAL S AND METHODS We performed a prospect i ve clinical study with 29 volunteers . Treatment was performed on the lower leg with a long pulsed Nd : YAG-Laser . Five test areas were treated 1 - 5 times in monthly intervals ; one served as control . Follow-up investigations were performed at each session , and 3 , 6 , and 12 months after the last therapy . No depilatory treatment except shaving was allowed during the time of follow-up . Percentual hair loss , short- and long-term side effects , and pain during the treatment were evaluated . RESULTS After one month , a hair loss of greater than 50 % was found in 44.9 % of the areas treated once . With up to five treatments , this percentage increased up to 71.5 % . One year after therapy , a greater than 50 % hair reduction was still present in 40 % of the five-treatment- areas and in 0 % of the areas treated only once . There were no permanent side effects despite one small scar after a folliculitis . CONCLUSIONS The long pulsed Nd : YAG is suitable to remove hair for more than 12 months effectively , although 4 - 5 sessions are necessary for these results . Blond hair can also be removed , although much less effective . No lasting side effects could be seen . Darker skin types or tanned skin can also be treated without side effects . A cooling may be advisable due to the pain reported by the volunteers OBJECTIVE To determine the safety and effectiveness of a long-pulsed Nd : YAG laser at 1064 nm in effecting long-term hair reduction in patients with darkly pigmented skin . DESIGN Nonr and omized before-after clinical and histological trial . SETTING Private practice , ambulatory care facility . PATIENTS Twenty women with skin phototypes IV through VI and dark brown to black terminal hair on the face , axillae , or legs . INTERVENTION A series of 3 long-pulsed ( 50-millisecond ) 1064-nm Nd : YAG laser treatments at fluences ranging from 40 to 50 J/cm(2 ) were delivered to the identified treatment areas on a monthly basis by a single operator . MAIN OUTCOME MEASURES Global clinical grading scores of comparable before-after treatment photographs were determined by 2 independent medical assessors during each laser session and 1 , 3 , 6 , and 12 months postoperatively . A dermatopathologist review ed unmarked histological specimens obtained at baseline , immediately after the initial laser treatment , and at 1 and 6 months after the final laser session . RESULTS Substantial hair reduction was seen after each of the 3 treatment sessions . Prolonged hair loss was observed 12 months after the final laser treatment ( 70%-90 % hair reduction ) . Axillary hair was substantially more responsive to laser irradiation than was hair located on the legs and face . Adverse effects included mild to moderate treatment pain and rare occurrences of vesiculation and transient pigmentary alteration without fibrosis or scarring . Histological tissue changes mirrored clinical response rates , with evidence of selective follicular injury without epidermal disruption . CONCLUSION The long-pulsed 1064-nm Nd : YAG laser is a safe and effective method of long-term hair reduction in patients with darkly pigmented skin Laser-assisted hair removal has been reported previously with the Nd : YAG laser , the long-pulse ruby laser , the long-pulse Alex and rite laser , and the short-pulse Alex and rite laser . Results with all these lasers have been successful ; however , it has been postulated that the long-pulse Alex and rite laser would have a lower complication rate and greater efficacy at identical fluences than the short-pulse Alex and rite laser . The authors chose to compare directly the pulsed Alex and rite lasers for speed of application , complications , and results . Eighteen patients who desired hair removal were entered into the study . There were 10 female and 8 male patients , with a mean age of 36 years . All skin types from Fitzpatrick classes I through VI were treated . The body areas treated consisted of the face , ears , neck , back , arms , upper thighs , bikini lines , legs , and breasts . One side of the body was treated with the short-pulse ( 2-msec ) Alex and rite laser ( Sharplan Epitouch 5100 ) . The other half was treated with a long-pulse ( 20-msec ) Alex and rite laser . Both lasers were set at the same fluence for each patient . Patients reported a 60 % to 80 % reduction in hair growth at 6 months . Both sides were identical with regard to return of hair growth and complications such as hypopigmentation . Both the long- and short-pulse Alex and rite laser systems yielded an effective method of hair reduction with minimal complications . Equal results and complications were obtained with the two systems . The only exception was that the length of the procedure was shorter with the short-pulse Alex and rite laser OBJECTIVE To determine the most effective treatment parameters for laser-assisted hair removal using a Q-switched neodymium : yttrium-aluminum-garnet ( Nd : YAG ) laser . DESIGN Prospect i ve study to determine the effectiveness of Q-switched ND : YAG laser-assisted hair removal under varying pretreatment protocol s. Hair growth was assessed after laser treatment , and the results were compared with those of wax epilation at 4 , 12 , and 24 weeks . SETTING A private ambulatory laser facility and academic referral center . INTERVENTION Laser-assisted hair removal was performed under 4 different pretreatment conditions . Eighteen areas of unwanted body and facial hair from 12 study subjects were divided into 4 quadrants . Wax epilation followed by application of a carbon-based solution and exposure to Q-switched Nd : YAG laser radiation was performed on 1 quadrant . A second quadrant was wax epilated and exposed to Q-switched Nd : YAG laser radiation without prior carbon solution application . A third quadrant was exposed to laser radiation alone , and a final quadrant was wax epilated to serve as the control . Follow-up evaluations at 1 , 3 , and 6 months consisted of photographic documentation , manual hair counts , and patient hair-density estimates . MAIN OUTCOME MEASURE Percentage of hair regrowth as assessed by objective hair counts and patient subjective evaluations . RESULTS Mean percentage of hair regrowth at 1 month was 39.9 % for the wax-carbon-laser quadrant , 46.7 % for the wax-laser quadrant , 66.1 % for the laser-alone quadrant , and 77.9 % for the wax control quadrant . The percentage of hair regrowth approximately doubled by 3 months but was significantly delayed in all laser-treated quadrants regardless of pretreatment protocol . Full hair regrowth in all anatomic locations was observed by month 6 . Patient subjective evaluations of hair density closely approximated hair count data . No adverse effects or long-term complications were observed . CONCLUSIONS A single hair-removal treatment with the Q-switched Nd : YAG laser is safe and effective in delaying hair growth for up to 3 months . Although the combination of pretreatment wax epilation and topical carbon solution application was effective , laser irradiation alone , with or without wax epilation , also provided a significant delay in hair growth BACKGROUND Recent reports indicate that laser hair removal is most effective on anagen hairs . However , no published trials have examined laser epilation after hair cycle synchronization . OBJECTIVE To evaluate the potential for enhanced laser hair removal after the induction of telogen hairs into anagen by wax epilation . METHODS We identified four 2.5-cm square areas with equivalent hair length and density on the backs of 13 dark-haired white men . To induce typically telogen hairs into anagen , two areas on each patient were wax epilated . Two weeks later , one waxed area and one unwaxed area were treated with a long-pulsed alex and rite laser . One month after laser treatment , a subjective comparison was made based on hair density , length , and thickness . RESULTS In 12 of 13 patients , lasered areas that had been pretreated with wax epilation were clearer of hair as compared with areas that had been pretreated by shaving ( P = 0.0034 ) . No significant difference was noted between waxed and unwaxed control areas that had not been laser treated ( P = 1.0 ) . CONCLUSION Wax epilation 2 weeks before laser hair removal improves cosmetic outcomes at 1 month . This effect may be secondary to the recruitment and heightened sensitivity of early anagen hairs Background Facial hirsutism is one of the characteristic features of polycystic ovary syndrome ( PCOS ) , and this can lead to high levels of depression and anxiety . BACKGROUND The use of lasers for removal of unwanted hair has been shown to be effective in temporarily controlling hair growth . Several lasers are currently utilized for this purpose . OBJECTIVE This study evaluates the short-term effectiveness and discomfort levels of the long-pulsed alex and rite laser and the topical suspension-assisted Q-switched Nd : YAG laser in a side-by-side comparison . METHODS Fifteen subjects were treated in the bilateral hair-bearing axilla , using one treatment with the alex and rite laser for the right and two treatments with the topical suspension-assisted Nd : YAG laser for the left . Reduction in hair regrowth was measured at 2 and 3 months following the first treatment by comparing the terminal hair count to the baseline values . Patients rated their pain on a scale of 0 - 10 immediately following the first treatment at each site . RESULTS The mean percentage reduction in hair regrowth 2 months following alex and rite laser treatment was 55 % and 73 % for the Nd : YAG laser-treated regions . After 3 months , alex and rite laser-treated patients showed a reduction of 19 % , while Nd : YAG laser-treated patients showed a 27 % reduction . Patients reported average pain values of 8 and 4 for the long-pulsed alex and rite and Nd : YAG laser sites , respectively . All differences were significant . CONCLUSION While the design of this study makes it difficult to compare the relative effectiveness of the lasers , both systems evaluated were shown to delay hair growth and provide patients with a satisfactory treatment BACKGROUND Unwanted facial and body hair is a common problem , generating a high level of interest for treatment innovations . Advances in laser technology over the past several years has led to the development and distribution of numerous red and infrared lasers and light sources to address this issue . Despite the impressive clinical results that have been reported with the use of individual laser hair removal systems , long-term comparative studies have been scarce . OBJECTIVE To compare the clinical and histologic efficacy , side effect profile , and long-term hair reduction of long-pulsed diode and long-pulsed alex and rite laser systems . METHODS Twenty women with Fitzpatrick skin types I – IV and dark terminal hair underwent three monthly laser-assisted hair removal sessions with a long-pulsed alex and rite laser ( 755 nm , 2-msec pulse , 10 mm spot ) and a long-pulsed diode laser ( 800 nm , 12.5 msec or 25 msec , 9 mm spot ) . Axillary areas were r and omly assigned to receive treatment using each laser system at either 25 J/cm2 or 40 J/cm2 . Follow-up manual hair counts and photographs of each area were obtained at each of the three treatment visits and at 1 , 3 , and 6 months after the final laser session . Histologic specimens were obtained at baseline , immediately after the initial laser treatment , and 1 and 6 months after the third treatment session . RESULTS After each laser treatment , hair counts were successively reduced and few patients found it necessary to shave the sparsely regrown hair . Optimal clinical response was achieved 1 month after the second laser treatment , regardless of the laser system or fluence used . Six months after the third and final treatment , prolonged clinical hair reduction was observed with no significant differences between the laser systems and fluences used . Histologic tissue changes supported the clinical responses observed with evidence of initial follicular injury followed by slow follicular regeneration . Side effects , including treatment pain and vesiculation , were rare after treatment with either laser system , but were observed more frequently with the long-pulsed diode system at the higher fluence of 40 J/cm2 . CONCLUSION Equivalent clinical and histologic responses were observed using a long-pulsed alex and rite and a long-pulsed diode laser for hair removal with minimal adverse sequelae . While long-term hair reduction can be obtained in most patients after a series of laser treatments , partial hair regrowth is typical within 6 months , suggesting the need for additional treatments to improve the rate of permanent hair removal Lasers have been established as effective treatment for hair removal , with possible long-term suppression of hair growth in treated areas . The purpose of this study was to assess long-term hair regrowth after treatment with the ruby laser . Volunteers recruited into the 1997–99 study were divided between three treatment groups , each having left and right treatment sides . Two treatments were given on both sides at monthly intervals . A third treatment was given r and omly to one side . Hair counts of the experimental sites were made at monthly intervals for 1 year . The three patient groups were : top lip ( 25 ) , axillae ( 25 ) and legs ( 19 ) . Long-term hair reduction was achieved in all patients . A single treatment reduced hair counts by up to 75 . Three treatments had an impact for 2 additional months , but not long term . Unexpected spontaneous hair reduction was found 5 months following treatment and lasted 2 months . This ruby laser produced a persistent two-thirds reduction in hair count over 8 months of follow-up . Extension of the follow-up to 12 months did not show significant regrowth . Existing experimental data , together with the results of this study , suggest that hair shaft damage is the key feature in achieving damage to the hair-producing mechanism . The correlation of treatment success and anagen growth phase is less likely INTRODUCTION / OBJECTIVE : This study aim ed to evaluate the safety and efficacy of a 3.5 ms Nd : YAG laser for the removal of hair in subjects with Fitzpatrick skin types I-IV . Thanks to a pulse shorter than the hair Thermal Relaxation time ( TRT ) , photothermolysis was thus achieved . METHODS : This study assessed the percentage of hair reduction at 1 month and at 3 months after a single Nd : YAG laser treatment ( Athos ; Quantel Médical , France ) ; 3.5 ms pulse , single shot to 3 Hz , a maximum fluence of 80 J/cm 2 , 4 mm spot , no cooling system , no anaesthesia . The treatment sites consisted of three adjacent squares ( optimum fluence , no treatment , -20 % optimum fluence ) . Computerized hair counting was realized on digital pictures . The phototype , pain , side effects and patient 's satisfaction were noted . Biopsies were performed 15 min after treatment . The enrolment consisted of 17 women , 22 - 60 years old , phototypes I-IV , with a follow-up at 1 month and 3 months of 25 sites . RESULTS : Counting at 1 month and at 3 months revealed a significant hair reduction compared with the control sites : 60 % at 1 month ( P < 0.001 ) and 24 % at 3 months ( P < 0.05 ) for optimal fluence ( 25 - 80 J/cm 2 ) , compared with 31 % and 0 % on the control sites ; values similar to those published for Nd : YAG or diode lasers . There were no adverse effects at all . Biopsies showed lesions from necrosis coagulation of the root sheaths and hair disruption to isolated apoptotic cells in the outer root sheath , depending on the fluence applied . CONCLUSION : Results from this study show that the Athos Nd : YAG is efficient and safe for removing pigmented hair in phototypes I-IV objective : to investigate the safety and effectiveness of a long pulsed Nd : YAG ( 1064 nm ) laser compared to a shorter wavelength intense pulse light system for assisted hair removal in volunteers with skin type 1V , V and VI . methods : Eleven patients of Fitzpatrick skin type IV – VI were recruited into the study . The area treated included the face ( upper lips , chin and jaw area ) , axillae and legs . One half of the body was treated with the long pulse Nd : YAG laser and the other half was treated with the IPL system r and omly under topical anesthesia . Degree of pain experienced during treatment , the treatment outcome and any complications were observed . Patients were review ed at 2 weeks and 6 weeks post‐treatment . results : Volunteers generally described pain from the IPL system as “ prolonged burning sensation ” but tolerable . Pain from Nd : YAG laser treatment was described as “ pinprick ” and more intense but tolerable . “ Slowing of hair growth”was reported with IPL and Nd : YAG , but with a greater effect from Nd : YAG . Sixty‐four percent and 73%(8/11 ) noticed hair reduction < 20 % after 6 weeks on IPL and Nd : YAG treated side respectively ( ns ) . Post‐inflammatory pigmentation occurred in some volunteers on the IPL treated sides whereas this was not seen on any Nd : YAG treated side , and three of these patients experienced blistering , followed by post‐inflammatory pigmentation . conclusion : In our experience the long pulse width 1064 nm Nd : YAG laser , which can penetrate 5–7 mm into the dermis depths to reach the whole length of the hair follicle , would be expected to produce sufficient follicular injury with less epidermal damage in patients with darker skin type compared to shorter wavelength laser and light system . BACKGROUND Alex and rite laser hair removal can be quite successful in lighter skin types . Effective hair removal in Asians can be difficult , and multiple treatments are usually required for effective treatment . OBJECTIVE To evaluate the safety and efficacy of alex and rite laser hair removal in Asian skin , to determine the benefit of multiple treatments , and to evaluate the value of test patches before laser treatment . METHODS One hundred forty-four Asian subjects with Fitzpatrick skin types III to V were treated with a cooled 40-ms alex and rite laser with fluences of 16 to 24 J/cm2 . Initially , all treated subjects underwent test patch application . After test patch application , 35 subjects with 66 anatomic sites received three treatments . Thirty-five subjects with 66 anatomic sites received two treatments , and 74 subjects with 124 anatomic received a single treatment . All subjects were followed for 9 months after their final treatment . RESULTS In subjects that were treated three times , a 55 % hair reduction was noted at 9 months after the third treatment . In subjects treated two times a 44 % hair reduction was noted at 9 months after the second treatment . In subjects treated only one time , a 32 % hair reduction was noted at 9 months after the single treatment . No subjects had scarring or long-term pigmentary changes . There appeared to be no correlation between test patch acute complications and those seen after actual treatments . CONCLUSION Although Asian skin can be effectively treated with a cooled , long-pulsed alex and rite laser , complications do occur . Laser hair removal efficacy was increased with multiple treatments . There does not appear to be an exact correlation in Asian skin between complications occurring after test patch treatment and those seen with subsequent treatments BACKGROUND Numerous lasers are currently available for hair removal , yet there are still few studies that have examined the role of fluence , light dose , hair color , and treatment number in laser hair reduction . OBJECTIVE To demonstrate the efficacy and safety of a scanning 800 nm diode laser for hair reduction . METHODS An 800 nm scanning diode laser was used to deliver 24 , 38 , or 48 J/cm2 to a 3 cm × 3 cm area of skin located on the back , groin/bikini area , or thigh in 36 adult patients with varying shades of brown or black hair . Patients received one to four treatments during the course of the study . Hair loss was evaluated at both 30 and 90 days after final treatment . Biopsies were obtained from 20 consenting patients . RESULTS Significant fluence-dependent hair reduction was demonstrated between treatment and control groups . At 48 J/cm2 , the highest dose , a mean hair reduction of 43 % was achieved 30 days after the final treatment , and 34 % was achieved 90 days after the final treatment . Darker hairs were more effectively treated than lighter hairs . CONCLUSIONS Hair reduction can be safely and effectively achieved using a scanning 800 nm diode laser BACKGROUND Laser epilation is based on the principle of selective photothermolysis , absorption of laser energy by the target chromophore melanin . It is cl aim ed that larger spot sizes may be more effective for hair removal at identical fluences . OBJECTIVE To compare the efficacy of 18- vs. 12-mm spot size in hair removal using a Gentlelase Alex and rite laser from C and ela Corporation ( Boston , MA ) . METHODS In this double-blind , r and omized control trial , patients underwent laser-assisted hair removal on the axillary region . Regions were r and omly selected and treated with either an 18- or a 12-mm spot size . Three treatments at 6-week intervals with a 755-nm Gentlelase Alex and rite laser ( C and ela Corp. , Canton , MA ) at a fluence of 16 J/cm2 with cooling and delay times of 60 ms . Hair counts were taken before each treatment session and compared . The mean percentage hair reduction and student 's paired t-test were used to compare 18 versus 12 mm versus control sites at each visit and compared it with the baseline hair count . RESULTS There was a 10.3 % difference in mean reduction favoring the 18-mm spot size treated area at the 6-month follow-up . CONCLUSION Our results indicate that a larger spot size appears to be more effective for laser assisted hair removal BACKGROUND AND OBJECTIVE To evaluate the effects on disruption of hair growth of the non-coherent filtered flashlamp intense pulsed light ( IPL ) source . MATERIAL S AND METHODS Twenty-eight sites on 23 patients with Fitzpatrick type I-III were enrolled using a single treatment IPL followed for three months post-treatment . Another 56 on 48 patients with Fitzpatrick skin types I-V r and omly enrolled for two treatments one month apart and followed for six months . STUDY DESIGN Prior to beginning treatment and at each follow-up visit hair counts were obtained by averaging three 1-cm2 areas on a clear acetate template placed over the skin . Repeat hair counts and photographs were obtained at 2 , 4 , 8 , and 12 weeks for the single treatment protocol and at additional 4 , 5 , and 6 months for the double treatment protocol . Parameters utilized were a 2.8 - 3.2 millisecond pulse duration typically for three pulses with thermal relaxation intervals of 20 - 30 milliseconds with a total fluence of 40 - 42 J/cm2 . RESULTS For the double treatment protocol hair clearance of 64 % was achieved immediately following the second treatment . By week 8 reduction of hair counts was 42 % . At 6 months , hair counts were reduced by 33 % . CONCLUSIONS Non-coherent IPL is an effective modality for long-term hair removal . IPL is safe with minimal side effects of epidermal injury or pigmentation change |
12,720 | 20,151,955 | We conclude that avoiding nitrous oxide does reduce the risk of postoperative nausea and vomiting , especially in women , but the overall impact is modest | Some , but not all studies have suggested intra-operative use of nitrous oxide is correlated with postoperative nausea and vomiting . | Background : Different anesthetic agents have different effects on cerebrovascular physiology . However , the importance of these differences In neuroanesthetic practice are unclear . In an effort to determine whether important clinical differences are present , the authors compared three anesthetic techniques in 121 adults undergoing elective surgical removal of a supratentorial , intracranial mass lesion . Methods : Patients were assigned r and omly to one of three groups . In group 1 ( n=40 ) , anesthesia was induced with propofol and maintained with fentanyl ( ≊10 µg/kg load , 2 - 3 µg · kg-1 · h-1 infusion ) and propofol ( 50 - 300 µg · kg-1 · mln-1 ) . In group 2 ( n=40 ) , anesthesia was induced with thiopental and maintained with isoflurane and nitrous oxide . Up to 2 µg/kg fentanyl was given after replacement of the bone flap . In group 3 ( n=41 ) , anesthesia was induced with thiopental and maintained with fentanyl ( ≊10 µg/kg load , 2 - 3 µg · kg-1 · h1 infusion ) , nitrous oxide , and low-dose Isoflurane , if required . Blood pressure , heart rate , expired gas concentrations , and ventilatory parameters were recorded automatically in all patients . Epidural intracranial pressure ( ICP ) was measured via the first burr hole , brain swelling was rated at the time of dural opening , and emergence was monitored closely . Preoperative computed tomography or magnetic resonance imaging scans were evaluated , and pre- and postoperative neurologic exams were performed by a neurosurgeon unaware of group assignments . Total hospital stay ( days ) and total hospital cost ( exclusive of physician charges ) also were review ed . Results : During induction , higher heart rates were seen in isoflurane/nitrous oxide patients , whereas mean arterial pressure was ≊10 mmHg less during the maintenance phase ( compared with both other groups ) . Otherwise , there were few intergroup hemodynamic differences . While there were no clinical ly important intergroup differences in mean ICP (±SD)—group 1 , ICP=12 ± 7 mmHg ; group 2,15 ± 12 mmHg ; group 3 , ICP=11 ± 8 mmHg — more isoflurane/nitrous oxide patients ( nine , group 2 ) had an ICP £ 24 mmHg than in the other groups ( two each ) . Emergence was , overall , more rapid with fentanyl/nitrous oxide . For example , the median time until the patient could be awakened by quiet verbal comm and , e.g. , “ Open your eyes , ” was 5 min , versus 10 min in the other groups . There were no relationships between ICP and any measurement of emergence ( e.g. , time to response to comm and s ) . Seven of 41 ( 17 % ) fentanyl/nitrous oxide patients vomited In the early postoperative period , compared with only 1 of 40 ( 2.5 % ) of those given propofol/fentanyl and 2 of 40 ( 5 % ) receiving isoflurane/nitrous oxide ( P=0.03 ) . There were no differences in the incidence of new postoperative deficits , total hospital stay , or cost . Conclusions : Although there are modest differences among the three tested anesthetics , short-term outcome was not affected . These results indicate that , despite their respective cerebrovascular effects , all of the anesthetic regimens used were acceptable in these patients undergoing elective surgery During the last years huge amounts of literature have been review ed systematic ally . Recently , guidelines have been proposed . For the first time a large prospect i ve study has been performed on the effect of combining antiemetics . In this review we try to propose a rational approach to postoperative nausea and vomiting . The scoring of patients at risk , rational anaesthetic agents , prophylactic administration of antiemetics to patients at risk and effective postoperative antiemetic treatment are suggested Background : Nitrous oxide rapidly inflates gas‐filled spaces such as the intestines ; but whether the result ing bowel distension is clinical ly important remains unclear . We therefore tested the hypothesis that nitrous oxide produces clinical ly important bowel distension The incidence of postoperative nausea and vomiting and requirements for anti-emetic medication were assessed in 80 female patients undergoing day-case anaesthesia during assisted conception therapy . Anaesthesia was induced with alfentanil 50 μg · kg−1 and propofol 1 mg · kg−1 ; atracurium 0.5 mg · kg−1 was given to facilitate tracheal intubation . The patients were allocated to receive either total intravenous maintenance of anaesthesia with an infusion of propofol and increments of alfentanil ( Group P ) or inhalational maintenance of anaesthesia with nitrous oxide and enflurane ( Group E ) . Postoperative nausea , retching , vomiting , requirements for anti-emetic therapy , and unplanned admission for overnight stay in hospital were recorded . Overall incidence of nausea was 64 % in group E and 39 % in Croup P ( P < 0.05 ) . Incidence of vomiting was 67 % in Group E and 34 % in Group P ( P < 0.05 ) . Metoclopramide was requested by 62 % of patients in Group E , and 32 % of those in Group P ( P < 0.05 ) ; 21 % of the patients in Group E were admitted to hospital overnight , while only 5 % of the patients in Group P required unscheduled admission to hospital ( P < 0.05 ) . We conclude that total intravenous anaesthesia with propofol and alfentanil is superior to inhalational maintenance with nitrous oxide and enflurane in that it is associated with less nausea and vomiting , less requirement for anti-emetic medication , and a lower probability of unplanned admission to hospital after day-care gynaecological surgery . RésuméL’incidence de nausées et vomissements en période postopératoire et le besoin de médication antiémétique a été évalué chez 80 patientes devant subir une anesthésie ( cas d’un jour ) pendant une séance de conception assistée . L’induction de l’anesthésie s’est faite à l’aide d’alfentanil 50 μg · kg−1 et de propofol 1 mg · kg−1 ; l’intubation endotrachéale a été facilitée à l’aide d’atracurium 0,5 mg · kg−1 . L’anesthésie était maintenue soit à l’aide d’une technique intraveineuse totale , en utilisant une infusion de propofol et des bolus d’alfentanil ( groupe P ) , soit à l’aide d’une technique d’inhalation en utilisant le protoxyde d’azote et l’enflurane ( groupe E ) . Pendant la période postopératoire , les nausées , les efforts de vomissement , les vomissements , le besoin de thérapie antiémétique , et les admissions hospitalières imprévues pour une nuit étaient notés . L’incidence globale de nausées était de 64 % dans le groupe E et 39 % dans le groupe P ( P < 0,05 ) . L’incidence de vomissements était de 67 % dans le groupe E et de 34 % dans le groupe P ( P < 0,05 ) . Soixante-deux pourcent des patientes du groupe E ont dem and é du métoclopramide , comparativement à 32 % du groupe P ( P < 0,05 ) ; 21 % des patientes du grope E ont été admises à l’hôpital pour une nuit , t and is que seulement 5 % des patientes du groupe P l’ont été ( P < 0,05 ) . Nous concluons que l’anesthésie à l’aide d’une technique intraveineuse totale , avec propofol et alfentanil , est supérieure à une anesthésie par inhalation à l’aide de protoxyde d’azote et d’enflurane car elle est associée à une incidence moins élevée de nausées et vomissements , un besoin moindre de médication antiémétique , et une probabilité plus faible d’admissions hospitalières imprévues après une chirurgie gynécologique d’un jour An intravenous anesthetic drug , propofol was considered to pose antiemetic action . A r and omized controlled trial was conducted to evaluate whether propofol could effectively reduce post-operative nausea and vomiting ( PONV ) compared to thiopental-nitrous oxide ( N2O ) . One-hundred and eight patients undergoing outpatient gynecologic laparoscopy were assigned to receive 3 techniques of anesthesia ; thiopental-N2O ( T/N ) , propofol-N2O ( P/N ) and total intravenous anesthesia ( TIVA ) using propofol ( P/P ) . The results showed that in the early period ( 0 - 5 hours ) , post-operative nausea in T/N , P/N and P/P groups was 72 per cent , 44 per cent and 31 per cent , respectively ( P = 0.002 ) , and post-operative vomiting was 58 per cent , 36 per cent and 11 per cent respectively ( P = 0.00014 ) . Patients in the P/N and P/P groups experienced nausea less frequently than the T/N group [ relative risk ( RR ) = 0.62 , ( 95 % CI 0.41 - 0.93 ) and RR = 0.42 ( 0.25 - 0.72 ) respectively ] . Patients in the P/N and P/P groups experienced vomiting less frequently than the T/N group [ RR = 0.62 ( 0.37 - 1.04 ) and RR = 0.19 ( 0.07 - 0.5 ) respectively ] . Two patients in the T/N group were admitted because of severe nausea and vomiting . In conclusion , TIVA using propofol and propofol-N2O anesthesia can significantly reduce the incidence of PONV in the early period . Concerning the economic crisis of the country as well as the quality of care , propofol-N2O would be the most appropriate anesthetic of choice 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 Refractory postoperative nausea and vomiting ( PONV ) requiring repeated treatment with antiemetic drugs is a miserable experience for the patient that may substantially increase the cost of care . As risk stratification may aid in prophylaxis and treatment , we explored risk factors for severe PONV in patients enrolled in a large international , r and omized controlled trial ( the ENIGMA trial ) . METHODS Two thous and and fifty patients , aged > or = 18 yr and undergoing surgery anticipated to exceed 2 h in duration , were recruited . Patients were r and omized to nitrous oxide ( N(2)O)-based or N(2)O-free anaesthesia . Choice of other anaesthetic , analgesic , and antiemetic drugs was left to the discretion of the anaesthetist . Anaesthetic depth was adjusted according to clinical judgement and , if available , bispectral index ( BIS ) monitoring . Severe PONV was defined as : ( i ) two or more episodes of expulsion of gastric contents at least 6 h apart ; ( ii ) received at least three doses of antiemetic medication for treatment of PONV , within 24 h of surgery ; or both . We used logistic regression , and classification and regression tree analysis , to define risk factors for severe PONV . RESULTS Three hundred and thirty-three ( 16.6 % ) patients experienced severe PONV . Age < 55 yr , female sex , abdominal surgery , N(2)O administration , absence of BIS monitoring , and longer duration of anaesthesia were predictors of severe PONV [ area under receiver operating characteristic curve=0.70 ( 95 % confidence interval : 0.67 - 0.73 ) ] . CONCLUSIONS Severe PONV was common and risk factors for it were similar to those reported in other studies that included all patients reporting nausea , vomiting , or both Eighty‐seven patients undergoing routine laparcscopy were divided r and omly into two groups to study the effect of nitrous oxide anaesthesia on the incidence of postoperative vomiting . Patients in group A received nitrous oxide as part of their anaesthetic , while in group B nitrous oxide was omitted . Significantly fewer patients in group B vomited when compared with group A ( 17 percent and 49 percent respectively ; p < 0.005 ) . We suggest that an anaesthetic technique which avoids nitrous oxide may be especially indicated in patients undergoing laparoscopy 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 STUDY OBJECTIVE To evaluate the effect of nitrous oxide ( N2O ) on the recovery profile and the incidence of postoperative nausea and vomiting ( PONV ) after office-based surgery performed under propofol anesthesia . DESIGN Prospect i ve , r and omized , single-blind study . SETTING Office-based surgical center . PATIENTS 69 ASA physical status I , II , and III healthy , consenting out patients undergoing superficial surgical procedures lasting 15 to 45 minutes . INTERVENTIONS After a st and ard propofol induction ( 1.5 mg.kg-1 i.v . ) , anesthesia was initially maintained with propofol , 100 micrograms.kg-1.min-1 i.v . , in combination with either air or N2O 65 % in oxygen . The propofol infusion rate was subsequently varied to maintain an adequate depth of anesthesia . All patients received local anesthetic infiltration prior to the surgical incision , as well as during the operation . No prophylactic antiemetics were administered . MEASUREMENTS AND MAIN RESULTS Recovery times and the incidences of PONV were recorded during the first 24 hours after surgery . Early and late recovery variables were similar in the two treatment groups ; however , 65 % N2O produced a 19 % decrease in the propofol maintenance dosage requirement . One patient ( 3 % ) experienced nausea prior to discharge in the propofol-N2O group , and two patients ( 6 % ) experienced nausea at home in the propofol alone group . None of the patients vomited or received antiemetic medication during the 24 hours postdischarge period . Ninety-seven percent of patients receiving propofol alone and all of the patients in the propofol-N2O group were " very satisfied " with their anesthetic experience . CONCLUSIONS In out patients undergoing office-based surgical procedures with propofol anesthesia , administration of 65 % N2O decreased the anesthetic requirement without increasing PONV . Therefore , use of a propofol-N2O combination may be a cost-effective alternative to propofol alone for office-based anesthesia A total of 110 patients undergoing elective abdominal hysterectomy were anesthetized in r and om order with either isoflurane in nitrous oxide and oxygen or isoflurane in air and oxygen . Fentanyl was used as an adjunct to isoflurane in all patients , 0.05 mg every 45 min . No difference was found between the two anesthetic techniques in the incidence of nausea , vomiting , or both during the first 24 hr after operation . The overall incidence was 62 and 67 % for air-O2 and N2O-O2 groups , respectively . Patients who had had nausea or vomiting after previous anesthetics had nausea or vomiting significantly more frequently than patients who did not . It is concluded that nitrous oxide does not contribute to the occurrence of nausea or vomiting after isoflurane anesthesia for gynecologic laparotomies We studied 40 patients undergoing minor gynaecological surgery , anaesthetized in r and om order with sevoflurane-nitrous oxide or thiopental-fentanyl . Operating conditions , pain , recovery and postoperative nausea and vomiting were assessed . For postoperative analgesia , all patients were given dypiron 1 g intravenous at the end of anaesthesia . Patients and gynaecologists were equally satisfied with both anaesthetic techniques . The time of surgery were higher in patients given sevoflurane , ( 7 versus 5 minutes ) this women had recovery faster ( 17 versus 72 minutes ) became orientated , followed orders ( 11 versus 19 minutes ) and were able to walk ( 17 versus 60 minutes ) significantly ( p < 0.05 ) earlier than those given thiopental . Modified Aldrete scores were also higher in sevoflurane group within the first hour after anaesthesia , there were no differences in woke up ( 9 versus 12 minutes ) vital constants , intrauterine bleeding , pain , and frequency of postoperative nausea and vomiting ( 10 % versus 10 % ) between the two groups . We conclude that sevofluranenitrous-oxide is preferable to thiopental-fentanyl in ultra-short anaesthesia for minor gynaecological surgery We have investigated the effect of nitrous oxide on the middle ear pressure , comparing inhalational anaesthesia with nitrous oxide and halothane and total intravenous anaesthesia with propofol-alfentanil . Fifty patients with normal healthy ears were divided into two groups . In one group ( n = 25 ) , anaesthesia was induced with thiopentone 6 mg kg-1 , and maintained with halothane 1 % and nitrous oxide 66 % in oxygen . In the other group ( n = 25 ) , anaesthesia was induced with alfentanil 25 micrograms kg-1 and propofol 2 mg kg-1 , and maintained with an infusion of alfentanil 10 micrograms kg-1 min-1 for the first 10 min and then with 0.5 microgram kg-1 min-1 and with propofol 10 mg kg-1 h-1 for the first 10 min , 8 mg kg-1 h-1 for the following 10 min and 6 mg kg-1 h-1 thereafter . Patients were ventilated with an oxygen-air mixture ( F1O2 = 0.33 ) . Middle ear pressures were measured during the pre- , intra- and post-anaesthetic period in both ears . A progressive rise was observed ( P < 0.05 ) in the first group , whereas values were within the normal limits clinical ly and there was no statistically significant change in those receiving total intravenous anaesthesia during the intra-anaesthetic period . The time to reach peak pressure with inhalational anaesthesia was 60 min ( 181.5 mmH2O ) and to return to normal was 30 min ( 49.5 mmH2O ) after cessation of nitrous oxide administration . The incidence of nausea and vomiting was less in the patients not receiving nitrous oxide Background : Remifentanil is commonly used to replace nitrous oxide in general anesthesia to avoid the side effects of the latter . However , there are reports that intraoperative remifentanil infusion can lead to acute opioid tolerance . In this study , the authors tried to determine the dose of remifentanil comparable in efficacy to 70 % nitrous oxide and to evaluate its effect on postoperative pain and morphine consumption after colorectal surgery using isoflurane anesthesia . Methods : Sixty adult patients undergoing open colorectal surgery were r and omly assigned to receive either remifentanil or 70 % nitrous oxide along with isoflurane anesthesia . After morphine analgesia titration in the postanesthesia care unit , patient-controlled analgesia was commenced . Morphine consumption and pain were scored at rest and during cough or movement for 24 h. Results : The mean remifentanil infusion rate was 0.17 & mgr;g · kg−1 · min−1 . The median visual analog pain score on arrival in the postanesthesia care unit was 1 ( 0–10 ) in the nitrous oxide group and 3 ( 0–9 ) in the remifentanil group ( P < 0.05 ) . Otherwise , there was no difference in pain scores at 5 , 10 , and 15 min and no difference in the total morphine consumption during the stay in the postanesthesia care unit . The two groups had similar total morphine consumption in the first 24 h and pain scores at rest and during movement . The incidence of postoperative nausea and vomiting was 10 % in both groups . There was no difference in the sedation scores . Conclusion : The substitution of 70 % nitrous oxide with remifentanil at a mean infusion rate of 0.17 & mgr;g · kg−1 · minute−1 for colorectal surgery did not affect postoperative opioid consumption BACKGROUND Nitrous oxide inactivates vitamin B12 and methionine synthase , thereby impairing DNA formation and , consequently , new cell formation . The gas also inhibits methionine production , which can reduce scar formation and depresses chemotactic migration by monocytes . Therefore , we assessed whether nitrous oxide increases the incidence of surgical wound infection . METHODS We recruited 418 patients aged 18 - 80 years , scheduled for colon resection that was expected to last more than 2 h , at three hospitals in Austria and Hungary . Patients were r and omly assigned 65 % intraoperative nitrous oxide ( n=208 ) or nitrogen ( n=206 ) , with remifentanil and isoflurane . The primary outcome was the incidence of clinical postoperative wound infection , analysed by intention to treat . FINDINGS 206 patients in the nitrous oxide group and 202 in the nitrogen group were included in the final analysis . Duration of surgery was longer in the nitrogen group ( 3.4 h [ 1.5 ] ) than in the nitrous oxide group ( 3.0 h [ SD 1.3 ] ) and arterial pressure ( 84 mm Hg [ 10 ] vs 81 mm Hg [ 9 ] ) , bispectral index values ( 53 [ 9 ] vs 44 [ 8 ] ) , and end-tidal isoflurane concentration ( 0.64 % [ 0.14 ] vs 0.56 % [ 0.13 ] ) were greater in patients given nitrogen than in those given nitrous oxide . Infection rate was 15 % ( 31/206 ) in patients given nitrous oxide and 20 % ( 40/202 ) in those given nitrogen ( p=0.205 ) . Additionally , the ASEPSIS wound healing score , wound collagen deposition , number of patients admitted to critical care unit , time to first food ingestion , duration of hospital stay , and mortality did not differ between treatment groups . INTERPRETATION Nitrous oxide does not increase the incidence of surgical wound infection We tested the hypothesis that the administration of nitrous oxide ( N2O ) causes major ( e.g. , myocardial infa rct ion , neuronal injury , hypoxemia , infection , death ) or minor ( e.g. , nausea , vomiting , headache , earache ) untoward effects in patients requiring anesthesia for 1.5–4 h. Given the higher morbidity and mortality associated with aging , we also tested whether aging increased any untoward effect of N2O . Finally , we investigated whether the substitution of N2O for a fraction of the anesthesia supplied by isoflurane altered the latter 's pharmacologic effects . We studied 270 patients scheduled for elective total hip arthroplasty ( n = 100 ) , carotid endarterectomy ( n = 70 ) , or transsphenoidal hypophysectomy ( n = 100 ) who were r and omly assigned within each surgical group to receive isoflurane with or without 60 % N2O . Regardless of patient age , we found no difference in major or minor untoward outcomes between anesthetic groups , nor a trend to suggest that a larger data cohort would reveal a significant adverse effect of N2O . The addition of N2O administration decreased the isoflurane requirement for clinical anesthesia but did not alter most of the clinical variables measured in practice , including blood pressure , heart rate , rate of recovery from anesthesia , development of postoperative pain , patient satisfaction with anesthesia , or duration of anesthesia or of hospitalization . Patients given N2O were no more likely to dream during anesthesia , remember events during anesthesia , or be frightened by those events . Our results support the continued use of N2O to anesthetize patients for elective surgery Patients admitted for day-case laparoscopy were assigned r and omly to receive nitrous oxide-oxygen or oxygen , with enflurane , during a st and ard anaesthetic technique . Postoperative morbidity , in particular nausea and vomiting , and ability to resume normal activity were assessed over the ensuing 48 h. Supplementary administration of propofol during the operative procedure was required significantly more often ( P less than 0.05 ) in the absence of nitrous oxide . There was no significant difference in the incidence of vomiting before discharge when nitrous oxide was omitted . The incidence and severity of nausea over the 48 h following operation was similar in both groups . There was no difference in analgesic or anti-emetic requirements before discharge and the time taken to resume normal activity was similar . It is concluded that nitrous oxide may be avoided readily in day-case laparoscopy without affecting postoperative morbidity or time taken to return to " street fitness " and normal activity A multimodal management strategy for the prevention of postoperative nausea and vomiting ( PONV ) appears to be superior to single-drug prophylaxis . We tested the hypothesis that a multimodal PONV prophylaxis regimen incorporating total IV anesthesia ( TIVA ) with propofol and a combination of ondansetron and droperidol is more effective than a combination of these antiemetics in the presence of an inhaled anesthetic . Ninety patients undergoing laparoscopic cholecystectomy were r and omized to one of three groups . Group 1 ( multimodal group ) received TIVA with propofol , droperidol , and ondansetron . Group 2 ( combination group ) received droperidol and ondansetron with isoflurane and nitrous oxide for the maintenance of anesthesia . Group 3 ( TIVA group ) received propofol for the induction and maintenance of anesthesia . The complete response rate ( no PONV and no rescue antiemetic ) at 2 h after surgery was 90 % , 63 % , and 66 % in Groups 1 , 2 , and 3 , respectively ( P < 0.05 , Group 1 versus Group 2 ) . At 24 h , the complete response rate was 80 % , 63 % , and 43 % in Groups 1 , 2 , and 3 , respectively ( P < 0.05 , Group 1 versus Group 3 ) . Patient satisfaction was also greater in the multimodal group than in the other two groups in the postanesthesia care unit ( P < 0.05 ) . In conclusion , the multimodal management strategy for PONV was associated with a higher complete response rate and greater patient satisfaction when compared with similar antiemetic prophylaxis with inhaled anesthesia or TIVA with propofol This study compares the induction , hemodynamic , and recovery characteristics of a general anesthetic with desflurane to one with propofol . Sixty out patients presenting for orthopedic surgery received either a propofol induction of anesthesia followed by desflurane and nitrous oxide ( Group 1 ) , a propofol induction followed by propofol infusion and nitrous oxide ( Group 2 ) , a desflurane and nitrous oxide induction and maintenance ( Group 3 ) , or a desflurane induction and maintenance ( Group 4 ) . The quality of induction was inferior in Groups 3 and 4 with more breath-holding and excitation than in Groups 1 and 2 . However , there was a more rapid emergence in Group 4 patients than any of the other groups . Group 4 patients were able to say their names ( 5.6 + /- 2.0 min vs 10.3 + /- 3.3 min , 8.6 + /- 3.1 min , and 9.3 + /- 1.5 min for Groups 1 , 2 , and 3 , respectively ) sooner after the discontinuation of anesthesia . Nonetheless , intermediate recovery was similar in Groups 2 and 4 being numerically but not statistically more rapid than in Groups 1 and 3 . This pattern of intermediate recovery was also demonstrated by psychomotor function test results . Although there was no difference between the groups in postoperative narcotic requirement , more patients in Group 3 vomited ( 50 % ) than in either Group 2 ( 0 % ) or Group 4 ( 12.5 % ) . Hemodynamically , the anesthetics were very similar . Although desflurane was a difficult drug to use for induction of anesthesia , this study demonstrates that desflurane is a suitable maintenance anesthetic for ambulatory surgery because it provides a rapid awakening and an intermediate recovery similar to propofol We have evaluated the effects of nitrous oxide on recovery following laparoscopic cholecystectomy in a prospect i ve , r and omised , double – blind study with 42 otherwise healthy patients . All patients received meperidine 1 mg/kg and atropine 6 μg/kg i m for premedication , and anaesthesia was induced with fentanyl 2 μg/ kg and thiopental 4—‐6 mg/kg . Succinylcholine was used for the intubation and muscle relaxation was achieved using vecuronium . Isoflurane with 70 % nitrous oxide in oxygen and fentanyl was used for maintenance of anaesthesia in group I ( n=19 ) , and isoflurane in air/oxygen and fentanyl in group II ( n = 23 ) . The postoperative ward staff and the surgeon evaluating the postoperative recovery were blinded to the anaesthetic technique . No differences were found in duration of operation and anaesthesia , need for postoperative analgesia or postoperative nausea treated medically . Recovery , judged by the Steward Coma Score , comprehension and collaboration , degree of sedation and orientation in time and space , was similar in the two groups . Postoperative hospital stay was 1 ( 1–4 ) day in the nitrous oxide group ( median ( 10–90th percentiles ) versus 2 ( 1–4 ) days in the air group . The time until patients were recovered , as judged by return to work and normal daily activities , was the same in the two groups : 8 ( 4–11 ) days in the nitrous oxide group and 8 ( 4—‐11 ) days in the air group . We conclude that nitrous oxide has no influence on recovery after laparoscopic cholecystectomy PURPOSE We performed this study to test the hypothesis that nitrous oxide produces clinical ly significant bowel distention during laparoscopic abdominal surgery . MATERIAL S AND METHODS Laparoscopic kidney donors were r and omized into 2 groups . Group 1 received N2O and oxygen inhalation through anesthesia , and group 2 received a mixture of air and oxygen . All patients received the same preanesthetic and anesthetic medications . The surgeon was blinded to the use of N2O . The surgeon was given the option to discontinue N2O use ( if it was used ) if he/she thought that the bowel distention was increasing surgical risk . Postoperative data were collected on bowel symptoms , pain and recovery . RESULTS A total of 28 patients were enrolled in the study , 12 of whom received N2O ( group 1 ) and 16 who did not receive N2O ( group 2 ) . Mild to moderate bowel distention was reported by the surgeons in 6 patients ( 50 % ) in group 1 and 1 patient only in group 2 ( 6 % , p=0.007 ) . Severe bowel distention was encountered in 4 patients , 3 of whom received N2O ( 25 % of group 1 ) . Nausea and vomiting on postoperative day 1 was reported by 50 % of patients in group 1 and 25 % of group 2 . There was no difference in the pain scores between the 2 groups . No intraoperative or postoperative complications were encountered . CONCLUSIONS The use of N2O anesthetic causes bowel distention in 50 % of abdominal laparoscopic donor nephrectomy operations . The distention was severe enough to interfere with the progress of surgery in 25 % of cases and the use of N2O had to be discontinued Prolonged ( several days or repeated ) exposure to nitrous oxide ( N2O ) can cause injury or death . To assess whether relatively prolonged anesthesia with N2O in normal patients might similarly cause untoward effects , we investigated whether the addition of N2O to isoflurane anesthesia caused injury to patients having surgical resection of acoustic neuroma lasting approximately 10 h. Twenty-six patients undergoing surgical resection of acoustic neuroma were r and omly assigned to a regimen that included or excluded N2O ( 50%-60 % ) during isoflurane anesthesia plus intravenous adjuvants . On average , slightly less isoflurane ( 0.24 % ) was used during anesthesia with N2O . We measured st and ard clinical variables ( blood pressure , heart rate ) , oxygen saturation , neurologic status , pain , and the incidence and type of morbid outcomes . Exposure to N2O did not increase the incidence of morbid outcomes ( including hepatic injury , infection , or hypoxemia ) , prolong hospitalization , or increase common postoperative complaints such as nausea , vomiting , coughing , or headache . Patients anesthetized with either regimen were equally satisfied with their anesthetic Background and objective A r and omized and prospect i ve study was performed to compare anaesthetic characteristics and stress hormone responses of two anaesthetic techniques . Methods Forty‐two patients undergoing day case excisional biopsy of breast mass were r and omly assigned to receive propofol – remifentanil or sevoflurane – N2O . Anaesthesia was induced and maintained either with sevoflurane and 50 % N2O in oxygen or with target‐controlled remifentanil and propofol in 50 % oxygen and air . Anaesthetic depth was monitored by the bispectral index . Results The times for induction ( 2.9 vs. 1.7 min ) and for laryngeal mask insertion ( 5.7 vs. 3.3 min ) were longer in the sevoflurane – N2O group than in the propofol – remifentanil group . However , apnoea ( 57.1 % vs. 9.5 % ) and bradycardia ( 23.8 % vs. 0 % ) were more prevalent with propofol – remifentanil . In the sevoflurane – N2O group , the emergence times to a verbal response ( 10.6 vs. 3.7 min ) , to extubation ( 11.8 vs. 4.0 min ) and to orientation ( 14.7 vs. 4.8 min ) were longer than in the propofol – remifentanil group . There were significantly more nausea ( 38.1 % vs. 4.8 % ) and vomiting ( 19.2 % vs. 0 % ) in the sevoflurane – N2O group than in the propofol – remifentanil group . The time to discharge was similar although there was less postoperative pain in the sevoflurane – N2O group . There were no differences in the perioperative cortisol responses in the two groups . Conclusions Smoother induction of anaesthesia was seen with sevoflurane – N2O . Propofol – remifentanil showed a quicker emergence with less nausea/vomiting . There were similar perioperative cortisol responses in the two anaesthetic techniques BACKGROUND The major purpose of this study is to evaluate and compare the clinical characteristics of sevoflurane-nitrous oxide and propofol-nitrous oxide anesthesias conveyed by laryngeal mask airway ( LMA ) in patients for gynecological procedures . METHODS Eighty female patients were r and omly assigned to one of the two groups : Group I , inhalational induction at vital capacity with 8 % sevoflurane and 67 % nitrous oxide in oxygen ; Group II , induction with intravenous propofol at 2 mg/kg followed by intravenous infusion at 6 mg/kg/hr . The LMA was inserted after loss of response to jaw thrusting . After successful insertion , in group I anesthesia was maintained with sevoflurane and 67 % nitrous oxide in O2 and in group II anesthesia was maintained with propofol at 6 mg/kg/hr and nitrous oxide 67 % in oxygen . Anesthetic profiles , including insertion event , postoperative nausea and vomiting , and hemodynamic alterations were compared . RESULTS Demographic data were comparable in the two groups . After induction , in group II unconsciousness was produced 59 sec shorter than that in group I for placement of LMA . Group I had a higher statistically significant rate of cough upon induction , and by the same token postoperative nausea and vomiting . There were no significant differences in hemodynamic alterations , as well as time to open eyes on comm and , and time to regain orientation . CONCLUSIONS Intravenous propofol in combination with 67 % nitrous oxide in oxygen technique provided better clinical profiles , compared with sevoflurane-nitrous oxide technique through the use of LMA in gynecological patients undergoing ambulatory short procedures SUMMARY Postanaesthetic sickness was observed for the first hour after operation in 167 women . Dilatation and curettage was performed in 95 . Each was given atropine before thiopentone induction of anaesthesia . In 45 patients anaesthesia was maintained with nitrous oxide and oxygen , and in 55 with open-drop ether . There was no significant difference in the incidence of sickness between the two series . Abdominal hysterectomy was performed in 72 patients . Each was given atropine before thiopentone induction . Anaesthesia was maintained in 36 patients with nitrous oxide and oxygen and in 36 with 2 per cent ether in air using an EMO Inhaler and Oxford Inflating Bellows . The incidence of sickness was significantly less in the ether group and this may be attributable to the uniformly low level of ether obtained using this technique STUDY OBJECTIVE The aim of the study was to compare the antiemetic efficacy and costs associated with 3 different anesthesia regimens used in gynecologic laparoscopy . DESIGN This was a r and omized , controlled study . SETTING The study was conducted at a university hospital . PATIENTS We studied 150 ASA physical status I or II patients , undergoing elective gynecologic laparoscopy with general anesthesia . INTERVENTION Patients were allocated into the following 3 groups : group P-preoperative placebo tablet , propofol induction , propofol-air/O2 maintenance ; group I + O-preoperative 8-mg ondansetron tablet , thiopental induction , isoflurane-N2O maintenance ; group I (control)-preoperative placebo tablet , thiopental induction , isoflurane-N2O maintenance . MEASUREMENTS The frequency of postoperative nausea and vomiting ( PONV ) , number needed to treat to prevent PONV , and the costs of the anesthetic drugs to prevent PONV in one additional patient were evaluated . MAIN RESULTS The frequency of PONV within the 24-hour study period was lowest in group I + O ( P , 38 % ; I + O , 33 % ; and I , 59 % ; P < 0.05 I + O vs I ) . The number needed to treat was 5 in group P and 4 in group I + O , compared with group I. The median costs of anesthetic drugs to prevent PONV in one additional patient were $ 65 in group P and dollar 68 in group I + O , compared with group I. CONCLUSIONS We conclude that in gynecologic laparoscopy , propofol-air/O2 anesthesia alone , and isoflurane-N2O anesthesia combined with an oral 8-mg dose of ondansetron had similar efficacy and costs to prevent PONV . Isoflurane-N2O anesthesia without ondansetron was less expensive , but was also less efficacious Background Although nitrous oxide ( N2O ) is used commonly during anesthesia , clinical ly relevant advantages – disadvantages of using this agent are not well established in the ambulatory setting . This study in women undergoing ambulatory gynecologic surgery compares outcomes in patients administered total intravenous anesthesia with propofol versus the propofol plus N2O . The primary outcome was the time to home readiness . Secondary outcomes included the incidence of postanesthetic adverse events . Methods Women presenting for elective ambulatory termination of pregnancy or gynecologic laparoscopy were induced with an intravenous sleep dose of propofol and fentanyl . After induction , subjects were r and omly allocated to maintenance anesthesia with propofol alone or propofol plus 65 % N2O . Patients were assessed by a blinded observer in the postanesthetic care unit at 20-min intervals to determine home readiness . Postoperative pain and nausea were measured with visual analog scales . Postoperative analgesics and antiemetics were recorded . The incidence of adverse events occurring after hospital discharge was assessed by a telephone interview 24 h postoperatively . Results A total of 740 patients received propofol alone , and 750 patients received propofol plus N2O . Mean home readiness times were not significantly different between treatment groups . There were no significant differences between groups in pain scores , nausea scores , analgesia administration , or antiemetic administration before discharge . There were no significant differences in the frequency of adverse events for 24 h after discharge from hospital . Conclusions Omission of N2O from a propofol-based anesthetic for ambulatory gynecologic surgery does not affect time to home readiness or the incidence of postoperative adverse events up to 24 h after discharge from hospital The purpose of this study was to ascertain whether total intravenous anesthesia ( TIVA ) with propofol and remifentanil differs from inhalational anesthesia with desflurane and nitrous oxide in terms of hemodynamics , recovery profile , and postoperative analgesic dem and in patients undergoing elective microsurgical vertebral disk resection . A total of 60 patients were r and omly assigned to receive TIVA with propofol and remifentanil or inhalational anesthesia with desflurane and nitrous oxide . The TIVA group ( n=30 ) then received 50%/50 % N2O/O2 . A constant infusion of remifentanil was provided at 0.125 μg/kg/min accompanied by propofol at 10 mg/kg/h in the first 10 min , 6 mg/kg/h in the second 10 min , then 4 mg/kg/h . The desflurane group ( n=30 ) received 50%/ 50 % N2O/O2 , with 5 % desflurane after intubation and 6 % before incision ; desflurane was administered in a minimum alveolar concentration 1 fashion during the operation . Hemodynamic , O2 saturation , and end-tidal CO2 data were recorded before induction , after intubation , after prone positioning , 5 , 10 , 15 , 20 , and 30 min into the operation , and at 15-min intervals thereafter until the end of the operation . Details on perioperative bradycardia , hypotension or hypertension , spontaneous breathing , extubation , eye opening , recovery time of ability to give name and date of birth , postoperative nausea and vomiting , shivering , agitation , and hypoxia were recorded . Patients anesthetized with desflurane responded to skin incision with increasing blood pressure and tachycardia ; however , no other hemodynamic differences were noted between the 2 groups . In the TIVA group , recovery times were shorter for spontaneous ventilation ( 2.33–3.53 min ) , extubation ( 3.13–3.88 min ) , eye opening ( 4.06–6.23 min ) , and being able to give name and date of birth ( 5.4–7.9 min ) compared with times in the desflurane group ( P<.05 ) . In theTIVA group , more postoperative shivering ( 16.7 % of patients ) and greater analgesic dem and were seen than in the desflurane group . Although nausea and vomiting were more common in the desflurane group , no difference in bronchospasm was reported . In theTIVA group , a shorter recovery period and a greater dem and for postoperative analgesia were seen . Because of the lack of residual analgesic effects , postoperative analgesic treatment should be initiated immediately in patients undergoing TIVA The effect of nitrous oxide on postoperative nausea/vomiting and alertness were studied in 50 patients undergoing elective upper abdominal surgery . The study period lasted 20 h. Patients were r and omly assigned to receive thiopentone‐fentanyl‐isoflurane‐pancuronium anaesthesia with either 70 % nitrous oxide‐oxygen ( Group I ) or air‐oxygen ( Group II ) . There were no differences between the groups regarding age , sex , weight or amount or per‐ and postoperative analgetics given . The mean inspiratory isoflurane concentrations were 0.6 % and 1.15 % in Groups I and II , respectively . The postoperative alertness was tested by a visual analogue scale ( 0–10 ) for 6 h postoperatively . Omitting nitrous oxide did not decrease the frequency of postoperative nausea , although the symptoms were milder in the air group . The patients without nitrous oxide were alert earlier , in spite of a higher isoflurane concentration : VAS from 5 to 8.7 vs from 2.8 to 6.9 during the first 6 postoperative hours PURPOSE The purpose of this study was to evaluate the effect of supplemental nitrous oxide on postoperative nausea and vomiting ( PONV ) after propofol anesthesia for orthognathic surgery in female and nonsmoking patients . PATIENTS AND METHODS We compared PONV in 28 ASA-I female nonsmoking patients undergoing orthognathic surgery . Anesthesia was induced with propofol combined with fentanyl , and tracheal intubation was facilitated with vecuronium . Anesthesia was maintained with propofol with or without nitrous oxide . No patient received neostigmine . PONV was assessed as score 0 ( no PONV ) , score 1 ( nausea ) , and score 2 ( vomiting ) during the 24-hour recovery period . RESULTS There were no differences in the patients ' characteristics , operation , anesthesia and emergence time , fluid transfusion , blood loss , urine output , and total propofol and fentanyl doses between the 2 groups . There was also no difference in PONV score in 2 groups . Only 1 patient in each group vomited . CONCLUSIONS It is suggested that supplemental nitrous oxide does not aggravate PONV after propofol anesthesia for orthognathic surgery in female nonsmoking patients A recent meta- analysis showed that omitting N2O significantly reduced postoperative vomiting ( POV ) compared with a N2O regime . Our study was design ed to evaluate the effect of the combination of desflurane with N2O versus desflurane alone on postoperative nausea and vomiting ( PONV ) in a subgroup of female patients and PONV was considered as the primary endpoint . After approval of the local Ethics Committee and informed consent 60 female in- patients ( ASA I & II ) , aged 18 - 65 y , scheduled for breast surgery with a duration of 1 - 3 h were included . Obese patients or patients with a history of PONV and motion sickness were excluded . No prophylactic anti-emetic therapy was allowed during the study . Patients received a st and ardized anesthetic technique consisting of propofol for induction , vecuronium and fentanyl for intubation , followed by desflurane with or without N2O ( r and omisation list ) and fentanyl supplements if required for maintenance of anesthesia . At the end of anesthesia PONV was recorded during 24 h in different periods . There were no significant differences between the groups with respect to demographic data and duration of anesthesia . In addition , there were no significant differences in the amount of intraoperative fentanyl or postoperative narcotics . The incidence of PONV was significantly higher in the group of patients receiving desflurane in N2O-O2 mixture compared with the group receiving desflurane in AIR-O2 mixture . The combination of desflurane with N2O in female patients undergoing breast surgery is associated with a significantly higher incidence of PONV and a higher need of antiemetic drugs , when compared to a N2O free regime One hundred patients of ASA status I or II , undergoing gynaecological or urological surgery were studied . Opioids were omitted from premedication and anaesthesia . Patients were allocated r and omly to one of two equal groups and were anaesthetized using a computer controlled infusion system , programmed to achieve theoretically any target blood propofol concentration . One group received 60 % nitrous oxide in oxygen while the other group received 100 % oxygen . Six patients in the nitrous oxide group had nausea and three of these patients vomited . Two patients in the oxygen group had nausea but no patient vomited . The frequency of nausea and vomiting in the two groups was not statistically different ( P > 0.05 ) . Theoretical blood propofol concentration shown to produce surgical anaesthesia was maintained in all patients . However 12 % of the patients that received nitrous oxide and 40 % of the patients that did not , responded to the surgical stimulus by limb movement . Patients in the oxygen group required higher rates of propofol infusion to maintain surgical anaesthesia Postoperative nausea and vomiting have been reported to be associated with the use of nitrous oxide . To further investigate this possibility , 780 patients undergoing anesthesia and surgery were r and omly divided into four groups : group I : enflurane/nitrous oxide/oxygen ; group II : enflurane/air/oxygen ; group III : isoflurane/nitrous oxide/oxygen ; and group IV : isoflurane/air/oxygen . The frequency of postoperative nausea and vomiting was ascertained in the recovery room and at 24-h follow-up by blinded observers . Other data collected included gender , age , body mass index , previous history of postoperative nausea and vomiting , and postoperative narcotic use . The authors found no association between the use of nitrous oxide and subsequent development of postoperative nausea and vomiting . Use of the 95 % confidence interval allowed the authors to project a maximum potential increase in the frequency of postoperative nausea and vomiting associated with nitrous oxide to be 5.4 % with enflurane and 9.7 % with isoflurane in the immediate postoperative period . Female gender , younger age , and a previous history of postoperative nausea and vomiting , but not body mass index , were found to be associated with postoperative nausea and vomiting ( P < 0.05 ) . It is concluded that there is no association between the use of nitrous oxide and the development of postoperative nausea and vomiting The role of nitrous oxide in postoperative emesis is controversial . This prospect i ve r and omized study was performed to compare the emetic sequelae and quality of recovery between a group of patients anesthetized with propofol alone and a group anesthetized with propofol plus nitrous oxide . Seventy patients , ASA grade I or II , scheduled for ambulatory gynecologic laparoscopy under general anesthesia were included . Most factors which could influence the incidence of postoperative emesis were controlled . The overall incidence of emetic sequelae during the first 24 h postoperatively was 25 % in the group anesthetized with propofol alone versus 29 % for the group anesthetized with propofol and nitrous oxide . The incidence of emetic sequelae requiring therapeutic intervention was 13 % and 6 % , respectively . This difference was not statistically significant . The group of patients who received propofol alone required an average propofol dose of 221.5 + /- 71.9 micrograms.kg-1.min-1 to maintain anesthesia compared with 162.5 + /- 43.9 micrograms.kg-1.min-1 for the group receiving propofol plus nitrous oxide ( P < 0.001 ) . The time from discontinuation of propofol to eye-opening and orientation was significantly longer in patients anesthetized with propofol alone . Otherwise , the recovery variables were comparable between the two groups . We conclude that supplementing propofol with nitrous oxide in patients undergoing ambulatory laparoscopy reduces the requirements of propofol , expedites immediate recovery ( emergence ) , and does not increase the incidence of postoperative emesis . This tends to confirm that there is no clinical advantage to omitting nitrous oxide Postoperative nausea and vomiting have been associated with the use of nitrous oxide . Alfentanil , when combined with nitrous oxide , also results in a high incidence of postoperative nausea and vomiting . To further define this emesis-potentiating effect of N2O , 119 patients were chosen for study and divided into two groups : group A ( n = 59 ) was administered a mixture of alfentanil , N2O , and O2 with 0.25 % isoflurane , group B ( n = 60 ) was administered a mixture of oxygen , room air , isofluorane , and alfentanil . The incidence of postoperative nausea and vomiting was ascertained by a blinded observer in the recovery room . All 119 patients were scheduled for extra-abdominal procedures ( excluding thoracotomial , intracranial , ophthalmologic , and middle ear surgery ) . Patients with a previous history of nausea and vomiting , hiatal hernias , reflux esophagitis , or morbid obesity were excluded . The incidence of vomiting was 5 % ( 3/60 ) in group B and 15 % ( 8/59 ) in group A ( P = 0.067 ) . Forty-four percent ( 26/59 ) of the patients in group A and 20 % ( 12/59 ) in group B were nauseated postoperatively ( P = 0.005 ) . Our data suggest that elimination of N2O from alfentanil-based anesthetics lessens the incidence of nausea Postanesthetic nausea and vomiting can delay discharge of out patients and can cause occasional admissions to hospital . Nitrous oxide ( N2O ) has been thought to increase this frequency , but previous studies have been indecisive . One hundred eighty-five unpremedicated out patients undergoing laparoscopic tubal ligation were studied to determine the effect of N2O on postanesthetic nausea and vomiting . The patients were divided by registration number , intubated , and given mixtures of either N2O-O2 enflurane or air-O2 enflurane . Intravenous ( IV ) lidocaine , administered initially prior to intubation to control bucking , was later omitted in r and omly chosen cases to determine its effect . The overall prevalence of nausea and vomiting was 29.2 % with N2O and 9.3 % with air ( p less than 0.001 ) . While the lidocaine subseries was small , it appeared to prevent nausea and vomiting , particularly when N2O was omitted . Further study is justified . Fentanyl , given postoperatively for pain , did not increase the prevalence of nausea and vomiting . It was concluded that N2O is associated with an increased prevalence of nausea and vomiting Two hundred and ten adult patients undergoing open cholecystectomy , vagotomy or gastrectomy were included in a r and omised multicentre study to compare postoperative nausea and vomiting , oxygen saturations for the first three postoperative nights , time to return of gastrointestinal function , mobilisation , and discharge from the hospital following induction and maintenance of anaesthesia with propofol and alfentanil or with thiopentone , nitrous oxide , isoflurane and alfentanil . Recovery from anaesthesia was significantly faster in the propofol group ( mean ( SD ) times to eye opening and giving correct date of birth of 14.0 ( SD 13.8 ) and 25.5 ( SD 29.5 ) minutes , and 18.5 ( SD 14.8 ) and 35.5 ( SD 37.2 ) minutes in the propofol and isoflurane groups respectively ) . There was significantly less nausea in the propofol group ( 15.4 % ) than in the isoflurane group ( 33.7 % ) in the first two postoperative hours ( p < 0.003 ) but not thereafter . There were no significant differences between the groups in any other recovery characteristics . The incidence of hypoxaemia ( arterial oxygen saturation less than 93 % ) was close to 70 % in both groups for the first three postoperative nights , indicating the need for oxygen therapy after major abdominal surgery This study was undertaken to compare desflurane with propofol anesthesia in out patients undergoing peripheral orthopedic surgery . Data were combined from two institutions participating in a multicenter study . Ninety-one patients , ASA physical status I or II , were each r and omly assigned to one of four groups . After administration of fentanyl ( 2 micrograms/kg ) and d-tubocurarine ( 3 mg ) , intravenous propofol was administered to induce anesthesia in groups I and II and desflurane in groups III and IV . Maintenance was provided by desflurane/N2O in groups I and III , propofol/N2O in group II , and desflurane/O2 in group IV . Emergence and recovery variables , psychometric test results , and side effects were recorded by observers unaware of the experimental treatment . Patients in group II experienced less nausea than other groups ( P = 0.002 ) despite this group having required more intraoperative fentanyl supplementation than groups III and IV ( P = 0.01 ) . Time to emergence , discharge , and psychometric test results were similar in all groups . Desflurane appears to be comparable with propofol as an outpatient anesthetic , facilitating rapid recovery and discharge home Since it has been suggested that the use of nitrous oxide ( N2O ) may contribute to bowel distention , we evaluated the effects of N2O on operating conditions during laparoscopic cholecystectomy in 50 healthy patients using a double-blind protocol design . All patients received the same preanesthetic medication ( midazolam , 2 mg intravenously ) and induction of anesthesia consisted of intravenously administered fentanyl 1.5 micrograms.kg-1 , thiopental 4 - 6 mg.kg-1 , and a nondepolarizing muscle relaxant . For maintenance of anesthesia , patients were r and omly assigned to one of two treatment groups : group 1 ( n = 26 ) received isoflurane with 70 % N2O in oxygen ( O2 ) , whereas group 2 ( n = 24 ) received isoflurane in an air/O2 mixture . The surgeon ( blinded to the anesthetic technique ) estimated the degree of technical difficulty before beginning the operation using a five-point scale . At 15-min intervals throughout the operation , the surgeon was asked to evaluate both " overall operating conditions " and degree of " bowel distension " using independent five-point scales . At the end of the operation , the surgeon was asked whether or not N2O had been used as part of the anesthetic technique . There were no significant intraoperative differences between the two groups with respect to operating conditions or bowel distension . More importantly , there was no time-related change in either variable during the course of the operation . Finally , the incidence of postoperative nausea and vomiting was similar in both treatment groups . The surgeon was able to correctly determine that N2O had been administered only 44 % of the time . Thus , N2O had no clinical ly apparent deleterious effects during laparoscopic cholecystectomy We compared esmolol and remifentanil infusions with respect to their effect on intraoperative hemodynamic stability and early recovery after outpatient laparoscopic surgery when administered as IV adjuvants during desflurane anesthesia . After premedication with midazolam 2 mg IV , anesthesia was induced with propofol 2 mg · kg−1 IV in combination with either esmolol 1 mg · kg−1 IV ( n = 27 ) or remifentanil 1 & mgr;g · kg−1 IV ( n = 26 ) and succinylcholine 1 mg · kg−1 IV according to a r and omized , double-blinded protocol . Anesthesia was initially maintained with des- flurane 2.5 % ( subsequently titrated to maintain an electroencephalogram-bispectral index value of 60 ) and nitrous oxide 65 % in oxygen . Before skin incision , an infusion of either esmolol ( 5 & mgr;g · kg−1 · min−1 ) or remifentanil ( 0.05 & mgr;g · kg−1 · min−1 ) was started and titrated to maintain the heart rate within 25 % of the baseline value . Mivacurium , 0.04 mg/kg IV , bolus doses were administered to maintain a stable peak inspiratory pressure . Esmolol ( 12.8 ± 13.1 & mgr;g · kg−1 · min−1 ) and remifentanil ( 0.04 ± 0.02 & mgr;g · kg−1 · min−1 ) infusions were equally effective in maintaining a stable heart rate during these laparoscopic procedures . Although the mivacurium requirement was larger in the Esmolol group ( 7 ± 5 vs 3 ± 4 mg ) , the Esmolol group reported a smaller incidence of postoperative nausea and vomiting ( 4 % vs 35 % ) . Both drugs were associated with frequent “ postanesthesia care unit bypass ” rates ( 78–81 % ) , short times to “ home readiness ” ( 119–120 min ) , excellent patient satisfaction ( 81–85 % ) , and rapid resumption of normal activities ( 2.6–3.2 d ) . Fast-tracked patients were ready for discharge home significantly earlier ( 112 ± 46 vs 151 ± 50 min ) . We concluded that esmolol infusion is an acceptable alternative to remifentanil infusion for maintaining hemodynamic stability during desflurane-based fast-track anesthesia for outpatient gynecologic laparoscopic surgery . Implication s Adjunctive use of a variable-rate infusion of esmolol during outpatient anesthesia with desflurane-nitrous oxide was associated with less postoperative nausea and vomiting than a remifentanil infusion . However , both adjuvants facilitated fast-tracking and lead to early discharge after laparoscopic tubal ligation surgery |
12,721 | 30,806,875 | Similarly , no superior effects of HIIT compared to MIE were found for quality of life or changes in lean mass , while evidence was provided for a larger reduction in fat mass .
Conclusion This systematic review showed that short-term HIIT induces similar positive effects on physical fitness and health-related outcomes as MIE but seems to be superior compared to UC .
Thus , HIIT might be a time-efficient intervention for cancer patients across all stages of therapy and aftercare .
Implication s for Cancer SurvivorsHigh-intensity interval training ( HIIT ) is superior compared to usucal care in improving physical fitness and health-related outcomes in cancer patients across all stages of therapy and aftercare .
Currently , there is no evidence for the benefits of HIIT compared to aerobic training of moderate intensity ( MIE ) for changes in cardiorespiratory fitness , lean mass and patient-reported outcomes .
Reductions in fat mass may be more pronounced in HIIT compared to MIE when training is performed in aftercare | Purpose This review and meta- analysis aim ed to evaluate the effects of high-intensity interval training ( HIIT ) compared to usual care ( UC ) or moderate-intensity training ( MIE ) on physical fitness and health-related outcomes in cancer patients across all stages of therapy and aftercare . | Purpose Exercise training is an effective and safe way to counteract cancer-related fatigue ( CRF ) and to improve health-related quality of life ( HRQoL ) . High-intensity interval training has proven beneficial for the health of clinical population s. The aim of this r and omized controlled trial was to compare the effects of resistance and high-intensity interval training ( RT – HIIT ) , and moderate-intensity aerobic and high-intensity interval training ( AT – HIIT ) to usual care ( UC ) in women with breast cancer undergoing chemotherapy . The primary endpoint was CRF and the secondary endpoints were HRQoL and cancer treatment-related symptoms . Methods Two hundred and forty women planned to undergo chemotherapy were r and omized to supervised RT – HIIT , AT – HIIT , or UC . Measurements were performed at baseline and at 16 weeks . Question naires included Piper Fatigue Scale , EORTC-QLQ-C30 , and Memorial Symptom Assessment Scale . Results The RT – HIIT group was superior to UC for CRF : total CRF ( p = 0.02 ) , behavior/daily life ( p = 0.01 ) , and sensory/physical ( p = 0.03 ) CRF . Role functioning significantly improved while cognitive functioning was unchanged for RT – HIIT compared to declines shown in the UC group ( p = 0.04 ) . AT – HIIT significantly improved emotional functioning versus UC ( p = 0.01 ) and was superior to UC for pain symptoms ( p = 0.03 ) . RT – HIIT reported a reduced symptom burden , while AT – HIIT remained stable compared to deteriorations shown by UC ( p < 0.01 ) . Only RT – HIIT was superior to UC for total symptoms ( p < 0.01 ) . Conclusions 16 weeks of resistance and HIIT was effective in preventing increases in CRF and in reducing symptom burden for patients during chemotherapy for breast cancer . These findings add to a growing body of evidence supporting the inclusion of structured exercise prescriptions , including HIIT , as a vital component of cancer rehabilitation . Trial registration Clinical trials.gov Registration Number : NCT02522260 Background Promoting quality of life ( QoL ) is a key priority in cancer care . We investigated the hypothesis that , in comparison to usual care , exercise post-neoadjuvant chemoradiation therapy/prior to surgical resection will reduce pain , fatigue , and insomnia , and will improve physical and mental health perceptions in patients with locally advanced stage rectal cancer . Methods In this non-r and omized controlled pilot trial , patients in the supervised exercise group ( EG ; Mage = 64 years ; 64 % male ) and in the control group ( CG ; Mage = 72 years ; 69 % male ) completed the European Organization for Research and Treatment of Cancer core Quality of Life question naire and the R AND 36-Item Health Survey three times : pre-neoadjuvant chemoradiation therapy ( Time 1 ; nEC = 24 ; nCG = 11 ) , post-neoadjuvant chemoradiation therapy/pre-exercise intervention ( Time 2 ; nEC = 23 ; nCG = 10 ) , and post-exercise intervention ( Time 3 ; nEC = 22 ; nCG = 10 ) . The 6-week exercise intervention was delivered in hospital and comprised of interval aerobic training . Patients trained in pairs three times per week for 30 to 40 min . Data were analyzed by Mann – Whitney tests and by Wilcoxon matched-pairs signed-rank tests . Results No significant between-group differences in changes were found for any of the outcomes . In both groups , fatigue levels decreased and physical health perceptions increased from pre- to post-exercise intervention . Pain levels also decreased from pre- to post-exercise intervention , albeit not significantly . Conclusions The findings from this study can be used to guide a more definitive trial as they provide preliminary evidence regarding the potential effects of pre-operative exercise on self-reported pain , fatigue , insomnia , and health perceptions in patients with locally advanced rectal cancer . Trial registration : This study has been registered with clinical trials.gov ( NCT01325909 ; March 29 , 2011 ) BACKGROUND Patients requiring surgery for locally advanced rectal cancer often additionally undergo neoadjuvant chemoradiotherapy ( NACRT ) , of which the effects on physical fitness are unknown . The aim of this feasibility and pilot study was to investigate the effects of NACRT and a 6 week structured responsive exercise training programme ( SRETP ) on oxygen uptake [ Formula : see text ] at lactate threshold ( [ Formula : see text ] ) in such patients . METHODS We prospect ively studied 39 consecutive subjects ( 27 males ) with T3 - 4/N+ resection margin threatened rectal cancer who completed st and ardized NACRT . Subjects underwent cardiopulmonary exercise testing at baseline ( pre-NACRT ) , at week 0 ( post-NACRT ) , and week 6 ( post-SRETP ) . Twenty-two subjects undertook a 6 week SRETP on a training bike ( three sessions per week ) between week 0 and week 6 ( exercise group ) . These were compared with 17 contemporaneous non-r and omized subjects ( control group ) . Changes in [ Formula : see text ] at [ Formula : see text ] over time and between the groups were compared using a compound symmetry covariance linear mixed model . RESULTS Of 39 recruited subjects , 22 out of 22 ( exercise ) and 13 out of 17 ( control ) completed the study . There were differences between the exercise and control groups at baseline [ age , ASA score physical status , World Health Organisation performance status , and Colorectal Physiologic and Operative Severity Score for the Enumeration of Mortality and Morbidity ( CR-POSSUM ) predicted mortality ] . In all subjects , [ Formula : see text ] at [ Formula : see text ] significantly reduced between baseline and week 0 [ -1.9 ml kg(-1 ) min(-1 ) ; 95 % confidence interval ( CI ) -1.3 , -2.6 ; P<0.0001 ] . In the exercise group , [ Formula : see text ] at [ Formula : see text ] significantly improved between week 0 and week 6 ( + 2.1 ml kg(-1 ) min(-1 ) ; 95 % CI + 1.3 , + 2.9 ; P<0.0001 ) , whereas the control group values were unchanged ( -0.7 ml kg(-1 ) min(-1 ) ; 95 % CI -1.66 , + 0.37 ; P=0.204 ) . CONCLUSIONS NACRT before rectal cancer surgery reduces physical fitness . A structured exercise intervention is feasible post-NACRT and returns fitness to baseline levels within 6 weeks . CLINICAL TRIAL REGISTRATION NCT 01325909 OBJECTIVES Poor aerobic fitness is a potential modifiable risk factor for long-term survival and quality of life in patients with lung cancer . This r and omized trial evaluates the impact of adding rehabilitation ( Rehab ) with high-intensity interval training ( HIIT ) before lung cancer surgery to enhance cardiorespiratory fitness and improve long-term postoperative outcome . METHODS Patients with operable lung cancer were r and omly assigned to usual care ( UC , n = 77 ) or to intervention group ( Rehab , n = 74 ) that entailed HIIT that was implemented only preoperatively . Cardiopulmonary exercise testing ( CPET ) and pulmonary functional tests ( PFTs ) including forced vital capacity ( FVC ) , forced expiratory volume ( FEV 1 ) and carbon monoxide transfer factor ( KCO ) were performed before and 1 year after surgery . RESULTS During the preoperative waiting time ( median 25 days ) , Rehab patients participated to a median of 8 HIIT sessions ( interquartile [ IQ ] 25 - 75 % , 7 - 10 ) . At 1 year follow-up , 91 % UC patients and 93 % Rehab patients were still alive ( P = 0.506 ) . Pulmonary functional changes were non-significant and comparable in both groups ( FEV 1 mean -7.5 % , 95 % CI , -3.6 to -12.9 and in KCO mean 5.8 % 95 % CI 0.8 - 11.8 ) Compared with preoperative CPET results , both groups demonstrated similar reduction in peak oxygen uptake ( mean -12.2 % 95 % CI -4.8 to -18.2 ) and in peak work rate ( mean -11.1 % 95 % CI -4.2 to -17.4 ) . CONCLUSIONS Short-term preoperative rehabilitation with HIIT does not improve pulmonary function and aerobic capacity measured at 1 year after lung cancer resection . TRIAL REGISTRY Clinical Trials.gov ; No. NCT01258478 ; www . clinical trials.gov Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVES The aim of this study was to determine whether ectopic fat depots are prospect ively associated with cardiovascular disease , cancer , and all-cause mortality . BACKGROUND The morbidity associated with excess body weight varies among individuals of similar body mass index . Ectopic fat depots may underlie this risk differential . However , prospect i ve studies of directly measured fat are limited . METHODS Participants from the Framingham Heart Study ( n = 3,086 ; 49 % women ; mean age of 50.2 years ) underwent assessment of fat depots ( visceral adipose tissue , pericardial adipose tissue , and periaortic adipose tissue ) using multidetector computed tomography and were followed up longitudinally for a median of 5.0 years . Cox proportional hazards regression models were used to examine the association of each fat depot ( per 1 SD increment ) with the risk of incident cardiovascular disease , cancer , and all-cause mortality after adjustment for st and ard risk factors , including body mass index . RESULTS Overall , there were 90 cardiovascular events , 141 cancer events , and 71 deaths . After multivariable adjustment , visceral adipose tissue was associated with cardiovascular disease ( hazard ratio : 1.44 ; 95 % confidence interval : 1.08 to 1.92 ; p = 0.01 ) and cancer ( hazard ratio : 1.43 ; 95 % confidence interval : 1.12 to 1.84 ; p = 0.005 ) . Addition of visceral adipose tissue to a multivariable model that included body mass index modestly improved cardiovascular risk prediction ( net reclassification improvement of 16.3 % ) . None of the fat depots were associated with all-cause mortality . CONCLUSIONS Visceral adiposity is associated with incident cardiovascular disease and cancer after adjustment for clinical risk factors and generalized adiposity . These findings support the growing appreciation of a pathogenic role of ectopic fat BACKGROUND Development of this guideline was undertaken by the Exercise for People with Cancer Guideline Development Group , a group organized by Cancer Care Ontario 's Program in Evidence -Based Care ( pebc ) . The purpose of the guideline was to provide guidance for clinicians with respect to exercise for patients living with cancer , focusing on the benefits of specific types of exercise , recommendations about screening requirements for new referrals , and safety concerns . METHODS Consistent with the pebc 's st and ardized approach , a systematic search was conducted for existing guidelines , and systematic literature search es were performed in medline and embase for both systematic review s and primary literature . Content and methodology experts performed an internal review , which was followed by an external review by targeted experts and intended users . RESULTS The search identified three guidelines , eighteen systematic review s , and twenty-nine r and omized controlled trials with relevance to the topic . The present guideline provides recommendations for the duration , frequency , and intensity of exercise appropriate for people living with cancer . It also provides recommendations for pre-exercise assessment , safety concerns , and delivery models . CONCLUSIONS There is sufficient evidence to show that exercise provides benefits in quality of life and muscular and aerobic fitness for people with cancer both during and after treatment , and that it does not cause harm . The present guideline is intended to support the Canadian Society for Exercise Physiology 's Canadian physical activity guidelines . The recommendations are intended for clinicians and institutions treating cancer patients in Ontario , and for policymakers and program planners involved in the delivery of exercise programs for cancer patients Purpose Peak oxygen consumption ( VO2peak ) is an important predictive factor for long-term prognosis in patients with non-small cell lung cancer ( NSCLC ) . The purpose of this study was to investigate whether 8 weeks of exercise training improves exercise capacity , as assessed by VO2peak , and other related factors in patients with NSCLC receiving targeted therapy . Methods A total of 24 participants with adenocarcinoma were r and omly assigned to either the control group ( n = 11 ) or the exercise group ( n = 13 ) . Subjects in the exercise group participated in individualized , high-intensity aerobic interval training of exercise . The outcome measures assessed at baseline and after 8 weeks were as follows : VO2peak and the percentage of predicted VO2peak ( % predVO2peak ) , muscle strength and endurance of the right quadriceps , muscle oxygenation during exercise , insulin resistance as calculated by the homeostasis model , high-sensitivity C-reactive protein , and quality of life ( QoL ) question naire inventory . Results No exercise-related adverse events were reported . After exercise training , VO2peak and % predVO2peak increased by 1.6 mL kg−1 min−1 and 5.3 % ( p < 0.005 ) , respectively ; these changes were associated with improvements in circulatory , respiratory , and muscular functions at peak exercise ( all p = 0.001 ) . The exercise group also had less dyspnea ( p = 0.01 ) and favorably lower fatigue ( p = 0.05 ) than baseline . Conclusions Patients with NSCLC receiving targeted therapy have quite a low exercise capacity , even with a relatively high QoL. Exercise training appears to improve exercise capacity and alleviate some cancer-related symptoms Purpose The aim of this study was to evaluate the effects of low-volume high-intensity interval training and continuous low to moderate intensity training on quality of life , functional capacity and cardiovascular disease risk factors in cancer survivors . Methods Cancer survivors within 24 months post-diagnosis were r and omly assigned into the low-volume high-intensity interval training group ( n = 8) or the continuous low to moderate intensity training group ( n = 8) group for 36 sessions ( 12 weeks ) of supervised exercise . The low-volume high-intensity interval training ( LVHIIT ) group performed 7 × 30 s intervals ( ≥85 % maximal heart rate ) and the continuous low to moderate intensity training ( CLMIT ) group performed continuous aerobic training for 20 min ( ≤55 % maximal heart rate ) on a stationary bike or treadmill . Results Significant improvements ( time ) were observed for 13 of the 23 dependent variables ( ES 0.05–0.61 , p ≤ 0.05 ) . An interaction effect was observed for six minute walk test ( 18.53 % [ 32.43–4.63 ] ES 0.50 , p ≤ 0.01 ) with the LVHIIT group demonstrating greater improvements . Conclusion These preliminary findings suggest that both interventions can induce improvements in quality of life , functional capacity and selected cardiovascular disease risk factors . The LVHIIT program was well tolerated by the participants and our results suggest that LVHIIT is the preferred modality to improve fitness ( 6MWT ) ; it remains to be seen which intervention elicits the most clinical ly relevant outcomes for patients . A larger sample size with a control group is required to confirm the significance of these findings Background Testicular cancer survivors ( TCS ) are at increased risk of cancer-related fatigue ( CRF ) , psychosocial impairment , and poor mental health-related quality of life ( HRQoL ) . Here , we examine the effects of high-intensity interval training ( HIIT ) on patient-reported outcomes ( PROs ) in TCS . Secondarily , we explore cardiorespiratory fitness as a mediator of intervention effects and select baseline characteristics as moderators of intervention effects . Methods TCS ( n = 63 ) were r and omly assigned to 12 weeks of supervised HIIT or usual care ( UC ) . PROs included CRF , depression , anxiety , stress , self-esteem , sleep quality , and HRQoL assessed at baseline , post-intervention , and 3-month follow-up . Results TCS ( median 7 years postdiagnosis ) completed 99 % of training sessions and achieved 98 % of target training intensity . ANCOVA revealed that , compared to UC , HIIT significantly improved post-intervention CRF ( p = 0.003 ) , self-esteem ( p = 0.029 ) , and multiple HRQoL domains ( ps ≤ 0.05 ) . Effects on CRF ( p = 0.031 ) and vitality ( p = 0.015 ) persisted at 3-month follow-up . Cardiorespiratory fitness changes mediated CRF and HRQoL improvements . CRF effects were larger for TCS with an inactive lifestyle , lower fitness , higher testosterone , and clinical fatigue at baseline . Conclusions HIIT significantly improves CRF and HRQoL in TCS . Mediation by cardiorespiratory fitness and moderation by clinical characteristics suggests opportunities for targeted exercise interventions to optimise PROs in TCS 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 Testicular cancer survivors ( TCS ) have an increased risk of treatment‐related cardiovascular disease ( CVD ) , which may limit their overall survival . We evaluated the effects of high‐intensity aerobic interval training ( HIIT ) on traditional and novel CVD risk factors and surrogate markers of mortality in a population ‐based sample of TCS Abstract To compare the effects of a 3‐week multimodal rehabilitation involving supervised high‐intensity interval training ( HIIT ) on female breast cancer survivors with respect to key variables of aerobic fitness , body composition , energy expenditure , cancer‐related fatigue , and quality of life to those of a st and ard multimodal rehabilitation program . A r and omized controlled trial design was administered . Twenty‐eight women , who had been treated for cancer were r and omly assigned to either a group performing exercise of low‐to‐moderate intensity ( LMIE ; n = 14 ) or a group performing high‐intensity interval training ( HIIT ; n = 14 ) as part of a 3‐week multimodal rehabilitation program . No adverse events related to the exercise were reported . Work economy improved following both HIIT and LMIE , with improved peak oxygen uptake following LMIE . HIIT reduced mean total body fat mass with no change in body mass , muscle or fat‐free mass ( best P < 0.06 ) . LMIE increased muscle and total fat‐free body mass . Total energy expenditure ( P = 0.45 ) did not change between the groups , whereas both improved quality of life to a similar high extent and lessened cancer‐related fatigue . This r and omized controlled study demonstrates that HIIT can be performed by female cancer survivors without adverse health effects . Here , HIIT and LMIE both improved work economy , quality of life and cancer‐related fatigue , body composition or energy expenditure . Since the outcomes were similar , but HIIT takes less time , this may be a time‐efficient strategy for improving certain aspects of the health of female cancer survivors Purpose Following colorectal cancer diagnosis and anti-cancer therapy , declines in cardiorespiratory fitness and body composition lead to significant increases in morbidity and mortality . There is increasing interest within the field of exercise oncology surrounding potential strategies to remediate these adverse outcomes . This study compared 4 weeks of moderate-intensity exercise ( MIE ) and high-intensity exercise ( HIE ) training on peak oxygen consumption ( V̇O2peak ) and body composition in colorectal cancer survivors . Methods Forty seven post-treatment colorectal cancer survivors ( HIE = 27 months post-treatment ; MIE = 38 months post-treatment ) were r and omised to either HIE [ 85–95 % peak heart rate ( HRpeak ) ] or MIE ( 70 % HRpeak ) in equivalence with current physical activity guidelines and completed 12 training sessions over 4 weeks . Results HIE was superior to MIE in improving absolute ( p = 0.016 ) and relative ( p = 0.021 ) V̇O2peak . Absolute ( + 0.28 L.min−1 , p < 0.001 ) and relative ( + 3.5 ml.kg−1.min−1 , p < 0.001 ) V̇O2 peak were increased in the HIE group but not the MIE group following training . HIE led to significant increases in lean mass ( + 0.72 kg , p = 0.002 ) and decreases in fat mass ( −0.74 kg , p < 0.001 ) and fat percentage ( −1.0 % , p < 0.001 ) , whereas no changes were observed for the MIE group . There were no severe adverse events . Conclusions In response to short-term training , HIE is a safe , feasible and efficacious intervention that offers clinical ly meaningful improvements in cardiorespiratory fitness and body composition for colorectal cancer survivors . Implication s for Cancer SurvivorsHIE appears to offer superior improvements in cardiorespiratory fitness and body composition in comparison to current physical activity recommendations for colorectal cancer survivors and therefore may be an effective clinical utility following treatment Background Exercise therapy is being explored in a variety of cancer population s to counteract treatment-related deconditioning . Higher intensity interval protocol s are being prescribed to improve physical function and attenuate surrogates of comorbidity in non-cancer population s. The purpose of this study is to explore the safety of higher intensity exercise stimuli on cardiorespiratory fitness ( VO2peak ) in breast cancer survivors . Methods Postmenopausal breast cancer survivors were r and omized into three groups : supervised aerobic interval training ( AIT ) , supervised continuous moderate exercise training ( CMT ) , and an unsupervised control group ( CON ) . For 6 weeks , AIT exercised between 70 and 100 % VO2peak , while CMT exercised between 60 and 70 % VO2peak . Both groups followed a matched-work design . Results Thirty-three participants completed the study ( age , 57.2 ( 9 ) years ; weight , 67.6 ( 12 ) kg ) with no adverse advents . Between-group baseline values were non-significant . VO2peak at baseline ( 25.3 ( 5.4 ) mL·kg−1·min−1 ) was below population norms . Compared to CON , cardiorespiratory fitness improved in AIT and CMT by 12 % ( P < 0.001 ) with no significant difference between exercise groups . AIT had a greater influence on lower extremity strength ( P = 0.026 ) and body weight ( P = 0.031 ) . Conclusion This pilot study provides evidence that similar to CMT , AIT can safely increase VO2peak in a small group of breast cancer survivors . Further exploration of the benefits of implementing higher intensity training protocol s is warranted Purpose : Evidence suggests that lean body mass ( LBM ) may be useful to normalize doses of chemotherapy . Data from a prospect i ve study were used to determine if the highest doses of 5-fluorouracil ( 5-FU ) per kilogram LBM would be associated with dose-limiting toxicity in stage II/III colon cancer patients treated with 5-FU and leucovorin . Experimental Design : Toxicity after cycle 1 was grade d according to National Cancer Institute Common Toxicity Criteria , version 2.0 . Muscle tissue was measured by computerized tomography . An extrapolation to the LBM compartment of the whole body was employed . Results : Mean values of 5-FU/LBM of the entire population were different in terms of presence or absence of toxicity ( P = 0.036 ) . A cut point of 20 mg 5-FU/kg LBM seemed to be a threshold for developing toxicity ( P = 0.005 ) . This observation was pertinent to women ( odds ratio , 16.73 ; P = 0.021 ) . Women in this study had a relatively low proportion of LBM relative to their body surface area . Conclusion : Our study shows that low LBM is a significant predictor of toxicity in female patients administered 5-FU using the convention of dosing per unit of body surface area . We conclude that variation in toxicity between females and males may be partially explained by this feature of body composition Introduction : Impairment in aerobic fitness is a potential modifiable risk factor for postoperative complications . In this r and omized controlled trial , we hypothesized that a high‐intensity interval training ( HIIT ) program enhances cardiorespiratory fitness before lung cancer surgery and therefore reduces the risk of postoperative complications . Methods : Patients with operable lung cancer were r and omly assigned to usual care ( UC ) ( n = 77 ) or preoperative rehabilitation based on HIIT ( Rehab ) ( n = 74 ) . Maximal cardiopulmonary exercise testing and the 6‐minute walk test were performed twice before surgery . The primary outcome measure was a composite of death and in‐hospital postoperative complications . Results : The groups were well balanced in terms of patient characteristics . During the preoperative waiting period ( median 25 days ) , the peak oxygen consumption and the 6‐minute walking distance increased ( median + 15 % , interquartile range , 25th to 75 percentile [ IQR25%–75 % , % ] = + 9 % to + 22 % , p = 0.003 and + 15 % , IQR25%–75 % = + 8 % to + 28 % , p < 0.001 , respectively ) in the Rehab group , whereas peak oxygen consumption declined in the UC group ( median –8 % , IQR25%–75 % = –16 % to 0 % ] , p = 0.005 ) . The primary end point did not differ significantly between the two groups : at least one postoperative complication developed in 27 of the 74 patients ( 35.5 % ) in the Rehab group and 39 of 77 patients ( 50.6 % ) in the UC group ( p = 0.080 ) . Notably , the incidence of pulmonary complications was lower in the Rehab compared with in the UC group ( 23 % versus 44 % , p = 0.018 ) , owing to a significant reduction in atelectasis ( 12.2 % versus 36.4 % , p < 0.001 ) , and this decrease was accompanied by a shorter length of stay in the postanesthesia care unit ( median –7 hours , IQR25%–75 % = –4 to –10 ) . Conclusions : In this r and omized controlled trial , preoperative HIIT result ed in significant improvement in aerobic performances but failed to reduce early complications after lung cancer resection |
12,722 | 28,601,917 | Postdiagnosis HRT use also showed a beneficial effect on breast cancer survival .
In the subgroup analyses , we found that patients who were current users at diagnosis or who received combined hormone therapy before diagnosis seemed to show more benefit from HRT use .
In conclusion , the average effect of HRT use seems not harmful to breast cancer survival . | Previous studies on the association between hormone replacement therapy ( HRT ) and breast cancer survival have yielded mixed results .
We aim ed to perform a meta- analysis to assess the association with all available studies . | CONTEXT The Women 's Health Initiative trial of combined estrogen plus progestin was stopped early when overall health risks , including invasive breast cancer , exceeded benefits . Outst and ing issues not previously addressed include characteristics of breast cancers observed among women using hormones and whether diagnosis may be influenced by hormone effects on mammography . OBJECTIVE To determine the relationship among estrogen plus progestin use , breast cancer characteristics , and mammography recommendations . DESIGN , SETTING , AND PARTICIPANTS Following a comprehensive breast cancer risk assessment , 16 608 postmenopausal women aged 50 to 79 years with an intact uterus were r and omly assigned to receive combined conjugated equine estrogens ( 0.625 mg/d ) plus medroxyprogesterone acetate ( 2.5 mg/d ) or placebo from 1993 to 1998 at 40 clinical centers . Screening mammography and clinical breast examinations were performed at baseline and yearly thereafter . MAIN OUTCOME MEASURES Breast cancer number and characteristics , and frequency of abnormal mammograms by estrogen plus progestin exposure . RESULTS In intent-to-treat analyses , estrogen plus progestin increased total ( 245 vs 185 cases ; hazard ratio [ HR ] , 1.24 ; weighted P<.001 ) and invasive ( 199 vs 150 cases ; HR , 1.24 ; weighted P = .003 ) breast cancers compared with placebo . The invasive breast cancers diagnosed in the estrogen plus progestin group were similar in histology and grade but were larger ( mean [ SD ] , 1.7 cm [ 1.1 ] vs 1.5 cm [ 0.9 ] , respectively ; P = .04 ) and were at more advanced stage ( regional/metastatic 25.4 % vs 16.0 % , respectively ; P = .04 ) compared with those diagnosed in the placebo group . After 1 year , the percentage of women with abnormal mammograms was substantially greater in the estrogen plus progestin group ( 716 [ 9.4 % ] of 7656 ) compared with placebo group ( 398 [ 5.4 % ] of 7310 ; P<.001 ) , a pattern which continued for the study duration . CONCLUSIONS Relatively short-term combined estrogen plus progestin use increases incident breast cancers , which are diagnosed at a more advanced stage compared with placebo use , and also substantially increases the percentage of women with abnormal mammograms . These results suggest estrogen plus progestin may stimulate breast cancer growth and hinder breast cancer diagnosis OBJECTIVES To analyze prospect ively the association between hormone replacement therapy ( HRT ) and mortality in women before old age . DESIGN AND METHODS A group of 11,667 women ( 91 % of the age cohort of the area ) aged 52 - 62 years from the population -based Kuopio Osteoporosis Risk Factor and Prevention Study were followed for 7 years in 1994 - 2001 . Information about HRT use and health events was obtained from two repeated question naires in 1989 and 1994 . Information about deaths and causes of death from the follow-up period was obtained from the Statistics Finl and . Cox 's proportional-hazards models were used to calculate risk of death related to the use of HRT . RESULTS At the start of follow-up , 2203 women had used HRT > 5 years , 3945 women < or = 5 years and 5519 women had never used it . During the follow-up , 361 deaths occurred . Compared with non-users of HRT , the adjusted hazard ratio ( HR ) of death from any cause was 1.05 ( 95 % confidence interval ( CI ) 0.80 - 1.36 ) in women who used HRT < or = 5 years and 1.06 ( 95 % CI 0.78 - 1.46 ) in women who used HRT > 5 years . The adjusted HR for coronary heart disease ( CHD ) mortality in women who used HRT < or = 5 years was 0.79 ( 95 % CI 0.36 - 1.73 ) , and in women who used HRT > 5 years , 2.16 ( 95 % CI 0.93 - 4.98 ) . For breast cancer mortality the adjusted HR for < or = 5 years of HRT use was 0.96 ( 95 % CI 0.32 - 2.82 ) and 2.62 ( 95 % CI 0.98 - 7.00 ) for > 5 years of HRT use . CONCLUSIONS History of HRT use does not affect overall or CHD mortality in women . More than 5 years of HRT use may increase the risk of breast cancer mortality Of 256 patients with breast cancer diagnosed between 1972 and 1981 , 102 have died ( mortality , 39.8 % ) . More hormone users had negative axillary nodes ( 57.1 % ) than did nonusers ( 41.8 % ) . The mortality of the hormone users ( 22.2 % ) was significantly lower ( p less than or equal to 0.01 ) than that of the nonusers ( 45.5 % ) . In 162 patients whose diagnosis of breast cancer was made prior to 1979 , the 5-year survival rate in hormone users was 76.2 % compared to 48.1 % in nonusers . During the prospect i ve phase of the study from 1975 to 1981 , the lowest incidence of breast carcinoma ( 67.3:100,000 ) was observed in the estrogen-progestogen users and was significantly lower than that of the untreated group ( 342.3:100,000 ) and lower than that expected from both the Third National Cancer Survey and the National Cancer Institute System for Electronic Evaluation and Retrieval ( SEER ) data ( p less than or equal to 0.01 ) . Estrogen therapy does not increase the risk of mammary malignancy , but added progestogen significantly decreases the risk BACKGROUND Hormone replacement therapy ( HRT ) is typically avoided for women with a history of breast cancer because of concerns that estrogen will stimulate recurrence . In this study , we sought to evaluate the impact of HRT on recurrence and mortality after a diagnosis of breast cancer . METHODS Data were assembled from 2755 women aged 35 - 74 years who were diagnosed with incident invasive breast cancer while they were enrolled in a large health maintenance organization from 1977 through 1994 . Pharmacy data identified 174 users of HRT after diagnosis . Each HRT user was matched to four r and omly selected nonusers of HRT with similar age , disease stage , and year of diagnosis . Women in the analysis were recurrence free at HRT initiation or the equivalent time since diagnosis . Rates of recurrence and death through 1996 were calculated . Adjusted relative risks were estimated by use of the Cox regression model . All statistical tests were two-sided . RESULTS The rate of breast cancer recurrence was 17 per 1000 person-years in women who used HRT after diagnosis and 30 per 1000 person-years in nonusers ( adjusted relative risk for users compared with nonusers = 0.50 ; 95 % confidence interval [ CI ] = 0.30 to 0.85 ) . Breast cancer mortality rates were five per 1000 person-years in HRT users and 15 per 1000 person-years in nonusers ( adjusted relative risk = 0.34 ; 95 % CI = 0.13 to 0.91 ) . Total mortality rates were 16 per 1000 person-years in HRT users and 30 per 1000 person-years in nonusers ( adjusted relative risk = 0.48 ; 95 % CI = 0.29 to 0.78 ) . The relatively low rates of recurrence and death were observed in women who used any type of HRT ( oral only = 41 % of HRT users ; vaginal only = 43 % ; both oral and vaginal = 16 % ) . No trend toward lower relative risks was observed with increased dose . CONCLUSION We observed lower risks of recurrence and mortality in women who used HRT after breast cancer diagnosis than in women who did not . Although residual confounding may exist , the results suggest that HRT after breast cancer has no adverse impact on recurrence and mortality Summary Nine hundred and eighty-four breast cancer patients were interviewed regarding exogenous hormonal use . This represents a r and om sample of breast cancer patients in Southern Sweden referred to the Department of Oncology at Lund for treatment between 1978 and 1997 ( excluding 1980 and 1981 ) with a 100 % follow-up . Ever-use of hormone replacement therapy ( HRT ) prior to diagnosis was significantly associated with a longer overall survival in women with their breast cancer diagnosed at ages 45 and above , relative risk ( RR ) of dying 0.73 ( 95 % confidence interval ( CI ) 0.62–0.87 ; P = 0.0005 ) . Ever use of HRT prior to breast cancer diagnosis was significantly positively associated with overall longer survival after adjustment for T-stage , N-stage , M-stage , year of diagnosis and age at diagnosis , RR of dying 0.78 ( 95 % CI 0.65–0.93 ; P = 0.006 ) . Hormone replacement therapy use and oestrogen receptor positivity were independently significantly associated with overall longer survival , P = 0.005 and P < 0.0001 , respectively , in one model . HRT use and progesterone receptor positivity were also independently significantly associated with longer overall survival , P = 0.003 and P = 0.0003 , respectively , in another model . The mode of diagnosis was known in 705 women . Mammography screening was not more common among HRT users compared with never-users , where this information was available . Both mammography screening and HRT use were independently associated with longer survival , P = 0.002 and P = 0.038 respectively It is well known that a family history of breast cancer is an important risk factor for the disease . A critical issue is how to advise patients with a family history of breast cancer about perimenopausal and postmenopausal use of hormone replacement therapy ( HRT ) . Hoskins and colleagues [ 1 ] have provided guidelines on assessment and counseling of women with such a history , including a recommendation that they avoid exogenous estrogens . A considerable body of literature has discussed the association of HRT and risk for breast cancer . Interpretation of available data is not consistent : Two meta-analyses [ 2 , 3 ] found a positive association , and two others [ 4 , 5 ] found no association . More recent studies have not clarified the issue [ 6 - 8 ] . Findings on increased risk in women with a family history of breast cancer have been more consistent . A meta- analysis [ 3 ] of five studies that had examined the issue suggested that the risk for breast cancer associated with HRT was elevated among women without a family history of breast cancer ( relative risk [ RR ] , 1.5 [ 95 % CI , 1.2 to 1.7 ] ) but was even greater among women with a family history ( RR , 3.4 [ CI , 2.0 to 6.0 ] ) . Of the studies not included in the meta- analysis , some [ 9 - 12 ] but not all [ 6 , 7 , 13 ] reported similar observations . Beyond the issue of the effects of HRT on the incidence of breast cancer , further consideration of the concomitant effect of HRT on risk for death is warranted . A recent report from the Nurses ' Health Study [ 8 ] suggests that hormonal therapy lasting at least 5 years is associated with a 45 % increase in the rate of death from breast cancer . Analytic epidemiologic studies suggest that women who receive HRT have a significantly lower risk for death , primarily because of protection against cardiovascular disease [ 14 - 17 ] . Thus , it is important to examine all-cause mortality when considering the risks and benefits of HRT use [ 18 ] , especially among women with a family history of breast cancer . As part of the Iowa Women 's Health Study , a prospect i ve cohort study of 41 837 women who were 55 to 69 years of age at baseline in 1986 , data were collected on self-reported family history of breast cancer in first-degree relatives and on history of HRT use . These data were used to examine the risks for postmenopausal breast cancer , case fatality , and total mortality . Methods The Iowa Women 's Health Study Cohort Participants in the Iowa Women 's Health Study were selected from a r and om sample of all women between 55 and 69 years of age who had a valid Iowa driver 's license in 1985 [ 19 ] . This sampling frame comprised approximately 94 % of female Iowa residents in that age range . The primary purpose of the study was to examine the association of obesity and body fat distribution with the incidence of cancer and mortality rate . A total of 41 837 women returned a mailed question naire ( response rate , 42.7 % ) . Three follow-up question naires mailed in October 1987 , August 1989 , and June 1992 were used to collect information on incident self-reported disease and each participant 's current residence . Only minor demographic differences were seen at baseline between respondents and nonrespondents [ 20 ] . Nonrespondents have subsequently been found to have a higher 5-year incidence of cancer and rate of death ( primarily death from diseases related to smoking ) [ 21 ] . The incidence of breast cancer , however , was similar among respondents and nonrespondents ( RR , 1.01 [ CI , 0.9 to 1.1 ] ) . Self-reported items on the baseline question naire included education level ; marital status ; smoking history ; usual alcohol intake during the past year ; physical activity ; reproductive history ; and history of various medical conditions , including diabetes and heart disease . We asked women whether they had menstruated in the past year and asked them to state the age at which and the reason why their periods had stopped ( natural menopause , surgery , medication , or other ) . We asked them whether they had ever used pills , other than birth control pills , which contain estrogen or other female hormones and how long they had used them . Response categories for duration of use were one month or less , 2 - 6 months , 7 - 12 months , 13 months-2 years , 3 - 5 years , or more than 5 years . Participants were asked whether their mothers , sisters , or daughters had ever had breast cancer . No information was collected on the number of relatives in a given category or on the age of relatives . For exclusion purpose s , we ascertained the presence of prevalent cancer by asking participants whether they had ever been told by a physician that they had any form of cancer , excluding skin cancer . Participants reported their current height and weight and their weight at 18 years of age . A paper measuring tape was sent so that a friend , spouse , or relative could measure the circumferences of the waist ( 1 inch above the umbilicus ) and the hips ( maximum ) . The height , weight , and circumference measurements obtained by this protocol are valid and reliable [ 22 ] . Anthropometric values were used to derive current body mass index ( weight in kg/height in m2 ) , body mass index at 18 years of age ( based on their current height ) , and the ratio of waist circumference to hip circumference . The second follow-up survey included questions on use of mammography , including whether the participants had ever undergone mammography and the length of time since the last mammography had been done . Cohort Follow-up Cases of breast cancer ( codes 500 to 509 of the International Classification of Diseases for Oncology , Second Edition ) among Iowa residents were ascertained through the State Health Registry of Iowa , which is part of the National Cancer Institute 's Surveillance , Epidemiology , and End Results Program ( SEER ) [ 23 ] . Each year , registry cases and cohort members were matched by a computer according to social security number , name , maiden name , and date of birth . Primary tumor site , date of diagnosis , nonspecific extent of disease , and tumor size were obtained for each incident cancer case from 1986 through 1993 . Information on deaths was obtained from the State Health Registry of Iowa for Iowa residents and from the National Death Index for women who did not respond to the three follow-up surveys . Causes of death were coded according to the International Classification of Diseases , Ninth Revision [ 24 ] . Data Analysis Participants with the following baseline characteristics were excluded from the analysis : premenopausal status ( n = 569 ) , total or partial mastectomy ( n = 1870 ) , history of any cancer other than skin cancer ( n = 2293 ) , and unknown family history of breast cancer ( n = 1186 ) . After women with these characteristics were excluded , 35 919 women remained in the at-risk cohort for analysis . Women were considered to be at risk for breast cancer from January 1986 through 31 December 1993 or until one of the following censoring events occurred : diagnosis of breast cancer , death , relocation to an area other than Iowa , or other loss to follow-up . Person-years of follow-up for the mortality analyses were calculated from completion of the 1986 baseline question naire until death or the end of 1993 . Characteristics of the women were collapsed into natural categories or quartiles . Use of HRT was categorized by status ( current , former , and never ) at baseline and by duration ( 5 years or > 5 years ) . To describe the association of family history , HRT , and other variables with the incidence of breast cancer and total mortality rate , we computed age-adjusted rates and 95 % CIs [ 25 ] ; multivariate-adjusted relative risks and 95 % CIs were derived through proportional hazards regression models by using the SAS program PHREG ( SAS Institute , Cary , North Carolina ) [ 26 ] . Multiplicative interactions were evaluated by comparing the 2 log likelihoods of models with and without the cross-product ( interaction ) terms within the context of proportional hazards regression . Results Risk Factors and Incidence of Breast Cancer After 8 years and more than 275 000 person-years of observation , 1085 cases of postmenopausal breast cancer were documented . The association of accepted risk factors [ 27 ] with incidence of breast cancer was evident in this cohort . Early age at menarche , late age at first birth , high waist-to-hip ratio , high body mass index , education , and alcohol intake were associated with increased risk ; high body mass index at 18 years of age was associated with decreased risk ( Table 1 ) . All subsequent analyses of the incidence of breast cancer include adjustment for these risk factors in addition to current age , type of menopause , and age at menopause . Table 1 . Multivariate-Adjusted Relative Risks for Potential Risk Factors for Breast Cancer among 35 919 Postmenopausal Women * Hormone Replacement Therapy and Incidence of Breast Cancer by Family History A family history of breast cancer in mothers or sisters was reported by 12.2 % of the cohort at risk . Approximately 38 % of the cohort at risk reported having ever received HRT . The frequency of reported use did not differ by family history : 38.3 % of women without a family history and 37.7 % of women with a family history ( P > 0.2 ) . Duration of use was similar ( P > 0.2 ) . After adjustment for the risk factors listed in Table 1 , the relative risks for breast cancer among women who had formerly received HRT for 5 years or less or for more than 5 years were 1.04 and 0.89 , respectively . The multivariate adjusted relative risks for current short-term ( 5 years ) and long-term ( > 5 years ) users of HRT were 1.34 ( CI , 0.98 to 1.82 ) and 1.17 ( CI , 0.90 to 1.51 ) , respectively . The age-adjusted incidence rates of breast cancer associated with HRT use by family history of breast cancer are shown in Table 2 . Among women without a family history of breast cancer , the rate of breast cancer in those who were currently receiving HRT and had been receiving it for at least 5 years was 41 cases per 10 000 person-years , a rate not significantly greater than the 36 This study examines the relationship between fatal breast cancer and use of estrogen replacement therapy ( ERT ) among women in a large prospect i ve study in the United States . After nine years of follow-up , 1,469 breast cancer deaths were observedin a cohort of 422,373 postmenopausal women who were cancer free at study entry and who supplied information on estrogen use . Results from Cox proportional hazards modeling , adjusted for 11 other potential risk factors , showed that ever-use of ERT was associated with a significantly decreased risk of fatal breast cancer ( rate ratio [RR]=0.84,95 percent confidence interval [CI]=0.75–0.94 ) . There was a moderate trend ( P=0.07 ) of decreasing risk with younger age at first use of ERT . This decreased risk was most pronounced in women who experienced natural menopause before the age of 40 years ( RR=0.59 , CI=0.40–0.87 ) . There was no discernible trend of increasing risk with duration of use in estrogen users at baseline or former users , nor was there any trend in years since last use in former users . The relationship between ERT and breast cancer mortality differed by age at menarche and by a self-reported history of breast cysts . No increased risk of fatal breast cancer with ERT was observed with estrogen use status ( baseline/former ) , age at first use , duration of use , or years since last use . These findings suggest that ever-use of ERT is associated with a 16 percent decreased risk of fatal breast cancer Hormone-replacement therapy ( HRT ) is widely used by post-menopausal women . Although this treatment may slightly increase the incidence of breast cancer , more and more cases are diagnosed while women are taking HRT . The purpose of this study was to ascertain the influence of HRT on prognostic factors and outcome of breast cancer . Data on all breast-cancer patients , including precise information on HRT , was prospect ively and systematic ally recorded in a data base . From 1985 to 1995 , 1379 post-menopausal women fulfilled the eligibility criteria for this study . All were treated by us ( P.B. and L.P. ) in our ward of a large public hospital of Marseilles , France . The clinical features , laboratory findings and survival rates in 142 HRT users who developed breast cancer while being treated were compared with those of 284 matched never user breast-cancer patients . Patients who developed breast cancer during HRT had fewer locally advanced cancers and smaller and better-differentiated cancers . Lymph-node involvement was significantly less frequent in the user group than in the non-user group ( non-significant ) . Estradiol receptivity was both qualitatively and quantitatively lower in users . There was no significant difference with regard to recurrence and metastasis-free survival and overall survival . We conclude that HRT does not affect the prognosis of breast cancer . Regular surveillance during HRT allows early detection of smaller lesions . The higher number of well-differentiated cancers and the distribution of hormone receptivity may reflect interaction between neoplastic tissue and exogenous hormones Background : A few studies have observed reduced breast cancer mortality in women who used hormone therapy before diagnosis . Due to the high prevalence of past and current hormone use , it is important to investigate whether these preparations are related to breast cancer mortality . Methods : To evaluate the influence of prediagnostic use of hormone therapy on breast cancer mortality , a prospect i ve cohort of 12,269 women ages 50 years or more diagnosed with incident invasive breast cancer and residents of Wisconsin , Massachusetts , or New Hampshire were enrolled in three phases beginning in 1988 . They were followed for death until December 31 , 2005 , using the National Death Index . Cumulative mortality and multivariable adjusted hazard rate ratios for breast cancer and other mortality causes were calculated for women according to any hormone therapy use , and for exclusive use of estrogen or estrogen-progestin ( EP ) . Results : During an average 10.3 years of follow-up , 1,690 deaths from breast cancer were documented . Cumulative mortality from breast cancer was lower among hormone therapy users , specifically current users at the time of diagnosis , and EP users , compared with nonusers . Adjusted survival varied by type and duration of hormone therapy before diagnosis . A reduced risk of death from breast cancer was associated with EP preparations ( hazard rate ratio , 0.73 ; 0.59 - 0.91 ) and with ≥5 years of EP use ( 0.60 ; 0.43 - 0.84 ) . No association was observed for women who were former or current users of E-alone preparations . Conclusions : Although use of combined EP preparations increases breast cancer risk , in this study , use of these hormones before diagnosis was associated with reduced risk of death after a breast cancer diagnosis . The better survival among users , particularly of EP , persisted after adjustment of screening , stage , and measured confounders . ( Cancer Epidemiol Biomarkers Prev 2008;17(4):864–71 OBJECTIVE Our purpose was to measure any adverse effect ( if one exists ) of hormone replacement therapy administered to breast cancer survivors . STUDY DESIGN Forty-one patients from a group of 77 patients who received hormone replacement therapy after therapy for breast cancer were matched with 82 comparison patients not receiving hormone replacement therapy . Both groups were taken from the same population on the basis of cancer registry of the Cancer Surveillance Program of Orange County and were compared with regard to survival results . RESULTS An analysis of survival time and disease-free time revealed no statistically significant difference between the two groups . CONCLUSIONS No obvious adverse effect of hormone replacement therapy could be shown in this pilot study . A case is made for a prospect i ve r and omized trial OBJECTIVE To reexamine the mortality experience of a cohort of long-term users of hormone replacement therapy ( HRT ) in comparison with that reported previously for the same cohort of women , paying particular attention to cardiovascular mortality , deaths from breast and endometrial cancer , and deaths attributed to suicide or suspected suicide . DESIGN Longitudinal cohort of 4544 long-term users of HRT amongst whom mortality is being monitored prospect ively in comparison with expected rates in the female population of Engl and and Wales ( taking account of age and calendar period ) . SUBJECTS 4544 women , all of whom were recruited from specialist menopause clinics around Britain and had taken at least one year 's continuous HRT at the time of recruitment to the study . MAIN OUTCOME MEASURES All cause mortality , cardiovascular mortality , deaths from female cancers , deaths attributed to suicide or suspected suicide . RESULTS Overall mortality ( based on 236 deaths over the entire study period from recruitment to December 1988 ) remained significantly lower than expected on the basis of national rates ( relative risk ( RR ) 0.56 , 95 % confidence limits ( CL ) 0.47 - 0.66 ) . When specific causes were considered , the only mortality ratios greater than unity were for injury , poisoning and violence ( 1.54 , 95 % CL 1.02 - 2.06 ) , and for suicide and suspected suicide ( ' suicide ' ) ( 2.40 , 95 % CL 1.68 - 3.11 ) . Comparison of the ratios for the 112 additional deaths with those obtained in our previous analysis revealed that one of the few ratios to show any increase was that for breast cancer mortality . This rose from a significant deficit of 0.55 ( 95 % CL 0.28 - 0.96 ) in the earlier period to 1.00 ( 95 % CL 0.55 - 1.45 ) in the later period . There was also a suggestion of an increase in breast cancer risk with increasing duration since first use of HRT . Most of the other cause-specific ratios were very similar over the two periods . The ratio of death from all circulatory diseases was notably lower in the later analysis ( RR 0.37 , 95 % CL 0.15 - 0.58 ) than in the earlier analysis ( 0.51 , 95 % CL 0.36 - 0.69 ) , as were all of the subcategories of cardiovascular death . The mortality ratio for cancer of the ovary and uterine adnexa fell from 1.12 in the previous analysis to 0.63 ( 95 % CL 0 - 1.41 ) . The mortality ratio for ' suicide ' also decreased , but was only slightly lower in the later period . As before , however , there was evidence of a relatively high prevalence of prior psychiatric problems amongst the recent ' suicide ' deaths , suggesting that the excess of deaths from ' suicide ' may be a manifestation of selection . CONCLUSION These data are consistent with a beneficial effect of HRT on cardiovascular diseases , although up date d information comparing progestogen-opposed and -unopposed treatment is not available . The increase in breast cancer mortality contrasts with the pattern for all other specific causes examined ; taken together with the suggestion of an increase in breast cancer mortality with increasing interval since first exposure to HRT , this finding is somewhat worrying We examined the relation between menopausal estrogen use and all-cause and cause-specific mortality in a cohort of over 49,000 women followed between 1979 and 1989 in the Breast Cancer Detection Demonstration Project ( BCDDP ) Follow-Up Study . We found a lower all-cause mortality rate among women who took estrogens [ rate ratio ( RR ) = 0.7 ; 95 % confidence interval ( CI ) = 0.7–0.8 ] , particularly current users ( RR = 0.3 ; 95 % CI = 0.2–0.4 ) , than among women who never took them . Additional analyses , however , revealed that women who had recently stopped taking estrogens had a higher all-cause mortality rate than women who had never taken them ( RR = 1.4 ; 95 % CI = 1.2–1.7 ) . Women who had recently stopped taking estrogens also had higher mortality rates from circulatory disease ( RR = 1.3 ; 95 % CI = 1.0–1.8 ) and cancer ( RR = 1.6 ; 95 % CI = 1.2–2.2 ) than women who never took them . The most likely explanation for these results is that women stop taking estrogens when they develop symptoms of serious illness . As a consequence of this “ healthy estrogen user survivor effect , ” nonexperimental studies are susceptible to overestimating the benefits of menopausal estrogen use , particularly current use , on mortality This study examines the impact of smoking , body mass index , alcohol consumption , hormone replacement therapy , and physical activity on all-cause mortality among 528 Danish women diagnosed with primary breast cancer . Participants were women enrolled in the Copenhagen City Heart Study . Prospect i ve self-reported exposure information was collected from four points of follow-up in 1976–1978 , 1981–1983 , 1991–1994 , and 2001–2003 . Kaplan – Meier survival curves and multivariate Cox regression analyses were performed adjusting for age , disease stage , adjuvant treatment , menopausal status , parity , alcohol intake , smoking , physical activity , body mass index , and hormone replacement therapy . The study shows that smoking for total mortality [ hazard ratio , 1.16 ; 95 % confidence interval , 1.05–1.29 ] and obesity for both total mortality ( 1.61 ; 1.12–2.33 ) and breast cancer-specific mortality ( 1.82 ; 1.11–2.99 ) were significantly associated with decreased survival after breast cancer diagnosis . A moderate alcohol intake of 1 - 6 units/week ( 0.85 ; 0.64–1.12 ) , 7–14 units/week ( 0.77 ; 0.56–1.08 ) , and treatment with hormone replacement therapy ( 0.79 ; 0.59–1.05 ) were less than 1 , but not statistically significantly associated with prolonged survival . A moderate physical activity of 2–4 h/week ( 1.07 ; 0.77–1.49 ) and a high physical activity of more than 4 h/week ( 1.00 ; 0.69–1.45 ) showed no association with survival after breast cancer diagnosis UNLABELLED Women who have been previously treated for breast cancer are usually advised to avoid hormone therapy for fear of increasing their risk of tumor recurrence . However , for some women , menopausal symptoms are so severe that their quality of life is poor . Because ethic committees are reticent to permit a double-blind r and omized trial , we performed a cohort study of hormone therapy after breast cancer . METHODS The study group comprised 1472 women with breast cancer . A total of 167 subjects had used an oral or transdermal estrogen after their treatment for breast cancer . Amongst these estrogen users , 152 ( 91 % ) had also used a progestin . In total , 106 other women had used a progestin alone as a treatment for menopausal flushes and not as a treatment for breast cancer . Cox regression analysis was performed using estrogen as a time-dependent covariate with disease-free interval as the outcome . RESULTS The uncorrected hazard ratio for the estrogen-progestin users was 0.67 ( 95 % confidence interval ( CI ) 0.38 - 1.16 ) and for the progestin alone users was 0.85 ( 95 % CI 0.44 - 1.65 ) . CONCLUSIONS This study was unable to demonstrate a significant increase in risk of breast cancer recurrence for women who used HRT and suggests that the time is now appropriate for a r and omized prospect i ve trial of hormone therapy after breast cancer AIMS To investigate the presumed influence of hormone replacement therapy ( HRT ) on the progression of and death due to breast cancer . METHODS In order to make a detailed analysis , we selected a group of 21 patients with the diagnosis of invasive breast cancer who had HRT after primary surgical treatment . Each patient from the selected group was compared with two patients from the control group with the diagnosis of invasive breast cancer who did not have HRT after primary surgical treatment . The control cases were matched to selected HRT patients with regard to age at time of the diagnosis , year of diagnosis , diameter of the tumour , metastatic spread in the axillary lymph nodes , and disease-free interval until applying HRT . The same criteria were applied in all analyses . The data were analysed by odds ratio ( OR ) calculation with a confidence interval of 95 % , taking into account residual malignancy and death due to breast cancer in both groups ( including carcinoma in the contralateral breast ) . RESULTS HRT was applied in 21 patients treated for breast cancer . In 33 % of them , radical mastectomy revealed metastases in the axillary lymph nodes . Hormone receptors could not be found in 57 % of patients . In the majority of patients the tumour measured 17.6 mm in diameter . HRT was started on average 62 months ( range 1 - 180 months ) after diagnosis , and lasted an average of 28 months ( range 3 72 months ) . All 21 patients used oestradiol as HRT , i.e. a non-conjugated oestrogen . Combined hormonal therapy ( oestrogens + progestagens ) was given to 95 % of patients with median age of 47 years ( range 41 - 59 years ) at the beginning of HRT . Relapse was observed in four patients ( 19 % ) of the HRT group ; of these , one had a carcinoma of the contralateral breast . In the control group , relapse was observed in five patients ( 11 % ) ; one of these five patients had a carcinoma of the contralateral breast . In the HRT group , there were no deaths among the patients with confirmed relapse , while one patient died in the control group . The estimated risk ( OR= 1.74 , 95%S CI 0.34 - 8.88 ) of relapse of breast cancer was calculated by comparing data from HRT users , who had received HRT for 28 months ( range 3 - 72 months ) on average , with data from the control group . The estimated risk of breast cancer relapse in HRT users who had been receiving HRT for less than 24 months was 0.65 ( OR = 0.65 , 95 % CI 0.02 - 7.85 ) . CONCLUSION Despite the inherent limitations of retrospective data and the need for prospect i ve r and omized trials to assess the possible influence of HRT on progression after breast cancer treatment , the present observations suggest that HRT treatment for less than 24 months does not appear to have a pronounced adverse effect on cancer outcome . Nevertheless , until appropriate clinical trials determine that HRT is safe , caution is needed Purpose : Breast cancer ( BC ) is the most frequent female carcinoma and the major cause of death in women aged 35–50 years . The total number of patients surviving BC and especially the morbidity rate of patients below the age of 55 years has increased significantly in the last several years . As a consequence , the number of BC patients suffering from the long-term effects of estrogen deficiency due to adjuvant treatment is increasing . At present , hormone replacement therapy ( HRT ) following BC treatment is applied individually and mainly depends on the severity of postmenopausal symptoms ( PMS ) experienced by these patients . Patients and Methods : In a retrospective study ( total n = 185 BC patients , 64 with and 121 without HRT ) , the effect of HRT during or after adjuvant therapy [ chemotherapy and / or ( anti- ) hormonotherapy ] has been investigated . The surveillance period was up to 60 months . Evaluated were HRT effects on ( 1 ) PMS measured by a comprehensive life quality question naire , ( 2 ) bone mineral density ( BMD ) measured by osteodensitometry and ( 3 ) morbidity as well as mortality rates . Results : Both groups did not differ with regard to tumor stage , lymph node involvement , metastasis , grading , and steroid hormone receptor status . A reduction in PMS was significant in women taking HRT ( p < 0.001 ) , especially in the subgroup of women ≤50 years ( p < 0.0001 ) . For both age groups , the median reduction in BMD ( z-score ) was less in women receiving HRT ( ≤50 years : without HRT –1.99 vs. with HRT –0.95 , p < 0.05 ; > 50 years : without HRT –2.29 vs. with HRT –1.19 , p < 0.01 ) . There were no statistically significant differences regarding morbidity and mortality ( p = 0.29 ) . Conclusion : In this study of BC patients , the use of HRT shows positive effects on PMS and BMD . There was no significant influence on morbidity or mortality . However , a reevaluation of HRT in the routine management of BC patients should await the results of prospect i ve r and omized trials OBJECTIVES The association between pre-diagnostic hormone replacement therapy ( HRT ) and breast cancer specific mortality as well as potential influences from other lifestyle factors on the association was investigated . STUDY DESIGN Female participants from the prospect i ve cohort " Diet , Cancer , and Health " diagnosed with breast cancer ( BC ) were identified and their pre-diagnostic HRT use evaluated for association with tumour biology and breast cancer outcome in multivariate analysis . MAIN OUTCOME MEASURE Breast cancer specific mortality . RESULTS Of the 1212 patients originally considered 1064 were included . Of these , 105 women died from breast cancer during a median follow-up of 6.3 years ( range 0.2 - 14.3 years ) . In multivariate analyses women who used HRT at enrolment into the cohort study had 47 % lower risk of dying from breast cancer as compared to women who had previously or never used HRT ( adjusted HR : 0.53 ; 95 % CI , 0.37 - 0.85 ) . Pre-diagnostic HRT use was associated with smaller tumour size at the time of diagnosis and a higher frequency of receptor positive breast cancer . Paradoxically , a high pre-diagnostic intake of vitamin D supplements was associated with HRT use but also with a higher BC specific mortality ( HR : 1.47 ; 95 % CI , 1.07 - 2.00 ) CONCLUSIONS : HRT use at enrolment was associated with breast tumours of smaller size at the time of diagnosis and positive receptor status , and with a lower BC mortality . The found association between vitamin D from supplements and higher BC mortality warrants further exploration BACKGROUND In the Women 's Health Initiative ( WHI ) r and omized trial , estrogen plus progestin increased both breast cancer incidence and mortality . In contrast , most observational studies associate estrogen plus progestin with favorable prognosis breast cancers . To address differences , a cohort of WHI observational study participants with characteristics similar to the WHI clinical trial was studied . METHODS We identified 41 449 postmenopausal women with no prior hysterectomy and mammogram negative within 2 years who were either not hormone users ( n = 25 328 ) or estrogen and progestin users ( n = 16 121 ) . Multivariable-adjusted Cox proportional hazard regression was used to calculate hazard ratios ( HRs ) with 95 % confidence intervals ( CI ) . All statistical tests were two-sided . RESULTS After a mean of 11.3 ( SD = 3.1 ) years , with 2236 breast cancers , incidence was higher in estrogen plus progestin users than in nonusers ( 0.60 % vs 0.42 % , annualized rate , respectively ; HR = 1.55 , 95 % CI = 1.41 to 1.70 , P < .001 ) . Women initiating hormone therapy closer to menopause had higher breast cancer risk with linear diminishing influence as time from menopause increased ( P < .001 ) . Survival after breast cancer , measured from diagnosis , was similar in combined hormone therapy users and nonusers ( HR = 1.03 , 95 % CI = 0.79 to 1.35 ) . On a population basis , there were somewhat more deaths from breast cancer , measured from cohort entry ( HR = 1.32 , 95 % CI = 0.90 to 1.93 , P = .15 ) , and more all-cause deaths after breast cancer ( HR = 1.65 , 95 % CI = 1.29 to 2.12 , P < .001 ) in estrogen plus progestin users than in nonusers . CONCLUSIONS Consistent with WHI r and omized trial findings , estrogen plus progestin use is associated with increased breast cancer incidence . Because prognosis after diagnosis on combined hormone therapy is similar to that of nonusers , increased breast cancer mortality can be expected |
12,723 | 26,835,597 | Overall , sleep was found to enhance motor performance in people after stroke in comparison to an equivalent time of wakefulness .
In addition , although evidence is limited , sleep only enhanced motor performance in people after stroke and not in age-matched healthy older adults .
In older adults the effect of a sleep intervention did - in general - not differ from equivalent periods of wakefulness .
The results suggest a delayed retention effect after longer breaks including sleep , hinting towards a changed learning strategy as a result of aging .
Current evidence for sleep dependent learning in people after stroke is promising , however sparse | There is extensive evidence for positive effects of sleep on motor learning in young individuals ; however , the effects of sleep on motor learning in people with stroke and in healthy older individuals are not well understood .
The aim of this systematic review was to quantify the association between sleep and procedural memory performance - a marker for motor learning - in healthy older people and people with stroke . | There is increasing evidence that sleep promotes off-line enhancement of a variety of explicitly learned motor tasks in young adults . However , whether sleep promotes off-line consolidation of implicitly learned motor tasks is still under question . Furthermore , the role of sleep in promoting transfer of learning remains unknown . This study examined the role of sleep in learning and transfer of learning of an implicit continuous motor task . Twenty-three neurologically intact individuals ( mean age 26.4 years ) were r and omly assigned to either a sleep group or a no-sleep group . The sleep group practice d a continuous tracking task in the evening and underwent retention and transfer testing the following morning , while the no-sleep group practice d the tracking task in the morning and underwent retention and transfer testing in the evening . The results show that in both the sleep and no-sleep groups , performance improved off-line without further practice for both the general skill and the sequence-specific skill . The results also indicate that sleep and time promote transfer of learning of both sequence-specific and general skill learning to a spatial and temporal variation of the motor task . These findings demonstrate that sleep does not play a critical role in promoting off-line learning and transfer of learning of an implicit continuous motor task Decline in cognitive functions , including impaired acquisition of novel skills , is a feature of older age that impacts activities of daily living , independence , and integration in modern societies Background and Purpose : The purpose of this study was to identify which characteristics of a multidimensional sequence containing motor , spatial , and temporal elements would be most salient for motor sequence learning and whether age might differentially affect this learning . Subjects : Younger ( n=11 , mean age=26.0 years ) , middle-aged ( n=13 , mean age=50.7 years ) , and older ( n=11 , mean age=77.5 years ) adults who were neurologically intact participated in the study . Methods : Participants practice d a sequencing task with repeated motor , spatial , and temporal dimensions for 2 days ; on a separate third day , participants completed retention and interference tests design ed to assess sequence learning and which elements of the sequence were learned . The mean median response time for each block of responses was used to assess motor sequence learning . Results : Younger and middle-aged adults demonstrated sequence-specific motor learning at retention testing via faster response times for repeated sequences than r and om sequences ; both of these groups showed interference for the motor dimension . In contrast , older adults demonstrated nonspecific learning ( ie , similar improvements in response time for both r and om and repeated sequences ) . These findings were shown by a lack of difference between r and om and repeated sequence performance in the older adult group both at retention testing and during interference tests . Conclusion and Discussion : Our data suggest that , when younger and middle-aged adults practice sequences containing multiple dimensions of movement , the motor element is most important for motor learning . The absence of sequence-specific change demonstrated by an older adult group that was healthy suggests an age-related impairment in motor learning that may have profound implication s for rehabilitation The frequencies of five common sleep complaints -- trouble falling asleep , waking up , awaking too early , needing to nap and not feeling rested -- were assessed in over 9,000 participants aged 65 years and older in the National Institute on Aging 's multicentered study entitled " Established Population s for Epidemiologic Studies of the Elderly " ( EPESE ) . Less than 20 % of the participants in each community rarely or never had any complaints , whereas over half reported at least one of these complaints as occurring most of the time . Between 23 % and 34 % had symptoms of insomnia , and between 7 % and 15 % percent rarely or never felt rested after waking up in the morning . In multivariate analyses , sleep complaints were associated with an increasing number of respiratory symptoms , physical disabilities , nonprescription medications , depressive symptoms and poorer self-perceived health . Sleep disturbances , particularly among older persons , oftentimes may be secondary to coexisting diseases . Determining the prevalence of specific sleep disorders , independent of health status , will require the development of more sophisticated and objective measures of sleep disturbances OBJECTIVE The present study examined whether the combination of a short daytime nap with caffeine , bright light and face washing was effective against mid-afternoon sleepiness . METHODS Ten young healthy adults participated in 5 experimental conditions ; those experiments were-Nap only : taking a 20 min nap ; Caffeine+Nap : taking 200 mg of caffeine followed by a nap ; Nap+Bright-light : being exposed to 2000 lx of bright light for 1 min immediately after napping ; Nap+Face-washing : washing their faces immediately after napping ; and No-Nap : taking a rest without sleep . These naps were taken at 12:40 hours . The subjects engaged in computer tasks for 15 min before napping and for 1 h after napping . RESULTS Caffeine+Nap was the most effective for subjective sleepiness and performance level ; its effects lasted throughout 1 h after napping . Nap+Bright-light was comparable with Caffeine+Nap , except for performance level . Nap+Face-washing showed mild and transient effects , however , it suppressed subjective sleepiness immediately after napping . CONCLUSIONS The effects of a short nap against mid-afternoon sleepiness could be enhanced by combining caffeine intake , exposure to bright light , or face washing . SIGNIFICANCE The present study would provide effective counter measures against mid-afternoon sleepiness and sleepiness related accidents Memory consolidation is facilitated by sleep . Specifying the functional domain of sleep-dependent consolidation ( SDC ) is important for identifying the neural mechanisms underlying this phenomenon . Previous work indicates that SDC may be limited to conditions in which learning is explicit . In the present study , we tested the hypothesis that SDC may also occur with implicit learning when learning benefits from the formation of context ual associations , a function associated with the hippocampus . Three versions of the serial-reaction-time task ( SRTT ) were examined , and SDC was assessed by comparing performance after 12 hr breaks that included or did not include sleep . SDC was observed in the Explicit condition . Two implicit conditions were compared . In the Implicit Non context ual condition , participants performed a concurrent tone-counting task with the pitch of each tone selected at r and om , precluding cross-dimensional associations . In the Implicit Context ual condition , participants responded to the color of the cues while the spatial location of the cues followed a correlated sequence . Whereas learning was observed in both implicit conditions , SDC was restricted to the context ual condition . Given that the formation of context ual associations is dependent on the hippocampus , we suggest that SDC is a hippocampus-mediated process OBJECTIVES To determine whether sleep benefits motor memory in healthy elderly adults and , if so , whether the observed sleep-related benefits are comparable with those observed in healthy young adults . DESIGN Repeated- measures cross-over design . SETTING Boston , Massachusetts ( general community ) and Harvard University . PARTICIPANTS Sixteen healthy older and 15 healthy young participants . MEASUREMENTS Motor sequence task ( MST ) performance was assessed at training and at the beginning and end of the retest session ; polysomnographic sleep studies were recorded for the elderly participants . RESULTS After 12 hours of daytime wakefulness , elderly participants showed a dramatic decline in MST performance on the first three retest trials , and only a nonsignificant improvement by the end of retest ( the last 3 retest trials ) . In contrast , when the same participants trained in the morning but were retested 24 hours after training , after a day of wake plus a night of sleep , they maintained their performance at the beginning of retest and demonstrated a highly significant 17.4 % improvement by the end of the retest session , essentially identical to the 17.3 % improvement seen in young participants . These strikingly similar improvements occurred despite the presence of other age-related differences , including overall slower motor speed , a lag in the appearance of sleep-dependent improvement , and an absence of correlations between overnight improvement and sleep architecture or sleep spindle density in the elderly participants . CONCLUSION These findings provide compelling evidence that sleep optimizes motor skill performance across the adult life span BACKGROUND Studies in young healthy volunteers provided evidence of a beneficial impact of an anodal time-varied transcranial direct current stimulation ( tDCS ) during early slow wave rich sleep on declarative memory but not on procedural memory . OBJECTIVE /HYPOTHESIS The present study investigated whether sleep-dependent memory consolidation can also be affected by slow oscillating tDCS in a population of elderly subjects . METHODS 26 subjects ( 69.1 years ± 7.7 years ) received bi-frontal anodal stimulation ( max . current density : 0.331 mA/cm(2 ) ) during early NREM sleep in a double-blind placebo-controlled r and omized crossover study . Stimulation effects on offline consolidation were tested by using a declarative and a procedural memory task . Furthermore , sleep stages were scored , EEG power was analyzed and spindle densities were assessed . RESULTS Independently from stimulation condition , performance in both memory tasks significantly decreased overnight . Stimulation revealed no significant effect on sleep-dependent memory consolidation . Verum tDCS was accompanied by significantly more time awake and significantly less NREM stage 3 sleep during five 1-min stimulation free intervals . CONCLUSIONS The results of the present study are in line with other studies showing that offline consolidation during sleep varies with age and is less pronounced in the elderly than in young or middle-aged subjects . Contrary to an almost identical positive study in young adults , slow oscillatory tDCS applied to the elderly failed to show a beneficial effect on memory consolidation in the present study Background Sleep has been demonstrated to enhance simple motor skill learning “ offline ” in young adults . “ Offline learning ” refers to either the stabilization or the enhancement of a memory through the passage of time without additional practice . It remains unclear whether a functional motor task will benefit from sleep to produce offline motor skill enhancement . Physical therapists often teach clients functional motor skills ; therefore , it is important to underst and how sleep affects learning of these skills . Objective The purpose of this study was to determine whether sleep enhances the learning of a functional motor task . Design A prospect i ve , cross-sectional , repeated- measures design was used . Methods Young participants who were healthy ( N=24 ) were r and omly assigned to either a sleep group or a no-sleep group . The sleep group practice d a novel walking task in the evening and underwent retention testing the following morning , and the no-sleep group practice d the task in the morning and underwent retention testing in the evening . Outcome measures included time around the walking path and spatiotemporal gait parameters . Results Only participants who slept after practicing the novel walking task demonstrated a significant offline improvement in performance . Compared with the no-sleep group , participants in the sleep group demonstrated a significant decrease in the time around the walking path , an increase in t and em velocity , an increase in t and em step length , and a decline in t and em step time . Limitations Time-of-day effect and inability to ensure a certain amount of sleep quantity and quality of participants were limitations of the study . Conclusions This study is the first to provide evidence that sleep facilitates learning clinical ly relevant functional motor tasks . Sleep is an important factor that physical therapists should consider when teaching clients motor skills A worksite study was conducted to examine whether a 15-min nap during a post-lunch rest period would affect subsequent alertness , performance , and nocturnal sleep in eight factory workers under a 3-week protocol . Subjects were asked to take the nap at 12:30 h on a reclining chair during the nap week , and to remain awake during the no-nap week . The order of these 2 weeks was counterbalanced between the subjects . During the third , follow-up week , each subject determined whether or not she/he would nap . Alertness on the job and nocturnal sleep were assessed using a sleep diary . Wrist activity was also recorded during sleep at night . Choice reaction time task ( RT ) was performed at 10:00 and 15:00 h every day of the nap week and every other day of the no-nap and follow-up weeks . Perceived alertness was significantly higher in the afternoon after nap than after no nap at the end of the week . Similar effects were observed during the follow-up week where almost half of the subjects napped . No significant differences between the three weeks were found for RT performance or nocturnal sleep . Workers ' attitudes toward the nap were favourable . Although further intervention research is required , our results suggest that post-lunch napping may have the potential to promote daytime alertness at work Background and Purpose : Although sleep has been shown to enhance motor skill learning , it remains unclear whether sleep enhances learning of a functional motor task in middle-aged and older individuals . The purpose of this study was to examine whether sleep enhances motor learning of a functional motor task in middle-aged and older adults . Methods : Twenty middle-aged and 20 older individuals were r and omly assigned to either the sleep condition or the no-sleep condition . Participants in the sleep condition practice d a novel walking task in the evening , and returned the following morning for retesting . Participants in the no-sleep condition practice d the walking task in the morning and returned the same day in the evening for a retest . Outcome measures included time around the walking path and spatiotemporal gait parameters . Results : Only the middle-aged and older adults in the sleep condition demonstrated significant off-line improvement in performance , measured as a decline in time to walk around the novel path and improvement in spatiotemporal gait parameters . The middle-aged and older adults in the no-sleep condition failed to demonstrate off-line improvements in performance of this functional task . Conclusions : This is the first study to provide evidence that sleep facilitates learning a clinical ly relevant functional motor task in middle-aged and older adults . Because many neurologic conditions occur in the middle-aged and older adults and sleep issues are very prevalent in many neurologic conditions , it is imperative that physical therapists consider sleep as a factor that may impact motor learning and recovery in these individuals . Video Abstract available . ( See Video , Supplemental Digital Content 1 , http://links.lww.com/JNPT/A73 ) for more insights from the authors |
12,724 | 24,938,937 | We found no data for the outcomes of acute toxicity , new ipsilateral breast primaries , costs , quality of life or consumer preference .
The limitations of the data currently available mean that we can not make definitive conclusions about the efficacy and safety or ways to deliver of PBI/APBI . | BACKGROUND Breast conserving therapy for women with breast cancer consists of local excision of the tumour ( achieving clear margins ) followed by radiation therapy ( RT ) .
RT is given to sterilize tumour cells that may remain after surgery to decrease the risk of local tumour recurrence .
Most true recurrences occur in the same quadrant as the original tumour .
Whole breast RT may not protect against the development of a new primary cancer developing in other quadrants of the breast .
In this Cochrane Review , we investigated the role of delivering radiation to a limited volume of the breast around the tumour bed ( partial breast irradiation : PBI ) sometimes with a shortened treatment duration ( accelerated partial breast irradiation : APBI ) .
OBJECTIVES To determine whether PBI/APBI is equivalent to or better than conventional or hypofractionated WBRT after breast conservation therapy for 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 ) PURPOSE To report interim cosmetic and toxicity results of a multicenter r and omized trial comparing accelerated partial-breast irradiation ( APBI ) using three-dimensional conformal external beam radiation therapy ( 3D-CRT ) with whole-breast irradiation ( WBI ) . PATIENTS AND METHODS Women age > 40 years with invasive or in situ breast cancer ≤ 3 cm were r and omly assigned after breast-conserving surgery to 3D-CRT APBI ( 38.5 Gy in 10 fractions twice daily ) or WBI ( 42.5 Gy in 16 or 50 Gy in 25 daily fractions ± boost irradiation ) . The primary outcome was ipsilateral breast tumor recurrence ( IBTR ) . Secondary outcomes were cosmesis and toxicity . Adverse cosmesis was defined as a fair or poor global cosmetic score . After a planned interim cosmetic analysis , the data , safety , and monitoring committee recommended release of results . There have been too few IBTR events to trigger an efficacy analysis . RESULTS Between 2006 and 2011 , 2,135 women were r and omly assigned to 3D-CRT APBI or WBI . Median follow-up was 36 months . Adverse cosmesis at 3 years was increased among those treated with APBI compared with WBI as assessed by trained nurses ( 29 % v 17 % ; P < .001 ) , by patients ( 26 % v 18 % ; P = .0022 ) , and by physicians review ing digital photographs ( 35 % v 17 % ; P < .001 ) . Grade 3 toxicities were rare in both treatment arms ( 1.4 % v 0 % ) , but grade 1 and 2 toxicities were increased among those who received APBI compared with WBI ( P < .001 ) . CONCLUSION 3D-CRT APBI increased rates of adverse cosmesis and late radiation toxicity compared with st and ard WBI . Clinicians and patients are caution ed against the use of 3D-CRT APBI outside the context of a controlled trial Between 1979–1987 , the National Cancer Institute conducted a r and omized , prospect i ve study of mastectomy ( MT ) versus breast conservation therapy ( BCT ) in the treatment of patients with early‐stage breast carcinoma . After a median potential follow‐up of 18.4 years , the authors present the up date d results Breast cancer multifocality was studied in mastectomy specimens by correlated specimen radiography and histologic techniques . The patients chosen for study were comparable to those eligible for breast‐conserving surgical therapy . Two study groups , one with 282 invasive cancers ( T1‐2 ) and the other with 32 intraductal cancers , were selected from a group of 399 consecutive cases by omitting patients who were clearly , or very probably , not c and i date s for breast‐conserving surgical therapy according to current trial criteria . Omitted patients included those with clinical ly and /or radiologically multifocal cancers and patients with tumor extension into the chest wall or skin ( 7 % ) . Also excluded were the socalled diffuse invasive cancers ( 8 % ) , the clinical ly and radiologically occult tumors ( 3 % ) , and the invasive cancers larger than 5 cm ( 3 % ) . Of the 282 invasive cancers , 105 ( 37 % ) showed no tumor foci in the mastectomy specimen around the reference mass . In 56 ( 20 % ) tumor foci were present within 2 cm , and in 121 ( 43 % ) tumor was found more than 2 cm from the reference tumor . In 75 ( 27 % ) the tumor foci beyond 2 cm were histologically noninvasive cancers , and in 46 cases ( 16 % ) they contained invasive cancers as well . A comparison between the group with reference tumors less than 2 cm and the group with reference tumors more than 2 cm in size showed no significant difference between the groups in terms of presence or absence of tumor foci or distance of tumor foci from the reference tumor . If the 264 invasive cancers in this series that were 4 cm or less in diameter had been removed with a margin of 3 to 4 cm , 7 % to 9 % of the patients would have had invasive cancer left in the remaining breast tissue , and 4 % to 9 % would have had foci of noninvasive cancer left in the remaining breast tissue . On the basis of the data on the distribution of tumor at different distances from the reference tumor , the current study estimates the expected rates of local recurrences after breast‐conserving surgical procedures relative to the extensiveness of the excision . The possible impact of postoperative local radiation therapy on the rates of expected local recurrence is discussed BACKGROUND AND PURPOSE To report the long-term results of a single-institution r and omized study comparing the results of breast-conserving treatment with partial breast irradiation ( PBI ) or conventional whole breast irradiation ( WBI ) . PATIENTS AND METHODS Between 1998 and 2004 , 258 selected women with pT1 pN0 - 1mi M0 , grade 1 - 2 , non-lobular breast cancer without the presence of extensive intraductal component and resected with negative margins were r and omized after BCS to receive 50 Gy WBI ( n=130 ) or PBI ( n=128 ) . The latter consisted of either 7 × 5.2 Gy high-dose-rate ( HDR ) multi-catheter brachytherapy ( BT ; n=88 ) or 50 Gy electron beam ( EB ) irradiation ( n=40 ) . Primary endpoint was local recurrence ( LR ) as a first event . Secondary endpoints were overall survival ( OS ) , cancer-specific survival ( CSS ) , disease-free survival ( DFS ) , and cosmetic results . RESULTS After a median follow up of 10.2 years , the ten-year actuarial rate of LR was 5.9 % and 5.1 % in PBI and WBI arms , respectively ( p=0.77 ) . There was no significant difference in the ten-year probability of OS ( 80 % vs 82 % ) , CSS ( 94 % vs 92 % ) , and DFS ( 85 % vs 84 % ) , either . The rate of excellent-good cosmetic result was 81 % in the PBI , and 63 % in the control group ( p<0.01 ) . CONCLUSIONS Partial breast irradiation delivered by interstitial HDR BT or EB for a selected group of early-stage breast cancer patients produces similar ten-year results to those achieved with conventional WBI . Significantly better cosmetic outcome can be achieved with HDR BT implants compared with the outcome after WBI 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 BACKGROUND Breast-conservation therapy for early-stage breast cancer is now an accepted treatment , but there is still controversy about its comparability with mastectomy . Between 1979 and 1987 , the National Cancer Institute conducted a r and omized , single-institution trial comparing lumpectomy , axillary dissection , and radiation with mastectomy and axillary dissection for stage I and II breast cancer . We up date the results of that trial after a median potential follow-up of 10.1 years . METHODS Two hundred forty-seven patients with clinical stage I and II breast cancer were r and omly assigned to undergo either modified radical mastectomy or lumpectomy , axillary dissection , and radiation therapy . The 237 patients who actually underwent r and omization have been followed for a median of 10.1 years . The primary end points were overall survival and disease-free survival . RESULTS At 10 years overall survival was 75 percent for the patients assigned to mastectomy and 77 percent for those assigned to lumpectomy plus radiation ( P = 0.89 ) . Disease-free survival at 10 years was 69 percent for the patients assigned to mastectomy and 72 percent for those assigned to lumpectomy plus radiation ( P = 0.93 ) . The rate of local regional recurrence at 10 years was 10 percent after mastectomy and 5 percent after lumpectomy plus radiation ( P = 0.17 ) after recurrences successfully treated by mastectomy were censored from the analysis . CONCLUSIONS In the management of stage I and II breast cancer , breast conservation with lumpectomy and radiation offers results at 10 years that are equivalent to those with mastectomy Patients with a clinical ly palpable breast carcinoma , 4 cm or less in diameter , and with no palpable nodes in the axilla were prospect ively entered into a r and omized clinical trial . A total of 713 patients were registered between November 1982 and December 1987 , of whom 708 are evaluable at a median follow-up of 37 months . Following excision of the primary tumour , patients were r and omly allocated either to have radiotherapy to the affected quadrant only ( LF group ) or to the whole breast and regional lymph node areas ( WF group ) . No adjuvant hormone or chemotherapy was prescribed . The primary tumour was reported as completely excised histologically in 80 % of cases , incompletely excised in 10 % , and no estimate was possible in 10 % . At six years from first r and omization , 96 % of the WF group and 92 % of the LF group have remained free of breast recurrence ( 94 % and 87 % actuarial breast recurrence-free survival at 5 years ) . Part of the difference may be explained by the 20 % recurrence rate in the breast for lobular carcinomas treated within the LF group . Of the WF group 14 patients ( 4 % ) developed recurrent disease in the axilla , compared to 50 patients ( 14 % ) in the LF group ( 95 % and 86 % actuarial axillary recurrent-free survival at 5 years ) . Patients with primary tumours histologically 1 cm or less in diameter had a 98 % actuarial 5-year survival compared with 74 % for those with tumours measuring 2 cm or more in diameter ( P = 0.003 ) . Continued follow-up of these patients will provide further information on the factors governing local/regional recurrence 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 PURPOSE To report the interim results from a study comparing the efficacy , toxicity , and cosmesis of breast-conserving treatment with accelerated partial breast irradiation ( APBI ) or whole breast irradiation ( WBI ) using 3-dimensional conformal external beam radiation therapy ( 3D-CRT ) . METHODS AND MATERIAL S 102 patients with early-stage breast cancer who underwent breast-conserving surgery were r and omized to receive either WBI ( n=51 ) or APBI ( n=51 ) . In the WBI arm , 48 Gy was delivered to the whole breast in daily fractions of 2 Gy , with or without additional 10 Gy to the tumor bed . In the APBI arm , patients received 37.5 Gy in 3.75 Gy per fraction delivered twice daily . Toxicity results were scored according to the Radiation Therapy Oncology Group Common Toxicity Criteria . Skin elasticity was measured using a dedicated device ( Multi-Skin-Test-Center MC-750-B2 , CKelectronic-GmbH ) . Cosmetic results were assessed by the physician and the patients as good/excellent , regular , or poor . RESULTS The median follow-up time was 5 years . No local recurrences were observed . No significant differences in survival rates were found . APBI reduced acute side effects and radiation doses to healthy tissues compared with WBI ( P<.01 ) . Late skin toxicity was no worse than grade 2 in either group , without significant differences between the 2 groups . In the ipsilateral breast , the areas that received the highest doses ( ie , the boost or quadrant ) showed the greatest loss of elasticity . WBI result ed in a greater loss of elasticity in the high-dose area compared with APBI ( P<.05 ) . Physician assessment showed that > 75 % of patients in the APBI arm had excellent or good cosmesis , and these outcomes appear to be stable over time . The percentage of patients with excellent/good cosmetic results was similar in both groups . CONCLUSIONS APBI delivered by 3D-CRT to the tumor bed for a selected group of early-stage breast cancer patients produces 5-year results similar to those achieved with conventional WBI BACKGROUND Breast irradiation after lumpectomy is an integral component of breast-conserving therapy that reduces the local recurrence of breast cancer . Because an optimal fractionation schedule ( radiation dose given in a specified number of fractions or treatment sessions over a defined time ) for breast irradiation has not been uniformly accepted , we examined whether a 22-day fractionation schedule was as effective as the more traditional 35-day schedule in reducing recurrence . METHODS Women with invasive breast cancer who were treated by lumpectomy and had pathologically clear resection margins and negative axillary lymph nodes were r and omly assigned to receive whole breast irradiation of 42.5 Gy in 16 fractions over 22 days ( short arm ) or whole breast irradiation of 50 Gy in 25 fractions over 35 days ( long arm ) . The primary outcome was local recurrence of invasive breast cancer in the treated breast . Secondary outcomes included cosmetic outcome , assessed with the European Organisation for Research and Treatment of Cancer ( EORTC ) Cosmetic Rating System . All statistical tests were two-sided . RESULTS From April 1993 through September 1996 , 1234 women were r and omly assigned to treatment , 622 to the short arm and 612 to the long arm . Median follow-up was 69 months . Five-year local recurrence-free survival was 97.2 % in the short arm and 96.8 % in the long arm ( absolute difference = 0.4 % , 95 % confidence interval [ CI ] = -1.5 % to 2.4 % ) . No difference in disease-free or overall survival rates was detected between study arms . The percentage of patients with an excellent or good global cosmetic outcome at 3 years was 76.8 % in the short arm and 77.0 % in the long arm ; the corresponding data at 5 years were 76.8 % and 77.4 % , respectively ( absolute difference = -0.6 % , 95 % CI = -6.5 % to 5.5 % ) . CONCLUSION The more convenient 22-day fractionation schedule appears to be an acceptable alternative to the 35-day schedule BACKGROUND The principal objective of the targeted intraoperative radiation therapy trial was to determine whether single-fraction intraoperative radiotherapy ( IORT ) targeted to the tumor bed provides equivalent local control compared with whole-breast irradiation in patients with early-stage invasive breast cancer . METHODS Patients were r and omized equally to IORT versus whole breast irradiation . Patients r and omized to IORT received tumor bed irradiation prescribed at 20 Gy to the surgical margins using soft x-rays ( 50 kV ) delivered with the Intrabeam Photon Radiosurgery System ( Zeiss Inc , Oberkochen , Germany ) . Patients r and omized to whole-breast irradiation received radiotherapy postoperatively . Prior wide local excision was allowed . Patients r and omized to IORT after initial breast-conserving surgery received IORT at a second operation . RESULTS A total of 779 patients were accrued at 16 institutions internationally . Five hundred sixty patients were r and omized before initial breast-conserving surgery . One hundred eighty-three patients were r and omized after initial breast-conserving surgery . The median follow-up time was 359 days . CONCLUSION Targeted IORT allowed the entire dose of radiotherapy to be administered in a single fraction at the time of breast-conserving surgery , thus avoiding the need for repeated radiotherapy treatments or placement of indwelling radiotherapy devices PURPOSE To determine whether three-dimensional conformal partial breast irradiation ( 3D-PBI ) spares lung tissue compared with whole breast irradiation ( WBI ) and to include the biologically equivalent dose ( BED ) to account for differences in fractionation . METHODS AND MATERIAL S Radiotherapy treatment plans were devised for WBI and 3D-PBI for 25 consecutive patients r and omized on the NSABP B-39/RTOG 0413 protocol at Mayo Clinic in Jacksonville , Florida . WBI plans were for 50 Gy in 25 fractions , and 3D-PBI plans were for 38.5 Gy in 10 fractions . Volume of ipsilateral lung receiving 2.5 , 5 , 10 , and 20 Gy was recorded for each plan . The linear quadratic equation was used to calculate the corresponding dose delivered in 10 fractions and volume of ipsilateral lung receiving these doses was recorded for PBI plans . Ipsilateral mean lung dose was recorded for each plan and converted to BED . RESULTS There was a significant decrease in volume of lung receiving 20 Gy with PBI ( median , 4.4 % vs. 7.5 % ; p < 0.001 ) , which remained after correction for fractionation ( median , 5.6 % vs. 7.5 % ; p = 0.02 ) . Mean lung dose was lower for PBI ( median , 3.46 Gy vs. 4.57 Gy ; p = 0.005 ) , although this difference lost significance after conversion to BED ( median , 3.86 Gy(3 ) vs 4.85 Gy(3 ) , p = 0.07 ) . PBI plans exposed more lung to 2.5 and 5 Gy . CONCLUSIONS 3D-PBI exposes greater volumes of lung tissue to low doses of radiation and spares the amount of lung receiving higher doses when compared with WBI PURPOSE To report the 7-year results of a prospect i ve study of accelerated partial breast irradiation ( APBI ) using interstitial high-dose-rate brachytherapy and compare the treatment results with those achieved by st and ard , whole breast radiotherapy ( WBRT ) , with or without a tumor bed boost ( TBB ) . METHODS AND MATERIAL S Between 1996 and 1998 , 45 prospect ively selected patients with T1N0-N1mi ( single nodal micrometastasis ) , nonlobular breast cancer without the presence of an extensive intraductal component and with negative surgical margins were treated with APBI using interstitial high-dose-rate implants . A total dose of 30.3 Gy ( n = 8) and 36.4 Gy ( n = 37 ) in seven fractions within 4 days was delivered to the tumor bed plus a 1 - 2-cm margin . During the same period , 80 patients , who met the eligibility criteria for APBI but who were treated with 50 Gy WBRT with ( n = 36 ) or without ( n = 44 ) a 10 - 16-Gy TBB , were selected as controls . The median follow-up for the APBI and control groups was 81 and 83 months , respectively . Local control , relapse-free survival , cancer-specific survival , late side effects , and cosmetic results were assessed . RESULTS The crude rate of total ipsilateral breast failure was 6.7 % ( 3 of 45 ) , 11.4 % ( 5 of 44 ) , and 8.3 % ( 3 of 36 ) for patients treated with APBI , WBRT , and WBRT + TBB , respectively . The differences in the 5- and 7-year actuarial rates of ipsilateral breast recurrence were not statistically significant among patients treated with APBI ( 4.4 % and 9.0 % ) , WBRT ( 4.7 % and 14.8 % ) , and WBRT + TBB ( 5.7 % and 9.5 % ) . No statistically significant difference in either the 7-year probability of relapse-free survival ( 79.8 % , 73.5 % , and 77.7 % for APBI , WBRT , and WBRT + TBB , respectively ) or cancer-specific survival ( 93.3 % , 92.9 % , and 93.9 % for APBI , WBRT , and WBRT + TBB , respectively ) was found . The 7-year actuarial elsewhere breast failure rate was 9.0 % in the APBI group and 8.3 % in the control group ( p = 0.80 ) . The rate of excellent/good cosmetic results was 84.4 % in the APBI group and 68.3 % in the control group ( p = 0.04 ) . The corresponding rates of asymptomatic fat necrosis were 20.0 % and 20.6 % . Symptomatic fat necrosis occurred in 1 patient ( 2.2 % ) treated with APBI . The incidence of Grade 2 or worse late radiation side effects was similar for both groups ( 26.7 % vs. 28.6 % ) . CONCLUSION Accelerated partial breast irradiation using interstitial high-dose-rate implants , with proper patient selection and quality assurance , yields similar 7-year results to those achieved with st and ard breast-conserving therapy . APBI does not increase the risk of elsewhere breast failures The purpose of this study was to evaluate the effect of breast irradiation on quality of life , including cosmetic outcome , for patients enrolled in a clinical trial BACKGROUND Previous findings from a clinical trial ( Protocol B-06 ) conducted by the National Surgical Adjuvant Breast and Bowel Project ( NSABP ) indicated the worth of lumpectomy and breast irradiation for treating breast cancer . After the discovery by NSABP staff members of falsified information on patients enrolled in the study by St. Luc Hospital in Montreal , separate audits were conducted at St. Luc Hospital and other participating institutions . We report the results of both audits and up date the study findings through an average of 12 years of follow-up . METHODS Patients with either negative or positive axillary nodes and tumors 4 cm or less in diameter were r and omly assigned to one of three treatments : total mastectomy , lumpectomy followed by breast irradiation , or lumpectomy without irradiation . Three cohorts of patients were analyzed . The first cohort included all 2105 r and omized patients , who were analyzed according to the intention-to-treat principle . The second cohort consisted of 1851 eligible patients in the first cohort with known nodal status who agreed to be followed and who accepted their assigned therapy ( among those excluded were 6 patients from St. Luc Hospital who were declared ineligible because of falsified biopsy date s ) . The third cohort consisted of the patients in the second cohort minus the 322 eligible patients from St. Luc Hospital ( total , 1529 patients ) . RESULTS Regardless of the cohort , no significant differences were found in overall survival , disease-free survival , or survival free of disease at distant sites between the patients who underwent total mastectomy and those treated by lumpectomy alone or by lumpectomy plus breast irradiation . After 12 years of follow-up , the cumulative incidence of a recurrence of tumor in the ipsilateral breast was 35 percent in the group treated with lumpectomy alone and 10 percent in the group treated with lumpectomy and breast irradiation ( P < 0.001 ) . CONCLUSIONS Our findings continue to indicate that lumpectomy followed by breast irradiation is appropriate therapy for women with either negative or positive axillary nodes and breast tumors 4 cm or less in diameter Breast conservation is a safe and effective alternative to mastectomy for the majority of women with early-stage breast cancer . Adjuvant radiation therapy lowers the risk of recurrence within the breast and also confers a survival benefit . Although acute side effects of radiation therapy are generally well tolerated ; efforts are ongoing to minimize the long-term side effects of radiation , most prominently atherosclerotic heart disease . Efforts to minimize radiation therapy are also underway . They include omitting treatment altogether in the elderly and using accelerated , hypofractionated whole-breast irradiation , and accelerated partial-breast irradiation . Several r and omized studies are ongoing to determine the efficacy , safety , and appropriate patients for these shorter treatments In 1990 , we published the results of a clinical trial involving 708 patients with breast carcinoma of 4 cm or less in diameter , who , following lumpectomy , were r and omized to have radiotherapy to the tumour bed only ( limited field , LF group ) or to the whole breast and regional nodes ( wide field , WF group ) . No adjuvant systemic therapy was prescribed . At the time the median follow-up was 37 months . We present the up date d results after an extended median follow-up of 65 months . The overall survival is 72.7 % and 71.2 % for the LF and WF groups respectively . The actuarial breast recurrence rate ( first event ) is 15 % ( LF ) versus 11 % ( WF ) for infiltrating ductal carcinoma , whereas , for infiltrating lobular carcinoma , the recurrence rate was 34 % ( LF ) versus 8 % ( WF ) . A high actual recurrence rate of 21 % ( LF ) and 14 % ( WF ) was also found for extensive ductal carcinoma in situ . It was extremely rare for medullary , mucoid or tubular carcinomas to recur . Salvage surgery was possible in 86 % ( LF ) and 90 % ( WF ) respectively . The recurrence rate in the breast following lumpectomy and wide field irradiation is comparable with others reported in the literature . This trial also shows the lumpectomy with limited field irradiation is feasible , albeit with a higher breast recurrence rate ; the latter could be reduced by improved selection and refinement of the technique PURPOSE To examine the incidence and clinical relevance of fat necrosis after accelerated partial-breast irradiation ( PBI ) using interstitial high-dose-rate brachytherapy ( HDR-BT ) in comparison with partial-breast electron irradiation ( ELE ) and whole-breast irradiation ( WBI ) . METHODS AND MATERIAL S Between 1998 and 2004 , 258 early-stage breast cancer patients were r and omized to receive 50 Gy WBI ( n = 130 ) or PBI ( n = 128 ) . The latter consisted of either 7 x 5.2 Gy HDR-BT ( n = 88 ) or 50 Gy ELE ( n = 40 ) . The incidence of fat necrosis , its impact on cosmetic outcome , accompanying radiologic features , and clinical symptoms were evaluated . RESULTS The 4-year actuarial rate of fat necrosis was 31.1 % for all patients , and 31.9 % , 36.5 % , and 17.7 % after WBI , HDR-BT and ELE , respectively ( p(WBI/HDR-BT ) = 0.26 ; p(WBI/ELE ) = 0.11 ; p(ELE/HDR-BT ) = 0.025 ) . The respective rate of asymptomatic fat necrosis was 20.2 % , 25.3 % , and 10 % of patients . The incidence of symptomatic fat necrosis was not significantly different after WBI ( 8.5 % ) , HDR-BT ( 11.4 % ) , and ELE ( 7.5 % ) . Symptomatic fat necrosis was significantly associated with a worse cosmetic outcome , whereas asymptomatic fat necrosis was not . Fat necrosis was detectable with mammography and /or ultrasound in each case . Additional imaging examinations were required in 21 % of cases and aspiration cytology in 42 % . CONCLUSIONS Asymptomatic fat necrosis is a common adverse event of breast-conserving therapy , having no significant clinical relevance in the majority of the cases . The incidence of both symptomatic and asymptomatic fat necrosis is similar after conventional WBI and accelerated partial-breast HDR-BT PURPOSE To present guidance for patients and physicians regarding the use of accelerated partial-breast irradiation ( APBI ) , based on current published evidence complemented by expert opinion . METHODS AND MATERIAL S A systematic search of the National Library of Medicine 's PubMed data base yielded 645 c and i date original research articles potentially applicable to APBI . Of these , 4 r and omized trials and 38 prospect i ve single-arm studies were identified . A Task Force composed of all authors synthesized the published evidence and , through a series of meetings , reached consensus regarding the recommendations contained herein . RESULTS The Task Force proposed three patient groups : ( 1 ) a " suitable " group , for whom APBI outside of a clinical trial is acceptable , ( 2 ) a " caution ary " group , for whom caution and concern should be applied when considering APBI outside of a clinical trial , and ( 3 ) an " unsuitable " group , for whom APBI outside of a clinical trial is not generally considered warranted . Patients who choose treatment with APBI should be informed that whole-breast irradiation ( WBI ) is an established treatment with a much longer track record that has documented long-term effectiveness and safety . CONCLUSION Accelerated partial-breast irradiation is a new technology that may ultimately demonstrate long-term effectiveness and safety comparable to that of WBI for selected patients with early breast cancer . This consensus statement is intended to provide guidance regarding the use of APBI outside of a clinical trial and to serve as a framework to promote additional clinical investigations into the optimal role of APBI in the treatment of breast cancer BACKGROUND St and ard curative schedules of radiotherapy to the breast deliver 25 fractions of 2.0 Gy over 5 weeks . In a r and omised trial , we tested whether fewer , larger fractions were at least as safe and as effective as st and ard regimens . In this analysis , we assessed the long-term results of tumour control in the same population . METHODS In 1986 - 98 , we r and omly assigned 1410 women with invasive breast cancer ( tumour stage 1 - 3 with a maximum of one positive node and no metastasis ) who had had local tumour excision of early stage breast cancer to receive 50 Gy radiotherapy given in 25 fractions , 39 Gy given in 13 fractions , or 42.9 Gy given in 13 fractions , all given over 5 weeks . The primary endpoint was late change in breast appearance , which has been reported elsewhere . Here , we report ipsilateral tumour relapse , one of the secondary endpoints . Relapse was defined as any appearance of cancer in the irradiated breast . Analysis was by intention to treat . FINDINGS After a median follow-up of 9.7 years ( IQR 7.8 - 11.8 ) for the 838 ( 95 % ) patients who survived , the risk of ipsilateral tumour relapse after 10 years was 12.1 % ( 95 % CI 8.8 - 15.5 ) in the 50 Gy group , 14.8 % ( 11.2 - 18.3 ) in the 39 Gy group , and 9.6 % ( 6.7 - 12.6 ) in the 42.9 Gy group ( difference between 39 Gy and 42.9 Gy groups , chi2 test , p=0.027 ) . The sensitivity of breast cancer to dose per fraction was estimated to be 4.0 Gy ( 95 % CI 1.0 - 7.8 ) , similar to that estimated for the late adverse effects in healthy tissue from breast radiotherapy . INTERPRETATION Breast cancer tissue is probably just as sensitive to fraction size as dose-limiting healthy tissues . If this finding is confirmed , radiotherapy schedules can be greatly simplified by the delivery of fewer , larger fractions without compromising effectiveness or safety , and possibly improving both PURPOSE To evaluate with a r and omized clinical trial the possibility of treating the index quadrant with external intensity-modulated radiotherapy ( IMRT ) in a selected group of patients with early-stage breast cancer and to analyze the acute toxicity . METHODS AND MATERIAL S From September 2005 , a r and omized Phase III clinical trial has been conducted to compare conventional ( tangential field ) fractionated whole breast treatment ( Arm A ) with accelerated partial breast irradiation plus intensity-modulated radiotherapy ( Arm B ) . For intensity-modulated radiotherapy , the clinical target volume was drawn with a uniform 1-cm margin around the surgical clips in three dimensions . The ipsilateral and contralateral breast , ipsilateral and contralateral lung , heart , and spinal cord were contoured as organs at risk . All the regions of interest were contoured according to the International Commission on Radiation Units and Measurements reports 50 and 62 recommendations . RESULTS In September 2008 , 259 patients were r and omized and treated . The mean clinical target volume in Arm B was 44 cm(3 ) and the mean planning target volume was 123 cm(3 ) . The mean value of the ratio between the planning target volume and the ipsilateral breast volume was 21 % . The rate of Grade 1 and Grade 2 acute skin toxicity was 22 % and 19 % in Arm A ( Radiation Therapy Oncology Group scale ) , respectively . The tolerance in Arm B was excellent with only 5 % Grade 1 and 0.8 % Grade 2 acute skin toxicity . The planning constraints were fully satisfied in most patients . In a very few cases , this was not possible because of very unfavorable anatomy . Quality assurance procedures were performed according to our internal quality assurance protocol , with excellent results . CONCLUSION In the present preliminary analysis , we have demonstrated that accelerated partial breast irradiation is feasible , with very low acute toxicity 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 Short‐term treatment failures following 43 segmental mastectomies without radiation therapy and 157 total mastectomies for primary operable breast cancer Stages I and II ( T1–2 , N0–1 , MO ) are compared . Although not r and omized by design , the patients in the two treatment groups were of similar age and had tumors of comparable histologic type , size , grade , and stage . The overall recurrence rates in an average follow‐up of 24 months ( range , 6–48 months ) were 5 % for patients treated by st and ard mastectomy and 19 % for those treated by segmental mastectomy . Recurrence rates in patients with the more commonly encountered carcinomas of 11 to 50 mm in size treated by surgery alone were 7.5 % for total mastectomy and 28.0 % for segmental mastectomy . Nearly all of this difference relates to a higher frequency of local recurrence in the segmental mastectomy group ( P = < 0.005 ) . Recurrent disease in both groups developed at comparable intervals , averaging 17 months for segmental mastectomy and 16 months for total mastectomy . Using a serial subgross technique , which permitted detection of clinical ly unsuspected involvement of resection margin by microscopic foci of carcinoma , it was noted that such involvement was an important prognostic indicator for local recurrence . Five of eleven breast resections with this feature developed local recurrence , compared with only 3 of 32 without such involvement of the resection margin . Cancer 52:2173‐2179 , 1983 BACKGROUND AND PURPOSE To evaluate the safety and effectiveness of accelerated partial breast irradiation ( APBI ) with multi-catheter brachytherapy . PATIENTS AND METHODS Between 11/2000 and 04/2005 , 274 patients participated . Patients were eligible for APBI if they had histologically confirmed breast cancer , a tumour diameter 3 cm , complete resection with clear margins 2 mm , negative axillary lymph nodes or singular nodal micro-metastasis , no distant metastases , hormone receptor-positive tumours , and were > /= 35 years . Patients were excluded if mammographically they showed a multicentric invasive growth pattern , poorly differentiated tumours , residual diffuse micro-calcifications , extensive intraductal component , or vessel invasion . Median follow-up was 32 months ( range ; 8 - 68 ) . RESULTS The local control rate was 99.3 % ( 272/274 ) , the 3 year-local-recurrence-free survival probability , 99.6 % . Peri-operative complications occurred in 5.5 % ( 15/274 ) : 9 ( 3.3 % ) experienced implant infection and 6 ( 2.2 % ) hematoma . Acute toxicity ( Grade 1/2 radio-dermatitis ) was seen in 6.6 % ( 18/274 ) . Late side effects > /= Grade 3 ( fibrosis , telangiectasia ) occurred in 1.8 % ( 4/274 ) . Cosmetic results were excellent/good in 94 % ( 253/274 ) . CONCLUSIONS This analysis underlined the safety and effectiveness of APBI in a carefully selected subgroup with favourable disease characteristics . Of course , longer follow-up and r and omised trials are necessary to conclusively assess the potential of APBI Prognostic factors predicting for breast recurrence following breast conserving surgery and radiotherapy have been identified in a prospect i ve r and omised trial comparing two different radiotherapy techniques . The first used megavoltage radiation to encompass the whole breast and regional nodes ( WF group ) . The second used an electron field directed to the tumour bed only ( LF group ) . With a median follow up of 8 years survival in both groups was the same ( 72 % ) . There was an increased rate of breast recurrence in the LF group : 25 % , compared to the WF group : 13 % ( P = 0.00008 ) , expressed in actuarial terms at 8 years . In a multivariate analysis of factors predicting for breast recurrence , once the difference in treatment technique is allowed for , only two factors were found to be significant : histological grade ( P = 0.013 ) and lymphovascular invasion in the histological specimen ( P = 0.037 ) BACKGROUND AND OBJECTIVES The objectives of this study were to test the feasibility of sole interstitial high-dose-rate brachytherapy ( HDR-BT ) after breast-conserving surgery ( BCS ) for T1 breast cancer in a phase I-II study , and to present the initial findings of a phase III trial comparing the efficacy of tumor bed radiotherapy ( TBRT ) alone with conventional whole breast radiotherapy ( WBRT ) . METHODS Forty-five prospect ively selected patients with T1 breast cancer undergoing BCS were enrolled into a phase I-II study of TBRT alone , using interstitial HDR implants . HDR-BT of 7 x 4.33 Gy ( n = 8) and 7 x 5.2 Gy ( n = 37 ) was delivered to the tumor bed . Based on the results of this phase I-II study , a further 126 patients were r and omized to receive 50 Gy WBRT ( n = 63 ) or TBRT alone ( n = 63 ) ; the latter consisted of either 7 x 5.2 Gy HDR-BT ( n = 46 ) or 50-Gy wide-field electron irradiation ( n = 17 ) . Breast cancer related events and side effects were assessed . RESULTS In the phase I-II study , at a median follow-up of 57 months , 2 ( 4.4 % ) local , 3 ( 6.7 % ) axillary , and 3 ( 6.7 % ) distant failures were observed . Two patients ( 4.4 % ) died of breast cancer . The 5-year probability of cancer-specific , relapse-free and local recurrence-free survival was 90.0 % , 85.9 % , and 95.6 % , respectively . The cosmetic results were judged to be excellent in 44 of 45 patients ( 97.8 % ) . Severe ( higher than grade 2 ) skin sequelae or fibrosis was not found . Symptomatic fat necrosis occurred in one patient ( 2.2 % ) . In the phase III study , at a median follow-up of 30 months , the locoregional tumor control was 100 % in both arms . The 3-year probability of cancer-specific and relapse-free survival was 98.1 % and 98.4 % in the WBRT group and 100 % and 94.4 % in the TBRT group , respectively ( P = NS ) . There was no significant difference between the two treatment arms regarding the incidence of radiation side effects . CONCLUSIONS Five-year results of our phase I-II study prove that sole HDR-BT of the tumor bed with careful patient selection and adequate quality assurance is a feasible alternative to WBRT . However , long-term results of phase III trials are required to determine the equivalence of TBRT alone , compared with WBRT in the management of selected patients with early breast cancer Summary Background The international st and ard radiotherapy schedule for breast cancer treatment delivers a high total dose in 25 small daily doses ( fractions ) . However , a lower total dose delivered in fewer , larger fractions ( hypofractionation ) is hypothesised to be at least as safe and effective as the st and ard treatment . We tested two dose levels of a 13-fraction schedule against the st and ard regimen with the aim of measuring the sensitivity of normal and malignant tissues to fraction size . Methods Between 1998 and 2002 , 2236 women with early breast cancer ( pT1 - 3a pN0 - 1 M0 ) at 17 centres in the UK were r and omly assigned after primary surgery to receive 50 Gy in 25 fractions of 2·0 Gy versus 41·6 Gy or 39 Gy in 13 fractions of 3·2 Gy or 3·0 Gy over 5 weeks . Women were eligible if they were aged over 18 years , did not have an immediate surgical reconstruction , and were available for follow-up . R and omisation method was computer generated and was not blinded . The protocol -specified principal endpoints were local-regional tumour relapse , defined as reappearance of cancer at irradiated sites , late normal tissue 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 IS RCT N59368779 . Findings 749 women were assigned to the 50 Gy group , 750 to the 41·6 Gy group , and 737 to the 39 Gy group . After a median follow up of 5·1 years ( IQR 4·4–6·0 ) the rate of local-regional tumour relapse at 5 years was 3·6 % ( 95 % CI 2·2–5·1 ) after 50 Gy , 3·5 % ( 95 % CI 2·1–4·3 ) after 41·6 Gy , and 5·2 % ( 95 % CI 3·5–6·9 ) after 39 Gy . The estimated absolute differences in 5-year local-regional relapse rates compared with 50 Gy were 0·2 % ( 95 % CI −1·3 % to 2·6 % ) after 41·6 Gy and 0·9 % ( 95 % CI −0·8 % to 3·7 % ) after 39 Gy . Photographic and patient self- assessment s suggested lower rates of late adverse effects after 39 Gy than with 50 Gy , with an HR for late change in breast appearance ( photographic ) of 0·69 ( 95 % CI 0·52–0·91 , p=0·01 ) . From a planned meta- analysis with the pilot trial , the adjusted estimates of α/β value for tumour control was 4·6 Gy ( 95 % CI 1·1–8·1 ) and for late change in breast appearance ( photographic ) was 3·4 Gy ( 95 % CI 2·3–4·5 ) . Interpretation The data are consistent with the hypothesis that breast cancer and the dose-limiting normal tissues respond similarly to change in radiotherapy fraction size . 41·6 Gy in 13 fractions was similar to the control regimen of 50 Gy in 25 fractions in terms of local-regional tumour control and late normal tissue effects , a result consistent with the result of START Trial B. A lower total dose in a smaller number of fractions could offer similar rates of tumour control and normal tissue damage as the international st and ard fractionation schedule of 50 Gy in 25 fractions AIMS Whole-breast radiotherapy ( WBRT ) after conservative surgery for early breast cancer is a routine st and ard of care . Despite this , a number of uncertainties in management still exist . Over recent years , a number of new technologies have allowed the development of partial-breast irradiation , with the intention of improving the risk-benefit relationship of routine breast radiotherapy . We report the results of a trial comparing partial- with WBRT , with prolonged follow-up . MATERIAL S AND METHODS Between 1986 and 1990 , 174 women were r and omised to receive conventional whole-breast radiotherapy ( WBRT ) ( 40 Gy in 15 fractions ) , with a tumour-bed boost or partial-breast irradiation by a variety of techniques . Recruitment was problematic , and the trial closed prematurely well before meeting its recruitment target . RESULTS A trend was observed towards higher local recurrence and a higher locoregional recurrence rate after irradiation of the tumour bed alone . Distant recurrence and survival were the same . CONCLUSIONS Conclusions are limited in view of the failure to complete accrual of the target of 400 participants , and in the context of the techniques of partial-breast radiotherapy used during this study , which would not compare with those in current use . Tumour-bed irradiation alone can not currently be recommended as routine treatment outside the context of clinical trial PURPOSE To present 5-year data on treatment efficacy , cosmetic results , and toxicities for patients enrolled on the American Society of Breast Surgeons MammoSite breast brachytherapy registry trial . METHODS AND MATERIAL S A total of 1440 patients ( 1449 cases ) with early-stage breast cancer receiving breast-conserving therapy were treated with the MammoSite device to deliver accelerated partial-breast irradiation ( APBI ) ( 34 Gy in 3.4-Gy fractions ) . Of 1449 cases , 1255 ( 87 % ) had invasive breast cancer ( IBC ) ( median size , 10 mm ) and 194 ( 13 % ) had ductal carcinoma in situ ( DCIS ) ( median size , 8 mm ) . Median follow-up was 54 months . RESULTS Thirty-seven cases ( 2.6 % ) developed an ipsilateral breast tumor recurrence ( IBTR ) , for a 5-year actuarial rate of 3.80 % ( 3.86 % for IBC and 3.39 % for DCIS ) . Negative estrogen receptor status ( p=0.0011 ) was the only clinical , pathologic , or treatment-related variable associated with IBTR for patients with IBC and young age ( < 50 years ; p=0.0096 ) and positive margin status ( p=0.0126 ) in those with DCIS . The percentage of breasts with good/excellent cosmetic results at 60 months ( n=371 ) was 90.6 % . Symptomatic breast seromas were reported in 13.0 % of cases , and 2.3 % developed fat necrosis . A subset analysis of the first 400 consecutive cases enrolled was performed ( 352 with IBC , 48 DCIS ) . With a median follow-up of 60.5 months , the 5-year actuarial rate of IBTR was 3.04 % . CONCLUSION Treatment efficacy , cosmesis , and toxicity 5 years after treatment with APBI using the MammoSite device are good and similar to those reported with other forms of APBI with similar follow-up PURPOSE To give recommendations on patient selection criteria for the use of accelerated partial-breast irradiation ( APBI ) based on available clinical evidence complemented by expert opinion . METHODS AND MATERIAL S Overall , 340 articles were identified by a systematic search of the PubMed data base using the keywords " partial-breast irradiation " and " APBI " . This search was complemented by search es of reference lists of articles and h and search ing of relevant conference abstract s and book chapters . Of these , 3 r and omized and 19 prospect i ve non-r and omized studies with a minimum median follow-up time of 4 years were identified . The authors review ed the published clinical evidence on APBI , complemented by relevant clinical and pathological studies of st and ard breast-conserving therapy and , through a series of personal communications , formulated the recommendations presented in this article . RESULTS The GEC-ESTRO Breast Cancer Working Group recommends three categories guiding patient selection for APBI : ( 1 ) a low-risk group for whom APBI outside the context of a clinical trial is an acceptable treatment option ; including patients ageing at least 50 years with unicentric , unifocal , pT1 - 2 ( < or=30 mm ) pN0 , non-lobular invasive breast cancer without the presence of an extensive intraductal component ( EIC ) and lympho-vascular invasion ( LVI ) and with negative surgical margins of at least 2 mm , ( 2 ) a high-risk group , for whom APBI is considered contraindicated ; including patients ageing < or=40 years ; having positive margins , and /or multicentric or large ( > 30 mm ) tumours , and /or EIC positive or LVI positive tumours , and /or 4 or more positive lymph nodes or unknown axillary status ( pNx ) , and ( 3 ) an intermediate-risk group , for whom APBI is considered acceptable only in the context of prospect i ve clinical trials . CONCLUSIONS These recommendations will provide a clinical guidance regarding the use of APBI outside the context of a clinical trial before large-scale r and omized clinical trial outcome data become available . Furthermore they should promote further clinical research focusing on controversial issues in the treatment of early-stage breast carcinoma |
12,725 | 15,832,693 | Findings suggest that many child psychotherapy treatment studies have not inadequately controlled for nonspecific factors such as attention and treatment intensity and have failed to assess specific mediators of change . | Abstract In the rising quest for evidence -based interventions , recent research often does not give adequate attention to “ nonspecific therapeutic factors , ” including the effects of attention , positive regard , and therapeutic alliance , as well as the effects of treatment dose , intensity and actual processes mediating therapeutic change . | OBJECTIVE To evaluate the relative efficacy of ( 1 ) individual cognitive-behavioral family-based therapy ( CBFT ) ; ( 2 ) group CBFT ; and ( 3 ) a waitlist control group in the treatment of childhood obsessive-compulsive disorder ( OCD ) . METHOD This study , conducted at a university clinic in Brisbane , Australia , involved 77 children and adolescents with OCD who were r and omized to individual CBFT , group CBFT , or a 4- to 6-week waitlist control condition . Children were assessed before and after treatment and at 3 months and 6 months following the completion of treatment using diagnostic interviews , symptom severity interviews , and self-report measures . Parental distress , family functioning , sibling distress , and levels of accommodation to OCD dem and s were also assessed . Active treatment involved a manualized 14-week cognitive-behavioral protocol , with parental and sibling components . RESULTS By an evaluable patient analysis , statistically and clinical ly significant pretreatment-to-posttreatment change occurred in OCD diagnostic status and severity across both individual and group CBFT , with no significant differences in improvement ratings between these conditions . There were no significant changes across measures for the waitlist condition . Treatment gains were maintained up to 6 months of follow-up . CONCLUSIONS Contrary to previous findings and expectations , group CBFT is as effective in reducing OCD symptoms for children and adolescents as individual treatment . Findings support the efficacy and durability of CBFT in treating childhood OCD The relative effectiveness of group care ( GC ) and multidimensional treatment foster care ( MTFC ) was compared in terms of their impact on criminal offending , incarceration rates , and program completion outcomes for 79 male adolescents who had histories of chronic and serious juvenile delinquency . Results show that boys who participated in MTFC had significantly fewer criminal referrals and returned to live with relatives more often . Multiple regression analyses showed that assignment to a treatment condition ( i.e. , GC or MTFC ) predicted official and self-reported criminality in follow-up beyond other well-known predictors of chronic juvenile offending ( i.e. , age at 1st offense , number of previous offenses , age at referral ) BACKGROUND Previous studies in non clinical sample s have shown psychosocial treatments to be efficacious in the treatment of adolescent depression , but few psychotherapy treatment studies have been conducted in clinical ly referred , depressed adolescents . METHODS One hundred seven adolescent patients with DSM-III-R major depressive disorder ( MDD ) were r and omly assigned to 1 of 3 treatments : individual cognitive behavior therapy , systemic behavior family therapy ( SBFT ) , or individual nondirective supportive therapy ( NST ) . Treatments were 12 to 16 sessions provided in as many weeks . Intent-to-treat analyses were conducted using all follow-up data . RESULTS Of the 107 patients enrolled in the study , 78 ( 72.9 % ) completed the study , 4 ( 3.7 % ) never initiated treatment , 10 ( 9.3 % ) had exclusionary criteria that were undetected at entry , 8 ( 7.5 % ) dropped out , and 7 ( 6.5 % ) were removed for clinical reasons . Cognitive behavior therapy showed a lower rate of MDD at the end of treatment compared with NST ( 17.1 % vs 42.4 % ; P = .02 ) , and result ed in a higher rate of remission ( 64.7 % , defined as absence of MDD and at least 3 consecutive Beck Depression Inventory scores < 9 ) than SBFT ( 37.9 % ; P = .03 ) or NST ( 39.4 % ; p = .04 ) . Cognitive behavior therapy result ed in more rapid relief in interviewer-rated ( vs both treatments , P = .03 ) and self-reported depression ( vs SBFT , P = .02 ) . All 3 treatments showed significant and similar reductions in suicidality and functional impairment . Parents ' views of the credibility of cognitive behavior therapy improved compared with parents ' views of both SBFT ( P = .01 ) and NST ( P = .05 ) . CONCLUSIONS Cognitive behavior therapy is more efficacious than SBFT or NST for adolescent MDD in clinical setting s , result ing in more rapid and complete treatment response OBJECTIVE To test the hypotheses that in children with attention-deficit/hyperactivity disorder ( ADHD ) ( 1 ) symptoms of ADHD , oppositional defiant disorder , and overall functioning are significantly improved by methylpheni date combined with intensive multimodal psychosocial treatment compared with methylpheni date alone and with methylpheni date plus attention control and ( 2 ) more children receiving combined treatment can be taken off methylpheni date . METHOD One hundred three children with ADHD ( ages 7 - 9 ) , free of conduct and learning disorders , who responded to short-term methylpheni date were r and omized for 2 years to ( 1 ) methylpheni date alone ; ( 2 ) methylpheni date plus psychosocial treatment that included parent training and counseling , social skills training , psychotherapy , and academic assistance , or ( 3 ) methylpheni date plus attention psychosocial control treatment . Assessment s included parent , teacher , and psychiatrist ratings , and observations in academic and gym classes . RESULTS Combination treatment did not lead to superior functioning and did not facilitate methylpheni date discontinuation . Significant improvement occurred across all treatments and continued over 2 years . CONCLUSIONS In stimulant-responsive children with ADHD , there is no support for adding ambitious long-term psychosocial intervention to improve ADHD and oppositional defiant disorder symptoms . Significant benefits from methylpheni date were stable over 2 years Sixty children , ages 7 - 17 years , who fulfilled Diagnostic and Statistical Manual of Mental Disorders ( 4th ed . ; American Psychiatric Association , 1994 ) diagnosis for various specific phobias were r and omized to ( a ) 1-session exposure treatment alone , ( b ) 1-session treatment with a parent present , or ( c ) wait-list control group for 4 weeks . After the waiting period , the wait-list patients were rer and omized to the active treatments . The patients ' phobias were assessed with behavioral approach tests ( approach behavior , experienced anxiety , and physiological reactions ) , whereas general anxiety , depression , phobic tendencies , and anxiety sensitivity were assessed with self-report inventories . Assessment s were done pre- , post- , and 1-year following treatment . Results showed that both treatment conditions did significantly better than the control condition , whereas the treatment groups did equally well on most measures , and the effects were maintained at follow-up . The implication s of these results are discussed This study evaluated the relative efficacy of an exposure-based contingency management ( CM ) treatment condition and an exposure-based cognitive self-control ( SC ) treatment condition relative to an education support ( ES ) control condition for treating children with phobic disorders . Eighty-one children and their parents completed a 10-week treatment program in which children and parents were seen in separate treatment sessions with the therapist , followed by a brief conjoint meeting . Children in both the CM and SC conditions showed substantial improvement on all of the outcome measures . These gains were maintained at 3- , 6- , and 12-month follow-ups . Interestingly , children in the ES condition also showed comparable improvements at posttreatment and at 3- , 6- , and 12-month follow-ups . Implication s of the findings are discussed with respect to knowledge development and clinical practice OBJECTIVE To evaluate two different parent-based therapies for preschool attention-deficit/hyperactivity disorder ( ADHD ) in a community sample . METHOD Three-year-old children displaying a preschool equivalent of ADHD ( n = 78 ) were r and omly assigned to either a parent training ( PT ; n = 30 ) , a parent counseling and support ( PCO&S ; n = 28 ) , or a waiting-list control group ( n = 20 ) . The PT group received coaching in child management techniques . The PC&S group received nondirective support and counseling . Measures of child symptoms and mothers ' well-being were taken before and after intervention and at 15 weeks follow-up . RESULTS ADHD symptoms were reduced ( F2,74 = 11.64 ; p < .0001 ) and mothers ' sense of well-being was increased by PT relative to both other groups ( F2,74 = 10.32 ; p < .005 ) . Fifty-three percent of children in the PT group displayed clinical ly significant improvement ( chi 2 = 4.08 ; p = .048 ) . CONCLUSIONS PT is a valuable treatment for preschool ADHD . PC&S had little effect on children 's behavior . Constructive training in parenting strategies is an important element in the success of parent-based interventions . Psychostimulants are not a necessary component of effective treatment for many children with preschool ADHD The state of the art for treatment efficacy studies now requires manual guided treatments and tests of therapist adherence . This report provides findings regarding adherence assessment of therapists participating in an investigation of treatment matching in adolescent substance abusers . The Group Sessions Rating Scale ( GSRS ) , a group-therapy process measure , was studied to determine its appropriateness for assessing group treatment of adolescents with a ) substance use disorders ( SUD ) , b ) interrater reliability , c ) internal consistency , and d ) ability to discriminate the active ingredients of cognitive-behavioral therapy ( CBT ) from interactional therapy ( IT ) . Interrater reliabilities were moderate to high , with those for CBT generally higher than those for IT . Internal consistency of CBT items was moderate , whereas those of IT were moderately high . Discriminability between the two treatment modalities was high . The frequency of active ingredients was generally therapy-specific : high for the relevant and low for the nonrelevant therapeutic modality items . The GSRS was found to be effective in the measurement of treatment process in adolescents with SUD OBJECTIVE A r and omized , controlled effectiveness trial of group cognitive-behavioral therapy ( CBT ) for depressed adolescent offspring of depressed parents in a health maintenance organization ( HMO ) was conducted . METHOD Potential adult cases were found by review ing antidepressant medication prescriptions , mental health appointments , and medical charts . Introductory study letters signed by each parent 's treating physician were mailed to the appropriate adults . Eligible offspring aged 13 to 18 who met current DSM-III-R criteria for major depression and /or dysthymia were r and omly assigned to either usual HMO care ( n = 47 ) or usual care plus a 16-session group CBT program ( n = 41 ) . Assessment s were conducted at baseline , after treatment , and at 12- and 24-month follow-up . RESULTS Using intent-to-treat analyses , the authors were unable to detect any significant advantage of the CBT program over usual care , either for depression diagnoses , continuous depression measures , nonaffective measures , or functioning outcomes . CONCLUSIONS Group CBT does not appear to be incrementally beneficial for depressed offspring of depressed parents who are receiving other mental health care . However , given that many other studies have found positive effects of CBT for youth depression , this single study should not be viewed as evidence that CBT is ineffective overall In this article , we examine the impact of two universal , grade 1 preventive interventions on the onset of tobacco smoking as assessed in early adolescence . The classroom-centered ( CC ) intervention was design ed to reduce the risk for tobacco smoking by enhancing teachers ' behavior management skills in first grade and , thereby , reducing child attention problems and aggressive and shy behavior-known risk behaviors for later substance use . The family-school partnership ( FSP ) intervention targeted these early risk behaviors via improvements in parent-teacher communication and parents ' child behavior management strategies . A cohort of 678 urban , predominately African-American , public school students were r and omly assigned to one of three Grade 1 classrooms at entrance to primary school ( age 6 ) . One classroom featured the CC intervention , a second the FSP intervention , and the third served as a control classroom . Six years later , 81 % of the students completed audio computer-assisted self-interviews . Relative to controls , a modest attenuation in the risk of smoking initiation was found for students who had been assigned to either the CC or FSP intervention classrooms ( 26 % versus 33 % ) ( adjusted relative risk for CC/control contrast=0.57 , 95 % confidence interval ( CI ) , 0.34 - 0.96 ; adjusted relative risk for FSP/control contrast=0.69 , 95 % CI , 0.50 - 0.97 ) . Results lend support to targeting the early antecedent risk behaviors for tobacco smoking Fifty-three child and adolescent psychiatric patients with depressive disorders were r and omly allocated to brief cognitive-behaviour therapy ( CBT ) or to a control treatment , relaxation training . Forty-eight patients completed the treatment phase of the trial , which comprised 5 - 8 treatment sessions . Post-treatment assessment s showed a clear advantage of CBT over relaxation on measures of both depression and overall outcome . However , there were no significant differences between the treatments on comorbid anxiety and conduct symptoms . At follow-up , the differences between the groups were reduced , partly because of a high relapse rate in the DTP group and partly because subjects in the relaxation group continued to recover OBJECTIVES This study examined ( 1 ) the effect of a cognitive-behavioral group intervention on anxiety , depression , and coping strategies in school-age children ( aged 7 - 12 years ) with Axis I anxiety disorders ; and ( 2 ) the effect of parental involvement on treatment outcomes . METHOD Parents and children ( N = 62 ) were r and omly assigned to one of three 12-week treatment conditions : parent and child intervention , child-only intervention , and parent-only intervention . Child anxiety , depression , and coping strategies were assessed before and after treatment . RESULTS All treatment groups reported fewer symptoms of anxiety and depression posttreatment and changes in their use of coping strategies . Children in the parent and child intervention used more active coping strategies posttreatment compared with children in the other 2 treatment conditions . Parents in this treatment condition reported a significantly greater improvement in their children 's emotional well-being than parents in the other treatment conditions . CONCLUSIONS Cognitive-behavioral group interventions reduced symptoms of anxiety and depression in school-age children with anxiety disorders . Concurrent parental involvement enhanced the effect on coping strategies . Further investigation is needed to corroborate the effectiveness of such short-term interventions and the maintenance of treatment effects 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 To evaluate the efficacy of multisystemic therapy ( MST ) in reducing attempted suicide among predominantly African American youths referred for emergency psychiatric hospitalization . METHOD Youths presenting psychiatric emergencies were r and omly assigned to MST or hospitalization . Indices of attempted suicide , suicidal ideation , depressive affect , and parental control were assessed before treatment , at 4 months after recruitment , and at the 1-year posttreatment follow-up . RESULTS Based on youth report , MST was significantly more effective than emergency hospitalization at decreasing rates of attempted suicide at 1-year follow-up ; also , the rate of symptom reduction over time was greater for youths receiving MST . Also , treatment differences in patterns of change in attempted suicide ( caregiver report ) varied as a function of ethnicity , gender , and age . Moreover , treatment effects were found for caregiver-rated parental control but not for youth depressive affect , hopelessness , or suicidal ideation . CONCLUSIONS Results generally support MST 's effectiveness at reducing attempted suicide in psychiatrically disturbed youngsters , whereas the effects of hospitalization varied based on informant and youth demographic characteristics Background : Settling and night waking problems are particularly prevalent , persistent , and generally considered difficult to treat in children with a learning disability , although intervention trials are few . Scarce re sources , however , limit access to proven behavioural treatments . Aims : To investigate the efficacy of a media based brief behavioural treatment of sleep problems in such children by comparing ( 1 ) face-to-face delivered treatment versus control and ( 2 ) booklet delivered treatment versus controls . Methods : The parents of 66 severely learning disabled children aged 2–8 years with settling and /or night waking problems took part in a r and omised controlled trial with a wait-list control group . Behavioural treatments were presented either conventionally face-to-face or by means of a 14 page easy to read illustrated booklet . A composite sleep disturbance score was derived from sleep diaries kept by parents . Results : Both forms of treatment were almost equally effective compared with controls . Two thirds of children who were taking over 30 minutes to settle five or more times per week and waking at night for over 30 minutes four or more times per week improved on average to having such settling or night waking problems for only a few minutes or only once or twice per week ( H = 34.174 , df = 2 , p<0.001 ) . These improvements were maintained after six months . Conclusions : Booklet delivered behavioural treatments for sleep problems were as effective as face-to-face treatment for most children in this population Undertook an evaluation of a cognitive-behavioral group family-based intervention for childhood anxiety disorders in Brisbane , Australia . The treatment aim ed to provide children and their families with skills in the management of anxiety and avoidance , problem solving , and mutual family support . Children ( n = 60 ) ranging from 7 to 14 years old who fulfilled diagnostic criteria for separation anxiety , overanxious disorder , or social phobia were r and omly allocated to 3 treatment conditions : group cognitive-behavioral therapy ( GROUP-CBT ) , group cognitive-behavioral therapy plus family management ( GROUP-FAM ) , and wait list ( WL ) . The effectiveness of the interventions was evaluated at posttreatment and 12-month follow-up . Results indicated that across treatment conditions , 64.8 % of children no longer fulfilled diagnostic criteria for an anxiety disorder in comparison with 25.2 % of children on the wait list . At 12-month FU , 64.5 % of children in the GROUP-CBT group and 84.8 % of children in the GROUP-FAM group were diagnosis free . Comparisons of children receiving GROUP-CBT with those receiving GROUP-FAM on self-report measures and clinician ratings indicated marginal added benefits from GROUP-FAM treatment . Results show that CBT interventions for childhood anxiety disorders can be effectively administered in a group format & NA ; This study reports on the results of a r and omized controlled trial that evaluated a caregiverbased intervention program for children with autism in community day‐care centers . Thirty‐five preschool children with a DSM III‐R diagnosis of autism or pervasive developmental disorder were r and omized to an experimental or control group . Children in the experimental group were enrolled in day care and their parents and child care workers received a 12‐week intervention consisting of lectures and on‐site consultations to day‐care centers . In addition , supportive work was undertaken with families . Control subjects received day care alone . In the experimental group , there were greater gains in language abilities , significant increases in caregivers ' knowledge about autism , greater perception of control on the part of mothers , and greater parent satisfaction . We conclude that this research design demonstrated that the intervention was significantly superior to day care alone Sixty-seven children aged 7 to 14 who met diagnostic criteria for an anxiety disorder were assigned to conditions according to parental anxiety level . Within these conditions , children were r and omly assigned to 1 of 2 treatments : child-focused cognitive-behavioral therapy ( CBT ) or child-focused CBT plus parental anxiety management ( CBT + PAM ) . At posttreatment , results indicated that within the child-anxiety-only condition , 82 % of the children in the CBT condition no longer met criteria for an anxiety disorder compared with 80 % in the CBT + PAM condition . Within the child + parental anxiety condition , 39 % in the CBT condition no longer met criteria compared with 77 % in the CBT + PAM condition . At follow-up , these differences were maintained , with some weakening over time . Results were not consistent across outcome measures . The interpretation and potential clinical implication s of these findings are discussed OBJECTIVE Treatment outcome for sexually abused preschool-age children and their parents was assessed , comparing the effectiveness of a cognitive-behavioral intervention to nondirective supportive treatment . METHOD Sixty-seven sexually abused preschool children and their parents were r and omly assigned to either ( 1 ) cognitive-behavioral therapy adapted for sexually abused preschool children ( CBT-SAP ) or ( 2 ) nondirective supportive therapy ( NST ) . Treatment consisted of 12 individual sessions for both the child and parent , monitored for integrity with the therapeutic model through intensive training and supervision , use of treatment manuals , and rating of audiotaped sessions . Parents completed the Child Behavior Checklist , the Child Sexual Behavior Inventory , and the Weekly Behavior Report to measure a variety of emotional and behavioral symptoms . RESULTS Within-group comparison of pretreatment and posttreatment outcome measures demonstrated that while the NST group did not change significantly with regard to symptomatology , the CBT-SAP group had highly significant symptomatic improvement on most outcome measures . Repeated- measures analyses of variance demonstrated group x time interactions on some variables as well . Clinical findings also supported the effectiveness of the CBT-SAP intervention over NST . CONCLUSIONS Findings provide strong preliminary evidence for the effectiveness of a specific cognitive-behavioral treatment model for sexually abused preschool children and their parents R and om assignment was made of 182 clinical ly referred marijuana- and alcohol-abusing adolescents to one of three treatments : multidimensional family therapy ( MDFT ) , adolescent group therapy ( AGT ) , and multifamily educational intervention ( MEI ) . Each treatment represented a different theory base and treatment format . All treatments were based on a manual and were delivered on a once-a-week outpatient basis . The therapists were experienced community clinicians trained to model-specific competence prior to the study and then supervised throughout the clinical trial . A theory-based multimodal assessment strategy measured symptom changes and prosocial functioning at intake , termination , and 6 and 12 months following termination . Results indicate improvement among youths in all three treatments , with MDFT showing superior improvement overall . MDFT participants also demonstrated change at the 1-year follow-up period in the important prosocial factors of school/academic performance and family functioning as measured by behavioral ratings . Results support the efficacy of MDFT , a relatively short-term , multicomponent , multitarget , family-based intervention in significantly reducing adolescent drug abuse and facilitating adaptive and protective developmental processes OBJECTIVE To conduct a controlled group outcome investigation of the efficacy of cognitive-behavioral treatment for school phobia . METHOD Fifty-six children with school phobia were r and omly assigned to 12 weeks of cognitive-behavioral therapy or an attention-placebo control condition . Pre- and posttreatment school attendance , self-reported anxiety and depression , and diagnostic status were compared . RESULTS Both the experimental and control treatments were equally effective at returning children to school . Both treatments also were effective in reducing children 's anxiety and depressive symptoms . Follow-up revealed no differences between groups when the children reentered school the next school year . CONCLUSIONS Overall , results suggest that psychosocial treatments are effective at returning school-phobic children to school and that the highly structured cognitive-behavioral approach may not be superior to more traditional educational and supportive treatment methods The study tested alternative intervention strategies to reduce escalation in problem behaviors among high-risk young adolescents ( 11 to 14 years old ) . A total of 158 families with young adolescents ( male and female ) participated in this study . Of these , 119 families were r and omly assigned to 1 of the following intervention conditions : ( a ) parent focus , ( b ) teen focus , ( c ) parent and teen focus , ( d ) self-directed change ( material s only ) . In addition , 39 families of young adolescents were recruited as a quasi-experimental control . Parent focus and teen focus interventions result ed in immediate beneficial effects in observed and reported family conflict . The parent intervention conditions showed immediate beneficial effects on behavior problems at school . Longitudinal trends suggest that the parent focus condition may reduce subsequent tobacco use , compared with all other approaches . Interventions that aggregated high-risk youths into groups , however , showed the highest escalations in tobacco use and problem behavior at school , beginning at termination and persisting to follow-up . These findings are discussed with respect to the need to re-evaluate strategies that aggregate high-risk youths into intervention programs and focus more on strategies to engage parents in prevention The Queensl and Early Intervention and Prevention of Anxiety Project evaluated the effectiveness of a cognitive-behavioral and family-based group intervention for preventing the onset and development of anxiety problems in children . A total of 1,786 7- to 14-year-olds were screened for anxiety problems using teacher nominations and children 's self-report . After recruitment and diagnostic interviews , 128 children were selected and assigned to a 10-week school-based child- and parent-focused psychosocial intervention or to a monitoring group . Both groups showed improvements immediately postintervention . At 6 months follow-up , the improvement maintained in the intervention group only , reducing the rate of existing anxiety disorder and preventing the onset of new anxiety disorders . Overall , the results showed that anxiety problems and disorders identified using child and teacher reports can be successfully targeted through an early intervention school-based program A family-based treatment for childhood anxiety was evaluated . Children ( n = 79 ) aged 7 to 14 who fulfilled diagnostic criteria for separation anxiety , overanxious disorder , or social phobia were r and omly allocated to 3 treatment conditions : cognitive-behavioral therapy ( CBT ) , CBT plus family management ( CBT + FAM ) , and waiting list . The effectiveness of the interventions was evaluated at posttreatment and at 6 and 12 months follow-up . The results indicated that across treatment conditions , 69.8 % of the children no longer fulfilled diagnostic criteria for an anxiety disorder , compared with 26 % of the waiting-list children . At the 12-month follow-up , 70.3 % of the children in the CBT group and 95.6 % of the children in the CBT + FAM group did not meet criteria . Comparisons of children receiving CBT with those receiving CBT + FAM on self-report measures and clinician ratings indicated added benefits from CBT + FAM treatment . Age and gender interacted with treatment condition , with younger children and female participants responding better to the CBT + FAM condition BACKGROUND Despite the frequently reported association between maternal depression and childhood psychopathological disorder , few studies have attempted to intervene with both conditions . AIMS To evaluate the effect of group cognitive-behavioural therapy ( CBT ) on child behaviour problems and maternal depression in a group of women with young children . METHOD An assessor-masked , r and omised placebo-controlled trial compared three treatments : CBT for depression and parenting skills enhancement ; a mothers ' support group ; and no intervention . An epidemiological ( general population ) sample was recruited . RESULTS Analysis showed no significant difference between the groups . Within-group comparison suggested that at the end of treatment and at 6-month and 12-month follow-up , child problems and maternal depression had improved significantly in the CBT group . CONCLUSIONS There was no statistically significant difference between groups . Both contact interventions seemed to provide some benefits to mothers with depression , with a possibly improved outcome result ing from CBT for children with behavioural problems . The results must be treated with caution This study evaluated the efficacy of cognitive-behavioral therapy ( CBT ) and interpersonal psychotherapy ( IPT ) with depressed adolescents in Puerto Rico . Seventy-one adolescents meeting Diagnostic and Statistical Manual of Mental Disorders ( 3rd ed . , rev . ; American Psychiatric Association , 1987 ) criteria for a diagnosis of depression were r and omly assigned to 1 of 3 conditions : CBT , IPT , or wait list ( WL ) . Pretreatment , posttreatment , and 3-month follow-up measures of depression symptoms , self-esteem , social adjustment , family emotional involvement and criticism , and behavioral problems were completed . Results suggest that IPT and CBT significantly reduced depressive symptoms when compared with the WL condition . IPT was superior to the WL condition in increasing self-esteem and social adaptation . Clinical significance tests suggested that 82 % of adolescents in IPT and 59 % of those in CBT were functional after treatment . The results suggest that both IPT and CBT are efficacious treatments for depressed Puerto Rican adolescents . IPT 's impact in other levels of outcome is discussed in terms of its consonance with Puerto Rican cultural values BACKGROUND One hundred and twenty-two children identified by teachers as at risk for behavioural or emotional problems were r and omly allocated to drama-group therapy or to a curriculum- studies control , based in school . METHODS One hundred and seventeen completed the intervention phase of the trial , which comprised 12 hour-long sessions . Post-intervention self-reports showed significant effects associated with both interventions . RESULTS However , there was a clear advantage of group therapy over both a waiting list control and curriculum studies , according to teacher reports . This was true also of categorical analyses focusing on those with the most severe symptoms . CONCLUSIONS These analyses confirmed sustained teacher-reported improvement over a year-long follow-up period This study examined the long-term substance use outcomes of 2 brief interventions design ed for general population families of young adolescents . Thirty-three public schools were r and omly assigned to 3 conditions : the 5-session Preparing for the Drug Free Years Program , the 7-session Iowa Strengthening Families Program , and a minimal contact control condition . The pretest involved 667 6th grade rs and their families . Assessment s included multiple measures of initiation and current use of alcohol , tobacco , and marijuana . Pretest data were collected in the 6th grade and the reported follow-up data were collected in the 10th grade . Significant intervention-control differences in initiation and current use were found for both interventions . It is concluded that brief family skills-training interventions design ed for general population s have the potential to reduce adolescent substance use and thus have important public health implication OBJECTIVE This trial examined the effects of both acute and maintenance cognitive-behavioral therapy ( CBT ) for depressed adolescents . METHOD Adolescents with major depression or dysthymia ( N = 123 ) were r and omly assigned to 1 of 3 eight-week acute conditions : adolescent group CBT ( 16 two-hour sessions ) ; adolescent group CBT with a separate parent group ; or waitlist control . Subsequently , participants completing the acute CBT groups were r and omly reassigned to 1 of 3 conditions for the 24-month follow-up period : assessment s every 4 months with booster sessions ; assessment s only every 4 months ; or assessment s only every 12 months . RESULTS Acute CBT groups yielded higher depression recovery rates ( 66.7 % ) than the waitlist ( 48.1 % ) , and greater reduction in self-reported depression . Outcomes for the adolescent-only and adolescent + parent conditions were not significantly different . Rates of recurrence during the 2-year follow-up were lower than found with treated adult depression . The booster sessions did not reduce the rate of recurrence in the follow-up period but appeared to accelerate recovery among participants who were still depressed at the end of the acute phase . CONCLUSIONS The findings , which replicate and exp and upon a previous study , support the growing evidence that CBT is an effective intervention for adolescent depression The effects of multisystemic therapy ( MST ) in treating violent and chronic juvenile offenders and their families in the absence of ongoing treatment fidelity checks were examined . Across 2 public sector mental health sites , 155 youths and their families were r and omly assigned to MST versus usual juvenile justice services . Although MST improved adolescent symptomology at posttreatment and decreased incarceration by 47 % at a 1.7-year follow-up , findings for decreased criminal activity were not as favorable as observed on other recent trials of MST . Analyses of parent , adolescent , and therapist reports of MST treatment adherence , however , indicated that outcomes were substantially better in cases where treatment adherence ratings were high . These results highlight the importance of maintaining treatment fidelity when disseminating complex family-based services to community setting Sixty-seven children ( ages 8 and 12 ) with social phobia were r and omized to either a behavioral treatment program design ed to enhance social skills and decrease social anxiety ( Social Effectiveness Therapy for Children , SET-C ) or an active , but nonspecific intervention ( Testbusters ) . Children treated with SET-C were significantly more improved across multiple dimensions , including enhanced social skill , reduced social fear and anxiety , decreased associated psychopathology , and increased social interaction . Furthermore , 67 % of the SET-C group participants did not meet diagnostic criteria for social phobia at posttreatment compared with 5 % of those in the Testbusters group . Treatment gains were maintained at 6-month follow-up . The results are discussed in terms of treatment of preadolescent children with social phobia and the durability of treatment effects OBJECTIVES To investigate the efficacy of a brief , manual-based group therapy for adolescents with poor anger control . A previously developed anger management treatment package of 10 to 12 sessions was condensed to a 4-session package to be given within 2 weeks . Immediate effectiveness and the transfer of skills were investigated ; anger management skills not only had to be acquired , they also had to be used in the adolescents ' natural social interactions . METHOD Fifty adolescent psychiatric in patients were selected for high levels of anger and r and omly assigned to treatment or control conditions . Pre- and posttreatment measures were administered to subjects and adults who rated the subjects ' behaviors . RESULTS Pre/post self-report measures , as well as behavior ratings by adults , indicated that the patients who went through the anger management series exhibited significantly improved skills . CONCLUSIONS These results suggested that the intervention for adolescents was effective even though it was condensed , but it should not be further abbreviated This study tested the hypothesis that dually diagnosed adolescent substance abusers could be matched to effective treatments on the basis of their comorbid psychopathology . Specifically , patients with externalizing disorders would have better outcomes when treated with cognitive-behavioral group treatment ( CBT ) , and subjects with internalizing disorders without comorbid externalizing disorders would fare better in interactional group treatment ( IT ) . Thirty-two dually diagnosed adolescent substance abusers were r and omized into two 12-week manual guided outpatient group psychotherapies : CBT and IT . At 3-month follow-up , no patient-treatment matching effects were identified . Adolescents assigned to CBT demonstrated a significant reduction in severity of substance use compared with those assigned to IT . Improvement in severity of family function showed a trend in favor of CBT . School function , peer-social relationships , legal problems , and psychiatric severity all showed a consistent nonsignificant direction in favor of CBT over IT . CBT appears to be a promising short-term psychosocial intervention for adolescents BACKGROUND Cognitive behavioral therapy has been shown to be more efficacious than alternative psychosocial interventions for the acute treatment of adolescents with major depressive disorder . However , the long-term impact of brief psychosocial interventions on the course of adolescent depression is not well established . METHODS One hundred seven adolescents with major depressive disorder r and omly assigned to 12 to 16 weeks of cognitive behavioral therapy , systemic behavioral family therapy , or nondirective supportive therapy were evaluated for 2 years after the psychotherapy trial to document the subsequent course and predictors of major depressive disorder . RESULTS There were no long-term differential effects of the 3 psychotherapies . Most participants ( 80 % ) recovered ( median time , 8.2 months from baseline ) , and 30 % had a recurrence ( median time , 4.2 months from recovery ) . Twenty-one percent were depressed during at least 80 % of the follow-up period . Severity of depression ( at baseline ) and presence of self-reported parent-child conflict ( at baseline and during the follow-up period ) predicted lack of recovery , chronicity , and recurrence . Despite the similarity to clinical ly referred patients at baseline , patients recruited via advertisement were less likely to experience a recurrence . CONCLUSIONS There were no significant differences in long-term outcome among cognitive behavioral therapy , systematic behavioral family therapy , and nondirective supportive therapy . While most participants in this study eventually recovered , those with severe depression and self-perceived parent-child conflict are at greater risk for chronic depression and recurrences Children with low school achievement frequently have behavior problems and interpersonal difficulties that pose a risk for psychosocial maladjustment . 39 boys were assessed and r and omly assigned to one of two group treatment conditions : ( a ) interpersonal cognitive problem-solving for whom training was provided through oral and written language activities that met children 's social and academic needs and ( b ) a language workshop , during which only academic difficulties were treated . Parents of children in both groups received group attention . Posttreatment assessment s indicated that boys in both conditions showed significant improvements on school achievement and behavior problems , as they were measured by behavior scales reported by mothers and by an academic achievement test . Children in the problem-solving group improved significantly more than the other group on most measures . These results suggest that work with interpersonal cognitive problem-solving skills combined with reading and writing activities is a useful means to produce improvements in child behavior and school achievement OBJECTIVE To compare the effectiveness of behavioral family systems therapy ( BFST ) with that of ego-oriented individual therapy ( EOIT ) as treatments for adolescents with anorexia nervosa . METHOD Thirty-seven adolescents meeting DSM-III-R criteria for anorexia nervosa were r and omly assigned to receive BFST or EOIT , in addition to a common medical and dietary regimen . In BFST , the family was seen conjointly , the parents were placed in control of the adolescent 's eating , distorted beliefs were targeted through cognitive restructuring , and strategic/behavioral interventions were used to change family interactions . In EOIT , the adolescent was seen individually , with an emphasis on building ego strength and uncovering the dynamics blocking eating ; parents were seen collaterally . Measures administered before , after , and at 1-year follow-up tapped body mass index , menstruation , eating attitudes , ego functioning , depression , and family interactions . RESULTS BFST produced greater weight gain and higher rates of resumption of menstruation than EOIT . Both treatments produced comparably large improvements in eating attitudes , depression , and eating-related family conflict , but very few changes occurred on ego functioning . CONCLUSIONS BFST and EOIT proved to be effective treatments for adolescents with anorexia nervosa , but BFST produced a faster return to health OBJECTIVE To evaluate the efficacy of child and caregiver participation in the cognitive-behavioral treatment of sexually abused children with posttraumatic stress symptoms . METHOD Thirty-six sexually abused children ( aged 5 - 17 years ) were r and omly assigned to a child-alone cognitive-behavioral treatment condition , a family cognitive-behavioral treatment condition , or a waiting-list control condition . RESULTS Compared with controls , children who received treatment exhibited significant improvements in posttraumatic stress disorder symptoms and self-reports of fear and anxiety . Significant improvements also occurred in relation to parent-completed measures and clinician ratings of global functioning . In general , parental involvement did not improve the efficacy of cognitive-behavioral therapy . Maintenance of improvement was evident at a 12-week follow-up assessment . CONCLUSIONS Cognitive-behavioral treatment was useful , but further research is required on caregiver involvement This study evaluated a parent problem-solving ( PPS ) intervention design ed to augment the effects of evidence -based therapy for children referred to treatment for aggressive and antisocial behavior . All children ( N = 127 , ages 6 - 14 years ) and their families received problem-solving skills training ( PSST ) , and parents received parent management training ( PMT ) . Families were r and omly assigned to receive or not to receive an additional component ( PPS ) that addressed parental stress over the course of treatment . Children improved with treatment ; the PPS intervention enhanced therapeutic change for children and parents and reduced the barriers that parents experienced during treatment . The implication s of the findings for improving evidence -based treatment as well as the limitations of adding components to treatment are detailed The present study examined the efficacy of group cognitive-behavioral therapy ( CBT ) in the treatment of childhood anxiety disorders . Thirty high-anxious children ( aged 9 - 12 years ) were assigned to either ( a ) group CBT ( n = 10 ) , ( b ) a psychological placebo intervention ( i.e. , emotional disclosure [ ED ] ; n = 10 ) , or ( c ) a no-treatment control condition ( n = 10 ) . Therapy outcome measures ( i.e. , children 's self-report of anxiety disorders symptoms , depression , and trait anxiety ) were obtained three months before treatment , at pretreatment , and at posttreatment . Results showed that levels of psychopathological symptoms remained relatively stable during the three months preceding treatment . Most importantly , pretreatment-posttreatment comparisons indicated that CBT was superior to ED and the no-treatment control condition . That is , only in the CBT condition significant reductions of anxiety disorders symptoms , trait anxiety , and depression were observed . These findings can be taken as further evidence for the efficacy of CBT in the treatment of childhood anxiety disorders Abstract Objective : To see whether a behaviourally based group parenting programme , delivered in regular clinical practice , is an effective treatment for antisocial behaviour in children . Design : Controlled trial with permuted block design with allocation by date of referral . Setting : Four local child and adolescent mental health services . Participants : 141 children aged 3 - 8 years referred with antisocial behaviour and allocated to parenting groups ( 90 ) or waiting list control ( 51 ) . Intervention : Webster-Stratton basic videotape programme administered to parents of six to eight children over 13 - 16 weeks . This programme emphasises engagement with parental emotions , rehearsal of behavioural strategies , and parental underst and ing of its scientific rationale . Main outcome measures : Semistructured parent interview and question naires about antisocial behaviour in children administered 5 - 7 months after entering trial ; direct observation of parent-child interaction . Results : Referred children were highly antisocial ( above the 97th centile on interview measure ) . Children in the intervention group showed a large reduction in antisocial behaviour ; those in the waiting list group did not change ( effect size between groups 1.06 SD ( 95 % confidence interval 0.71 to 1.41 ) , P<0.001 ) . Parents in the intervention group increased the proportion of praise to ineffective comm and s they gave their children threefold , while control parents reduced it by a third ( effect size between groups 0.76 ( 0.16 to 1.36 ) , P=0.018 ) . If the 31 children lost to follow up were included in an intention to treat analysis the effect size on antisocial behaviour was reduced by 16 % . Conclusions : Parenting groups effectively reduce serious antisocial behaviour in children in real life conditions . Follow up is needed to see if the children 's poor prognosis is improved and criminality prevented . What is already known on this topic Children who persistently display a high level of antisocial behaviour are at high risk of social rejection , juvenile delinquency , and long term unemployment ; the cost to society is high While some behaviourally based parenting programmes have been shown to be effective in university centre trials with volunteers or specially selected cases , most trials of psychological treatments for children in real life setting s have shown no effect What this study adds An evidence based intervention is available for use in regular clinical practice that effectively reduces antisocial behaviour in referred children The intervention works well with children at risk of criminality from a combination of highly antisocial behaviour , multiple psychopathology , and social The study aim ed to investigate a group of children with severe learning disabilities , challenging daytime behaviour , and severe sleep problems to see if successful behavioural treatment of the children 's sleep problems result ed in reduced daytime challenging behaviour as reported by mothers and teachers . A r and omised controlled trial of behavioural interventions for the children 's sleep problems was conducted ( N = 30 ) . The intervention group received an individually tailored behavioural programme and were supported by telephone calls from the therapist . Baseline assessment s of the children 's behaviour were made using the Aberrant Behavior Checklist and were repeated 1 month and 3 months after the start of intervention . There were no behavioural changes that were specific to children in the treatment group . However , improvements in some behaviours were seen in both the intervention and the control group at the 1-month and 3-month assessment s and there was agreement between mothers ' and teachers ' reports for many of these changes . The results suggest that nonspecific effects of participating in the study ( including an increased sleep duration , which was seen in both groups ) , rather than resolution of sleep problem per se , may have a beneficial effect on child behaviour and these factors need to be identified for therapeutic use BACKGROUND Postnatal depression is associated with adverse child cognitive and socio-emotional outcome . It is not known whether psychological treatment affects the quality of the mother-child relationship and child outcome . AIMS To evaluate the effect of three psychological treatments on the mother-child relationship and child outcome . METHOD Women with post-partum depression ( n=193 ) were assigned r and omly to routine primary care , non-directive counselling , cognitive-behavioural therapy or psychodynamic therapy . The women and their children were assessed at 4.5 , 18 and 60 months post-partum . RESULTS Indications of a positive benefit were limited . All three treatments had a significant benefit on maternal reports of early difficulties in relationships with the infants ; counselling gave better infant emotional and behaviour ratings at 18 months and more sensitive early mother-infant interactions . The treatments had no significant impact on maternal management of early infant behaviour problems , security of infant-mother attachment , infant cognitive development or any child outcome at 5 years . CONCLUSIONS Early intervention was of short-term benefit to the mother-child relationship and infant behaviour problems . More-prolonged intervention may be needed . Health visitors could deliver this This r and omized experimental prevention study ( a ) evaluated the effectiveness of a parent-training program in a sample of 238 divorcing mothers with sons in Grade s 1 - 3 and ( b ) provided an experimental test of coercion theory . The intervention produced reductions in observed coercive parenting , prevented decay in positive parenting , and generally improved effective parenting practice s in comparisons of mothers in experimental and control groups . Moreover , coercion theory was supported . Improved parenting practice s correlated significantly with improvements in teacher-reported school adjustment , child-reported maladjustment , and mother-reported maladjustment . The intervention indirectly benefitted child outcomes through improved parenting practice s for a model based on child report and , to a lesser extent , on teacher report . The intervention did not produce direct effects on child outcomes Fifty children aged 7 - 14 years with a principal diagnosis of social phobia were r and omly assigned to either child-focused cognitive-behaviour therapy ( CBT ) , CBT plus parent involvement , or a wait list control ( WLC ) . The integrated CBT program involved intensive social skills training combined with grade d exposure and cognitive challenging . At posttreatment , significantly fewer children in the treatment conditions retained a clinical diagnosis of social phobia compared to the WLC condition . In comparison to the WLC , children in both CBT interventions showed significantly greater reductions in children 's social and general anxiety and a significant increase in parental ratings of child social skills performance . At 12-month follow-up , both treatment groups retained their improvement . There was a trend towards superior results when parents were involved in treatment , but this effect was not statistically significant The influence of family management skills ( i.e. , supervision , discipline , and positive adult-youth relationship ) and deviant peer association on youth antisocial behavior was examined within the context of a r and omized clinical trial contrasting multidimensional treatment foster care and services-as-usual group care . Participants were male adolescents with histories of chronic and serious juvenile delinquency who were m and ated into residential care by the juvenile court . As hypothesized , family management skills and deviant peer association mediated the effect of treatment condition and accounted for 32 % of the variance in subsequent antisocial behavior |
12,726 | 15,674,888 | There was no difference between CCPT and other airway clearance techniques in terms of respiratory function measured by st and ard lung function tests .
Studies undertaken during acute exacerbations demonstrated relatively large gains in respiratory function irrespective of airway clearance technique .
Longer-term studies demonstrated smaller improvements or deterioration over time .
This review demonstrated no advantage of CCPT over other airway clearance techniques in terms of respiratory function .
There was a trend for participants to prefer self-administered airway clearance techniques . | BACKGROUND Cystic fibrosis is an inherited life-limiting disorder , characterised by pulmonary infections and thick airway secretions .
Chest physiotherapy has been integral to clinical management in facilitating removal of airway secretions .
Conventional chest physiotherapy techniques ( CCPT ) have depended upon assistance during treatments , while more contemporary airway clearance techniques are self-administered , facilitating independence and flexibility .
OBJECTIVES To compare CCPT with other airway clearance techniques in terms of their effects on respiratory function , individual preference , adherence , quality of life and other outcomes . | STUDY OBJECTIVE To compare the intrapulmonary percussive ventilator ( IPV ) to chest physiotherapy ( P&PD ) with respect to acute changes in ( 1 ) pulmonary function and ( 2 ) sputum physical properties in patients with cystic fibrosis ( CF ) . DESIGN R and omized crossover . SETTING Community-based CF referral center . PARTICIPANTS Nine nonhospitalized person ( range , 7 to 40 years ; median , 12.4 years ) with moderate to excellent Shwachman scores . INTERVENTIONS Three treatment regimens : ( 1 ) 2.5 mg albuterol delivered via IPV ( internal percussive component activated ) ; ( 2 ) 2.5 mg . albuterol delivered via IPV ( internal percussive component inactivated ) , followed by P&PD ; and ( 3 ) 2.5 mg albuterol delivered via updraft nebulizer , followed by P&PD . MEASUREMENTS AND RESULTS Outcome measures included pulmonary function testing ( PFTs ) and quantitative and qualitative sputum analysis . Among the three treatment groups , there were no significant differences in the change in predicted PFTs 1 h or 4 h after treatment , nor in the volume of sputum expectorated in the first 4 or in the subsequent 20 h. Among patients receiving IPV , more serious disease was associated with greater improvement in FEF25 - 75 1 h after treatment , but these differences disappeared by 4 h. There were no meaningful differences in viscoelastic characteristics of sputum expectorated after each treatments . Participants reported general satisfaction with no adverse effects while using IPV . CONCLUSIONS This initial pilot study suggests ( 1 ) stable patients with CF tolerated one treatment of IPV without adverse sequelae , and ( 2 ) IPV was as effective as st and ard aerosol and P&PD in improving short-term PFT results and enhancing sputum expectoration We studied the acute effects of 4 different chest physical therapy regimens using a r and omised cross-over design in 14 patients with cystic fibrosis . Treatment A consisted of postural drainage , percussion and vibration ; treatment B of postural drainage and periodic application of a face mask with positive expiratory pressure ( PEP ) ; treatment C of PEP in the sitting position ; treatment D of the forced expiration technique in the sitting position . In terms of sputum expectorated , treatments B and C were superior to treatment D and especially to treatment A ( p less than 0.05 ) . Skin oxygen tension , PSO2 was monitored continuously during and for 35 min after treatment . A substantial and prolonged decay in PSO2 was observed during treatment A , quite different from other patterns seen . During and even following treatment C , an increase in PSO2 was noted . PEP was well accepted by the patients , who preferred treatment C , and we suggest it is incorporated in chest physical therapy regimens if the therapeutic objective is to increase expectoration To compare the short-term effects of postural drainage with clapping ( PD ) and autogenic drainage ( AD ) on oxygen saturation , pulmonary function , and sputum recovery , we studied ten patients with cystic fibrosis ( CF ) r and omly treated with PD or AD on separate days . Pulse oximetry was monitored and sputum was collected during and for 1 h following each treatment . Pulmonary function was measured before and then 1 , 15 , and 60 min after each treatment . There was no significant difference in the amount of sputum recovered with AD ( 14.0 + /- 3.5 g ) vs PD ( 10.4 + /- 3.0 g ) and no significant differences in pulmonary function occurred . Oxygen saturation during PD fell from 93.3 + /- 0.7 % to 91.2 + /- 0.8 % ( p < 0.01 ) and required 15 min following treatment to return to baseline . Oxygen saturation did not fall during AD and increased to 94.5 + /- 0.7 % by 1 h following treatment ( baseline , 93.3 + /- 0.8 % ; p < 0.01 ) . We conclude that AD is less likely to produce oxygen desaturation and may be better tolerated by patients with CF , while producing similar benefits in sputum clearance The use of a positive expiratory pressure ( PEP ) mask was compared with postural drainage in the treatment of 10 patients with cystic fibrosis . The patients were allocated r and omly in a crossover fashion to the two regimens and evaluated initially by a physiotherapist and over a 4 week treatment period by use of a diary card . There was no significant difference in sputum production or change in lung function between each technique as assessed by the physiotherapist . Diary card evaluation also failed to demonstrate a difference in sputum production , symptom score or peak expiratory flow rate between the 4 week treatment periods . It was concluded that PEP mask therapy is an acceptable and effective alternative to postural drainage in interval therapy of patients with cystic fibrosis , although the patients have tended to revert to postural drainage during acute exacerbations We studied the effectiveness of some of the components of a physiotherapy regimen on the removal of mucus from the lungs of 6 subjects with cystic fibrosis . On 5 r and omized study days , after inhalation of a 99mTc-human serum albumin aerosol to label primarily the large airways , the removal of lung radioactivity was measured during 40 min of ( a ) spontaneous cough while at rest ( control ) , ( b ) postural drainage , ( c ) postural drainage plus mechanical percussion , ( d ) combined maneuvers ( postural drainage , deep breathing with vibrations , and percussion ) administered by a physiotherapist , ( e ) directed vigorous cough . Measurements continued for an additional 2 h of quiet rest . Compared with the control day , all forms of intervention significantly improved the removal of mucus : cough ( p less than 0.005 ) , physiotherapy maneuvers ( 0.005 less than or equal to p less than 0.01 ) , postural drainage ( p less than 0.05 ) , and postural drainage plus percussion ( p less than 0.01 ) . However , there was no significant difference between regimented cough alone and therapist-administered combined maneuvers , nor between postural drainage alone and with mechanical percussion . We conclude that in cystic fibrosis , vigorous , regimented cough sessions may be as effective as therapist-administered physiotherapy in removing pulmonary secretions . Postural drainage , although better than the control maneuver , was not as effective as cough and was not enhanced by mechanical percussion . Frequent , vigorous self-directed cough sessions are potentially as useful as more complex measures for effective bronchial toilet Bronchial hygiene therapy is a st and ard part of the treatment of patients with cystic fibrosis ( CF ) . Coughing alone promotes sputum expectoration and is probably the primary effective component of st and ard bronchial hygiene therapy . The purpose of this study was to determine whether substituting regular exercise , which also promotes coughing , for two of three daily bronchial hygiene treatments would affect the expected improvements in pulmonary function and exercise response in hospitalized patients with CF . Seventeen patients with CF hospitalized ( means length of stay = 13.0 + /- 2.6 days ) for an acute exacerbation of their pulmonary disease participated in the study . The patients were r and omly assigned to either a group that participated in two cycle ergometer exercise sessions and one bronchial hygiene treatment session per day ( EX Group [ n = 9 ] ) or a group that participated in three bronchial hygiene treatment sessions per day ( PD Group [ n = 8 ] ) . Pulmonary functions and responses to a progressive , incremental cycle ergometer exercise test were measured on admission and before discharge . Bronchial hygiene therapy consisted of postural drainage , in six positions , with chest percussion and vibration . Therapeutic exercise was of moderate intensity and was individually adjusted based on the patient 's heart rate and arterial oxygen saturation response to the admission exercise test . Coughing was encouraged during and after all treatments . Pulmonary function and exercise response were significantly improved over the period of hospitalization in both groups ; the improvements were the same in the two groups . These results indicate that , in some hospitalized patients with CF , exercise therapy may be substituted for at least part of the st and ard protocol of bronchial hygiene therapy Impaired mucociliary clearance due to defective ion and water transport and the effects of chronic airway infections lead to stasis of secretions and progressive pulmonary damage in patients with cystic fibrosis ( CF ) . Methods to improve removal of tenacious lung secretions in CF patients contribute to slowing the decline in respiratory function . We have evaluated an intrapulmonary percussive ventilator ( IPV ) , which is a device design ed to enhance airway clearance and preserve lung function . A previous pilot study by us had determined that the device was acceptable to patients and is safe . We undertook a 6 month parallel comparative trial of the IPV versus st and ard , manual chest physiotherapy in 16 CF children and adults . No significant differences in spirometric measures , numbers of hospitalizations , use of oral or IV antibiotics , or anthropometric measurements were detected between the st and ard aerosol/chest physiotherapy group and the IPV group over the duration of the trial . Patient acceptance , as determined by participant survey , was good . The device appeared to be safe and durable . It was concluded that the IPV is as effective as st and ard aerosol and chest physiotherapy in preserving lung function and anthropometric measures , and there was no difference in the use of antibiotics and hospitalizations Promotion of sputum expectoration by chest physiotherapy is an essential part of cystic fibrosis management . The role of exercise in improving sputum expectoration and lung function in these patients is more contentious . We therefore investigated the effect of adding an exercise programme to conventional chest physiotherapy in eight adult subjects ( four male ) with cystic fibrosis . Subjects were treated on two non-consecutive days of the second week of a course of in-patient antibiotic therapy in a cross-over fashion . On the exercise and physiotherapy day , subjects exercised 60 min before physiotherapy . On the physiotherapy alone day , subjects rested for 60 min instead of exercising . Physiotherapy was administered on both study days ( postural drainage , percussion , deep breathing , vibrations , forced expiratory technique and coughing ) . Lung function tests were performed at baseline , after exercise or rest and again immediately and 30 min after physiotherapy . Sputum weights were measured in the 60 min of exercise or rest ( period A ) and for the 60 min physiotherapy period and 30 min after physiotherapy ( period B ) . Mean total sputum expectoration ( period A and B ) was 14 g on physiotherapy alone and 21.5 g ( 4.8 ) on exercise and physiotherapy ( mean difference 7.5 g , 95 % CI 1.4 - 13.6 g , P = 0.02 ) . Mean sputum weights during period A ( i.e. rest vs. exercise ) on physiotherapy alone and exercise and physiotherapy were 2.6 and 7 g respectively ( mean difference 4.4 g , 95 % CI-0.07 - 8.8 g , P = 0.053 ) . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE We report the results of a long-term comparative trial of physiotherapy by the positive expiratory pressure ( PEP ) technique with a PEP mask ( Astra Meditec ) versus conventional postural drainage and percussion ( PD&P ) . Forty patients , ages 6 to 17 years , with Shwachman scores between 52 and 93 , attending the cystic fibrosis clinic were enrolled in the study and r and omly assigned to one of two groups . Group A ( control ) continued to perform physiotherapy by using PD&P for a 1-year period , whereas patients assigned to group B performed physiotherapy with the PEP technique for the same period . Compliance with physiotherapy was closely monitored for both groups throughout the study . Clinical status and pulmonary function ( forced vital capacity [ FVC ] , FEV1 , and FEF25 - 75 ) were measured at 3-month intervals . Group B ( PEP ) demonstrated improved pulmonary function in all parameters as measured by change in percent predicted value for age , gender , and height . The changes in pulmonary function over the study period were : FVC , + 6.57 ; FEV1 , + 5.98 ; and FEF25 - 75 , + 3.32 . This improvement was significantly different from that of group A ( PD&P ) whose pulmonary function declined in all parameters ( FVC , -2.17 ; FEV1 , -2.28 ; FEF25 - 75 , -0.24 ) . The differences between treatment groups were statistically significant for the changes in FVC ( p = 0.02 ) and FEV(1 ) ( p = 0.04 ) . Our results indicate that for our patients with cystic fibrosis , pulmonary physiotherapy with the PEP technique was superior to conventional physiotherapy with the PD&P technique In Pol and the st and ard treatment of pulmonary manifestation of cystic fibrosis consists of physiotherapy techniques of postural drainage with clapping . However many studies demonstrated that various alternative airway clearance techniques performed in Europe the last few years have been more effective than postural drainage . The aim of the study was a comparative analysis of the efficiency of selected chest physiotherapy methods used in the treatment of children with cystic fibrosis . We studied 21 patients , aged 5 - 18 ( x 10.57 ) , who were hospitalised in the Paediatric Clinic of National Research Institute of Mother and Child in Warsaw , Pol and . We compared five chest physiotherapy techniques : 1 - postural drainage with clapping , 2 - postural drainage with clapping and vibration , 3 - active cycle of breathing technique , 4 - Flutter(R ) , 5 - Flutter(R ) with relaxation . Every investigated drainage method was tested by each patient according to a determined procedure . The following indices were measured : weight of coughed up sputum , oxygen saturation ( SaO2 ) before , during and after drainage , peak expiratory flaw ( PEF ) before and after drainage . The biggest quantity of sputum determined by its coughed up weight was with active cycle of breathing technique ( x 2.126 g ) . In comparison , in patients using postural drainage with clapping and clapping with vibration average sputum expectoration was 0.895 and 1.012 g. Flutter device is recommended for individual usage . Our findings demonstrate that the Flutter with relaxation effectively facilitates removal of mucus from airways ( Flutter - x 1.48 g , Flutter with relaxation - x 2.012 g ) . We observed PEF decrease ( p > 0.05 ) during postural drainage with clapping and vibration . There were no significant differences in SaO2 between the values before and after drainage in every investigated technique Chest physiotherapy ( CPT ) is recommended for the clearance of bronchial secretions in the management of patients with cystic fibrosis ( CF ) . The Flutter valve ( Sc and ipharm , Birmingham , AL ) has been introduced as an alternative method to CPT for airway mucus clearance . The objective of this study was to compare the short-term effects of CPT and the Flutter valve on pulmonary function and exercise tolerance in patients with cystic fibrosis . Twenty-three patients , 5 to 21 years of age , were r and omized to receive one of two interventions : CPT or the Flutter valve , upon admission to the hospital for a 2-week treatment of pulmonary exacerbation . Pulmonary function testing ( PFTs ) and the 6-min walk test were performed on admission , day 7 , and day 14 of hospitalization . Data analysis indicated no significant differences between the two groups on admission . Both groups showed improvement in pulmonary function test results , but the Flutter group had a higher mean forced vital capacity ( FVC ) and forced expiratory volume in 1 sec ( FEV(1 ) ) compared to the CPT group after 1 week of intervention . Both groups continued to improve during the 2-week intervention , with no significant difference in FVC or FEV(1 ) between groups by the end of 2 weeks . Mean forced expiratory flow rate between 25 - 75 % of vital capacity ( FEF(25 - 75 ) ) , 6-min walk distance , and resting arterial oxyhemoglobin saturation ( SaO(2 ) ) showed little change by day 7 , but improved significantly ( P < 0.05 ) by day 14 of hospitalization in both groups , with no significant difference between groups . This study demonstrated that patients using the Flutter device had better pulmonary function after 1 week of therapy and similar improvement in pulmonary function and exercise tolerance compared to CPT after 2 weeks of therapy , suggesting that Flutter valve therapy is an acceptable alternative to st and ard CPT during in-hospital care of patients with CF Supervised directed coughing was compared to conventional physiotherapy ( postural drainage , vibration and /or percussion and coughing ) in 38 patients with cystic fibrosis aged 9 - 18 years admitted to hospital with an exacerbation of their pulmonary symptoms . Assessment included objective measures of pulmonary function and sputum characteristics . Both treatment groups showed significant improvement at the end of the 2-week period . When the patients were grade d according to their pulmonary disease , those with mild-moderate disease demonstrated a significant improvement in both treatment groups whereas those with severe lung disease showed little improvement with either treatment . Directed coughing is as effective as conventional physiotherapy in the management of patients with cystic fibrosis admitted to hospital for treatment of an exacerbation of their pulmonary symptoms There is controversy about the need for postural drainage physiotherapy in asymptomatic infants with cystic fibrosis ( CF ) . We aim ed to compare the effectiveness of st and ard postural drainage chest physiotherapy ( SPT ) with a modified physiotherapy regimen without head-down tilt ( MPT ) in young infants with CF . Twenty newly diagnosed infants with CF ( mean age , 2.1 months ; range , 1 - 4 ) were r and omized to SPT or MPT . Parents kept a detailed symptom and treatment diary for the following 12 months . Serial chest radiographs , taken at diagnosis , 12 months , 2(1/2 ) years , and 5 years after diagnosis , were assessed using the Brasfield score . Pulmonary function tests were compared between groups after 5 years . Of the 20 infants , 16 ( 80 % ) completed the review at 12 months , and 14 ( 70 % ) at 2(1/2 ) and 5 years . Patients receiving SPT had more days with upper respiratory tract symptoms than those on MPT ( 70 + /- 32.8 vs. 37 + /- 24.9 days ; P = 0.04 ) and required longer courses of antibiotics ( 23 + /- 28.5 vs. 14 + /- 11.2 days ; P = 0.05 ) . Chest x-ray scores were similar at diagnosis but were worse at 2(1/2 ) years for those receiving SPT ( P = 0.03 ) . Forced vital capacity and forced expired volume in 1 sec ( FEV(1 ) ) at 5 - 6 years was lower for SPT than for MPT ( P < 0.05 ) . In conclusion , MPT was associated with fewer respiratory complications than SPT in infants with CF The aim of this study was to determine whether repeated maximum inspiratory vital capacity manoeuvres against a fixed resistance increased effective short-term sputum clearance in adults with cystic fibrosis ( CF ) . Twenty adults with CF were r and omised to receive , on alternate days , either st and ardised physiotherapy ( SP ) for 30 min , comprising postural drainage and the active cycle of breathing technique , or a series of resistive inspiratory manoeuvres ( RIM ) at 80 % of their maximum sustained inspiratory pressure developed between residual volume and total lung capacity during the first 4 days of the treatment of an exacerbation of respiratory symptoms . Expectorated sputum was collected during and for 30 min after each treatment and weighed . Total protein , immunoreactive interleukin (IL)‐8 and human neutrophil elastase ( HNE ) concentrations , and the amount of each component expectorated , were determined . Compared with SP , RIM increased sputum weight two-fold , independent of treatment order or day . The concentrations of protein , IL-8 and HNE in sputum were similar for both treatments , while the quantity expectorated was greater with RIM treatment . In conclusion , short-term resistive inspiratory manoeuvres treatment was more effective at clearing sputum and inflammatory mediators than st and ardised physiotherapy We compared st and ard chest physical therapy and postural drainage ( CPT/PD ) with a new airway clearance therapy called high-frequency chest wall oscillation ( HFCWO ) in a group of stable cystic fibrosis ( CF ) patients . In this crossover trial , 29 CF patients ( 15 males , 14 females ) , aged 7 - 47 years that met the inclusion criteria were r and omly assigned to alternate CPT/PD and HFCWO , on a daily basis , over a 4 day period . Each patient received 2 days of each form of therapy ; treatment frequency and the length of treatment were the same for both techniques . Expectorated secretions were collected during each 30 minute therapy session and for 15 minutes following treatment . The wet and dry weights of collected secretions were determined gravimetrically , and the therapy methods were compared . Significantly more sputum was expectorated during HFCWO than during CPT/PD as determined by both the wet ( P < 0.001 ) and the dry ( P < 0.01 ) measurements . This study suggests that HFCWO is at least as effective as manual CPT/PD in clearing secretions from the airways in patients with cystic fibrosis STUDY OBJECTIVE To compare the effect of high-frequency oral airway oscillation , high-frequency chest wall oscillation , and conventional chest physical therapy ( CPT ) on weight of expectorated sputum , pulmonary function , and oxygen saturation in out patients with stable cystic fibrosis ( CF ) . DESIGN Prospect i ve r and omized trial . SETTING Pediatric pulmonary division of a tertiary care center . PATIENTS Fourteen out patients with stable CF recruited from the CF center . INTERVENTIONS Two modes of oral airway oscillation ( 1 : frequency 8 Hz ; inspiratory to expiratory [ I : E ] ratio 9:1 ; 2 : frequency 14 Hz ; I : E ratio 8:1 ) , two modes of chest wall oscillation ( 1 : frequency 3 Hz ; I : E ratio 4:1 ; 2 : frequency 16 Hz ; I : E ratio 1:1 , alternating with frequency 1.5 Hz , I : E ratio 6:1 ) , and CPT ( clapping , vibration , postural drainage , and encouraged coughing ) were applied during the first 20 min of 4 consecutive hours . MEASUREMENTS AND RESULTS Sputum was collected on an hourly basis for a total of 6 consecutive hours . During the first and the last hour , patients collected sputum without having any treatment and underwent pulmonary function tests ( PFTs ) . Oxygen saturation was measured at 30-min intervals during hours 1 to 6 . For the first 20 min of the second to the fifth hour , patients received one of the treatments . To assess the effect of the intervention , the weight of expectorated sputum during hours 2 to 6 was averaged and expressed as percentage of the weight expectorated during the first hour ( baseline ) . For the five treatment modalities , mean sputum dry and wet weights ranged between 122 % and 185 % of baseline . There was no statistically significant difference among the treatment modalities . As measured by sputum wet weight , all oscillatory devices tended to be less effective than CPT ( p=0.15 ) . As measured by dry weight , oral airway oscillation at 8 Hz with an I : E ratio of 9:1 and CPT tended to be more effective than the other treatment modalities ( p=0.57 ) . None of the treatment modalities had an effect on PFTs and oxygen saturation and all were well tolerated . CONCLUSION In out patients with stable CF , high-frequency oscillation applied via the airway opening or via the chest wall and CPT have comparable augmenting effects on expectorated sputum weight without changing PFTs or oxygen saturation . In contrast to CPT , high-frequency oral airway and chest wall oscillations are self-administered , thereby containing health-care expenses The aim of our study was to compare the short-term efficacy of three different chest physiotherapy ( CPT ) regimens ( PD , postural drainage ; PEP , positive expiratory pressure physiotherapy ; HFCC , high-frequency chest compression physiotherapy ) on patients with cystic fibrosis ( CF ) hospitalized for an acute pulmonary exacerbation . Sixteen patients with CF , 8 males , 8 females , aged 15 - 27 years ( mean , 20.3 + /- 4 ) , met the inclusion criteria : 1 ) age over 14 years ; 2 ) mild or moderate airway obstruction ; 3 ) sputum volume > 30 mL/day ; 4 ) being proficient in PD and PEP CPT . Patients at admission had ( mean + /- SD ) forced volume in 1 second ( FEV1 ) 52.2 + /- 21.9 percent predicted ; Shwachman-Kulczycki clinical score 65.1 + /- 11 points ; Chrispin-Norman chest radiography score 18.6 + /- 4.3 points . The three CPT regimens and a control-treatment ( CONT ) were administered in a r and om sequence , each patient receiving each treatment twice a day ( in 50 minute sessions ) for 2 consecutive days . During CONT and for 30 minutes after each session only spontaneous coughing was allowed . Wet and dry weight of sputum were recorded during the 50-minute sessions and 30 minutes afterward . Lung function was measured before and 30 minutes after each session . For each treatment a score was given by the patient for efficacy , and by both the patient and the physiotherapist for tolerance . Wet and dry weights of sputum collected during the sessions were greater for all CPT regimens than for CONT ( P < 0.001 , P < 0.0001 ) . No significant differences between the three CPT regimens for both wet and dry weights were found when the number of coughs was taken into account . ( ABSTRACT TRUNCATED AT 250 WORDS Clearance of bronchial secretions is essential in the management of cystic fibrosis ( CF ) patients admitted for acute pulmonary exacerbation . Conventional physiotherapy ( CPT ) is labor-intensive , time-consuming , expensive , and may not be available as frequently as desired during hospitalization . High frequency chest compression ( HFCC ) , which uses an inflatable vest linked to an air-pulse delivery system , may offer an attractive alternative . To study this , we prospect ively studied 50 CF patients admitted for acute pulmonary exacerbation who were r and omly allocated to receive either HFCC or CPT three times a day . On admission , clinical status and pulmonary function tests ( PFT ) in the HFCC group were not significantly different from those measured in the CPT group . Significant improvements in clinical status and PFT were observed after 7 and 14 d of treatment , and were similar in the two study groups , leading to patient discharge after similar periods of hospitalization . We conclude that HFCC and CPT are equally safe and effective when used during acute pulmonary exacerbations in CF patients . We speculate that HFCC may provide an adequate alternative in management of CF patients in a hospital setting This study is a quantitative comparison of the sputum produced by 12 subjects with cystic fibrosis ( CF ) who received high-frequency chest compression ( HFCC ) and st and ard chest physical therapy ( CPT ) in r and omized order . Six subjects routinely used manual CPT and six routinely used the HFCC . None had acute infections or hospitalization in the six weeks before the study . Two certified respiratory therapists alternated subjects and CPT vs HFCC order during the two weeks of the matched study . For all sessions , the expectorated sputum was collected in preweighed cups , which were reweighed immediately after collection and again after evaporation to dryness . The wet and dry weights of the sputum produced as a result of the two techniques were significantly different , with HFCC having greater weight . Regardless of the mode of therapy , the sputum produced by the subjects who regularly received HFCC had greater water content than did the sputum produced by those subjects who regularly received CPT . No significant difference was found between the two therapists regarding sputum expectorated by the subjects during CPT . These results show that sputum production by subjects with CF who receive CPT by certified respiratory therapists can be as great as the sputum produced by the same subjects who receive HFCC . The results also suggest that unknown factors attributed to the therapists may produce different levels of effort from time to time that may decrease the respiratory therapists ' effectiveness , whereas the HFCC therapy may be more consistently effective because it is entirely machine based ABSTRACT . Twenty‐eight patients suffering from cystic fibrosis , with an age range of 8‐21 years entered a r and omised cross‐over trial to study the efficacy of the Positive Expiratory Pressure ( PEP ) mask as a method of chest physiotherapy , both on its own and in conjunction with other physiotherapy techniques . Twenty‐four of these patients completed the trial consisting of 4 treatment programmes each lasting one month and with no wash‐out period between them . Five of these patients went on to a fifth programme of Forced Expiratory Technique ( FET ) alone . At the end of the trial , no significant difference was found between the programmes as regards growth , Shwachman score , Chrispin — Norman score or pulmonary function tests . Twenty‐three patients chose to continue using the PEP mask in conjunction with FET long‐term as their chest physiotherapy programme as they felt it was an effective treatment allowing increased independence , with postural drainage being kept to a minimum Both the immediate and long-term effects of chest physical therapy administered by a parent were evaluated in eight children with cystic fibrosis . Spirometric and plethysmographic evaluations were performed pre-CPT and at 5 and 30 minutes post-CPT . The pre-CPT measurements after a three-week period with no CPT were compared with the values while receiving CPT on a regular twice daily basis . There was a significant decrease after three weeks without CPT for FVC ( P less than 0.025 ) , FEV1 ( P less than 0.005 ) , FEF25 - 75 ( P less than 0.005 ) , and Vmax60TLC ( P less than 0.025 ) . When the patients had been receiving CPT on a regular basis , the only immediate effect was an increase in PEFR after 30 minutes post-CPT ( P less than 0.05 ) . After three weeks without CPT , there were increases at 30 minutes post-CPI for FVC ( P less than 0.005 ) and Vmax60TLC ( P less than 0.05 ) . These findings indicate that although there may be little immediate functional improvement when CPT is received on a regular basis , a three-week period without CPT leads to a worsening of the functional status , which is reversed with renewal of regular CPT Because of the time and the emotional cost involved in performing daily conventional chest physiotherapy in patients with cystic fibrosis , a 3-year prospect i ve study was undertaken to compare the long-term effects of postural drainage accompanied by percussion and the forced expiratory technique with the effects of the forced expiratory technique alone . Patients who performed the forced expiratory technique alone had mean annual rates of decline that were significantly different from zero for forced expiratory volume in 1 second ( p less than 0.001 ) , forced expiratory flow between 25 % and 75 % of vital capacity ( p less than 0.001 ) , and Shwachman clinical score ( p less than 0.004 ) . In the group performing conventional physiotherapy with percussion and postural drainage , only the mean annual rate of decline for forced expiratory flow between 25 % and 75 % of vital capacity was significantly different from zero ( p less than 0.03 ) , and it was significantly different from the mean rate of decline associated with the forces expiratory technique alone ( p less than 0.04 ) . We conclude that conventional chest physiotherapy should remain a st and ard component of therapy in cystic fibrosis Routine chest physiotherapy ( CPT ) is an important component of prophylactic therapy in children with cystic fibrosis ( CF ) and requires a significant commitment of time and energy . It is important , therefore , to establish CPT as a positive experience . In this study , we evaluated the effect of recorded music as an adjunct to CPT . Specifically , we compared the use of newly composed music , familiar music , and the family 's usual routine on children 's and parents ' enjoyment of CPT and the parents ' perception of time taken to complete CPT . Enjoyment and perception of time were evaluated via question naires design ed specifically for this study . Participants were caregivers of one or more children with CF who were aged between 4(1/2 ) months and 24 months at the commencement of the clinical trial and required CPT on a daily basis . Participants were r and omly allocated into control and treatment groups . Control group participants experienced two conditions consecutively : no audiotape ( NT ; control ) and familiar music tape ( FT ; placebo control ) . Treatment group participants were given the treatment music tape ( TT ) , which was composed and compiled by a music therapist . After baseline assessment , evaluation occurred at two 6-weekly intervals . Children 's enjoyment increased significantly after use of the TT ( + 1 . 25 units ) compared to NT ( -0.5 units ; P = 0.03 ) , as did parents ' enjoyment ( + 1.0 vs. 0.0 units , P = 0.02 ) . Children 's enjoyment did not change significantly after use of the FT ( + 0.75 units ) compared to NT ( n.s . ) . Likewise , parents ' enjoyment did not change significantly after use of the FT ( + 1.0 units , n.s . ) . There was no change in perception of time after use of the TT ( -4.5 vs. + 0.2 min , n.s . ) or the FT ( + 3.3 min , n.s . ) . These results indicate that children 's and parents ' enjoyment of CPT significantly increased after the use of specifically composed and recorded music as an adjunct . We therefore recommend that recorded music , such as that provided in this study , be given to parents to use as an adjunct to CPT when their young children are diagnosed with CF , in order to assist the establishment of a positive routine STUDY OBJECTIVE A preliminary study comparing the efficacy and safety of the flutter device ( Flutter ) to st and ard , manual chest physiotherapy ( CPT ) in hospitalized cystic fibrosis ( CF ) patients undergoing an acute pulmonary exacerbation . DESIGN Open label , comparative trial with alternate assignment . SETTING Community and childrens ' hospital acute-care wards . PARTICIPANTS Twenty-two CF patients ( ages 8 to 44 years ) undergoing a total of 33 hospitalizations for acute pulmonary exacerbation . INTERVENTIONS Complete pulmonary function tests ( PFTs ) were done at baseline ( admission ) , weekly , and upon discharge from the hospital . Clinical score ( CS ) was determined at the time of hospital admission and at discharge . Participants were assigned to receive supervised Flutter therapy or st and ard , manual CPT four times per day during the hospitalization . Patients were monitored for complications , including hemoptysis , hypoxemia , and pneumothorax . RESULTS The groups ( CPT and Flutter ) did not differ at baseline in demographics or Shwachman score , nor was length of hospitalization different . Significant improvements were noted from admission to discharge in CS and PFT results within each group . Mean percent change in CS and PFT results between CPT and Flutter groups showed no significant difference from hospital admission to discharge . Subsequent power analysis using the observed difference in percent change from admission to discharge for FEV1 indicated that to attain 80 % power at alpha = 0.05 , a sample of 219 subjects in each group would be necessary . SUMMARY Comparative trials of airway clearance techniques with sufficient sample size are lacking . Although the Flutter appears to be a useful device for independent , cost-effective , and safe administration of CPT in this pilot study , a much larger clinical trial would be necessary to make definitive conclusions Chest physiotherapy still remains one of the most important aspects in the treatment of chest complications of cystic fibrosis . A mechanical device that allows the patient with cystic fibrosis to do his own chest physiotherapy will be of great benefit if it is as effective as manual percussion . 14 patients with cystic fibrosis using mechanical and manual percussion physiotherapy were studied by measuring sputum volumes , and FEV and FVC . Results with mechanical percussor were as good as with the manual percussor and , therefore , it would be reasonable for the older patient to use the former on his own We compared the efficacy of manual and mechanical chest percussion during hospitalization for acute exacerbations of cystic fibrosis by evaluating changes in spirometry values . Fifty-one participants were r and omly assigned to receive manual or mechanical chest percussion three times a day . Twenty-two participated during one subsequent admission and were assigned to the opposite form of chest percussion . The two groups were equal in severity of illness ( mean National Institutes of Health score ( + /- SEM ) : manual = 66.7 + /- 2.2 ; mechanical = 35.8 + /- 2.2 ; p = not significant ) . Mean improvement in forced expiratory volume at 1 second , forced vital capacity , and forced expiratory flow between 25 % and 75 % of forced vital capacity ( + /- SEM ) for manual percussion was 32.6 % + /- 7 % , 27.2 % + /- 5 % , and 38.1 % + /- 10 % , and for mechanical percussion was 28.5 % + /- 4 % , 28.7 % + /- 4 % , and 25.1 % + /- 8 % , respectively ; p = not significant . Our participants did not prefer mechanical chest percussion . Although equal efficacy of outpatient therapy remains to be proved , this study suggests that patients can be encouraged to use the form of chest percussion that they prefer The use of the ' PEP ' mask with forced expiratory coughing was compared with conventional physiotherapy over a one month period . No difference was shown in symptom scores , sputum production , or simple lung function tests . The mask was well accepted and allowed independent treatment by older patients |
12,727 | 26,121,115 | There is insufficient evidence to determine whether the choice of topical agent or dressing affects the healing of arterial leg ulcers | BACKGROUND It is estimated that people in industrialised countries have a 1 % chance of suffering from a leg ulcer at some time in their life .
The majority of leg ulcers are associated with circulation problems ; poor blood return in the veins causes venous ulcers ( around 70 % of ulcers ) and poor blood supply to the legs causes arterial ulcers ( around 22 % of ulcers ) .
Treatment of arterial leg ulcers is directed towards correcting the poor arterial blood supply , for example by correcting arterial blockages ( either surgically or pharmaceutically ) .
If the blood supply has been restored , these arterial ulcers can heal following principles of good wound care .
Dressings and topical agents make up a part of good wound care for arterial ulcers but there are many products available and it is unclear what impact these have on ulcer healing .
This is an up date of a review first published in 2003 .
OBJECTIVES To determine whether topical agents and wound dressings affect healing in arterial ulcers .
To compare healing rates , patient-centred outcomes and costs between wound dressings and topical agents . | BACKGROUND The treatment of chronic leg ulcers remains a stubborn problem in many patients . Topical 2 % ketanserin ointment , a 5HT2-serotoninergic blocking agent , has been reported to improve healing of decubitus , venous , diabetic and ischaemic ulcers . METHOD The present double-blind intra-individual comparative study was performed in 12 women with diabetes presenting with at least two similar leg ulcers . In each subject , the two lesions were r and omly assigned to be treated for 8 weeks by 2 % ketanserin ointment or its unmedicated vehicle . OBJECTIVE assessment s of the dynamics of wound healing were performed using computerized morphometry . Evaluations were performed at 2-week intervals for 8 weeks . RESULTS A significant decrease in relative wound area was observed on the ketanserin-treated ulcers compared with the placebo group . CONCLUSION Topical ketanserin is a valuable therapy for difficult-to-treat leg ulcers 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 Chronic skin ulcers such as diabetic ulcers and venous leg ulcers are increasing and are a costly problem in healthcare . We have developed a novel artificial dermis , collagen/gelatin sponge ( CGS ) , which is capable of sustained release of basic fibroblast growth factor ( bFGF ) for more than 10 days . The objective of this study was to investigate the safety and efficacy of CGS impregnated with bFGF in the treatment of chronic skin ulcers . Patients with chronic skin ulcers that had not healed in at least 4 weeks were treated with CGS impregnated with bFGF at 7 or 14 μg/cm(2 ) after debridement , and the wound bed improvement was assessed 14 days after application . Wound bed improvement was defined as a granulated and epithelialized area on day 14 with a proportion to the baseline wound area after debridement of 50 % or higher . The wound area , the wound area on day 14 , and the granulation area on day 14 were independently measured by blinded review ers in a central review using digital images of wounds taken with a calibrator . Patients were followed up until 28 days after application to observe the adverse reactions related to the application of CGS . From May 2010 to June 2011 , 17 patients were enrolled and , in 16 patients , the wound bed improved . Among the r and omized patients in step 2 , no significant difference was seen between the low-dose group and the high-dose group . No serious adverse reactions were observed . Adverse reactions with a clear causal relationship to the study treatment were mild and patients quickly recovered from them . This study is the first-in-man clinical trial of CGS and showed the safety and efficacy of CGS impregnated with bFGF in the treatment of chronic skin ulcers . This combination therapy could be a promising therapy for chronic skin ulcers OBJECTIVE To assess whether topical morphine is pharmacologically effective in relieving pain from ulcers caused by arterial insufficiency and identify whether this effect is central ly or peripherally mediated . METHOD The analgesic effect of a topically applied hydrogel containing 0.5 % of morphine was evaluated in a double-blind , placebo-controlled , three-way crossover pilot study involving nine patients with painful arterial leg ulcers . All patients had a baseline pain intensity of at least 5 on a 10-point numeric rating scale . They received the following three treatments in r and om order : morphine hydrogel plus a subcutaneous ( SC ) placebo infusion ; placebo gel plus a SC infusion of 5 mg morphine over six hours and a placebo gel plus a SC placebo infusion . Each treatment lasted one day . Pain was assessed during the first 24 hours after application of the hydrogel and the start of the subcutaneous infusion . RESULTS There was a statistically significant difference between average baseline pain scores and those reported during treatment , but this difference was not clinical ly relevant . The three treatments did not differ in terms of the pain relief provided . CONCLUSION Topical morphine does not have a clinical ly relevant analgesic effect in patients with painful arterial leg ulcers . Further research should focus on ulcers of other aetiology OBJECTIVE To determine the healing effect of topical becaplermin gel vs hydrogel dressing on hypertensive leg ulcers . DESIGN R and omized , double-blind , parallel-assignment , controlled study . SETTING Ambulatory or hospitalized patients from 17 dermatology departments . PATIENTS Among 64 consecutive r and omized patients with 1 or more hypertensive leg ulcers who fulfilled all inclusion criteria , 59 received the allocated intervention , and findings were analyzed . INTERVENTION Becaplermin gel ( human recombinant platelet-derived growth factor-BB , 0.1 % , in hydrogel ) or hydrogel dressing was applied , both in doses of 1 cm/cm(2 ) , once daily for 8 weeks . Follow-up continued for 4 weeks beyond the final gel application . MAIN OUTCOME MEASURES The primary end point was complete wound closure rate after 8 weeks of treatment . Secondary end points were percentages of patients with complete wound closure at week 12 ; changed ulcer area after treatment vs baseline ; and changed ulcer-related pain and health-related quality of life during the study . RESULTS Complete wound closure rates were comparable after 8 weeks for becaplermin ( 5 of 28 patients ) and hydrogel ( 3 of 31 patients ) ( 8 percentage-point difference ; 95 % confidence interval , -10 % to 26 % ) . No statistically significant differences were observed between the 2 groups for percentages of complete closure at week 12 , changed ulcer area at week 8 , or changed ulcer-related pain and quality of life during the study ( P > .05 for all comparisons ) . CONCLUSIONS Topical becaplermin gel is not superior to hydrogel dressing for hypertensive leg ulcer wound closure . Surgical management by grafting remains the most promising treatment strategy but requires further evaluation . Trial Registration clinical trials.gov Identifier : NCT00970697 BACKGROUND Elase is a widely used ointment consisting of a combination of 2 proteolytic enzymes , fibrinolysin and desoxyribonuclease ( DNAse ) . It is said to promote debridement of necrotic and purulent debris from skin ulcers . OBJECTIVE Our purpose was to assess the efficacy and safety of this ointment and its components in the treatment of chronic ulcers of the lower extremity . METHODS This was a double-blind , r and omized , prospect i ve study of 84 patients with leg ulcers exhibiting necrotic and purulent debris , who were treated for 21 days with twice-daily applications of the ointment , fibrinolysin , DNAse , or who received the ointment vehicle ( placebo ) . We assessed 6 efficacy features : ulcer size , purulent exu date , necrotic tissue , erythema , pain , and overall condition of the lesion at days 8 , 15 , and 21 after initiation of treatment . We also assessed the frequency of adverse effects . RESULTS All treatments produced some improvement in the efficacy parameters and overall condition of the ulcers by week 3 , but no statistically significant difference was found when compared with placebo . No serious adverse effects were noted . A later retrospective re analysis of the data found a statistically significant reduction of purulent exu date only at days 3 and 7 of treatment in the group treated with the complete ointment , but not in the other features . CONCLUSION The proteolytic ointment provides no long-term clinical benefit in reducing purulent exu date , pain , erythema , necrotic tissue , or overall condition of chronic leg ulcers when compared with either of its two components or placebo OBJECTIVE To evaluate the performance ( efficacy , safety and acceptability ) of a new micro-adherent absorbent dressing ( UrgoClean ® ) compared with a hydrofiber dressing ( Aquacel ® ) in the local management of venous leg ulcers , in the debridement stage . METHOD A non-inferiority European r and omised controlled clinical trial ( RCT ) was conducted in 37 centres , on patients presenting with venous or predominantly venous , mixed aetiology leg ulcers at their sloughy stage ( with more than 70 % of the wound bed covered with slough at baseline ) . Patients were followed over a 6-week period and assessed weekly . The primary judgement criteria was the relative regression of the wound surface area after the 6-week treatment period . Secondary endpoints were the relative reduction of sloughy tissue and the percentage of patients presenting with a debrided wound . RESULTS Altogether , 159 patients were r and omised to either UrgoClean ( test group ; n=83 ) or Aquacel ( control group ; n=76 ) dressings . Regarding the wound healing process predictive factors ( wound area , duration , ABPI value , recurrence ) , at baseline , the two groups were well balanced , for both wound and patient characteristics . Compression therapy was administered to both groups and after a median 42-day treatment period , the percentage of relative reduction of the wound surface area was very similar ( -36.9 % vs -35.4 % in the UrgoClean and control groups , respectively ) . When considering the secondary criteria at week 6 , the relative reduction of sloughy tissue was significantly higher in the UrgoClean group than in the control group ( -65.3 % vs -42,6 % ; p=0.013 ) . The percentage of debrided wounds was also significantly higher in the test group ( 52.5 % vs 35.1 % ; p=0.033 ) . CONCLUSION This ' EARTH ' RCT confirmed that the UrgoClean dressing has similar efficacy and safety compared to Aquacel . However , UrgoClean also showed better autolytic properties than the control group in the management of venous leg ulcers at the sloughy stage . The new UrgoClean dressing therefore represents a promising therapeutic option within the current range of autolytic dressings available . DECLARATION OF INTEREST This study was sponsored by a grant from the pharmaceutical company Laboratoires Urgo . S. Bohbot and O. Tacca are employees of Laboratoires Urgo . S. Meaume , J. Dissemond and G. Perceau have received monetary compensation as presenters for Laboratoires Urgo . Data management and statistical analyses were conducted independently by Vertical ( Paris , France ) Abstract Aims / Introduction Dysregulated inflammatory response is believed to be an important factor in the pathogenesis of several late complications of diabetes mellitus . β‐Glucans are potent inducers of immune function . The present r and omized , double blind , two‐center , placebo‐controlled study was undertaken to explore safety , tolerability and efficacy of soluble β‐1,3/1,6‐glucan ( SBG ) as a local treatment of diabetic foot ulcers . Material s and Methods A total of 60 patients with type 1 or 2 diabetes and lower extremity ulcers ( Wagner grade 1–2 , Ankle/Brachial Index ≥0.7 ) received SBG or a comparator product ( methylcellulose ) locally three times weekly up to 12 weeks in addition to conventional management scheme . A total of 54 patients completed the study . Results A tendency for shorter median time to complete healing in the SBG group was observed ( 36 vs 63 days , P = 0.130 ) . Weekly percentage reduction in ulcer size was significantly higher in the SBG group than in the methylcellulose group between weeks 1–2 , 3–4 and 5–6 ( P < 0.05 ) . The proportion of ulcers healed by week 12 was also in favor of SBG ( 59 % vs 37 % , P = 0.09 ) , with a significantly higher healing incidence in the SBG group at week 8 ( 44 % vs 17 % , P = 0.03 ) . SBG was safe and well tolerated . There was a clinical ly significant difference regarding the incidence of serious adverse events in favor of the SBG treatment . Conclusions Local treatment of diabetic lower extremity ulcers with β‐1,3/1,6‐polyglucose shows good safety results . This β‐glucan preparation shows promising potential as a treatment accelerating cutaneous healing . Further studies are required to confirm this effect . This trial was registered with Clinical Trials.gov ( no. NCT00288392 ) 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 Klion ointment has been used for the cleansing of crural ulcer in 28 patients . The results of treatment were compared to a control group of 17 patients treated with another method . In response to metronidazole the ulcers were cleared within 1 - 3 weeks , discharge ceased , and the accompanying inflammation and pain were also moderated . The starting proliferation and epithelization indicated the favourable action of Klion ointment form the st and point of the complete wound healing process Chitosan , a natural polysaccharide derivate from chitin , offers a promising alternative bio material for use in wound dressings . In this work , the safety and efficacy of a next-generation KA01 chitosan wound dressing in facilitating the healing of nonhealing chronic wounds was studied . This open multicenter comparative prospect i ve r and omized clinical study was conducted at three medical centers in China . A total of 90 patients ( 45 in test group and 45 in control group ) with unhealed chronic wounds including pressure ulcers , vascular ulcers , diabetic foot ulcers , and wounds with minor infections , or at risk of infection , were treated with the next generation chitosan wound dressing as the test article or traditional vaseline gauze as a control . Baseline assessment s were undertaken with the primary end point being wound area reduction . The secondary end points included pain reduction ( using the NRS11 pain scale ) at dressing change , wound exu date levels , wound depth and duration of the treatment . After 4 weeks treatment , the wound area reduction was significantly greater in the test group ( 65.97 ± 4.48 % ) than the control group ( 39.95 ± 4.48 % ) . The average pain level in the test group was 1.12 ± 0.23 and 2.30 ± 0.23 in the control group . The wound depth was also lower in the test group 0.30 ± 0.48 cm than the control group 0.54 ± 0.86 cm . The level of exu date fell and the dressing could be removed integrally in both the test and control groups . The mean duration of the test group was 27.31 ± 5.37 days and control group 27.09 ± 6.44 days . No adverse events were reported in either group . In conclusion this open multicenter comparative prospect i ve r and omized clinical study has provided compelling evidence that the next generation chitosan wound dressing can enhance wound progression towards healing by facilitating wound reepithelialization and reducing the patients pain level . Furthermore the dressing was shown to be clinical ly safe and effective in the management of chronic wounds OBJECTIVE : The primary objective of this study was to evaluate if a topical silver dressing that consists of silver alginate powder is effective in managing chronic wounds that exhibit signs of critical colonization and promoting wound healing . METHOD : This was a prospect i ve , open-label , 4-week r and omized controlled trial . The primary end points of the study were changes in signs associated with critical colonization and in wound surface areas . All subjects were evaluated at weeks 0 , 2 , and 4 at the end of the study . SUBJECT AND SETTING S : Participants between 18 and 85 years of age were recruited from 2 wound care clinics in Canada . The study was review ed and approved by research ethics boards . DATA ANALYSIS : Analyses of this study were carried out based on intent-to-treat principle ; t tests were used to determine if the means were statistically different between treatment groups . RESULTS : Thirty-four subjects participated and completed in the study . In the control group , the mean infection checklist score was 2.2 at baseline and 2.3 at week 4 ( t 9 = −0.36 , P = .73 ) . In the silver alginate powder group , the infection score reduced from 3.3 at baseline to 1.3 at week 4 ; the result was significant ( t 23 = 7.62 , P < .00 ) . The difference in average surface reduction over time between the 2 groups was statistically significant ( t 32 = 3.56 , P < .001 ) . Subjects r and omized to the silver group achieved a greater surface reduction than those who were r and omized to the use of foam dressing as the control . CONCLUSION : Silver alginate powder is an effective treatment option for wounds with increased bacterial burden Previous studies have suggested that topically applied platelet-derived wound healing factors ( PDWHF ) accelerate wound healing by stimulating angiogenesis , fibroblast proliferation , and collagen synthesis . To assess the ability of platelet factors to facilitate healing of chronic cutaneous ulcers we performed a r and omized , prospect i ve , double-blind , placebo-controlled study of topical PDWHF in 18 patients with 26 lower extremity wounds refractory to conventional therapy . Wounds were present for at least 8 weeks ( mean , 5.5 + /- 4.3 months ) . They were extensively debrided initially and were measured and photographed at weekly intervals for 12 weeks . Eight patients with nine wounds were treated with placebo solution ( controls ) , and 10 patients with 17 wounds were treated with PDWHF ( treatment group ) . Seventy-eight percent of patients had diabetes mellitus , 72 % had occlusive peripheral vascular disease , and 28 % had venous disease ; distribution of these disorders was equivalent in both groups . Ankle-brachial indexes , which were often spuriously elevated , averaged 0.93 + /- 0.54 in controls and 1.04 + /- 0.56 in patients treated with PDWHF ( p greater than 0.5 ) . Mean transcutaneous oxygen tension was 37.8 + /- 11.9 mmHg in controls and 37.1 + /- 9.1 mmHg in patients treated with PDWHF . Initial wound area was larger in controls than in the patients treated with PDWHF ( 28.9 + /- 45.2 cm2 vs 13.0 + /- 4.4 cm2 ) , but this difference was not statistically significant ( p = 0.19 ) . Three ( 33 % ) wounds ( in two patients ) healed in controls , and four ( 24 % ) wounds ( in three patients ) healed in the PDWHF group ( p greater than 0.5 ) . The rate of healing in controls was 1.9 + /- 2.7 cm2/week . ( ABSTRACT TRUNCATED AT 250 WORDS We performed a r and omized , double‐blind study of the efficacy of locally applied zinc oxide on the healing of leg ulcers . Thirty‐seven geriatric patients , nineteen with arterial and eighteen with venous leg ulcers , were treated either with a gauze compress medicated with zinc oxide ( 400 μg ZnO/cm2 ) or with an identical compress without zinc oxide . The treatment was assessed from ulcer size measurements and the presence or abscncc of granulation and ulcer debridement over a period of 8 weeks . The zinc‐treated patients ( 83 % success rate ) responded significantly better ( P < 0·05 ) than the placebo‐treated patients ( 42 % success rate ) . The results suggest that healing of leg ulcers is improved after the addition of zinc oxide to the local regimen The analgesic effect of EMLA 5 % cream for surgical cleansing of leg ulcers was investigated in an open study and in a double-blind comparison with placebo . Eighty patients with ulcers of venous or arterial origin participated . The cream was applied under occlusion and removed before cleansing . Plasma concentrations of lidocaine and prilocaine were assessed . The maximum individual concentrations were 0.8 microgram/ml for lidocaine and 0.08 microgram/ml for prilocaine . Pain was assessed according to a verbal rating scale and on a 100 mm visual analogue scale . The median VAS pain scores for EMLA and placebo were 18.5 and 84 mm ( p less than 0.01 ) . There were no severe adverse reactions . The results show that there is a need for pain control in surgical debridement of leg ulcers and that EMLA cream gives satisfactory analgesia for this procedure Although chronic wounds have a high socio-economic impact , data on comparative effectiveness of treatments are rare . UrgoStart ( ® ) is a hydroactive dressing containing a nano-oligosaccharide factor ( NOSF ) . This study aim ed at evaluating the cost-effectiveness of this NOSF-containing wound dressing in vascular leg ulcers compared with a similar neutral foam dressing ( UrgoCell ( ® ) Contact ) without NOSF . Cost-effectiveness analysis from the perspective of the German statutory health care system was performed using a decision tree model for a period of 8 weeks . Cost and outcome data were derived from the clinical study ' Challenge ' suggesting a response rate ( ≥40 % wound size reduction ) of UrgoStart ( ® ) of 65·6 % versus 39·4 % for the comparator . In the treatment model , effect-adjusted costs of € 849·86 were generated after 8 weeks for treatment with UrgoStart ( ® ) versus € 1335·51 for the comparator result ing in an effect-adjusted cost advantage of € 485·64 for UrgoStart ( ® ) . In linear sensitivity analyses , the outcomes were stable for varying assumptions on prices and response rates . In an 8-week period of treatment for vascular leg ulcers , UrgoStart ( ® ) shows superior cost-effectiveness when compared with the similar neutral foam dressing without any active component ( NOSF ) . As demonstrated within a r and omised , double-blind clinical trial , UrgoStart ( ® ) is also more effective in wound area reduction than the neutral foam dressing . Wound healing was not addressed in this clinical trial . Follow-up data of 12 months to allow for reulceration assessment were not generated Importance Difficult-to-heal wounds pose clinical and economic challenges , and cost-effective treatment options are needed . Objective The aim of this study is to determine the cost-effectiveness of extracellular matrix ( ECM ) relative to st and ard of care ( SC ) on wound closure for the treatment of mixed arterial/venous ( A/V ) or venous leg ulcers ( VLUs ) . Design , setting , and participants A two-stage Markov model was used to predict the expected costs and outcomes of wound closure for ECM and SC . Outcome data used in the analysis were taken from an 8-week r and omized clinical trial that directly compared ECM and SC . Patients were followed up for an additional 6 months to assess wound closure . Forty-eight patients completed the study ; 25 for ECM and 23 for SC . SC was defined as a st and ard moist wound dressing . Transition probabilities for the Markov states were estimated from the clinical trial . Main outcomes and measures The economic outcome of interest was direct cost per closed-wound week . Re source utilization was based on the treatment regimen used in the clinical trial . Costs were derived from st and ard cost references . The payer ’s perspective was taken . Results ECM-treated wounds closed , on average , after 5.4 weeks of treatment , compared with 8.3 weeks for SC wounds ( P=0.02 ) . Furthermore , complete wound closure was significantly higher in patients treated with ECM ( P<0.05 ) , with 20 wounds closed in the ECM group ( 80 % ) and 15 wounds closed in the SC group ( 65 % ) . After 8 months , patients treated with ECM had substantially higher closed-wound weeks compared with SC ( 26.0 weeks versus 22.0 weeks , respectively ) . Expected direct costs per patient were $ 2,527 for ECM and $ 2,540 for SC ( a cost savings of $ 13 ) . Conclusion and relevance ECM yielded better clinical outcomes at a slightly lower cost in patients with mixed A/V and VLUs . ECM is an effective treatment for wound healing and should be considered for use in the management of mixed A/V and VLUs BACKGROUND Current treatment modalities for chronic leg ulcers are time consuming , expensive , and only moderately successful . Recent data suggest that creating a subatmospheric pressure by vacuum-assisted closure ( V.A.C. , KCI Concepts , San Antonio , Texas ) therapy supports the wound healing process . METHODS The efficacy of vacuum-assisted closure in the treatment of chronic leg ulcers was prospect ively studied in a r and omized controlled trial in which 60 hospitalized patients with chronic leg ulcers were r and omly assigned to either treatment by V.A.C. or therapy with conventional wound care techniques . The primary outcome measure was the time to complete healing ( days ) . Statistical analysis was performed on the intention-to-treat basis . RESULTS The median time to complete healing was 29 days ( 95 % confidence interval [ CI ] , 25.5 to 32.5 ) in the V.A.C. group compared with 45 days ( 95 % CI , 36.2 to 53.8 ) in the control group ( P = .0001 ) . Further , wound bed preparation during V.A.C. therapy was also significantly shorter at 7 days ( 95 % CI 5.7 to 8.3 ) than during conventional wound care at 17 days ( 95 % CI , 10 to 24 , P = .005 ) . The costs of conventional wound care were higher than those of V.A.C. Both groups showed a significant increase in quality of life at the end of therapy and a significant decrease in pain scores at the end of follow-up . CONCLUSIONS V.A.C. therapy should be considered as the treatment of choice for chronic leg ulcers owing to its significant advantages in the time to complete healing and wound bed preparation time compared with conventional wound care . Particularly during the preparation stage , V.A.C. therapy appears to be superior to conventional wound care techniques Wound healing produced by isotonic saline irrigation via a special dressing was compared with that produced by conventional saline dressings in 12 in patients with 18 leg ulcers . Patients served as their own controls . Wound cleansing was estimated by fibrin crust disappearance and granulation tissue formation . Both occurred earlier during irrigation . Wound contraction was similar during the two treatments . Wound blood flow , estimated by means of a laser Doppler flowmeter , increased earlier with irrigation BACKGROUND Phenytoin , introduced in 1937 as an antiseizure medication , has since been reported to promote wound healing when applied as a topical agent . This study was undertaken to evaluate its effectiveness in chronic skin ulcers . METHODS Seventy-five in patients with chronic skin ulcers were included in this controlled trial . Forty patients were treated with topical phenytoin , and 35 patients with conventional saline dressings . Assessment of the wounds included wound area , bacteriologic cultures , and clinical assessment by blind observers at baseline and every 7 days thereafter over the 4-week treatment period . RESULTS Wound area reduction was greater in the phenytoin group than in controls . Fifty percent of phenytoin-treated wounds had negative cultures by day 7 , compared to 17 % of controls . Healthy granulation tissue appeared earlier with phenytoin . At the end of the fourth week , 29 of 40 phenytoin-treated ulcers had healed completely versus 10 of 35 controls . CONCLUSIONS Topical phenytoin appears to be an effective , inexpensive , and widely available therapeutic agent in wound healing . Further clinical use and evaluation is merited This study compares the costs of dressings used in the treatment of patients with a variety of wound aetiologies . The two dressings investigated were a hydrocolloid dressing and a hydrocellular dressing . Secondary objectives included a comparison of dressing durability , time to complete healing , ease of wound cleansing and dressing removal . The study was an open prospect i ve single-centre r and omised parallel group trial involving 100 patients , treated in the community , who were r and omised to the two dressing groups . For all aetiologies except pressure sores , the costs of the hydrocolloid dressing were less than the costs of the hydrocellular dressings . Similar healing rates were observed in the leg ulcer and ' other wound ' groups . There were , however , significant differences in the number of healed wounds observed in patients with pressure sores treated with the hydrocellular dressing BACKGROUND Following encouraging reports on the use of granulocyte-macrophage colony-stimulating factor ( GM-CSF ) to treat wounds in animals and in man , we conducted a study to test the usefulness of this drug in patients with chronic leg ulcers . METHODS Patients received a single perilesional injection of GM-CSF , the effect of which was observed weekly and compared with that of a placebo injection in a control group . RESULTS Treated patients fared much better than controls , prompting an early termination of the study : of 16 GM-CSF treated patients , 3 ( 19 % ) had their ulcers healed by week 1 ; 8 ( 50 % ) were healed by week 8 ; only 1 of 9 controls had the ulcer healed by week 1 ( 11 % ) , and that was the only ulcer of the group that healed at all . We observed no significant side effects or changes in the hematological and biochemical parameters studied . CONCLUSION GM-CSF seems a very useful drug for the healing of leg ulcers Recent research suggests that statins might be useful in the process of wound healing , playing a positive immune-modulatory role , improving microvascular function and reducing oxidative stress . The aim of this pilot study was to evaluate the efficacy of topic application of Simvastatin-based cream in the treatment of chronic vascular cutaneous ulcers , comparing this type of treatment to a collagen-based dressing , proven to be effective for ulcer treatment . A total of 20 ulcers were studied in 2 Groups of r and omly-chosen patients for a period of one month . In the first Group a 0.5 % Simvastatin-based cream was topically administered , while the second Group ( control ) was treated with an absorbable type I bovine collagen-based medication . Each week , wound healing progress was observed in both Groups , and the ulcers photographed . Wound healing rate was calculated by considering the absolute change in area and by the formula " healing ratio ( % ) = [ ( Area0 - Areat4)/Area0 ] × 100 , " both sets of data being related to the days comprised in the study in order to calculate healing rate per day . Statistical analysis was performed by Student t test . Study endpoint equaling the time-course changes of ulcer areas . At the end of the study , when considering absolute change in area , the experimental Group appeared to heal better and faster than the control Group although differences between the Groups were not statistically significant . Conversely , rates of wound healing in the experimental and control Groups were 46.88 % and 64 % respectively , revealing statistically significant differences . ( P < 0.05 ) . In conclusion , topic application of a simvastatin-based cream proved to be well- tolerated but not effective in the management of vascular leg ulcers in a 4 week-period Though essential oils are a proven antiseptic , little work has investigated their use on chronic wounds . This article describes the progress and problems of a small study of five patients , who were treated with lavender and chamomile essential oils The use of a 2 % ointment formulation of ketanserin , an S2-serotoninergic blocking agent , was investigated in a r and omized double-blind clinical trial for its effect on the healing of wounds of patients with decubitus , venous , and ischemic skin ulcers . The result demonstrates a significant difference in favor of the ketanserin-treated group ( 35 patients ) versus the placebo-treated group ( 37 patients ) on the basis of two factors : formation of granulation tissue and epithelialization . In addition , a significant difference of 150 % in the initial velocity of wound closure was observed in favor of the patients treated with ketanserin . This effect was persistent during the entire study period Marked progress has been made in the management of chronic wounds in recent years . However , every attempt to protect the wound edges has been unsatisfactory and in many cases the products used were not developed for the purpose of skin protection Pain prevents the effective cleansing of many leg ulcers . Pain relief during debridement has been reported after topical anaesthesia with EMLA cream . The purpose of this study was to assess and compare the pain intensity during debridement after different lengths of application time of EMLA . Fifty-nine patients , stratified for leg ulcer type , were r and omised to 10 , 20 or 60 minutes treatment with EMLA prior to debridement . The pain was rated by each patient on a 100-mm visual analogue scale ( VAS ) . Pain intensity during debridement decreased significantly with increasing duration of EMLA application ( p = 0.001 ) . The median values of the VAS pain scores were 41 , 20 and 8 in the 10- , 20- and 60- minute groups respectively . A minimum of 20 minutes application time gives substantial pain relief in the majority of patients Clinical trials of PDWHF are ongoing and the final results are not yet available ; however early lessons learned have allowed us to modify these trials . It is anticipated that the patient accrual will be completed within the next six months , and the last patient will complete the trial within the next year . At that time , we hope to have new insight into the role of PDWHF in the treatment of lower extremity ulcers . At this time , we are encouraged by the early improvement seen in patients entering the PDWHF versus saline trial . Preliminary results suggest that PDWHF improves the healing of diabetic ulcers of the lower extremity The study presented is a multicentric , prospect i ve , open and comparative study design ed with the objective of evaluating the performance of an antibacterial hydrocolloid dressing with hydroactivated silver ( Comfeel Plata ) , when used to activate the healing process in wounds with high bacterial load , clinical signs of infection or malodour . Additionally , once the wound bed was appropriately prepared , a comparison in terms of efficacy was made between , on the one h and , continued treatment with the antibacterial hydrocolloid dressing , and , on the other h and , continued treatment with other dressings specifically design ed for the proliferative phase of healing . Included into this study were 43 patients with chronic ulcers who were divided into two parallel treatment groups : In one group , Comfeel Plata ( Coloplast AIS ) was used until complete wound healing or for a maximum of 10 - 12 weeks , and in the second group Comfeel Plata ( Coloplast A/S ) was used until a clean wound bed was obtained and until the wound showed signs of positive evolution , at which moment the treatment was continued until complete healing or for a maximum of 10 - 12 weeks with dressings without silver design ed especially for the proliferative phase of healing [ Alione , Comfeel or Biatain ( Coloplast AIS ) ] . The results obtained from the various study parameters indicate that the use of Comfeel Plata in the treatment of infected or colonized wounds prepares the wound bed and facilitates more rapid healing , and that the use of Comfeel Plata effectively reduces pain and malodour . The results indicate that once a clean wound bed is obtained , the use of a dressing without silver specifically for the proliferative phase will facilitate healing Heavy microbial contamination has been associated with delayed wound healing and infection in both acute and chronic wounds . A prospect i ve , r and omized , 5-week controlled , open label , multicenter study was conducted to determine whether using antimicrobial gauze containing polyhexamethylene biguanide in wounds that require packing will result in a greater reduction of bacterial colony counts than using a gauze without polyhexamethylene biguanide ( the control ) . Twenty-one subjects were r and omized to the treatment or control dressing . Wounds were evenly distributed with respect to etiology and both study groups had a median baseline wound size of 7 cm2 . At baseline , 15 microbial isolates were recovered and counted in treatment group wounds and 12 were recovered in the controls . At Week 1 , six isolates were recovered from subjects in the polyhexamethylene biguanide antimicrobial gauze treatment group while 10 were recovered in the control . Change in polymicrobial bioburden was most prominent during the first few weeks of the study in the polyhexamethylene biguanide group . Polymicrobial counts in the treatment group remained reduced for the following three study weeks , returning to baseline at Week 4 . In the control group , the number of polymicrobial cultures rose to 60 % above baseline at Week 4 . Two wounds of subjects r and omized to the polyhexamethylene biguanide antimicrobial gauze healed ; one wound in the control group healed . Polyhexamethylene biguanide antimicrobial gauze dressing could be an important adjunct to control the polymicrobial bioburden of delayed closure surgical wounds , pressure ulcers , and diabetic foot ulcers . Additional studies seem warranted One of the main functions of wound dressings is to control water vapour transmission rate ( WVTR ) from wounded skin . In this paper , the influence of hydrocolloid , knitted viscose and gauze dressings was evaluated through in vivo measurement of WVTR in burns and chronic leg ulcers utilizing an evaporimeter . The results suggest that the evaporative water vapour loss from exposed skin wounds depends mainly on the wound depth , and that chronic leg ulcers have the same level of the WVTR as full thickness burns . Compared with the knitted viscose and gauze dressings , hydrocolloid dressing has a greater effect on reducing evaporative water loss , with WVTR being 20 - 30 % of that of exposed wounds under the conditions used in this study . This result is in agreement with that obtained in an in vitro evaluation The treatment of moderately to heavily exuding wounds requires a dressing that will remove excess exu date while ensuring optimum conditions at the wound site and preventing maceration of the surrounding skin tissue . This prospect i ve , stratified , r and omised clinical trial was design ed to assess the performance and safety of a new polyurethane foam dressing compared with a hydrocellular dressing . Both dressings are currently available to community nurses for the treatment of these wound types . Sixty-one patients recruited to the trial . They were grouped according to wound type : 20 leg ulcers , 20 Grade 2 or Grade 3 pressure sores and 21 other wounds that included traumatic , acute and chronic wounds and burns . Patients were r and omized to treatment and dressing changes and assessment s were undertaken as required . Condition of the wound and surrounding skin , comfort , ease of use and leakage from the dressing were monitored at each assessment . Treatment continued for six weeks or until the wound was lightly exuding ( defined as absence of leakage with the dressing remaining in place for more than four days on two consecutive occasions ) . Photographs and tracings of the wounds were taken weekly . The results showed that the two dressings were similar in performance in that they could remain in place for approximately 2.5 days , irrespective of wound type . There were no statistically significant differences in surrounding skin condition , reduction in wound size , patient comfort or ease of application and removal |
12,728 | 23,188,480 | Video interventions were variably effective for modifying health behaviors depending on the target behaviors to be influenced .
Video interventions appear to be effective in breast self-examination , prostate cancer screening , sunscreen adherence , self-care in patients with heart failure , HIV testing , treatment adherence , and female condom use .
However , videos have not shown to be effective in influencing addiction behaviors when they are not tailored .
Compared to loss-framing , gain-framed messages may be more effective in promoting certain types of health behavior change . | This systematic review examines the effectiveness of videos in modifying health behaviors . | BACKGROUND A r and omized trial was conducted to test the effectiveness of a videotape for increasing mammography screening among a multiethnic sample of older women . METHODS A multiethnic sample of Caucasian , African-American , and Hispanic women between the ages of 50 and 70 was recruited from Resident Lists compiled by the State of Massachusetts . After completing a baseline question naire , women were r and omized to receive either a videotape or pamphlet about mammography and recontacted at 2 and 12 months after baseline to assess attitudes , beliefs , and mammography screening . A total of 581 women completed question naires at all three time points . RESULTS At baseline , approximately 75 % of women reported having a mammogram in the past year and 90 % reported having one in the past 2 years . Rates did not differ between groups . At the 12-month follow-up , mammography rates , adjusted for baseline screening , were 80.4 % in the video and 74.8 % in the pamphlet group . Logistic regression analysis of mammography at 12 months ( within past year vs. > 1 year ago ) controlling for baseline mammogram produced an odds ratio of 1.48 for the video group that was not significantly different from unity ( 95 % CI = 0.95 - 2.28 ) . CONCLUSIONS The videotape had a small effect on increasing mammography screening . Although the effect was smaller than more intensive interventions , the video is a convenient , low cost , and easily implemented method to increase mammography screening Background Whether early detection and treatment of prostate cancer ( PCa ) will reduce disease-related mortality remains uncertain . As a result , tools are needed to facilitate informed decision making . While there have been several decision aids ( DAs ) developed and tested , very few have included an exercise to help men clarify their values and preferences about PCa screening . Further , only one DA has utilized an interactive web-based format , which allows for an expansion and customization of the material . We describe the development of two DAs , a booklet and an interactive website , each with a values clarification component and design ed for use in diverse setting s. Methods We conducted two feasibility studies to assess men 's ( 45 - 70 years ) Internet access and their willingness to use a web- vs. a print-based tool . The booklet was adapted from two previous versions evaluated in r and omized controlled trials ( RCTs ) and the website was created to closely match the content of the revised booklet . Usability testing was conducted to obtain feedback regarding draft versions of the material s. The tools were also review ed by a plain language expert and the interdisciplinary research team . Feedback on the content and presentation led to iterative modifications of the tools . Results The feasibility studies confirmed that the Internet was a viable medium , as the majority of men used a computer , had access to the Internet , and Internet use increased over time . Feedback from the usability testing on the length , presentation , and content of the material s was incorporated into the final versions of the booklet and website . Both the feasibility studies and the usability testing highlighted the need to address men 's informed decision making regarding screening . Conclusions Informed decision making for PCa screening is crucial at present and may be important for some time , particularly if a definitive recommendation either for or against screening does not emerge from ongoing prostate cancer screening trials . We have detailed our efforts at developing print- and web-based DAs to assist men in determining how to best meet their PCa screening preferences . Following completion of our ongoing RCT design ed to test these material s , our goal will be to develop a dissemination project for the more effective tool . Trial Registration OBJECTIVE Adherence to self-care behaviors improves heart failure ( HF ) morbidity and life quality . We examined short-term impact of video education ( VE ) in addition to st and ard education ( SE ) on HF healthcare utilization and self-care behavior adherence . METHODS One hundred and twelve hospitalized patients were r and omly assigned to SE ( n=53 ) or SE plus VE ( n=59 ) . Differences between groups were analyzed in patients who underwent 3-month follow-up ( 39 SE and 37 VE patients ) . Mean age was 60+/-14 years ; mean HF length was 57 months . RESULTS Three-month healthcare utilization was similar between groups but VE patients needed less extra diuretic dosing ( P<0.02 ) , received more HF literature ( P<0.03 ) , and had less healthcare team telephone communication ( P<0.04 ) . VE patients had greater sign/symptom reduction ( P<0.04 ) ; especially related to edema ( P<0.01 ) and fatigue ( P<0.01 ) and initiated more actions for edema ( P<0.05 ) and dyspnea ( with exercise or rest , both P<0.01 ) . Overall , VE patients had a higher mean self-care behavior score ( P<0.01 ) , reflecting greater self-care adherence . CONCLUSION Video education prompts self-care behavior adherence to control worsening signs/symptoms of volume overload . During 3-month follow-up , utilization of most healthcare re sources was unchanged . PRACTICE IMPLICATION S VE is a useful adjunct to in-person education In this study we compared 3 methods of conducting the preanesthetic visit . We prospect ively studied 197 consecutive surgical patients who were to undergo general anesthesia . The patients were r and omized to a routine preanesthetic interview , a brochure plus an interview , or a self-made documentary video plus an interview . After the preanesthetic visit , the degree of patient satisfaction and information gain was quantified by a question naire for each method . The questions on patient satisfaction were assessed on a six-point scale , and those on information gain were assessed on a multiple-choice basis . The video plus interview group showed the highest point scores ( 98 % of the possible maximum sum point score in patient satisfaction and 93 % of the maximum sum score in information gain ) . In contrast , the patients of the brochure plus interview group revealed 93 % for patient satisfaction and 80 % for information gain , and in the st and ard interview group , the corresponding figures were 91 % and 72 % , respectively . The maximum sum scores in patient satisfaction and information gain were significantly different between the interview and the video groups , but not between the interview and the brochure groups . Therefore , these data suggest that the use of a documentary video to supplement a preoperative interview may enhance patient satisfaction and maximize information gain Background Although many men who have sex with men ( MSM ) in Peru are unaware of their HIV status , they are frequent users of the Internet , and can be approached by that medium for promotion of HIV testing . Methods We conducted an online r and omized controlled trial to compare the effect of HIV-testing motivational videos versus st and ard public health text , both offered through a gay website . The videos were customized for two audiences based on self- identification : either gay or non-gay men . The outcomes evaluated were ‘ intention to get tested ’ and ‘ HIV testing at the clinic . ’ Findings In the non-gay identified group , 97 men were r and omly assigned to the video-based intervention and 90 to the text-based intervention . Non-gay identified participants r and omized to the video-based intervention were more likely to report their intention of getting tested for HIV within the next 30 days ( 62.5 % vs. 15.4 % , Relative Risk ( RR ) : 2.77 , 95 % Confidence Interval ( CI ) : 1.42–5.39 ) . After a mean of 125.5 days of observation ( range 42–209 days ) , 11 participants r and omized to the video and none of the participants r and omized to text attended our clinic requesting HIV testing ( p = 0.001 ) . In the gay-identified group , 142 men were r and omized to the video-based intervention and 130 to the text-based intervention . Gay-identified participants r and omized to the video were more likely to report intentions of getting an HIV test within 30 days , although not significantly ( 50 % vs. 21.6 % , RR : 1.54 , 95 % CI : 0.74–3.20 ) . At the end of follow up , 8 participants who watched the video and 10 who read the text visited our clinic for HIV testing ( Hazard Ratio : 1.07 , 95 % CI : 0.40–2.85 ) . Conclusion This study provides some evidence of the efficacy of a video-based online intervention in improving HIV testing among non-gay-identified MSM in Peru . This intervention may be adopted by institutions with websites oriented to motivate HIV testing among similar MSM population s. Trial registration Clinical trials.gov OBJECTIVE The Centers for Disease Control and Prevention recommends that HIV testing be a st and ard part of medical care ; however , testing is voluntary and some patients decline . We evaluated 2 brief interventions to promote rapid HIV testing among STD clinic patients who initially declined testing . METHOD Using a r and omized controlled trial , patients either viewed an educational digital video disc ( DVD ) or participated in stage-based behavioral counseling ( SBC ) provided by a nurse . Sixty clients presenting for care at a STD clinic who initially declined HIV testing at registration and during risk behavior screening participated in the study . RESULTS The primary outcome was whether patients agreed to be tested for HIV . The secondary outcomes included attitudes , knowledge , and stage-of-change regarding HIV testing . Patients receiving both interventions improved their attitudes and knowledge about testing ( ps < .01 ) . Patients receiving SBC agreed to testing more often ( 45 % ) than did patients who viewed the DVD ( 19 % ; p < .05 ) . CONCLUSIONS Brief interventions can increase rapid HIV testing acceptance among patients who are reluctant to be tested ; counseling guided by behavioral science theory is more effective than a well- design ed information-based intervention BACKGROUND Morbidity and mortality from colorectal cancer ( CRC ) are heightened among the socioeconomically disadvantaged . METHOD A r and omized controlled trial was conducted to evaluate the efficacy of a videotaped intervention using peer educators as well as a health professional to increase compliance with fecal occult blood test ( FOBT ) screening . Participants were 160 older individuals attending a medical outpatient clinic . Compliance with FOBT use was the dependent measure . Demographic variables , family history of CRC , viewing the videotape , perceived risk , self-efficacy , physician recommendation , knowledge about CRC screening , and intent to use the FOBT were independent measures . RESULTS Approximately 41 % of participants complied with FOBT screening . Significant relationships were found between intent and family history of CRC , viewing the video , perceived risk , self-efficacy , and CRC knowledge . However , none of these variables was significantly related to compliance with FOBT use . CONCLUSIONS Although modest compliance rates were shown for both experimental and control groups , their compliance did not differ significantly . Further investigation of the impact of a video as part of an enhanced intervention program should be considered OBJECTIVES : The success of colonoscopy depends on high- quality bowel preparation by patients ; yet inadequate preparation is common . We developed and tested an educational booklet to improve bowel preparation quality . METHODS : We conducted patient cognitive interviews to identify knowledge and belief barriers to colonoscopy preparation . We used these interviews to create an educational booklet to enhance preparatory behaviors . We then prospect ively r and omized patients scheduled for outpatient colonoscopy at a VA Medical Center to receive usual instructions vs. the booklet before colonoscopy . Patients in both groups received st and ard pharmacy instructions for single-dose bowel preparation ; the protocol did not specify which purgatives to prescribe . The primary outcome was preparation quality based on blinded ratings using the vali date d Ottawa score . We performed bivariate analyses to compare mean scores between groups using a t-test , and logistic regression to measure the booklet effect on preparation quality , adjusting for potential confounders . RESULTS : A total of 436 patients were r and omized between arms . In an intention-to-treat analysis of the primary outcome , mean Ottawa scores were superior in patients allocated to booklet vs. controls ( P=0.03 ) . An intention-to-treat analysis of the secondary outcome revealed a “ good ” preparation in 68 vs. 46 % of booklet and control patients , respectively ( P=0.054 ) . In a per- protocol analysis limited to patients who actually received the booklet , preparation was good in 76 vs. 46 % patients , respectively ( P<0.00001 ) . Regression analysis revealed that booklet receipt increased the odds of good preparation by 3.7 times ( 95 % confidence interval=2.3–5.8 ) . CONCLUSIONS : Provision of a novel educational booklet considerably improves preparation quality in patients receiving single-dose purgatives . The effect of the booklet on split-dose purgatives remains untested and will be evaluated in future research Abstract BACKGROUND : Little is known about the relative advantages of video versus internet-based decision aids to facilitate shared medical decision making . This study compared internet and video patient education modalities for men considering the prostate specific antigen ( PSA ) test . METHODS : Two hundred and twenty-six men , aged 50 years or older , and scheduled to complete a physical examination at an HMO Health Appraisal Clinic were r and omly assigned to access a website ( N=114 ) or view a 23-minute videotape in the clinic ( N=112 ) prior to deciding whether they wanted to be screened for prostate cancer . RESULTS : There were no between-groups differences in participants ’ ratings of convenience , effort , or satisfaction following exposure to the decision aid . Participants assigned to the video group were more likely to review the material s than individuals assigned to the internet group ( 98.2 % vs 53.5 % ) . Participants in the video group showed significantly greater increases in PSA knowledge and were more likely to decline the PSA test than individuals assigned to the internet group . However , participants in the internet group who review ed the entire online presentation showed similar increases in PSA knowledge as video participants . Only 5 % of all participants visited other websites to inform themselves about the PSA test . CONCLUSIONS : Overall , the video was significantly more effective than the Internet in educating participants about benefits and risks of PSA screening OBJECTIVE To examine the effectiveness of 2 condom promotion videotapes on self-efficacy , intentions , and behavior . DESIGN Two hundred twenty college students completed social-cognitive and behavioral measures and were then r and omly assigned to receive one of two 30-min condom promotion videotapes ( male or female student presenters ) or to a wait-list control condition . Participants who watched 1 of the videotapes completed immediate posttest measures , and 85 % of participants completed a 4-month follow-up . MAIN OUTCOME MEASURES Self-efficacy for condom use , intentions to use condoms , use of condom during last sex , and consistent condom use over the last month . RESULTS Participants who received either video reported greater self-efficacy to refuse to have unprotected sex and intentions than controls at follow-up . Individuals who received either video were more likely than controls to report using a condom during last sex with a regular partner , and those who watched the female presenter were more likely to report consistent condom use . CONCLUSION Participants benefited in terms of self-efficacy and intentions from receiving either video , but both men and women benefited more in terms of condom use behavior from receiving the female video . Future research is needed to determine whether opposite-sex speaker videos could be beneficial with a larger ( and more sexually active ) sample and whether these effects are maintained over time Background : Until there is a definitive demonstration that early diagnosis and treatment of prostate cancer reduces disease-related mortality , it is imperative to promote informed screening decisions by providing balanced information about the potential benefits and risks of prostate cancer screening . Within a community/academic collaboration , we conducted a r and omized trial of a printed booklet and a videotape that were design ed for African American ( AA ) men . The purpose of the trial was to determine the effect of the interventions on knowledge , decisional conflict , satisfaction with the screening decision , and self-reported screening . Methods : Participants were 238 AA men , ages 40 to 70 years , who were members of the Prince Hall Masons in Washington , DC . Men were r and omly assigned to the ( a ) video-based information study arm , ( b ) print-based information study arm , or ( c ) wait list control study arm . Intervention material s were mailed to men at home . Assessment s were conducted at baseline , 1 month , and 12 months postintervention . Multivariate analyses , including ANCOVA and logistic regression , were used to analyze group differences . Results : The booklet and video result ed in a significant improvement in knowledge and a reduction in decisional conflict about prostate cancer screening , relative to the wait list control . Satisfaction with the screening decision was not affected by the interventions . Self-reported screening rates increased between the baseline and the 1-year assessment , although screening was not differentially associated with either of the interventions . In exploratory analyses , prostate-specific antigen testing at 1 year was more likely among previously screened men and was associated with having low baseline decisional conflict . Conclusions : This study represents one of the first r and omized intervention trials specifically design ed to address AA men 's informed decision making about prostate cancer screening . We have developed and evaluated culturally sensitive , balanced , and disseminable material s that improved knowledge and reduced decisional conflict about prostate cancer screening among AA men . Due to the high incidence and mortality rates among AA men , there is a need for targeted educational material s , particularly material s that are balanced in terms of the benefits and risks of screening . ( Cancer Epidemiol Biomarkers Prev 2006;15(11):2179–88 Abstract OBJECTIVE : To assess the effect of video and pamphlet interventions on patient prostate cancer ( CaP ) screening knowledge , decision-making participation , preferences , and behaviors . DESIGN : R and omized , controlled trial . SETTING : Four midwestern Veterans Affairs medical facilities . PATIENTS / PARTICIPANTS : One thous and , one hundred fifty-two male veterans age 50 and older with primary care appointments at participating facilities were r and omized and 893 completed follow-up . INTERVENTIONS : Patients were r and omized to mailed pamphlet , mailed video , or usual care/control . MEASUREMENTS AND MAIN RESULTS : Outcomes assessed by phone survey 2 weeks postintervention included a 10-item knowledge index ; correct responses to questions on CaP natural history , treatment efficacy , the prostate-specific antigen ( PSA ) ’s predictive value , and expert disagreement about the PSA ; whether screening was discussed with provider ; screening preferences ; and PSA testing rates . Mean knowledge index scores were higher for video ( 7.44 ; P=.001 ) and pamphlet ( 7.26 ; P=.03 ) subjects versus controls ( 6.90 ) . Video and pamphlet subjects reported significantly higher percentages of correct responses relative to controls to questions on CaP natural history ( 63 % , 63 % , and 54 % , respectively ) ; treatment efficacy ( 19 % , 20 % , and 5 % ) , and expert disagreement ( 28 % , 19 % , and 8 % ) , but not PSA accuracy ( 28 % , 22 % , and 22 % ) . Pamphlet subjects were more likely than controls to discuss screening with their provider ( 41 % vs 32 % ; P=.03 ) but video subjects were not ( 35 % ; P=.33 ) . Video and pamphlet subjects were less likely to intend to have a PSA , relative to controls ( 63 % , 65 % , and 74 % , respectively ) . PSA testing rates did not differ significantly across groups . CONCLUSIONS : Mailed interventions enhance patient knowledge and self-reported participation in decision making , and alter screening preferences . The pamphlet and video interventions evaluated are comparable in effectiveness . The lower-cost pamphlet approach is an attractive option for clinics with limited re sources OBJECTIVES To compare online video and pamphlet education at improving patient comprehension and adherence to sunscreen use , and to assess patient satisfaction with the two educational approaches . METHODS In a r and omized controlled trial , 94 participants received either online , video-based education or pamphlet-based education that described the importance and proper use of sunscreen . Sun protective knowledge and sunscreen application behaviors were assessed at baseline and 12 weeks after group-specific intervention . RESULTS Participants in both groups had similar levels of baseline sunscreen knowledge . Post- study analysis revealed significantly greater improvement in the knowledge scores from video group members compared to the pamphlet group ( p=0.003 ) . More importantly , video group participants reported greater sunscreen adherence ( p<0.001 ) . Finally , the video group rated their education vehicle more useful and appealing than the pamphlet group ( p<0.001 ) , and video group participants referred to the video more frequently ( p=0.018 ) . CONCLUSION Video-based learning is a more effective educational tool for teaching sun protective knowledge and encouraging sunscreen use than written material s. PRACTICE IMPLICATION S More effective patient educational methods to encourage sun protection activities , such as regular sunscreen use , have the potential to increase awareness and foster positive , preventative health behaviors against skin cancers Abstract Background Videotaped education material s to teach breast self-examination ( BSE ) are used worldwide . However , evaluation of videotaped BSE instructions is lacking . Methods Premenopausal women ( mean age 33.4 ± 11.2 years ) without history of breast cancer were approached to participate in this experimental study and r and omly assigned to a video intervention group ( VG ; n = 130 ; length of the video = 15 min ) or non-video comparison group ( NVG ; n = 121 ) . All participants answered a question naire on BSE behavior and health beliefs . No additional training was given . The total duration of the session including completion of the question naire was 15 min for the NVG and 30 min for the VG . Three months later , changes in BSE behavior were compared in the two groups . The influence of health beliefs on actual BSE behavior was investigated as well . Results Women of both the VG and NVG performed BSE significantly more frequently at follow-up than at baseline . Analysis of covariance , using the baseline BSE-frequency as co-variate and the follow-up BSE frequency as the dependent variable , revealed that women in the VG ( adjusted mean = 7.9 times per year , 95%CI = 6.5–9.4 ) performed BSE more frequently than women of the NVG ( adjusted mean = 6.1 times per year , 95%CI = 4.6–7.5 ) ( F = 4.2 , df = 2 , p = 0.02 ) . Among motivational predictors , having an example of a role model ( modeling ) was shown by regression analysis to explain the greatest amount of variance ( 13 % ) in BSE frequency . Conclusion Use of an educational videotape increased the frequency of BSE among premenopausal women The value of mailed educational videotapes as a means of enhancing compliance with drug therapy was studied . Members of a health maintenance organization with a pharmacy cl aim for benazepril , metoprolol , simvastatin , or transdermal estrogen were r and omly assigned to a study group or a control group . Subjects in the study group were mailed one of four videotape programs giving information on the drug prescribed and the inferred disease state . Control subjects received no educational material s. Subjects were enrolled from July 1 , 1993 , through January 2 , 1994 . Refill data were collected from July 1 , 1993 , through April 1 , 1994 . The medication possession ratio ( MPR ) was calculated as the total number of days ' supply of a drug obtained by a member divided by the number of days between the time of enrollment and April 1 , 1994 , or the date the member was terminated from the plan . A subject was deemed compliant if his or her MPR was > or = 0.80 . There were no significant differences in mean MPRs between the study group ( n = 1993 ) and the control group ( n = 2253 ) . None of the mean MPRs was > or = 0.80 , although 44 % of control subjects and 46 % of study -group subjects were compliant . Of 97 respondents to a survey mailed to a r and omly selected subset of the study group , almost 87 % reported that they had viewed the videotapes , and of these subjects , about 88 % said they found them very useful or somewhat useful . A one-time mailing of videotapes to patients , with no individual follow-up , did not increase compliance with the medications monitored OBJECTIVE Study impact of health literacy on educational intervention for patients " Living with Coronary Artery Disease . " METHODS 187 patients were r and omized to : VHS/DVD plus printed booklet ; or booklet alone prior to scheduled visit . Main outcome measures included CAD knowledge assessment , clinical outcomes ( weigh and blood pressure ) and health behaviors ( diet , exercise , and smoking ) ; while functional health literacy was assessed as a possible predictor variable . RESULTS Knowledge scores and health behaviors improved following both interventions . Those receiving the booklet and video also had a significant improvement in exercise , and weight loss . There was a trend ( p=0.07 ) towards greater improvement in test scores among those receiving the booklet plus video . Patients with lower health literacy benefited as much as higher literacy patients . CONCLUSIONS Incorporation of an educational program into clinical visits for patients with chronic disease improved disease-specific knowledge and prompted patients to become activated and involved in their care , improving health behaviors and outcomes . Lower health literacy was not a barrier to this beneficial effect . PRACTICE IMPLICATION S Patients with lower health literacy may also benefit from educational , shared decision-making interventions This study examined the effects of two methods of teaching perineal massage on the rates of practice of perineal massage , of episiotomy , and of lacerations in primiparas at birth . Couples in 20 r and omly selected sections of four prenatal class series received routine printed and verbal instruction and a 12-minute video demonstration of perineal massage , or only the routine printed and verbal instruction . Women reported their practice rates in daily diary records , which were mailed to the research er weekly . Hospital records provided delivery data . Of the 83 women , 23 ( 28 % ) practice d perineal massage : 16 ( 35.6 % ) in the experimental group , 7 ( 18.4 % ) controls . Even though the rate of practice almost doubled among experimental group women , the videotape instruction method was statistically nonsignificant . Episiotomy and laceration rates were not affected by teaching method . More severe lacerations occurred among the experimental group ; however , the control group had almost four times as many severe ( 21 % ) as minor ( 5.3 % ) lacerations . The experimental group had twice as many severe ( 28.9 % ) as minor ( 13.3 % ) lacerations . These results were also nonsignificant Objective : To test a model design ed to increase willingness of patients presenting to the emergency department off hours to be tested for human immunodeficiency virus ( HIV ) by using a pretest counseling video as a substitute for face-to-face counseling . Methods : We conducted a r and omized controlled trial comparing the rate of testing in patients r and omized to receive video counseling with immediate testing ( video group ) versus st and ard care , which was referral to counseling and testing the next day ( st and ard referral group ) . Results : Fifty percent of 805 eligible patients consented to participate in the study , indicating willingness to be tested . The HIV testing rate was higher in the video group 92.6 % ( 187 of 202 ) than in the st and ard referral group 4.5 % ( 9 of 202 ) ( difference = 88.1 % , 95 % confidence interval : 83.5%–92.7 % ) . Thirty percent of 187 patients in the video group who were tested returned for their results ; 8 of 9 patients in st and ard care returned to be tested and to get their results . Conclusion : Half of the patients who were solicited for HIV testing agreed to be tested . When testing was immediate the patient was more likely to have the test completed This study examines smoking cessation content posted on youtube.com . The search terms “ quit smoking ” and “ stop smoking ” yielded 2,250 videos in October 2007 . We examined the top 100 as well as 20 r and omly selected videos . Of these , 82 were directly relevant to smoking cessation . Fifty-one were commercial productions that included antismoking messages and advertisements for hypnosis and NicoBloc fluid . Thirty-one were personally produced videos that described personal experiences with quitting , negative health effects , and advice on how to quit . Although smoking cessation content is being shared on YouTube , very little is based on strategies that have been shown to be effective Objective To evaluate the effectiveness of an educational video on osteoporosis at increasing knowledge and preventive health behaviors . Design A total of 195 women between 35 and 80 years of age without documented osteopenia or osteoporosis , who presented for a gynecological examination in an outpatient setting , were enrolled . Of this number , 98 women were r and omly assigned to the intervention group that viewed the video before their office visit , and 97 women were assigned to a control group and saw their physician in a routine manner . After their visit , all participants answered a question naire that assessed their knowledge of osteoporosis and baseline health-related behaviors . Three months later , a follow-up question naire was mailed to participants , eliciting whether preventive behavior had commenced . Frequencies were compared using the Fisher exact test ( 2-tailed ) . Continuous variables were analyzed using the Student 's t test . Results The two groups had no statistically significant differences in demographics . The intervention group scored a mean of 92 % compared with a mean of 80 % in the control group on the initial osteoporosis assessment question naire ( P < 0.001 ) . The 3-month follow-up question naire demonstrated that significantly more women in the intervention group started taking calcium supplements ( 26.5 % v 4.9 % ; P < 0.001 ) , started taking vitamin D supplements ( 20.6 % v 6.6 % ; P = 0.02 ) , started a program of weight-bearing exercise ( 13.3 % v 1.7 % ; P = 0.03 ) , and started hormone therapy ( 8 % v 1 % ; P = 0.04 ) . Conclusion The use of an educational video on osteoporosis seems to improve patient knowledge and may positively impact health-related behaviors PURPOSE The efficacy of prostate cancer screening is uncertain , and professional organizations recommend educating patients about potential harms and benefits . We evaluated the effect of a videotape decision aid on promoting informed decision making about prostate cancer screening among primary care patients . METHODS A group of 160 men , 45 to 70 years of age , with no history of prostate cancer , were r and omized to view or not to view a 20-minute educational videotape before a routine office visit at a university-based family medicine clinic . The subjects were contacted again 1 year after their visit to assess their receipt of prostate cancer screening ( digital rectal examination [ DRE ] or prostate-specific antigen [ PSA ] testing ) , their satisfaction with their screening decision , and knowledge retention since the baseline assessment . RESULTS Follow-up assessment s were completed for 87.5 % of the intervention subjects and 83.8 % of the control subjects . The rate of DRE did not differ between the 2 groups . Prostate-specific antigen testing was reported by 24 of 70 ( 34.3 % ) intervention subjects and 37 of 67 ( 55.2 % ) control subjects ( P = .01 ) . African American men were more likely to have had PSA testing ( 9 of 16 , 56.3 % ) than were white men ( 13 of 46 , 28.3 % ) ( P = .044 ) . Satisfaction with the screening decision did not differ between the study groups . Intervention subjects were more knowledgeable of prostate cancer screening than were control subjects , although these differences declined within 1 year ( P < .001 ) . CONCLUSIONS Decision aids for prostate cancer screening can have a long-term effect on screening behavior and appear to promote informed decision making OBJECTIVES --To determine the effects of three different methods of providing health education on the uptake of cervical smear testing among Asian women , and to evaluate the acceptability of different health education material s. DESIGN -- Prospect i ve cohort study over one year of effects of written material s by post , personal visit to give written material s , and personal visit to show a video on the uptake of smear testing . Techniques included a personally administered question naire . SETTING --Leicester , a city with a large Asian population . SUBJECTS--737 r and omly selected Asian women aged 18 to 52 who were not recorded on the central cytology laboratory 's computer as ever having had a cervical smear test . 159 declined to participate or were not contactable . INTERVENTIONS --Women were r and omised into four groups : visited and shown a video ( 263 ) , visited and shown a leaflet and fact sheet ( 219 ) , posted a leaflet and fact sheet ( 131 ) , not contacted at all ( 124 ) . MAIN OUTCOME MEASURES --Cervical smear test recorded on computer within four months after intervention . RESULTS --57 ( 37 % , 26 % of group ) of the women visited and given leaflets and 80 ( 47 % , 30 % of group ) shown the video attended for cervical smears . Only six ( 5 % ) of those who were not contacted and 14 ( 11 % ) of those sent leaflets had a smear test during the study . CONCLUSION --Health education interventions increased the uptake of cervical cytology among Asian women in Leicester who had never been tested . Personal visits were most effective irrespective of the health education material s used , but there was some evidence that home viewed videos may be particularly effective in one of the most hard to reach groups : Urdu speaking , Pakistani Moslems . Written translated material s sent by post were ineffective Radon and cigarette smoking have synergistic effects on lung cancer risk . Electric utility company bill stuffers offered free radon test kits to households with at least one smoker . Participating households ( n = 1364 ) were r and omized within a 2 x 2 design to evaluate the main effects of brief telephone counseling and a targeted video on smoking cessation and the establishment of new household smoking bans . Phone counseling was associated with cessation at 3-month follow-up but neither intervention led to 12-month or sustained cessation . While neither intervention had a significant effect on new bans , there were trends in the predicted direction and the combination of the two significantly increased new bans compared with no intervention . The presence of children in the household was associated with new bans . While few households had high levels of radon , such levels were associated with radon mitigation behaviors . Together with a previous study , these results suggest radon risk is a useful and inexpensive way to engage smoking households in risk reduction behaviors , especially the institution of household smoking bans The female condom is effective in preventing sexually transmitted diseases and when used properly reduces risk of HIV infection among women . This field experiment evaluated the effect of a video presentation on reported use of and satisfaction with the female condom . Participants were 100 women tested for HIV infection in a community agency . Ages ranged from 17 to 62 years , and one fifth of the sample were African American or Hispanic . The 23 women who viewed an instructional video were significantly more likely than 13 of the control group of 50 to try the condom and report to the research er . Video viewing was unrelated to liking the product and future intent to use . Almost three quarters of those who used the condoms reported they liked and would use them Background and objectives Decisions about the dissemination of HIV interventions need to be informed by evidence of their cost-effectiveness in reducing negative health outcomes . Having previously shown the effectiveness of a single-session video-based group intervention ( VOICES/VOCES ) in reducing incidence of sexually transmitted diseases ( STD ) among male African American and Latino clients attending an urban STD clinic , this study estimates its cost-effectiveness in terms of disease averted . Methods Cost-effectiveness was calculated using data on effectiveness from a r and omized clinical trial of the VOICES/VOCES intervention along with up date d data on the costs of intervention from four replication sites . STD incidence and self-reported behavioral data were used to make estimates of reduction in HIV incidence among study participants . Results The average annual cost to provide the intervention to 10 000 STD clinic clients was estimated to be US$ 447 005 , with a cost per client of US$ 43.30 . This expenditure would result in an average of 27.69 HIV infections averted , with an average savings from averted medical costs of US$ 5 544 408 . The number of quality adjusted life years saved averaged 387.61 , with a cost per HIV infection averted of US$ 21 486 . Conclusions This brief behavioral intervention was found to be feasible and cost-saving when targeted to male STD clinic clients at high risk of contracting and transmitting infections , indicating that this strategy should be considered for inclusion in HIV prevention programming BACKGROUND Education plays a key role in the development of self-management skills for people with type 2 diabetes , although there is limited evidence for the use of video education . AIMS To develop a video-based lifestyle education programme for people newly diagnosed with type 2 diabetes and to evaluate changes in knowledge , biomedical indices and quality of life . METHODS Forty-two newly diagnosed type 2 diabetic subjects were recruited and r and omly allocated to either a video education or control group . Data were collected at baseline and 6 months after the intervention . Subjects ( 43 % male ) had a mean ( SD ) age of 60.8 ( 9.6 ) years , weight 89.5 ( 15.5 ) kg , BMI 31.3 ( 5.1 ) kg m(2 ) , glycated haemoglobin ( A1c ) 7.4 (1.7)% , total cholesterol 4.7 ( 1.2 ) mmol L(-1 ) , high-density lipoprotein cholesterol 1.15 ( 0.34 ) mmol L(-1 ) , triglycerides 1.8 ( 1.0 ) mmol L(-1 ) , low-density lipoprotein cholesterol 2.8 ( 1.0 ) mmol L(-1 ) , pedometer reading 5721 ( 3446 ) steps per day . There were 63.7 % correct answers given to the ADKnowl question naire and the WHO-5 Well-Being score was 65.8 % . RESULTS At 6 months , the intervention group showed increased knowledge compared to controls ( 74.3 % versus 56.4 % correct answers , P < or = 0.0001 ) . Although there were no significant differences in changes over 6 months between the two groups , the intervention group showed improvements in A1c ( -0.7 % , P = 0.024 ) , total cholesterol ( -0.5 mmol L(-1 ) , P = 0.017 ) , low-density lipoprotein cholesterol ( -0.5 , P = 0.018 ) and increased physical activity measured by pedometer ( 1266 steps per day , P = 0.043 ) from baseline , with no significant changes in the control group . CONCLUSIONS A brief video intervention increased diabetes knowledge amongst those newly diagnosed with type 2 diabetes and may comprise an effective way of directing education to such individuals Objectives : To evaluate the reach and effectiveness of a diabetes self-management DVD compared to classroom-based instruction . Methods : A hybrid preference/r and omized design was used with participants assigned to Choice v. R and omized and DVD v. Class conditions . One hundred and eighty-nine adults with type 2 diabetes participated . Key outcomes included self-management behaviours , process measures including DVD implementation and hypothesized mediators and clinical risk factors . Results : In the Choice condition , four times as many participants chose the mailed DVD as selected Class-based instruction ( 38.8 v. 9.4 % , p<0.001 ) . At the 6-month follow-up , the DVD produced results generally not significantly different than classroom-based instruction , but a combined Class plus DVD condition did not improve outcomes beyond those produced by the classes alone . Discussion : The DVD appears to have merit as an efficient and appealing alternative to brief classroom-based diabetes education , and the hybrid design is recommended to provide estimates of programme reach OBJECTIVE The objective of this research was to examine the effectiveness of a brief behavioral intervention , provided at the time of diagnosis of pelvic inflammatory disease , on subsequent behaviors by patients who were urban adolescents in a community in which sexually transmitted infection was prevalent . METHODS 121 adolescents aged 15 to 21 years with mild to moderate pelvic inflammatory disease were enrolled in a r and omized trial . All participants received st and ardized care , completed baseline audio computerized self-interviews , received full courses of medication at discharge , and were interviewed after the 2-week treatment course . The intervention group also watched a 6-minute intervention video . MAIN OUTCOME MEASURES Medication completion , temporary sexual abstinence during the 14-day treatment period , partner notification , partner treatment , and return for 72-hour follow-up were studied . Data were evaluated using multivariate regression analysis . RESULTS Of the participants , 61 % were located and could participate in the 2-week interview by the disease intervention specialist . The intervention participants had higher rates of 72-hour follow-up ( 32 % vs. 16 % ) and partner treatment ( 71 % vs. 53 % ) in bivariate analyses at a P = 0.1 level . There were no differences in medication completion ( 66 % vs. 66 % ) , sexual abstinence ( 78 % vs. 89 % ) , or partner notification ( 88 % vs. 92 % ) . Only the partner-treatment finding persisted in multivariate models ( AOR = 3.10 ; 95 % CI , 1.03 - 9.39 , P = .045 ) . CONCLUSIONS Adolescent girls r and omized to a community-specific video intervention at diagnosis of pelvic inflammatory disease were three times more likely to have their partners treated than those in the control group . Given the value of partner treatment in secondary prevention of sexually transmitted diseases , this video may be an essential component of discharge programming in urgent care setting s. Additional structural supports may be necessary to facilitate improved adherence to other key adherence behaviors BACKGROUND Whereas much is known about single lifestyle-related health risk factor prevalence and covariates , more research is needed to eluci date the interactions among multiple healthy lifestyle factors and variables that may predict adherence to these factors . Such data may guide both clinical and health policy decision making and person-centered approaches to population health improvement . METHODS We document the prevalence and cluster patterns of multiple healthy lifestyle factors among a r and om sample of adolescents ( n = 616 ) , adults ( n = 585 ) , and seniors ( n = 685 ) from a large Midwestern health plan . Modifiable , lifestyle-related health factors assessed included physical activity , nonsmoking , high- quality diet , and healthy weight for all subjects ; adults and seniors were also asked about their alcohol consumption . Second , we sought to identify characteristics associated with the likelihood of meeting recommendations for healthy lifestyle factors . The healthy lifestyle factors sum score was categorized into three levels , that is , 0 to 2 , 3 , or 4 to 5 healthy lifestyle factors ( 4 for adolescents ) , and we used ordinal logistic regression to estimate the odds of meeting each of these criteria from several demographic characteristics and disease states . RESULTS Overall , only 14.5 % of adolescent , adult , and senior health plan members meet recommended guidelines for four common healthy lifestyle factors . Only 10.8 % of adults and 12.8 % of seniors met all five behavior-related factors . For adolescents , only being nondepressed was associated with an increased likelihood to be in adherence to multiple healthy lifestyle factors ( odds ratio [OR]=2.15 ; p < 0.05 ) . For adults , being in the 50- to 64-year-old cohort ( OR=1.46 , p<0.05 ) , having a college degree ( OR=1.65 ; p < 0.05 ) , and having no chronic disease ( OR=1.92 ; p < 0.05 ) were all associated with an increased likelihood to be in adherence to multiple healthy lifestyle factors . For seniors , having a college degree ( OR=1.61 ; p < 0.05 ) , was the only variable associated with an increased likelihood to be in adherence to multiple healthy lifestyle factors . CONCLUSIONS A small proportion of health plan members meet multiple recommended healthy lifestyle guidelines at once . This analysis identifies population subgroups of specific interest and importance based on adherence to multiple healthy lifestyle factors , and predictors for increased likelihood to be in adherence to multiple healthy lifestyle factors . It presents a potentially useful summary measure based on person-centered measures of healthy lifestyle factors . Clinicians may derive meaningful information from analyses that address adherence to multiple healthy lifestyle factors . Health systems administrators may use this information to influence health policy and re source allocation decisions . Further studies are needed to assess the usefulness of this comprehensive lifestyle-related health measure as a metric of progress toward public health goals , or as a clinical metric that conveys information on future health status and directs interventions at the individual level The impact of a ten-minute , soap opera-style videotape on knowledge and treatment behavior of black men with gonorrhea was tested in r and omized clinical trials . The videotape , shown to individual patients after diagnosis , produced a sizeable increase in the percentage of patients who returned for their test-of-cure examination : while only 43.3 % of control group patients returned , 53.5 % of those in the videotape group did so ; chi 2(1 ) = 9.0 ; P less than 0.003 . In a follow-up study , similar results were found : videotape group ( 59.0 % ) , control group ( 39.1 % ) ; chi 2(1 ) = 6.2 ; P less than 0.015 . The videotape also produced large , significant increases in patient knowledge , as measured by a test administered during patients ' clinic visit ( P less than 0.0001 ) . No measureable effect of the videotape was detected on patients ' willingness to refer sexual contacts for treatment . The findings suggest that clinic-based educational material s , particularly soap opera-style videotapes that engender audience identification , create emotional significance for the viewer , and model requisite communication skills , may have a significant role to play in control of sexually transmitted diseases Context Many patients who might benefit from colorectal cancer screening do not get screening . Time pressure may prevent physicians from fully educating their patients about colorectal cancer screening . Contribution In this r and omized , controlled trial , an educational video about colorectal cancer screening mailed to patients before a primary care visit did not increase the rate of screening compared with usual care . Caution s The video focused on sigmoidoscopy rather than colonoscopy , and the study sample had a higher than average baseline rate of colorectal cancer screening . Colorectal cancer is a major cause of cancer death ( 1 ) . Evidence about screening test effectiveness ( 2 ) continues to mount , and guidelines from many organizations promote several screening options ( 3 - 7 ) . Rates of screening , however , remain lower than rates of other preventive services ( 8 - 10 ) . Barriers to screening are numerous . Physicians report inadequate time to educate patients and facilitate decision making ( 11 , 12 ) . Contributing factors include competing dem and s placed on clinicians ( 13 ) and the need to manage acute problems ( 12 , 14 ) . Prominent patient barriers include lack of knowledge about colorectal cancer and fears of cancer and screening tests ( 15 , 16 ) . Interventions to increase screening have generally focused on individual providers and clinical systems . Provider education programs , use of support staff , on-site sigmoidoscopy services , and reminder systems have all increased testing ( 11 , 16 - 23 ) . Patient-focused interventions have used education , reminders , and cost reduction to increase use of fecal occult blood testing ( 17 - 19 ) and sigmoidoscopy ( 20 , 21 ) . This study examined the effectiveness of an educational video design ed to increase colorectal cancer screening , particularly via sigmoidoscopy ; the video was mailed to patients ' homes before a scheduled periodic health examination . We studied the effectiveness of this patient education video for several reasons . First , the information that patients need for colorectal cancer screening is complex and voluminous because of the multiple screening options and the increased emphasis on informed decision making and informed consent ( 22 - 26 ) . Clinicians view time dem and s and competing medical needs as screening barriers ( 27 - 29 ) . The video contains considerable information , and thus clinicians can spend less time explaining the information to patients . Second , video assures st and ardized content that is not subject to providers ' individual opinions or weak communication skills . Video overcomes some weaknesses of mass media health messages : brevity , superficial rendering of complex issues , and lack of opportunity for review ( 30 ) . Third , the public is more oriented toward viewing than reading , and video is particularly attractive to population s with low literacy ( 31 , 32 ) . Last , to our knowledge no other study has evaluated the effect of a mailed video ( an aspect that solves in-clinic logistic problems ) independent of other systems changes ( 21 ) . Methods Study Overview We used a r and omized , controlled design to assess the effectiveness of a video intended to encourage discussion of colorectal cancer screening with the primary care provider and increase use of screening , particularly by sigmoidoscopy . St and ardized telephone interviews were conducted twice . Participants completed the baseline interview several weeks before their scheduled visit and were then r and omly assigned within age and sex strata to the experimental or the control group . Follow-up assessment was completed 4 to 6 months after the periodic examination . Study Sites Participants were recruited from 5 sites in central Massachusetts . Most were patients in internal medicine and family medicine clinics of an academic medical center ( university practice ) . Other sites were a suburban clinic of a staff-model health maintenance organization ( HMO ) ; 3 university-affiliated , community-based practice s ; a rural practice ; and 2 suburban practice s , which were combined for analyses because of small sample sizes and similar patient population s ( community practice s ) . The Committee for the Protection of Human Subjects of the University of Massachusetts Medical School and the Institutional Review Board of Fallon Community Health Plan review ed and approved the study . Participant Recruitment Eligible participants were patients 50 to 74 years of age who had an upcoming periodic health assessment and were eligible for sigmoidoscopy according to screening guidelines ( no sigmoidoscopy within 5 years or colonoscopy within 10 years ) . A computerized appointment system identified potentially eligible participants because appointments are coded by type , including appointments for physical examinations , and by appointment length ( 30 minutes ) . Records used to determine previous tests varied by site and included patient information systems , medical records , and a log of completed procedures . To assure sex and age representation ( men age 50 to 64 years , men age 65 to 74 years , women age 50 to 64 years , and women age 65 to 74 years ) , we determined that a sample size of 225 in each of the younger agesex groups and a sample size of 100 in each of the older agesex groups would assure 80 % power to detect significant differences ( at an level of 0.05 ) ranging from 7 % to 16 % depending on the outcome in the comparison group overall . Patients were enrolled from February 1999 through December 2000 . We sent 1883 eligible patients an invitation letter several weeks before their appointment . Of the 1788 who were contacted by telephone , 1575 ( 88 % ) consented to participate . Consenting persons were screened for additional eligibility criteria . Those excluded reported recent ( n= 339 ) or planned ( n= 26 ) tests ; did not undergo scheduled sigmoidoscopy in the past 10 months ( n= 3 ) ; reported a colorectal cancer diagnosis or related symptoms ( n= 30 ) ; canceled their periodic examination appointment ( n= 41 ) ; could not participate because of illness , death , disability , or dementia or because they were institutionalized ( n= 69 ) ; did not speak English ( n= 35 ) ; had a spouse enrolled in the study ( n= 17 ) ; had moved out of the area ( n= 12 ) ; or were older than 74 years of age ( n= 2 ) . The baseline sample consisted of 1001 persons . After the baseline interview was completed , we sorted consenting participants into the 4 sexage groups . A computer-generated r and om-number table determined assignment in each group . The project director , who was not located at any clinical site , allocated enrollees to the intervention or control group using the computer-generated assignment , tracked group assignment , and mailed intervention material s. The project director was the only individual with knowledge of or access to group or individual assignment . The interviewer was blinded to group assignment at both baseline ( conducted before r and omization ) and follow-up interviews . Subsequently , 63 patients were not eligible : 50 did not keep an index appointment , and 13 could not participate because of death , poor health , or decline in cognitive inability . Of the 938 persons eligible for follow-up ( 97.9 % ) , 926 were contacted by an interviewer who was blinded to group assignment , and 918 completed the follow-up interview . Intervention The objective of the video was to encourage patients to discuss colorectal cancer screening , particularly using sigmoidoscopy , with their physician at their upcoming appointment . This intervention builds on the promising literature about the effectiveness of video to improve health behavior ( 30 , 33 - 35 ) , increase patient knowledge ( 36 - 40 ) , reduce anxiety ( 41 , 42 ) , and provide role modeling ( 43 ) . The intervention consisted of a 15-minute video titled Say Yes to the Test . Development was guided by the PRECEDE/PROCEED model for health promotion planning ( 44 ) and the behavioral model of utilization ( 45 ) , incorporating elements of social cognitive theory ( 46 , 47 ) . We were also interested in testing a mailed outreach strategy . Showing videos in busy clinics is logistically difficult , presenting time , equipment , noise , space , and privacy problems . Friedman and colleagues ( 48 ) found that episodic technical difficulties hindered video education in the clinic setting . Mead and colleagues ( 49 ) reported that patient education material s ( video , pamphlets , posters ) placed in clinic waiting rooms did not increase use of preventive services . Of note , widespread ownership of video players and affordable per-unit cost make a mail-out approach feasible . The video , hosted by a nationally known actress who has had colorectal cancer , described screening by using graphics , footage of physicians discussing screening importance , and footage of a patient undergoing sigmoidoscopy . It addressed benefits and barriers to sigmoidoscopy , primarily with clips of several patients who had screening-detected colorectal cancer , and featured patients discussing sigmoidoscopy experiences ( 50 ) . Barriers included minimal knowledge of colorectal cancer , lack of screening information , low perceived risk , fear of cancer , and expectation of pain and embarrassment ( 16 , 20 , 51 - 60 ) . Videos were mailed to each participant 's home before the scheduled physical examination ; each package contained a letter , signed by the primary care physician , encouraging the participant to view the video . Participants in the control group received usual care with no special material s. Data Collection and Measures Fifteen- to 20-minute telephone surveys were conducted at baseline and 4 to 6 months after the primary care appointment . The timing of the follow-up survey allowed all recommended tests to be scheduled and completed . We developed survey items by using our previous work ( 50 , 61 ) and other studies ( 62 ) . The survey described all tests : For example , a fecal occult blood test was defined as a test taken at home , with cards mailed back . The follow-up survey also covered the intervention group 's experience with the video . Colorectal Cancer Screening Few studies have defined the association of physician-patient communication with physical activity levels in patients with peripheral arterial disease . We hypothesized that a face-to-face intervention versus video watching would improve physical activity levels in patients with peripheral arterial disease . The authors conducted a r and omized trial involving 2 interventions . The face-to-face intervention included a brief dialogue with patients to underst and their perceptions of peripheral arterial disease and importance of walking . The comparison group watched a video that included an overview of peripheral arterial disease . The primary outcome was changed from baseline to follow-up in levels of physical activity . Fifty-one patients with peripheral arterial disease were r and omized . There were no statistically significant differences between the 2 groups in reported activity level or walking ability at 12 weeks . For within group changes , the patients in the video-watching group improved their walking speed ( 8.5 % ; SD = 4.1 ; P = .05 ) . Patients with peripheral arterial disease may benefit from the use of an educational video to increase the use of unsupervised physical activity . Further research is needed to identify interventions that can increase the use of unsupervised physical activity in this population |
12,729 | 27,729,748 | MRI indicates good and poor response by mrTRG1 - 3 and mrTRG4 - 5 , respectively | AIM To define good and poor regression using pathology and magnetic resonance imaging ( MRI ) regression scales after neo-adjuvant chemotherapy for rectal cancer . | PURPOSE To evaluate the impact of preoperative chemoradiation with raltitrexed ( Tomudex(1 ) ) on tumor response , sphincter preservation , and toxicity in patients with locally advanced rectal cancer . METHODS AND MATERIAL S Between 1998 and 2002 , 54 consecutive patients with Stage T3 or T2N+ resectable rectal carcinoma were treated with preoperative chemoradiation , i.v . bolus of raltitrexed on Days 1 , 19 , and 38 and concurrent 50 Gy external beam radiotherapy . Surgery was performed 6 - 8 weeks after the end of chemoradiation . RESULTS No patients had Grade 4 acute toxicity . Grade 3 acute toxicity occurred in 16.6 % of cases and was hematologic in 6 patients and GI in 2 . The overall clinical response rate was 88.8 % , with a complete response in 5.5 % , partial response in 83.3 % , and no change in 9.2 % . No patient showed disease progression . All patients underwent surgery . Sphincter saving was obtained in 83.3 % of patients . No perioperative mortality occurred , and the perioperative morbidity rate was 5.5 % . Of 20 resected patients ( 37 % ) who were c and i date s for abdominoperineal resection at diagnosis ( anorectal ring distance < or = 30 mm ) , 13 ( 65 % ) underwent a sphincter-saving procedure . At pathologic examination , 13 ( 24 % ) of 54 patients had a complete pathologic response ( pT0 ) and 10 ( 18.5 % ) had rare isolated residual cancer cells ( pT , microscopic foci ) . Overall , 42.5 % had major downstaging . The tumor regression grade ( TRG ) , using M and ard 's score system , was also applied and was TRG1 in 13 patients , TRG2 in 11 , TRG3 in 20 , and TRG4 in 10 patients ; no patient had TRG5 . CONCLUSION The use of raltitrexed in a neoadjuvant chemoradiation schedule promoted high pathologic tumor downstaging and use of a sphincter-saving procedure . The low toxicity profile supports the rationale to explore raltitrexed combined with other drugs with different biologic targets Background Magnetic resonance imaging ( MRI ) methods for chemoradiotherapy ( CRT ) response assessment of rectal cancer include posttreatment T staging ( ymrT ) , tumor regression grading ( mrTRG ) , volume reduction posttreatment , and modified RECIST measurement . We compared these methods in identifying good versus poor responders with the histopathological st and ards of T stage ( ypT ) and tumor regression grading ( TRG ) . Methods A total of 86 patients underwent CRT in a prospect i ve phase II trial for MRI-defined locally advanced rectal cancer . Two readers independently assessed MRIs for ymrT , mrTRG , volume change , and RECIST . Parameters for each case were categorized as good or poor response and analyzed against ypT and TRG by univariate logistic regression . Results A total of 83 patients had evaluable imaging , and 78 had final pathology ( five did not undergo surgery ) . Of these , 34 patients had good response ( ypT0 - 3a ) and 44 had poor response ( > ypT3a ) . Also , 27 patients had favorable pathologic TRG ( predominant fibrosis ) and 51 had unfavorable TRG ( predominant tumor ) . Good mrTRG and ymr < T3b stage were both significantly ( P = 0.001 ) associated with favorable pathology odds ratio [ OR ] = 16.11 ( 95 % confidence interval [ 95 % CI ] : 3.36–77.29 ) and 17.50 ( 95 % CI : 5.38–56.89 ) , respectively . RECIST measurements and volume reduction of > 80 % showed an OR of 3.23 ( 95 % CI : 1.14–9.17 ) , 4.25 ( 95 % CI : 0.92–15.45 ) , respectively , for a good ypT score ( P = 0.028 ) , but there was no association for histopathological TRG . Conclusion Favorable and unfavorable histopathology are predicted by both ymrT and mrTRG , and we recommend these parameters for post-treatment assessment of rectal cancers treated with CRT PURPOSE We assessed the impact of tumor regression grading ( TRG ) and its value in correlation to established prognostic factors in a cohort of rectal carcinoma patients treated by preoperative chemoradiotherapy ( CRT ) . PATIENTS AND METHODS TRG was evaluated on surgical specimens of 385 patients treated within the preoperative CRT arm of the CAO/ARO/AIO-94 trial : 50.4 Gy was delivered , fluorouracil was given in the first and fifth week , and surgery was performed 6 weeks thereafter . TRG was determined by the amount of viable tumor versus fibrosis , ranging from TRG 4 when no viable tumor cells were detected , to TRG 0 when fibrosis was completely absent . TRG 3 was defined as regression more than 50 % with fibrosis outgrowing the tumor mass , TRG 2 was defined as regression less than 50 % , and TRG 1 was defined basically as a morphologically unaltered tumor mass . We performed an initially unplanned , hypothesis-generating analysis with respect to the prognostic value of this TRG system . RESULTS TRG 4 , 3 , 2 , 1 , 0 was found in 10.4 % , 52.2 % , 13.8 % , 15.3 % , and 8.3 % of the resected specimens , respectively . Five-year disease-free survival ( DFS ) after CRT and curative resection was 86 % for TRG 4 , 75 % for grouped TRG 2 + 3 , and 63 % for grouped TRG 0 + 1 ( P = .006 ) . On multivariate analysis , the pathologic T category and the nodal status after CRT were the most important independent prognostic factors for DFS . CONCLUSION In this exploratory analysis , complete ( TRG 4 ) and intermediate pathologic response ( TRG 2 + 3 ) suggested improved DFS after preoperative CRT . TRG assessment should be implemented in pathologic evaluation and prospect ively vali date d in further studies PURPOSE The aim this study was to determine the pathologic complete response ( pCR ) rate defined as tumor regression grade 1 ( TRG1 ) and toxicity profile of the combination of high-dose pre-operative radiotherapy and simultaneous UFT/leucovorin ( LV ) in patients with locally advanced rectal cancer . MATERIAL S/ METHODS Eligibility included biopsy proven rectal adenocarcinoma ; T3-T4 N0-N2 ; performance status < 2 ( ECOG ) and adequate blood , hepatic and renal function . Treatment consisted of radiotherapy 54 Gy at 1.8 Gy/day and UFT 300 mg/m(2)/day and LV 60 mg/day , given simultaneously daily for 6 weeks . Surgery was performed within 4 - 6 weeks period after chemoradiotherapy . Patients who did not achieve TGR1 were to receive 4 cycles of adjuvant UFT/LV on days 1 - 28 , every 5 weeks . RESULTS Sixty-eight patients were included . All but one received full dose of radiation and 62 had the total planned pre-operative UFT/LV dose . Grade 3 toxicities were diarrhea 7 % and proctitis 3 % . Complete resection was achieved in 62 patients ( 91 % ) . Tumor regression grade 1 ( TRG1 ) was seen in 11 patients ( 16 % ) . Forty-eight patients received adjuvant UFT/LV . Grade 3 toxicity during adjuvant UFT/LV included diarrhea 12 % , asthenia 4 % , neutropenia 2 % , and h and -foot syndrome 2 % . The 3-year disease-free survival was 71 % . CONCLUSIONS Simultaneous high-dose pre-operative localized radiation therapy concurrent with UFT/LV is feasible and has a low toxicity profile . This schedule is highly effective and merits further investigation BACKGROUND AND PURPOSE To explore the utility of tumour regression grading ( TRG , the amount of residual tumour cells in relation to extension of fibrosis ) after chemoradiation of rectal cancer . MATERIAL S AND METHODS Of 131 patients who received preoperative chemoradiation in the frame of the r and omized trial , pathological complete response ( pCR , TRG0 ) , good regression ( TRG1 ) , moderate regression ( TRG2 ) , and poor regression ( TRG3 ) were recorded in 17 % , 31 % , 31 % , and 22 % of patients , respectively . RESULTS The rates of ypN-positive category for TRG0 , TRG1 , TRG2 , and TRG3 groups were 5 % , 23 % , 45 % , and 46 % , respectively , p=0.001 . When ypT-category and TRG were evaluated by the logistic regression analysis , only ypT-category remained significant for independent prediction of the risk for mesorectal nodal metastases , p=0.006 . The 4-year ( median follow-up ) disease-free survival ( DFS ) for TRG0 , TRG1 , TRG2 , and TRG3 groups were 91 % , 67 % , 54 % , and 47 % . When patients with persistent disease ( TRG1 vs. TRG2 vs. TRG3 ) were analyzed separately , TRG had no prognostic value for DFS , p=0.402 . CONCLUSIONS TRG in patients with residual cancer had no prognostic value for the incidence of nodal disease and for DFS . Our findings and literature data question the need for the inclusion of TRG assessment into a routine pathological report AIM The value of grading tumor regression after neoadjuvant therapy of rectal carcinoma was evaluated . PATIENTS AND METHODS Analysis was carried out using prospect i ve data of 225 patients with rectal carcinoma treated by neoadjuvant radiochemotherapy followed by radical resection with curative intent . For the histological regression grading , the method of Dworak et al. ( 1997 ) was used with a slight modification . RESULTS After neoadjuvant radiochemotherapy , the most important prognostic factors are pathologically assessed circumferential resection margin , quality of surgery ( plane of surgery ) , and the ypT and ypN classification . In addition , the histological regression grade of primary tumor and regional lymph nodes influence outcome , especially the local recurrence rate . CONCLUSION After neoadjuvant therapy , the histological tumor regression grading should be assessed . A regression grading system based on the proposals of Dworak et al. ( 1997 ) is recommended PURPOSE To assess magnetic resonance imaging ( MRI ) and pathologic staging after neoadjuvant therapy for rectal cancer in a prospect ively enrolled , multicenter study . METHODS In a prospect i ve cohort study , 111 patients who had rectal cancer treated by neoadjuvant therapy were assessed for response by MRI and pathology staging by T , N and circumferential resection margin ( CRM ) status . Tumor regression grade ( TRG ) was also assessed by MRI . Overall survival ( OS ) was estimated by using the Kaplan-Meier product-limit method , and Cox proportional hazards models were used to determine associations between staging of good and poor responders on MRI or pathology and survival outcomes after controlling for patient characteristics . RESULTS On multivariate analysis , the MRI-assessed TRG ( mrTRG ) hazard ratios ( HRs ) were independently significant for survival ( HR , 4.40 ; 95 % CI , 1.65 to 11.7 ) and disease-free survival ( DFS ; HR , 3.28 ; 95 % CI , 1.22 to 8.80 ) . Five-year survival for poor mrTRG was 27 % versus 72 % ( P = .001 ) , and DFS for poor mrTRG was 31 % versus 64 % ( P = .007 ) . Preoperative MRI-predicted CRM independently predicted local recurrence ( LR ; HR , 4.25 ; 95 % CI , 1.45 to 12.51 ) . Five-year survival for poor post-treatment pathologic T stage ( ypT ) was 39 % versus 76 % ( P = .001 ) ; DFS for the same was 38 % versus 84 % ( P = .001 ) ; and LR for the same was 27 % versus 6 % ( P = .018 ) . The 5-year survival for involved pCRM was 30 % versus 59 % ( P = .001 ) ; DFS , 28 versus 62 % ( P = .02 ) ; and LR , 56 % versus 10 % ( P = .001 ) . Pathology node status did not predict outcomes . CONCLUSION MRI assessment of TRG and CRM are imaging markers that predict survival outcomes for good and poor responders and provide an opportunity for the multidisciplinary team to offer additional treatment options before planning definitive surgery . Postoperative histopathology assessment of ypT and CRM but not post-treatment N status were important postsurgical predictors of outcome Purpose : Preoperative radiochemotherapy is widely used in the treatment of locally advanced rectal cancer . The predictive value of response to neoadjuvant treatment remains uncertain . We retrospectively evaluated the impact of downstaging and tumor regression as prognostic factors and its influence on the ability to perform sphincter-sparing surgery . Patients and Methods : A total of 72 consecutive patients with advanced rectal cancer were included in this retrospective analysis . All patients were treated with preoperative 5-fluorouracil-based chemotherapy and pelvic radiation with a total dose of 50.4 Gy followed by surgery 6 weeks later . Results : A sphincter-preserving procedure could be performed on 42 patients , and in all 72 patients complete resection ( R0 ) was achieved . A pathological complete response ( ypT0 , ypN0 ) was achieved in 8 ( 11 % ) patients . None of the patients showing a complete pathological response relapsed or died during the follow-up period . At a median follow-up of 28 months , 65 patients were alive , none of these patients had local recurrence and 15 patients had metastatic disease . Patients showing a complete pathological response had a significantly better 2-year disease-free survival compared to patients with ≥10 % residual tumor cells ( p = 0.024 ) . Patients < 65 years showed a significantly better response rate , compared with those > 65 years of age ( p = 0.036 ) . Acute toxicity was moderate . Conclusion : Preoperative radiochemotherapy is an effective and safe treatment for patients with locally advanced rectal cancer . Pathological parameters after preoperative radiochemotherapy , including tumor regression grading , could be correlated with disease-free survival . The impact of tumor regression grading needs to be further vali date d in prospect i ve clinical trials . Hintergrund : Die präoperative Radiochemotherapie ( RChT ) gefolgt von einer Operation stellt heute die St and ardbeh and lung für Patienten mit lokal fortgeschrittenem Rektumkarzinom dar . Der Vorhersagewert des Ansprechens auf eine neoadjuvante RChT ist nicht definiert . Wir untersuchten retrospektiv die Bedeutung des Tumoransprechens ( Downstaging ) und der Tumorregression als prognostische Faktoren und ihren Einfluss , eine sphinktererhaltende Operation zu ermöglichen . Material und Method e : Die vorliegende Analyse umfasst 72 konsekutive Patienten mit fortgeschrittenen Rektumkarzinomen , die i m Zeitraum Januar 1999 bis Dezember 2006 eine neoadjuvante RChT erhielten . Die Beh and lung best and aus einer perkutanen Radiotherapie mit 50,4 Gy und einer simultanen 24-h-Dauerinfusion von 5-Fluorouracil ( Woche 1 und 5 ) gefolgt von einer radikalen Tumorresektion . Neben dem Ansprechen des Tumors i m Sinne eines Downstagings wurden mögliche prognostische Faktoren analysiert . Ergebnisse : Nach einer medianen Nachbeobachtungszeit von 28 Monaten kam es bei keinem Patienten zu einem Lokalrezidiv und bei allen 72 Patienten gelang eine komplette Resektion ( R0 ) . Das Ansprechen auf die neoadjuvante RChT i m Sinne einer histopathologischen Tumorregression konnte als relevanter Prognosefaktor für das krankheitsfreie Überleben herausgearbeitet werden ( Abbildung 1 ) . 8 Patienten ( 11 % ) erreichten eine histopathologische komplette Remission ( ypT0 , ypN0 ) . Darüber hinaus zeigten Patienten unter 65 Jahre ein signifikant besseres Ansprechen auf die präoperative RChT i m Sinne eines Downstagings als Patienten über 65 Jahre ( p = 0,036 ) . Die Akuttoxizität der neoadjuvanten Therapie ist moderat . Schlussfolgerung : Die neoadjuvante RChT mit anschließender radikaler Resektion ist eine effektive und sichere Beh and lung lokal fortgeschrittener Rektumkarzinome . Die Tumorregression konnte mit dem krankheitsfreien Überleben korreliert werden . Inwieweit die Tumorregression als valider Prognoseparameter angesehen werden kann , muss in prospektiven klinischen Studien überprüft werden F high risk of local recurrence and poor survival has been eported in patients with locally advanced ( T3/T4 Nx ) rectal ancer . Hence , intensification of treatment by using preoprative chemoradiation ( CRT ) has been explored in phase /II trials . In these studies pathologic complete response pCR ) has been employed to demonstrate efficacy , and rates ary between 15 % to 30 % . pCR is an attractive , objective ly easurable endpoint which can be available in the short erm because surgical resection usually takes place within –8 weeks of the completion of treatment . R and omized preoperative studies in resectable cancer ( 1 , ) have suggested that total doses of 45 Gy will result in nly a 3–4 % pCR rate with preoperative radiotherapy lone . A significant increase in pCR and clinical complete esponse has been achieved by radiotherapy dose escalation sing local endocavitary 50kv contact radiotherapy ( 3 ) . This trategy appears to provide better downstaging , and signifcantly increased the rate of sphincter preservation without ranslating into an improvement in overall survival . Howver , it seems intuitively unlikely that dose escalation to a mall volume , which will eventually be resected surgically , ould impact on survival . However , the validity of infernces from these data sets is limited by the inherent hetergeneity of combining patients from different stages of isease , different selection procedures , different pathologic echniques , and varying quality assurance . In r and omized phase III studies , the addition of 5-flurouracil to preoperative radiation also increases the pCR ate over radiotherapy alone , and provides evidence for mprovements in locoregional control ( 1 , 2 ) , but has not ranslated into an improvement in disease-free or overall urvival . Nevertheless , preoperative CRT remains the stanard of care in patients with locally advanced rectal cancer . Factors associated with a greater chance of a pCR include otal radiation dose , initial T stage , overall size , and the nterval between the completion of radiotherapy and surery BACKGROUND Patients with poor-risk rectal cancer defined by MRI can be at high risk of disease recurrence despite st and ard chemoradiotherapy and optimum surgery . We aim ed to assess the safety and long-term efficacy of neoadjuvant chemotherapy with capecitabine and oxaliplatin before chemoradiotherapy and total mesorectal excision , a treatment strategy developed to enhance the outcome of this population . METHODS Between November , 2001 , and August , 2005 , we enrolled eligible patients with poor-risk rectal cancer defined by high-resolution MRI and without metastatic disease . The protocol was amended in January , 2004 , following clinical ly significant cardiotoxic events ( nine events in eight of 77 patients ) , to exclude patients with a recent history of clinical ly significant cardiac problems . Patients received 12 weeks of neoadjuvant capecitabine and oxaliplatin ( oxaliplatin 130 mg/m2 on day 1 with capecitabine 1000 mg/m2 twice daily for 14 days every 3 weeks ) followed by chemoradiotherapy ( 54 Gy over 6 weeks ) with capecitabine ( 825 mg/m2 twice daily ) , total mesorectal excision , and 12 weeks of postoperative adjuvant capecitabine ( 1250 mg/m2 twice daily for 14 days every 3 weeks ) . The primary endpoint was pathological complete response rate . We followed up patients for a median of 55 months ( IQR 47 - 67 ) . Efficacy analyses were undertaken for the intention-to-treat population , unless otherwise specified . This study is registered with Clinical Trials.gov , number NCT00220051 . FINDINGS 105 eligible patients were enrolled . Radiological response rates after neoadjuvant chemotherapy and chemoradiotherapy were 74 % ( 78/105 ) and 89 % ( 93/105 ) , respectively . 97 patients underwent surgery , of whom 95 underwent total mesorectal excision , of whom 93 had microscopically clear resection margins and 21 had pathological complete response ( 21/105 [ 20 % ] ) . 3-year progression-free and overall survival were 68 % ( 95 % CI 59 - 77 ) and 83 % ( 76 - 91 ) , respectively . 3-year relapse-free survival for patients who had complete resection was 74 % ( 65 - 83 ) . Following the protocol amendment for cardiovascular safety , only one further thromboembolic event was reported ( fatal pulmonary embolism ) . INTERPRETATION Intensification of systemic therapy with neoadjuvant combination chemotherapy before st and ard treatment is feasible in poor-risk potentially operable rectal cancer , with acceptable safety and promising long-term outcomes . Future development of this multidisciplinary treatment strategy in r and omised trials is warranted . FUNDING UK National Health Service , Sanofi-Aventis PURPOSE We previously described the prognostic impact of tumor regression grading ( TRG ) on the outcome of patients with rectal carcinoma treated with preoperative chemoradiotherapy ( CRT ) in the CAO/ARO/AIO-94 trial . Here we report long-term results after a median follow-up of 132 months . PATIENTS AND METHODS TRG after preoperative CRT was determined in 386 surgical specimens by the amount of viable tumor cells versus fibrosis , ranging from TRG 4 ( no viable tumor cells ) to TRG 0 ( no signs of regression ) . Clinicopathologic parameters and TRG were correlated to the cumulative incidence of local recurrence , distant metastasis , and disease-free survival ( DFS ) . RESULTS Ten-year cumulative incidence of distant metastasis and DFS were 10.5 % and 89.5 % for patients with TRG 4 ( complete regression ) , 29.3 % and 73.6 % for TRG 2 and 3 ( intermediate regression ) , and 39.6 % and 63 % for TRG 0 and 1 ( poor regression ) , respectively ( P = .005 and P = .008 , respectively ) . On multivariable analysis , residual lymph node metastasis ( ypN+ ) and TRG were the only independent prognostic factors for cumulative incidence of distant metastasis ( P < .001 and P = .035 , respectively ) and DFS ( P < .001 and P = .039 , respectively ) , whereas local recurrence was significantly affected by ypN status ( P < .001 ) and lymphatic invasion ( P = .026 ) . CONCLUSION Complete and intermediate tumor regressions were associated with improved long-term outcome in patients with rectal carcinoma after preoperative CRT independent of clinicopathologic parameters . This classification system needs to be prospect ively tested in multiple data sets to vali date its reproducibility in a wider setting |
12,730 | 29,627,509 | Conclusion : Neuroimaging studies suggest that abnormalities in hippocampus , amygdala , iFG , uncus and areas linked with emotional regulation ( dlPFC and ACC ) , predict a good outcome to psychotherapy in anxiety disorders .
HighlightsNeuroimaging studies suggest that hippocampus , amygdala , iFG , uncus dlPFC and ACC predict a good outcome to psychotherapy in anxiety disorders | & NA ; Anxiety disorders are the largest group of mental disorders and a leading cause of impairment , implicating in high costs for health systems and society .
Effective pharmacological and psychological treatments are available , but a significant fraction of these patients does not respond adequately to these treatments .
The objective of this study is to identify neuroimaging findings that could predict response to psychotherapy in anxiety disorders . | R and omized controlled trials have yielded promising results for internet-delivered cognitive behavior therapy ( iCBT ) for patients with social anxiety disorder ( SAD ) . The present study investigated anxiety-related neural changes after iCBT for SAD . The amygdala is a critical hub in the neural fear network , receptive to change using emotion regulation strategies and a putative target for iCBT . Twenty-two subjects were included in pre- and post-treatment functional magnetic resonance imaging at 3 T assessing neural changes during an affective face processing task . Treatment outcome was assessed using social anxiety self-reports and the Clinical Global Impression-Improvement ( CGI-I ) scale . ICBT yielded better outcome than ABM ( 66 % vs. 25 % CGI-I responders ) . A significant differential activation of the left amygdala was found with relatively decreased reactivity after iCBT . Changes in the amygdala were related to a behavioral measure of social anxiety . Functional connectivity analysis in the iCBT group showed that the amygdala attenuation was associated with increased activity in the medial orbitofrontal cortex and decreased activity in the right ventrolateral and dorsolateral ( dlPFC ) cortices . Treatment-induced neural changes with iCBT were consistent with previously reported studies on regular CBT and emotion regulation in general Patients with anxiety disorders exhibit excessive neural reactivity in the amygdala , which can be normalized by effective treatment like cognitive behavior therapy ( CBT ) . Mechanisms underlying the brain ’s adaptation to anxiolytic treatments are likely related both to structural plasticity and functional response alterations , but multimodal neuroimaging studies addressing structure – function interactions are currently missing . Here , we examined treatment-related changes in brain structure ( gray matter ( GM ) volume ) and function ( blood – oxygen level dependent , BOLD response to self-referential criticism ) in 26 participants with social anxiety disorder r and omly assigned either to CBT or an attention bias modification control treatment . Also , 26 matched healthy controls were included . Significant time × treatment interactions were found in the amygdala with decreases both in GM volume ( family-wise error ( FWE ) corrected PFWE=0.02 ) and BOLD responsivity ( PFWE=0.01 ) after successful CBT . Before treatment , amygdala GM volume correlated positively with anticipatory speech anxiety ( PFWE=0.04 ) , and CBT-induced reduction of amygdala GM volume ( pre – post ) correlated positively with reduced anticipatory anxiety after treatment ( PFWE⩽0.05 ) . In addition , we observed greater amygdala neural responsivity to self-referential criticism in socially anxious participants , as compared with controls ( PFWE=0.029 ) , before but not after CBT . Further analysis indicated that diminished amygdala GM volume mediated the relationship between decreased neural responsivity and reduced social anxiety after treatment ( P=0.007 ) . Thus , our results suggest that improvement-related structural plasticity impacts neural responsiveness within the amygdala , which could be essential for achieving anxiety reduction with CBT Background Amygdala is considered as the core pathogenesis of generalized social anxiety disorder ( GSAD ) . However , it is still unclear whether effective group cognitive behavioral therapy ( CBT ) could modulate the function of amygdala-related network . We aim ed to examine the resting-state functional connectivity ( rsFC ) of the amygdala before and after group CBT . Methods Fifteen patients with GSAD were scanned on a 3 T MR system before and after 8 weeks of group CBT . For comparison , nineteen healthy control participants also underwent baseline fMRI scanning . We used bilateral amygdala as seed regions and the rsFC maps of the right and left amygdala were created separately in a voxel-wise way . Clusters survived two-tailed Gaussian R and om Field ( GRF ) correction at p < 0.05 ( voxel z value > 2.3 ) . Results Compared with baseline , patients with CBT showed significantly decreased connectivity of the left amygdala with the right putamen , the left dorsal medial prefrontal cortex ( dmPFC ) and the right dorsal anterior cingulate cortex ( dACC ) . Especially , the changes of the connectivity between the left amygdala and the dACC positively correlated with changes of the anxiety symptom in patients . Furthermore , in relative to controls , patients showed higher connectivity of left amygdala with dmPFC and dACC at baseline , while normal after CBT . Conclusions Short-term group CBT could down-regulate the abnormal higher connectivity of prefrontal-amygdala network , along with clinical improvement . This may provide a potential biomarker to monitor the treatment effect of CBT in GSAD patients Social anxiety disorder ( SAD ) is characterized at a neurobiological level by disrupted activity in emotion regulation neural circuitry . Previous work has demonstrated amygdala hyperreactivity and disrupted prefrontal responses to social cues in individuals with SAD ( Kim et al. , 2011 ) . While exposure-based psychological treatments effectively reduce SAD symptoms , not all individuals respond to treatment . Better underst and ing of the neural mechanisms involved offers the potential to improve treatment efficacy . In this study , we investigated functional connectivity in emotion regulation neural circuitry in a r and omized controlled treatment trial for SAD . Participants with SAD underwent fMRI scanning while performing an implicit emotion regulation task prior to treatment ( n=62 ) . Following 12 weeks of cognitive behavioral therapy , acceptance and commitment therapy , or wait-list , participants completed a second scan ( n=42 ) . Psychophysiological interaction analyses using amygdala seed regions demonstrated differences between SAD and healthy control participants ( HC ; n=16 ) in right amygdala-vmPFC connectivity . SAD participants demonstrated more negative amygdala-to-vmPFC connectivity , compared to HC participants , an effect that was correlated with SAD symptom severity . Post-treatment symptom reduction was correlated with altered amygdala-to-vm/vlPFC connectivity , independent of treatment type . Greater symptom reduction was associated with more negative amygdala-to-vm/vlPFC connectivity . These findings suggest that effective psychological treatment for SAD enhances amygdala-prefrontal functional connectivity Background : Cognitive behavioral therapy ( CBT ) is an effective treatment for panic disorder with agoraphobia ( PD/AG ) . It is unknown , how variants of CBT differentially modulate brain networks involved in PD/AG . This study was aim ed to evaluate the effects of therapist-guided ( T+ ) versus self-guided ( T- ) exposure on the neural correlates of fear conditioning in PD/AG . Method : In a r and omized , controlled multicenter clinical trial in medication-free patients with PD/AG who were treated with 12 sessions of manualized CBT , functional magnetic resonance imaging ( fMRI ) was used during fear conditioning before ( t1 ) and after CBT ( t2 ) . Quality -controlled fMRI data from 42 patients and 42 healthy subjects ( HS ) were obtained . Patients were r and omized to two variants of CBT ( T+ , n = 22 , and T- , n = 20 ) . Results : The interaction of diagnosis ( PD/AG , HS ) , treatment group ( T+ , T- ) , time point ( t1 , t2 ) and stimulus type ( conditioned stimulus : yes , no ) revealed activation in the left hippocampus and the occipitotemporal cortex . The T+ group demonstrated increased activation of the hippocampus at t2 ( t2 > t1 ) , which was positively correlated with treatment outcome , and a decreased connectivity between the left inferior frontal gyrus and the left hippocampus across time ( t1 > t2 ) . Conclusion : After T+ exposure , contingency-encoding processes related to the posterior hippocampus are augmented and more decoupled from processes of the left inferior frontal gyrus , previously shown to be dysfunctionally activated in PD/AG . Linking single procedural variants to neural substrates offers the potential to inform about the optimization of targeted psychotherapeutic interventions BACKGROUND Neurofunctional changes underlying effective antianxiety treatments are incompletely characterized . This study explored the effects of citalopram and cognitive-behavioral therapy on regional cerebral blood flow ( rCBF ) in social phobia . METHODS By means of positron emission tomography with oxygen 15-labeled water , rCBF was assessed in 18 previously untreated patients with social phobia during an anxiogenic public speaking task . Patients were matched for sex , age , and phobia severity , based on social anxiety question naire data , and r and omized to citalopram medication , cognitive-behavioral group therapy , or a waiting-list control group . Scans were repeated after 9 weeks of treatment or waiting time . Outcome was assessed by subjective and psychophysiological state anxiety measures and self-report question naires . Questions were readministered after 1 year . RESULTS Symptoms improved significantly and roughly equally with citalopram and cognitive-behavioral therapy , whereas the waiting-list group remained unchanged . Four patients in each treated group and 1 waiting-list patient were classified as responders . Within both treated groups , and in responders regardless of treatment approach , improvement was accompanied by a decreased rCBF-response to public speaking bilaterally in the amygdala , hippocampus , and the periamygdaloid , rhinal , and parahippocampal cortices . Between-group comparisons confirmed that rCBF in these regions decreased significantly more in treated groups than control subjects , and in responders than nonresponders , particularly in the right hemisphere . The degree of amygdalar-limbic attenuation was associated with clinical improvement a year later . CONCLUSIONS Common sites of action for citalopram and cognitive-behavioral treatment of social anxiety were observed in the amygdala , hippocampus , and neighboring cortical areas , ie , brain regions subserving bodily defense reactions to threat The 16-item Quick Inventory of Depressive Symptomatology ( QIDS ) , a new measure of depressive symptom severity derived from the 30-item Inventory of Depressive Symptomatology ( IDS ) , is available in both self-report ( QIDS-SR(16 ) ) and clinician-rated ( QIDS-C(16 ) ) formats . This report evaluates and compares the psychometric properties of the QIDS-SR(16 ) in relation to the IDS-SR(30 ) and the 24-item Hamilton Rating Scale for Depression ( HAM-D(24 ) ) in 596 adult out patients treated for chronic nonpsychotic , major depressive disorder . Internal consistency was high for the QIDS-SR(16 ) ( Cronbach 's alpha = .86 ) , the IDS-SR(30 ) ( Cronbach 's alpha = .92 ) , and the HAM-D(24 ) ( Cronbach 's alpha = .88 ) . QIDS-SR(16 ) total scores were highly correlated with IDS-SR(30 ) ( .96 ) and HAM-D(24 ) ( .86 ) total scores . Item-total correlations revealed that several similar items were highly correlated with both QIDS-SR(16 ) and IDS-SR(30 ) total scores . Roughly 1.3 times the QIDS-SR(16 ) total score is predictive of the HAM-D(17 ) ( 17-item version of the HAM-D ) total score . The QIDS-SR(16 ) was as sensitive to symptom change as the IDS-SR(30 ) and HAM-D(24 ) , indicating high concurrent validity for all three scales . The QIDS-SR(16 ) has highly acceptable psychometric properties , which supports the usefulness of this brief rating of depressive symptom severity in both clinical and research setting Background : The present study examined the prevalence of social phobia in the Swedish general population and demographic characteristics associated with this anxiety disorder . Methods : Data were obtained by means of a postal survey administrated to 2000 r and omly selected adults . A question naire , vali date d against clinical interviews and established social phobia scales , was used to assess social distress in a broad range of phobic situations , as well as the diagnostic criteria for social phobia corresponding to DSM-IV . Interpretable question naires were obtained from 1202 respondents ( 60.1 % ) . Results : The point prevalence of social phobia was estimated at 15.6 % , but prevalence rates varied between 1.9 and 20.4 % across the different levels of distress and impairment used to define cases . Public speaking was the most common social fear . Social phobia was associated with female gender , low educational attainment , psychiatric medication use , and lack of social support . Conclusions : Although the exact diagnostic boundaries for social phobia are difficult to determine , it can be concluded that social anxiety is a distressing problem for a considerable proportion of the general population BACKGROUND Learning by conditioning is a key ability of animals and humans for acquiring novel behavior necessary for survival in a changing environment . Aberrant conditioning has been considered a crucial factor in the etiology and maintenance of panic disorder with agoraphobia ( PD/A ) . Cognitive-behavioral therapy ( CBT ) is an effective treatment for PD/A. However , the neural mechanisms underlying the effects of CBT on conditioning processes in PD/A are unknown . METHODS In a r and omized , controlled , multicenter clinical trial in medication-free patients with PD/A who were treated with 12 sessions of manualized CBT , functional magnetic resonance imaging ( fMRI ) was used during fear conditioning before and after CBT . Quality -controlled fMRI data from 42 patients and 42 healthy subjects were obtained . RESULTS After CBT , patients compared to control subjects revealed reduced activation for the conditioned response ( CS+ > CS- ) in the left inferior frontal gyrus ( IFG ) . This activation reduction was correlated with reduction in agoraphobic symptoms from t1 to t2 . Patients compared to control subjects also demonstrated increased connectivity between the IFG and regions of the " fear network " ( amygdalae , insulae , anterior cingulate cortex ) across time . CONCLUSIONS This study demonstrates the link between cerebral correlates of cognitive ( IFG ) and emotional ( " fear network " ) processing during symptom improvement across time in PD/A. Further research along this line has promising potential to support the development and further optimization of targeted treatments BACKGROUND Functional magnetic resonance imaging ( fMRI ) holds promise as a noninvasive means of identifying neural responses that can be used to predict treatment response before beginning a drug trial . Imaging paradigms employing facial expressions as presented stimuli have been shown to activate the amygdala and anterior cingulate cortex ( ACC ) . Here , we sought to determine whether pretreatment amygdala and rostral ACC ( rACC ) reactivity to facial expressions could predict treatment outcomes in patients with generalized anxiety disorder ( GAD ) . METHODS Fifteen subjects ( 12 female subjects ) with GAD participated in an open-label venlafaxine treatment trial . Functional magnetic resonance imaging responses to facial expressions of emotion collected before subjects began treatment were compared with changes in anxiety following 8 weeks of venlafaxine administration . In addition , the magnitude of fMRI responses of subjects with GAD were compared with that of 15 control subjects ( 12 female subjects ) who did not have GAD and did not receive venlafaxine treatment . RESULTS The magnitude of treatment response was predicted by greater pretreatment reactivity to fearful faces in rACC and lesser reactivity in the amygdala . These individual differences in pretreatment rACC and amygdala reactivity within the GAD group were observed despite the fact that 1 ) the overall magnitude of pretreatment rACC and amygdala reactivity did not differ between subjects with GAD and control subjects and 2 ) there was no main effect of treatment on rACC-amygdala reactivity in the GAD group . CONCLUSIONS These findings show that this pattern of rACC-amygdala responsivity could prove useful as a predictor of venlafaxine treatment response in patients with GAD The possibility of individualized treatment prediction has profound implication s for the development of personalized interventions for patients with anxiety disorders . Here we utilize r and om forest classification and pre-treatment functional magnetic resonance imaging ( fMRI ) data from individuals with generalized anxiety disorder ( GAD ) and panic disorder ( PD ) to generate individual subject treatment outcome predictions . Before cognitive behavioral therapy ( CBT ) , 48 adults ( 25 GAD and 23 PD ) reduced ( via cognitive re appraisal ) or maintained their emotional responses to negative images during fMRI scanning . CBT responder status was predicted using activations from 70 anatomically defined regions . The final r and om forest model included 10 predictors contributing most to classification accuracy . A similar analysis was conducted using the clinical and demographic variables . Activations in the hippocampus during maintenance and anterior insula , superior temporal , supramarginal , and superior frontal gyri during re appraisal were among the best predictors , with greater activation in responders than non-responders . The final fMRI-based model yielded 79 % accuracy , with good sensitivity ( 0.86 ) , specificity ( 0.68 ) , and positive and negative likelihood ratios ( 2.73 , 0.20 ) . Clinical and demographic variables yielded poorer accuracy ( 69 % ) , sensitivity ( 0.79 ) , specificity ( 0.53 ) , and likelihood ratios ( 1.67 , 0.39 ) . This is the first use of r and om forest models to predict treatment outcome from pre-treatment neuroimaging data in psychiatry . Together , r and om forest models and fMRI can provide single-subject predictions with good test characteristics . Moreover , activation patterns are consistent with the notion that greater activation in cortico-limbic circuitry predicts better CBT response in GAD and PD & NA ; Effective psychiatric treatments ameliorate excessive anxiety and induce neuroplasticity immediately after the intervention , indicating that emotional components in the human brain are rapidly adaptable . Still , the interplay between structural and functional neuroplasticity is poorly understood , and studies of treatment‐induced long‐term neuroplasticity are rare . Functional and structural magnetic resonance imaging ( using 3 T MRI ) was performed in 13 subjects with social anxiety disorder on 3 occasions over 1 year . All subjects underwent 9 weeks of Internet‐delivered cognitive behaviour therapy in a r and omized cross‐over design and independent assessors used the Clinical ly Global Impression‐Improvement ( CGI‐I ) scale to determine treatment response . Gray matter ( GM ) volume , assessed with voxel‐based morphometry , and functional blood‐oxygen level‐dependent ( BOLD ) responsivity to self‐referential criticism were compared between treatment responders and non‐responders using 2 × 2 ( group × time ; pretreatment to follow‐up ) ANOVA . At 1‐year follow‐up , 7 ( 54 % ) subjects were classified as CGI‐I responders . Left amygdala GM volume was more reduced in responders relative to non‐responders from pretreatment to 1‐year follow‐up ( Z = 3.67 , Family‐Wise Error corrected p = 0.02 ) . In contrast to previous short‐term effects , altered BOLD activations to self‐referential criticism did not separate responder groups at follow‐up . The structure and function of the amygdala changes immediately after effective psychological treatment of social anxiety disorder , but only reduced amygdala GM volume , and not functional activity , is associated with a clinical response 1 year after CBT . HighlightsLong‐term amygdala gray matter volume reduction corresponds to less social anxiety . In contrast , amygdala response alterations are not present at 1‐year follow‐up . Decreased anxiety can not solely be explained by attenuated neural activation . The interplay between amygdala volume and function might be a treatment mechanism Cognitive behavioral therapy ( CBT ) is " gold st and ard " psychotherapy for social anxiety disorder ( SAD ) . Cognitive models posit that preferential processing of threat mediates excessive forms of anxiety , which is supported by exaggerated amygdala , insula , and cortical reactivity to threatening socio-emotional signals in SAD . However , little is known about neural predictors of CBT success or the mechanisms by which CBT exerts its therapeutic effects . Functional magnetic resonance imaging ( fMRI ) was conducted during responses to social signals of threat ( fearful/angry faces ) against positive signals ( happy faces ) in 14 patients with SAD before and after 12 weeks of CBT . For comparison , 14 healthy control ( HC ) participants also underwent two fMRI scans , 12 weeks apart . Whole-brain voxel-wise analyses showed therapeutic success was predicted by enhanced pre-treatment activation to threatening faces in higher-order visual ( superior and middle temporal gyrus ) , cognitive , and emotion processing areas ( dorsal anterior cingulate cortex , dorsomedial prefrontal cortex ) . Moreover , a group by time interaction was revealed in prefrontal regions ( dorsomedial , medial gyrus ) and insula . The interaction was driven by relatively greater activity during threat processing in SAD , which significantly reduced after CBT but did not significantly predict response to CBT . Therefore , pre-treatment cortical hyperactivity to social threat signals may serve as a prognostic indicator of CBT success in SAD . Collectively , CBT-related brain changes involved a reduction in activity in insula , prefrontal , and extrastriate regions . Results are consistent with cognitive models , which associate decreases in threat processing bias with recovery |
12,731 | 24,566,200 | Despite limitations in some individual studies , our review identified generally consistent associations between depression and adverse outcomes . | BACKGROUND Although prospect i ve studies , systematic review s , and meta-analyses have documented an association between depression and increased morbidity and mortality in a variety of cardiac population s , depression has not yet achieved formal recognition as a risk factor for poor prognosis in patients with acute coronary syndrome by the American Heart Association and other health organizations .
The purpose of this scientific statement is to review available evidence and recommend whether depression should be elevated to the status of a risk factor for patients with acute coronary syndrome . | BACKGROUND Whether there is an association between depression at the time of acute myocardial infa rct ion and subsequent risk of cardiac complications and death remains controversial . Most studies of this risk factor have been limited to patients of single institutions , and this might account for the varying results . We prospect ively evaluated patients admitted to 5 tertiary care and 5 community hospitals and followed them for 1 year to measure the prevalence and prognostic impact of depressive symptoms after acute myocardial infa rct ion . METHODS Patients were recruited for the study by trained nurse interviewers who had documented acute myocardial infa rct ion within 2 - 3 days of admission . The nurses collected information from the medical records and asked study subjects to complete the Beck Depression Inventory question naire during their stay in hospital and using a mailed question naire 30 days , 6 months and 1 year later . We obtained information on vital status for patients lost to follow-up from a central death registry . RESULTS Of the 587 study subjects , 550 ( 94 % ) completed the Beck Depression Inventory at baseline and 191 ( 35 % ) had a score of 10 or more , indicating at least mild depression . Rates of depression did not vary over the follow-up period and were similar among patients admitted to tertiary care or community hospitals . Depressed patients were more likely to undergo catheterization ( 57 % v. 47 % , 95 % confidence interval [ CI ] around the difference 0.1%-19.6 % ) and were more likely to undergo percutaneous coronary intervention ( 32 % v. 24 % , 95 % CI around the difference 0.1%-16.2 % ) within 30 days of first admission to hospital . Patients with depression on admission had higher rates of a composite of cardiac complications , including recurrent ischemia , infa rct ion or congestive heart failure during their first stay in hospital or readmission for angina , recurrent acute myocardial infa rct ion , congestive heart failure or arrhythmia ( adjusted hazard ratio 1.4 , 95 % CI 1.05 - 1.86 ) , compared with patients who were not depressed on admission . After 1 year , death rates were higher among patients who were depressed at admission ( 30 patients , 16 % ) compared with nondepressed patients ( 28 patients , 8 % ) , although the difference was not statistically significant ( hazard ratio 1.3 , 95 % CI 0.59 - 3.05 ) . INTERPRETATION Depressive symptoms are common after acute myocardial infa rct ion and are associated with a slight increase in risk of in-hospital catheterization and angiography and readmission because of cardiac complications . Death was infrequent , with no statistically significant difference between the 2 groups Background —Women have an unexplained worse outcome after myocardial infa rct ion ( MI ) compared with men in many studies . Depressive symptoms predict adverse post-MI outcomes and are more prevalent among women than men . We examined whether depressive symptoms contribute to women ’s worse outcomes after MI . Methods and Results —In a prospect i ve multicenter study ( PREMIER ) , 2411 ( 807 women ) MI patients were enrolled . Depressive symptoms were assessed with the Patient Health Question naire . Outcomes included 1-year rehospitalization , presence of angina using the Seattle Angina Question naire , and 2-year mortality . Multivariable analyses were used to evaluate the association between sex and these outcomes , adjusting for clinical characteristics . The depressive symptoms score was added to the models to evaluate whether it attenuated the association between sex and outcomes . Depressive symptoms were more prevalent in women compared with men ( 29 % versus 18.8 % , P<0.001 ) . After adjusting for demographic factors , comorbidities , and MI severity , women had a mildly higher risk of rehospitalization ( hazard ratio , 1.20 ; 95 % CI , 1.04 to 1.40 ) , angina ( odds ratio , 1.32 ; 95 % CI , 1.00 to 1.75 ) , and mortality ( hazard ratio , 1.27 ; 95 % CI , 0.98 to 1.64 ) . After adding depressive symptoms to the multivariable models , the relationship further declined toward the null , particularly for rehospitalization ( hazard ratio , 1.14 ; 95 % CI , 0.98 to 1.34 ) and angina ( odds ratio , 1.22 ; 95 % CI , 0.91 to 1.63 ) , whereas there was little change in the estimate for mortality ( hazard ratio , 1.24 ; 95 % CI , 0.95 to 1.62 ) . Depressive symptoms were significantly associated with each of the study outcomes with a similar magnitude of effect in both women and men . Conclusions —A higher prevalence of depressive symptoms in women modestly contributes to their higher rates of rehospitalization and angina compared with men but not mortality after MI . Our results support the recent recommendations of improving recognition of depressive symptoms after MI BACKGROUND Depression is associated with an increased risk for mortality after acute myocardial infa rct ion ( MI ) . The purpose of this study was to determine whether low heart rate variability ( HRV ) mediates the effect of depression on mortality . METHODS Twenty-four-hour ambulatory electrocardiograms were obtained from 311 depressed patients with a recent acute MI who were enrolled in the Enhancing Recovery in Coronary Heart Disease ( ENRICHD ) clinical trial and from 367 nondepressed patients who met the ENRICHD medical inclusion criteria . St and ard HRV indexes were extracted from the recordings . RESULTS The log of very low-frequency ( LnVLF ) power , an index of HRV derived from power spectral analysis of the electrocardiogram signal ( 0.0033 - 0.04 Hz [ in milliseconds squared ] ) , was lower in the depressed than in the nondepressed patients ( P<.001 ) . There were 47 deaths ( 6.1 % ) during a 30-month follow-up . After adjusting for potential confounders , the depressed patients remained at higher risk for all-cause mortality compared with the nondepressed patients ( hazard ratio , 2.8 ; 95 % confidence interval [ CI ] , 1.4 - 5.4 ; P<.003 ) . When LnVLF power was entered into the model , the hazard ratio for depression dropped to 2.1 ( 95 % CI , 1.1 - 4.2 ; P = .03 ) . The proportion of the risk for depression attributable to LnVLF power was 0.27 ( 95 % CI , 0.23 - 0.31 ; P<.001 ) . CONCLUSIONS Low HRV partially mediates the effect of depression on survival after acute MI . This finding helps to clarify the physiological mechanisms underlying depression 's role as a risk factor for mortality in patients with coronary heart disease . It also raises the possibility that treatments that improve both depression and HRV might also improve survival in these patients Background — The American Heart Association ( AHA ) statement has recommended routine screening for depression in coronary artery disease with a 2-stage implementation of the Patient Health Question naire ( PHQ ) . Because there is little evidence on feasibility , accuracy , and impact of such a program on depression recognition in coronary patients , the AHA recommendation has met substantial debate and criticism . Methods and Results — Before the AHA statement was released , the Mid America Heart and Vascular Institute ( MAHVI ) had implemented a depression screening protocol for patients with acute myocardial infa rct ion that was virtually identical to the AHA recommendations . To ( 1 ) evaluate this MAHVI quality improvement initiative , ( 2 ) compare MAHVI depression recognition rates with those of other hospitals , and ( 3 ) examine health care providers ' implementation feedback , we compared the results of the MAHVI screening program with data from a parallel prospect i ve acute myocardial infa rct ion registry and interviewed MAHVI providers . Depressive symptoms ( PHQ-2 , PHQ-9 ) were assessed among 503 MAHVI acute myocardial infa rct ion patients and compared with concurrent depression assessment s among 3533 patients at 23 US centers without a screening protocol . A qualitative summary of providers ' suggestions for improvement was also generated . A total of 135 ( 26.8 % ) eligible MAHVI patients did not get screened . Among screened patients , 90.9 % depressed ( PHQ-9 ≥10 ) patients were recognized . The agreement between the screening and registry data using the full PHQ-9 was 61.5 % for positive cases ( PHQ-9 ≥10 ) but only 35.6 % for the PHQ-2 alone . Although MAHVI had a slightly higher overall depression recognition rate ( 38.3 % ) than other centers not using a depression screening protocol ( 31.5 % ) , the difference was not statistically significant ( P=0.31 ) . Staff feedback suggested that a single-stage screening protocol with continuous feedback could improve compliance . Conclusions — In this early effort to implement a depression screening protocol , a large proportion of patients did not get screened , and only a modest impact on depression recognition rates was realized . Simplifying the protocol by using the PHQ-9 alone and providing more support and feedback may improve the rates of depression detection and treatment CONTEXT Depression and low perceived social support ( LPSS ) after myocardial infa rct ion ( MI ) are associated with higher morbidity and mortality , but little is known about whether this excess risk can be reduced through treatment . OBJECTIVE To determine whether mortality and recurrent infa rct ion are reduced by treatment of depression and LPSS with cognitive behavior therapy ( CBT ) , supplemented with a selective serotonin reuptake inhibitor ( SSRI ) antidepressant when indicated , in patients enrolled within 28 days after MI . DESIGN , SETTING , AND PATIENTS R and omized clinical trial conducted from October 1996 to April 2001 in 2481 MI patients ( 1084 women , 1397 men ) enrolled from 8 clinical centers . Major or minor depression was diagnosed by modified Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria and severity by the 17-item Hamilton Rating Scale for Depression ( HRSD ) ; LPSS was determined by the Enhancing Recovery in Coronary Heart Disease Patients ( ENRICHD ) Social Support Instrument ( ESSI ) . R and om allocation was to usual medical care or CBT-based psychosocial intervention . INTERVENTION Cognitive behavior therapy was initiated at a median of 17 days after the index MI for a median of 11 individual sessions throughout 6 months , plus group therapy when feasible , with SSRIs for patients scoring higher than 24 on the HRSD or having a less than 50 % reduction in Beck Depression Inventory scores after 5 weeks . MAIN OUTCOME MEASURES Composite primary end point of death or recurrent MI ; secondary outcomes included change in HRSD ( for depression ) or ESSI scores ( for LPSS ) at 6 months . RESULTS Improvement in psychosocial outcomes at 6 months favored treatment : mean ( SD ) change in HRSD score , -10.1 ( 7.8 ) in the depression and psychosocial intervention group vs -8.4 ( 7.7 ) in the depression and usual care group ( P<.001 ) ; mean ( SD ) change in ESSI score , 5.1 ( 5.9 ) in the LPSS and psychosocial intervention group vs 3.4 ( 6.0 ) in the LPSS and usual care group ( P<.001 ) . After an average follow-up of 29 months , there was no significant difference in event-free survival between usual care ( 75.9 % ) and psychosocial intervention ( 75.8 % ) . There were also no differences in survival between the psychosocial intervention and usual care arms in any of the 3 psychosocial risk groups ( depression , LPSS , and depression and LPSS patients ) . CONCLUSIONS The intervention did not increase event-free survival . The intervention improved depression and social isolation , although the relative improvement in the psychosocial intervention group compared with the usual care group was less than expected due to substantial improvement in usual care patients BACKGROUND Depression predicts worse outcomes after myocardial infa rct ion ( MI ) , but whether its time course in the month following MI has prognostic importance is unknown . Our objective was to evaluate the prognostic importance of transient , new , or persistent depression on outcomes at 6 months after MI . METHODS In a prospect i ve registry of acute MI ( Prospect i ve Registry Evaluating outcomes after Myocardial Infa rct ion : Events and Recovery [ PREMIER ] ) , depressive symptoms were measured in 1873 patients with the Patient Health Question naire ( PHQ ) during hospitalization and 1 month after discharge and were classified as transient ( only at baseline ) , new ( only at 1 month ) , or persistent ( at both times ) . Outcomes at 6 months included ( 1 ) all-cause rehospitalization or mortality and ( 2 ) health status ( angina , physical limitation , and quality of life using the Seattle Angina Question naire ) . RESULTS Compared with nondepressed patients , all categories of depression were associated with higher rehospitalization or mortality rates , more frequent angina , more physical limitations , and worse quality of life . The adjusted hazard ratios for rehospitalization or mortality were 1.34 , 1.71 , and 1.42 for transient , new , and persistent depression , respectively ( all P<.05 ) . Corresponding odds ratios were 1.62 , 2.73 , and 2.64 ( all P<.01 ) for angina and 1.69 , 2.25 , and 3.27 ( all P<.05 ) for physical limitation . Depressive symptoms showed a stronger association with health status compared with traditional measures of disease severity . CONCLUSION Depressive symptoms after MI , irrespective of whether they persist , subside , or newly develop in the first month after hospitalization , are associated with worse outcomes after MI CONTEXT Depressive symptoms predict adverse cardiovascular outcomes in patients with coronary heart disease , but the mechanisms responsible for this association are unknown . OBJECTIVE To determine why depressive symptoms are associated with an increased risk of cardiovascular events . DESIGN AND PARTICIPANTS The Heart and Soul Study is a prospect i ve cohort study of 1017 out patients with stable coronary heart disease followed up for a mean ( SD ) of 4.8 ( 1.4 ) years . SETTING Participants were recruited between September 11 , 2000 , and December 20 , 2002 , from 12 outpatient clinics in the San Francisco Bay Area and were followed up to January 12 , 2008 . MAIN OUTCOME MEASURES Baseline depressive symptoms were assessed using the Patient Health Question naire ( PHQ ) . We used proportional hazards models to evaluate the extent to which the association of depressive symptoms with subsequent cardiovascular events ( heart failure , myocardial infa rct ion , stroke , transient ischemic attack , or death ) was explained by baseline disease severity and potential biological or behavioral mediators . RESULTS A total of 341 cardiovascular events occurred during 4876 person-years of follow-up . The age-adjusted annual rate of cardiovascular events was 10.0 % among the 199 participants with depressive symptoms ( PHQ score > or = 10 ) and 6.7 % among the 818 participants without depressive symptoms ( hazard ratio [ HR ] , 1.50 ; 95 % confidence interval , [ CI ] , 1.16 - 1.95 ; P = .002 ) . After adjustment for comorbid conditions and disease severity , depressive symptoms were associated with a 31 % higher rate of cardiovascular events ( HR , 1.31 ; 95 % CI , 1.00 - 1.71 ; P = .04 ) . Additional adjustment for potential biological mediators attenuated this association ( HR , 1.24 ; 95 % CI , 0.94 - 1.63 ; P = .12 ) . After further adjustment for potential behavioral mediators , including physical inactivity , there was no significant association ( HR , 1.05 ; 95 % CI , 0.79 - 1.40 ; P = .75 ) . CONCLUSION In this sample of out patients with coronary heart disease , the association between depressive symptoms and adverse cardiovascular events was largely explained by behavioral factors , particularly physical inactivity Background — Data on the possible association between depressive disorders and inflammatory markers are scarce and inconsistent . We investigated whether subjects with depressive mood had higher levels of a wide range of inflammatory markers involved in coronary heart disease ( CHD ) incidence and examined the contribution of these inflammatory markers and depressive mood to CHD outcome . Methods and Results —We built a nested case-referent study within the Prospect i ve Epidemiological Study of Myocardial Infa rct ion ( PRIME ) study of healthy middle-aged men from Belfast and France . We considered the baseline plasma sample from 335 future cases ( angina pectoris , nonfatal myocardial infa rct ion , coronary death ) and 670 matched controls ( 2 controls per case ) . Depressive mood characterized men whose baseline depression score ( 13-item modification of the Welsh depression subscale ) was in the fourth quartile ( mean score , 5.75 ; range , 4 to 12 ) . On average , men with depressive mood had 46 % , 16 % , and 10 % higher C-reactive protein , interleukin-6 , and intercellular adhesion molecule-1 levels , respectively , independently of case-control status , social characteristics , and classic cardiovascular risk factors ; no statistical difference was found for fibrinogen . The odds ratios of depressive mood for CHD were 1.35 ( 95 % CI , 1.05 to 1.73 ) in univariate analysis and 1.50 ( 95 % CI , 1.04 to 2.15 ) after adjustment for social characteristics and classic cardiovascular risk factors . The latter odds ratio remained unchanged when each inflammatory marker was added separately , and in this analysis , each inflammatory marker contributed significantly to CHD event risk . Conclusions —These data support an association of depressive mood with inflammatory markers and suggest that depressive mood is related to CHD even after adjustment for these inflammatory markers Although depression is clearly associated with increased mortality after acute myocardial infa rct ion , there is a paucity of data examining the impact of depression on patients with unstable angina ( UA ) . We analyzed the relation between depressive symptoms and all-cause mortality in patients with UA who were enrolled in a prospect i ve multicenter study of depression and acute coronary syndrome ( ACS ) . Depressive symptoms were measured with the Beck Depression Inventory ( BDI ) within 1 week of the ACS event , and patients were selected for a BDI score 0 to 4 or ≥ 10 . Our sample included 209 patients with UA , with 104 ( 50 % ) having a BDI score ≥ 10 . Proportional hazards analyses adjusted for variables including left ventricular ejection fraction , Global Registry of Acute Coronary Events risk score , and Charlson co-morbidity index . In multivariable analyses , a BDI score ≥ 10 was associated with increased risk of 42-month all-cause mortality ( hazard ratio 2.04 , 95 % confidence interval 1.20 to 3.46 , p = 0.008 ) compared to a BDI score 0 to 4 . In conclusion , our results confirm and extend previous evidence linking depression to worse outcomes in UA and suggest that interventions that address depression may be worth examining across the spectrum of risk in ACS OBJECTIVE To examine the independent impact of major depression and hostility on mortality rate at 6 months and 12 months after discharge from the hospital in patients with a myocardial infa rct ion . METHOD Three hundred thirty-one patients were prospect ively evaluated for depression with a modified version of the National Institute of Mental Health Diagnostic Interview Schedule for major depressive episode . The Cook Medley Hostility Scale data were analyzed by chi(2 ) procedures for nominal and categoric data , and Student t test was used for continuous data types . RESULTS Depression was a significant predictor of death at 12 months ( P = . 04 ) but not at 6 months ( P = .08 ) . Hostility was not found to be a predictor of death at 6 months or 12 months . CONCLUSIONS Major depression in patients hospitalized after myocardial infa rct ion is a significant univariable predictor of death at 12 months , although it was not a statistically significant predictor after adjusting for other variables . Hostility is not a predictor of death . Prospect i ve studies are needed to determine the impact of aggressive treatment of depression on post-myocardial infa rct ion survival Objective : The Enhancing Recovery in Coronary Heart Disease study was a multicenter clinical trial in which patients with depression and /or low perceived social support after an acute myocardial infa rct ion were r and omly assigned to an intervention consisting of cognitive behavior therapy and , in some cases , sertraline , or to usual care . There was no difference in survival between the groups . A possible reason why the intervention failed to affect survival is that too many patients with mild , transient depression were enrolled . Another is that some patients died too soon to complete the intervention . This analysis evaluates whether there was a difference in late ( ie , ≥6 months after the myocardial infa rct ion ) mortality among initially depressed patients who had a Beck Depression Inventory score ≥10 and a past history of major depression , and who completed the 6-month post-treatment assessment . It also examines the relationship between change in depression and late mortality . Methods : Out of the 1,165 ( 47 % ) of the Enhancing Recovery in Coronary Heart Disease study participants who met our criteria , 57 died in the first 6 months , and 858 ( 409 usual care , 449 intervention ) completed the 6-month assessment . Cox regression was used to analyze survival . Results : The intervention did not affect late mortality . However , intervention patients whose depression did not improve were at higher risk for late mortality than were patients who responded to treatment . Conclusions : Patients whose depression is refractory to cognitive behavior therapy and sertraline , two st and ard treatments for depression , are at high risk for late mortality after myocardial infa rct ion OBJECTIVE The reporting of depressive symptoms following myocardial infa rct ion may be confounded by complaints originating from the myocardial infa rct ion . Therefore , it is difficult to estimate the effects of post-myocardial infa rct ion depression and its treatment on cardiovascular prognosis . The authors ' goal was to study the relationship between depressive symptom dimensions following myocardial infa rct ion and both somatic health status and prospect i ve cardiovascular prognosis . METHOD In two studies of myocardial infa rct ion patients ( N=494 and 1,972 ) , the Beck Depression Inventory was used to determine the dimensional structure of depressive symptoms following myocardial infa rct ion . Three symptom dimensions-somatic/affective , cognitive/affective , and appetitive-were compared with baseline left ventricular ejection fraction , Charlson comorbidity index , Killip class , and previous myocardial infa rct ion . The relationship between depressive symptom dimensions and prospect i ve cardiovascular mortality and cardiac-related readmissions was also examined ( mean follow-up duration = 2.5 years ) . RESULTS Somatic/affective symptoms were associated with poor health status ( left ventricular ejection fraction , Charlson comorbidity index , Killip class , and previous myocardial infa rct ion ) and predicted cardiovascular mortality and cardiac events . Cognitive/affective symptoms were only marginally associated with somatic health status and not with cardiovascular death and cardiac events . Appetitive symptoms were related to somatic health status but did not predict cardiovascular death or cardiac events . CONCLUSIONS Somatic/affective depressive symptoms following myocardial infa rct ion were confounded by somatic health status yet were prospect ively associated with cardiac prognosis even after somatic health status was controlled . Cognitive/affective depressive symptoms were only marginally related to health status and not to cardiac prognosis . These findings suggest that treatment of depression following myocardial infa rct ion might improve cardiovascular prognosis when it reduces somatic/affective symptoms OBJECTIVE To determine if the diagnosis of major depression in patients hospitalized following myocardial infa rct ion ( MI ) would have an independent impact on cardiac mortality over the first 6 months after discharge . DESIGN Prospect i ve evaluation of the impact of depression assessed using a modified version of the National Institute of Mental Health Diagnostic Interview Schedule for major depressive episode . Cox proportional hazards regression was used to evaluate the independent impact of depression after control for significant clinical predictors in the data set . SETTING A large , university-affiliated hospital specializing in cardiac care , located in Montreal , Quebec . PATIENTS All consenting patients ( N = 222 ) who met established criteria for MI between August 1991 and July 1992 and who survived to be discharged from the hospital . Patients were interviewed between 5 and 15 days following the MI and were followed up for 6 months . There were no age limits ( range , 24 to 88 years ; mean , 60 years ) . The sample was 78 % male . PRIMARY OUTCOME MEASURE Survival status at 6 months . RESULTS By 6 months , 12 patients had died . All deaths were due to cardiac causes . Depression was a significant predictor of mortality ( hazard ratio , 5.74 ; 95 % confidence interval , 4.61 to 6.87 ; P = .0006 ) . The impact of depression remained after control for left ventricular dysfunction ( Killip class ) and previous MI , the multivariate significant predictors of mortality in the data set ( adjusted hazard ratio , 4.29 ; 95 % confidence interval , 3.14 to 5.44 ; P = .013 ) . CONCLUSION Major depression in patients hospitalized following an MI is an independent risk factor for mortality at 6 months . Its impact is at least equivalent to that of left ventricular dysfunction ( Killip class ) and history of previous MI . Additional study is needed to determine whether treatment of depression can influence post-MI survival and to assess possible underlying mechanisms BACKGROUND Individual symptoms of post-myocardial infa rct ion ( MI ) depression may be differentially associated with cardiac prognosis , in which somatic/affective symptoms appear to be associated with a worse cardiovascular prognosis than cognitive/affective symptoms . These findings hold important implication s for treatment but need to be replicated before conclusions regarding treatment can be drawn . We therefore examined the relationship between depressive symptom dimensions following MI and both disease severity and prospect i ve cardiac prognosis . METHOD Patients ( n=473 ) were assessed on demographic and clinical variables and completed the Beck Depression Inventory ( BDI ) within the first week of hospital admission for acute MI . Depressive symptom dimensions were associated with baseline left ventricular ejection fraction ( LVEF ) and prospect i ve cardiac death and /or recurrent MI . The average follow-up period was 2.8 years . RESULTS Factor analysis revealed two symptom dimensions -- somatic/affective and cognitive/affective -- in the underlying structure of the BDI , identical to previous results . There were 49 events attributable to cardiac death ( n=23 ) or recurrent MI ( n=26 ) . Somatic/affective ( p=0.010 ) but not cognitive/affective ( p=0.153 ) symptoms were associated with LVEF and cardiac death/recurrent MI . When controlling for the effects of previous MI and LVEF , somatic/affective symptoms remained significantly predictive of cardiac death/recurrent MI ( hazard ratio 1.31 , 95 % confidence interval 1.02 - 1.69 , p=0.038 ) . Previous MI was also an independent predictor of cardiac death/recurrent MI . CONCLUSIONS We confirmed that somatic/affective , rather than cognitive/affective , symptoms of depression are associated with MI severity and cardiovascular prognosis . Interventions to improve cardiovascular prognosis by treating depression should be targeted at somatic aspects of depression OBJECTIVE Depression following myocardial infa rct ion is associated with an increased risk of cardiac events , but attempts to alter cardiovascular prognosis by providing antidepressive treatment have not been successful . This may be because of the limited effects of antidepressive treatment on depression itself . The authors assessed whether nonresponse to treatment of post-myocardial infa rct ion depression is associated with new cardiac events . METHOD The authors made a subgroup analysis of a multicenter r and omized , clinical trial on the effects of antidepressant treatment for post-myocardial infa rct ion depression . Patients were enrolled in double-blind , placebo-controlled treatment with mirtazapine ( 30 mg/day ) and , in the case of insufficient treatment response after 8 weeks , open treatment with citalopram . Patients were classified as responders to antidepressants ( at least 50 % reduction in Hamilton Depression Rating scale [ HAM-D ] score or HAM-D score < 9 at 24 weeks ) ( N=43 ) or as nonresponders ( N=27 ) and compared to untreated control subjects ( N=98 ) on cardiac events ( cardiac mortality or cardiac-related hospital admission ) after 24 weeks post-r and om assignment and within 18 months after index infa rct ion . RESULTS The event rate was 25.6 % among nonresponders , 11.2 % among untreated control subjects , and 7.4 % among responders . In relation to untreated comparison subjects , nonresponders had a hazard ratio of 2.66 for new cardiovascular events , which remained after the authors controlled for potential confounders ( hazard ratio=2.92 ) . CONCLUSIONS This study provides further preliminary evidence that nonresponse to treatment of post-myocardial infa rct ion depression may be associated with cardiac events . Efforts should be dedicated to developing more effective treatments for depressed patients with myocardial infa rct ion BACKGROUND In patients with acute myocardial infa rct ion ( AMI ) , depressive symptoms increase the risk for cardiac events . Recently , the S allele of the serotonin transporter ( 5-HTT ) gene-linked polymorphic region was shown to reduce transcription of this gene and thus reduce serotonin reuptake , and this allele is linked with depressive symptoms as well as other psychiatric diseases . However , the influence of the S allele on depressive symptoms and cardiac events after AMI is unclear . METHODS To investigate whether the S allele was associated with depressive symptoms and cardiac events after AMI , we prospect ively examined depressive symptoms and new cardiac events in 2509 genotyped patients with AMI . RESULTS Depressive symptoms were more common in patients with the S allele than in those without it ( 48.3 % vs 35.0 % , P = .02 ) . Multivariate analysis revealed that the S allele was independently associated with depressive symptoms ( odds ratio 2.19 , 95 % confidence interval [ CI ] 1.21 - 3.98 , P = .01 ) . Cardiac events ( cardiac death , revascularization , heart failure , reinfa rct ion , arrhythmia , and unstable angina ) were more frequent in patients with the S allele than in those without it ( 31.3 % vs 22.3 % , P = .046 ) . Multivariate Cox regression analysis revealed an association between the S allele and an increased risk for cardiac events ( hazard ratio [ HR ] 1.69 , 95 % CI 1.03 - 2.78 , P = .04 ) . However , the HR became insignificant after an adjustment for depressive symptoms ( HR 1.30 , 95 % CI 0.84 - 2.01 , P = .24 ) . CONCLUSIONS The S allele in the 5-HTT gene-linked polymorphic region is associated with an increased risk for subsequent cardiac events , which is mediated , at least in part , by the depressive symptoms in patients after AMI A relationship between cigarette smoking and major depressive disorder was suggested in previous work involving nonr and omly selected sample s. We conducted a test of this association , employing population -based data ( n = 3213 ) collected between 1980 and 1983 in the St Louis Epidemiologic Catchment Area Survey of the National Institute of Mental Health . A history of regular smoking was observed more frequently among individuals who had experienced major depressive disorder at some time in their lives than among individuals who had never experienced major depression or among individuals with no psychiatric diagnosis . Smokers with major depression were also less successful at their attempts to quit than were either of the comparison groups . Gender differences in rates of smoking and of smoking cessation observed in the larger population were not evident among the depressed group . Furthermore , the association between cigarette smoking and major depression was not ubiquitous across all psychiatric diagnoses . Other data are cited indicating that when individuals with a history of depression stop smoking , depressive symptoms and , in some cases , serious major depression may ensue CONTEXT Major depressive disorder ( MDD ) after acute coronary syndrome ( ACS ) is associated with an increased mortality rate . We observed the participants of the Sertraline Antidepressant Heart Attack R and omized Trial ( SADHART ) to establish features of MDD associated with long-term mortality . OBJECTIVES To determine whether the following variables were associated with long-term mortality : baseline depression severity , previous MDD episodes , onset of MDD before or after the ACS event , 6 months of sertraline hydrochloride therapy , and mood improvement independent of treatment . DESIGN SADHART was a double-blind , placebo-controlled , r and omized trial comparing the safety and antidepressant efficacy of sertraline vs placebo in 369 patients with ACS who met criteria for MDD . The trial was completed in June 2000 , and follow-up for vital status was completed in September 2007 . SETTING Academic research . PARTICIPANTS SADHART participants . MAIN OUTCOME MEASURES Vital status was determined in 361 participants ( 97.8 % ) during a median follow-up of 6.7 years . RESULTS During the study , 75 participants ( 20.9 % ) died . Neither previous episodes of MDD , nor onset before or after the index ACS , nor an initial 6 months of sertraline treatment was associated with long-term mortality . Cox proportional hazards regression models showed that baseline MDD severity ( hazard ratio , 2.30 ; 95 % confidence interval , 1.28 - 4.14 ; P < .006 ) and failure of MDD to improve substantially during treatment with either sertraline or placebo ( hazard ratio , 2.39 ; 95 % confidence interval , 1.39 - 2.44 ; P < .001 ) were strongly and independently associated with long-term mortality . Marked improvement in depression ( Clinical Global Impression-Improvement subscale score of 1 ) was associated with improved adherence to study medication . CONCLUSIONS Severity of MDD measured within a few weeks of hospitalization for ACS or failure of MDD to improve during the 6 months following ACS predicted more than a doubling of mortality over 6.7 years of follow-up . Because persistent depression increases mortality and decreases medication adherence , physicians need to aggressively treat depression and be diligent in promoting adherence to guideline cardiovascular drug therapy Previous research has focused on the relation between depression after an acute coronary syndrome ( ACS ) and subsequent cardiac morbidity and mortality . However , the relation between depression and quality of life during recovery remains unclear . We investigated whether symptoms of depression during hospitalization for ACS or the course of depressive symptoms after ACS predict physical health status 12 months after ACS , controlling for physical health status at the time of the ACS . This was a prospect i ve study of 425 patients with ACS assessed with the Beck Depression Inventory ( BDI ) and Short Form 12 ( SF-12 ) Health Survey during hospitalization and 12 months later . Linear regression was used to assess the relation between in-hospital BDI scores and BDI symptom trajectory after ACS with physical health status 12 months later , controlling for baseline physical health status , age , gender , Killip class , history of acute myocardial infa rct ion , and cardiac diagnosis . Baseline BDI scores predicted 12-month physical health ( p < 0.001 ) . Compared with nondepressed patients , only patients with persistent symptoms of depression were at risk for poorer physical health . Patients with newly developed depressive symptoms after ACS were at slightly increased risk for worsened physical health ( p = 0.060 ) , whereas patients with transient depressive symptoms were not at increased risk . In conclusion , these results underscore the importance of assessing depression at the time of ACS and on an ongoing basis OBJECTIVES The purpose of this research was to study whether incident and non-incident depression after myocardial infa rct ion ( MI ) are differentially associated with prospect i ve fatal and non-fatal cardiovascular events . BACKGROUND Post-MI depression is defined as the presence of depression after MI . However , only about one-half of post-MI depressions represent an incident episode , whereas the other half are ongoing or recurrent depressions . We investigated whether these subtypes differ in cardiovascular prognosis . METHODS A total of 468 MI patients were assessed for the presence of an International Classification of Diseases-10 depressive disorder during the year after index MI . A comparison was made on new cardiovascular events ( mean follow up : 2.5 years ) between patients with no , incident , and non-incident post-MI depression by survival analysis . RESULTS Compared with non-depressed patients , those with an incident depression had an increased risk of cardiovascular events ( hazard ratio [ HR ] 1.65 ; 95 % confidence interval [ CI ] 1.02 to 2.65 ) , but not those with a non-incident depression ( HR 1.12 ; 95 % CI 0.61 to 2.06 ) , which remained after controlling for confounders ( HR 1.76 ; 95 % CI 1.06 to 2.93 and HR 1.39 ; 95 % CI 0.74 to 2.61 , respectively ) . CONCLUSIONS Only patients with incident post-MI depression have an impaired cardiovascular prognosis . A more detailed subtyping of post-MI depression is needed , based on an integration of recent findings on the differential impact of depression symptom profiles and personality on cardiac outcomes OBJECTIVE The purpose of this study was to assess gender differences in the impact of depression on 1-year cardiac mortality in patients hospitalized for an acute myocardial infa rct ion ( MI ) . METHODS Secondary analysis was performed on data from two studies that used the Beck Depression Inventory ( BDI ) to assess depression symptoms during hospitalization : a prospect i ve study of post-MI risk and a r and omized trial of psychosocial intervention ( control group only ) . The sample included 896 patients ( 283 women ) who survived to discharge and received usual posthospital care . Multivariate logistic regression analysis was used to assess the risk of 1-year cardiac mortality associated with baseline BDI scores . RESULTS There were 290 patients ( 133 women ) with BDI scores > or = 10 ( at least mild to moderate symptoms of depression ) ; 8.3 % of the depressed women died of cardiac causes in contrast to 2.7 % of the nondepressed . For depressed men , the rate of cardiac death was 7.0 % in contrast to 2.4 % of the nondepressed . Increased BDI scores were significantly related to cardiac mortality for both genders [ the odds ratio for women was 3.29 ( 95 % confidence interval ( CI ) = 1.02 - 10.59 ) ; for men , the odds ratio was 3.05 ( 95 % CI = 1.29 - 7.17 ) ] . Control for other multivariate predictors of mortality in the data set ( age , Killip class , the interactions of gender by non-Q wave MI , gender by left ventricular ejection fraction , and gender by smoking ) did not change the impact of the BDI for either gender . CONCLUSIONS Depression in hospital after MI is a significant predictor of 1-year cardiac mortality for women as well as for men , and its impact is largely independent of other post-MI risks The frequency of ventricular premature complexes and the degree of impairment of left ventricular ejection fraction are major predictors of cardiac mortality and sudden death in the year after acute myocardial infa rct ion . Recent studies have implicated psychosocial factors , including depression , the interaction of social isolation and life stress , and type A-B behavior pattern , as predictors of cardiac events , controlling for known parameters of disease severity . However , results tend not to be consistent and are sometimes contradictory . The present investigation was design ed to test the predictive association between biobehavioral factors and clinical cardiac events . This evaluation occurred in the context of a prospect i ve clinical trial , the Cardiac Arrhythmia Pilot Study ( CAPS ) . Five-hundred two patients were recruited with greater than or equal to 10 ventricular premature complexes/hour or greater than or equal to 5 episodes of nonsustained ventricular tachycardia , recorded 6 to 60 days after a myocardial infa rct ion . Baseline behavioral studies , conducted in approximately 66 % of patients , included psychosocial question naires of anxiety , depression , social desirability and support , and type A-B behavior pattern . In addition , blood pressure and pulse rate reactivity to a portable videogame was assessed . The primary outcome was scored on the basis of mortality or cardiac arrest . Results indicated that the type B behavior pattern , higher levels of depression and lower pulse rate reactivity to challenge were significant risk factors for death or cardiac arrest , after adjusting statistically for a set of known clinical predictors of disease severity . The implication of these results for future research relating behavioral factors to cardiac endpoints is discussed Mild to moderate levels of depressive symptoms as characterized by Beck Depression Inventory ( BDI ) scores of > or = 10 are associated with decreased survival after acute myocardial infa rct ion ( AMI ) . We investigated whether lower levels of depressive symptoms are also associated with increased mortality risk after AMI . We prospect ively studied 285 patients with AMI who survived to discharge for evidence , at the time of hospitalization , of a DSM-IIIR mood disorder ( using a structured clinical interview ) and for symptoms of depression ( using the BDI ) . The overall mortality rate at 4 months was 6.7 % . Multiple logistic regression ( chi-square 35.79 , p < or = 0.001 ) revealed that the independent predictors of mortality were : age > or = 65 years , left ventricular ejection fraction < 35 % , diabetes mellitus , and any depression ( DSM-IIIR mood disorder or BDI > or = 10 ) present at the time of AMI . Among patients > or = 65 years old with left ventricular ejection fraction < 35 % , the 4-month mortality was 12 % . However , in this same group , those with any depression at the time of AMI had a 4-month mortality of 50 % ( relative risk 4.1 , p = 0.01 ) . Among patients aged > or = 65 years , the mortality according to BDI scale grouping 0 to 3 , 4 to 9 , and 10 + was 2.6 % , 17.1 % , and 23.3 % , respectively ( p < 0.002 ) . Highest mortality rates were observed in patients with most severe depressive symptoms . However , compared with those without depression , higher mortality was also observed at very low levels of depressive symptoms ( BDI 4 to 9 ) not generally considered clinical ly significant and below the level usually considered predictive of increased post-AMI mortality Objective : Controversy remains over whether the association between depression and mortality in patients with acute coronary syndrome ( ACS ) is confounded by incomplete adjustment for measures of known prognostic markers . We assessed a ) whether depression was associated with the most comprehensive empirically derived index of clinical mortality predictors : the Global Registry of Acute Coronary Events ( GRACE ) risk score for predicting 6-month mortality after discharge for ACS ; and b ) whether depression remained an independent predictor of all-cause mortality after adjustment for the GRACE score and left ventricular dysfunction . Methods : We surveyed prospect ively 457 patients with ACS ( aged 25–92 years ; 41 % women , 13 % black , and 11 % Hispanic ) , hospitalized between May 2003 and June 2005 . Depressive symptoms were assessed with the Beck Depression Inventory ( BDI ) and diagnosis of major depressive disorder ( MDD ) was made by a structured psychiatric interview , within 1 week of hospitalization . Results : Despite differences in individual components of the GRACE score between depressed and nondepressed participants , neither depression measure was associated with overall GRACE score . For participants with MDD , the mean ± st and ard deviation GRACE score was 84 ± 33 , compared with 92 ± 31 for those without MDD ( p = .09 ) . Using Cox proportional hazards regression analysis , MDD and depressive symptom severity each predicted mortality after controlling for GRACE score and left ventricular dysfunction ( adjusted hazard ratio for MDD = 2.51 ; 95 % Confidence Interval = 1.45–4.37 ) . Conclusion : Depression is not simply a marker of clinical indicators that predict all-cause mortality after ACS . This strengthens the assertion that there is something unique in the association between depression and post-ACS prognosis , independent of known prognostic markers . ACS = acute coronary syndrome ; MI = myocardial infa rct ion ; LVEF = left ventricular ejection fraction ; GRACE = Global Registry of Acute Coronary Events ; BDI = Beck Depression Inventory ; MDD = major depressive disorder OBJECTIVE To compare the survival of elderly patients hospitalized for acute myocardial infa rct ion who have emotional support with that of patients who lack such support , while controlling for severity of disease , comorbidity , and functional status . DESIGN A prospect i ve , community-based cohort study . SETTING Two hospitals in New Haven , Connecticut . PATIENTS Men ( n = 100 ) and women ( n = 94 ) 65 years of age or more hospitalized for acute myocardial infa rct ion between 1982 and 1988 . MEASUREMENTS Social support , age , gender , race , education , marital status , living arrangements , presence of depression , smoking history , weight , and physical function were assessed prospect ively using question naires . The presence of congestive heart failure , pulmonary edema , and cardiogenic shock ; the position of infa rct ion ; in-hospital complications ; and history of myocardial infa rct ion were assessed using medical records . Comorbidity was defined using an index based on the presence of eight conditions . RESULTS Of 194 patients , 76 ( 39 % ) died in the first 6 months after myocardial infa rct ion . In multiple logistic regression analyses , lack of emotional support was significantly associated with 6-month mortality ( odds ratio , 2.9 ; 95 % CI , 1.2 to 6.9 ) after controlling for severity of myocardial infa rct ion , comorbidity , risk factors such as smoking and hypertension , and sociodemographic factors . CONCLUSIONS When emotional support was assessed before myocardial infa rct ion , it was independently related to risk for death in the subsequent 6 months OBJECTIVES This study examined the impact of depressive symptoms and social support on 2-year sudden cardiac death ( SCD ) risk , controlling for fatigue symptoms . METHODS Myocardial infa rct ion ( MI ) patients ( N = 671 ) participating in the Canadian Amiodarone Myocardial Infa rct ion Arrhythmia Trial completed measures of depression , hostility , and social support . RESULTS After controlling for significant biological predictors , psychosocial predictors of increased SCD risk in the survival analysis were greater social network contacts ( RR = 1.04 ; 95 % CI = 1.01 - 1.06 ; p < .007 ) , lower social participation ( RR = 0.98 ; 95 % CI = 0.96 - 1.00 ; p < .05 ) , and , in placebo-treated patients , elevated depressive symptoms ( RR = 2.45 ; 95 % CI = 1.14 - 5.35 ; p < .02 ) . Fatigue was associated with SCD ( RR = 1.31 ; 95 % CI = 1.11 - 1.53 ; p < .001 ) , and , when included in the model , diminished the influence of depression ( RR = 1.73 ; 95 % CI = 0.75 - 3.98 ; p = .20 ) . When the cognitive-affective depressive symptoms were examined separately from somatic symptoms , there was a trend for an association between cognitive-affective symptoms and SCD in placebo-treated patients after controlling for fatigue ( RR = 1.09 ; 95 % CI = 0.99 - 1.19 , p < .06 ) . CONCLUSIONS Symptoms of depression and fatigue overlap in patients with MI . The trend for the cognitive-affective symptoms of depression to be associated with SCD risk , even after controlling for dyspnea/fatigue , suggests that the association between depression and mortality after AMI can not be entirely explained as a confound of cardiac-related fatigue . The independent contribution of social participation suggests a role of both depressive symptomatology and social factors in influencing mortality risk after MI OBJECTIVES The purpose of this study was to examine prospect ively whether inflammation explains the relationship between depression and cardiovascular disease ( CVD ) . BACKGROUND It is unclear whether inflammation is a mechanism linking depression to CVD . METHODS We measured C-reactive protein ( CRP ) and interleukin (IL)-6 in 559 women with suspected coronary ischemia who completed the Beck Depression Inventory ( BDI ) at baseline and were followed over 5.9 years . We considered indicators of past and current depression to classify women into 3 groups : 1 ) depression , having both elevated depressive symptoms ( BDI > or = 10 ) and a previous diagnosis of depression requiring treatment ; 2 ) possible depression , having either indicator but not both ; and 3 ) no depression , having neither indicator of depression . The main outcome was incidence of CVD events ( hospital stays for nonfatal myocardial infa rct ion , stroke , congestive heart failure , and CVD-related mortality ) . RESULTS Compared with women without depression , women with depression had a 70 % higher CRP ( p = 0.0008 ) and a 25 % higher IL-6 ( p = 0.04 ) , whereas women with possible depression had 30 % higher CRP ( p = 0.02 ) and 28 % higher IL-6 ( p = 0.01 ) . Depression was a significant predictor of CVD ( hazard ratio 2.58 , p = 0.0009 ) , but possible depression was not ( hazard ratio 1.12 , p = 0.68 ) . Adjustment for other patient factors did not substantially affect the results . Addition of CRP decreased the estimate for depression by 13 % and addition of IL-6 decreased it by 4 % . Both depression and inflammatory biomarkers remained independent predictors of outcome . CONCLUSIONS Despite their robust association with depression , inflammatory biomarkers explain only a small portion of the association between depression and CVD incidence The ENRICHD clinical trial , which compared an intervention for depression and social isolation to usual care , failed to decrease the rate of mortality and recurrent acute myocardial infa rct ion ( AMI ) in post-AMI patients . One explanation for this is that depression was not associated with increased mortality in these patients . The purpose of this study was to determine if depression was associated with an increased risk of mortality in a sub sample of the ENRICHD trial 's depressed patients compared with a group of nondepressed patients recruited for an ancillary study . Three hundred fifty-eight depressed patients with an acute AMI from the ENRICHD clinical trial and 408 nondepressed patients who met the ENRICHD medical inclusion criteria were followed for up to 30 months . There were 47 deaths ( 6.1 % ) and 57 nonfatal AMIs ( 7.4 % ) . After adjusting for other risk factors , depressed patients were at higher risk for all-cause mortality ( hazard ratio 2.4 , 95 % confidence interval 1.2 to 4.7 ) but not for nonfatal recurrent infa rct ion ( hazard ratio 1.2 , 95 % confidence interval 0.7 to 2.0 ) compared with nondepressed patients . In conclusion , depression was an independent risk factor for death after AMI , but it did not have a significant effect on mortality until nearly 12 months after the acute event , nor did it predict nonfatal recurrent infa rct ion Depression during hospitalization for myocardial infa rct ion ( MI ) is associated with subsequent mortality , but whether this risk persisted long term is not well studied . This study was performed to determine whether depression during hospitalization for MI , which predicted mortality at 4 months , predicted mortality 8 years later . This was a prospect i ve observational study of 284 hospitalized patients with MI . Major depression and dysthymia were assessed using structured interview for Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition , and depressive symptoms , using the Beck Depression Inventory . Mortality was determined using the Social Security Death Index . Mean age during MI hospitalization was 64.8 years , 43.0 % of patients were women , 66.7 % had hypertension , and 35.7 % had diabetes mellitus . Any depression ( major depression , dysthymia , and /or Beck Depression Inventory score > or = 10 ) was present in 76 patients ( 26.8 % ) . The 8-year mortality rate was 47.9 % ( 136 deaths ) . Any depression at the time of MI was not associated with mortality at 8 years in unadjusted ( hazard ratio 1.25 , 95 % confidence interval 0.87 to 1.81 , p = 0.22 ) or multivariate models ( hazard ratio 0.76 , 95 % confidence interval 0.47 to 1.24 , p = 0.27 ) . In conclusion , depression after MI was associated with increased short-term mortality , but its relation with mortality over time appeared to wane , at least in a group of older patients who had multiple co-morbidities Since the mid-1980s , an impressive body of epidemiological research has examined links between depression and coronary heart disease ( CHD ) . Depression is more common in patients with CHD than in those without heart disease , with ≥20 % of hospitalised patients after a myocardial infa rct ion ( MI ) meeting modified psychiatric criteria for major depressive disorder (MDD).1 While available data suggest that depression rates are lower in patients with stable CHD than in hospitalised patients , depression is still more common than in the general community . Depression is associated with increased chances of developing CHD in apparently healthy subjects . In patients with CHD depression predicts cardiac admissions and death , increased healthcare costs and utilisation of services.2 3 There is evidence of an increased cardiac risk associated with measures of depression symptoms as well as with diagnosed MDD , and of a dose – response relationship between depression severity and prognosis in patients with CHD . Many plausible biological explanations have been suggested . The quantity and strength of the epidemiological data is comparable to that leading to the general acceptance of several other cardiac risk factors . Why , then , is depression not considered a major risk factor ? Should it be ? Updating our previous systematic review s3 4 to include publications through 15 September 2009 , we found reports based on prospect i ve studies , using established measures of depression published from at least 28 distinct cohorts each made up of more than 500 people who were apparently CHD-free at baseline , and at least 59 separate studies that examined depression as a predictor of risk for poor prognosis in sample s of at least 100 patients with known CHD . The great majority of the 130 articles based on these studies document statistically significant relationships between depression and cardiac outcomes , and most , but not all , demonstrate that these relationships remain significant after statistical adjustment for a 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 |
12,732 | 17,630,270 | Intensified patient care appears to be the most promising intervention in terms of improved adherence to lipid-lowering drugs . | OBJECTIVE Poor patient adherence to lipid-lowering medication is a major contributory factor in the lack of success in treating hyperlipidaemia .
The objective of this review was to assess the effect of adherence-enhancing interventions for lipid-lowering medication . | The value of mailed educational videotapes as a means of enhancing compliance with drug therapy was studied . Members of a health maintenance organization with a pharmacy cl aim for benazepril , metoprolol , simvastatin , or transdermal estrogen were r and omly assigned to a study group or a control group . Subjects in the study group were mailed one of four videotape programs giving information on the drug prescribed and the inferred disease state . Control subjects received no educational material s. Subjects were enrolled from July 1 , 1993 , through January 2 , 1994 . Refill data were collected from July 1 , 1993 , through April 1 , 1994 . The medication possession ratio ( MPR ) was calculated as the total number of days ' supply of a drug obtained by a member divided by the number of days between the time of enrollment and April 1 , 1994 , or the date the member was terminated from the plan . A subject was deemed compliant if his or her MPR was > or = 0.80 . There were no significant differences in mean MPRs between the study group ( n = 1993 ) and the control group ( n = 2253 ) . None of the mean MPRs was > or = 0.80 , although 44 % of control subjects and 46 % of study -group subjects were compliant . Of 97 respondents to a survey mailed to a r and omly selected subset of the study group , almost 87 % reported that they had viewed the videotapes , and of these subjects , about 88 % said they found them very useful or somewhat useful . A one-time mailing of videotapes to patients , with no individual follow-up , did not increase compliance with the medications monitored OBJECTIVE : Noxious adverse effects frequently limit patient acceptance of niacin and bile acid sequestrants ( BAS ) , first-line agents in the management of hypercholesterolemia . The purpose of this study was to determine whether telephone contacts from a healthcare professional could improve drug adherence and tolerance in patients prescribed these medications . PATIENTS AND METHODS : This was a r and omized , single-blind trial of telephone contacts vs. no intervention in patients with hyperlipidemia who were prescribed either niacin or BAS in a large , Veterans Affairs , lipid clinic . Patients r and omized to telephone contact ( n=81 ) received weekly calls from a trained healthcare professional during the first month of drug therapy . Counseling regarding adverse effects , and prescriptions to overcome minor adverse effects , were provided as needed to patients during the telephone contact . RESULTS : Significant differences were not observed between groups in the drug discontinuance rate , adherence assessed by two independent methods , or in the final dosage of medication ingested . CONCLUSIONS : Telephone contacts do not improve either adherence or tolerance to niacin or BAS . Alternative approaches to enhance acceptance of these medications requires further evaluation BACKGROUND Noncompliance with cardiovascular therapy and prevention initiatives is well documented . OBJECTIVES The purpose of the First Myocardial Infa rct ion ( MI ) Risk Reduction Program , an open-label drug registry involving mainly primary -care patients at increased risk of a first MI , was to examine the effects of postal and telephone reminders , as well as demographic and other baseline characteristics , on patient self-reported compliance with pravastatin treatment . A second objective was to determine whether regimen adherence was associated with the adoption of other lifestyle modifications recommended to decrease the risk of coronary artery disease . METHODS Patients with risk scores of > or = 4 on a scale of -1 to + 16 for men and -1 to + 17 for women on the First Heart Attack Risk Test were considered to be at increased risk of a first MI and eligible for enrollment in the registry program . An elevated total cholesterol level despite dietary interventions was an additional inclusion criterion . Patients were prospect ively r and omized ( 4:1 ) to either an intervention involving postal and telephone reminders ( about coronary risk reduction and medication compliance ) , which were sent during the first 2 months of pravastatin treatment , or usual care . Both groups received reminder postcards at 4 and 5 months , in addition to counseling by physicians about coronary risk reduction . At 3 and 6 months ( or study discontinuation ) , patients completed and mailed to the program-coordinating center question naires concerning compliance with care , including current use of prescribed pravastatin , as well as self-reported adoption of other lifestyle modifications , such as changing eating habits , losing weight , increasing physical activity , and /or quitting smoking . Compliance with pravastatin therapy and with these coronary risk-reducing behaviors was also assessed by physicians at the 3-month follow-up visit . RESULTS A total of 10,335 patients were in the intervention group , and 2765 received usual care . The 2 groups were well balanced at baseline with respect to age , race , and total cholesterol values . Neither early reminders nor baseline patient characteristics were significantly associated with reported pravastatin compliance rates , which were approximately 79 % overall . However , according to self-reports at 6 months , regimen compliance was associated with the adoption of other coronary risk-reducing behaviors . CONCLUSIONS The results of this study suggest that early telephone and postal reminders do not improve compliance with drug treatment or with recommended coronary risk-reducing behaviors During the last quarter of the third year of follow-up in the Helsinki Heart Study , compliance to medication was measured in 1739 patients with digoxin used as a marker substance , capsule counting and a compliance question naire . The estimates for good and poor compliers were found to be highly dependent on the method and the cut-off points chosen for the compliance allocation . The methods studied here were more reliable for the detection of poor rather than good compliance . In the poor compliance group , defined with the use of the digoxin marker , there was 39 % of subjects who returned less than 5 % of their capsule dosage or reported a deviation less than 5 % . In the good compliance group , defined by the digoxin marker , only 11.8 % of patients either returned or reported a deviation of at least 25 % of their dose . The compliance was better when measured by the question naire than by capsule counting . The size of the poor compliance group , defined by the use of the digoxin marker , was as large as a group who had returned at least 27 % of their capsule dose and a group who had reported a deviation of 11 % or more from their dosing schedule . The size of the group allocated to the good compliance category by the use of the digoxin marker was equivalent in size to a group of patients who had returned less than 15 % of their prescribed dose or reported a deviation of less than 6 % from their prescription . When the strictest criteria for the combination of all three methods were used , 57 % of subjects were classified as good and 31 % as poor compliers to medication in the third year of the primary prevention trial design ed to reduce the incidence of coronary heart disease STUDY OBJECTIVE To assess the accuracy of patient-kept diaries relative to electronic monitoring of compliance with isosorbide dinitrate prescribed 3 times/day for ischemic heart disease . DESIGN Unblinded , prospect i ve , three-phase study . METHODS Patients with coronary artery disease prescribed isosorbide dinitrate 3 times/day were asked to record the time of administration of each dose in a pocket diary while being monitored for compliance with a computerized Medication-Event Monitoring System ( MEMS-4 ) vial that electronically recorded the date and time the vial was opened . RESULTS Sixty-eight stable out patients with documented coronary artery disease who were prescribed isosorbide dinitrate 3 times/day were evaluated . Based on a prospect ively chosen definition including a nitrate-free period , the mean ( + /-SD ) overall compliance rates were 71 % ( + /-30 ) versus 55 % ( + /-32 ) for the patient-kept diaries and the MEMS vials respectively ( p = 0.001 ) . The concordance between patient-kept diaries and MEMS data indicate that 67 % of patients overestimate their compliance when using a self-recording tool . An average of 30 % of diary entries were in error compared with the MEMS vial recordings . CONCLUSIONS Patient-kept diaries statistically overestimate actual compliance relative to that determined by MEMS devices . Given the prevalence of the use of diaries as the predominant tool on which research ers depend to document compliance with study drugs , our findings suggest that this practice should be reevaluated specifically when the time of the dose and documentation of administration are critical to qualifying the outcome of drug therapy . Such is the case with isosorbide dinitrate use in patients with ischemic heart disease . Furthermore , the overall poor compliance documented in this study suggests that the utility of isosorbide dinitrate prescribed 3 times/day be reevaluated as a clinical ly effective antianginal drug The efficacy , safety , and tolerability of a moderate dose , 3-drug lipid-lowering regimen were evaluated among 29 male patients with hyperlipidemia and coronary artery disease . In an initial 12-month phase , regular niacin , 500 mg qid , lovastatin , 20 mg bid , and colestipol , 10 g/bid , were given with dose adjustment for lipid targets and side effects . This was followed by 2 r and om sequence crossover phases ( 8 months each ) alternating regular niacin with a polygel controlled-release formulation of niacin for use in this regimen . Lipid , lipoprotein , apoprotein , and clinical chemistry determinations were obtained at baseline , during the initial phase , at the 2 crossover phases , and at 6 weeks after therapy . A final question naire queried specific side effects and overall preferences . Low-/high-density lipoprotein ( LDL/HDL ) changed from means of 215/46 mg/dl at baseline , to 94/59 mg/dl after run-in , to 85/52 mg/dl after 8 months of controlled-release niacin , and to 98/56 mg/dl after 8 months of regular niacin ( regular niacin vs controlled-release niacin , p < 0.005/<0.05 ) . The target of LDL < or = 100 mg/dl was achieved at 8 months by 83 % of these patients with controlled-release niacin and by 52 % with regular niacin ( p < 0.01 ) . Compliance was 95 % with controlled-release niacin versus 85 % with regular niacin ( p < 0.001 ) . The controlled-release niacin and regular niacin regimens did not differ in terms of uric acid , glucose , insulin , or asparate aminotransferase levels . Overall , 21 % of patients called the 3 drugs " very easy " and 72 % " fairly easy " to take . The controlled-release niacin-containing regimen was preferred by 21 patients and the regular niacin by 4 . In conclusion , these regimens achieve striking lipid changes among hyperlipidemic patients . Controlled release is the preferred niacin preparation in terms of LDL reduction , compliance , patient preference , and achieving the National Cholesterol Education Program guideline of LDL < or = 100 mg/dl . The 2 niacin preparations did not differ in evidence of toxicity This r and omized , controlled trial evaluated the impact of personalized follow-up on compliance rates in high-risk patients receiving combination lipid-lowering therapy over 2 years . A r and om sample of 30 patients 7 - 30 days after cardiac surgery had baseline fasting low-density lipoprotein levels higher than 130 mg/dl . All patients received lovastatin 20 mg/day and colestipol 5 g twice/day . Weekly telephone contact was made with each patient for 12 weeks . Short- and long-term compliance was assessed by pill and packet counts and refill records . Compliance and lipid profile results were significantly better in the intervention group ( p<0.05 ) up to 2 years after the start of therapy than in the control group for all parameters except high-density lipoprotein . However , this effect was not apparent during the first 12 weeks of therapy . Short-term telephone follow-up favorably affected compliance and lipid profile results up to 2 years after start of therapy OBJECTIVE To analyse the efficacy of health education ( HE ) through group session with postal back-up in furthering compliance with therapy for Lipaemia . DESIGN Controlled clinical trial , with r and om distribution . SETTING Primary care . PATIENTS 110 patients with Hypercholesterolaemia , with new diagnoses or not in treatment , in which medical treatment with statins was indicated as a start or change in medication . INTERVENTIONS They were distributed in two groups at r and om , with observation four months after being included in the study and appointments after one , two and four months . 1 . Control group ( CG ) : 55 patients who received HE from their family doctor . 2 . Intervention group ( IG ) : 55 patients whose HE was monitored : a ) a group HE session and b ) back-up by letter sent to their homes . MEASUREMENTS AND RESULTS Patients whose consumption was between 80 and 110 % of the amount prescribed were defined as compliant . The pill count was recorded . The percentages of compliant patients and mean compliance ( chi squared , Student 's t ) were analysed . 108 individuals , 41 men and 67 women , completed the trial . There was no difference between the two groups as to age , sex , evolution time , number of diseases and dosage of medicines consumed . 71.3 % were compliant ( CI , 62.8 - 79.8 % ) , CG = 61.8 % and IG 81.1 % ( p < 0.05 ) . The mean percentage of compliance was 86.1 + /- 14.3 overall , with CG = 83.8 + /- 14 and IG 88.5 + /- 14 ( p = NS ) . CONCLUSIONS The HE intervention with a group session and postal back-up is an effective way of improving therapeutic compliance in cases of hypercholesterolaemia 1 . To control the bias caused by poor medication compliance in the Helsinki Heart Study three methods were used to measure medication compliance during the total 5 years follow up time : continuous capsule counting , semi-annual urine gemfibrozil analysis and a new method , the digoxin marker at the end of the third and fifth study years . 2 . The serum lipid responses to gemfibrozil treatment varied linearly with the level of medication compliance , e.g. the mean change in serum total cholesterol was -11.4 % among those whose apparent capsule consumption was greater than or equal to 90 % of the scheduled dosage , -11.2 % among those who had greater than or equal to 90 % positive gemfibrozil analyses and -11.4 % among those with good compliance according to both digoxin marker measurements . In contrast the mean serum cholesterol change was only -0.02 % if the mean daily capsule count was less than 50 % , -1.7 % with fewer than 50 % positive gemfibrozil analyses and -1.1 % if the result was poor in both digoxin marker measurements . 3 . Combining the different method findings revealed that the cholesterol changes tended to be small in those groups who had poor compliance classification measured by any of the methods , even if the other results showed good compliance |
12,733 | 23,235,655 | Log dose-response data revealed linear dose-related effects on blood total cholesterol , low-density lipoprotein (LDL)-cholesterol and triglycerides .
There was no significant dose-related effects of atorvastatin on blood high-density lipoprotein (HDL)-cholesterol .
Blood total cholesterol , LDL-cholesterol and triglyceride lowering effect of atorvastatin was dependent on dose . | BACKGROUND Atorvastatin is one of the most widely prescribed drugs and the most widely prescribed statin in the world .
It is therefore important to know the dose-related magnitude of effect of atorvastatin on blood lipids .
OBJECTIVES To quantify the dose-related effects of atorvastatin on blood lipids and withdrawals due to adverse effects ( WDAE ) . | BACKGROUND Inflammation and oxidative stress are associated with atrial fibrillation ( AF ) . Statins have antioxidant and anti-inflammatory properties . We tested if atorvastatin reduced AF recurrence after DC cardioversion ( CV ) by modifying systemic oxidative stress and inflammation ( NCT00252967 ) . METHODS AND RESULTS In a r and omized , double-blinded , placebo-controlled trial , patients with atrial fibrillation/flutter ( AF ) were r and omized to receive either atorvastatin 80 mg ( n = 33 ) or placebo ( n = 31 ) before CV . Treatment was continued for 12 months or until AF recurred . Serum oxidative stress markers ( ratios of oxidized to reduced glutathione and cysteine , derivatives of reactive oxygen species , isoprostanes ) and inflammatory markers ( high-sensitivity C- reactive protein [ hs-CRP ] , interleukin-6 [ IL-6 ] , interleukin-1β[IL-1β ] , tumor necrosis factor alpha [ TNFα ] ) were measured at baseline and on follow-up . AF recurred in 22 ( 66.7 % ) of atorvastatin and 26 ( 83.9 % ) of placebo group ( P = 0.2 ) . The adjusted hazard ratio of having recurrence on atorvastatin versus on placebo was 0.99 ( 95 % CI : 0.98 - 1.01 , P = 0.3 ) . There was no significant difference in the time to recurrence using Kaplan-Meier survival estimates ( median [ IR ] : 29 [ 2 - 145 ] days versus 22 [ 7 - 70 ] days , P = 0.9 ) . Although no significant effect was seen on oxidative stress , 2 of 4 inflammatory markers , IL-6 ( adjusted OR : 0.59 , 95 % CI : 0.35 - 0.97 , P = 0.04 ) and hs-CRP ( adjusted OR : 0.59 , 95 % CI : 0.37 - 0.95 , P = 0.03 ) were significantly lowered with atorvastatin . Cholesterol levels significantly decreased with atorvastatin ( P = 0.03 ) . CONCLUSIONS High-dose atorvastatin did not reduce the recurrence of AF after CV . It reduced selective markers of inflammation without affecting systemic oxidative stress . Failure of atorvastatin to prevent AF recurrence may be due to its failure to affect oxidative stress In a multicenter , open-label trial , 696 Hispanic patients with low-density lipoprotein ( LDL ) cholesterol levels > or = 130 and < or = 300 mg/dl and triglyceride levels < 400 mg/dl at medium or high risk of coronary heart disease were r and omized to receive 10 or 20 mg of rosuvastatin or 10 or 20 mg of atorvastatin for 6 weeks . At week 6 , LDL cholesterol was decreased more by 10 mg of rosuvastatin than by 10 mg of atorvastatin ( 45 % vs 36 % , p < 0.0001 ) and more by 20 mg of rosuvastatin than by 20 mg of atorvastatin ( 50 % vs 42 % , p < 0.0001 ) . Significantly greater decreases were also observed with rosuvastatin for total cholesterol , non-high-density lipoprotein cholesterol , apolipoprotein-B , and lipid ratios compared with milligram-equivalent doses of atorvastatin . Overall , National Cholesterol Education Program Adult Treatment Program III LDL cholesterol goals were achieved by 78 % and 88 % of patients who received 10 and 20 mg of rosuvastatin and by 60 % and 73 % of patients who received 10 and 20 mg of atorvastatin , respectively . Among high-risk patients , the LDL cholesterol goal of < 100 mg/dl was achieved by 74 % and 91 % of patients who received 10 and 20 mg of rosuvastatin and by 52 % and 62 % who received 10 and 20 mg of atorvastatin , respectively . All treatments were well tolerated , and adverse events were similar in frequency across treatment groups . No cases of myopathy or rhabdomyolysis were observed . In conclusion , treatment with rosuvastatin and atorvastatin produced beneficial lipid changes in this group of Hispanic patients that appear comparable in magnitude to those observed in primarily non-Hispanic white study population s. These benefits were accompanied by a favorable safety profile that suggests no concerns particular to this population Statin therapy may target both hypercholesterolemia and cholestasis in primary biliary cirrhosis ( PBC ) . However , little is known about the efficacy and safety of statins in PBC . The aim of this single‐center study was therefore to prospect ively examine the effects of atorvastatin on serum markers of cholestasis , aminotransferases , and lipid and bile acid metabolism as well as inflammatory and immunological markers in patients with PBC . Fifteen patients with early‐stage PBC and an incomplete biochemical response to ursodeoxycholic acid ( UDCA ) therapy ( defined as alkaline phosphatase 1.5‐fold above the upper limit of normal after 1 year ) were treated with atorvastatin 10 mg/day , 20 mg/day , and 40 mg/day for 4 weeks , respectively . Serum levels of alkaline phosphatase increased during atorvastatin 20 mg and 40 mg ( P < 0.05 ) , whereas leucine aminopeptidase and γ‐glutamyltransferase remained unchanged . No statistical differences in overall serum ALT , AST , bilirubin , and IgM levels were observed . However , atorvastatin was discontinued in 1 out of 15 patients because of ALT 2‐fold above baseline , and 2 patients showed ALT elevations 3‐fold above the upper limit of normal at the end of the atorvastatin treatment period . Serum total cholesterol and low‐density lipoprotein cholesterol levels decreased by 35 % and 49 % , respectively ( P < 0.001 ) . Precursors of cholesterol bio synthesis ( lanosterol , desmosterol , lathosterol ) showed a similar pattern . No changes in serum bile acid levels and composition were observed during treatment . Conclusion : Atorvastatin does not improve cholestasis in PBC patients with an incomplete biochemical response to UDCA but effectively reduces serum cholesterol levels . ( HEPATOLOGY 2007 . OBJECTIVE The primary objective of this study was to assess the cost-effectiveness of the most commonly prescribed doses of rosuvastatin , atorvastatin , simvastatin , and pravastatin for managing various lipid parameters in patients with hypercholesterolemia over a 1-year time horizon from a Canadian health care perspective . METHODS Incremental cost-effectiveness ratios ( ICERs ) were estimated for br and ed rosuvastatin compared with br and ed atorvastatin , generic simvastatin , and generic pravastatin in patients with hypercholesterolemia in terms of percent reduction in low-density lipoprotein cholesterol ( LDL-C ) and total cholesterol (TC)/high-density lipoprotein cholesterol ( HDL-C ) ratio , as well as in TC , HDL-C , triglycerides ( TG ) , apolipoprotein ( Apo ) B , the ApoB/ApoA-I ratio , and attainment of the Canadian LDL-C goal . The pharmacoeconomic model was constructed for a 1-year time horizon using efficacy data from a r and omized , open-label trial including 2268 adults and the wholesale acquisition costs of br and ed rosuvastatin and atorvastatin and generic simvastatin and pravastatin in British Columbia . RESULTS The most commonly prescribed doses of each of the 4 statins in British Columbia were as follows : rosuvastatin 10 mg ( 75.8 % of all rosuvastatin doses ) ; atorvastatin 10 and 20 mg ( 46.4 % and 35.3 % , respectively , of all atorvastatin doses ) ; simvastatin 20 and 40 mg ( 42.5 % and 31.8 % , respectively , of all simvastatin doses ) ; and pravastatin 20 and 40 mg ( 55.0 % and 34.1 % , respectively , of all pravastatin doses ) . Rosuvastatin 10 mg was dominant ( ie , was more effective at a lower cost ) relative to atorvastatin 10 and 20 mg , simvastatin 20 and 40 mg , and pravastatin 40 mg in terms of reductions in LDL-C , TC/ HDL-C ratio , TC , ApoB , and ApoB/ApoA-I ratio , increases in HDL-C , and attainment of the LDL-C goal . Compared with pravastatin 20 mg , the ICER per percent reduction in LDL-C , TC/HDL-C ratio , TC , TG , ApoB , or ApoB/ApoA-I or increase in HDL-C ranged from $ 3.89 to $ 26.07 ; the value for 1 additional patient achieving the LDL-C goal was $ 419.75 . When the statin doses were aggregated based on the Canadian statin-utilization pattern , rosuvastatin was dominant relative to atorvastatin on all effectiveness measures evaluated . When rosuvastatin was compared with generic simvastatin and pravastatin , the annual costs for 1 additional patient achieving the LDL-C goal were $ 144.51 and $ 373.91 , respectively . Based on the sensitivity analysis , rosuvastatin was associated with the highest probability of cost-effectiveness compared with the other statins over a broad range of monetary values per unit of clinical effect . CONCLUSION When percent changes in lipid parameters and rates of LDL-C goal attainment were considered in patients with hypercholesterolemia in British Columbia , rosuvastatin 10 mg was more cost-effective than the most frequently used doses of atorvastatin ( 10 and 20 mg ) , generic simvastatin ( 20 and 40 mg ) , and generic pravastatin ( 20 and 40 mg ) The primary objective of this 6-week , parallel-group , open-label , r and omized , multicenter trial was to compare rosuvastatin with atorvastatin , pravastatin , and simvastatin across dose ranges for reduction of low-density lipoprotein ( LDL ) cholesterol . Secondary objectives included comparing rosuvastatin with comparators for other lipid modifications and achievement of National Cholesterol Education Program Adult Treatment Panel III and Joint European Task Force LDL cholesterol goals . After a dietary lead-in period , 2,431 adults with hypercholesterolemia ( LDL cholesterol > or = 160 and < 250 mg/dl ; triglycerides < 400 mg/dl ) were r and omized to treatment with rosuvastatin 10 , 20 , 40 , or 80 mg ; atorvastatin 10 , 20 , 40 , or 80 mg ; simvastatin 10 , 20 , 40 , or 80 mg ; or pravastatin 10 , 20 , or 40 mg . At 6 weeks , across-dose analyses showed that rosuvastatin 10 to 80 mg reduced LDL cholesterol by a mean of 8.2 % more than atorvastatin 10 to 80 mg , 26 % more than pravastatin 10 to 40 mg , and 12 % to 18 % more than simvastatin 10 to 80 mg ( all p < 0.001 ) . Mean percent changes in high-density lipoprotein cholesterol in the rosuvastatin groups were + 7.7 % to + 9.6 % compared with + 2.1 % to + 6.8 % in all other groups . Across dose ranges , rosuvastatin reduced total cholesterol significantly more ( p < 0.001 ) than all comparators and triglycerides significantly more ( p < 0.001 ) than simvastatin and pravastatin . Adult Treatment Panel III LDL cholesterol goals were achieved by 82 % to 89 % of patients treated with rosuvastatin 10 to 40 mg compared with 69 % to 85 % of patients treated with atorvastatin 10 to 80 mg ; the European LDL cholesterol goal of < 3.0 mmol/L was achieved by 79 % to 92 % in rosuvastatin groups compared with 52 % to 81 % in atorvastatin groups . Drug tolerability was similar across treatments Background : Coronary heart disease ( CHD ) is the number one cause of death in Western societies . Elevated levels of plasma low-density lipoprotein ( LDL ) cholesterol and triglycer ides ( TG ) increase the risk for CHD . 3-Hydroxy-3-methylglutaryl conenzyme A ( HMG- CoA ) reductase inhibitors effectively reduce plasma cholesterol levels in patients with hypercholesterolemia . This study assesses the safety and dose-related effects of atorvastatin calcium on lipoprotein fractions in patients with LDL cholesterol levels between 160 mg/dL ( 4.1 mM ) and 250 mg/dL ( 6.5 mM ) or less and TG levels of 400 mg/dL ( 4.5 mM ) or less . Methods and Results : Sixty-five patients were enrolled in a 6-week , r and omized , placebo- controlled , parallel-group study . Patients received placebo or atorvastatin 10 , 20 , 40 , 60 , or 80 mg once daily . Adjusted mean decreases in LDL cholesterol for patients receiving ator vastatin 10 , 20 , 40 , 60 , and 80 mg were 37 % , 42 % , 50 % , 52 % , and 59 % , respectively , com pared with a mean increase of 0.3 % for patients receiving placebo ; the differences between each of the atorvastatin dose groups and placebo were statistically significant ( P = .0001 ) . Total cholesterol , triglycerides , and apolipoprotein B were significantly reduced in atorva statin groups ( P = .0001 ) . Adverse events were similar in the placebo and atorvastatin treat ment groups . No patient had a serious adverse event or withdrew because of an adverse event during this study . Conclusions : Atorvastatin effectively lowered plasma LDL cholesterol , triglycerides , and apoB levels in a dose-related manner . Atorvastatin was well tolerated in hyperlipidemic patients over a 6-week period Atherogenesis involves the migration of leukocytes into vascular subendothelial space , a process mediated by endothelial and leukocyte cell adhesion molecules . Endothelial molecules are assessed indirectly via serum levels , but leukocyte molecules can be assessed directly . We have therefore hypothesized that leukocyte adhesion molecules are altered to a greater degree in hypercholesterolemia than serum endothelial adhesion molecules . We examined 29 subjects with hypercholesterolemia and 27 controls at baseline and after 12 weeks of atorvastatin treatment ( 20 mg/day ) . Expression of leukocyte integrins CD11a , CD11b , CD18 , and CD49d and of L-selectin was measured by flow cytometry . Serum ICAM-1 , E-selectin and von Willebr and factor were measured by ELISA . Expression of leukocyte adhesion molecules was significantly higher in patients at baseline than in the controls , except for CD11a . Expression significantly decreased after atorvastatin in most adhesion molecules except for CD11b . In contrast , there was no effect of hypercholesterolemia and /or atorvastatin on the serum endothelial molecules . Leukocyte but not endothelial adhesion molecules were influenced by hypercholesterolemia and by lipid lowering treatment . Leukocyte molecules may therefore be a more sensitive marker of atherogenesis than endothelial molecules . Our results support the role of increased leukocyte adhesiveness in atherogenesis Objective : To compare the effects of combination niacin extended-release + simvastatin ( NER/S ) versus atorvastatin alone on apolipoproteins and lipid fractions in a post hoc analysis from SUPREME , a study which compared the lipid effects of niacin extended-release + simvastatin and atorvastatin in patients with hyperlipidemia or mixed dyslipidemia . Patients and methods : Patients ( n = 137 ) with dyslipidemia ( not previously receiving statin therapy or having discontinued any lipid-altering treatment 4–5 weeks prior to the study ) received NER/S ( 1000/40 mg/day for four weeks , then 2000/40 mg/day for eight weeks ) or atorvastatin 40 mg/day for 12 weeks . Median percent changes in apolipoprotein ( apo ) A-1 , apo B , and the apo B : A-I ratio , and nuclear magnetic resonance lipoprotein subclasses from baseline to week 12 were compared using the Wilcoxon rank-sum test and Fisher ’s exact test . Results : NER/S treatment produced significantly greater percent changes in apo A-I and apo B : A-I , and , at the final visit , apo B < 80 mg/dL was attained by 59 % versus 33 % of patients , compared with atorvastatin treatment ( P = 0.003 ) . NER/S treatment result ed in greater percent reductions in calculated particle numbers for low-density lipoprotein ( LDL , 52 % versus 43 % ; P = 0.022 ) , small LDL ( 55 % versus 45 % ; P = 0.011 ) , very low-density lipoprotein ( VLDL ) and total chylomicrons ( 63 % versus 39 % ; P < 0.001 ) , and greater increases in particle size for LDL ( 2.7 % versus 1.0 % ; P = 0.007 ) and VLDL ( 9.3 % versus 0.1 % ; P < 0.001 ) , compared with atorvastatin . Conclusion : NER/S treatment significantly improved apo A-I levels and the apo B : A-I ratio , significantly lowered the number of atherogenic LDL particles and VLDL and chylomicron particles , and increased the mean size of LDL and VLDL particles , compared with atorvastatin BACKGROUND Heart failure has been associated with impaired endothelial function , increased inflammatory process and elevated oxidative stress status . Both statins and vitamin E separately improve endothelial function in patients with hypercholesterolemia and /or advanced atherosclerosis . AIM To evaluate the effect of atorvastatin alone or in combination with vitamin E on endothelial function and serum levels of interleukin-6 ( IL-6 ) , tumor necrosis factor alpha ( TNF-alpha ) and vascular cells adhesion molecule ( sVCAM-1 ) in patients with ischemic heart failure . METHODS Thirty-eight male patients with ischemic cardiomyopathy were r and omly divided into three groups and received either atorvastatin 10 mg/day ( n = 14 ) , a combination of atorvastatin 10 mg/day plus vitamin E 400 IU/day ( n = 12 ) , or no statin or antioxidant treatment ( n=12 , controls ) for 4 weeks . Forearm blood flow ( FBF ) was measured using venous occlusion strain-gauge plethysmography . Forearm vasodilatory response to reactive hyperemia ( RH% ) or to nitrate ( NTG% ) was defined as the percent change of FBF from rest to the maximum flow during reactive hyperemia or after nitrate administration , respectively . RESULTS RH% was significantly improved in both the atorvastatin-treated ( p < 0.01 ) and atorvastatin plus vitamin E groups ( p < 0.05 ) , but the increase was significantly higher in the atorvastatin-treated group ( p < 0.05 ) . Serum levels of IL-6 , TNF-alpha and sVCAM-1 were decreased in the atorvastatin-treated group ( p < 0.05 for all ) , but remained unaffected in the other two groups ( p = NS for all ) . CONCLUSIONS Low dose atorvastatin treatment improves endothelial function and reduces the expression of proinflammatory cytokines and adhesion molecules in patients with ischemic heart failure , an effect partly depressed by vitamin BACKGROUND This double-blind , multicenter , r and omized trial compared rosuvastatin and atorvastatin for reducing low-density lipoprotein cholesterol ( LDL-C ) in adults with hypercholesterolemia and a high risk of coronary heart disease . METHODS After a 6-week dietary lead-in period , patients with LDL-C levels > or = 160 and < 250 mg/dL and triglyceride levels < or = 400 mg/dL were r and omly assigned to 24 weeks ' treatment in 1 of 3 groups , each with forced dose titrations at 12 and 18 weeks . Starting and titrated doses for each group were rosuvastatin 5 , 20 , and 80 mg ( n = 127 ) ; rosuvastatin 10 , 40 , and 80 mg ( n = 128 ) ; and atorvastatin 10 , 40 , and 80 mg ( n = 128 ) . RESULTS At 24 weeks , LDL-C was reduced significantly more with 80 mg rosuvastatin ( combined rosuvastatin group ) than with atorvastatin 80 mg ( 60 % vs 52 % [ P < .001 ] ) . At 12 weeks , rosuvastatin 5 and 10 mg reduced LDL-C significantly more than atorvastatin 10 mg ( 40 % [ P < .01 ] , 47 % [ P < .001 ] vs 35 % ) . At 18 weeks , LDL-C reductions were also significantly greater in both rosuvastatin groups than in the atorvastatin group ( 52 % [ P < .01 ] , 59 % [ P < .001 ] vs 47 % ) . Consequently , more patients receiving rosuvastatin achieved LDL-C goals . Total cholesterol , high-density lipoprotein cholesterol ( HDL-C ) , non-HDL-C , apolipoproteins B and A-I , and all lipid ratios were more favorably modified by rosuvastatin at 24 weeks ( P < .01 ) . Effects of the 2 agents on triglycerides were similar . CONCLUSIONS Rosuvastatin was more efficacious than atorvastatin in modifying lipids in patients with hypercholesterolemia and a high coronary heart disease risk STUDY OBJECTIVE To compare the cost/1 % reduction in low-density lipoprotein cholesterol ( LDL ) and the cost/patient achieving the National Cholesterol Education Program Adult Treatment Panel III ( NCEP ATP III ) LDL goal based on the results of the Statin Therapies for Elevated Lipid Levels Compared Across Doses to Rosuvastatin ( STELLAR ) trial . DESIGN Cost-efficacy analysis . INTERVENTION Investigators in the STELLAR trial evaluated percentage reductions in LDL and achievement of the ATP III LDL goal for various doses of atorvastatin , pravastatin , rosuvastatin , and simvastatin . We derived efficacy estimates for these four statins from the results of this trial . We also derived drug acquisition costs from the average wholesale prices to estimate the cost/1 % reduction in LDL levels and the cost/patient achieving the ATP III LDL goal . MEASUREMENTS AND MAIN RESULTS In the STELLAR trial , doses of rosuvastatin produced reductions in LDL significantly greater than those of equivalent milligram/milligram doses of atorvastatin , simvastatin , or pravastatin . The annual acquisition cost/percentage LDL reduction was lower with rosuvastatin at doses of 10 mg ( 20.92 dollars ) , 20 mg ( 18.28 dollars ) , and 40 mg ( 17.42 dollars ) than with the other statins analyzed . Rosuvastatin also had a lower average cost/patient achieving the ATP III LDL goal over 6 weeks than that of the other statins . CONCLUSION Although the long-term clinical benefits and safety data from the increased LDL reduction achieved with rosuvastatin remain uncertain , rosuvastatin may be the most cost-effective statin among those analyzed in terms of acquisition cost/1 % reduction in LDL levels and in terms of patients achieving ATP III LDL goals . On the basis of the efficacy estimates from the STELLAR trial in conjunction with acquisition cost , a potential cost savings could be realized from the use of rosuvastatin OBJECTIVES We sought to identify single nucleotide polymorphisms associated with mild statin-induced side effects . BACKGROUND Statin-induced side effects can interfere with therapy . Single nucleotide polymorphisms in cytochrome P450 enzymes impair statin metabolism ; the reduced function SLCO1B1 * 5 allele impairs statin clearance and is associated with simvastatin-induced myopathy with creatine kinase ( CK ) elevation . METHODS The STRENGTH ( Statin Response Examined by Genetic Haplotype Markers ) study was a pharmacogenetics study of statin efficacy and safety . Subjects ( n = 509 ) were r and omized to atorvastatin 10 mg , simvastatin 20 mg , or pravastatin 10 mg followed by 80 mg , 80 mg , and 40 mg , respectively . We defined a composite adverse event ( CAE ) as discontinuation for any side effect , myalgia , or CK > 3x upper limit of normal during follow-up . We sequenced CYP2D6 , CYP2C8 , CYP2C9 , CYP3A4 , and SLCO1B1 and tested 7 reduced function alleles for association with the CAE . RESULTS The CAE occurred in 99 subjects ( 54 discontinuations , 49 myalgias , and 9 CK elevations ) . Sex was associated with CAE ( percent female in CAE vs. no CAE groups , 66 % vs. 50 % , p < 0.01 ) . SLCO1B1 * 5 was associated with CAE ( percent with > or = 1 allele in CAE vs. no CAE groups , 37 % vs. 25 % , p = 0.03 ) and those with CAE with no significant CK elevation ( p < or = 0.03 ) . Furthermore , there was evidence for a gene-dose effect ( percent with CAE in those with 0 , 1 , or 2 alleles : 19 % , 27 % , and 50 % , trend p = 0.01 ) . Finally , the CAE risk appeared to be greatest in those carriers assigned to simvastatin . CONCLUSIONS SLCO1B1 * 5 genotype and female sex were associated mild statin-induced side effects . These findings exp and the results of a recent genome-wide association study of statin myopathy with CK > 3x normal to milder , statin-induced , muscle side effects The lipid-lowering effects of rosuvastatin and atorvastatin were determined across their dose ranges in a 6-week , r and omized , double-blind trial . Three hundred seventy-four hypercholesterolemic patients with fasting low-density lipoprotein ( LDL ) cholesterol > or = 160 but < 250 mg/dl ( > or = 4.14 but < 6.47 mmol/L ) and fasting triglycerides < 400 mg/dl ( < 4.52 mmol/L ) and without active arterial disease within 3 months of entry received once-daily rosuvastatin ( 5 , 10 , 20 , 40 , or 80 mg [ n = 209 ] ) or atorvastatin ( 10 , 20 , 40 , or 80 mg [ n = 165 ] ) . The percentage decrease in plasma LDL cholesterol versus dose was log-linear for each drug , ranging from -46.6 % to -61.9 % for rosuvastatin 10 and 80 mg , compared with -38.2 % to -53.5 % for atorvastatin 10 and 80 mg . The dose curve for rosuvastatin yielded an 8.4 % greater decrease in LDL cholesterol compared with atorvastatin at any given dose ( p < 0.001 ) . Similarly greater decreases were observed for rosuvastatin across the dose range in total cholesterol ( -4.9 % ) , non-high-density lipoprotein ( non-HDL ) cholesterol ( -7.0 % ) , apolipoprotein B ( -6.3 % ) , and related ratios versus atorvastatin ( all p < 0.001 ) . Because dose responses for HDL cholesterol , triglycerides , and apolipoprotein A-I were non-log-linear and nonparallel between the 2 drugs , percentage changes from baseline were compared at each dose . Significantly greater increases for rosuvastatin compared with atorvastatin were observed for HDL cholesterol at 40 and 80 mg , and for apolipoprotein A-I at 80 mg . Significantly greater triglyceride decreases were seen at 80 mg with atorvastatin over rosuvastatin . Both rosuvastatin and atorvastatin were well tolerated over 6 weeks Reduction in plasma lipids has been recognized as one of the primary cardiovascular risk reduction strategies in the secondary prevention of coronary heart disease ( CHD ) . The primary end points of TARGET TANGIBLE were the safety ( adverse events and laboratory measurements ) and efficacy ( responder rates ) of therapy with atorvastatin versus simvastatin with the aim of achieving low-density lipoprotein ( LDL ) cholesterol lowering to < or = 100 mg/dl ( 2.6 mmol/L ) . A total of 3,748 CHD patients with LDL cholesterol levels > or = 130 mg/dl ( 3.4 mmol/L ) entered a run-in diet phase of 6 weeks without any lipid-lowering drug therapy . At the end of the diet phase , 2,856 patients met the lipid criteria and were r and omized to active treatment for 14 weeks . Patients received 10 to 40 mg of either drug in an optional titration design at 2:1 r and omization for atorvastatin versus simvastatin . Adverse event rates were statistically equivalent ( p<0.01 ) for simvastatin ( 35.7 % ) and for atorvastatin patients ( 36.3 % ) . Both drugs were well tolerated ; < 5 % of patients in both groups were withdrawn due to adverse events . In all , 37 atorvastatin patients ( 2 % ) and 27 simvastatin patients ( 3 % ) had serious adverse events . Drug-related side effects ( elevations in creatine kinase , liver enzymes ) occurred in both groups at similar rates with 10 atorvastatin patients ( 0.5 % ) and 5 simvastatin patients ( 0.5 % ) presenting confirmed transaminase elevations > 3 x the upper limit of the normal range . Significantly fewer patients in the atorvastatin group ( n = 724 ) required titration to 40 mg compared with the simvastatin group ( n = 514 ) ( 38 % vs. 54 % , respectively ; p<0.001 ) . Atorvastatin result ed in a significantly greater number of patients reaching the LDL cholesterol goal than those treated with simvastatin , with 67 % of atorvastatin patients and 53 % of simvastatin patients reaching the target LDL cholesterol level of < or = 100 mg/dl ( 2.6 mmol/L ) ( p<0.001 ) . Both atorvastatin and simvastatin are safe for use by patients in the secondary prevention of CHD , with patients in both drug groups having similar adverse event rates . Despite the use of concomitant medications there was no drug-induced rhabdomyolysis with either atorvastatin or simvastatin BACKGROUND Type 2 diabetes mellitus ( T2DM ) is associated with a high risk for coronary heart disease ( CHD ) . A variety of lipoprotein and apolipoprotein ( Apo ) ratios have been proposed that may reflect the balance of cholesterol delivery and removal at the arterial wall and provide an assessment of CHD risk that is supplemental to low-density lipoprotein cholesterol ( LDL-C ) , the primary guide for cholesterol-lowering therapy in patients at risk . OBJECTIVE To examine changes in lipoprotein and apolipoprotein ratios in the VYTAL trial of hypercholesterolemic patients with T2DM . METHODS Changes in the ratios LDL-C/high-density lipoprotein cholesterol ( HDL-C ) , total cholesterol (TC)/HDL-C , non-HDL-C/HDL-C , and ApoB/ApoA-I were assessed in this r and omized , double-blind , parallel-group study that enrolled T2DM patients with LDL-C ≥100 mg/dL for 6-week treatments with either the usual daily starting doses of atorvastatin ( ATORVA ) 10 or 20 mg or ezetimibe/simvastatin ( EZE/SIMVA ) 10/20 mg , or the next highest doses ( ATORVA 40 mg , EZE/SIMVA 10/40 mg ) . Changes in lipoprotein and apolipoprotein ratios , prespecified exploratory endpoints , were analyzed using analysis of variance . RESULTS Efficacy results were based on 1198 patients with sufficient data among 1229 r and omized patients . Baseline lipoproteins , apolipoproteins , and ratios were comparable among treatment groups . EZE/SIMVA produced significantly greater reductions compared with ATORVA in each lipoprotein or apolipoprotein ratio at each dose comparison ( P < 0.001 ) . For example , reductions from baseline in TC/HDL-C were ATORVA 10 mg , -30.2 % ; ATORVA 20 mg -34.9 % ; EZE/SIMVA 10/20 mg , -41.6 % ; ATORVA 40 mg , -37.9 % ; and EZE/SIMVA 10/40 mg , -43.5 % . Tolerability of the two treatments was similar . CONCLUSION For the doses assessed , EZE/SIMVA was more effective compared with ATORVA in lowering the lipoprotein and apolipoprotein ratios that might be considered secondary measures of CHD risk Guidelines stress the importance of the simultaneous management of multiple cardiovascular risk factors . This can in part be achieved by coadministration of lipid-lowering and antihypertensive treatments . Potential pharmacodynamic interaction between drugs should be investigated as part of developing single-pill combinations . The Respond trial assessed whether combining amlodipine to treat hypertension and atorvastatin to treat dyslipidemia affected the action of either monotherapy . A total of 1660 hypertensive patients with dyslipidemia received 1 of 15 combinations of amlodipine ( placebo , 5 , or 10 mg ) and atorvastatin ( placebo , 10 , 20 , 40 , or 80 mg ) in a 3 x 5 factorial r and omized , placebo-controlled design . At 8 weeks , combination-treated patients experienced dose-related and statistically significant reductions in systolic blood pressure , low-density lipoprotein cholesterol , and Framingham risk score . Overall , coadministered atorvastatin and amlodipine was well tolerated and without adverse pharmacodynamic interaction ; combination treatment did not affect the low-density lipoprotein cholesterol-lowering efficacy and safety of atorvastatin , or the systolic blood pressure-lowering efficacy and safety of amlodipine BACKGROUND Few published data in particular from the United States indicate that the implementation of guidelines for prevention of coronary heart disease ( CHD ) is far from optimal . The objective of our study was to identify the type and prevalence of lipid-lowering medications in a German outpatient CHD population and to examine the impact of applied treatment regimens on serum lipid levels . METHODS Retrospective analysis of the washout phase of 2,856 CHD patients requiring lipid-lowering medication . Data are derived from a multicenter , r and omized , open-label , parallel group clinical trial comparing the safety and efficacy of atorvastatin versus simvastatin in 591 centers in Germany . Medical history , physical examination , and serum lipid levels were obtained at the beginning of the washout phase ( Week -6 ) and at the end of the washout phase ( Week -1 , i.e. , 5 weeks after the discontinuation of all prior lipid-lowering medications ) . The data at Week -6 represented the lipid levels under real life conditions . The difference from the data at Week -1 reflected the therapeutic effects achieved by the previous lipid-lowering treatment . RESULTS The mean low-density lipoprotein cholesterol ( LDL-C ) level at Week -6 was 173.4 + /- 42.5 mg/dl . Only 176 ( 6.2 % ) of 2,856 CHD patients were found to meet the target LDL-C level of < 115 mg/dl at Week -6 , only 76 ( 2.7 % ) patients had LDL-C levels < 100 mg/dl , and 363 ( 12.7 % ) patients had LDL-C levels < 130 mg/dl . After discontinuation of all prior lipid-lowering medications , mean LDL-C increased to 187.2 + /- 44.0 mg . This means that only a marginal 7.4 % reduction in LDL-C level was achieved under real life treatment conditions . This limited LDL-C reduction was due mainly to the low prevalence of lipid-lowering treatment ( 65.5 % of patients did not receive any medication at all ) and inadequate dosing . With respect to the effect on LDL-C and total cholesterol , statins alone were superior to fibrates . CONCLUSION The study shows that there is a wide gap between treatment guidelines and real life treatment patterns in Germany . Awareness of the risks of high cholesterol levels has to be increased among both patients and physicians . Available treatment guidelines should be better implemented SUMMARY In the Statin Therapies for Elevated Lipid Levels compared Across doses to Rosuvastatin ( STELLAR ) trial , the efficacy of rosuvastatin calcium ( Crestor * ) was compared with that of atorvastatin ( Lipitor † ) , simvastatin ( Zocor‡ ) , and pravastatin ( Pravachol§ ) for lowering plasma low-density lipoprotein cholesterol ( LDL-C ) after 6 weeks of treatment . In this multicenter , parallel-group , open-label trial , adults with hypercholesterolemia were r and omized to treatments with rosuvastatin 10 , 20,40 , or 80 mg , atorvastatin 10 , 20,40 , or 80 mg , simvastatin 10,20,40 , or 80 mg , or pravastatin 10 , 20 , or 40 mg . Efficacy and safety results from this trial have been previously published . The additional analyses included in this report show that 53 % ( 83/156 ) to 80 % ( 125/157 ) of patients in the rosuvastatin 10- to 40-mg groups achieved LDL-C levels < 100 mg dl−1 ( < 2.6 mmol l−1 ) , compared with 18 % ( 28/158 ) to 70 % ( 115/165 ) of patients who received atorvastatin , 8 % ( 13/165 ) to 53 % ( 86/163 ) of patients who received simvastatin , and 1 % ( 1/160 ) to 8 % ( 13/161 ) of patients who received pravastatin . Other additional analyses showed that more patients in the rosuvastatin 10- to 40-mg groups than in the comparator groups who were at high risk of coronary heart disease according to National Cholesterol Education Program Adult Treatment Panel ( ATP ) III , Joint European Societies , or Canadian guidelines achieved the LDL-C goals of < 100 mg dl−1 ( < 2.6 mmol l−1 ) ( 55 % to 77 % compared with 0 to 64 % ) , < 3.0 mmol l−1 ( < 116 mg dl−1 ) ( 76 % to 94 % compared with 6 % to 81 % ) , and < 2.5 mmol l−1 ( < 97 mg dl−1 ) ( 47 % to 69 % compared with 0 to 53 % ) , respectively . Results favoring rosuvastatin versus the comparators were also reported for patients : ( a ) who had triglycerides > 200 mg dl−1 ( > 2.3 mmol l−1 ) , and achieved both ATP III LDL-C and non-high-density lipoprotein cholesterol ( non-HDL-C ) goals ( 80 % to 84 % versus 15 % to 84 % ) ; ( b ) overall who achieved the Canadian LDL-C goals of < 2.5 ( < 97 mg dl−1 ) to < 5.0 mmol l−1 ( < 193mg/dl ) ( 85 % to 91 % versus 44 % to 86 % ) ; and ( c ) who achieved all 3 Canadian goals for LDL-C , triglycerides ( < 3.0 mmol l−1 [ < 266 mg dl−1 ] to < 2.0 mmol l−1 [ < 177 g dl−1 ] ) , and the total cholesterol/high-density lipoprotein-cholesterol ratio ( < 4 to < 7 ) ( 70 % to 83 % versus 35 % to 79 % ) . * Crestor is a registered trademark of the AstraZeneca group of companies and is licensed to AstraZeneca from Shionogi & Co , Ltd , Osaka , Japan . † Lipitor is a registered trademark of Pfizer Inc. ‡ Zocor is a registered trademark of Merck & Co. , Inc. § Pravachol is a registered trademark of Bristol-Myers Squibb Company |
12,734 | 21,763,343 | Although r and omized control trials have not been done , clinical evidence favors the addition of a macrolide to a beta-lactam for the treatment of pneumococcal pneumonia and supports a role for macrolides in the treatment of all-cause CAP without regard to their anti-microbial activity .
The weight of several retrospective studies suggests that statins be considered in treating acute CAP .
Further support for the use of statins derives from the high association between pneumonia and acute myocardial infa rct ion .
Aspirin might also be of benefit in treating patients hospitalized for pneumonia because of its anti-inflammatory activity as well as its benefits in acute myocardial infa rct ion .
Ibuprofen is not of benefit in treating sepsis in humans and glitazones may increase the risk of severe pneumonia | Despite the availability of excellent antibiotics , the mortality from community-acquired pneumonia ( CAP ) remains substantial .
Most deaths occur during the first week of hospitalization .
Because antibiotics rapidly eradicate bacteria from pulmonary secretions , an ongoing inflammatory response may be responsible for the poor outcome , and treatment with immunomodulatory drugs might be beneficial in this setting .
Macrolides and statins exert a broad range of anti-inflammatory effects . | 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 Abstract Inflammatory pathways are involved in the development of atherosclerosis . Interaction of vessel wall cells and invading monocytes by cytokines may trigger local inflammatory processes . 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ( statins ) are st and ard medications used in cardiovascular diseases . They are thought to have anti-inflammatory capacities , in addition to their lipid-lowering effects . We investigated the anti-inflammatory effect of statins in the cytokine-mediated-interaction-model of human vascular smooth muscle cells ( SMC ) and human mononuclear cells ( MNC ) . In this atherosclerosis-related inflammatory model LPS ( lipopolysaccharide , endotoxin ) , as well as high mobility group box 1 stimulation result ed in synergistic ( i.e. over-additive ) IL-6 ( interleukin-6 ) production as measured in ELISA . Recombinant IL-1 , tumour necrosis factor-α and IL-6 mediated the synergistic IL-6 production . The st and ard anti-inflammatory drugs aspirin and indomethacin ( Indo ) reduced the synergistic IL-6 production by 60 % . Simvastatin , atorvastatin , fluvastatin or pravastatin reduced the IL-6 production by 53 % , 50 % , 64 % and 60 % , respectively . The inhibition by the statins was dose dependent . Combination of statins with aspirin and /or Indo result ed in complete inhibition of the synergistic IL-6 production . The same inhibitors blocked STAT3 phosphorylation , providing evidence for an autocrine role of IL-6 in the synergism . MNC from volunteers after 5 day aspirin or simvastatin administration showed no decreased IL-6 production , probably due to drug removal during MNC isolation . Taken together , the data show that anti-inflammatory functions ( here shown for statins ) can be sensitively and reproducibly determined in this novel SMC/MNC coculture model . These data implicate that statins have the capacity to affect atherosclerosis by regulating cytokine-mediated innate inflammatory pathways in the vessel wall OBJECTIVES Our aim was to investigate if the peroxisome proliferator-activated receptor (PPAR)-gamma agonist pioglitazone modulates inflammation through PPARalpha mechanisms . BACKGROUND The thiazolidinediones ( TZDs ) pioglitazone and rosiglitazone are insulin-sensitizing PPARgamma agonists used to treat type 2 diabetes ( T2DM ) . Despite evidence for TZDs limiting inflammation and atherosclerosis , questions exist regarding differential responses to TZDs . In a double-blinded , placebo-controlled 16-week trial among recently diagnosed T2DM subjects ( n = 34 ) , pioglitazone-treated subjects manifested lower triglycerides and lacked the increase in soluble vascular cell adhesion molecules (sVCAM)-1 evident in the placebo group . Previously we reported PPARalpha but not PPARgamma agonists could repress VCAM-1 expression . Since both triglyceride-lowering and VCAM-1 repression characterize PPARalpha activation , we studied pioglitazone 's effects via PPARalpha . METHODS Pioglitazone effects on known PPARalpha responses -- lig and binding domain activation and PPARalpha target gene expression -- were tested in vitro and in vivo , including in wild-type and PPARalpha-deficient cells and mice , and compared with the effects of other PPARgamma ( rosiglitazone ) and PPARalpha ( WY14643 ) agonists . RESULTS Pioglitazone repressed endothelial TNFalpha-induced VCAM-1 messenger ribonucleic acid expression and promoter activity , and induced hepatic IkappaBalpha in a manner dependent on both pioglitazone exposure and PPARalpha expression . Pioglitazone also activated the PPARalpha lig and binding domain and induced PPARalpha target gene expression , with in vitro effects that were most pronounced in endothelial cells . In vivo , pioglitazone administration modulated sVCAM-1 levels and IkappaBalpha expression in wild-type but not PPARalpha-deficient mice . CONCLUSIONS Pioglitazone regulates inflammatory target genes in hepatic ( IkappaBalpha ) and endothelial ( VCAM-1 ) setting s in a PPARalpha-dependent manner . These data offer novel mechanisms that may underlie distinct TZD responses Introduction The benefit of corticosteroids as adjunctive treatment in patients with severe community-acquired pneumonia ( CAP ) requiring hospital admission remains unclear . This study aim ed to evaluate the impact of corticosteroid treatment on outcomes in patients with CAP . Methods This was a prospect i ve , double-blind and r and omized study . All patients received treatment with ceftriaxone plus levofloxacin and methyl-prednisolone ( MPDN ) administered r and omly and blindly as an initial bolus , followed by a tapering regimen , or placebo . Results Of the 56 patients included in the study , 28 ( 50 % ) were treated with concomitant corticosteroids . Patients included in the MPDN group show a more favourable evolution of the pO2/FiO2 ratio and faster decrease of fever , as well as greater radiological improvement at seven days . The time to resolution of morbidity was also significantly shorter in this group . Six patients met the criteria for mechanical ventilation ( MV ) : five in the placebo group ( 22.7 % ) and one in the MPDN group ( 4.3 % ) . The duration of MV was 13 days ( interquartile range 7 to 26 days ) for the placebo group and three days for the only case in the MPDN group . The differences did not reach statistical significance . Interleukin (IL)-6 and C-reactive protein ( CRP ) showed a significantly quicker decrease after 24 h of treatment among patients treated with MPDN . No differences in mortality were found among groups . Conclusions MPDN treatment , in combination with antibiotics , improves respiratory failure and accelerates the timing of clinical resolution of severe CAP needing hospital admission . Trial Registration International St and ard R and omized Controlled Trials Register , IS RCT N22426306 Objective To determine whether statins protect against all cause mortality after a diagnosis of pneumonia . Design Cohort study using propensity score based method to control for differences between people prescribed and not prescribed statins . Setting United Kingdom Health Improvement Network data base , which contains electronic primary care medical records of more than six million patients . Participants Every patient starting a statin between 1995 and 2006 ( 129 288 ) matched with up to five non-statin users ( n=600 241 ) ; 9073 patients had a recorded diagnosis of pneumonia , of whom 1398 were using a statin . Main outcome measure All cause mortality within six months of diagnosis of pneumonia . Results Among users and non-users of statins with comparable propensity scores , 95/942 users and 686/3615 non-users died on the day that pneumonia was diagnosed . In the following six month period , 109/847 statin users died compared with 578/2927 non-users , giving an adjusted hazard ratio of 0.67 ( 0.49 to 0.91 ) . If these observed benefits translated into clinical practice , 15 patients would need to be treated with a statin for six months after pneumonia to prevent one death . Conclusions Compared with people who were not taking statins , the risk of dying in the six month period after pneumonia was substantially lower among people who were already established on long term statin treatment when the pneumonia occurred . Whether some or all of this protective effect would be obtained if statin treatment begins when a patient first develops pneumonia is not known . However , given that statins are cheap , safe , and well tolerated , a clinical trial in which people with pneumonia are r and omised to a short period of statin treatment is warranted Recent studies suggest that statins and angiotensin-converting enzyme ( ACE ) inhibitors may have beneficial effects for some types of infections . The present study aim ed to examine the association of outpatient use of these medications on 30-day mortality for subjects aged > 65 yrs and hospitalised with community-acquired pneumonia . A retrospective national cohort study was conducted using the Department of Veterans Affairs administrative data including subjects aged ≥65 yrs hospitalised with community-acquired pneumonia , and having ≥1 yr of prior Veterans Affairs outpatient care . In total , 8,652 subjects were identified with a mean age of 75 yrs , 98.6 % were male , and 9.9 % of subjects died within 30 days of presentation . In this cohort , 18.1 % of subjects were using statins and 33.9 % were using ACE inhibitors . After adjusting for potential confounders , current statin use ( odds ratio ( OR ) 0.54 , 95 % confidence interval ( CI ) 0.42–0.70 ) and ACE inhibitor use ( OR 0.80 , 95 % CI 0.68–0.89 ) were significantly associated with decreased 30-day mortality . Use of statins and angiotensin-converting enzyme inhibitors prior to admission is associated with decreased mortality in subjects hospitalised with community-acquired pneumonia . R and omised controlled trials are needed to examine whether the use of these medications in patients hospitalised with community-acquired pneumonia may be beneficial Background Recent studies suggested that administration of corticosteroids may improve clinical outcomes in patients with severe pneumonia . Objectives The aim of this study was to assess the effectiveness of corticosteroids as an adjunctive therapy in community-acquired pneumonia ( CAP ) requiring hospitalization . Design and Setting An open label , prospect i ve , r and omized control study was conducted from September 2003 to February 2004 in a community general hospital in Japan . Patients Thirty-one adult CAP patients who required hospitalization were enrolled . Measurements and Results Fifteen patients received 40 mg of prednisolone intravenously for 3 days ( steroid group ) . Sixteen patients did not receive prednisolone ( control group ) . Both groups were also evaluated for their adrenal function . The primary endpoint was length of hospital stay . Secondary endpoints were duration of intravenous ( IV ) antibiotics and time required to stabilize vital signs . Both groups demonstrated similar baseline characteristics and length of hospital stay , and yet a shorter duration of IV antibiotics was observed in the steroid group ( p < 0.05 ) . In addition , vital signs were stabilized earlier in the steroid group ( p < 0.05 ) . These differences were more prominent in the moderate – severe subgroup but not as significant in the mild – moderate subgroup . The prevalence of relative adrenal insufficiency ( RAI ) in both groups was high ( 43 % ) , yet there was no difference in baseline characteristics between patients , with or without RAI . In multiple regression models , RAI seemed to have no influence on clinical courses . Conclusions In moderate – severe CAP , administration of corticosteroids promotes resolution of clinical symptoms and reduces the duration of intravenous antibiotic therapy In the study presented here , data collected prospect ively from 340 adult patients hospitalised in five countries with bacteremic pneumococcal CAP and treated with a ß-lactam + /− a macrolide were analysed retrospectively to evaluate the efficacy of this antimicrobial combination . Univariate and multivariate analyses revealed no significant effect on case fatality rate when a macrolide/ß-lactam regimen was used as initial therapy . Results were not affected by severity of illness , or by excluding patients who died within 2 days of admission . Identified predictors of death in a multivariate regression model were age > 65 years ( OR=2.6 ) , two or more lung lobes affected ( OR=2.2 ) , and severity of disease as estimated using the acute physiology score (APS)>8 Objective To determine if statin therapy reduces the incidence of severe sepsis and the levels of inflammatory cytokines in patients with acute bacterial infection . Design Double-blind placebo controlled r and omized clinical trial . Setting Department of medicine and medical intensive care unit in a tertiary university medical center . Patients and participants A total of 83 patients with suspected or documented bacterial infection were enrolled . We r and omly assigned 42 patients to receive 40 mg of simvastatin orally , followed by 20 mg of simvastatin , and 41 to receive matching placebo . Measurements and results The study was prematurely terminated due to slow recruitment rate . Here we report the analysis of the secondary outcome : change in cytokines levels at 72 h. Both groups were evenly matched in terms of co-morbidity and severity of illness on admission . Four of the 83 patients enrolled developed severe sepsis , two in each group . No difference was observed in other clinical variables and there were no mortalities . Cytokine levels were r and omly assessed in 40 patients ( 20 in each group ) . Both TNF-α and IL-6 levels were significantly reduced in the simvastatin group ( p = 0.02 and p = 0.02 , respectively ) , while no such difference was observed in the placebo group ( p = 0.35 and 0.39 , respectively ) . Conclusions Statin therapy may be associated with a reduction in the levels of inflammatory cytokines in patients with acute bacterial infections . Large controlled trials will determine if this reduction will translate into a clinical benefit STUDY OBJECTIVE To determine if the use of statins affects pneumonia-related outpatient visits , hospitalizations with survival , and deaths . DESIGN Population -based , retrospective , nested case-control analysis . DATA SOURCE United Kingdom-based General Practice Research Data base . PARTICIPANTS The study population ( 134,262 patients aged > or = 30 yrs ) consisted of 55,118 patients who took statins and /or fibrates , 29,144 patients with hyperlipidemia not taking lipid-lowering agents , and 50,000 r and omly selected patients without hyperlipidemia and without lipid-lowering treatment . MEASUREMENTS AND MAIN RESULTS We identified 1253 patients with pneumonia and matched them with 4838 control subjects based on age , sex , general practice , and index date . After adjusting for comorbidity and frequency of visits to general practitioners , we calculated the risks ( odds ratios with 95 % confidence intervals ) of uncomplicated pneumonia , hospitalization for pneumonia with survival , and fatal pneumonia in participants who used statins compared with those who did not . Current statin users had a significantly reduced risk of fatal pneumonia ( adjusted odds ratio 0.47 , 95 % confidence interval 0.25 - 0.88 ) and slightly but not significantly reduced risks of uncomplicated pneumonia and pneumonia hospitalization with survival . Recent or past statin use and fibrate use at any time were not associated with a reduced risk of pneumonia . CONCLUSION Current use of statins was associated with a reduced risk of pneumonia . The risk reduction was particularly strong in the subgroup of patients with fatal pneumonias We hypothesize that hydrocortisone infusion in severe community-acquired pneumonia attenuates systemic inflammation and leads to earlier resolution of pneumonia and a reduction in sepsis-related complications . In a multicenter trial , patients admitted to the Intensive Care Unit ( ICU ) with severe community-acquired pneumonia received protocol -guided antibiotic treatment and were r and omly assigned to hydrocortisone infusion or placebo . Hydrocortisone was given as an intravenous 200-mg bolus followed by infusion at a rate of 10 mg/hour for 7 days . Primary end-points of the study were improvement in Pa(O(2)):FI(O(2 ) ) ( Pa(O(2)):FI(O(2 ) ) > 300 or > /= 100 increase from study entry ) and multiple organ dysfunction syndrome ( MODS ) score by Study Day 8 and reduction in delayed septic shock . Forty-six patients entered the study . At study entry , the hydrocortisone group had lower Pa(O(2)):FI(O(2 ) ) , and higher chest radiograph score and C-reactive protein level . By Study Day 8 , treated patients had , compared with control subjects , a significant improvement in Pa(O(2)):FI(O(2 ) ) ( p = 0.002 ) and chest radiograph score ( p < 0.0001 ) , and a significant reduction in C-reactive protein levels ( p = 0.01 ) , MODS score ( p = 0.003 ) , and delayed septic shock ( p = 0.001 ) . Hydrocortisone treatment was associated with a significant reduction in length of hospital stay ( p = 0.03 ) and mortality ( p = 0.009 ) BACKGROUND Whether addition of corticosteroids to antibiotic treatment benefits patients with community-acquired pneumonia who are not in intensive care units is unclear . We aim ed to assess effect of addition of dexamethasone on length of stay in this group , which might result in earlier resolution of pneumonia through dampening of systemic inflammation . METHODS In our double-blind , placebo-controlled trial , we r and omly assigned adults aged 18 years or older with confirmed community-acquired pneumonia who presented to emergency departments of two teaching hospitals in the Netherl and s to receive intravenous dexamethasone ( 5 mg once a day ) or placebo for 4 days from admission . Patients were ineligible if they were immunocompromised , needed immediate transfer to an intensive-care unit , or were already receiving corticosteroids or immunosuppressive drugs . We r and omly allocated patients on a one-to-one basis to treatment groups with a computerised r and omisation allocation sequence in blocks of 20 . The primary outcome was length of hospital stay in all enrolled patients . This study is registered with Clinical Trials.gov , number NCT00471640 . FINDINGS Between November , 2007 , and September , 2010 , we enrolled 304 patients and r and omly allocated 153 to the placebo group and 151 to the dexamethasone group . 143 ( 47 % ) of 304 enrolled patients had pneumonia of pneumonia severity index class 4 - 5 ( 79 [ 52 % ] patients in the dexamethasone group and 64 [ 42 % ] controls ) . Median length of stay was 6·5 days ( IQR 5·0 - 9·0 ) in the dexamethasone group compared with 7·5 days ( 5·3 - 11·5 ) in the placebo group ( 95 % CI of difference in medians 0 - 2 days ; p=0·0480 ) . In-hospital mortality and severe adverse events were infrequent and rates did not differ between groups , although 67 ( 44 % ) of 151 patients in the dexamethasone group had hyperglycaemia compared with 35 ( 23 % ) of 153 controls ( p<0·0001 ) . INTERPRETATION Dexamethasone can reduce length of hospital stay when added to antibiotic treatment in non-immunocompromised patients with community-acquired pneumonia . FUNDING None To determine the impact of initial antimicrobial choice on 30-day mortality rate in patients with community-acquired pneumonia due to Streptococcus pneumoniae ( CAP-SP ) , a prospect i ve , observational study was conducted in 35 Spanish hospitals . A total of 638 patients with CAP-SP were identified . Antimicrobials were chosen by the attending physician . Patients were grouped into the following categories : β-lactam monotherapy ( n = 251 ) , macrolide monotherapy ( n = 37 ) , β-lactam plus macrolide ( n = 198 ) , levofloxacin alone/combination ( n = 48 ) , and other combinations ( n = 104 ) . The reference category was β-lactam+macrolide . The 30-day survival probability was 84.9 % . Using multivariate survival analysis , factors related to mortality in the entire population were : bilateral disease , suspected aspiration , shock , HIV infection , renal failure and pneumonia severity index ( PSI ) score Class IV versus I – III and categories V versus I – III . The association of β-lactams+macrolides was not better than the use of β-lactams alone . The current authors analysed the different groups of patients with significant mortality/morbidity : intensive care unit , PSI Class > III , renal failure , chronic lung disease and bacteraemia . Only in patients with PSI Class > III , who had undergone initial antimicrobial choice classified as other combinations , were associated with higher mortality . In conclusion , the current authors have not demonstrated an independent association between initial antimicrobial regimen and 30-day mortality in community-acquired pneumococcal pneumonia patients , except for those with a higher pneumonia severity index score Macrolides may influence the inflammatory response to an infection by mechanisms that are unrelated to their antimicrobial effect . Indeed , erythromycin and other macrolides inhibit cytokine production and induce degranulation of neutrophils in vitro . CXC chemokines are small chemotactic cytokines that specifically influence neutrophil functions . To determine the effect of a clinical ly relevant dose of erythromycin on the production of CXC chemokines and neutrophil degranulation , six healthy humans received a 30 min iv infusion of erythromycin ( 1000 mg ) . Whole blood obtained before and at various times after the infusion was stimulated ex vivo with heat-killed Streptococcus pneumoniae . Ex vivo production of the CXC chemokines interleukin 8 ( IL-8 ) and epithelial cell-derived neutrophil attractant 78 ( ENA-78 ) , in whole blood obtained after erythromycin infusion , was lower than that in blood drawn before erythromycin infusion ( maximum inhibition post-infusion : 32.9 + /- 6.5 % and 35.2 + /- 12.6 % decrease in production , respectively , expressed as percentage change relative to production before infusion of erythromycin , both P < 0.05 ) . In contrast , infusion of erythromycin was associated with an enhanced capacity of whole blood to release the neutrophil degranulation products bactericidal/permeability increasing protein ( BPI ) , human neutrophil elastase ( HNE ) and human lactoferrin ( HLF ) upon stimulation with S. pneumoniae . Effects of erythromycin were greatest 4 h after infusion was stopped , when BPI , HNE and HLF concentrations were increased by + 107.6 + /- 33.5 % , + 134.7 + /- 34.8 % and + 205.9 + /- 55.9 % , respectively ( expressed as percentage change relative to production before infusion of erythromycin ) ( all P < 0 . 05 ) . These results indicate the ability of erythromycin to reduce CXC chemokine production and to enhance neutrophil degranulation in human blood To assess the association between inclusion of a macrolide in a beta-lactam-based empirical antibiotic regimen and mortality among patients with bacteremic pneumococcal pneumonia , 10 years of data from a data base were analyzed . The total available set of putative prognostic factors was subjected to stepwise logistic regression , with in-hospital death as the dependent variable . Of the 409 patients analyzed , 238 ( 58 % ) received a beta-lactam plus a macrolide and 171 ( 42 % ) received a beta-lactam without a macrolide . Multivariate analysis revealed 4 variables to be independently associated with death : shock ( P<.0001 ) , age of > or=65 years ( P=.02 ) , infections with pathogens that have resistance to both penicillin and erythromycin ( P=.04 ) , and no inclusion of a macrolide in the initial antibiotic regimen ( P=.03 ) . For patients with bacteremic pneumococcal pneumonia , not adding a macrolide to a beta-lactam-based initial antibiotic regimen is an independent predictor of in-hospital mortality . However , only a r and omized study can definitively determine whether this association is due to a real effect of macrolides The purpose of this study was to examine the impact of antimicrobial monotherapy vs combination therapy on length of stay and mortality for patients with Streptococcus pneumoniae pneumonia . Thirty-nine percent of patients received monotherapy , while 61 % received combination therapy . Although there was no significant difference in mortality ( OR 1.25 , 95 % CI = 0.25–6.8 ) , there was a significant increase in length of stay for patients who received combination therapy ( p = 0.02 ) . Patients with bacteremic pneumococcal pneumonia treated with empiric combination therapy had no significant difference in mortality ; however , they did have increased length of stay after adjusting for severity of illness . R and omized controlled trials are needed to determine what is the optimal empiric antimicrobial regime for patients with community-acquired pneumonia A controlled trial was carried out to investigate whether the rate of recovery from pneumonia treated with ampicillin is dose related . Sixty-three patients received 1 g ampicillin daily and 63 received 2 g ampicillin daily for seven or 14 days depending on the rate of response . Twenty patients in each of these groups received , in addition , 20 mg prednisolone daily for seven days . The treatment groups were comparable and the results of treatment were similar in the four groups . The only difference which was of statistical significance was that a larger proportion of patients receiving 1 g ampicillin daily became afebrile within one week . All the ampicillin rashes occurred in the patients receiving 2 g ampicillin daily with and without prednisolone . Ampicillin 1 g daily appears to be adequate dosage in the treatment of pneumonia , and the rate of recovery has not been shown to be accelerated by using 2 g. No deleterious effects were noted with additional prednisolone therapy and this appeared to increase the rate at which the patients became afebrile , although the figures were not statistically significant Inhibition of platelet thromboxane A(2 ) ( TXA(2 ) ) by aspirin is critical in patients with acute myocardial infa rct ion ( AMI ) , but some patients have persistent platelet TXA(2 ) production within 48 hours of the onset of AMI . Statins are known to reduce TXA(2 ) in aspirin-free patients with hypercholesterolemia . We hypothesized that treatment with aspirin plus atorvastatin could reduce persistent TXA(2 ) synthesis and aspirin resistance in patients with AMI . We evaluated platelet function in 184 aspirin-treated patients within 48 hours of the onset of AMI . Patients were divided into group A ( treated with aspirin alone , n = 139 ) and group B ( treated with aspirin plus atorvastatin , n = 45 ) . We studied collagen-induced platelet TXA(2 ) synthesis , serotonin ( (14)C-5HT ) release and recruitment , and adenosine diphosphate- , arachidonic acid- , and collagen-induced platelet aggregation . Persistent TXA(2 ) synthesis was detected in 25 % and 9 % of groups A and B , respectively ( p = 0.03 ) . TXA(2 ) , arachidonic acid-aggregation , and collagen-induced responses were significantly reduced in patients receiving dual treatment compared to those receiving aspirin monotherapy . Atorvastatin did not modify platelet reactivity in patients with efficiently blocked TXA(2 ) synthesis . These results strongly suggest a direct effect of the statin on platelet eicosanoid synthesis . This was confirmed in vitro by incubating washed aspirin-free and aspirin ( 1 muM)-treated platelets from normal subjects with 1 to 20 microM atorvastatin . Atorvastatin in vitro significantly reduced platelet TXA(2 ) synthesis and collagen-induced aggregation . In conclusion , atorvastatin combined with aspirin early in the onset of the acute event significantly reduced persistent TXA(2 ) and TXA(2)-dependent aspirin resistance . This could contribute to the clinical benefit of atorvastatin in patients with AMI BACKGROUND Statins have potent anti-inflammatory effects in laboratory studies of pulmonary inflammation . We investigated whether statin users had improved outcome when admitted with community-acquired pneumonia . METHODS We carried out a prospect i ve observational study of patients admitted to the hospital with community-acquired pneumonia between January 2005 and November 2007 . The use of statins , angiotensin-converting enzyme inhibitors , beta-blockers , and aspirin were recorded . The outcomes of interest were 30-day mortality , need for mechanical ventilation or inotropic support , and the development of complicated pneumonia . RESULTS On multivariate logistic regression , statin use was associated with significantly lower 30-day mortality ( adjusted odds ratio [ AOR ] 0.46 , 95 % confidence interval [ CI ] , 0.25 - 0.85 , P=.01 ) and development of complicated pneumonia ( AOR 0.44 , 95 % CI , 0.25 - 0.79 , P=.006 ) . There was no effect on requirement of mechanical ventilation or inotropic support ( AOR 0.93 , 95 % CI , 0.49 - 1.76 , P=.8 ) . Patients prescribed statins had more severe pneumonia ( median Pneumonia Severity Index 4 , interquartile range [ IQR ] 3 - 4 ) compared with patients not prescribed cardiovascular drugs ( median Pneumonia Severity Index 3 , IQR 2 - 4 , P < .0001 ) . Despite this , C-reactive protein levels on admission were significantly lower in patients prescribed statins ( median 119 mg/L , IQR 46 - 215 ) compared with patients prescribed no cardiovascular drugs ( 182 mg/L , IQR 66 - 326 , P < .0001 ) . On multivariate logistic regression , statin use was independently protective against a C-reactive protein that failed to fall by 50 % or more at day 4 ( AOR 0.50 , 95 % CI 0.27 - 0.92 , P=.02 ) . CONCLUSIONS Statin use is associated with reduced markers of systemic inflammation and improved outcomes in patients admitted with community-acquired pneumonia We prospect ively identified cases of pneumococcal pneumonia and used stringent criteria to stratify them into bacteremic and nonbacteremic cases . Although patients were distributed among racial groups in proportion to all patients seen at this medical center , the proportion of African-Americans with bacteremic disease was significantly increased . All patients had at least 1 underlying condition predisposing to pneumococcal infection , and most had several . Although the mean number of predisposing factors was greater among bacteremic patients than nonbacteremic patients , only alcohol ingestion was significantly more common . Nearly one-third of patients had substantial anemia ( hemoglobin < or = 10 g/dL ) on admission , which may have predisposed to infection . In the case of other laboratory abnormalities , such as albumin , creatinine , and bilirubin , it was difficult to determine which abnormality might have predisposed to pneumococcal infection and which might have result ed from it . The radiologic appearance was varied . Airspace consolidation and air bronchogram on chest X-ray were highly associated with bacteremic disease , as was the presence of pleural effusion . Although the Pneumonia Patient Outcomes Research Team ( PORT ) risk score was a predictor of mortality , it did not help to predict the presence of bacteremia in an individual case . Most patients who died in the first week in hospital were bacteremic , and a high PORT risk score with bacteremia reliably predicted a high likelihood of a fatal outcome . Eleven patients had extrapulmonary disease with meningitis , empyema , and septic arthritis predominating ; all of these patients were bacteremic . The antibiotic susceptibility of our strains correlated well with those that have been reported in the United States during the years of this study . The use of numerous antibiotics of different classes in many patients , especially those who were the most ill , precluded analysis of outcome based on antibiotic therapy . Only 17 patients had been vaccinated . Since nearly all patients had conditions for which pneumococcal vaccine is recommended and more than one-third had been hospitalized in the preceding 6 months , the low rate of vaccination can be regarded as a missed opportunity to administer a potentially beneficial vaccine BACKGROUND Community-acquired pneumonia is a major cause of death in third world countries . Antimicrobial therapy may have little impact on the natural history of patients with severe pneumonia . We hypothesized that the intrapulmonary production of tumor necrosis factor-alpha ( TNF-alpha ) may be responsible for the progressive lung injury and shock commonly seen in patients with severe pneumonia after commencing antibiotic therapy . AIM To investigate the effects of a single bolus of hydrocortisone on the clinical course and serum TNF-alpha levels of patients with severe community-acquired pneumonia . DESIGN R and omized placebo-controlled study . SETTING Multidisciplinary ICU of a tertiary care teaching hospital . PATIENTS AND METHODS Patients with three or more British Thoracic Society criteria of severe pneumonia were studied . Patients were r and omized to receive either a single dose of hydrocortisone ( 10 mg/kg ) or placebo 30 min prior to commencing antibiotic therapy . Patients were treated with cefotaxime and other antibiotics as clinical ly indicated . Blood for TNF-alpha was taken at the time of hospital admission and repeated 2 , 6 , and 12 h after starting antibiotic therapy . RESULTS Thirty patients were studied : 16 received placebo and 14 received hydrocortisone . The patients who received placebo tended to be sicker than the patients who received hydrocortisone . The baseline TNF-alpha value was 989 + /- 374 pg/ml in the placebo group and 827 + /- 394 pg/ml in the hydrocortisone group . In both groups of patients , the TNF-alpha levels did not change significantly with time . There was no correlation between the TNF-alpha levels and the APACHE II score , lung injury score , or outcome . The only variable that predicted outcome was the APACHE II score . CONCLUSION Bactericidal antibiotics do not increase serum TNF-alpha levels in patients with severe pneumonia . Hydrocortisone given prior to antibiotic treatment had no effect on the serum TNF-alpha levels or the clinical course of patients with severe community-acquired pneumonia BACKGROUND In patients with sepsis the production of arachidonic acid metabolites by cyclooxygenase increases , but the pathophysiologic role of these prostagl and ins is unclear . In animal models , inhibition of cyclooxygenase by treatment with ibuprofen before the onset of sepsis reduces physiologic abnormalities and improves survival . In pilot studies of patients with sepsis , treatment with ibuprofen led to improvements in gas exchange and airway mechanics . METHODS From October 1989 to March 1995 , we conducted a r and omized , double-blind , placebo-controlled trial of intravenous ibuprofen ( 10 mg per kilogram of body weight [ maximal dose , 800 mg ] , given every six hours for eight doses ) in 455 patients who had sepsis , defined as fever , tachycardia , tachypnea , and acute failure of at least one organ system . RESULTS In the ibuprofen group , but not the placebo group , there were significant declines in urinary levels of prostacyclin and thromboxane , temperature , heart rate , oxygen consumption , and lactic acidosis . With ibuprofen therapy there was no increased incidence of renal dysfunction , gastrointestinal bleeding , or other adverse events . However , treatment with ibuprofen did not reduce the incidence or duration of shock or the acute respiratory distress syndrome and did not significantly improve the rate of survival at 30 days ( mortality , 37 percent with ibuprofen vs 40 percent with placebo ) . CONCLUSIONS In patients with sepsis , treatment with ibuprofen reduces levels of prostacyclin and thromboxane and decreases fever , tachycardia , oxygen consumption , and lactic acidosis , but it does not prevent the development of shock or the acute respiratory distress syndrome and does not improve survival Platelet activation contributes to microvascular thrombosis and organ failure in systemic inflammation . We tested the hypothesis whether anti-platelet drugs might favourably affect outcome in patients at risk for organ failure as well as in a mouse model of endotoxin shock . Two hundred twenty-four consecutive patients who were admitted for community acquired pneumonia over a time period of 5 years to a University Hospital were enrolled ; about 20 % of whom received anti-platelet drugs ( acetylsalicylic acid , thienopyridines ) for secondary prevention of cardiovascular disease . Patients with anti-platelet drugs were about 12 years old but did not differ in SOFA score and routine laboratory parameters at admission . Logistic regression and 2 × 2 table analysis in age-matched subgroups indicated that anti-platelet drugs may reduce the need of intensive care treatment ( odds ratio ( OR ) 0.32 [ 95 % confidential interval : 0.10–1.00 ] and 0.19 [ 0.04–0.87 ] , respectively ) . In age-matched subgroups , the use of anti-platelet drugs was also associated with a shorter stay in hospital ( 13.9 ± 6.2 vs. 18.2 ± 10.2 days ; p < 0.02 ) . In the animal model Balb/c mice were pre-treated with clopidogrel ( added to drinking water ) for 4 days prior to intraperitoneal ( i.p . ) administration of endotoxin ( lipopolsaccharide ( LPS ) from Escherichia coli 0111:B4 ) . Within the first 48 hours after LPS there were no differences between clopidogrel and control animals ( n = 26 each ) in macro-haemodynamics . However , clopidogrel abolished the LPS-induced drop in platelet count and reduced fibrin deposition in lung tissue . Using DNA microarray technology , we could show that clopidogrel suppressed endotoxin-induced up-regulation of inflammation-relevant genes , including arachidonate-5-lipoxygenase activating protein and leukotriene B4 receptor 1 . According to our data a possible benefit of anti-platelet drugs in patients on risk for systemic inflammation and organ failure should be tested in a prospect i ve trial Objectives To determine whether statins reduce mortality or need for admission to intensive care in patients admitted to hospital with community acquired pneumonia ; and to assess whether previously reported improvements in sepsis related outcomes were a result of the healthy user effect . Design Population based prospect i ve cohort study . Setting Six hospitals in Capital Health , Edmonton , Alberta , Canada . Participants Adults admitted to hospital with pneumonia and categorised according to use of statins for at least one week before admission and during hospital stay . Main outcome measures Composite of in-hospital mortality or admission to an intensive care unit . Results Of 3415 patients with pneumonia admitted to hospital , 624 ( 18 % ) died or were admitted to an intensive care unit . Statin users were less likely to die or be admitted to an intensive care unit than non-users ( 50/325 ( 15 % ) v 574/3090 ( 19 % ) , odds ratio 0.80 , P=0.15 ) . After more complete adjustment for confounding , however , the odds ratios changed from potential benefit ( 0.78 , adjusted for age and sex ) to potential harm ( 1.10 , fully adjusted including propensity scores , 95 % confidence interval 0.76 to1.60 ) . Conclusions Statins are not associated with reduced mortality or need for admission to an intensive care unit in patients with pneumonia ; reports of benefit in the setting of sepsis may be a result of confounding BACKGROUND The introduction of conjugate pneumococcal vaccination for children has reduced the burden of invasive disease due to pneumococcal conjugate vaccine ( PCV ) types ( i.e. , serotypes 9V , 14 , 6B , 18C , 23F , 19F , and 4 ) in adults . As nonvaccine serotypes become predominant causes of invasive disease among adults , it is necessary to evaluate the disease severity and mortality associated with infection due to nonvaccine serotypes , compared with PCV serotypes , in adults . METHODS The association of pneumococcal serotype and host-related variables with disease severity and mortality was statistically examined ( with multivariable analysis ) in 796 prospect ively enrolled , hospitalized adult patients with bacteremia due to Streptococcus pneumoniae . RESULTS In multivariate analyses of risk in patients with invasive pneumococcal disease , older age ( age , > or = 65 years ; P = .004 ) , underlying chronic disease ( P = .025 ) , immunosuppression ( P = .035 ) , and severity of disease ( P < .001 ) were significantly associated with mortality ; no association was found between nosocomial infection with invasive serotypes 1 , 5 , and 7 and mortality . The risk factors meningitis ( P = .001 ) , suppurative lung complications ( P < or = .001 ) , and preexisting lung disease ( P = .051 ) were significantly associated with disease severity , independent of infecting serotype . No differences were seen in disease severity or associated mortality among patients infected with PCV serotypes , compared with patients infected with nonvaccine serotypes . CONCLUSIONS Our data support the notion that host factors are more important than isolate serotype in determining the severity and outcome of invasive pneumococcal disease and that these outcomes are unlikely to change in association with nonvaccine serotype infection in the post-conjugate vaccine era Retrospective studies have suggested that combination antibiotic therapy for severe bacteremic pneumococcal pneumonia may reduce mortality . We assessed this issue in a prospect i ve , multicenter , international observational study of 844 adult patients with bacteremia due to Streptococcus pneumoniae . The effect of combination antibiotic therapy versus monotherapy on mortality was examined by univariate analyses and by logistic regression models . The 14-day mortality was not significantly different for the two groups . However , among critically ill patients , combination antibiotic therapy was associated with lower 14-day mortality ( 23.4 versus 55.3 % , p = 0.0015 ) . This improvement in survival was independent of country of origin , intensive care unit support , class of antibiotics , or in vitro activity of the antibiotics prescribed . Combination antibiotic therapy improved survival among critically ill patients with bacteremic pneumococcal illness Oxidative stress during sepsis induces tissue damage , leading to organ dysfunction and high mortality . The antioxidant effects of vitamin E have been reported in several diseases , but not in sepsis . Statins have cholesterol-independent anti-inflammatory effects that are related to a decrease of isoprenoid proteins and oxidative stress . Therefore , we evaluated superoxide anion ( O2 ° − ) production and ex vivo effects of vitamin E and simvastatin in sepsis . Fourteen healthy volunteers , 14 intensive care unit ( ICU ) nonseptic , and 14 ICU patients with sepsis were included in this prospect i ve study . Plasma cholesterol , triglyceride , and vitamin E levels were determined by routine laboratory tests . Superoxide anion production was measured in the venous blood by chemiluminescence technique after phorbol myristate acetate stimulation . Effects of vitamin E and simvastatin on O2 ° − production was investigated ex vivo . Luminescence was indexed to the leukocyte count . We also investigated the in vitro effect of simvastatin on translocation of NADPH oxidase p21 Rac2 subunit in THP-1 monocytic cell line . The ratio of vitamin E/cholesterol + triglycerides was significantly decreased in septic as compared with nonseptic patients and volunteers . The O2 ° − production was significantly higher in the group of septic patients than in the others , regardless of the polymorphonuclear leukocyte count . Vitamin E and simvastatin induced ex vivo an inhibition of O2 ° − production of 20 % and 40 % respectively . In vitro , simvastatin inhibited phorbol myristate acetate-induced- O2 ° − production by monocytes through NADPH oxidase inactivation . We conclude that sepsis is associated with a significant decrease in vitamin E and an overproduction of O2 ° −. Vitamin E and simvastatin lessen this phenomenon through NADPH oxidase inactivation To evaluate the effects of roxithromycin in patients with chronic lower respiratory tract disease including diffuse panbronchiolitis , we studied lymphocyte function-associated antigen-1 ( LFA-1 ) and Mac-1 , neutrophil adhesion molecules , using peripheral neutrophils from healthy volunteers and from patients with chronic lower respiratory tract disease . The number of Mac-1 expressed on neutrophils of the patients was significantly greater ( 0.68 + /- 0.16 ) than in the healthy subjects ( 0.45 + /- 0.14 ) , while the number of LFA-1 expressed on neutrophils of the patients was nearly similar to that in the healthy volunteers ( 0.95 + /- 0.10 vs 0.89 + /- 0.11 ) . The neutrophil numbers in bronchoalveolar lavage fluid and the number of Mac-1 expressed on peripheral neutrophils significantly decreased in all patients who responded clinical ly to a low dose of roxithromycin for a long period of time ( 56.0 + /- 25.2 vs. 22.7 + /- 19.7 % , p < 0.05 and 0.70 + /- 0.16 vs. 0.59 + /- 0.08 , p < 0.05 , respectively ) , whereas roxithromycin had no effect on the quantitative expression of LFA-1 ( 0.96 + /- 0.14 to 1.00 + /- 0.09 , not significant ) in all responders |
12,735 | 20,706,166 | Conclusions : CHWs can improve outcomes for underserved population s for some health conditions . | Objectives : We conducted a systematic review on outcomes and costs of community health worker ( CHW ) interventions .
CHWs are increasingly expected to improve health outcomes cost-effectively for the underserved . | BACKGROUND African Americans suffer disproportionately from diabetes complications , but little research has focused on how to improve diabetic control in this population . There are also few or no data on a combined primary care and community-based intervention approach . METHODS We r and omly assigned 186 urban African Americans with type 2 diabetes ( 76 % female , mean A SD age 59 A 9 years ) to 1 of 4 parallel arms : ( 1 ) usual care only ; ( 2 ) usual care + nurse case manager ( NCM ) ; ( 3 ) usual care + community health worker ( CHW ) ; ( 4 ) usual care + nurse case manager/community health worker team . Using the framework of the Precede-Proceed behavioral model , interventions included patient counseling regarding self-care practice s and physician reminders . RESULTS The 2-year follow-up visit was completed by 149 individuals ( 84 % ) . Compared to the Usual care group , the NCM group and the CHW group had modest declines in HbA(1c ) over 2 years ( 0.3 and 0.3 % , respectively ) , and the combined NCM/CHW group had a greater decline in HbA(1c ) ( 0.8 % . P = 0.137 ) . After adjustment for baseline differences and /or follow-up time , the combined NCM/CHW group showed improvements in triglycerides ( -35.5 mg/dl ; P = 0.041 ) and diastolic blood pressure , compared to the usual care group ( -5.6 mmHg ; P = 0.042 ) . CONCLUSIONS Combined NCM/CHW interventions may improve diabetic control in urban African Americans with type 2 diabetes . Although results were clinical ly important , they did not reach statistical significance . This approach deserves further attention as a means to reduce the excess risk of diabetic complications in African Americans BACKGROUND The goal of our study was to measure the effectiveness of a home-based intervention for prevention of low birth weight with 154 high-risk , low-income black women attending a prenatal clinic in Clevel and . METHODS Based on previous research , risk was defined by clinic registration between the 17th and 28th weeks of gestation , low family functioning score , and experience of at least one stressful life event prior to registration . Optional factors included being a smoker , a low maternal weight-height ratio , being age 27 or older , and a previous premature birth . A 21-item family function screen previously vali date d in a similar population was the primary determinant of psychosocial risk . Low birth weight was defined as weight less than 2,500 g regardless of gestational age . RESULTS There was no decrease in the rate of low birth weight for women who received four home visits focusing on smoking , drug and nutrition education , support , and links with community services , compared to women who received no visits . The number of prenatal visits was significantly higher in the intervention group , but an increased number of prenatal visits did not correlate with a reduced rate of low birth weight . Despite previous research , the family function screen was not an effective predictor of low birth weight in our study . A revised equation involving a history of previous premature birth , smoking , and a low maternal weight-height ratio did predict low birth weight . CONCLUSIONS These findings question the utility of short-term psychosocial interventions for influencing low birth-weight rates in low-income black clinic population s. The family function screen was not cross vali date d. Integration of any psychosocial intervention with the routine prenatal care occurring in the obstetrical clinic is suggested for future research We evaluated the single and combined effects of introducing a motivational video and peer counseling into four matched WIC clinics on breastfeeding initiation and continuation at 7 - 10 days among African-American WIC participants . Of the 242 women with complete data , 48 % initiated breastfeeding , but only 31 % were still breastfeeding at 7 - 10 days . Initiation was associated with cesarean delivery , infant feeding instruction , no artificial milk discharge pack , attending the peer counselor only-intervention site , and intention to breastfeed . Continuation was influenced by infant feeding instruction , no artificial milk discharge pack , and intention to breastfeed . Overall , trends toward a positive impact of the breastfeeding promotion activities were evident but weak , and largely gone by 7 - 10 days postpartum OBJECTIVES To evaluate the costs of implementing a church-based , telephone-counseling program for increasing mammography use , and to identify the components of costs and the likely cost-effectiveness in hypothetical communities with varying characteristics . DATA SOURCES / STUDY SETTING An ethnically and socioeconomically diverse sample of 1,443 women recruited from 45 churches participating in the Los Angeles Mammography Promotion ( LAMP ) program were followed from 1995 to 1997 . STUDY DESIGN Churches were stratified into blocks and r and omized into three intervention arms-telephone counseling , mail counseling , and control . We surveyed participants before and after the intervention to collect data on mammography use and demographic characteristics . DATA COLLECTION / EXTRACTION METHODS We used call records , activity reports , and interviews to collect data on the time and material s needed to organize and carry out the intervention . We constructed a st and ard model of costs and cost-effectiveness based on these data and the Year One results of the LAMP program . PRINCIPAL FINDINGS The cost in material s and overhead to the church site was $ 10.89 per participant and $ 188 per additional screening . However , when the estimated cost for church volunteers ' time was included , the cost of the intervention increased substantially . CONCLUSIONS A church-based program to promote the use of mammography would be feasible for many churches with the use of volunteer labor and re sources Purpose Large-scale effectiveness trials design ed to translate evidence -based diabetes care to community setting s are few . Studies describing these methods among high-risk minority population s are particularly limited . Methods The authors describe Project Sugar , a r and omized controlled trial conducted in 2 phases : Project Sugar 1 ( 1994 - 1999 ) , which piloted a 4-arm clinic and homebased intervention using nurse case management and community health workers in 186 urban African Americans with type 2 diabetes , and Project Sugar 2 ( 2000 - 2005 ) , which examined effectiveness of this intervention among 542 diabetic , urban African Americans . Results and Conclusions Project Sugar had success with regard to recruitment and retention , both in phase 1 ( 80 % rate at 24 months ) and phase 2 ( > 90 % at 24 months ) . Using the RE- AIM framework , planning and research design for Project Sugar 2 is described in detail for elements that contributed to the reach , effectiveness , adoption , implementation , and maintenance of this study within a minority community setting . In addition to successful strategies , challenges to conducting effectiveness trials in an inner-city African American community are identified PURPOSE The purpose of this r and omized controlled trial is to determine the effectiveness of an intervention led by promotoras ( community lay workers ) on the glycemic control , diabetes knowledge , and diabetes health beliefs of Mexican Americans with type 2 diabetes living in a major city on the Texas-Mexico border . METHODS One hundred fifty Mexican American participants were recruited at a Catholic faith-based clinic and r and omized into 2 groups . Personal characteristics , acculturation , baseline A1C level , diabetes knowledge , and diabetes health beliefs were measured . The intervention was culturally specific and consisted of participative group education , telephone contact , and follow-up using inspirational faith-based health behavior change postcards . The A1C levels , diabetes knowledge , and diabetes health beliefs were measured 3 and 6 months postbaseline , and the mean change between the groups was analyzed . RESULTS The 80 % female sample , with a mean age of 58 years , demonstrated low acculturation , income , education , health insurance coverage , and strong Catholicism . No significant changes were noted at the 3-month assessment , but the mean change of the A1C levels , F(1 , 148 ) = 10.28 , P < .001 , and the diabetes knowledge scores , F(1 , 148 ) = 9.0 , P < .002 , of the intervention group improved significantly at 6 months , adjusting for health insurance coverage . The health belief scores decreased in both groups . CONCLUSIONS The intervention result ed in decreased A1C levels and increased diabetes knowledge , suggesting that using promotoras as part of an interdisciplinary team can result in positive outcomes for Mexican Americans who have type 2 diabetes . Clinical implication s and recommendations for future research are suggested OBJECTIVES A community trial was undertaken to evaluate the effectiveness of the North Carolina Breast Cancer Screening Program , a lay health advisor network intervention intended to increase screening among rural African American women 50 years and older . METHODS A stratified r and om sample of 801 African American women completed baseline ( 1993 - 1994 ) and follow-up ( 1996 - 1997 ) surveys . The primary outcome was self-reported mammography use in the previous 2 years . RESULTS The intervention was associated with an overall 6 percentage point increase ( 95 % confidence interval [ CI ] = -1 , 14 ) in community-wide mammography use . Low-income women in intervention counties showed an 11 percentage point increase ( 95 % CI = 2 , 21 ) in use above that exhibited by low-income women in comparison counties . Adjustment for potentially confounding characteristics did not change the results . CONCLUSIONS A lay health advisor intervention appears to be an effective public health approach to increasing use of screening mammography among low-income , rural population Objective : To evaluate the effectiveness of a lay delivered intervention to reduce Latino children ’s exposure to environmental tobacco smoke ( ETS ) . The a priori hypothesis was that children living in households that were in the intervention group would have lower exposure over time than measurement only controls . Design : A two group , r and omised control trial was conducted . Setting : Areas of San Diego county with a large Latino population . Participants : 143 Latino parent – child pairs . Intervention : Trained bicultural and bilingual Latina lay community health advisors , or promotoras , conducted problem solving aim ed at lowering the target child ’s exposure to ETS in the household . Six home and telephone sessions were delivered by the promotoras over a four month period . Main outcome measures : Outcome measures were collected at baseline , immediately post-intervention , three months post-intervention , and 12 months post-intervention . Four outcomes were considered : ( 1 ) parent ’s paper- and -pencil reports of the child ’s past month exposure ; ( 2 ) hair sample s from the child analysed for past month nicotine ; ( 3 ) hair sample s from the child analysed for past month cotinine ; and ( 4 ) per cent confirmed reducers . Results : There were no significant condition-by-time interactions , the term indicative of a differential intervention effect . Significant or near significant time main effects were seen for children ’s hair cotinine , per cent confirmed reducers , and , in particular , parent reports of exposure . Conclusions : Applying a lay promotora model to deliver the behavioural problem solving intervention unfortunately was not effective . A likely explanation relates to the difficulty of delivering a relatively complex intervention by lay women untrained in behaviour change theory and research methods OBJECTIVES This study examined differences between nurses and paraprofessionals in implementation of a home visiting program for low-income , first-time parents during pregnancy and the first 2 years of the child 's life . METHODS Mothers were r and omly assigned to either a nurse-visited ( n = 236 ) or a paraprofessional-visited ( n = 244 ) condition . Nurse- and paraprofessional-visited families were compared on number and length of visits , topics covered , number of program dropouts , and relationship with home visitor . RESULTS On average , nurses completed more visits than paraprofessionals ( 28 vs 23 ; P < .001 ) and spent a greater proportion of time on physical health issues during pregnancy ( 38 % vs 27 % ; P < .001 ) and on parenting issues during infancy ( 46 % vs 32 % ; P < .001 ) . Paraprofessionals conducted visits that lasted longer and spent a greater proportion of time on environmental health and safety issues ( 15 % vs 7 % pregnancy ; 15 % vs 8 % infancy ; P < .001 ) . While home visitors were viewed equally positively by mothers , nurses had fewer dropouts than did paraprofessionals ( 38 % vs 48 % ; P = .04 ) . More paraprofessional-visited families than nurse-visited families experienced staff turnover . CONCLUSIONS Nurses and paraprofessionals , even when using the same model , provide home visiting services in different ways OBJECTIVE To assess the effectiveness of a volunteer-driven outreach program on immunization rates in children younger than 2 years . DESIGN R and omized controlled trial . SETTING Pediatric ambulatory clinics in New York , NY . PATIENTS A total of 163 children were r and omly assigned to receive services from the volunteer-driven outreach program or to serve as control subjects . All children were ( 1 ) younger than 2 years , ( 2 ) no-shows for a scheduled appointment in the pediatric clinic , and ( 3 ) due or overdue for a vaccine . INTERVENTION Immunization outreach , tracking , and follow-up were provided by community volunteers throughout follow-up ( mean , 6.5 months ) . Control children were notified of immunization status at enrollment but received no further contact until the conclusion of follow-up ( mean , 6.4 months ) . MAIN OUTCOME MEASURE Immunization status 6 months after enrollment . RESULTS Significantly more intervention children were up-to- date with their vaccination series than controls ( 75 % vs. 54 % ; P = .03 ) . Children in the control group were 2.8 times more likely to be late for a vaccine than intervention children ( odds ratio = 2.8 ; P = .02 ) . In addition , an immunization delay of longer than 30 days at enrollment was a significant predictor of final immunization delay ( odds ratio = 2.6 ; P = .02 ) . CONCLUSIONS This volunteer-driven program significantly improved immunization rates among intervention children compared with controls . Results confirm previous findings that indicate an increased risk of an incomplete immunization series by 2 years of age among children who fall behind early in their primary vaccination series . However , control children were almost 3 times more likely to be late ( for > or = 1 vaccines ) than intervention children , regardless of whether an earlier immunization delay was present OBJECTIVES This study assessed the effectiveness of telephone counseling in a church-based mammography promotion intervention trial . METHODS Thirty churches were r and omized to telephone counseling and control conditions ; telephone interview data were used in assessing intervention effects on mammography adherence . Separate analyses were conducted for baseline-adherent participants ( maintaining adherence ) and baseline-nonadherent participants ( conversion to adherence ) . RESULTS Year 1 follow-up data indicated that the telephone counseling intervention maintained mammography adherence among baseline-adherent participants and reduced the nonadherence rate from 23 % to 16 % . CONCLUSIONS Partnerships between the public health and faith communities are potentially effective conduits to promote maintenance of widely endorsed health behaviors such as regular cancer screening Introduction The Tepeyac Project is a church-based health promotion project that was conducted from 1999 through 2005 to increase breast cancer screening rates among Latinas in Colorado . Previous reports evaluated the project among Medicare and Medicaid enrollees in the state . In this report , we evaluate the program among enrollees in the state 's five major insurance plans . Methods We compared the Tepeyac Project 's two interventions : the Printed Intervention and the Promotora Intervention . In the first , we mailed culturally tailored education packages to 209 Colorado Catholic churches for their use . In the second , promotoras ( peer counselors ) in four Catholic churches delivered breast-health education messages personally . We compared biennial mammogram cl aims from the five insurance plans in the analysis at baseline ( 1998–1999 ) and during follow-up ( 2000–2001 ) for Latinas who had received the interventions . We used generalized estimating equations ( GEE ) analysis to adjust rates for confounders . Results The mammogram rate for Latinas in the Printed Intervention remained the same from baseline to follow-up ( 58 % [ 2979/5130 ] vs 58 % [ 3338/5708 ] ) . In the Promotora Intervention , the rate was 59 % ( 316/536 ) at baseline and 61 % ( 359/590 ) at follow-up . Rates increased modestly over time and varied widely by insurance type . After adjusting for age , income , urban versus rural location , disability , and insurance type , we found that women exposed to the Promotora Intervention had a significantly higher increase in biennial mammograms than did women exposed to the Printed Intervention ( GEE parameter estimate = .24 [ ±.11 ] , P = .03 ) . Conclusion For insured Latinas , personally delivering church-based education through peer counselors appears to be a better breast-health promotion method than mailing printed educational material s to churches OBJECTIVE To examine the effectiveness of home visiting by paraprofessionals and by nurses as separate means of improving maternal and child health when both types of visitors are trained in a program model that has demonstrated effectiveness when delivered by nurses . METHODS A r and omized , controlled trial was conducted in public- and private-care setting s in Denver , Colorado . One thous and one hundred seventy-eight consecutive pregnant women with no previous live births who were eligible for Medicaid or who had no private health insurance were invited to participate . Seven hundred thirty-five women were r and omized to control , paraprofessional , or nurse conditions . Nurses completed an average of 6.5 home visits during pregnancy and 21 visits from birth to the children 's second birthdays . Paraprofessionals completed an average of 6.3 home visits during pregnancy and 16 visits from birth to the children 's second birthdays . The main outcomes consisted of changes in women 's urine cotinine over the course of pregnancy ; women 's use of ancillary services during pregnancy ; subsequent pregnancies and births , educational achievement , workforce participation , and use of welfare ; mother-infant responsive interaction ; families ' home environments ; infants ' emotional vulnerability in response to fear stimuli and low emotional vitality in response to joy and anger stimuli ; and children 's language and mental development , temperament , and behavioral problems . RESULTS Paraprofessional-visited mother-child pairs in which the mother had low psychological re sources interacted with one another more responsively than their control-group counterparts ( 99.45 vs 97.54 st and ard score points ) . There were no other statistically significant paraprofessional effects . In contrast to their control-group counterparts , nurse-visited smokers had greater reductions in cotinine levels from intake to the end of pregnancy ( 259.0 vs 12.32 ng/mL ) ; by the study child 's second birthday , women visited by nurses had fewer subsequent pregnancies ( 29 % vs 41 % ) and births ( 12 % vs 19 % ) ; they delayed subsequent pregnancies for longer intervals ; and during the second year after the birth of their first child , they worked more than women in the control group ( 6.83 vs 5.65 months ) . Nurse-visited mother-child pairs interacted with one another more responsively than those in the control group ( 100.31 vs 98.99 st and ard score points ) . At 6 months of age , nurse-visited infants , in contrast to their control-group counterparts , were less likely to exhibit emotional vulnerability in response to fear stimuli ( 16 % vs 25 % ) and nurse-visited infants born to women with low psychological re sources were less likely to exhibit low emotional vitality in response to joy and anger stimuli ( 24 % vs 40 % and 13 % vs 33 % ) . At 21 months , nurse-visited children born to women with low psychological re sources were less likely to exhibit language delays ( 7 % vs 18 % ) ; and at 24 months , they exhibited superior mental development ( 90.18 vs 86.20 Mental Development Index scores ) than their control-group counterparts . There were no statistically significant program effects for the nurses on women 's use of ancillary prenatal services , educational achievement , use of welfare , or their children 's temperament or behavior problems . For most outcomes on which either visitor produced significant effects , the paraprofessionals typically had effects that were about half the size of those produced by nurses . CONCLUSIONS When trained in a model program of prenatal and infancy home visiting , paraprofessionals produced small effects that rarely achieved statistical or clinical significance ; the absence of statistical significance for some outcomes is probably attributable to limited statistical power to detect small effects . Nurses produced significant effects on a wide range of maternal and child outcomes There is little documentation about the recruitment process for church-based health education programs . In this study , the authors recruit African American , Latino , and white churches and women members ( age 50 to 80 ) for a r and omized church-based trial of mammography promotion in Los Angeles County . Efforts to enhance recruitment began 10 months before churches were invited to participate and included a variety of community-based strategies . Subsequently , 45 churches were recruited over a 5-month period through group pastor breakfast meetings and church-specific follow-up . In close collaboration with the 45 churches , the authors administered church-based surveys over 6 months and identified 1,967 age-eligible women who agreed to be contacted by the program team . It was found that an extended re source intensive period of relationship-building and community-based activities were necessary to conduct church-based programs effectively , particularly among older and ethnically diverse urban population Background —Black subjects with a family history of premature coronary heart disease ( CHD ) have a marked excess risk , yet barriers prevent effective risk reduction . We tested a community-based multiple risk factor intervention ( community-based care [ CBC ] ) and compared it with “ enhanced ” primary care ( EPC ) to reduce CHD risk in high-risk black families . Methods and Results —Black 30- to 59-year-old siblings of a prob and with CHD aged < 60 years were r and omized for care of BP ≥140/90 mm Hg , LDL cholesterol ≥3.37 mmol/L , or current smoking to EPC ( n=168 ) or CBC ( n=196 ) and monitored for 1 year . EPC and CBC were design ed to eliminate barriers to care . The CBC group received care by a nurse practitioner and a community health worker in a community setting . The CBC group was 2 times more likely to achieve goal levels of LDL cholesterol and blood pressure compared with the EPC group ( 95 % CI , 1.11 to 4.20 and 1.39 to 3.88 , respectively ) with adjustment for baseline levels of age , sex , education , and baseline use of medications . The CBC group demonstrated a significant reduction in global CHD risk , whereas no reduction was seen in the EPC group ( P<0.0001 ) . Conclusions —Eliminating known barriers may not be sufficient to reduce CHD risk in primary care setting s. An alternative community care model that addresses barriers may be a more effective way to ameliorate CHD risk in high-risk black families OBJECTIVE To describe family identification , family engagement , and service delivery in a statewide home visiting program for at-risk families of newborns . SETTING Six target communities of Hawaii 's Healthy Start Program ( HSP ) , which incorporates 1 ) early identification of at-risk families of newborns via population -based screening and assessment , and 2 ) paraprofessional home visiting to improve family functioning , promote child health and development , and prevent child maltreatment . DESIGN Cross-sectional study : describes early identification process and family characteristics associated with initial enrollment . Longitudinal study : describes home visiting process and characteristics associated with continued participation . SUBJECTS Cross-sectional study : civilian births in 6 communities ( n = 6553 ) . Longitudinal study : at-risk families in the intervention group of a r and omized trial of the HSP ( n = 373 ) . MEASURES PROCESS completeness and timeliness of early identification and home visiting activities ; family characteristics : sociodemographics , child abuse risk factors , infant biologic risk . RESULTS Early identification staff determined risk status for 84 % of target families . Families with higher risk scores , young mothers with limited schooling , and families with infants at biologic risk were more likely to enroll in home visiting . Half of those who enrolled were active at 1 year with an average of 22 visits . Families where the father had multiple risk factors and where the mother was substance abusing were more likely to have > /=12 visits ; mothers who were unilaterally violent toward the father were less likely . Most families were linked with a medical home ; linkage rates for other community re sources varied widely by type of service . Half of families overall , but > /=80 % of those active at 1 year , received core home visiting services . Performance varied by program site . CONCLUSIONS It is challenging to engage and retain at-risk families in home visiting . Service monitoring must be an integral part of operations INTRODUCTION Mammography is underused by certain groups of women , in particular poor and minority women . We developed a lay health advisor ( LHA ) intervention based on behavioral theories and tested whether it improved mammography attendance in Robeson County , NC , a rural , low-income , triracial ( white , Native American , African American ) population . METHODS A total of 851 women who had not had a mammogram within the past year were r and omly assigned to the LHA intervention ( n = 433 ) or to a comparison arm ( n = 418 ) during 1998 - 2002 . Rates of mammography use after 12 - 14 months ( as verified by medical record review ) were compared using a chi-square test . Baseline and follow-up ( at 12 - 14 months ) surveys were used to obtain information on demographics , risk factors , and barriers , beliefs , and knowledge about mammography . Linear regression , Mantel-Haenszel statistics , and logistic regression were used to compare barriers , beliefs , and knowledge from baseline to follow-up and to identify baseline factors associated with mammography . RESULTS At follow-up , 42.5 % of the women in the LHA group and 27.3 % of those in the comparison group had had a mammogram in the previous 12 months ( relative risk = 1.56 , 95 % confidence interval [ CI ] = 1.29 to 1.87 ) . Compared with those in the comparison group , women in the LHA group displayed statistically significantly better belief scores ( difference = 0.46 points on a 0 - 10 scale , 95 % CI = 0.15 to 0.77 ) and reduced barriers at follow-up ( difference = -0.77 points , 95 % CI = -1.02 to -0.53 ) , after adjusting for baseline scores . CONCLUSIONS LHA interventions can improve mammography utilization . Future studies are needed to assess strategies to disseminate effective LHA interventions to underserved population BACKGROUND North American Chinese women have lower levels of Papanicolaou ( Pap ) testing than other population subgroups . We conducted a r and omized controlled trial to evaluate the effectiveness of two alternative cervical cancer screening interventions for Chinese women living in North America . METHODS Four hundred and eighty-two Pap testing underutilizers were identified from community-based surveys of Chinese women conducted in Seattle , Washington , and Vancouver , British Columbia . These women were r and omly assigned to one of two experimental arms or control status . Several Chinese- language material s were used in both experimental arms : an education-entertainment video , a motivational pamphlet , an educational brochure , and a fact sheet . Women in the first experimental group ( outreach worker intervention ) received the material s , as well as tailored counseling and logistic assistance , during home visits by trilingual , bicultural outreach workers . Those in the second experimental group ( direct mail intervention ) received the material s by mail . The control group received usual care . Follow-up surveys were completed 6 months after r and omization to ascertain participants ' Pap testing behavior . All statistical tests were two-sided . RESULTS A total of 402 women responded to the follow-up survey ( 83 % response rate ) . Of these women , 50 ( 39 % ) of the 129 women in the outreach group , 35 ( 25 % ) of the 139 women in the direct mail group , and 20 ( 15 % ) of the 134 women in the control group reported Pap testing in the interval between r and omization and follow-up data collection ( P<.001 for outreach worker versus control , P = .03 for direct mail versus control , and P = .02 for outreach worker versus direct mail ) . Intervention effects were greater in Vancouver than in Seattle . CONCLUSION Culturally and linguistically appropriate interventions may improve Pap testing levels among Chinese women in North America OBJECTIVE To present the results of an intervention trial to enhance parents ' home-safety practice s through pediatric safety counseling , home visits , and an on-site children 's safety center where parents receive personalized education and can purchase reduced-cost products . DESIGN Pediatricians were r and omized to a st and ard- or an enhanced-intervention group . Parents of their patients were enrolled when the patient was 6 months or younger and observed until 12 to 18 months of age . SETTING A hospital-based pediatric resident continuity clinic that serves families living in low-income , inner-city neighborhoods . PARTICIPANTS First- and second-year pediatric residents and their patient-parent dyads . INTERVENTIONS Parents in the st and ard-intervention group received safety counseling and referral to the children 's safety center from their pediatrician . Parents in the enhanced-intervention group received the st and ard services plus a home-safety visit by a community health worker . OUTCOMES Home observers assessed the following safety practice s : reduction of hot-water temperature , poison storage , and presence of smoke alarms , safety gates for stairs , and ipecac syrup . RESULTS The prevalence of safety practice s ranged from 11 % of parents who stored poisons safely to 82 % who had a working smoke alarm . No significant differences in safety practice s were found between study groups . However , families who visited the children 's safety center compared with those who did not had a significantly greater number of safety practice s ( 34 % vs 17 % had > or 3 ) . CONCLUSIONS Home visiting was not effective in improving parents ' safety practice s. Counseling coupled with convenient access to reduced-cost products appears to be an effective strategy for promoting children 's home safety OBJECTIVES We sought to promote cervical cancer screening among Vietnamese American women in Santa Clara County , Calif. METHODS In 2001 - 2004 , we recruited and r and omized 1005 Vietnamese American women into 2 groups : lay health worker outreach plus media-based education ( combined intervention ) or media-based education only . Lay health workers met with the combined intervention group twice over 3 to 4 months to promote Papanicolaou ( Pap ) testing . We used question naires to measure changes in awareness , knowledge , and Pap testing . RESULTS Testing increased among women in both the combined intervention ( 65.8 % to 81.8 % ; P<.001 ) and media-only ( 70.1 % to 75.5 % ; P<.001 ) groups , but significantly more in the combined intervention group ( P=.001 ) . Among women never previously screened , significantly more women in the combined intervention group ( 46.0 % ) than in the media-only group ( 27.1 % ) obtained tests ( P<.001 ) . Significantly more women in the combined intervention group obtained their first Pap test or obtained one after an interval of more than 1 year ( became up-to- date ; 45.7 % to 67.3 % , respectively ; P<.001 ) than did those in the media-only group ( 50.9 % to 55.7 % , respectively ; P=.035 ) . CONCLUSIONS Combined intervention motivated more Vietnamese American women to obtain their first Pap tests and to become up-to- date than did media education alone BACKGROUND Reminder-recall interventions have improved immunization rates in numerous studies . OBJECTIVE To evaluate the impact of large-scale , registry-based reminder-recall interventions on low immunization rates in an inner-city population . DESIGN R and omized , controlled , effectiveness trial . SETTING Fulton County , Georgia . PARTICIPANTS A total of 3050 children ( 76 % black , 14 % Hispanic , 7 % white , and 3 % other or unknown ; median age , 9 months ; range , 1 - 14 months ) identified in an immunization registry as receiving health care in the public sector . INTERVENTIONS Each child was r and omly assigned to 1 of 4 groups : control ( usual care ) , autodialer ( automated telephone or mail reminder recall ) , outreach ( in-person telephone , mail , or home visit recall ) , and combination ( autodialer with outreach backup ) . Interventions continued until the child reached 24 months of age . MAIN OUTCOME MEASURE Completion by the age of 24 months of the 4 - 3 - 1 - 3 vaccination series based on intention-to-treat analysis . RESULTS A total of 260 ( 34 % ) of the 763 patients in the control group , 306 ( 40 % ) of the 763 in the autodialer group , 284 ( 37 % ) of the 760 in the outreach group , and 293 ( 38 % ) of 764 in the combination group completed the vaccination series . CONCLUSION Large-scale , registry-based reminder-recall interventions produced only small improvements in low immunization rates of an inner-city population OBJECTIVES To determine the long-term effect of a community-based risk reduction intervention at five years after completion of a one-year r and omized clinical trial and to determine the sustainability of the beneficial effects seen one year after the intervention . METHODS 30- to 59- year-old African American siblings of prob and s with premature coronary heart disease ( CHD ) were r and omized for care of multiple CHD risk factors to either one year of community-based care ( CBC ) provided by a nurse practitioner/community health worker team or enhanced usual care ( EUC ) . At five years , 307 ( 84.6 % ) of the siblings returned for reevaluation . MAIN OUTCOME MEASURES Changes in and achievement of goal levels of low-density lipoprotein cholesterol ( LDL-C ) , systolic and diastolic blood pressure ( SBP and DBP , respectively ) , and smoking cessation at five years . RESULTS No significant differences were seen between groups in mean LDL-C , SBP , and DBP or in the overall percentages achieving goal LDL-C , blood pressure , or smoking status . Changes after completion of the intervention suggest that the CBC group lost the beneficial effects for mean LDL-C and for percentage at goal LDL-C , while the EUC group continued to improve . CBC was associated with greater sustainability and less refractoriness of one-year results for LDL-C and blood pressure goals . CONCLUSIONS Although no group differences were found in mean risk factor levels at five years , data indicate that CBC is both feasible and associated with earlier sustainability of positive risk factor changes compared with EUC This study investigated the effectiveness of a community-academic health center partnership , utilizing nurse-supervised indigenous community health workers , in decreasing the blood pressure in an urban African-American population . A four-year r and omized clinical trial was conducted in the S and town-Winchester community , which has an excess prevalence of high blood pressure , in order to test the effectiveness of 2 different levels of intervention intensity on increasing the control of high blood pressure . Community health workers were trained and certified in blood pressure management , monitoring , education and counseling , social support mobilization , and community outreach and follow up . The primary results were a significant decrease in mean systolic and diastolic pressures after both levels of intervention , and a significant increase in the percentage of individuals with controlled high blood pressure . Surprisingly , no differences in results were observed between the 2 levels of intervention intensity . This study supports the use of community-based partnership efforts , and the utilization of indigenous health workers , to enhance the control of high blood pressure in a high-risk , African-American urban population This article describes the evaluation of a community-based participatory research ( CBPR ) community health worker ( CHW ) intervention to improve children 's asthma-related health by reducing household environmental triggers for asthma . After r and omization to an intervention or control group , 298 households in Detroit , Michigan , with a child , aged 7 to 11 , with persistent asthma symptoms participated . The intervention was effective in increasing some of the measures of lung function ( daily nadir Forced Expiratory Volume at one second [ p = .03 ] and daily nadir Peak Flow [ p = .02 ] ) , reducing the frequency of two symptoms ( “ cough that wo n't go away , ” “ coughing with exercise ” ) , reducing the proportion of children requiring unscheduled medical visits and reporting inadequate use of asthma controller medication , reducing caregiver report of depressive symptoms , reducing concentrations of dog allergen in the dust , and increasing some behaviors related to reducing indoor environmental triggers . The results suggest a CHW environmental intervention can improve children 's asthma-related health , although the pathway for improvement is complex INTRODUCTION The Community Trial of Mammography Promotion assessed the effectiveness of mammography promotion by community volunteer groups in rural areas . Three interventions were tested . One used an individual counseling strategy , one used a community activities strategy , and a third combined the two strategies . METHODS The effects of the interventions were tested by r and omizing 40 communities either to the study interventions or to a control group . A cohort of 352 women from each community was r and omly selected and used to evaluate the interventions ' effectiveness . Of these , 6592 women were eligible for screening mammography at baseline and follow-up and were successfully interviewed prior to and after study intervention activities . RESULTS Although the interventions did not significantly increase women 's overall use of mammography , the community activities intervention increased use at follow-up by regular users over baseline by 2.9 % ( p = 0.01 ) . Intervention appears to have increased the use of mammography among certain groups of women who were not regular users at baseline , including those in communities without female physicians ( 10 % to 16 % ; p < 0.05 ) , and among women with no health insurance ( 10 % to 23 % ; p < /= 0.05 ) . CONCLUSION Volunteers can effectively promote mammography in rural communities INTRODUCTION We conducted a r and omized controlled trial to determine if an in-home educational intervention conducted by lay health workers ( LHWs ) could increase adherence among low-income , inner-city , African-American women to breast and cervical cancer screening schedules . METHODS We recruited 321 African-American women from diverse inner-city sources . After baseline interviews , they were r and omly assigned to either the intervention ( n = 163 ) or the control ( n = 158 ) group . Those in the intervention group were visited in their homes up to three times by LHWs who provided a culturally sensitive educational program that emphasized the need for screening . RESULTS Ninety-three ( 93 ) women in the intervention group and 102 in the control group completed the postintervention interview . For Pap smears , the increase in screening was similar in both groups . For clinical breast exams ( CBEs ) , however , there was a modest increase in the intervention group . The improvement was greatest for mammography , for which there was a 10 % to 12 % increase . Among women who were not on recommended schedules at baseline , the improvement was substantial and greater in the intervention group . CONCLUSIONS LHWs ' intervention appeared to improve the rate at which inner-city women obtained CBEs and mammograms , but had no effect on Pap smears . A high attrition rate weakened our ability to make conclusive statements about the exact impact of the intervention BACKGROUND Few studies compare the influence of different types of dietary interventions on the dietary practice s of Latinas in the short and long term . The present study examined the 1-year impact of two innovative behavior-change approaches to reduce dietary fat and increase fiber . DESIGN Three-group r and omized controlled trial : ( 1 ) personalized dietary counseling via lay heath advisors ( promotoras ) plus tailored print material s delivered via the mail , ( 2 ) tailored mailed print material s only , and ( 3 ) targeted mailed " off-the-shelf " material s. SETTING / PARTICIPANTS A total of 357 Latinas were r and omly assigned to the three aforementioned conditions . INTERVENTION Promotora and tailored print material s. MAIN OUTCOME MEASURES Fat intake ( total grams of fat and percent calories from dietary fat ) and number of grams of dietary fiber . RESULTS Earlier work reported that at immediate post-intervention the promotora group achieved significantly lower levels of total fat grams , and lower levels of energy intake , total saturated fat , total carbohydrates , glucose , and fructose than the targeted group . However , the present longitudinal analyses suggest that the effects achieved by the promotoras dissipated over the 12-month follow-up period while the effects of the tailored group concurrently improved . CONCLUSIONS The high interactivity ( i.e. , calls , visits ) of the promotora condition may have been the most salient reinforcer and may have led to further tailoring , making this type of intervention more effective than the comparison groups in the short term . Further research should explore whether booster sessions involving promotoras help to maintain the impact over time OBJECTIVES We assessed the effectiveness of a community health worker intervention focused on reducing exposure to indoor asthma triggers . METHODS We conducted a r and omized controlled trial with 1-year follow-up among 274 low-income households containing a child aged 4 - 12 years who had asthma . Community health workers provided in-home environmental assessment s , education , support for behavior change , and re sources . Participants were assigned to either a high-intensity group receiving 7 visits and a full set of re sources or a low-intensity group receiving a single visit and limited re sources . RESULTS The high-intensity group improved significantly more than the low-intensity group in its pediatric asthma caregiver quality -of-life score ( P=.005 ) and asthma-related urgent health services use ( P=.026 ) . Asthma symptom days declined more in the high-intensity group , although the across-group difference did not reach statistical significance ( P=.138 ) . Participant actions to reduce triggers generally increased in the high-intensity group . The projected 4-year net savings per participant among the high-intensity group relative to the low-intensity group were 189 - 721 dollars . CONCLUSIONS Community health workers reduced asthma symptom days and urgent health services use while improving caregiver quality -of-life score . Improvement was greater with a higher-intensity intervention Pediatric asthma is a growing public health issue , disproportionately affecting low-income people and people of color . Exposure to indoor asthma triggers plays an important role in the development and exacerbation of asthma . We describe the implementation of the Seattle-King County Healthy Homes Project , a r and omized , controlled trial of an outreach/education intervention to improve asthma-related health status by reducing exposure to allergens and irritants in the home . We r and omly assigned 274 low-income children with asthma ages 4 - 12 to either a high- or a low-intensity group . In the high-intensity group , community health workers called Community Home Environmental Specialists ( CHES ) conducted initial home environmental assessment s , provided individualized action plans , and made additional visits over a 12-month period to provide education and social support , encouragement of participant actions , provision of material s to reduce exposures ( including bedding encasements ) , assistance with roach and rodent eradication , and advocacy for improved housing conditions . Members of the low-intensity group received the initial assessment , home action plan , limited education during the assessment visit , and bedding encasements . We describe the recruitment and training of CHES and challenges they faced and explain the assessment and exposure reduction protocol s addressing dust mites , mold , tobacco smoke , pets , cockroaches , rodents , dust , moisture , and toxic or hazardous chemicals . We also discuss the gap between the practice s recommended in the literature and what is feasible in the home . We accomplished home interventions and participants found the project very useful . The project was limited in resolving structural housing quality issues that contributed to exposure to indoor triggers OBJECTIVE Three types of case management were compared to determine their relative effectiveness in helping people with severe mental illness who were homeless or at risk of homelessness . METHODS Subjects recruited from a psychiatric emergency room and inpatient units were r and omly assigned to one of the three treatment conditions : broker case management , in which the client 's needs were assessed , services were purchased from multiple providers , and the client was monitored ; assertive community treatment only , in which comprehensive services were provided for an unlimited period ; and assertive community treatment augmented by support from community workers , who assisted with activities of daily living and were available for leisure activities . Of 165 subjects recruited , 135 were followed for 18 months . RESULTS Compared with clients assigned to broker case management , clients assigned to assertive community treatment only and assertive community treatment with community workers had superior outcomes on several variables . They were number of contacts with the assigned treatment program , re source utilization ( for example , use of entitlements ) , severity of thought disorder , activity level , and client satisfaction . Clients in the assertive community treatment only condition achieved more days in stable housing than those in the other two treatment conditions . No significant treatment group effects were found on income , self-esteem , or substance abuse . CONCLUSIONS Assertive community treatment is superior to broker case management in assisting individuals with serious mental illness who are at risk of homelessness Perinatal child abuse prevention projects are increasingly favored but rarely evaluated . The paper describes an experimental evaluation of the Child Parent Enrichment Project ( CPEP ) . Women were referred to the project during or just after pregnancy if identified as at-risk of engaging in child abuse by community professionals . Clients were r and omly assigned to CPEP services ( n=24 ) or traditional community services ( n=26 ) . CPEP services involved six months of home visiting by paraprofessional women and linkage to other formal and informal community re sources . Multivariate Analysis of Covariance on posttest scores , controlling for pretest scores , show advantage for the CPEP group in prenatal care , birth outcomes , better reports of child temperament , and better indicators of child welfare . CPEP mothers tended to report better well-being . No significant differences were demonstrated for levels of formal and informal support . Reports of child abuse were similar for both groups . Consumer satisfaction indicates that clients valued the program . The preliminary results argue for further use and evaluation of perinatal child abuse prevention services OBJECTIVE In this study the authors compared the cost-effectiveness of three approaches to case management for individuals with severe mental illness who were at risk for homelessness : assertive community treatment alone , assertive community treatment with community workers , and brokered case management ( purchase of services ) . METHOD Individuals were r and omly assigned to the three treatment conditions and followed for 18 months . Eligibility requirements included a severe DSM-III axis I diagnosis , such as schizophrenia , and either current homelessness or risk for homelessness based on prior history of homelessness . Participants were recruited from the emergency rooms and inpatient units of local psychiatric hospitals . Data on 85 people were available for analyses : 28 in assertive community treatment alone , 35 in assertive community treatment with community workers , and 22 receiving brokered case management ( purchase of services ) . RESULTS Clients assigned to the two assertive community treatment conditions had more contact with their treatment programs , experienced greater reductions in psychiatric symptoms , and were more satisfied with their treatment than clients in the brokered condition . There was no statistically significant difference between treatment conditions in terms of the total costs of treating the participants . However , the assertive community treatment conditions spent less money on inpatient services than brokered case management , but more on case management services and maintenance ( i.e. , food stamps , housing subsidies , and Supplemental Security Income payments ) . CONCLUSIONS Assertive community treatment has better client outcomes at no greater cost and is , therefore , more cost-effective than brokered case management OBJECTIVE To describe the short-term impact of the intervention known as Por La Vida ( PLV ) on cancer screening for Latinas in San Diego , California . METHODS Thirty-six lay community workers ( consejeras ) were recruited and trained to conduct educational group sessions . Each consejera recruited approximately 14 peers from the community to participate in the program . The consejeras were r and omly assigned to either a twelve-week cancer screening intervention group or a control group in which they participated in an equally engaging program entitled " Community Living Skills . " Pre- and post-intervention self-report information was obtained from project participants on the use of cancer screening examinations . Outcome measures were changes in the percentages of women who had breast and cervical cancer screening test within the past year before and after the intervention occurred . Experimental and control groups were compared using t-tests . Analyses were conducted using both consejeras and participants as the unit of analysis . RESULTS The increase in the use of the cancer screening test was higher in the PLV cancer intervention group in comparison to women in the community living skills control group . CONCLUSIONS Key to the PLV intervention model is the identification of natural helpers in the Latino community and their subsequent training in intervention based on social learning theory using culturally appropriate educational material s. The model is an effective and viable approach for increasing the use of cancer screening tests in Latinas of low socioeconomic level and low level of acculturation OBJECTIVES Injury is a major US public health problem , particularly in urban minority communities . This paper evaluates the impact of the Safe Block Project , a comprehensive injury prevention trial , on home hazards and injury prevention knowledge in a poor urban African-American community . METHODS Nine census tracts in the community were allocated to either the intervention area or the control area . The intervention , carried out by trained community outreach workers , consisted of ( 1 ) home modification for simple prevention measures , ( 2 ) home inspection accompanied by information about home hazards , and ( 3 ) education about selected injury prevention practice s. Approximately 12 months after the intervention , r and om sample s of control and intervention homes were assessed for home hazards and injury prevention knowledge . RESULTS A significantly larger proportion of intervention homes than control homes had functioning smoke detectors , syrup of ipecac , safely stored medications , and reduced electrical and tripping hazards . No consistent differences were observed between control and intervention homes on home hazards requiring major effort to correct . CONCLUSIONS There was a distinct difference between control and intervention homes with respect to safety knowledge and home hazards requiring minimal to moderate effort to correct . The Safe Block Project could serve as a model for future urban injury prevention efforts Study Design . R and omized , controlled trial . Objective . To evaluate a four‐session self‐management group intervention for patients with pain in primary care , led by trained lay persons with back pain . The intervention was design ed to reduce patient worries , encourage self‐care , and reduce activity limitations . Background Data . R and omized trials of educational interventions suggest that activating interventions may improve back pain outcomes . Expert opinion increasingly regards effective self‐management of back pain as important in achieving good outcomes . In this study , an educational intervention design ed to activate patients and support effective self‐management was evaluated . Methods . Six to 8 weeks after a primary care visit for back pain , patients were invited to participate in an educational program to improve back pain self‐management . Those showing interest by returning a brief question naire became eligible for the study . Participants ( n = −255 ) r and omly were assigned to either a self‐management group intervention or to a usual care control group . The effect of the intervention , relative to usual care , was assessed 3 , 6 , and 12 months after r and omization , controlling for baseline values . The intervention consisted of a four‐session group applying problem‐solving techniques to back pain self‐management , supplemented by educational material s ( book and videos ) supporting active management of back pain . The groups were led by lay persons trained to implement a fully structured group protocol . The control group received usual care , supplemented by a book on back pain care . Results . Participants r and omly assigned to the self‐management groups reported significantly less worry about back pain and expressed more confidence in self‐care . Rol and Disability Question naire Scores were significantly lower among participants in the self‐management groups relative to the usual care controls at 6 months ( P = 0.007 ) , and this difference was sustained at 12 months at borderline significance levels ( P = 0.09 ) . Among self‐management group participants , 48 % showed a 50 % or greater reduction in Rol and Disability Question naire Score at 6 months , compared with 33 % among the usual care controls . Conclusions . Self‐management groups led by trained lay persons following a structured protocol were more effective than usual care in reducing worries , producing positive attitudes toward self‐care , and reducing activity limitations among patients with back pain in primary care Perinatal child abuse prevention projects are rarely rigorously evaluated . Women were referred to the Child Parent Enrichment Project ( CPEP ) project during or just after pregnancy if identified as at-risk of engaging in child abuse by community professionals . Clients were r and omly assigned to CPEP services ( n = 97 ) or traditional community services ( n = 94 ) . CPEP services are based on ecological theory and involve six months of home visiting by paraprofessional women and linkage to other formal and informal community re sources . No advantages on self-report measures for the CPEP group were measured at posttest , and follow-up reports of child abuse were similar for both groups . Consumer satisfaction indicates that clients highly valued the program . Some indication of greater success with families with less serious problems was observed . The results argue for caution regarding the capacities of perinatal child abuse prevention services to serve the high-risk clientele they often receive Participants ( N=357 ) were r and omly assigned to 1 of 3 conditions : lay health advisor ( promotora ) plus tailored print material s , tailored print material s only ( tailored ) , or off-the-shelf print material s ( control ) . The primary outcomes were calories from fat and daily grams of fiber . Secondary outcomes included total energy intake , total and saturated fat intake , and total carbohydrates . Adjusted for baseline values , calories from fat were 29 % , 30 % , and 30 % for the promotora , tailored , and control conditions , respectively , and grams of fiber consumed were 16 g , 17 g , and 16 g. Significant Condition X Time interactions were not observed between baseline and 12-weeks postintervention . The LHA condition achieved significantly lower levels of energy intake , total fat and saturated fat , and total carbohydrates . The relative superiority of the promotora condition may derive from the personal touch achieved in the face-to-face interactions or from the women 's use of print material s under the promotora 's guidance Research ers at Johns Hopkins University conducted a r and omized clinical trial to test the effect of nurse case management and community health worker interventions on diabetes control among inner city African Americans . The results demonstrated that the greatest improvement occurred when nurse case managers and community health workers worked together . This study has implication s for how nurse/home health aide collaboration can enhance diabetes management in home care PURPOSE This study examines the effectiveness of the Witness Project , a culturally competent cancer education program that trains cancer survivors to promote early detection and increased breast self-examination and mammography in a population of rural , underserved , African American women . DESCRIPTION OF STUDY The primary setting for the Witness Project-an intensive , community-based , culturally sensitive educational program that incorporates spirituality and faith-was the African American church . Baseline and 6-month follow-up surveys were obtained from 206 African American women in two intervention counties and from 204 African American women in two control counties in the rural Mississippi River Delta region of Arkansas . RESULTS Witness Project participants significantly increased ( P < .0001 ) their practice of breast self-examination and mammography ( P < .005 ) compared with the women in the control counties . CLINICAL IMPLICATION S These results demonstrate that intensive , community-based , culturally sensitive educational programming incorporating the spiritual environment of the faith community , such as the Witness Project , can positively influence breast cancer screening behaviors among rural , underserved African American women . Through the use of community churches and cancer survivors , breast cancer screening activities can be improved in this population OBJECTIVES This study assessed the effectiveness of enhanced tracking and follow-up services provided by community health workers in promoting medical follow-up of persons whose elevated blood pressures were detected during blood pressure measurement at urban community sites . METHODS In a r and omized controlled trial , 421 participants received either enhanced or usual referrals to care . Participants were 18 years or older , were either Black or White , and had blood pressure greater than or equal to 140/90 mm Hg and income equal to or less than 200 % of poverty . The primary outcome measure was completion of a medical follow-up visit within 90 days of referral . RESULTS The enhanced intervention increased follow-up by 39.4 % ( 95 % confidence interval [ CI ] = 14 % , 71 % ; P = .001 ) relative to usual care . Follow-up visits were completed by 65.1 % of participants in the intervention group , compared with 46.7 % of those in the usual-care group . The number needed to treat was 5 clients ( 95 % CI = 3 , 13 ) per additional follow-up visit realized . CONCLUSIONS Enhanced tracking and outreach increased the proportion of persons with elevated blood pressure detected during community measurement who followed up with medical care This paper describes the design and methodology of the Community Hypertension Intervention Project ( CHIP ) . CHIP is investigating the environmental and psychosocial factors related to treatment adherence and examining the effects of combining usual hypertension care with the effects of three interventions design ed to improve patient compliance with treatment for high blood pressure in a high-risk , underserved minority population . Thirteen hundred and sixty-seven inner-city hypertension patients ( 75 % black and 25 % Hispanic ) have agreed to participate in the 4-year longitudinal study . These participants were r and omized to usual care or one of three intervention groups : individualized counseling sessions ; home visits/ discussion groups ; or computerized appointment-tracking system . Participants are representative of the surrounding , predominantly low-income minority community and are treated in a hospital-based clinic and in a private clinic in the community . About 65 % have blood pressure levels considered to be out of control . It was concluded that structural changes at the clinic site , along with the targeted interventions , would improve patient satisfaction , increase treatment adherence , and improve blood pressure control Examined the moderating effects of risk status on the impact of home intervention in a follow-up study of children with failure-to-thrive ( FTT ) . Two types of risk ( demographic and maternal negative affectivity ) and two levels of intervention were examined . In this r and omized clinical trial , all children received services in a multidisciplinary growth and nutrition clinic , and half the children also received home visits from a lay home visitor for 1 year . There were no effects of demographic risk , maternal negative affectivity , or intervention status on child outcome at the close of the home intervention . However , at age 4 , more than 1 year after the home intervention ended , there were effects of the home intervention on motor development among all children and on cognitive development and behavior during play among children of mothers who reported low levels of negative affectivity . Results highlight the importance of conducting follow-up assessment s in the evaluation of home intervention services , and suggest that among low-SES families of children with FTT , home intervention may be most useful among mothers with low negative affectivity Objectives . To assess the effectiveness of breast health promoting messages administered by salon stylists to clients in the salon setting . Methods . Forty salons in an urban , minority area were r and omly assigned to provide messages to clients or to serve as controls . Pre-intervention surveys were completed by 1,185 salon clients . Following program initiation , assessment s of 1,210 clients were conducted . Results . Among women completing surveys at control salons , 10 % reported exposure to breast health messages , as opposed to 37 % at experimental salons ( OR 5.4 , 95 % CI 3.7–7.9 ) . Self-reported exposure to stylist-delivered messages was associated with improved breast self-examination rates ( OR 1.6 , 95 % CI 1.2–2.1 ) and with greater intentions to have a clinical breast examination ( OR 1.9 , 95 % CI 1.1–3.3 ) . Conclusion . Hair salons are a potentially important venue for promotion of health behaviors related to breast cancer detection Examined the effects of a home-based intervention on mother-infant interaction among drug-using women and their infants . At 2 weeks postpartum , mothers and infants were r and omly assigned to either an intervention ( n = 84 ) or a control ( n = 87 ) group . Control families received brief monthly tracking visits , and intervention families received weekly visits by trained lay visitors . Mother-infant interaction was evaluated at 6 months through observation of feeding . Although there were no direct effects of the intervention , in the control group , mothers who continued to use drugs were less responsive to their babies than mothers who were drug free . In the intervention group , drug use was not associated with maternal responsiveness . Weekly home-based intervention may be a protective strategy for children of drug-using women because it disrupts the relation between ongoing maternal drug use and low maternal responsiveness Our goal was to describe the development and implementation of an intervention on cancer prevention for Latinas in San Diego , Calif. Thirty-six lay community workers ( " consejeras " ) were recruited and trained to conduct educational group sessions . Each consejera recruited approximately 14 peers from the community to participate in the program ( total number = 512 ) . Half of the consejeras were r and omly assigned to a control group , in which they participated in an equally engaging program entitled " Community Living Skills . " Implementation of the intervention was assessed by qualitative and quantitative methods . Preintervention and postintervention self-report information was obtained from project participants on access to health care services , cancer knowledge , preventive measures , and previous cancer-screening examinations . Base-line data suggest that lack of knowledge , costs of cancer-screening tests , and the lack of a regular health care provider are the major obstacles against obtaining cancer-screening tests . Predisposing factors , such as fear and embarrassment , also constitute barriers to getting regular cervical cancer screening . Preliminary analysis indicates that the Por La Vida intervention increases use of cancer-screening tests in comparison to a community living skills control group . Universal access to health care would remove some of the major financial barriers to cancer screening . The Por La Vida program attempts to overcome the substantial barriers by reaching out to low-income Latinas and by providing information regarding the availability , acceptability , and preventive nature of cancer-screening tests BACKGROUND Part of the payoff of immunization registries may be to lower costs of immunization intervention . However , registry-based intervention costs have not been evaluated in a community setting . METHODS The purpose of this study was to prospect ively measure the cost of three equally effective registry-based interventions , evaluate how the size of the targeted population affects cost estimates , and compare these results with previously reported studies . A total of 3050 children aged < 12 months were r and omized to one of four study arms : ( 1 ) computer-generated telephone messages ( autodialer ) , ( 2 ) outreach worker , ( 3 ) autodialer with outreach worker backup , or ( 4 ) usual care . The cost data collected included capital equipment , supplies , travel , and personnel . RESULTS Monthly costs of the three registry-based intervention types were ( 1 ) autodialer , $ 1.34 per child ; ( 2 ) outreach worker , $ 1.87 per child , and ( 3 ) combination , $ 2.76 per child . Personnel costs represented the majority of incremental costs for all three interventions . Increasing the number of children targeted sharply decreased the cost per child for the autodialer but had only a modest effect on outreach costs . The monthly costs for outreach were substantially lower than previously reported for nonregistry-based interventions in part because of differences in the number of children who were followed up . Monthly costs for the autodialer intervention were slightly higher than previously reported , but several published studies excluded important costs . CONCLUSIONS By facilitating the management of a larger cohort of children , some registry-based immunization interventions appear to be less costly than nonregistry interventions . Further work is needed to establish whether registry maintenance costs may be recouped in part by these savings Colorectal cancer ( CRC ) is the second leading cause of cancer-related deaths in the United States . Racial disparities in CRC incidence and mortality have been well documented . In addition , lower rates of CRC screening among ethnic minorities have been reported . Therefore , we tested the effectiveness of a patient navigator ( PN ) in increasing compliance with CRC screening in a minority community health setting . Men and women aged 50 or older attending a primary care practice were enrolled if they had not had a fecal occult blood test within the past year , a sigmoidoscopy or barium enema within the past 3–5 years , or a colonoscopy within the past 10 years . Participants were r and omly assigned either to receive navigator services ( PN+ ) or not to receive navigator services ( PN− ) . There were no demographic differences between the two groups . Within 6 months of physician recommendation , 15.8 % in the PN+ group had complied with an endoscopic examination , compared with only 5 % in the PN− group ( P=.019 ) . The PN+ groups also demonstrated higher rates of fecal occult blood test completion ( 42.1 % vs. 25 % , P=.086 ) . Thus , a PN system successfully increases CRC screening rates among a predominantly minority population of low socioeconomic status The WATCH ( Wellness for African Americans Through Churches ) Project was a r and omized trial comparing the effectiveness of 2 strategies to promote colorectal cancer preventive behaviors among 587 African American members of 12 rural North Carolina churches . Using a 2 X 2 factorial research design , the authors compared a tailored print and video ( TPV ) intervention , consisting of 4 individually tailored newsletters and targeted videotapes , with a lay health advisor ( LHA ) intervention . Results showed that the TPV intervention significantly improved ( p < .05 ) fruit and vegetable consumption ( 0.6 servings ) and recreational physical activity ( 2.5 metabolic task equivalents per hour ) and , among those 50 and older ( n = 287 ) , achieved a 15 % increase in fecal occult blood testing screening ( p = .08 ) . The LHA intervention did not prove effective , possibly because of suboptimal reach and diffusion OBJECTIVES The purpose of this study was to measure the effectiveness of re source mothers in reducing adverse consequences of maternal phenylketonuria . METHODS Nineteen pregnancies in the re source mothers group were compared with 64 pregnancies in phenylketonuric women without re source mothers . Weeks to metabolic control and offspring outcome were measured . RESULTS Mean number of weeks to metabolic control was 8.5 ( SE = 2.2 ) in the re source mothers group , as compared with 16.1 ( SE = 1.7 ) in the comparison group . Infants of women in the re source mothers group had larger birth head circumferences and higher developmental quotients . CONCLUSIONS The re source mothers program described here improves metabolic control in pregnant women with phenylketonuria A r and omized controlled intervention tested the effectiveness of a community health worker ( CHW ) program in increasing compliance with annual preventive exams among uninsured Hispanic women living in a rural U.S.-Mexico border area . During 1999 - 2000 , household surveys were administered to women aged 40 and older . Uninsured women not receiving routine comprehensive preventive care were invited to participate in a free comprehensive clinical exam . Participants in the initial exam were eligible to participate in the CHW ( promotora ) intervention . Women were r and omized to one of two intervention arms . One arm received a post-card reminder for an annual preventive exam , the other a postcard reminder and follow-up visit by a promotora . Receiving the promotora intervention was associated with a 35 % increase in rescreening over the postcard-only reminder ( risk ratio [ RR ] = 1.35 , 95 % confidence interval 0.95 - 1.92 ) . Using promotoras to increase compliance with routine screening exams is an effective strategy for reaching this female population Objective . To examine the effects of prenatal and infancy home visiting by paraprofessionals and by nurses from child age 2 through age 4 years . Methods . We conducted , in public and private care setting s in Denver , Colorado , a r and omized , controlled trial with 3 arms , ie , control , paraprofessional visits , and nurse visits . Home visits were provided from pregnancy through child age 2 years . We invited 1178 consecutive , low-income , pregnant women with no previous live births to participate , and we r and omized 735 ; 85 % were unmarried , 47 % Mexican American , 35 % white non-Mexican American , 15 % black , and 3 % American Indian/Asian . Outcomes consisted of maternal reports of subsequent pregnancies , participation in education and work , use of welfare , marriage , cohabitation , experience of domestic violence , mental health , substance use , and sense of mastery ; observations of mother-child interaction and the home environment ; tests of children 's language and executive functioning ; and mothers ' reports of children 's externalizing behavior problems . Results . Two years after the program ended , women who were visited by paraprofessionals , compared with control subjects , were less likely to be married ( 32.2 % vs 44.0 % ) and to live with the biological father of the child ( 32.7 % vs 43.1 % ) but worked more ( 15.13 months vs 13.38 months ) and reported a greater sense of mastery and better mental health ( st and ardized scores [ mean = 100 , SD = 10 ] of 101.25 vs 99.31 and 101.21 vs 99.16 , respectively ) . Paraprofessional-visited women had fewer subsequent miscarriages ( 6.6 % vs 12.3 % ) and low birth weight newborns ( 2.8 % vs 7.7 % ) . Mothers and children who were visited by paraprofessionals , compared with control subjects , displayed greater sensitivity and responsiveness toward one another ( st and ardized score [ mean = 100 , SD = 10 ] of 100.92 vs 98.66 ) and , in cases in which the mothers had low levels of psychologic re sources at registration , had home environments that were more supportive of children 's early learning ( score of 24.63 vs 23.35 ) . Nurse-visited women reported greater intervals between the births of their first and second children ( 24.51 months vs 20.39 months ) and less domestic violence ( 6.9 % vs 13.6 % ) and enrolled their children less frequently in preschool , Head Start , or licensed day care than did control subjects . Nurse-visited children whose mothers had low levels of psychologic re sources at registration , compared with control group counterparts , demonstrated home environments that were more supportive of children 's early learning ( score of 24.61 vs 23.35 ) , more advanced language ( score of 91.39 vs 86.73 ) , superior executive functioning ( score of 100.16 vs 95.48 ) , and better behavioral adaptation during testing ( score of 100.41 vs 96.66 ) . There were no statistically significant effects of either nurse or paraprofessional visits on the number of subsequent pregnancies , women 's educational achievement , use of substances , use of welfare , or children 's externalizing behavior problems . Conclusions . Paraprofessional-visited mothers began to experience benefits from the program 2 years after the program ended at child age 2 years , but their first-born children were not statistically distinguishable from their control group counterparts . Nurse-visited mothers and children continued to benefit from the program 2 years after it ended . The impact of the nurse-delivered program on children was concentrated on children born to mothers with low levels of psychologic re sources The study was design ed to test the relative effectiveness of a Navigator intervention delivered face-to-face or by telephone to urban Native American women . The effectiveness of the intervention was evaluated using a design that included a pretest , r and om assignment to face-to-face or telephone group , and posttest . The Social Cognitive Theory-based intervention was a tailored education program developed to address individual risk factors for breast cancer . At posttest , self-reported mammograms in the past year increased from 29 % to 41.3 % in the telephone group and from 34.4 % to 45.2 % in the face-to-face group . There was no difference in change from pretest to posttest between the telephone and face-to-face groups . Navigators can be effective in increasing adherence to recommendations for screening mammography among urban American Indian women This experimental study attempts to determine if an in-home educational intervention conducted by lay health workers ( LHWs ) can increase adherence among low-income , inner-city black women to schedules for screening for breast cancer and cervical cancer , as well as increase the women 's knowledge and change their attitudes regarding these cancers . This paper is a description of the purpose s , hypotheses , design , subject recruitment , intervention , and evaluation of the study conducted by Morehouse School of Medicine . Subjects were recruited from a variety of sources , including patients seen in a community health center , women referred by the National Black Women 's Health Project ( NBWHP ) , residents of public and senior citizen housing projects , and persons identified in various community setting s. Fewer than half of those asked to participate agreed to do so . The 321 women who were recruited were demographically diverse . Overall , about half of these volunteer subjects self-reported at least one Papanicolaou ( Pap ) smear and one breast examination within a year before enrollment in the study . There was little variation by source of recruitment in compliance with screening recommendations , except that referrals from NBWHP were more likely ( P less than 0.01 ) to have had a Pap test and breast self-examination , while residents of public housing projects were somewhat less likely to have done so . About 35 percent of participants ages 35 and older had a mammogram within an appropriate interval . Participants were r and omly assigned to intervention and control groups . Women in the intervention group were visited in their homes by LHWs on three occasions ; the LHWs provided education on cancer and reproductive health . The groups were comparable in their baseline sociodemographic status and previous screening history OBJECTIVES To assess cervical cancer screening behaviors among underserved women participating in an intervention design ed to increase mammography use . METHODS This was a r and omized trial of 897 women from three racial groups ( white , African American , Native American ) living in a rural county in North Carolina . Baseline and followup surveys were completed by 815 women ; 775 women provided data to be included in these analyses . The intervention group received an educational program focused on mammography delivered by a lay health advisor , and the control group received a physician letter/brochure focusing on Pap tests . RESULTS Women in both the intervention ( OR 1.70 ; 1.31 , 2.21 , p < 0.001 ) and control groups ( OR 1.38 ; 1.04 , 1.82 , p = 0.025 ) significantly increased cervical cancer screening rates within risk appropriate guidelines . No differences by racial group were documented . Women categorized in the high-risk group for developing cervical cancer ( > 2 sexual partners , age < 18 years at first sexual intercourse , smoker ; treated for sexually transmitted disease [ STD ] or partner with treated STD ) significantly ( OR 1.88 ; 1.54 , 2.28 , p < 0.001 ) increased Pap test completion . However , a nonsignificant increase ( OR 1.25 ; 0.87 , 1.79 , p = 0.221 ) in Pap test completion was demonstrated in women categorized as low risk for cervical cancer . CONCLUSIONS This study suggests that women in an intensive behavioral intervention design ed to increase mammography use may also increase Pap test completion , similar to a minimal intervention focused only on increasing Pap test completion . These results have implication s for the design and evaluation of behavioral intervention studies BACKGROUND Adherence to tuberculosis evaluation is poor in a high-risk population such as the homeless . OBJECTIVE To test two interventions aim ed at improving adherence to tuberculosis evaluation and to identify predictors of adherence . METHODS We conducted a r and omized clinical trial in shelters and food lines in the inner city of San Francisco , Calif. We r and omized 244 eligible subjects infected with tuberculosis to ( 1 ) peer health adviser ( assistance by a peer [ n = 83 ] ) , ( 2 ) monetary incentive ( $ 5 payment [ n = 82 ] ) , or ( 3 ) usual care ( referral slips and bus tokens only [ n = 79 ] ) . The primary outcome of the study was adherence to a first follow-up appointment at the tuberculosis clinic , where subjects were evaluated for active tuberculosis and the need for isoniazid prophylaxis . RESULTS Of the subjects assigned to a monetary incentive , 69 ( 84 % ) completed their first follow-up appointment , compared with 62 subjects ( 75 % ) assigned to a peer health adviser and 42 subjects ( 53 % ) assigned to usual care . Adherence was higher in the monetary incentive and peer health adviser groups than in the usual care group ( P < .001 and P = .004 , respectively ) . Patients not using intravenous drugs and patients 50 years of age or older were more likely to adhere to a first follow-up appointment ( odds ratios [ 95 % confidence intervals ] , 2.5 [ 1.3 to 5.0 ] and 3.3 [ 1.2 to 8.8 ] , respectively ) . Among the 173 tuberculosis-infected subjects who completed their appointment , isoniazid therapy was started for 72 individuals , and three cases of active tuberculosis were identified . CONCLUSION A monetary incentive or a peer health adviser is effective in improving adherence to a first follow-up appointment in homeless individuals infected with tuberculosis . A monetary incentive appears to be superior . Intravenous drug users and young individuals are at high risk for poor adherence to referral OBJECTIVE To determine the effect of a bicultural community health worker ( CHW ) on completion of diabetes education in an inner-city Hispanic patient population and to evaluate the impact of completion of the education program on patient knowledge , self-care behaviors , and glycemic control . RESEARCH DESIGN AND METHODS Patients were r and omized into CHW intervention and non-CHW intervention groups . All patients received individualized , comprehensive diabetes education from a certified diabetes nurse educator after baseline demographic information , diabetes knowledge , diabetes self-care practice s , and glycohemoglobin levels were assessed . Rates of education program completion were determined . Diabetes knowledge , self-care practice s , and glycohemoglobin levels were reassessed at program completion and at a later postprogram follow-up medical appointment and compared to baseline . Logistic regression analysis and the Mantel-Haenszel χ2 statistic were used to determine the effect of the CHW assignment on program completion . Analyses of covariance were performed with end-of-treatment behavior scores , knowledge scores , and glycohemoglobin levels as outcome variables , controlling for baseline values and testing for the effect of CHW assignment . RESULTS Of 64 patients enrolled in the study , 40 ( 63 % ) completed and 24 ( 37 % ) dropped out before completing the diabetes education program . Of the patients having CHW intervention , 80 % completed the education program , compared with 47 % of patients without CHW intervention ( P = 0.01 ) . “ Dropouts ” were younger ( age 47.5 ± 12.5 years [ mean ± SD ] ) compared with patients who completed the program ( 55.9 ± 9.9 years ) ( P = 0.004 ) . Dropout status showed no significant relationship to educational level achieved or literacy level . For the program “ completers , ” knowledge levels and selected self-care practice s significantly improved , and glycohemoglobin levels improved from a baseline level of 11.7 % to 9.9 % at program completion ( P = 0.004 ) and 9.5 % at the postprogram follow-up ( P < 0.001 ) . The effect of the CHW assignment on program completion , controlling for financial status and language spoken , was extremely robust ( P = 0.007 ) . The effect of the CHW on knowledge , self-care behavior , or glycohemoglobin outcome variables was not statistically significant . CONCLUSIONS These findings suggest that intervention with a bicultural CHW improved rates of completion of a diabetes education program in an inner-city Hispanic patient population irrespective of literacy or educational levels attained . Our data further suggests that completion of individualized diabetes educational strategies leads to improved patient knowledge , self-care behaviors , and glycemic control OBJECTIVE To evaluate the efficacy of a home-based intervention on the growth and development of children with nonorganic failure to thrive ( NOFTT ) . DESIGN R and omized clinical trial . PARTICIPANTS The NOFTT sample included 130 children ( mean age , 12.7 months ; SD , 6.4 ) recruited from urban pediatric primary care clinics serving low income families . All children were younger than 25 months with weight for age below the fifth percentile . Eligibility criteria included gestational age of at least 36 weeks , birth weight appropriate for gestational age , and no significant history of perinatal complications , congenital disorders , chronic illnesses , or developmental disabilities . Children were r and omized into two groups : clinic plus home intervention ( HI ) ( n = 64 ) or clinic only ( n = 66 ) . There were no group differences in children 's age , gender , race , or growth parameters , or on any of the family background variables . Most children were raised by single , African-American mothers who received public assistance . Eighty-nine percent of the families ( 116 of 130 ) completed the 1-year evaluation . INTERVENTIONS All children received services in a multidisciplinary growth and nutrition clinic . A community-based agency provided the home intervention . Families in the HI group were scheduled to receive weekly home visits for 1 year by lay home visitors , supervised by a community health nurse . The intervention provided maternal support and promoted parenting , child development , use of informal and formal re sources , and parent advocacy . MEASUREMENTS Growth was measured by st and ard procedures and converted to z scores for weight for height and height for age to assess wasting and stunting . Cognitive and motor development were measured with the Bayley Scales of Infant Development , and language development was measured by the Receptive/Expressive Emergent Language Scale . Both scales were administered at recruitment and at the 12-month follow-up . Parent-child interaction was measured by observing mothers and children during feeding at recruitment and at the 12-month follow-up , and the quality of the home was measured by the Home Observation Measure of the Environment 18 months after recruitment . ANALYSES Repeated- measures multivariate analyses of covariance were used to examine changes in children 's growth and development and parent-child interaction . Analyses of covariance were used to examine the quality of the home . Independent variables were intervention status and age at recruitment ( 1.0 to 12.0 vs 12.1 to 24.9 months ) . Maternal education was a covariate in all analyses . When changes in developmental status and parent-child interaction were examined , weight for height and height for age at recruitment were included as covariates . RESULTS Children 's weight for age , weight for height , and height for age improved significantly during the 12-month study period , regardless of intervention status . Children in the HI group had better receptive language over time and more child-oriented home environments than children in the clinic-only group . The impact of intervention status on cognitive development varied as a function of children 's ages at recruitment , with younger children showing beneficial effects of home intervention . There were no changes in motor development associated with intervention status . During the study period , children gained skills in interactive competence during feeding , and their parents became more controlling during feeding , but differences were not associated with intervention status . CONCLUSIONS Findings support a cautious optimism regarding home intervention during the first year of life provided by trained lay home visitors . Early home intervention can promote a nurturant home environment effectively and can reduce the developmental delays often experienced by low income , urban infants with NOFTT : Subsequent investigations of home intervention should consider alternative options for toddlers with NOFTT |
12,736 | 27,366,212 | Conclusions : SGT may be an acceptable option as rescue treatment .
However , cure rates are , at best , moderate and this approach has never been compared with a well-devised empirical therapy .
The evidence in favor of SGT as rescue therapy is currently insufficient to recommend its use | Background : Susceptibility-guided therapies ( SGTs ) have been proposed as preferable to empirical rescue treatments after two treatment failures .
The aim of this study was to perform a systematic review and meta- analysis evaluating the effectiveness and efficacy of SGT as third-line therapy . | Background : An antimicrobial susceptibility test for Helicobacter pylori before second‐line treatment is often performed , although whether the test is truly necessary remains unknown BACKGROUND & AIMS The major obstacle to 100 % effective eradication of Helicobacter pylori infection is represented by antimicrobial-resistant H. pylori strains . This r and omized study was design ed to evaluate whether regimens based on pretreatment susceptibility testing were more effective and cost saving compared with st and ard nonsusceptibility testing-based therapy in the eradication of H. pylori infection . METHODS We studied 150 consecutive H. pylori-infected dyspeptic subjects . Patients were r and omly assigned to omeprazole 20 mg twice daily , clarithromycin 500 mg twice daily , and metronidazole 500 mg twice daily for 7 days or to omeprazole 20 mg twice daily and 2 antimicrobials chosen based on susceptibility testing . H. pylori status was reevaluated 12 weeks after the end of treatment by the (13)C-urea breath test . RESULTS Susceptibility testing-based regimens led to the following results . ( 1 ) Eradication rates were 97.3 % ( 95 % confidence interval [ CI ] , 91.2%-99.5 % ) ( 71 of 73 ) and 94.6 % ( 95 % CI , 87.6%-98.3 % ) ( 71 of 75 ) in the per- protocol and intention-to-treat analysis , respectively . These were significantly higher ( P < 0.005 ) than eradication rates obtained without susceptibility testing , that is , 79.4 % ( 95 % CI , 69.1%-87.6 % ) ( 58 of 73 ) and 77.3 % ( 95 % CI , 66.9%-85.7 % ) ( 58 of 75 ) in the per- protocol and intention-to-treat analyses , respectively . ( 2 ) There were savings of approximately $ 5 U.S. per patient compared with st and ard triple therapy . CONCLUSIONS Pretreatment antimicrobial susceptibility testing is more effective and cost saving and , in health systems that confirm cost advantage , microbial susceptibility testing should be routinely used for eradication of H. pylori infection Helicobacter pylori eradication rates by triple therapy with a proton pump inhibitor , amoxicillin , and clarithromycin at st and ard doses depend on bacterial susceptibility to clarithromycin and patient CYP2C19 genotypes . We examined the usefulness of a personalized therapy for H. pylori infection based on these factors as determined by genetic testing . First , optimal lansoprazole dosing schedules that would achieve sufficient acid inhibition to allow H. pylori eradication therapy in each of different CYP2C19 genotype groups were determined by a 24‐h intragastric pH monitoring . Next , 300 H. pylori‐positive patients were r and omly assigned to the st and ard regimen group ( lansoprazole 30 mg twice daily ( b.i.d . ) ) , clarithromycin 400 mg b.i.d . , and amoxicillin 750 mg b.i.d . for 1 week ) or the tailored regimen group based on CYP2C19 status and bacterial susceptibility to clarithromycin assessed by genetic testing . Patients with failure of eradication underwent the second‐line regimen . The per‐patient cost required for successful eradication was calculated for each of the groups . In the first‐line therapy , the intention‐to‐treat eradication rate in the tailored regimen group was 96.0 % ( 95 % CI=91.5–98.2 % , 144/150 ) , significantly higher than that in the st and ard regimen group ( 70.0 % : 95 % CI=62.2–77.2 % , 105/150 ) ( P<0.001 ) . Final costs per successful eradication in the tailored and st and ard regimen groups were $ 669 and $ 657 , respectively . In conclusion , the pharmacogenomics‐based tailored treatment for H. pylori infection allowed a higher eradication rate by the initial treatment without an increase of the final per‐patient cost for successful eradication . However , the precise cost‐effectiveness of this strategy remains to be determined 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 Helicobacter pylori eradication therapies do not achieve 100 % success rates . Antibiotic resistant strains are among the major causes of failure . Current recommendations concerning the management of treatment failures are not fully clear AIM : Eradication therapy with proton pump inhibitor , clarithromycin and amoxicillin fails in a considerable number of cases . A rescue therapy still fails in more than 20 % of the cases . Our aim was to evaluate the efficacy and tolerability of a third-line levofloxacin-based regimen in patients with two consecutive Helicobacter pylori eradication failures . METHODS : Design : Prospect i ve multicenter study . Patients : In whom a first treatment with omeprazole-clarithromycin-amoxicillin and a second with omeprazole-bismuth-tetracycline-metronidazole ( or ranitidine bismuth citrate with these antibiotics ) had failed . Intervention : A third eradication regimen with levofloxacin ( 500 mg b.i.d . ) , amoxicillin ( 1 g b.i.d . ) , and omeprazole ( 20 mg b.i.d . ) was prescribed for 10 days . Outcome : Eradication was confirmed with 13C-urea breath test 4–8 wk after therapy . RESULTS : One-hundred patients were initially included , and nine were lost for follow-up . All patients but five took all the medications correctly . Per- protocol and intention-to-treat eradication rates were 66 % ( 95 % CI = 56–75 % ) and 60 % ( 50–70 % ) . Adverse effects were reported in 25 % of the patients , mainly including metallic taste ( 8 % ) , nausea ( 8 % ) , myalgia/arthralgia ( 5 % ) , and diarrhea ( 4 % ) ; none of them were severe . CONCLUSION : Levofloxacin-based rescue therapy constitutes an encouraging empirical third-line strategy after multiple previous H. pylori eradication failures with key antibiotics such as amoxicillin , clarithromycin , metronidazole , and tetracycline Successful eradication of Helicobacter pylori after failure of st and ard triple therapy is difficult because of the higher resistance to metronidazole and clarithromycin . We evaluated the efficacy of susceptibility-guided vs. empiric retreatment for H. pylori after at least one treatment failure and determined the prevalence of posttreatment antibiotic resistance . Forty-nine patients in whom at least one treatment regimen for H. pylori eradication had failed underwent gastric biopsy and culture and were retreated according to the in vitro susceptibility results . Findings were compared with those for 49 control patients referred to our center for a 13C-urea breath test . H. pylori eradication was assessed by urea breath test at least 6 weeks after retreatment in both groups . Susceptibility-guided retreatment was associated with better eradication rates than empiric treatment . The difference remained significant in stratified and multivariate analysis . Susceptibility-guided retreatment appears to be significantly more effective than empiric retreatment in eradicating H. pylori after at least one previous treatment failure BACKGROUND Levofloxacin has been proposed as an alternative to classic therapy in secondary resistance to Helicobacter pylori . AIM To evaluate primary and secondary resistance of H. pylori to levofloxacin , and to test the role of susceptibility test on the efficacy of levofloxacin-based triple therapy . METHODS Eighty consecutive dyspeptic patients with positive (13)C-urea breath test never treated were r and omly allocated into group A(1 ) ( 40 patients ) and group B(1 ) ( 39 patients ) . Eighty-three patients already treated unsuccessfully with positive (13)C-urea breath test were divided into group A(2 ) ( 51 patients ) and group B(2 ) ( 32 patients ) . Patients in group A(1 ) and group A(2 ) underwent upper gastrointestinal endoscopy for H. pylori susceptibility test to amoxicillin , clarithromycin , tinidazole , rifabutin , and levofloxacin . These patients were treated with levofloxacin ( 500 mg b.i.d . ) , amoxicillin ( 1 g b.i.d . ) and esomeprazole ( 20 mg b.i.d . ) for 10 days if sensitive to these two antibiotics . If H. pylori was found resistant to amoxicillin and /or levofloxacin the treatment was based on the indications of the susceptibility test . Patients in group B(1 ) and group B(2 ) were treated empirically with levofloxacin , amoxicillin , and esomeprazole at the same dose and duration as group A. All patients underwent (13)C-urea breath test 2 months after the end of therapy . RESULTS The antibiotic resistance of H. pylori strains in group A(1 ) and group A(2 ) was ( % ) : amoxicillin : 2.4 , 10 ; clarithromycin : 21.9 , 43.1 ; tinidazole : 31.7 , 70 ; rifabutin : 2.4 , 4 ; and levofloxacin : 9.7 , 12.2 , respectively . In group A(1 ) with susceptibility test-driven therapy , eradication was 97.2 % , and in group B(1 ) with empirical treatment , 94.1 % ( n.s . ) . In group A(2 ) with susceptibility test , eradication was 97.5 % , whereas in group B(2 ) with empirical treatment 81.2 % ( p < .01 ) . CONCLUSION Primary and secondary resistance of H. pylori to levofloxacin is approximately 10 % of the tested strains . The susceptibility test does not influence therapeutic outcome of triple therapy with amoxicillin and levofloxacin in patients never treated , while it is determinant for patients who were previously treated without success BACKGROUND & AIMS Eradication of Helicobacter pylori using empiric therapy has become difficult as a result of increasing resistance to antibiotics . We evaluated the efficacy of specific treatments , selected based on response of bacterial sample s to culture with clarithromycin , levofloxacin , and metronidazole , for patients infected with resistant strains of H pylori . METHODS We performed a prospect i ve study at a single center of 236 consecutive patients with persistent H pylori infection , despite 1 or more treatment attempts , and documented resistance to at least 1 antimicrobial agent ( based on bacterial culture tests ) . Biopsy sample s were collected by endoscopy and cultured in selective media . Patients received either 10 days of levofloxacin ( 250 mg twice daily for 131 patients with susceptible infections ) or 12 days of rifabutin ( 150 mg once daily for 105 patients resistant to levofloxacin ) in combination with amoxicillin ( 1 g twice daily ) and esomeprazole ( 40 mg twice daily ) . Efficacy of eradication was determined by the (13)C-urea breath test , 6 to 8 weeks after therapy . Compliance and side effects were determined via personal interviews at the end of therapy . Rifabutin toxicity was monitored by analysis of blood sample s. RESULTS H pylori infection was cured in 118 of the patients who received levofloxacin triple therapy ( 90 % ; 95 % confidence interval , 85%-95 % ) and 93 of the patients who received rifabutin triple therapy ( 88.6 % ; 95 % confidence interval , 82%-95 % ) . In each group , the cure rate did not differ significantly between patients infected with H pylori strains resistant to single or multiple antibiotics . Mild side effects occurred in 15.5 % and 14.9 % of patients resistant to single or multiple antibiotics , respectively , and self-limiting neutropenia was observed in 1 ( 0.7 % ) case . CONCLUSIONS Selection of triple therapy with either levofloxacin or rifabutin , based on results from bacterial culture tests , cures H pylori infection in about 90 % who did not previously respond to antibiotics Background Helicobacter pylori eradication therapy with a proton pump inhibitor ( PPI ) , clarithromycin , and amoxicillin fails in > 20 % of cases . A rescue therapy with PPI – amoxicillin – levofloxacin still fails in > 20 % of patients . Aim To evaluate the efficacy and tolerability of a bismuth-containing quadruple regimen in patients with two consecutive eradication failures . Methods Prospect i ve multicenter study of patients in whom 1st treatment with PPI – clarithromycin – amoxicillin and 2nd with PPI – amoxicillin – levofloxacin had failed . A 3rd eradication regimen with a 7- to 14-day PPI ( st and ard dose b.i.d . ) , bismuth subcitrate ( 120 mg q.i.d . or 240 mg b.i.d . ) , tetracycline ( from 250 mg t.i.d . to 500 mg q.i.d . ) and metronidazole ( from 250 mg t.i.d . to 500 mg q.i.d . ) . Eradication was confirmed by 13C-urea-breath-test 4–8 weeks after therapy . Compliance was determined through question ing and recovery of empty medication envelopes . Adverse effects were evaluated by means of a question naire . Results Two hundred patients ( mean age 50 years , 55 % females , 20 % peptic ulcer/80 % uninvestigated-functional dyspepsia ) were initially included , and two were lost to follow-up . In all , 97 % of patients complied with the protocol . Per- protocol and intention-to-treat eradication rates were 67 % ( 95 % CI 60–74 % ) and 65 % ( 58–72 % ) . Adverse effects were reported in 22 % of patients , the most common being nausea ( 12 % ) , abdominal pain ( 11 % ) , metallic taste ( 8.5 % ) , and diarrhea ( 8 % ) , none of them severe . Conclusion A bismuth-containing quadruple regimen is an acceptable third-line strategy and a safe alternative after two previous H. pylori eradication failures with st and ard clarithromycin- and levofloxacin-containing triple therapies AIM To determine the effectiveness of a third , culture-guided , treatment of H. pylori infection after two unsuccessful attempts . PATIENTS AND METHODS Forty-two consecutive patients with a diagnosis of peptic ulcer were included in an open prospect i ve and multicenter study . After two unsuccessful attempts at eradication ( demonstrated by positive urea breath test ) , all patients underwent endoscopy and H. pylori infection was confirmed by urease test , histology and culture ( Pylori-Agar , Bio Merieux , France ) . Antibiotic susceptibility to metronidazole , amoxicillin , tetracycline and clarithromycin was defined by E-test . Thirty-nine patients received a two-week quadruple culture-guided therapy defined by the protocol , which considered sensitivity data and previous allergies to antibiotics ( one culture was contaminated , one patient refused treatment and one was allergic to tetracycline and amoxicillin and was resistant to metronidazole and clarithromycin ) . Compliance was monitored by pill counting and eradication was defined as a negative urea breath test six weeks after the end of treatment . RESULTS Sensitivity data were obtained in 41 patients . Intention-to-treat analysis revealed that overall eradication was achieved in 60 % ( 24/40 ) . Eighteen strains ( 43.9 % ) were resistant to metronidazole , 21 ( 51.2 % ) were resistant to clarithromycin and 8 ( 19.5 % ) were resistant to both drugs . None of the strains were resistant to amoxicillin or tetracycline . We used mainly two kinds of quadruple therapy in the 39 patients . Despite good compliance with treatment based on omeprazole ( 20 mg/12 h ) , bismuth subcitrate ( 120 mg/6 h ) , tetracycline ( 500 mg/4 h ) and clarithromycin ( 500 mg/ 12 h ) ( OBTC ) eradication was achieved in only 9 of 19 patients ( 47.4 % ; CI : 24.4 - 71.1 ) ( one patient failed to attend the urea breath test ) . Nineteen clarithromycin-resistant patients received amoxicillin ( 1,000 mg/12 h ) instead of clarithromycin ( OBTA ) and this treatment was effective in 14 ( 73.7 % ; CI : 48.8 - 90.9 ) . Eradication was achieved in one patient who was allergic to amoxicillin and resistant to clarithromycin and metronidazole and who received ciprofloxacin ( 500 mg/8 h ) instead of clarithromycin ( OBTCipro ) . No clinical factors associated with eradication failure were found . CONCLUSIONS Despite the use of two-week , high-dose , quadruple and culture-guided combinations of drugs , a third treatment was frequently unsuccessful . The lowest eradication rate was obtained in patients with H. pylori strains sensitive to all antibiotics ; therefore , we believe that other factors could influence eradication rates . New prospect i ve and r and omized studies are needed in this subgroup of patients to find effective treatments Background : The resistance of Helicobacter pylori to antibiotics has been advocated as a major cause of treatment failure , and antimicrobial sensitivity testing has been proposed to improve efficacy ; however , its role before first‐line therapy has not been investigated in detail Antibiotic resistance has begun to impair the ability to cure Helicobacter pylori infection Aim : To compare the efficacy of different regimens in patients in whom previous Helicobacter pylori eradication therapy has failed Objective Resistance to antibiotics is the major cause of treatment failure of Helicobacter pylori infection . A study was conducted to assess prospect ively the antibacterial resistance rates of H pylori in Europe and to study the link between outpatient antibiotic use and resistance levels in different countries . Design Primary antibiotic resistance rates of H pylori were determined from April 2008 to June 2009 in 18 European countries . Data on yearly and cumulative use over several years of systemic antibacterial agents in ambulatory care for the period 2001–8 were expressed in Defined Daily Doses ( DDD ) per 1000 inhabitants per day . The fit of models and the degree of ecological association between antibiotic use and resistance data were assessed using generalised linear mixed models . Results Of 2204 patients included , H pylori resistance rates for adults were 17.5 % for clarithromycin , 14.1 % for levofloxacin and 34.9 % for metronidazole , and were significantly higher for clarithromycin and levofloxacin in Western/ Central and Southern Europe ( > 20 % ) than in Northern European countries ( < 10 % ) . Model fit improved for each additional year of antibiotic use accumulated , but the best fit was obtained for 2005 . A significant association was found between outpatient quinolone use and the proportion of levofloxacin resistance ( p=0.0013 ) and between the use of long-acting macrolides only and clarithromycin resistance ( p=0.036 ) . Conclusion In many countries the high rate of clarithromycin resistance no longer allows its empirical use in st and ard anti-H pylori regimens . The knowledge of outpatient antibiotic consumption may provide a simple tool to predict the susceptibility of H pylori to quinolones and to macrolides and to adapt the treatment strategies BACKGROUND Helicobacter pylori treatment failure may be due to resistance to macrolides and 5-nitroimidazoles . AIM To test whether a preliminary in vitro susceptibility test of H. pylori to tinidazole and clarithromycin and a consequent specific regimen could improve the eradication rate . METHODS A total of 109 consecutive H. pylori-positive patients with dyspeptic symptoms were included . At endoscopy , biopsy from the antrum was obtained for H. pylori culture and antimicrobial susceptibility testing . Fifty-six patients were treated with omeprazole , tinidazole and clarithromycin for 10 days ( group OTC ) and 53 patients received therapy on the basis of the susceptibility test ( group SUSC ) . Treatment success was evaluated by the 13C-urea breath test 1 month after the end of therapy . RESULTS Eight patients dropped out . Overall primary resistance to clarithromycin , tinidazole and both antibiotics was 13 % , 33 % and 4 % , respectively . In group OTC , H. pylori was eradicated in 81 % and 75 % of patients by per protocol and intention-to-treat analysis , respectively . Per protocol and intention-to-treat eradication rates for group SUSC were 98 % and 91 % ( P < 0.05 vs. group OTC ) . CONCLUSIONS These data show that in H. pylori infection , antibiotic therapy based on the results of culture and susceptibility testing gives , in comparison to st and ard therapy , a significant improvement in eradication rate BACKGROUND Using quadruple clarithromycin-containing regimens for Helicobacter pylori eradication is controversial with high rates of macrolide resistance . AIM To evaluate antibiotic resistance rates and the efficacy of empirical and tailored nonbismuth quadruple ( concomitant ) therapy in a setting with cure rates < 80 % for triple and sequential therapies . METHODS 209 consecutive naive H. pylori-positive patients without susceptibility testing were empirically treated with 10-day concomitant therapy ( proton pump inhibitors ( PPI ) , amoxicillin 1 g , clarithromycin 500 mg , and metronidazole 500 mg ; all drugs b.i.d . ) . Simultaneously , 89 patients with positive H. pylori culture were r and omized to receive triple versus concomitant therapy for clarithromycin-susceptible H. pylori , and sequential versus concomitant therapy for clarithromycin-resistant strains . Eradication was confirmed with ¹³C-urea breath test or histology 8 weeks after completion of treatment . RESULTS Per- protocol ( PP ) and intention-to-treat eradication rates after empirical concomitant therapy without susceptibility testing were 89 % ( 95%CI:84 - 93 % ) and 87 % ( 83 - 92 % ) . Antibiotic resistance rates were : clarithromycin , 20 % ; metronidazole , 34 % ; and both clarithromycin and metronidazole , 10 % . Regarding clarithromycin-susceptible H. pylori , concomitant therapy was significantly better than triple therapy by per protocol [ 92 % ( 82 - 100 % ) vs 74 % ( 58 - 91 % ) , p = 0.05 ] and by intention to treat [ 92 % ( 82 - 100 % ) vs 70 % ( 57 - 90 % ) , p = 0.02 ] . As for antibiotic-resistant strains , eradication rates for concomitant and sequential therapies were 100 % ( 5/5 ) vs 75 % ( 3/4 ) , for clarithromycin-resistant/metronidazole-susceptible strains and 75 % ( 3/4 ) vs 60 % ( 3/5 ) for dual-resistant strains . CONCLUSIONS Empirical 10-day concomitant therapy achieves good eradication rates , close to 90 % , in setting s with multiresistant H. pylori strains . Tailored concomitant therapy is significantly superior to triple therapy for clarithromycin-susceptible H. pylori and at least as effective as sequential therapy for resistant strains A third line treatment is needed in roughly 5 % of patients infected with Helicobacter pylori . Few data have been reported on efficacy of treatment regimens in these patients Background A st and ard third‐line therapy for Helicobacter pylori infection is lacking , and antimicrobial sensitivity data for patients who failed eradication therapy are often unavailable in clinical practice . We therefore design ed the prospect i ve study to assess the efficacy of levofloxacin , amoxicillin , bismuth and rabeprazole quadruple therapy as a third‐line treatment for H. pylori infection BACKGROUND AND AIM Helicobacter pylori ( H. pylori ) eradication rates using the PPI/AC regimen ( proton pump inhibitor + amoxicillin + clarithromycin ) are declining . We trialed tailoring eradication regimens according to clarithromycin ( CAM ) susceptibility . METHODS The subjects were 70 H. pylori positive adults . They were r and omly allocated to a tailored group and a control group . In the tailored group , subjects with CAM-sensitive strains were given PPI/AC eradication therapy , and those with CAM-resistant strains were given PPI/AM ( metronidazole instead of clarithromycin ) therapy . The control group were all given PPI/AC therapy . CAM sensitivity was measured by collecting fecal specimens , and extracting the DNA . The 23S rRNA domain , associated with CAM susceptibility in H. pylori , was amplified using a nested polymerase chain reaction ( PCR ) , and DNA sequencing was used to detect point mutations at A2143 G and A2144 G . RESULTS Eradication rates were 94.3 % in the tailored group and 71.4 % in the control group . In particular , the eradication rate was 100 % for CAM-resistant strains in the tailored group . CONCLUSIONS In Japan , where CAM-resistant H. pylori strains are expected to continue to increase , tailored eradication therapy according to CAM sensitivity will be of benefit |
12,737 | 19,565,556 | Hyperuricemia may modestly increase the risks of both stroke incidence and mortality . | OBJECTIVE To assess the association between hyperuricemia and risk of stroke incidence and mortality because hyperuricemia is hypothesized to be a risk factor for stroke and other cardiovascular disease , but , to date , results from observational studies are conflicting . | Background and Purpose — The role of uric acid as a risk factor for myocardial infa rct ion is controversial , and little is known about its role as a risk factor for stroke . Recent evidence suggests that uric acid may be an important causal agent in cardiovascular disease , for example , by inducing renal disease and hence hypertension . We investigated the association between serum uric acid and coronary heart disease and stroke in a large prospect i ve population -based study . Methods — The study was based on 4385 participants of the Rotterdam Study who , at baseline ( 1990 to 1993 ) , were ≥55 years of age , free from stroke and coronary heart disease , and had blood taken . Follow-up for incident stroke and myocardial infa rct ion was complete until January 1 , 2002 . Data were analyzed with Cox proportional hazards models with adjustment for relevant confounders . Results — Average follow-up was 8.4 years . High serum uric acid levels were associated with risk of myocardial infa rct ion and stroke ; age- and sex-adjusted hazard ratios ( 95 % CIs ) for highest versus lowest quintile of uric acid were 1.68 ( 1.24 to 2.27 ) for cardiovascular disease ( 515 cases ) , 1.87 ( 1.12 to 3.13 ) for myocardial infa rct ion ( 194 cases ) , 1.57 ( 1.11 to 2.22 ) for stroke ( 381 cases ) , 1.77 ( 1.10 to 2.83 ) for ischemic stroke ( 205 cases ) , and 1.68 ( 0.68 to 4.15 ) for hemorrhagic stroke ( 46 cases ) . Adjustment for other vascular risk factors only slightly attenuated these associations . Associations were stronger in persons without hypertension than in those with hypertension . Conclusions — Uric acid is a strong risk factor for myocardial infa rct ion and stroke BACKGROUND The role of serum uric acid ( SUA ) as a risk factor for cardiovascular disease ( CVD ) remains controversial . Little is known about its predictive value for mortality from congestive heart failure ( CHF ) and stroke , particularly in elderly , post-menopausal women . METHODS The relation of SUA to risk of death from total CVD , CHF , stroke and coronary heart disease ( CHD ) was examined prospect ively in a large cohort of 28613 elderly Austrian women ( mean age 62.3 years ) , followed-up for a median of 15.2 years . Adjusted Cox proportional hazards models were calculated to evaluate SUA as an independent predictor for fatal CVD events . RESULTS SUA in the highest quartile ( > or=5.41 mg/dL ) was significantly associated with mortality from total CVD ( p<0.0001 ) , showing a clear dose-response relationship ; the adjusted hazard ratio ( 95%CI ) in comparison to the lowest SUA quartile was 1.35 ( 1.20 - 1.52 ) . In subgroup analyses SUA was independently predictive for deaths from acute and subacute ( p<0.0001 ) and chronic forms ( p=0.035 ) of CHD , yielding adjusted hazard ratios for the highest versus lowest SUA quartile of 1.58 ( 1.19 - 2.10 ) and 1.25 ( 1.01 - 1.56 ) , respectively . SUA was further significantly related to fatal CHF ( p<0.0001 ) and stroke ( p=0.018 ) ; the adjusted hazard ratios for the highest versus lowest SUA quartile were 1.50 ( 1.04 - 2.17 ) and 1.37 ( 1.09 - 1.74 ) , respectively . CONCLUSIONS These findings , for the first time , demonstrate that SUA is an independent predictor for all major forms of death from CVD including acute , subacute and chronic forms of CHD , CHF and stroke in elderly , post-menopausal women BACKGROUND The role of serum uric acid ( SUA ) as an independent risk factor for cardiovascular disease ( CVD ) remains controversial , and little is known about its prognostic importance for mortality from congestive heart failure ( CHF ) and stroke . Few large-scale epidemiologic studies with sufficient follow-up have addressed the association of SUA and CVD mortality in apparently healthy men across a wide age range . METHODS A cohort of 83 683 Austrian men ( mean age , 41.6 years ) was prospect ively followed for a median of 13.6 years . We used Cox proportional hazards models adjusted for established risk factors to evaluate SUA as an independent predictor for CVD mortality . RESULTS The highest quintile of SUA concentration ( > 398.81 mumol/L ) was significantly related to mortality from CHF ( P = 0.03 ) and stroke ( P < 0.0001 ) ; adjusted hazard ratios ( 95 % confidence interval ) for the highest vs lowest quintiles of SUA were 1.51 ( 1.03 - 2.22 ) and 1.59 ( 1.23 - 2.04 ) , respectively . SUA was not associated , however , with mortality from acute , subacute , or chronic forms of coronary heart disease ( CHD ) after adjustment for potential confounding factors ( P = 0.12 ) . Age was a significant effect modifier for the relation of SUA to fatal CHF ( P = 0.05 ) , with markedly stronger associations found in younger individuals . CONCLUSIONS Our study demonstrates for the first time in a large prospect i ve male cohort that SUA is independently related to mortality from CHF and stroke . Although increased SUA is not necessarily a causal risk factor , our results suggest the clinical importance of monitoring and intervention based on the presence of an increased SUA concentration , especially because SUA is routinely measured The association of serum uric acid with cardiovascular disease has been appreciated for nearly half a century ( 1 ) . Several prospect i ve studies have shown an association between baseline hyperuricemia and incident coronary heart disease , cardiovascular disease , and death ( 2 - 10 ) . Despite the strength of these associations , uric acid has not been established as a causal risk factor for cardiovascular disease . Instead , uric acid seems inextricably linked to hypertension , dyslipidemia , and disordered glucose metabolism , which play a causal role in the pathogenesis of cardiovascular disease . As such , uric acid may be merely a marker of risk for cardiovascular disease . Several recent reports , however , have attempted to dispel this notion ( 3 , 9 , 11 - 14 ) . Using data from the First National Health and Nutrition Examination Study ( NHANES I ) , Freedman and colleagues ( 3 ) demonstrated that each 60-mol/L increment in uric acid level was associated with a 48 % increase in risk for incident ischemic heart disease among women . Furthermore , a growing body of laboratory and clinical evidence suggests that uric acid plays a role in platelet adhesiveness ( 15 - 17 ) , formation of free radicals ( 18 ) , and oxidative stress ( 19 , 20 ) . As a result of this growing controversy , we revisited this question in the Framingham Heart Study sample . Longer and more contemporary follow-up and more outcome events allowed us to exp and on a previous Framingham report [ 2 ] . In this paper , we describe the relation of baseline serum uric acid level to 1 ) incident coronary heart disease events [ death from coronary heart disease , recognized myocardial infa rct ion , and coronary insufficiency ] , 2 ) death from cardiovascular disease , and 3 ) death from all causes . Because previous studies ( 2 , 3 , 7 , 21 ) have suggested that uric acid is more strongly associated with adverse events in women than in men , we chose a priori to perform sex-specific analyses . Methods Study Sample The selection criteria and study design of the Framingham Heart Study and the Framingham Offspring Study have been described elsewhere ( 22 , 23 ) . Original participants of the Framingham Heart Study who took part in the 13th biennial examination ( 1972 to 1976 ) and adult participants in the first examination of the Framingham Offspring Study ( 1971 to 1975 ) were eligible for this investigation ( n=7940 ) . Blood sample s for uric acid measurement were obtained in 7650 ( 96.3 % ) persons . Participants were excluded ( n=887 ) for the following reasons : use of more than 2 g of salicylates per day ( n=17 ) , missing covariate or follow-up data ( n=117 ) , and prevalent cardiovascular disease ( n=753 ) . The remaining 6763 participants were followed prospect ively until 1994 . Baseline Measurements and Definitions Medical histories and physical examinations were performed for each participant at every clinic visit . Systolic and diastolic blood pressure were measured twice in the left arm of seated participants by using a mercury-column sphygmomanometer positioned near eye level . The average of the two readings was used for each blood pressure variable . The diagnosis of hypertension was based on a systolic blood pressure of 140 mm Hg or higher , a diastolic blood pressure of 90 mm Hg or higher , or the current use of antihypertensive drugs ( 24 ) . Height and weight were measured at each examination , and body mass index was calculated as the weight in kilograms divided by the square of the height in meters . Participants who reported smoking at least one cigarette per day during the year before the examination were classified as current smokers . Alcohol use was ascertained by self-report and was categorized as ounces of ethanol consumed per week . Menopause was defined as the absence of menses for 1 year or more . Diabetes was defined on the basis of a nonfasting blood glucose level of 11.1 mmol/L ( 200 mg/dL ) or greater , a fasting blood glucose level of 7.8 mmol/L ( 140 mg/dL ) or greater , or the use of insulin or an oral hypoglycemic agent . Serum uric acid levels were measured with an autoanalyzer that used a phosphotungstic acid reagent ( 25 ) . Cholesterol levels were determined according to the Abell-Kendall method ( 26 ) . Outcome Events The primary outcome measures were incident coronary heart disease events , death from cardiovascular disease ( coronary heart disease , congestive heart failure , stroke , or other cardiovascular disease ) , and death from all causes . Coronary heart disease events included the following : death from coronary heart disease ( available information suggested coronary heart disease as the probable cause ) , recognized myocardial infa rct ion ( serial electrocardiographic changes leading to development of new pathologic Q waves , characteristic increase and decrease in serum myocardial markers with a suggestive clinical history , or evidence at necropsy of new or recent infa rct ion ) , and coronary insufficiency ( prolonged ischemic chest discomfort associated with transient repolarization abnormality , without criteria for myocardial infa rct ion ) . Events that were more equivocal , such as unrecognized myocardial infa rct ion and angina pectoris , were not included as coronary heart disease events for this analysis . A panel of three physicians determined the outcome events according to previously published criteria ( 27 ) after review ing Framingham Heart Study and outside hospital and physician records . Statistical Analysis Separate analyses were performed for men and women . All participants were divided according to sex-specific uric acid quintiles . Crude event rates were calculated for each quintile . Cox proportional-hazards regression models ( 28 ) were used to examine the relations of uric acid quintiles ( with quintile 1 as the reference category ) and the relation of uric acid level as a continuous variable to incidence of coronary heart disease events , cardiovascular disease mortality rates , and all-cause mortality rates . For comparative purpose s , hazard ratios were calculated without adjustment . For inferential purpose s , hazard ratios were calculated with adjustment for age only and also with adjustment for age and other clinical variables associated with uric acid level or atherosclerotic events : body mass index ( kg/m2 ) , diabetes ( yes/no ) , systolic blood pressure ( mm Hg ) , current diuretic use ( yes/no ) , use of antihypertensive medications other than diuretics ( yes/no ) , left ventricular hypertrophy shown on electrocardiography ( yes/no ) , total cholesterol level ( mmol/L ) , smoking status ( yes/no ) , alcohol use ( ounces consumed per week ) , and menopausal status in women ( yes/no ) . Post hoc subgroup analyses were done to determine any possible relations between quintiles of uric acid and the outcome events in participants stratified according to diuretic use and hypertension status . All analyses were performed on a Sun UltraSPARC computer ( Sun Microsystems , Mountain View , California ) using SAS software ( SAS Institute , Cary , North Carolina ) ( 29 ) . A two-sided P value less than 0.05 was the criterion for statistical significance . Results Participant Characteristics Table 1 shows the baseline clinical characteristics for men and women . The mean uric acid level was 379 mol/L in men ( range , 119 to 738 mol/L ) and 285 mol/L in women ( range , 24 to 696 mol/L ) . The effect of age on mean serum uric acid level is illustrated in the Figure . In men , uric acid levels changed minimally with age . In women , mean serum uric acid levels gradually increased from the fourth to the seventh decades of life . Furthermore , among women 30 to 54 years of age , the mean serum uric acid level was 5 to 13 mol/L greater in those who were postmenopausal ( data not shown ) . Table 1 . Baseline Clinical Characteristics Figure . Mean serum uric acid level by sex and 5-year age group . Uric Acid Level and Outcome Events There were 117 376 person-years of follow-up . In men , 394 coronary heart disease events , 232 deaths due to cardiovascular disease , and 729 deaths from all causes occurred . As a continuous variable , baseline uric acid level was not associated with increased risk for any end point in men . In fully adjusted Cox models , for every 60-mol/L increase in serum uric acid level , hazard ratios were as follows : 0.91 ( 95 % CI , 0.83 to 0.99 ) for coronary heart disease , 0.95 ( CI , 0.86 to 1.06 ) for death from cardiovascular disease , and 0.97 ( CI , 0.91 to 1.03 ) for death from all causes . In men , baseline quintile of serum uric acid level was also not associated with increased risk for any outcome measure . Uric acid level was inversely related to coronary heart disease in the full multivariable adjusted model ( Table 2 ) . Table 2 . Relations of Serum Uric Acid Level to Coronary Heart Disease , Death from Cardiovascular Disease , and Death from All Causes In women , 223 coronary heart disease events , 197 deaths from cardiovascular disease , and 731 deaths from all causes occurred . From quintile 1 to quintile 5 , crude rates increased more than threefold for coronary heart disease ( from 1.9 to 7.5 per 1000 person-years ) , death from cardiovascular disease ( from 1.3 to 7.0 per 1000 person-years ) and death from all causes ( from 6.3 to 21.8 per 1000 person-years ) ( Table 2 ) . In unadjusted Cox models in which quintile 1 was the reference category , risk significantly increased with increasing uric acid quintile for all three outcome measures ( P<0.001 for trend ) . This trend diminished after adjustment for age but remained significant for coronary heart disease ( P=0.002 ) , death from cardiovascular disease ( P=0.009 ) , and death from all causes ( P=0.03 ) . In fully adjusted Cox models , baseline uric acid level was no longer associated with increased risk for coronary heart disease ( P>0.2 for trend ) , death from cardiovascular disease ( P=0.23 ) , or death from all causes ( P>0.2 ) . Similar relations were found when baseline uric acid level was assessed as a continuous variable . In the fully adjusted models , hazard ratios for every 60-mol/L increase in serum uric acid level were as follows : 1.05 ( CI , 0.94 to 1.17 ) for Little is known about uric acid role for cardiovascular events in the Asian-Pacific countries with relatively low coronary heart disease ( CHD ) but high stroke events . Also , there is scanty evidence for repeated measures of uric acid levels among population . We examined associations of basic and repeated measures of uric acid level with CHD and stroke events in one Taiwanese adult community prospect ively . Cox proportional hazards models , treating uric acid as baseline and time-dependent covariates , were used to assess the 11-year risk of CHD and stroke events . Among 3602 adult subjects older than 35 years , 86 incident CHD and 155 incident stroke cases were identified . The rate ratios of hyperuricemia ranged between 2.00 and 3.96 , with higher risk ratios in women than in men . The rate differences and population attributable fractions were also higher in women than in men , implying that women had high risk of uric acid on cardiovascular events . After adjustment for age effect , time-dependent uric acid was associated with significant CHD risk in both genders ( hazard risk [ HR ] 1.43 , 95 % CI : 1.10 - 1.87 in men and HR 1.22 , 95 % CI : 1.03 - 1.44 in women ) . But the magnitude of hazard risks decreased after adjusting more atherosclerotic risk factors for CHD . For stroke event , the age-adjusted hazard risk of time-dependent continuous uric acid level was 1.23 ( 95 % CI : 1.00 - 1.54 ) in men and 1.36 ( 95 % CI : 1.05 - 1.75 ) in women . Multiple adjustment by risk factors demonstrated that uric acid was still a significant predictor for stroke in women ( HR 1.32 , 95 % CI : 1.00 - 1.73 ) . The similar hazard risk patterns existed for binary categories of hyperuricemia . Subgroup analyses demonstrated uric acid had significant risk only in hypertension and metabolic syndrome subgroups , not in their counterparts . We concluded that uric acid , in the baseline and time-dependent variables , could predict cardiovascular events in the community of relatively low CHD but high stroke risk in Taiwan Therapeutic strategies against free radicals have mostly focused on the augmentation of antioxidant defenses ( eg , vitamins C and E ) . A novel approach is to prevent free radical generation by the enzyme system xanthine oxidase . We examined whether the inhibition of xanthine oxidase with allopurinol can improve endothelial function in subjects with type 2 diabetes and coexisting mild hypertension compared with control subjects of a similar age . We examined 23 subjects ( 11 patients with type 2 diabetes and 12 healthy age-matched control subjects ) in 2 parallel groups . The subjects were administered 300 mg allopurinol in a r and omized , placebo-controlled study in which both therapies were administered for 1 month . Endothelial function was assessed with bilateral venous occlusion plethysmography , in which the forearm blood flow responses to intra-arterial infusions of endothelium-dependent and -independent vasodilators were measured . Allopurinol significantly increased the mean forearm blood flow response to acetylcholine by 30 % ( 3.16+/-1.21 versus 2.54+/-0.76 mL. 100 mL(-1 ) . min(-1 ) allopurinol versus placebo ; P=0.012 , 95 % CI 0.14 , 1.30 ) but did not affect the nitroprusside response in patients with type 2 diabetes . There was no significant impact on either endothelium-dependent or -independent vascular responses in age-matched control subjects . Allopurinol improved endothelial function to near-normal levels . Regarding markers of free radical activity , the level of malondialdehyde was significantly reduced ( 0.30+/-0.04 versus 0 . 34+/-0.05 micromol/L for allopurinol versus placebo , P=0.03 ) in patients with type 2 diabetes but not in control subjects . The xanthine oxidase inhibitor allopurinol improves endothelial dysfunction in patients with type 2 diabetes with mild hypertension but not in matched control subjects . In the former group , allopurinol restored endothelial function to near-normal levels BACKGROUND Uric acid stabilizes platelet aggregation and enhances thrombotic tendency . OBJECTIVE To examine the relationship between raised serum uric acid and subsequent cardiovascular events ( mortality , myocardial infa rct ion , stroke ) . METHODS This is a longitudinal study in a small r and om number ( 418 ) of patients in Kinshasa , Congo . In this hospital-based study , uricemia was determined with respect to gender , obesity and hypertension as well correlated with traditional cardiovascular risk factors . A univariate regression model was used to investigate the association of serum uric acid with the incidence of mortality , stroke and myocardial infa rct ion . RESULTS Serum uric acid was higher ( P<0.05 ) in obese women and men as well in hypertensives , than in their controls . The significant ( P<0.05 and 0.001 ) highest frequency of hyperuricemia was observed in both diabetic and hypertensive patients . Blood pressure ( BP ) was higher ( P<0.001 ) in patients with hyperuricemia than in those with normal serum uric acid . Serum uric acid was significantly correlated with body weight , BP , glucose , fibrinogen , urea , creatinin and total cholesterol . In men , hyperuricemia was significantly ( P<0.01 ) associated with a twofold increased risk of both myocardial infa rct ion and stroke incidence . However , hyperuricemia was significantly related to a double risk of all mortality and stroke onset . CONCLUSION Our results indicate that hyperuricemia among african patients is a strong predictor of myocardial infa rct ion in men , stroke in both sexes and all causes of mortality in women Background Increased serum uric acid ( SUA ) levels are linked to obesity , dyslipidemia , diabetes and hypertension . Whether SUA carries a risk for coronary heart disease ( CHD ) and stroke remains uncertain . Design A prospect i ve cohort study . Methods Of an original cohort of middle-aged workers who were examined in 1963 and followed-up for 23 years , 9125 men , free of CHD at entry , are included in this study . Subjects were divided into quintiles according to baseline SUA levels . Hazard ratios ( HR ) for all-cause , CHD , and stroke mortality were estimated in SUA quintiles , with the third serving as a referent . Results During follow-up , 2893 deaths were recorded , including 830 ascribed to CHD and 292 to stroke . The HR for all death [ 1.22 , 95 % confidence interval ( CI ) 1.09–1.37 ] and CHD ( 1.29 , 95 % CI 1.05–1.58 ) were increased in the upper SUA quintile . Fatal stroke showed a U-shaped relationship as both the upper ( HR 1.48 , 95 % CI 1.02–2.17 ) and bottom ( HR 1.43 , 95 % CI 0.99–2.08 ) quintiles were associated with a higher risk . Adjustment for confounders reduced the HR of the upper quintile for all outcomes , but did not attenuate the association of the bottom quintile with stroke ( HR 1.52 , 95 % CI 1.04–2.23 ) . When analysed separately by stroke type , the latter association seemed to be stronger for hemorrhagic ( HR 3.27 , 95 % CI 1.14–9.33 ) than for ischemic stroke ( HR 1.34 , 95 % CI 0.87–2.05 ) . Conclusion In addition to findings supporting increased mortality among hyperuricemic subjects , we identified an association between low SUA levels and fatal stroke , which deserves further investigation CONTEXT Hyperuricemia is a predictor for the development of hypertension and is commonly present in new-onset essential hypertension . Experimentally increasing uric acid levels using a uricase inhibitor causes systemic hypertension in animal models . OBJECTIVE To determine whether lowering uric acid lowers blood pressure ( BP ) in hyperuricemic adolescents with newly diagnosed hypertension . DESIGN , SETTING , AND PATIENTS R and omized , double-blind , placebo-controlled , crossover trial ( September 2004-March 2007 ) involving 30 adolescents ( aged 11 - 17 years ) who had newly diagnosed , never-treated stage 1 essential hypertension and serum uric acid levels > or = 6 mg/dL. Participants were treated at the Pediatric Hypertension Clinic at Texas Children 's Hospital in Houston . Patients were excluded if they had stage 2 hypertension or known renal , cardiovascular , gastrointestinal tract , hepatic , or endocrine disease . INTERVENTION Allopurinol , 200 mg twice daily for 4 weeks , and placebo , twice daily for 4 weeks , with a 2-week washout period between treatments . The order of the treatments was r and omized . MAIN OUTCOME MEASURES Change in casual and ambulatory blood pressure . RESULTS For casual BP , the mean change in systolic BP for allopurinol was -6.9 mm Hg ( 95 % confidence interval [ CI ] , -4.5 to -9.3 mm Hg ) vs -2.0 mm Hg ( 95 % CI , 0.3 to -4.3 mm Hg ; P = .009 ) for placebo , and the mean change in diastolic BP for allopurinol was -5.1 mm Hg ( 95 % CI , -2.5 to -7.8 mm Hg ) vs -2.4 ( 95 % CI , 0.2 to -4.1 ; P = .05 ) for placebo . Mean change in mean 24-hour ambulatory systolic BP for allopurinol was -6.3 mm Hg ( 95 % CI , -3.8 to -8.9 mm Hg ) vs 0.8 mm Hg ( 95 % CI , 3.4 to -2.9 mm Hg ; P = .001 ) for placebo and mean 24-hour ambulatory diastolic BP for allopurinol was -4.6 mm Hg ( -2.4 to -6.8 mm Hg ) vs -0.3 mm Hg ( 95 % CI , 2.3 to -2.1 mm Hg ; P = .004 ) for placebo . Twenty of the 30 participants achieved normal BP by casual and ambulatory criteria while taking allopurinol vs 1 participant while taking placebo ( P < .001 ) . CONCLUSIONS In this short-term , crossover study of adolescents with newly diagnosed hypertension , treatment with allopurinol result ed in reduction of BP . The results represent a new potential therapeutic approach , although not a fully developed therapeutic strategy due to potential adverse effects . These preliminary findings require confirmation in larger clinical trials . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00288184 The relationship between serum uric acid ( SUA ) and risk of coronary heart disease ( CHD ) mortality remains controversial , particularly in diabetic subjects . The aim of the present study is to evaluate whether SUA independently predicts CHD mortality in non-insulin-dependent elderly people from the general population and to investigate the interactions between SUA and other risk factors . Five hundred and eighty-one subjects aged ≥65 years with non-insulin-dependent diabetes mellitus were prospect ively studied in the frame of the CArdiovascular STudy in the ELderly ( CASTEL ) . Historical and clinical data , blood tests and 12-year fatal events were recorded . SUA as a continuous item was divided into tertiles and , for each tertile , adjusted relative risk ( RR ) with 95 % confidence intervals ( CI ) was derived from multivariate Cox analysis . CHD mortality was predicted by SUA in a J-shaped manner . Mortality rate was 7.9 % ( RR 1.28 , CI 1.05–1.72 ) , 6.0 % ( reference tertile ) and 12.1 % ( RR 1.76 , CI 1.18–2.27 ) in the increasing tertiles of SUA , respectively , without any difference between genders . In diabetic elderly subjects , SUA independently predicts the risk of CHD mortality in a J-shaped manner Although several studies report an association between hyperuricemia and coronary artery disease , little is known about the effect of hyperuricemia and gout on the risk of peripheral arterial disease ( PAD ) . Data on 283 incident clinical cases of PAD during a r and omized controlled trial of multiple cardiovascular risk factor intervention are evaluated . The serum uric acid levels among these individuals are compared with those of individuals who did not develop PAD during the study period . Multivariate logistic regression analyses measure the risk of developing PAD associated with higher levels of serum uric acid after adjusting for the effect of traditional vascular risk factors . Age and smoking are independently associated with development of PAD , with odds ratios of 1.08 ( 95 % confidence interval [ CI ] , 1.06 - 1.09 ) and 3.83 ( 95 % CI , 2.49 - 5.91 ) per year , respectively . Hyperuricemia ( serum uric acid level , > 7.0 mg/dL ) is an independent risk factor , with an odds ratio of 1.23 , but the confidence interval of the estimate is wide ( 95 % CI , 0.98 - 1.54 ) . In this multivariate model , a history of gout was associated with an odds ratio of 1.33 ( 95 % CI , 1.07 - 1.66 ) . Serum uric acid level is independently associated with a higher ( but statistically nonsignificant ) risk of PAD . A history of gouty arthritis is an independent and statistically significant predictor of incidence of PAD even after adjustment for the effect of underlying hyperuricemia A positive association between hyperuricemia and cardiovascular disease has been reported , but no study has evidence d yet the precise role of serum uric acid in the development of cardiovascular disease . In addition , no epidemiological studies have so far documented a decreased risk of cancer among people with hyperuricemia , even though the antioxidant action of uric acid has recently been stressed to inhibit DNA damage . The present prospect i ve cohort study investigates the relationship between hyperuricemia and health hazards in a Japanese working population . The subjects were 49,413 Japanese male railroad workers , aged 25 - 60 years at enrollment . Serum uric acid and other baseline data were provided by annual health-survey records from 1975 to 1982 . The vital status of the subjects was traced until the end of 1985 for those who remained alive . During an average 5.4-year study period , 984 deaths were recorded . Those with serum uric acid over 8.5 mg/dl showed elevated relative risks ( RRs ) of death in all causes ( RR 1.62 , p<0.01 ) , coronary heart disease ( RR 1.52 ) , stroke ( RR 2.33 , p<0.01 ) , hepatic disease ( RR 3.58 , p<0.01 ) , and renal failure ( RR 8.52 , p<0.01 ) , as compared with those with serum uric acid levels of 5.0 - 6.4mg/dl . The RR of death in all causes still remains statistically significant when adjusted by age and serum total cholesterol ( 2.00 , p<0.01 ) , age and alcohol intake ( 1.85 , p<0.001 ) , age and smoking ( 1.69 , p<0.001 ) , age and gout treatment ( 1.61 , p<0.05 ) , and also age and BMI ( 1.50 , p < 0.05 ) . On the other h and , the RR of all causes decreased but was still above 1.0 when adjusted by age and blood glucose ( 1.62 ) , age and systolic blood pressure ( 1.32 ) , age and GOT ( 1.23 ) , and also age and history of cardiovascular disease ( 1.17 ) . These results showed that hyperuricemia has a strong association with the RRs of death in all causes , coronary heart disease , stroke , hepatic disease and renal failure , and indicated that serum uric acid seems to be a considerable risk factor for reduced life expectancy Objective Although many epidemiological studies have suggested that increased serum uric acid levels are a risk factor for mortality , this relationship remains uncertain . This cohort study examined the effects of serum uric acid level on death from cancer , atherosclerotic cardiovascular disease ( ASCVD ) or all causes in men . Method A 9-year , prospect i ve cohort study was carried out with 22 698 Korean men , aged 30 to 77 years , who received health insurance from the National Health Insurance Corporation and who underwent biennial , secondary medical evaluations in 1992–1996 . The main outcome measures were death from cancer , ASCVD or all causes , compared by quintiles of serum uric acid level . At baseline , the mean ( SD ) level of serum uric acid was 354.4 ( 98.1 ) μmol/l . Results During 199 746 person-years of follow-up , there were 387 cancer deaths , 323 ASCVD ( 99 ischaemic heart disease , 192 stroke ) deaths and 1625 all-cause deaths . In multivariate Cox proportional hazards models , having controlled for age , current smoking , diabetes , hypertension and hypercholesterolaemia , uric acid levels were not associated with mortality from cancer , ASCVD or all causes . However , for those with diabetes , uric acid levels were associated with mortality from all causes even after full adjustment of the covariates . When the interaction term was included in the multivariate model , there was significant interactive effect of uric acid with diabetes ( RR = 1.26 , 95 % confidence interval 1.02–1.55 ) on the risk of all cause of death , whereas the effects of uric acid itself did not attain significance . Conclusion These findings indicate that uric acid level is not an independent risk factor for death from cancer , ASCVD or all causes |
12,738 | 26,822,633 | In patients with acute thromboembolism ( DVT or PE ) aged 18 years or older , considerable uncertainty surrounds the use of a 10-mg or a 5-mg loading dose for initiation of warfarin to achieve an INR of 2.0 to 3.0 on the fifth day of therapy . | BACKGROUND Venous thromboembolism ( VTE ) is a common condition in hospital patients .
Considerable controversy is ongoing regarding optimal initial warfarin dosing for patients with acute deep venous thrombosis ( DVT ) and pulmonary embolism ( PE ) .
Achieving a therapeutic international normalized ratio ( INR ) with warfarin as soon as possible is important because this minimizes the duration of parenteral medication necessary to attain immediate anticoagulation , and it potentially decreases the cost and inconvenience of treatment .
Although a 5-mg loading-dose nomogram tends to prevent excessive anticoagulation , a 10-mg loading-dose nomogram may achieve a therapeutic INR more quickly .
This is an up date of a review first published in 2013 .
OBJECTIVES To evaluate the efficacy of a 10-mg warfarin nomogram compared with a 5-mg warfarin nomogram among patients with VTE . | BACKGROUND Patients with acute proximal deep-vein thrombosis are usually treated first in the hospital with intravenous st and ard ( unfractionated ) heparin . However , the longer plasma half-life , better bioavailability after subcutaneous administration , and more predictable anticoagulant response of low-molecular-weight heparins make them attractive for possible home use . We compared these two approaches . METHODS Patients with acute proximal deep-vein thrombosis were r and omly assigned to receive either intravenous st and ard heparin in the hospital ( 253 patients ) or low-molecular-weight heparin ( 1 mg of enoxaparin per kilogram of body weight subcutaneously twice daily ) administered primarily at home ( 247 patients ) . The study design allowed out patients taking low-molecular-weight heparin to go home immediately and hospitalized patients taking low-molecular-weight heparin to be discharged early . All the patients received warfarin starting on the second day . RESULTS Thirteen of the 247 patients receiving low-molecular-weight heparin ( 5.3 percent ) had recurrent thromboembolism , as compared with 17 of the 253 patients receiving st and ard heparin ( 6.7 percent ; P=0.57 ; absolute difference , 1.4 percentage points ; 95 percent confidence interval , -3.0 to 5.7 ) . Five patients receiving low-molecular-weight heparin had major bleeding , as compared with three patients receiving st and ard heparin . After r and omization , the patients who received low-molecular-weight heparin spent a mean of 1.1 days in the hospital , as compared with 6.5 days for the st and ard-heparin group ; 120 patients in the low-molecular-weight- heparin group did not need to be hospitalized at all . CONCLUSIONS Low-molecular-weight heparin can be used safely and effectively to treat patients with proximal deep-vein thrombosis at home Warfarin induction is accomplished by titrating dosage to coagulation test results . Algorithms can guide this process but not identify the starting dose . We hypothesized that an initial warfarin dose approximating the maintenance value would safely enhance rapidity of induction . In a r and omized trial we compared a fixed-dose to a maintenance-dose strategy for beginning warfarin therapy . To predict the maintenance dose among patients with differing warfarin requirements we performed regression analysis on clinical factors derived from chart review . Four community hospitals supplied records for retrospective analysis . The prospect i ve trial was conducted in one , a 350-bed teaching institution . A sample of in patients anticoagulated during 1998 formed the development set for retrospective study ; a 1999 sample formed the validation set . A one year trial recruited consecutive eligible in patients initiated on warfarin . We r and omly assigned patients to a first warfarin dose calculated using our regression formula or fixed at 5 mg . All patients ' subsequent doses were determined ( as a percentage of initial ) from coagulation testing . We compared days to anticoagulation , hospitalized hours , complications , and activity of factor II and protein C in a patient sample at intervals after induction . Weight , age , serum albumin , and presence of malignancy explained 25 - 30 % of variance in maintenance dose . Ninety patients ( 44 calculated-dose and 46 st and ard-dose ) evaluated in the clinical trial . Mean time to anticoagulation ( among patients achieving anticoagulation ) was 4.2 and 5.0 days , respectively ( p = 0.007 ) . We observed no significant differences in other endpoints . Individualized initial dosing may safely hasten warfarin induction BACKGROUND Warfarin sodium therapy is usually initiated with a loading dose to reduce the time required to elevate the international normalized ratio ( INR ) . Warfarin loading doses are associated with early overanticoagulation and the development of a potential hypercoagulable state ; they also may not hasten achieving an INR value between 2.0 and 3.0 . This study was design ed to prospect ively confirm our observation that a 5-mg warfarin sodium loading dose is as effective as a 10-mg loading dose in achieving a therapeutic INR for 2 consecutive days on days 3 and 4 or 4 and 5 of therapy . METHODS Fifty-three patients initiating warfarin therapy with a target INR of 2.0 to 3.0 were r and omly allocated to receive an initial dose of 5 or 10 mg of warfarin . Subsequent doses were based on dosing algorithms . The INR was measured daily for 5 days . The primary end point of the study was the proportion of patients whose INR values were between 2.0 and 3.0 on 2 consecutive daily determinations on days 3 , 4 , or 5 of the study and whose INR did not exceed 3.0 at any point during the study . RESULTS Five ( 24 % ) of 21 patients in the 10-mg group and 21 ( 66 % ) of 32 patients in the 5-mg group achieved the primary end point ( relative risk 2.22 , 95 % confidence interval 1.30 - 3.70 [ P < .003 ] ) . A trend toward less overanticoagulation was seen in the 5-mg warfarin group . CONCLUSION A 10-mg loading dose of warfarin is unlikely to be more effective than a 5-mg loading dose in achieving an INR of 2.0 to 3.0 by day 4 or 5 of therapy Context The optimal methods for achieving therapeutic levels of anticoagulation with warfarin remain uncertain . Contribution In this r and omized trial of two warfarin dosing nomograms , a 10-mg initiation dose led to a therapeutic international normalized ratio ( INR ) 1.4 days sooner than a 5-mg initiation dose . The two nomograms had the same rate of adverse events and the same proportion of INR values greater than 5.0 . Clinical Implication s Physicians can more quickly get their patients to a therapeutic INR with warfarin by using a dosing nomogram that starts with a 10-mg dose rather than a 5-mg initiation dose . The Editors The management of venous thromboembolism has improved substantially in the past 10 years . Conventional therapy consists of unfractionated or low-molecular-weight heparin for 5 to 7 days , together with oral anticoagulation with warfarin given for a minimum of 3 months ( 1 , 2 ) . Low-molecular-weight heparin facilitates outpatient treatment , and warfarin is usually initiated within 24 hours . Clinical trials have demonstrated that low-molecular-weight heparin may be safely discontinued after 5 days once the international normalized ratio ( INR ) has remained greater than 1.9 for 24 hours ( 2 , 3 ) . Nurses or pharmacists often coordinate outpatient management of venous thromboembolism with appropriate physician support ( 4 ) . For outpatient therapy , minimizing the time to a therapeutic INR is advantageous because it potentially decreases the cost and inconvenience of low-molecular-weight heparin therapy . The initiation of warfarin treatment is problematic , however , because of variations in dose response . A dosing nomogram to facilitate safe , timely warfarin initiation to achieve therapeutic INRs would be useful . We previously developed and tested a nomogram for the initiation of warfarin therapy using a 10-mg loading dose and found that it was superior to st and ard physician practice because it result ed in shorter time to a therapeutic INR ( 5 ) . This nomogram , however , required daily INR testing and was therefore not ideal for outpatient management . We subsequently revised the nomogram so that it requires INR assessment s only on days 3 and 5 during the first 8 days of therapy . We found that the revised nomogram was successful : Almost 90 % of patients had a therapeutic INR by the 5th day of treatment ( 6 ) . The objective of our current study was to perform a r and omized , controlled trial comparing the effectiveness and feasibility of a warfarin nomogram using a 10-mg loading dose with those of a nomogram using a 5-mg loading dose for the management of out patients with acute venous thromboembolism . Methods Patients Consecutive out patients with a diagnosis of objective ly confirmed acute venous thromboembolism ( deep venous thrombosis or pulmonary embolism ) who presented to the thrombosis clinics of four Canadian academic centers were c and i date s for study inclusion . Patients were not admitted to the study if they had a baseline INR greater than 1.4 , had thrombocytopenia ( platelet count < 50 109 cells/mL ) , were younger than 18 years of age , required hospitalization , had received oral anticoagulant therapy within the previous 2 weeks , or were at high risk for major bleeding ( as judged by the attending physician ) . Design This study was a r and omized , double-blind ( physicianpatient ) , controlled trial . R and omization was stratified by study center and presence of active malignant disease . The r and omization sequence was computer generated by the trial statistician . The details of the r and omization sequence , which were not known to the investigators or to the study coordinator , were contained in sets of sequentially numbered , opaque , sealed envelopes . The outside of each envelope was marked only with the name of the hospital , whether the patient had a malignant condition , and a patient number . Patients were assigned to 5-mg or 10-mg warfarin induction by using previously vali date d nomograms ( Table 1 and Figure 1 ) ( 6 , 7 ) . The 5-mg nomogram , as published , specifies a dose range on each day after the first day of treatment with no indication of how to choose the dose ( 7 ) . For the current study , we chose the higher dose whenever a range was indicated . The research ethics boards at each of the participating institutions approved the study , and informed consent was obtained from all participants . Table 1 . 5-mg Warfarin Initiation Nomogram Figure 1 . 10-mg warfarin initiation nomogram . Interventions Study participants were r and omly allocated to warfarin induction with a 10-mg or 5-mg warfarin nomogram ( Table 1 and Figure 1 ) ( 6 , 7 ) . Baseline data collected included demographic characteristics ( age , sex ) , diagnosis , weight , presence of active malignant disease , complete blood count , and INR . International normalized ratios were measured in local licensed clinical laboratories . Treatment was initiated on the first day ( day 1 ) with subcutaneous low-molecular-weight heparin ( dalteparin [ 200 U/kg of body weight ] or tinzaparin [ 175 U/kg ] ) . Low-molecular-weight heparin was continued for a minimum of five daily injections until the INR was therapeutic ( > 1.9 ) . The initial warfarin dose was determined by using treatment allocation . All warfarin doses were administered in the evening , and blood sample s for INR assessment s were drawn before 10:00 a.m. Patients in the 10-mg group received 10 mg of warfarin on each of the first 2 days , whereas patients in the 5-mg group were given 5 mg on each of the first 2 days . Subsequent dose adjustments after day 3 were made by using the respective nomograms . International normalized ratios were measured in all patients on the mornings of days 3 , 4 , and 5 . The 10-mg nomogram , unlike the 5-mg nomogram , did not require an INR measurement on day 4 for dosing ; however , a measurement was performed for study end point purpose s only . If a patient did not have a therapeutic INR by day 5 , the INR was measured daily until it was therapeutic . Local attending physicians directed management of warfarin monitoring from day 8 to day 90 . End Points The primary end point of the study was time in days to a therapeutic INR ( > 1.9 ) . The secondary end points included the proportion of patients whose INRs were within the therapeutic range ( 2.0 to 3.0 ) on the 5th day , incidence of recurrent venous thromboembolism within 90 days of diagnosis ( as defined by previously published criteria [ 2 , 3 ] ) , incidence of major bleeding within 28 days of diagnosis ( as defined by previously published criteria [ 2 , 3 ] ) , number of INR measurements greater than 5 , absolute number of INR assessment s in the first 28 days , and 90-day survival . An adjudication committee consisting of three study investigators evaluated all clinical events in a blinded fashion , and end points were determined by consensus . Hypothesis We tested the hypothesis that patients managed with a 10-mg warfarin induction nomogram would achieve therapeutic INRs more rapidly than patients managed with a 5-mg warfarin nomogram . We believed these improvements would occur without increased risk for bleeding . Sample Size Using data from our pilot nomogram to estimate st and ard deviation ( 1 day ) , we calculated that 92 patients per group would be required to show a 0.5-day difference in time to a therapeutic INR ( 90 % power ; two-sided = 0.05 ) . We considered a 0.5-day difference to be the minimal clinical ly important difference because it would yield a significant proportion of patients who would not require low-molecular-weight heparin therapy beyond 5 days . Statistical Analysis All statistical analyses were performed according to a pre-established analysis plan and by intention to treat . We used SPSS software for all analyses ( SPSS , Inc. , Chicago , Illinois ) . Baseline characteristics were described by using descriptive statistics . Mean time to therapeutic INR was compared between the groups by using the unpaired Student t-test . Proportions ( including the proportion in each group with a therapeutic INR on day 5 ) were compared by using the unadjusted chi-square test . No interim analyses were conducted . Two-sided significance tests were used throughout , and a P value less than 0.05 was considered statistically significant . Multiple linear regression was performed to explore determinants of time to therapeutic INR ( after appropriate testing was done to prove the suitability of this analysis ) . Biologically plausible predictors ( age , sex , weight , presence of cancer , and treatment assignment ) were included in the original model . Backward stepwise regression was performed , and a P value greater than 0.20 was used for variable removal . Results Between August 1999 and June 2000 , 210 patients were approached for participation in the study . Two patients were excluded because they had a baseline INR greater than 1.4 , 2 were excluded because they required hospitalization , and 5 were excluded because they had received warfarin in the previous 2 weeks . The last patient completed follow-up in September 2000 . A total of 201 eligible , consenting patients were enrolled and r and omly assigned to treatment ( Table 2 ) . One hundred four patients were assigned to the 10-mg group , and 97 were assigned to the 5-mg group . The baseline characteristics of both groups were similar , although the 10-mg group included more men . The overall age range was 18 to 98 years , and 32 patients ( 16 % ) were older than 75 years of age . All patients were followed for 90 days . Table 2 . Comparison of the 10-mg and 5-mg Nomogram Groups Patients in the 10-mg group achieved a therapeutic INR 1.4 days earlier than patients in the 5-mg group ( P < 0.001 ) . In addition , many more patients in the 10-mg group than in the 5-mg group achieved a therapeutic INR by day 5 ( 83 % vs. 46 % ; P < 0.001 ) ( Figure 2 ) . The 5-mg group also required more INR assessment s in the first 28 days ( 9.1 vs. 8.1 ; P = 0.04 ) . Only two episodes of major bleeding were observed , one in each group , and rates of recurrence of venous thromboembolism did not differ significantly between Background — Pharmacogenetic-guided dosing of warfarin is a promising application of “ personalized medicine ” but has not been adequately tested in r and omized trials . Methods and Results — Consenting patients ( n=206 ) being initiated on warfarin were r and omized to pharmacogenetic-guided or st and ard dosing . Buccal swab DNA was genotyped for CYP2C9 * 2 and CYP2C9 * 3 and VKORC1C1173 T with a rapid assay . St and ard dosing followed an empirical protocol , whereas pharmacogenetic-guided dosing followed a regression equation including the 3 genetic variants and age , sex , and weight . Prothrombin time international normalized ratio ( INR ) was measured routinely on days 0 , 3 , 5 , 8 , 21 , 60 , and 90 . A research pharmacist unblinded to treatment strategy managed dose adjustments . Patients were followed up for up to 3 months . Pharmacogenetic-guided predicted doses more accurately approximated stable doses ( P<0.001 ) , result ing in smaller ( P=0.002 ) and fewer ( P=0.03 ) dosing changes and INRs ( P=0.06 ) . However , percent out-of-range INRs ( pharmacogenetic=30.7 % , st and ard=33.1 % ) , the primary end point , did not differ significantly between arms . Despite this , when restricted to wild-type patients ( who required larger doses ; P=0.001 ) and multiple variant carriers ( who required smaller doses ; P<0.001 ) in exploratory analyses , results ( pharmacogenetic=29 % , st and ard=39 % ) achieved nominal significance ( P=0.03 ) . Multiple variant allele carriers were at increased risk of an INR of ≥4 ( P=0.03 ) . Conclusions — An algorithm guided by pharmacogenetic and clinical factors improved the accuracy and efficiency of warfarin dose initiation . Despite this , the primary end point of a reduction in out-of-range INRs was not achieved . In subset analyses , pharmacogenetic guidance showed promise for wild-type and multiple variant genotypes 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 ) Purpose : A r and omized controlled trial was conducted in patients initiating warfarin to determine whether algorithms that incorporate genotypes affecting warfarin metabolism and function , and Vitamin K metabolism improve prediction of therapeutic warfarin dose and anticoagulation management . Methods : A total of 230 patients were r and omized to either a clinical arm where dosing algorithms considered only clinical information or an interventional arm where dosing algorithms used clinical and genotypic variables ( CYP2C9 , CYP4F2 , and VKORC1 ) . Subjects in the interventional arm were genotyped within 5 hours , and the initial dose was informed by genotype . Primary endpoints were absolute prediction error relative to therapeutic dose , and time in therapeutic target range during the first 14 days . Secondary endpoints included time to stable dose in therapeutic range , time to first international normalization ratio > 4 , and warfarin-related adverse events . Results : The model including genetics more accurately identified therapeutic dose twice as often as the clinical model ( 65.3 % vs. 34.7 % ) ( P < 0.0001 ) . Patients in the interventional arm did not achieve greater time in therapeutic range . Study arms were similar regarding time to international normalization ratio > 4 and adverse events . Conclusion : Genotype-informed dosing clearly improved prediction of therapeutic dose beyond that available with clinical parameters . Genetic information did not affect time in therapeutic target range during the first 14 days of therapy . Current management practice s with the vagaries in dose adjustment after warfarin initiation exert a strong influence on traditional clinical outcomes OBJECTIVES To compare a new low-dose warfarin induction regimen with the Fennerty regimen in elderly in patients . DESIGN Age-stratified , r and omized prospect i ve study . SUBJECTS 120 age-stratified elderly in patients . INTERVENTIONS Each patient was r and omized to either the new induction regimen or to a modified Fennerty regimen . MAIN OUTCOMES MEASURES Days to therapeutic International Normalized Ratio ( INR > 2 ) ; days in the therapeutic range ( INR 2 - 3 ) during induction ; number of patients with INR > 4.5 ; ability of day 4 INR to predict day 8 warfarin dose . RESULTS The mean time to therapeutic INR was longer for the new induction regimen than modified Fennerty regimen in patients aged 65 - 75 years [ 4.6 ( mean ) + /- 1.6 ( SD ) days vs 3.8 + /- 0.8 days ; P = 0.03 ] and in patients aged > 75 years ( 4.5 + /- 1.4 days vs 3.5 + /- 0.7 days ; P = 0.003 ) . Patients spent more time in the therapeutic INR range with the new induction regimen [ 3.0 + /- 1.3 days vs 2.7 + /- 1.3 days ( P = 0.03 ) for those aged 65 - 75 years and 2.9 + /- 1.1 days vs 2.4 + /- 1.3 days ( P = 0.04 for those aged > 75 years ] . Fewer patients using the new regimen had INRs > 4.5 in the first 8 days [ 1 ( 3 % ) vs 6 ( 20 % ) for 65 - 75 years ( P < 0.05 ) and 1 ( 3 % ) vs 11 ( 37 % ) for > 75 years ( P < 0.01 ) ] . The ability to predict the maintenance dose to within 1 mg was 55 % for both regimens . CONCLUSION The low-dose regimen has important clinical advantages over the Fennerty regimen for anticoagulating elderly in patients Warfarin anticoagulation effect is characterized by marked variability , some of which has been attributed to CYP2C9 polymorphisms . This study prospect ively examines whether a priori knowledge of CYP2C9 genotype may improve warfarin therapy . Patients were r and omly assigned to receive warfarin by a vali date d algorithm ( “ control ” , 96 patients ) or CYP2C9 genotype‐adjusted algorithms ( “ study ” , 95 patients ) . The first therapeutic international normalized ratio and stable anticoagulation were reached 2.73 and 18.1 days earlier in the study group , respectively ( P<0.001 ) . The faster rate of initial anticoagulation was driven by a 28 % higher daily dose in the study group ( P<0.001 ) . Study group patients spent more time within the therapeutic range ( 80.4 vs 63.4 % , respectively , P<0.001 ) and experienced less minor bleeding ( 3.2 vs 12.5 % , P<0.02 , respectively ) . In conclusion , CYP2C9 genotype‐guided warfarin therapy is more efficient and safer than the “ average‐dose ” protocol . Future research should focus on construction of algorithms that incorporate other polymorphisms ( VKORC1 ) , host factors , and environmental influences Patients starting oral anticoagulant therapy after heart valve replacement initially require a lower target international normalized ratio ( INR ) ( 2.0 , range 1.5 to 2.6 ) because of a higher risk of bleeding until pericardial wires are removed . In a previous retrospective analysis , we observed a higher sensitivity to warfarin in these patients compared with nonsurgical patients . In a r and omized clinical trial , we compared a fixed , lower dose of warfarin ( 2.5 mg ) with the st and ard treatment consisting of a 5-mg loading dose , then adjusted to the target INR during the first 5 days of anticoagulation . INRs were measured daily , but the fixed dose was only modified on day 3 if the INR was < 1.5 or > 3.0 . One hundred ninety-seven patients were considered eligible for the study . The 2 groups were well matched according to age , gender , body mass index , concomitant treatments , and type of valves implanted . The proportion of INRs > 2.6 during the study period was 42.5 % in the 5-mg group and 26.2 % in the 2.5-mg group ( p < 0.05 ) , and the proportion of INRs > 3.0 on day 3 was 23.9 % and 9.5 % ( p < 0.05 ) , respectively . In the 2.5-mg group , 35.7 % of patients had an INR < 1.5 on day 3 and had the dose increased ( vs 3.5 % , p < 0.001 ) ; however , in the 5-mg group , 95.6 % had the initial dose reduced , 49.6 % had the dose withheld for at least 1 day , and the mean dose during the 5 days of study was 3.08 mg . Average time to achieve therapeutic range was higher in the 2.5-mg group ( 2.72 vs 1.98 days , p < 0.0001 ) , but the approach to the targeted INR was more regular , and the gap between target and mean INR on day 5 was smaller . There were no bleeding or thromboembolic complications in either group . Thus , a lower loading dose of warfarin in patients after heart valve replacement reduces excessive anticoagulation and offers a more regular achievement of the therapeutic target by reducing the number of dose adjustments . Daily monitoring of the INR is still recommended In order to investigate whether a more intensive initial oral anticoagulation still would be safe and effective , we performed a prospect i ve r and omized study in patients with deep vein thrombosis . They received either the conventional regimen of oral anticoagulation ( " low-dose " ) and heparin or a more intense oral anticoagulation ( " high-dose " ) with a shorter period of heparin treatment . In the first part of the study 129 patients were r and omized . The " low-dose " group reached a stable therapeutic prothrombin complex (PT)-level after 4.3 and the " high-dose " group after 3.3 days . Heparin was discontinued after 6.0 and 5.0 days respectively . There was no difference in significant hemorrhage between the groups , and no clinical signs of progression of the thrombosis . In the second part of the study another 40 patients were r and omized , followed with coagulation factor II , VII , IX and X and with repeated venograms . A stable therapeutic PT-level was achieved after 4.4 ( " low-dose " ) and 3.7 ( " high-dose " ) days , and heparin was discontinued after 5.4 and 4.4 days respectively . There were no clinical hemorrhages , the activity of the coagulation factors had dropped to the same level in both groups at the time when heparin was discontinued and no thromboembolic complications occurred . Our oral anticoagulation regimen with heparin treatment for an average of 4.4 - 5 days seems safe and reduces in-patient costs Background The Clarification of Optimal Anticoagulation through Genetics ( COAG ) trial is a large , multicenter , double-blinded , r and omized trial to determine whether use of a genotype-guided dosing algorithm ( using clinical and genetic information ) to initiate warfarin treatment will improve anticoagulation status when compared to a dosing algorithm using only clinical information . Purpose This article describes prospect i ve alpha allocation and balanced alpha allocation for the design of the COAG trial . Methods The trial involves two possibly heterogeneous population s , which can be distinguished by the difference in warfarin dose as predicted by the two algorithms . A statistical approach is detailed , which allows an overall comparison as well as a comparison of the primary endpoint in the subgroup for which sufficiently different doses are predicted by the two algorithms . Methods of allocating alpha for these analyses are given — a prospect i ve alpha allocation and allocating alpha so that the two analyses have equal power , which we call a ‘ balanced alpha allocation . ’ Results We show how to include an analysis of the primary endpoint in a subgroup as a co- primary analysis . Power can be improved by incorporating the correlation between the overall and subgroup analyses in a prospect i ve alpha allocation approach . Balanced alpha allocation for the full cohort and subgroup tests to achieve the same desired power for both of the primary analyses is discussed in detail . Limitations In the COAG trial , it is impractical to stratify the r and omization on subgroup membership because genetic information may not be available at the time of r and omization . If imbalances in the treatment arms in the subgroup are found , they will need to be addressed . Conclusions The design of the COAG trial assures that the subgroup in which the largest treatment difference is expected is elevated to a co- primary analysis . Incorporating the correlation between the full cohort and the subgroup analyses provides an improvement in power for the subgroup comparison , and further improvement may be achieved via a balanced alpha allocation approach when the parameters involved in the sample size calculation are reasonably well estimated . Clinical Trials 2010 ; 7 : 597—604 . Warfarin levels are monitored by measuring the prothrombin time , which responds to reductions in levels of three vitamin K-dependent clotting factors : factors II , VII , and X [ 1 , 2 ] . During the first 48 hours of treatment , the anticoagulant effect of warfarin is caused mainly by a reduction in the activity of factor VII , which has a half-life of 6 hours . In contrast , the antithrombotic effect of warfarin ( which is thought to be caused primarily by a reduction in the activity of factor II ) is delayed for as long as 60 hours [ 3 , 4 ] . Therefore , during the first 48 hours of therapy , the anticoagulant and antithrombotic effects of warfarin may be dissociated . In addition , because the half-life of the vitamin K-dependent anticoagulant protein , protein C , is similar to that of factor VII [ 5 ] , the early anticoagulant effect of warfarin ( which results from reduction of factor VII ) could be counteracted by a procoagulant effect ( which results from reduction of protein C ) [ 6 ] . Warfarin treatment is often initiated with a 10-mg loading dose and then reduced to a level that maintains the international normalized ratio ( INR ) within the therapeutic range . An alternative approach is to start warfarin therapy at a dose of 5 mg , which is the average dose required to maintain an INR of 2.0 to 3.0 . Although a 10-mg loading dose produces a more rapid increase in the prothrombin time , this effect is caused largely by a decrease in factor VII levels and therefore may not produce a more rapid antithrombotic effect . The 10-mg loading dose has three potential short-comings . First , if heparin is discontinued as soon as the INR reaches the therapeutic range , thrombus extension may occur . This is because the antithrombotic effect of warfarin may not yet have manifested . Second , elderly or vitamin K-deficient patients may be exposed to an unnecessary risk for bleeding [ 7 - 12 ] . Third , protein C levels can be excessively decreased before the full antithrombotic effect of warfarin has been completely expressed through the reduction of factor II . On the basis of these considerations , we did a study to compare the relative effects of 5- and 10-mg loading doses of warfarin on four surrogate laboratory markers of efficacy and safety . Methods Patients with no contraindications to warfarin who required anticoagulation ( target INR , 2.0 to 3.0 ) were invited to participate in the trial between June and November 1994 at The Hamilton Civic Hospitals ( Ontario , Canada ) . Enrollment was targeted at 50 patients . All patients gave written , informed consent , and the study was approved by the local internal review board . Patients were assigned by r and om number table to receive warfarin at an initial dose of 5 or 10 mg . Subsequent doses were determined on the basis of nomograms that were developed before the study began through an iterative process . Because the study used laboratory outcomes , patients and health care professionals were not blinded to treatment assignments . Patients were followed for a maximum of 108 hours , during which time they received five doses of warfarin . Blood sample s were taken before warfarin therapy was initiated , 12 hours after the first dose of warfarin , and at 24-hour intervals for 5 days . Blood was collected into vacuum-sealed containers that contained 0.102 mol of buffered sodium citrate per liter . To obtain platelet-free plasma , the sample was double centrifuged at 1700 g and frozen at 70C for batch assays [ 13 ] . The prothrombin time was measured using Thromborel S ( International Sensitivity Index 1.06 , Behring Diagnostics , Kanata , Ontario , Canada ) and reported as an INR [ 14 ] . Heparin does not increase the prothrombin time in patients receiving both warfarin and heparin if this thromboplastin reagent is used . Factors II , VII , IX , and X were assayed by using the one-stage clotting method [ 15 ] . Protein C levels were measured by using a functional clotting assay ( Dade International , Mississauga , Ontario , Canada ) [ 16 ] . Treatment of supratherapeutic INRs with vitamin K was left to the discretion of the attending physician . The outcome measures were the time required to achieve an INR of 2.0 to 3.0 , the proportion of INR values greater than 3.0 , the time course for reductions in levels of factors II and X , and the time course for reduction in protein C levels . Additional data included levels of factors VII and IX . Results Fifty-one consecutive patients were enrolled in the trial . Two were excluded after one dose of warfarin : One died , and one required cardiac catheterization . Twenty-five patients were r and omly assigned to receive a 10-mg loading dose of warfarin ; 24 were assigned to receive a 5-mg loading dose . The two groups did not differ in age ; weight ; or frequency of acute thromboembolism , cancer , or surgery during or immediately before the study period . Forty-eight patients received concomitant heparin therapy for all or part of the study period . Beginning on study day 2 , the dose of warfarin was adjusted using a nomogram . Warfarin doses in the two groups were similar except on days 1 and 2 . The 10-mg group achieved an INR greater than 2.0 statistically significantly sooner than did the 5-mg group ( Table 1 ) . At 36 hours , 11 of 25 patients ( 44 % [ CI , 34 % to 54 % ] ) in the 10-mg group had INRs of 2.0 or greater compared with 2 of 24 patients ( 8 % [ CI , 3 % to 14 % ] ) in the 5-mg group ( P = 0.005 ) . At 60 hours , 9 of 25 patients in the 10-mg group ( 36 % [ CI , 17 % to 54 % ] ) had INRs greater than 3.0 compared with none of 23 patients in the 5-mg group ( P = 0.002 ) . Five patients ( 4 in the 10-mg group and 1 in the 5-mg group ) received vitamin K. These patients had INRs of 4.8 to 9.3 and received 0.5 to 2.0 mg of vitamin K subcutaneously . No patient bled . Table 1 . International Normalized Ratios for Patients Assigned to Receive a 5- or 10-mg Loading Dose of Warfarin * Levels of factors II and X declined slowly , and no substantial differences were seen between the 5- and 10-mg groups . In contrast , levels of factor VII and protein C decreased more rapidly and were statistically significantly lower in the 10-mg group than in the 5-mg group at 36 and 60 hours ( Figure 1 ) . Figure 1 . Plasma levels of coagulation factors in patients receiving a 10-mg ( striped bars ) or 5-mg ( white bars ) loading dose of warfarin for each of six time points assessed . top middle bottom Discussion We compared the relative effects of 5- and 10-mg loading doses of warfarin . The time course of reduction in levels of factor II was used as a surrogate end point for clinical efficacy , and excessive elevation of the prothrombin time and unopposed reduction in protein C levels were used as surrogate end points for safety . Patients who received a 10-mg loading dose of warfarin achieved INRs greater than 2.0 more rapidly than did patients who received a 5-mg loading dose . However , because this change in the INR was entirely caused by the early reduction of factor VII levels in the 10-mg group , it may not reflect an antithrombotic effect of warfarin , which is thought to result from a reduction in factor II levels . Two separate experimental observations in rabbits support this idea : The first is the early report of a 5-day delay in achieving an antithrombotic effect with warfarin , although the prothrombin time was first prolonged into the therapeutic range and the level of factor VII was markedly reduced after 2 days of treatment [ 17 ] . This observation provides the rationale for overlapping heparin and warfarin therapy for 5 days during the initiation of anticoagulant therapy [ 17 , 18 ] . The second is the finding that the antithrombotic effect of warfarin is abrogated by the infusion of factor II and ( to a lesser extent ) factor X [ 18 ] . In our study , the rate of reduction in levels of factor II and factor X activity were similar in the 5- and 10-mg groups . On the other h and , the 10-mg loading dose was associated with a significantly more rapid decrease in protein C activity ( which decreased before levels of factors X and II were substantially reduced ) than that seen in the 5-mg group and an excessive prolongation of the INR . The combination of markedly reduced protein C levels and near-normal levels of factors II and X over the first 2 days of warfarin therapy could produce a hypercoagulable state , and excessive prolongation of the INR could create a higher risk for bleeding . Our study is limited because we used surrogate markers for efficacy and safety . A much larger trial using clinical outcome measures is needed to determine whether the surrogate markers that we used are clinical ly relevant . Nevertheless , our findings suggest that both regimens result in a therapeutic INR in most patients by day 5 of treatment . From Hamilton Civic Hospital , McMaster University , and The Hamilton Civic Hospitals Research Centre , Hamilton , Ontario , Canada St and ard treatment for venous thromboembolism is parenteral heparin followed by warfarin . In this study we assess whether a st and ardized method of ordering warfarin reduces the duration of hospitalization . Consecutive patients were r and omized to receive warfarin managed by attending physicians or by a nomogram . Patients were stratified according to primary or secondary venous thromboembolism . Prothrombin times were measured daily and heparin was given for a minimum of 5 days and stopped when the International Normalized Ratio was > 1.9 . Patients were followed for 3 months . There were 111 patients , 80 with primary and 31 with secondary venous thromboembolism . Overall there were no differences between the two warfarin groups with respect to length of admission . Given the prolonged duration of admission in many patients with secondary venous thromboembolism , a subset analysis was conducted on the 80 patients with primary venous thromboembolism . Patients in the st and ard group stayed significantly longer than patients in the nomogram group ( 6.0 vs. 5.6 days , p = 0.02 ) . The warfarin nomogram as tested is safe and leads to a significantly shorter length of stay for patients with primary venous thromboembolism as compared to st and ard practice BACKGROUND Rapid genetic screening for cytochrome P450 ( CYP ) 2C9 variants may play a role in improving the efficacy and safety of warfarin in individuals with CYP2C9 variants . The feasibility of prospect i ve CYP2C9 model-based warfarin dosing has not yet been assessed . OBJECTIVES To evaluate the feasibility of applying a CYP2C9 gene-based warfarin dosing model in clinical practice . DESIGN Prospect i ve , r and omized , single-blinded clinical pilot trial . SETTING Large multispecialty group practice . PATIENTS C and i date s were recruited from a list of clinic patients eligible for warfarin initiation . This included patients with newly diagnosed thromboembolic disease or atrial arrhythmia , as well as patients anticipating elective valvuloplasty or arthroplasty . Patients who previously received warfarin were excluded . INTERVENTIONS Subjects were r and omized to receive either 1 ) a st and ard initiation dose of 5 mg warfarin/day , or 2 ) rapid CYP2C9 genotyping and an initiation dose determined using parameters estimated from a previously published multivariate model [ including age , body size , co-morbidity ( e.g. , diabetes ) , clinical indication ( e.g. , valvuloplasty ) and CYP2C9 genotype ] . MEASUREMENTS Primary outcome measurements were patient willingness to participate , physician willingness to refer , sample processing time , ability to administer calculated dosage and adequacy of follow-up . LIMITATIONS This pilot trial was design ed to assess the feasibility of model-based warfarin dosing . Power was insufficient for statistical comparison of adverse event rates . RESULTS Forty-three of 117 patients had no prior warfarin treatment and were eligible . Five declined to participate . Twenty patients were r and omized to a st and ard initiation dose of 5 mg daily . Eighteen patients were r and omized to model-based dosing . All but one participant received the assigned initiation dose . Blood draw to dosage calculation time ( including genotyping ) required approximately 4 hours . Six adverse events occurred within the st and ard dosing group , and two adverse events occurred within the model-based dosing group . CONCLUSIONS Prospect i ve application of a multivariate CYP2C9 gene-based warfarin dosing model is feasible BACKGROUND The efficacy and safety of enoxaparin in outpatient treatment of deep vein thrombosis have been well studied . The present study aim ed to compare the efficacy of a 10-mg loading dose of warfarin with 5 mg of the drug and enoxaparin in achieving the international normalized ratio ( INR ) range . METHODS This r and omized clinical trial was performed in the emergency department ( ED ) of our study . International normalized ratio was checked daily for 7 days and on the 14th day . Based on the patient 's INR on the third day , the doses were adjusted . Patients received enoxaparin ( 1.5 mg/kg per day ) simultaneously until the therapeutic range of INR was achieved for 2 consecutive days . RESULT The side effects were compatible in both groups . There was a significant difference in the INR rates of the 2 groups recorded on the third , fourth , and seventh days . CONCLUSION The 10-mg loading dose of warfarin induces the therapeutic range of INR earlier than the 5-mg dose without causing any significant difference in the side effects . More cases in the 10-mg group had INR levels higher than 3 ; the very dose , therefore , is recommended as the loading dose in cases of out patients with deep vein thrombosis referring to the ED . Tight control of INR , after the third day of treatment , is also recommended in these cases There remains considerable controversy regarding optimal initial warfarin dosing in patients with acute venous thromboembolism . Therefore , an open-label , r and omized trial comparing 2 warfarin initiation nomograms ( 5 vs 10 mg ) was conducted in patients with acute venous thromboembolism . All participants received fondaparinux for > or = 5 days as a " bridge " to warfarin . The primary end point was defined as the number of days necessary to achieve 2 consecutive international normalized ratio laboratory test values > 1.9 . A total of 50 patients were enrolled and r and omly assigned to each of the treatment arms . The median time to 2 consecutive international normalized ratios was 5 days in the 2 groups . There was no statistical difference in achieving the primary end point using either the 5- or the 10-mg nomogram ( p = 0.69 ) . These results should provide clinicians with increased warfarin dosing options in patients presenting with acute venous thromboembolism Venous thromboembolic disease causes significant morbidity and mortality in both hospitalized and nonhospitalized patients . The mean annual incidence in the United States is 48 per 100 000 for deep venous thrombosis and 23 per 100 000 for pulmonary embolism , according to an epidemiologic study conducted in Massachusetts ( 1 ) . A similar study in Sweden showed an annual incidence of 160 new cases of deep venous thrombosis per 100 000 inhabitants ( 2 ) . Five to 10 days of unfractionated heparin is a common recommended initial treatment for deep venous thrombosis . This treatment maintains the activated partial thromboplastin time above 1.5 times its control value ( 3 , 4 ) , as calibrated by protamine titration or an antifactor Xa assay . Another recommended initial treatment is 5 to 10 days of weight-adjusted low-molecular-weight heparin followed by at least 3 months of oral anticoagulant therapy ( 3 - 7 ) . Low-molecular-weight heparins are now frequently being used in place of unfractionated heparin for both prevention and treatment of venous thromboembolism ( 3 , 8) . R and omized trials and meta-analyses have shown subcutaneously administered low-molecular-weight heparins to have antithrombotic efficacy equal to ( 9 - 12 ) or greater than ( 13 - 16 ) that of continuously infused unfractionated heparin in the initial treatment of deep venous thrombosis and equal to that of unfractionated heparin in the treatment of pulmonary embolism ( 17 , 18 ) . However , many of these studies enrolled small numbers of patients ( 9 - 13 , 15 , 16 ) , used primarily venographic plethysmographic or scintigraphic end points ( 9 - 11 , 13 , 16 ) , and sometimes excluded patients with pulmonary embolism ( 11 , 15 ) . Most trials of twice-daily low-molecular-weight heparin adjusted treatment regimens according to patient weight without laboratory monitoring . However , several studies suggest that once-daily weight-adjusted dosage of a low-molecular-weight heparin is as effective in the treatment of proximal deep venous thrombosis as adjusted dosages of intravenous unfractionated heparin ( 14 , 19 ) or twice-daily low-molecular-weight heparin ( 20 ) . Since low-molecular-weight heparins differ in their physicochemical and pharmacologic characteristics , study results that apply to one can not be extended to another ( 21 , 22 ) . We conducted the present study to determine whether enoxaparin administered subcutaneously once or twice per day is as effective as continuously infused unfractionated heparin in the treatment of patients with acute , symptomatic venous thromboembolic disease . Methods Study Description This parallel-group , r and omized , partially blinded , international , multicenter clinical trial compared continuously infused unfractionated heparin ( adjusted to maintain activated partial thromboplastin time within a defined range ) with two weight-adjusted dosages of enoxaparin administered subcutaneously once or twice daily . The study was conducted in 74 hospitals in 16 countries , including the United States , several European countries , Australia , and Israel , and was approved by the institutional review board or ethics committees at each location . Written informed consent was obtained from each patient . Four committees participated in this study : an Advisory Committee ; an Outcome Adjudication Committee , which provided blinded outcome assignments for incidence of recurrent venous thromboembolic disease , major or minor hemorrhage , immune thrombocytopenia , and cause of death ; an independent Safety Committee ; and a Vascular Imaging Committee , which review ed all baseline venograms and all vascular imaging studies in a blinded manner to determine whether deep venous thrombosis was present at baseline and whether objective evidence of recurrence existed . Patient Characteristics Patients were required to be at least 18 years of age and willing to remain hospitalized during r and omized therapy . The primary inclusion criteria were symptomatic lower-extremity deep venous thrombosis confirmed by venography or ultrasonography ( if venography was inconclusive ) , symptomatic pulmonary embolism confirmed by high-probability ventilationperfusion scanning , or positive pulmonary angiography with confirmation of lower-extremity deep venous thrombosis . All eligible patients underwent baseline lung scanning or angiography . Exclusion criteria were more than 24 hours of previous treatment with heparin or warfarin ; need for thrombolytic therapy ; known hemorrhagic risk , including active hemorrhage , active intestinal ulcerative disease , known angiodysplasia , or eye , spinal , or central nervous system surgery within the previous month ; renal insufficiency ( serum creatinine concentration>180 mol/L [ 2.03 mg/dL ] ) ; severe hepatic insufficiency ; allergy to heparin , protamine , porcine products ( both heparin and enoxaparin are derived from pork intestinal mucosa ) , iodine , or contrast media ; history of heparin-associated thrombocytopenia or heparin- or warfarin-associated skin necrosis ; treatment with other investigational therapeutic agents within the previous 4 weeks ; inferior vena cava interruption ; or known pregnancy or lactation . Treatments Within each center , consecutive eligible patients were r and omly assigned sequentially to one of three treatment groups . R and omization was done without stratification in blocks of six , according to ascending r and omization number . The numbers were affixed to sealed treatment kits that contained study medication and were provided by the study sponsor . Patients assigned to enoxaparin received a weight-adjusted subcutaneous dose . Two blinded regimens were tested : 1.0 mg/kg of body weight twice daily or 1.5 mg/kg once daily . Several clinical trials have shown the twice-daily regimen to be effective and safe ( 16 , 23 , 24 ) . The once-daily dosage was chosen on the basis of results of pharmacokinetic studies that showed it to have a suitable pharmacokinetic profile in healthy volunteers and to be well tolerated in the treatment of patients with venous thromboembolism ( 25 , 26 ) . In these previous studies , therapeutic antifactor Xa levels were present for up to 18 hours in both volunteers and patients , and measurable levels were present for up to 24 hours . A total of three injections , study drug and placebo , were given each day to maintain blinding for volume of solutions and frequency of administration . Patients assigned to the nonblinded unfractionated heparin group received an intravenous bolus dose and infusion on the basis of an approved institution-specific nomogram . In most cases , administration was as follows : Six hours after the initial bolus , the activated partial thromboplastin time was measured and the dose was adjusted to maintain the specified value , which was between 55 and 80 seconds in most centers ( 4 - 7 ) . Activated partial thromboplastin time was measured at least daily during unfractionated heparin treatment . Enoxaparin and heparin treatments were continued for at least 5 days , and warfarin was started within 72 hours of initial study drug administration . Forty-three patients received phenprocoumon in place of warfarin sodium . Prothrombin time was measured daily , and patients could be discharged from the hospital after the international normalized ratio was found to be between 2.0 and 3.0 on 2 consecutive days . Oral anticoagulation was continued for at least 3 months . Study Assessment s Observers who were aware of treatment assignment assessed patients daily and monthly during the 3-month follow-up for worsening or recurrence of deep venous thrombosis or pulmonary embolism , hemorrhage , adverse events , changes in concomitant medications and adequacy of warfarin use , and warfarin adherence . For patients receiving unfractionated heparin , adherence was defined as an activated partial thromboplastin time within or above the therapeutic range on the second day of treatment . For patients receiving enoxaparin , adherence was defined as at least 10 doses of study medication given with no dosing errors . Adherence to warfarin therapy was defined as having at least one international normalized ratio value greater than or equal to 2.0 between day 4 and the last dose of study treatment during the initial treatment period . These definitions of treatment adherence were established before the analysis of the study outcomes . Efficacy Analysis The efficacy analysis was performed on two study sample s : all treated patients , who received at least one dose of study medication , and evaluable patients , which excluded all patients who met at least one of the criteria for nonevaluability . These criteria were no confirmed deep venous thrombosis at baseline , insufficient study therapy , placement of an inferior vena cava filter , two r and om assignments , and no 3-month follow-up . Insufficient study therapy was defined as one or more missed enoxaparin doses among at least eight consecutive enoxaparin doses or less than 4 consecutive days of heparin infusion . The definition of insufficient study therapy was established before analysis of study outcomes . These two study sample s were analyzed to strengthen the conclusion of equivalence among the treatment groups . The homogeneity of the results of the two analyses is considered to be more supportive of the conclusion of equivalence than the results of either analysis alone . Primary clinical end points were recurrent deep venous thrombosis or pulmonary embolism within 3 months of r and omization . Patients with symptoms of recurrent thrombosis underwent confirmatory testing with venography , ultrasonography , or both . Patients presenting with signs or symptoms of pulmonary embolism underwent lung perfusion scanning , pulmonary angiography , or both . Clinical symptoms and supportive findings on objective tests ; extension of existing thrombi or new thrombi for venography , angiography , or ultrasonography ; or high-probability defect patterns on perfusion scans were required to confirm recurrent thrombosis . Prespecified subgroup analyses were performed on the basis of patient AIM A warfarin loading protocol adjusting doses for age was compared to both Fennerty 's protocol ( Fenn ) and empirical dosing ( Emp ) . METHODS Patients beginning warfarin were r and omised to receive doses according to either the age adjusted ( Age ) protocol or Fenn . Data were retrospectively collected for patients who had begun warfarin in the previous six months to represent empirical dosing . The study was performed on in patients being commenced on warfarin for the first time at two teaching hospitals . MAIN OUTCOME MEASURES Endpoints were time to reach a stable , therapeutic International Normalised Ratio ( INR ) between 2 - 3 , the number of patients experiencing an INR > or = 4 in the first week and the number of patients who had a dose held in the first week . RESULTS Thirty-five patients were assessed in the Age group , 28 in the Fenn group , and 123 patients for the Emp group . Patients using the Age protocol achieved a stable , therapeutic INR more rapidly than either the Fenn ( p=0.003 , log rank test ) or Emp ( p<0.001 ) group . The Age group had a lower proportion of patients experiencing an INR > or = 4 in the first week ( p<0.05 ) as well as a lower proportion having doses held in the first week ( p<0.01 ) . There were no differences between Emp and Fenn for any of the endpoints . CONCLUSION Adjustment of warfarin loading doses for age exhibits clear superiority over the use of Fenn or Emp . This becomes increasingly important as the average age of patients being warfarinised increases , with the recognition that atrial fibrillation requires anticoagulation . Fenn consistently overdosed elderly patients , especially those aged 80 years and older BACKGROUND Low-molecular-weight heparin is known to be safe and effective for the initial treatment of patients with proximal deep-vein thrombosis . However , its application to pulmonary embolism or previous episodes of thromboembolism has not been studied . METHODS We r and omly assigned 1021 patients with symptomatic venous thromboembolism to fixed-dose , subcutaneous low-molecular-weight heparin ( reviparin sodium ) or adjusted-dose , intravenous unfractionated heparin . Oral anticoagulant therapy with a coumarin derivative was started concomitantly and continued for 12 weeks . Approximately one third of the patients had associated pulmonary embolism . The outcome events studied over the 12 weeks were symptomatic recurrent venous thromboembolism , major bleeding , and death . We sought to determine whether low-molecular-weight heparin is at least equivalent to unfractionated heparin in patients with venous thromboembolism . RESULTS Twenty-seven of the 510 patients assigned to low-molecular-weight heparin ( 5.3 percent ) had recurrent thromboembolic events , as compared with 25 of the 511 patients assigned to unfractionated heparin ( 4.9 percent ) . The difference of 0.4 percentage point indicates that the two therapies have equivalent value according to our predetermined definition of equivalence . Sixteen patients assigned to low-molecular-weight heparin ( 3.1 percent ) and 12 patients assigned to unfractionated heparin ( 2.3 percent ) had episodes of major bleeding ( P= 0.63 ) , and the mortality rates in the two groups were 7.1 percent and 7.6 percent , respectively ( P=0.89 ) . CONCLUSIONS Fixed-dose , subcutaneous low-molecular-weight heparin is as effective and safe as adjusted-dose , intravenous unfractionated heparin for the initial management of venous thromboembolism , regardless of whether the patient has pulmonary embolism or a history of venous thromboembolism |
12,739 | 30,066,049 | Conclusions Comprehensive chromosome screening-based PGD/S can improve clinical pregnancy and live birth rates without adversely affecting functioning in childhood at least up to age 9 . | Background In in vitro fertilization ( IVF ) treatment , preimplantation genetic diagnosis/screening ( PGD/S ) attempts to detect chromosomal abnormalities in embryos before implantation .
Using the meta-analytic and qualitative review approaches , this study aims to evaluate the effect of PGD/S on clinical pregnancy , live births , and childhood outcomes . | OBJECTIVE To assess the potential benefit of preimplantation aneuploidy testing on the outcome of in vitro fertilization ( IVF ) for women of advanced maternal age ( AMA ) . DESIGN Prospect i ve r and omized clinical trial . SETTING Private IVF clinic . PATIENT(S ) Sixty-two infertile AMA couples undergoing fertility treatment . INTERVENTION(S ) Fluorescent in situ hybridization ( FISH ) for chromosomes X , Y , 13 , 15 , 16 , 17 , 18 , 21 , and 22 . MAIN OUTCOME MEASURE(S ) Preimplantation aneuploidy testing of biopsied blastomeres on day 3 of development . RESULT ( S ) Fertilization and blastocyst developmental rates were similar for the test and control groups : 80 % versus 77.4 % and 49 % versus 48.2 % , respectively . The average number of embryos transferred was comparable at 2.2 for the test group and 2.7 for the control group . Implantation rates were also equivalent across the two groups : 37.3 % in the control group versus 36.5 % in the test group . Nevertheless , the spontaneous abortion rate was observed to be lower for the test group : 25.9 % versus 32.26 % in the control group . This result ed in an observed increase in delivery rates for the test group : 78 % versus 67.74 % in the control group . CONCLUSION ( S ) Preimplantation aneuploidy testing does not appear to statistically significantly improve outcome parameters in infertile AMA patients ; however , a trend toward a decrease in the spontaneous abortion rate with a subsequent higher delivery rate was observed BACKGROUND Single-embryo transfer is a well-accepted strategy to avoid multiple pregnancies in an assisted reproductive technology ( ART ) programme . Besides the morphological quality and embryo kinetics up to the blastocyst stage , preimplantation genetic screening ( PGS ) of aneuploidy has been advocated as an adjuvant approach to select the embryo . METHODS Couples with a female partner younger than 36 were r and omly assigned to undergo transfer of a single blastocyst in a cycle with or without PGS using FISH for the chromosomes X , Y , 13 , 16 , 18 , 21 , 22 . RESULTS After the enrolment of 120 of the projected 447 patients in each group , study recruitment was terminated prematurely on the basis of futility . The observed live birth delivery rates after ART were 30.8 versus 30.8 % per r and omized patient , 34.6 versus 34.6 % per cycle initiated , 37.8 versus 37.0 % per aspirated cycle and 41.6 versus 43.5 % per embryo transfer for the control versus the PGS group , respectively , with absolute between-group differences ( 95 % CI ; P value ) of 0 % ( -11.7 to 11.7 ; P = 1.00 ) , 0 % ( -12.7 to 12.7 ; P = 1.00 ) , -0.8 % ( -14.2 to 12.7 ; P = 0.91 ) and 2.1 % ( -12.7 to 16.7 ; P = 0.79 ) , respectively . Even in this younger age group , only 61 % of the embryos had a normal diploid status . CONCLUSIONS The absence of a beneficial treatment effect in this r and omized clinical trial provides no arguments in favour of PGS to improve live birth delivery rate following single-embryo transfer in women under the age 36 . Clinical Trials.gov : NCT00670059 Meiotic errors during oocyte maturation are considered the major contributors to embryonic aneuploidy and failures in human IVF treatment . Various technologies have been developed to screen polar bodies , blastomeres and trophectoderm cells for chromosomal aberrations . Array-CGH analysis using bacterial artificial chromosome ( BAC ) arrays is widely applied for preimplantation genetic diagnosis ( PGD ) using single cells . Recently , an increase in the pregnancy rate has been demonstrated using array-CGH to evaluate trophectoderm cells . However , in some countries , the analysis of embryonic cells is restricted by law . Therefore , we used BAC array-CGH to assess the impact of polar body analysis on the live birth rate . A disadvantage of polar body aneuploidy screening is the necessity of the analysis of both the first and second polar bodies , result ing in increases in costs for the patient and complex data interpretation . Aneuploidy screening results may sometimes be ambiguous if the first and second polar bodies show reciprocal chromosomal aberrations . To overcome this disadvantage , we tested a strategy involving the pooling of DNA from both polar bodies before DNA amplification . We retrospectively studied 351 patients , of whom 111 underwent polar body array-CGH before embryo transfer . In the group receiving pooled polar body array-CGH ( aCGH ) analysis , 110 embryos were transferred , and 29 babies were born , corresponding to live birth rates of 26.4 % per embryo and 35.7 % per patient . In contrast , in the control group , the IVF treatment was performed without preimplantation genetic screening ( PGS ) . For this group , 403 embryos were transferred , and 60 babies were born , result ing in live birth rates of 14.9 % per embryo and 22.7 % per patient . In conclusion , our data show that in the aCGH group , the use of aneuploidy screening result ed in a significantly higher live birth rate compared with the control group , supporting the benefit of PGS for IVF couples in addition to the suitability and effectiveness of our polar body pooling strategy BACKGROUND It is generally accepted that the age-related increased aneuploidy rate is correlated with reduced implantation and a higher abortion rate . Therefore , advanced maternal age ( AMA ) couples are a good target group to assess the possible benefit of preimplantation genetic diagnosis for aneuploidy screening ( PGD-AS ) on the outcome after assisted reproductive technology ( ART ) . METHODS A prospect i ve r and omized controlled clinical trial ( RCT ) was carried out comparing the outcome after blastocyst transfer combined with PGD-AS using fluorescence in situ hybridization ( FISH ) for the chromosomes X , Y , 13 , 16 , 18 , 21 and 22 in AMA couples ( aged > or = 37 years ) with a control group without PGD-AS . From the 400 ( 200 for PGD-AS and 200 controls ) couples that were allocated to the trial , an oocyte pick-up was performed effectively in 289 cycles ( 148 PGD-AS cycles and 141 control cycles ) . RESULTS Positive serum HCG rates per transfer and per cycle were the same for PGD-AS and controls : 35.8 % ( 19.6 % ) [ % /per embryo transfer ( per cycle ) ] and 32.2 % ( 27.7 % ) , respectively ( NS ) . Significantly fewer embryos were transferred in the PGD-AS group than in the control group ( P<0.001 ) . The implantation rate ( with fetal heart beat ) was 17.1 % in the PGD-AS group versus 11.5 % in the control group ( not significant ; P=0.09 ) . We observed a normal diploid status in 36.8 % of the embryos . CONCLUSIONS This RCT provides no arguments in favour of PGD-AS for improving clinical outcome per initiated cycle in patients with AMA when there are no restrictions in the number of embryos to be transferred STUDY QUESTION Do preimplantation genetic diagnosis ( PGD ) couples experience higher levels of stress during pregnancy and the perinatal period compared with couples who conceive spontaneously ( SC ) or with ICSI ? SUMMARY ANSWER PGD couples did not experience more psychological stress during pregnancy and beyond than ICSI or SC couples . WHAT IS ALREADY KNOWN Previous studies have shown that assisted reproduction technology ( ART ) couples are more prone to pregnancy-related anxieties than SC couples , but display depressed feelings to an equal or lesser extent . However , only one study has focused on a female PGD sample , which may be a more vulnerable group than other ART groups , due to the potentially complex hereditary background , adverse childhood experiences and losses . In that study , PGD women experienced a reduction in state anxiety , and maternal-antenatal attachment did not differ from normative data . Unfortunately , no data exist on pregnancy-related anxiety , depression and parental-antenatal attachment . Valuable information from both parents ( e.g. : couples ) is also lacking . STUDY DESIGN , SIZE , DURATION For this longitudinal prospect i ve study question naire , data from 185 women and 157 men ( 157 couples ) were collected between February 2012 until April 2014 . Data were analysed using multilevel analysis . The couples conceiving after PGD , ICSI or SC were followed from the first trimester of the pregnancy until the third month post-partum . PARTICIPANTS / MATERIAL S , SETTING , METHODS A total of 60 PGD , 58 ICSI and 69 SC couples were initially recruited by various departments of Universitair Ziekenhuis Brussel ( UZ Brussel ) . At each trimester ( T1 : 12 - 14 weeks , T2 : 20 - 22 weeks , T3 : 30 - 32 weeks ) of pregnancy , depression ( EPDS ) , pregnancy-related anxieties ( PRAQ ) and parental-antenatal attachment ( M/PAAS ) were recorded . At T4 ( 3 months post-partum ) , depression ( EPDS ) was assessed again . In the first trimester ( T1 ) broad socio-demographic data and at T4 perinatal health data of both mother and child were recorded . Differences between conception groups over time were analysed using multilevel analyses , taking into account covariation between measurements and within couples . Several perinatal covariates as well as social desirability , coping and adult attachment style were controlled for . MAIN RESULTS AND THE ROLE OF CHANCE All three conception groups had similar scores for depression during pregnancy and beyond . Also , pregnancy-related anxiety scales did not differ among the three groups . All groups also followed a similar trajectory in time regarding their scores for anxiety , depression and parental-antenatal attachment . ART groups did not give more socially desirable answers than SC controls . The subsequent moderators : coping and adult attachment style did not add any relevant information . No interaction effects occurred between gender and conception groups . LIMITATIONS , REASONS FOR CAUTION The participants were Caucasian , Dutch-speaking couples , with medium to high socio-economic status , from a single centre . Our data should be replicated by multicultural and multicentre studies . Furthermore , the inclusion of an additional control group of couples who did not opt for PGD but for prenatal diagnosis may point to the most beneficial strategy for the couple . WIDER IMPLICATION S OF THE FINDINGS PGD parents invest a similar amount of time and emotion in their future children compared with controls . This implies that successful PGD treatment makes an important psychological contribution towards the well-being of couples given their complex hereditary and family background s. STUDY FUNDING /COMPETING INTERESTS This research project was funded by grants from the internal research council of the Vrije Universiteit Brussel ( OZR ) , the Flemish Fonds Wetenschappelijk Onderzoek ( FWO ) and the Wetenschappelijk Fonds Willy Gepts ( WGFG ) . UZ Brussel and the Centre for Medical Genetics have received several educational grants for organizing the data collection , from IBSA , Ferring , Organon , Shering-Plough , Merck and Merck Belgium . M.B. has received consultancy and speaker 's fees from Organon , Serono Symposia and Merck STUDY QUESTION Does embryo biopsy inherent to preimplantation genetic screening ( PGS ) affect neurological , cognitive and behavioural development of 4-year-old children ? SUMMARY ANSWER PGS does not seem to affect neurological , cognitive and behavioural development of 4-year-old singletons ; however , our data suggest that it may be associated with altered neurodevelopment in twins . WHAT IS KNOWN ALREADY Evidence concerning the safety of PGS on neurodevelopmental outcome in offspring is scarce . The present study provides information on neurodevelopmental , cognitive and behavioural outcome of 4-year-old PGS offspring . STUDY DESIGN , SIZE , DURATION A prospect i ve , assessor-blinded follow-up study of children born to women who participated in a multi-centre RCT on the effect of IVF with or without PGS . PARTICIPANTS / MATERIAL S , SETTING , METHODS At 4 years , 49 children ( 31 singletons , 9 sets of twins ) born following IVF with PGS and 64 children ( 42 singletons , 11 sets of twins ) born following IVF without PGS ( controls ) were assessed ( post-natal attrition 18 % ) . Neurological development was evaluated with the st and ardized , age-specific and sensitive neurological examination according to Hempel , result ing in a neurological optimality score ( NOS ) , a fluency score and the rate of adverse neurological outcome . Primary outcome was the fluency score , as fluency of movements is easily reduced by subtle dysfunction of the brain . Cognitive development was evaluated with the Kaufman Assessment Battery for Children ; behavioural development was evaluated with the Child Behavior Checklist . The effect of PGS was analysed with a mixed effects model . MAIN RESULTS AND THE ROLE OF CHANCE Based on the intention to treat analysis , neurodevelopmental outcome of PGS children was similar to that of controls . However , additional analyses indicated that PGS affected neurodevelopmental outcome of twins in a different way than that of singletons . The fluency score of singletons born following PGS was similar to that of control singletons [ mean values , 95 % confidence intervals ( CIs ) : 12.2 ( 11.5;12.8 ) and 12.2 ( 11.6;12.8 ) ] , respectively , P = 0.977 ) that was also true for the other neurodevelopmental parameters . The fluency score of PGS twins was significantly lower than that of control twins [ mean values , 95 % CIs : 10.6 ( 9.8;11.3 ) and 12.3 ( 11.5;13.1 ) ] , respectively , P = 0.001 ) ; the same was true for the NOS . In addition , PGS in twins was associated with a higher sequential intelligence quotient score . On the other h and , other neurodevelopmental parameters were similar for PGS twins and control twins . Post hoc sample size calculation for the primary outcome parameter , the fluency score , indicated that the study groups , including the subgroups of singletons and twins , were adequately powered . LIMITATIONS , REASONS FOR CAUTION We assessed singletons and twins who contributed to the generalizability of the study . A limitation of our study is the relative small size of our study groups and the selective dropout in both groups ( dropouts PGS group : higher gestational age ; control group : less well-educated parents ) . These preclude the conclusion that PGS per se is not associated with neurodevelopmental , cognitive and behavioural problems in singletons and the conclusion that PGS is associated with altered neurodevelopmental outcome in twins . WIDER IMPLICATION S OF THE FINDINGS The need for careful long-term monitoring of children born following embryo biopsy remains , as it is still applied in the form of PGD and it is still unknown whether embryo biopsy affects long-term neurodevelopmental outcome Blastocysts more commonly have a normal karyotype than cleavage-stage embryos do . Moreover , blastocysts have also made a metabolic transition from catabolism and recycling of the oocyte 's reserves and re sources , processes that fuel the first 3 days of cleavage . Although not all blastocysts are karyotypically equal , it is still to be determined to what extent a mosaic karyotype might be a normal feature among embryos , both at the cleavage stage and the blastocyst stage-- and when looking for karyotypic abnormalities by embryo biopsy might help the chance of implantation rather than harm it . It is also still impractical to look at all the chromosomes that can , through their aneuploidy , st and in the way of successful embryonic and fetal development . We report a r and omized clinical trial of blastocyst biopsy followed by preimplantation genetic screening ( PGS ) for aneuploidy using 5-colour FISH . The trial was suspended and then terminated early when we were unable to show an advantage for PGS . If we are correct in assuming that mitotic non-disjunction is common by the stage of the blastocyst ( and that it is much less ominous than meiotic non-disjunction ) , then further studies of effective PGS of blastocysts for aneuploidy require methods of analysis that cover all the chromosomes and can differentiate the triallelic and monoallelic states of meiotically derived aneuploidies from the biallelic state of mitotic aneuploidies OBJECTIVE To verify whether advantages can derive from the implementation of preimplantation genetic diagnosis for aneuploidy in patients with a poor prognosis of full-term pregnancy , compared with conventional treatment procedures . DESIGN A r and omized , controlled study . SETTING Reproductive Medicine Unit of the Società Italiana Studi Medicina della Riproduzione , Bologna , Italy . PATIENT(S ) In a total of 262 stimulated cycles , women presented with the following poor-prognosis indications : maternal age of > or = 36 years ( n = 157 ) , > or =3 previous IVF failures ( n = 54 ) , and an altered karyotype ( n = 51 ) . After giving consent , 127 patients underwent preimplantation genetic diagnosis for aneuploidy , whereas 135 controls underwent assisted zona hatching . INTERVENTION(S ) Analysis of chromosomes XY , 13 , 14 , 15 , 16 , 18 , 21 , and 22 was carried out with the fluorescence in situ hybridization technique in a blastomere biopsied from day 3 embryos . Assisted zona hatching was performed on day 3 embryos from the control group . MAIN OUTCOME MEASURE(S ) Embryo morphology and chromosomal status , number of transferred embryos , clinical pregnancies , implantation rates , and abortions . RESULT ( S ) In the study group , 717 embryos were analyzed by fluorescence in situ hybridization , and 60 % were chromosomally abnormal . A mean of 2.3+/-0.9 euploid embryos were transferred in 99 cycles , result ing in 37 clinical pregnancies ( 37 % ) and a 22.5 % ongoing implantation rate . In the control group , 126 cycles were performed with 3.2+/-1.3 embryos transferred , yielding 34 clinical pregnancies ( 27 % ) and a 10.2 % ongoing implantation rate . CONCLUSION ( S ) The advantage of selecting embryos with a normal chromosome complement has an immediate impact on the ongoing implantation rate , especially in patients aged > or = 38 years and carriers of an altered karyotype OBJECTIVE To determine the usefulness of semiconductor-based next-generation sequencing ( NGS ) for cleavage-stage preimplantation genetic diagnosis ( PGD ) of aneuploidy . DESIGN Prospect i ve case-control study . SETTING A private center for reproductive medicine . PATIENT(S ) A total of 45 patients underwent day-3 embryo biopsy with PGD and fresh cycle transfer . Additionally , 53 patients , matched according to age , anti-Müllerian hormone levels , antral follicles count , and infertility duration were selected as controls . INTERVENTION(S ) Choice of embryos for transfer was based on the PGD NGS results . MAIN OUTCOME MEASURE(S ) Clinical pregnancy rate ( PR ) per embryo transfer ( ET ) was the primary outcome . Secondary outcomes were implantation and miscarriage rates . RESULT ( S ) The PR per transfer was higher in the NGS group ( 84.4 % vs. 41.5 % ) . The implantation rate ( 61.5 % vs. 34.8 % ) was higher in the NGS group . The miscarriage rate was similar in the 2 groups ( 2.8 % vs. 4.6 % ) . CONCLUSION ( S ) We demonstrate the technical feasibility of NGS-based PGD involving cleavage-stage biopsy and fresh ETs . Encouraging data were obtained from a prospect i ve trial using this approach , arguing that cleavage-stage NGS may represent a valuable addition to current aneuploidy screening methods . These findings require further validation in a well- design ed r and omized controlled trial . CLINICAL TRIAL REGISTRATION NUMBER ACTRN12614001035617 OBJECTIVE To evaluate the usefulness of preimplantation genetic screening ( PGS ) using fluorescence in situ hybridization ( FISH ) for two different indications : repetitive implantation failure ( RIF ) and advanced maternal age ( AMA ) . DESIGN Two prospect i ve , r and omized controlled trials with patients allocated in two arms : blastocyst transfer on day 5 ( group A ) or PGS with transfer on day 5 ( group B ) . SETTING University-affiliated private clinics . PATIENT(S ) The RIF study included women < 40 years with three or more failed IVF cycles without other known causal factors ( 91 patients ) . The AMA study included intracytoplasmic sperm injection patients aged between 41 and 44 ( 183 patients ) . INTERVENTION(S ) In the PGS group , single-cell day 3 biopsy was performed with aneuploidy screening for chromosomes 13 , 15 , 16 , 17 , 18 , 21 , 22 , X , and Y. In both the blastocyst transfer group and the PGS group , ET was performed on day 5 . MAIN OUTCOME MEASURE(S ) Live-birth rate per patient and per started cycle . RESULT ( S ) A significant increase in live-birth rates per patient was found in the PGS group compared with the blastocyst group for the AMA study ( 30/93 patients [ 32.3 % ] vs. 14/90 patients [ 15.5 % ] ; odds ratio , 2.585 ; confidence interval , [ 1.262 - 5.295 ] ) . In the RIF study no significant differences were observed ( 23/48 patients [ 47.9 % ] vs. 12/43 patients [ 27.9 % ] ) . CONCLUSION ( S ) PGS with FISH was shown to be beneficial for the AMA group OBJECTIVE To determine whether the routine use of preimplantation genetic screening ( PGS ) in " good prognosis " women improves in vitro fertilization ( IVF ) cycle outcome . DESIGN R and omized , controlled , prospect i ve clinical study . SETTING Private infertility clinic . PATIENT(S ) Infertile women predicted to have a good prognosis as defined by : age < 39 years , normal ovarian reserve , body mass index < 30 kg/m(2 ) , presence of ejaculated sperm , normal uterus , < or=2 previous failed IVF cycles . INTERVENTION(S ) Patients were r and omized to the PGS group or the control group on day 3 after oocyte retrieval ; 23 women underwent blastomere biopsy on day 3 after fertilization ( PGS group ) , and 24 women underwent routine IVF ( control group ) . All embryos were transferred on day 5 or 6 after fertilization . MAIN OUTCOME MEASURE(S ) Pregnancy , implantation , multiple gestation , and live birth rates . RESULT ( S ) No statistically significant differences were found between the PGS and control groups with respect to clinical pregnancy rate ( 52.4 % versus 72.7 % ) . However , the embryo implantation rate was statistically significantly lower for the PGS group ( 31.7 % versus 62.3 % ) as were the live birth rate ( 28.6 % versus 68.2 % ) and the multiple birth rate ( 9.1 % versus 46.7 % ) . CONCLUSION ( S ) In a " good prognosis " population of women , PGS does not appear to improve pregnancy , implantation , or live birth rates Background : Recent studies suggest that in vitro fertilization ( IVF ) and intracytoplasmic sperm injection ( ICSI ) are associated with suboptimal cardiometabolic outcome in offspring . It is unknown whether preimplantation genetic screening ( PGS ) , which involves embryo biopsy , affects blood pressure ( BP ) , anthropometrics , and the frequency of received medical care . Methods : In this prospect i ve multicenter follow-up study , we assessed BP , anthropometrics , and received medical care of 4-y-old children born to women who were r and omly assigned to IVF/ICSI with PGS ( n = 49 ) or without PGS ( controls ; n = 64 ) . We applied linear and generalized linear mixed-effects models to investigate possible effects of PGS . Results : BP in the PGS and control groups was similar : 102/64 and 100/64 mm Hg , respectively . Main anthropometric outcomes in the PGS vs. control group were : BMI : 16.1 vs. 15.8 ; triceps skinfold : 108 vs. 98 mm ; and subscapular skinfold : 54 vs. 53 mm ( all P values > 0.05 ) . More PGS children than controls had received paramedical care ( speech , physical , or occupational therapy : 14 ( 29 % ) vs. 9 ( 14 % ) ; P = 0.03 in multivariable analysis ) . The frequency of medicial treatment was comparable . Conclusion : PGS does not seem to affect BP or anthropometrics in 4-y-old children . The higher frequency of received paramedical care after PGS may suggest an effect of PGS on subtle developmental parameters BACKGROUND Single embryo transfer ( SET ) provides the most certain means to reduce the risk of multiple gestation . Regrettably , prospect i ve trials of SET have demonstrated reductions in per-cycle delivery rates . A vali date d method of comprehensive chromosome screening ( CCS ) has the potential to optimize SET by transferring only euploid embryos . This retrospective study evaluates the efficacy of SET with CCS in an infertile population . METHODS Overall and age-controlled ongoing pregnancy rates ( OPR ) were compared between women undergoing SET following CCS ( CCS-SET , n= 140 ) and those undergoing SET without aneuploidy screening ( control SET , n= 182 ) . All transfers were at the blastocyst stage , with CCS performed after trophectoderm biopsy of exp and ed blastocysts and analysis with rapid PCR allowing for fresh transfer . RESULTS In the CCS-SET and control SET groups , an OPR of 55.0 and 41.8 % , respectively , was obtained . The OPR was lower for the control group ( P < 0.01 ) despite a younger age than the CCS group ( 37.3 ± 3.4 versus 34.2 ± 3.9 years ; P < 0.001 ) . Birthweight and gestational age at delivery were equivalent . The proportion of clinical pregnancies result ing in miscarriage was higher in the control group ( 24.8 versus 10.5 % , P < 0.01 ) , with more patients requiring surgical interventions for aneuploid pregnancies . There was one monozygotic twin delivery in the CCS group and none in the control group . CONCLUSIONS Compared with traditional blastocyst SET , SET after trophectoderm biopsy and rapid PCR-based CCS increases OPR and reduces the miscarriage rate . The enhanced selection empowered by CCS with SET may provide a practical way to eliminate multi-zygotic multiple gestation without compromising clinical outcomes per cycle BACKGROUND Advanced maternal age ( AMA ) is an important parameter that negatively influences the clinical pregnancy rate in IVF , in particular owing to the increased embryo aneuploidy rate . It has thus been suggested that only transferring euploid embryos in this patient group would improve the pregnancy rate . The purpose of this study was to test whether employing preimplantation genetic screening ( PGS ) in AMA patients would increase the clinical pregnancy rate . METHODS We conducted a two-center , r and omized controlled trial ( RCT ) to analyze the outcome of embryo transfers in AMA patients ( > or=38 years of age ) after PGS using FISH analysis for chromosomes X , Y , 13 , 16 , 18 , 21 and 22 . The PGS group was compared with a control group . The primary outcome measure was clinical pregnancy rate after 6 - 7 weeks of gestation per r and omized patient . RESULTS The study was terminated early as an interim analysis showed a very low conditional power of superiority for the primary outcome . Of the 320 patients calculated to be included in the study , 56 and 53 patients were r and omized into the PGS and control groups , respectively . The clinical pregnancy rate in the PGS group was 8.9 % ( 95 % CI , 2.9 - 19.6 % ) compared with 24.5 % ( 95 % CI , 13.8 - 38.3 % ) in the control group , giving a difference of 15.6 % ( 95 % CI , 1.8 - 29.4 % , P = 0.039 ) . CONCLUSIONS Although the study was terminated early , this RCT study provides evidence against the use of PGS for AMA patients when performing IVF . TRIAL REGISTRATION NUMBER IS RCT N38014610 Aim of this study was to evaluate the effect of preimplantation genetic screening ( PGS ) on neurodevelopmental outcome in children . We conducted a prospect i ve follow-up study of children born to women r and omly assigned to in vitro fertilization with or without PGS . Primary outcome was adverse neurologic outcome at 18 mo ; secondary outcomes were types of minor neurologic dysfunction ( MND ) , neurologic outcome before 18 mo , neonatal intensive care admission , and congenital malformations . Twenty women in the PGS group participated with 25 children and 26 women in the control group participated with 31 children . Five PGS pregnancies ( 25 % ) and four control pregnancies ( 15 % ) result ed in birth of at least one child with an adverse neurologic outcome ( adjusted odds ratio : 2.3 [ 0.4–12.0 ] ) . Dysfunction in fine motor abilities and posture and muscle tone dysregulation tended to be present more frequently after PGS . Neurologic outcome before 18 mo , neonatal intensive care admission , and prevalence of congenital malformations were similar in study and control pregnancies . Nevertheless , at child level , rates of adverse outcome were higher after PGS . In conclusion , outcome in pregnancies after in vitro fertilization ( IVF ) with and without PGS was similar . The small sample size precludes the conclusion that PGS is not associated with less favorable neurologic outcome . Safety of new assisted reproductive techniques should be evaluated before large-scale implementation OBJECTIVE To evaluate the effect of preimplantation genetic screening ( PGS ) on neurodevelopmental outcomes in children . DESIGN Prospect i ve , assessor-blinded , follow-up study of children born to women r and omly assigned to in vitro fertilization or intracytoplasmic sperm injection ( IVF/ICSI ) with or without PGS . SETTING University Medical Center , Groningen , and Academic Medical Center , Amsterdam , the Netherl and s. PATIENT(S ) Fifty-four PGS children and 77 controls . INTERVENTION(S ) PGS . MAIN OUTCOME MEASURE(S ) Mental , psychomotor , neurologic , and behavioral outcomes in 2-year-old children as measured with the Bayley Scales of Infant Development , the Hempel neurologic examination , and the Child Behavior Check List . RESULT ( S ) The mental , psychomotor , and behavioral outcomes at 2 years in children born after IVF with and without PGS were similar overall . The PGS children showed lower neurologic optimality scores than the control children . Scores on all tests were within the normal range . CONCLUSION ( S ) Conception with PGS does not seem to be associated with impaired mental , psychomotor , or behavioral outcomes by age 2 . However , the lower neurologic optimality scores found in the PGS children may signal less favorable long-term neurologic outcomes in PGS children . Our findings stress the need for safety evaluations with new assisted reproductive techniques before large-scale implementation OBJECTIVE To examine whether embryo biopsy for preimplantation genetic diagnosis ( PGD ) influences neonatal outcomes . DESIGN Prospect i ve follow-up cohort . SETTING Tertiary university-affiliated medical center . PATIENT(S ) 242 children born after PGD , 242 children born after intracytoplasmic sperm injection ( ICSI ) ( 158 singletons and 42 twins pairs in each group ) , and 733 children born after a spontaneous conception ( SC ) ( 493 singletons , 120 twins pairs ) , matched for maternal age , parity , and body mass index . INTERVENTION(S ) None . MAIN OUTCOME MEASURE(S ) Gestational age , birth weight , prematurity ( < 37 and < 34 weeks ) , low birth weight ( < 2,500 g , very low birth weight , < 1,500 g ) , and intrauterine growth restriction ( < 10th percentile for gestational age ) . RESULT ( S ) For singletons , the mean birth weight was higher after SC compared with ICSI but not compared with PGD . Mean gestational ages were lower after PGD and ICSI compared with SC . The low birth weight and intrauterine growth restriction rates were 4.4 % , 12.0 % , and 5.7 % and 5.1 % , 9.5 % , and 5.5 % for PGD , ICSI , and SC , respectively . Similar results were found when controlled for the number of embryos transferred and cryopreservation . The results for twins exhibited similar but less statistically significant trends . Polar body and blastomere biopsies provided similar outcomes . CONCLUSION ( S ) Embryo biopsy itself did not cause intrauterine growth restriction or low birth weight compared with SC , despite lower gestational ages with PGD . The worsened outcomes in ICSI compared with PGD pregnancies may be due to the infertility itself OBJECTIVE To determine if cleavage- or blastocyst-stage embryo biopsy affects reproductive competence . DESIGN Paired r and omized clinical trial . SETTING Academic-assisted reproduction program . PATIENT(S ) Attempting conception through IVF . INTERVENTION(S ) After selecting two embryos for transfer , one was r and omized to biopsy and the other to control . Both were transferred within shortly thereafter . The biopsy was su bmi tted for microarray analysis and single-nucleotide polymorphism ( SNP ) profiling . Buccal DNA obtained from the neonate after delivery had microarray analysis and SNP profile compared with that of the embryonic DNA . A match confirmed that the biopsied embryo implanted and developed to term , whereas a nonmatch indicated that the control embryo had led to the delivery . MAIN OUTCOME MEASURE(S ) Paired analysis of the delivery rates of the transferred embryos . Either twin delivery or failure to deliver represents equivalent outcomes for the biopsied and control embryos . In contrast , singletons were determined to be from the biopsied or the control embryo . RESULT ( S ) Blastomere biopsy on day 3 of development result ed in a significant reduction in sustained implantation . Only 30 % of biopsied embryos had sustained implantation and ultimately developed into live-born infants versus 50 % of unbiopsied controls , a relative reduction of 39 % . In contrast , sustained implantation rates were equivalent ( 51 % vs. 54 % ) for biopsied and control blastocysts . CONCLUSION ( S ) Cleavage-stage biopsy markedly reduced embryonic reproductive potential . In contrast , trophectoderm biopsy had no measurable impact and may be used safely when embryo biopsy is indicated . CLINICAL TRIAL REGISTRATION NUMBER NCT01219504 BACKGROUND Infertility treatment has an acknowledged psychological impact on women and their partners ; however , information about the development of parental well-being after child birth is inconclusive . Preimplantation genetic screening ( PGS ) has been suggested to increase the efficacy of infertility treatments , but the effect it may have on parental well-being is unknown . AIM To evaluate parental distress and anxiety at one and two years after successful infertility treatment and to explore variables that might affect parental outcome , including PGS and child behaviour . STUDY DESIGN Follow-up of a r and omised controlled trial ( RCT ) on the efficacy of PGS . SUBJECTS Parents ( n=101 ) that successfully underwent IVF/ICSI with or without PGS . OUTCOME MEASURES At one and two years , parental distress and anxiety were assessed with the General Health Question naire 30 and State Trait Anxiety Inventory , respectively . At two years , child development and behaviour were assessed with the Dutch Bayley Scales of Infant Development-II and the Child Behaviour Checklist 1½-5 , respectively . RESULTS PGS had no effect on parental distress or anxiety . Child behaviour problems were associated with parental distress and anxiety . There was a main effect of time on parental distress , with distress levels decreasing over time . CONCLUSIONS We found no objection to PGS related to parental psychological distress and anxiety . When parental psychological problems are present after infertility treatment , the results of this study could be useful to support counselling OBJECTIVE To verify the percentage of chromosomally abnormal preimplantation embryos in patients with a poor prognosis and possibly to increase the chance of implantation by selecting chromosomally normal embryos . DESIGN A prospect i ve , r and omized , controlled study . SETTING In vitro fertilization program at the Reproductive Medicine Unit of the Società Italiana Studi Medicina della Riproduzione , Bologna , Italy . PATIENT(S ) In a total of 28 stimulated cycles , the maternal age was > or = 38 years and /or the patient had > or = 3 previous IVF failures , factors that indicated a poor prognosis . After consent , 11 patients underwent preimplantation genetic diagnosis for aneuploidy , whereas 17 controls underwent assisted zona hatching . INTERVENTION(S ) Simultaneous analysis of chromosomes X , Y , 13 , 18 , and 21 in a blastomere biopsied from day-3 embryos . Chromosomal analysis was performed with fluorescence in situ hybridization . Assisted zona hatching was performed on day-3 embryos from the control-group patients . MAIN OUTCOME MEASURE(S ) Embryo morphology , results of fluorescence in situ hybridization , clinical pregnancies , and implantation . RESULT ( S ) In the study group , a total of 61 embryos were analyzed by fluorescence in situ hybridization , and 55 % were chromosomally abnormal . Embryo transfer with at least one normal embryo was performed in 10 cycles . Four clinical pregnancies result ed , with a 28.0 % implantation rate . In the control group , 41 embryos were transferred in 17 cycles after the assisted zona hatching procedure , yielding four clinical pregnancies and an 11.9 % implantation rate . CONCLUSION ( S ) Infertile patients classified as having a poor prognosis have a high percentage of chromosomally abnormal embryos . The advantage of selecting and transferring embryos with normal fluorescence in situ hybridization results has an immediate impact on implantation This r and omized , controlled trial verifies whether patients with recurrent failed implantation benefit from preimplantation genetic diagnosis for aneuploidy , as compared with conventional assisted reproduction treatment procedures . Two hundred patients with recurrent failed implantation were r and omized into two groups . A total of 139 patients underwent ovarian stimulation , and preimplantation genetic screening was performed in 72 patients . Analysis of chromosomes X , Y , 13 , 16 , 18 , 21 and 22 was carried out using fluorescence in-situ hybridization in blastomeres of day-3 cleavage-stage embryos in the study group . The primary endpoint was implantation rate . Secondary endpoints were embryonic morphology and chromosomal status , number of transferred embryos and clinical pregnancy rate . With regard to the implantation rate , there was no significant difference between the study group ( 21.4 % ) and the control group ( 25.3 % ) . The number of embryos transferred was significantly lower in the study group , namely 1.4 ( SD 1.0 ) versus 2.1 ( SD 1.0 ) in the control group ( P < 0.05 ) . The clinical pregnancy rate was not significantly different between the groups ( 25.0 % in the study group versus 40.3 % in the control group ) . It can be concluded that preimplantation genetic screening does not increase the implantation rates after IVF-intracytoplasmic sperm injection in women with repeated implantation failure STUDY QUESTION Do preschool preimplantation genetic diagnosis ( PGD ) children differ in their cognitive and psychomotor development from children born after ICSI and spontaneous conception ( SC ) ? SUMMARY ANSWER The cognitive development of PGD pre-schoolers was comparable to children born after ICSI and SC but motor development differed between ICSI and SC groups . STUDY DESIGN , SIZE DURATION The cognitive abilities and motor skills of 5- to 6-year-old singletons born after PGD ( n = 47 ) were assessed in comparison with 49 ICSI and 48 SC children in a prospect i ve , case-controlled , matched follow-up study between April 2011 and May 2013 . PARTICIPANTS / MATERIAL S , SETTING , METHODS PGD singletons , ICSI and SC children of preschool age were examined with the Wechsler Preschool and Primary Scale of Intelligence ( WPSSI-III-NL ) and the Movement ABC ( M ABC ) . The WPSSI-III-NL revealed scores for Full IQ , Verbal IQ and Performance IQ . The M ABC yields a total score and comprising scores for measurements of balance , dexterity and ball skills . Since embryo biopsy is the only technical difference between the PGD and ICSI procedures , ICSI children were included as controls . These children were part of a Dutch-speaking cohort of children conceived after assisted reproduction technology ( ART ) at the Universitair Ziekenhuis Brussel ( UZ Brussel ) who received longitudinal follow-up . The SC children acted as a second control group similar to the fertile PGD sample and in contrast to the ICSI group . The SC group was recruited through announcements in a variety of media . The children were matched for age , gender , birth order and educational level of the mother . The assessment s carried out for the ART groups were blinded whenever possible . The data were analysed using analysis of covariance ( ANCOVA ) and partial eta squared ( η(2 ) ) , which was used as a measurement of effect size . MAIN RESULTS AND THE ROLE OF CHANCE The overall cognitive development of PGD singletons did not differ from controls [ P = 0.647 , η(2 ) = 0.006 ; 95 % confidence interval ( CI ) ( 0 , 0.043 ) ] . The partial IQ scores for Verbal and Performance intelligence revealed similar results . Analysis of motor development based on the total score as well as subscales did indicate a significant difference between the three conception groups [ P = 0.033 , η(2 ) = 0.050 , 95 % CI ( 0 , 0.124 ) ] . Post hoc analysis indicated that the significant difference was situated between performances of ICSI and SC children . Balance capacities [ P = 0.004 , η(2 ) = 0.079 , 95 % CI ( 0.025 , 0.163 ) ] and its post hoc analysis yielded equivalent results . Motor capacities of PGD singletons , however , did not differ from any of the two other conception groups . LIMITATIONS , REASONS FOR CAUTION Given that we only assessed Caucasian singletons born after PGD , caution is required when drawing more general inferences from our results . The small sample size may be a limitation . A priori power analysis , however , revealed that at least 52 children per group were needed to detect a medium effect and 80 % power using ANCOVA . Originally our sample met this threshold but we had to exclude six cases in order to remove outliers and due to missing data . WIDER IMPLICATION S OF THE FINDINGS Long-term follow-up of children born after embryo biopsy , in this case for PGD , is needed to confirm that the development of these children remains comparable to ICSI and SC children . Our findings do support the safety of the PGD technique and will reassure patients with hereditary genetic diseases regarding the health of their future offspring conceived with PGD . STUDY FUNDING /COMPETING INTERESTS Funding for this study was obtained from the OZR ( Research group of the Vrije Universiteit Brussel ) , the FWO ( Fonds Wetenschappelijk Onderzoek ) and the Wetenschappelijk Fonds Willy Gepts . The UZ Brussel and the Centre of Medical Genetics received funding from pharmaceutical firms for data collection . UZ Brussel and the Centre for Medical Genetics have received many educational grants for organizing the data collection , from IBSA , Ferring , Organon , Shering-Plough , Merck and Merck Belgium . M.B. has received consultancy and speaker 's fees from Organon , Serono Symposia and Merck STUDY QUESTION Does Day-3 cleavage-stage PGS affect neurodevelopment of 9-year-old IVF offspring ? SUMMARY ANSWER We did not find evidence of adverse consequences of Day-3 cleavage-stage PGS on neurodevelopment of 9-year-old IVF offspring , although children born after IVF with or without PGS often had a non-optimal neurological condition . WHAT IS KNOWN ALREADY Knowledge on long-term sequelae for development and health of children born following PGS is lacking . This is striking as evidence accumulates that IVF itself is associated with increased risk for impaired health and development in the offspring . STUDY DESIGN SIZE , DURATION This prospect i ve , assessor-blinded , multicentre , follow-up study evaluated development and health of 9-year-old IVF children born to women who were r and omly assigned to IVF with PGS ( PGS group ) or without PGS ( control group ) . The follow-up examination at 9 years took place between March 2014 and May 2016 . PARTICIPANTS / MATERIAL S , SETTING , METHODS In total , 408 women were included and r and omly assigned to IVF with or without Day-3 cleavage-stage PGS . This result ed in 52 ongoing pregnancies in the PGS group and 74 in the control group . In the PGS group , 59 children were born alive ; in the control group , 85 children were born alive . At the age of 9 years , 43 children born after PGS and 56 control children participated in the study . Our primary outcome was the neurological optimality score , a sensitive measure of neurological condition assessed with a st and ardized , age-specific test ( Touwen test ) . Secondary outcomes were adverse neurological condition ( neurologically abnormal and the complex form of minor neurological dysfunction ) , cognitive development ( intelligence quotient and specific domains ) , behaviour ( parental and teacher 's question naires ) , blood pressure and anthropometrics . MAIN RESULTS AND THE ROLE OF CHANCE Neurodevelopmental outcome of PGS children did not differ from that of controls ; the neurological optimality scores ( mean values [ ( 95 % CI ] : PGS children 51.5 [ 49.3 ; 53.7 ] , control children 53.1 [ 50.5 ; 55.7 ] ) were not significantly different . The prevalences of adverse neurological outcome ( in all but one child implying the presence of the complex form of minor neurological dysfunction ) did not differ between the groups ( PGS group 17/43 [ 40 % ] , control group 19/56 [ 34 % ] ) , although the prevalence of complex minor neurological dysfunction in both groups was rather high . Also intelligence quotient scores of the two groups were not significantly different ( PGS group 114 [ 108 ; 120 ] ) ; control group 117 [ 109 ; 125 ] ) , and the behaviour , blood pressure and anthropometrics of both groups did not differ . Mean blood pressures of both groups were above the 60th percentile . LIMITATIONS REASONS FOR CAUTION The power analysis of the study was not based on the number of children needed for the follow-up study , but on the number of women who were needed to detect an increase in ongoing pregnancy rates after PGS . In addition , our study evaluated embryo biopsy in the form of PGS at cleavage stage ( Day-3 embryo biopsy ) , while currently PGS at blastocyst stage ( Day-5 embryo biopsy ) is recommended and increasingly being used . WIDER IMPLICATION S OF THE FINDINGS Our findings indicate that PGS in cleavage stage embryos is not associated with adverse effects on neurological , cognitive and behavioural development , blood pressure and anthropometrics of offspring at 9 years . This is a reassuring finding as embryo biopsy in the forms of PGS and PGD is increasingly applied . However , both groups of IVF offspring showed high prevalences of the clinical ly relevant form of minor neurological dysfunction , which is a point of concern for the IVF community . In addition , our study confirms findings of others that IVF offspring may be at risk of an unfavourable cardiovascular outcome . These findings are alarming and highlight the importance of research on the underlying mechanisms of unfavourable neurodevelopmental and cardiovascular outcomes in IVF offspring . STUDY FUNDING /COMPETING INTEREST(S ) The r and omized controlled trial was financially supported by the Organization for Health Research and Development ( ZonMw ) , The Netherl and s ( Grant number 945 - 03 - 013 ) . The follow-up was financially supported by the University Medical Center Groningen ( Grant number : 754510 ) , the Cornelia Foundation , and the graduate schools BCN and Share , Groningen , The Netherl and s. The sponsors of the study had no role in study design , data collection , data analysis , data interpretation or writing of the report . There are no conflicts of interest . TRIAL REGISTRATION NUMBER IS RCT N76355836 OBJECTIVE The major objective of this study was to determine whether the embryo biopsy procedure might cause growth restriction or affect health outcome of children . STUDY DESIGN Auxological data and physical findings were compared at birth and age 2 for 102 children ( 70 singletons and 32 twins ) born after PGD/PGS and 102 matched children born after intracytoplasmic sperm injection ( ICSI ) in a prospect i ve study . RESULTS No statistically significant differences regarding weight , height and head circumference st and ard deviation scores ( SDS ) at birth and at age two years were observed . At two years of age the mean BMI SDS tended to be lower in PGD/PGS children ( p=0.058 ) . PGD/PGS babies had been more often breastfed ( p=0.013 ) , but mostly during a shorter time . The prevalence of major as well as minor congenital anomalies , hospital admissions and surgical interventions was similar . CONCLUSION Children born after embryo biopsy applied in PGD/PGS present similar prenatal and postnatal growth and health outcome in the first two years of life compared to ICSI children . Up till now , PGD and PGS appear not to be associated with a higher risk for health problems OBJECTIVE To determine the clinical value of preimplantation genetic diagnosis for aneuploidy screening ( PGD-A ) in women of advanced maternal age ( AMA ; between 38 and 41 years ) . DESIGN This was a multicenter , r and omized trial with two arms : a PGD-A group with blastocyst transfer , and a control group with blastocyst transfer without PGD-A. SETTING Private reproductive centers . PATIENT(S ) A total of 326 recruited patients fit the inclusion criteria , and 205 completed the study ( 100 in the PGD-A group and 105 in the control group ) . INTERVENTION(S ) Day-3 embryo biopsy , array comparative genomic hybridization , blastocyst transfer , and vitrification . MAIN OUTCOME MEASURE(S ) Primary outcomes were delivery and live birth rates in the first transfer and cumulative outcome rates . RESULT ( S ) The PGD-A group exhibited significantly fewer ETs ( 68.0 % vs. 90.5 % for control ) and lower miscarriage rates ( 2.7 % vs. 39.0 % for control ) . Delivery rate after the first transfer attempt was significantly higher in the PGD-A group per transfer ( 52.9 % vs 24.2 % ) and per patient ( 36.0 % vs. 21.9 % ) . No significant differences were observed in the cumulative delivery rates per patient 6 months after closing the study . However , the mean number of ETs needed per live birth was lower in the PGD-A group compared with the control group ( 1.8 vs. 3.7 ) , as was the time to pregnancy ( 7.7 vs. 14.9 weeks ) . CONCLUSION ( S ) Preimplantation genetic diagnosis for aneuploidy screening is superior compared with controls not only in clinical outcome at the first ET but also in dramatically decreasing miscarriage rates and shortening the time to pregnancy OBJECTIVE To determine whether blastocyst biopsy and rapid quantitative real-time polymerase chain reaction (qPCR)-based comprehensive chromosome screening ( CCS ) improves in vitro fertilization ( IVF ) implantation and delivery rates . DESIGN R and omized controlled trial . SETTING Academic reproductive medicine center . PATIENT(S ) Infertile couples in whom the female partner ( or oocyte donor ) is between the ages of 21 and 42 years who are attempting conception through IVF . INTERVENTION(S ) Embryonic aneuploidy screening . MAIN OUTCOME MEASURE(S ) Sustained implantation and delivery rates . RESULT ( S ) We transferred 134 blastocysts to 72 patients in the study ( CCS ) group and 163 blastocysts to 83 patients in the routine care ( control ) group . Sustained implantation rates ( probability that an embryo will implant and progress to delivery ) were statistically significantly higher in the CCS group ( 89 of 134 ; 66.4 % ) compared with those from the control group ( 78 of 163 ; 47.9 % ) . Delivery rates per cycle were also statistically significantly higher in the CCS group . Sixty one of 72 treatment cycles using CCS led to delivery ( 84.7 % ) , and 56 of 83 ( 67.5 % ) control cycles ultimately delivered . Outcomes were excellent in both groups , but use of CCS clearly improved patient outcomes . CONCLUSION ( S ) Blastocyst biopsy with rapid qPCR-based comprehensive chromosomal screening results in statistically significantly improved IVF outcomes , as evidence d by meaningful increases in sustained implantation and delivery rates . CLINICAL TRIAL REGISTRATION NUMBER NCT01219283 STUDY QUESTION Do full term singletons born after preimplantation genetic diagnosis ( PGD ) differ in their psychosocial functioning from children born after intracytoplasmic sperm injection ( ICSI ) and spontaneous conceived controls ( SC ) ? SUMMARY ANSWER The psychosocial maturation process of 5 - 6-year-old PGD children is comparable between the three conception groups ( PGD , ICSI and SC ) . WHAT IS ALREADY KNOWN In general , a lot of research has been published regarding follow-up of children born after artificial reproductive technologies ( ART ) , which mainly is reassuring . But the ART population itself is marked by broad diversity [ IVF , ICSI , gamete donation , preimplantation genetic screening ( PGS ) or PGD ] which complicates comparisons . Some literature concerning the socio-emotional development of PGD/PGS children is available and it suggests a normal maturation process . However , the complex reality of PGD families ( e.g. safety of the technique and psychological burden of genetic histories ) asks for an exclusive PGD sample with matched control groups and a multi-informant approach . STUDY DESIGN , SIZE , DURATION Between April 2011 and May 2013 , the psychosocial wellbeing of preschoolers and their families born after PGD was assessed in a prospect i ve case-controlled , matched follow-up study , with a multi-informant approach . PARTICIPANTS / MATERIAL S , SETTING , METHODS A group of 47 PGD , 50 ICSI and 55 SC 5 - 6-year-old children participated in a follow-up study performed at the Centre for Medical Genetics of the Universitair Ziekenhuis Brussel ( UZ Brussel ) . Assessment s took place in the hospital and in kindergartens . Children performed the Bene-Anthony family relations test ( FRT ) , yielding their perceptions upon family relationships . Parents and teachers completed the child behaviour checklist ( CBCL ) and Caregiver Teacher Report Form ( C-/TRF ) , respectively . Parental and family functioning were measured by the NEO-FFi , the parenting stress index ( PSI ) , the Greenberger Work-Parenting Investment Question naire and the Marlowe-Crowne Social Desirability Scale ( MCSDS ) . Statistical analysis was performed by using analysis of covariance ( ANCOVA ) . MAIN RESULTS AND THE ROLE OF CHANCE No differences were detected between the psychosocial development of PGD children and the control groups . Parents did not differ in reporting problem behaviour and they were stricter than teachers . Concerning family functioning the ART parents scored comparable with each other . PGD and ICSI mothers were emotionally more stable [ NEO-FFi Neuroticism/emotionality : P = 0.013 , η(2 ) = 0.066 ; 95 % confidence interval ( CI ) 95 % ( 0.003;0.148 ) ] . They experienced less parental stress in general [ PSI , Total stress : P = 0.001 , η(2 ) = 0.102 , 95 % CI ( 0.02;0.192 ) ] and on different sublevels opposed to their SC counterparts . Yet ART mothers presented higher ratings on the NEO-FFi Conscientiousness [ P = 0.011 , η(2 ) = 0.064 ; 95 % CI ( 0.003;0.144 ) ] indicating a higher feeling of competence and goal directedness . Mediation analysis confirmed : PGD and ICSI mothers who experienced less family stress were emotionally more stable . A power analysis indicated that a sample with 152 children is sufficient to detect a medium size effect with 80 % power using ANCOVA . LIMITATIONS , REASONS FOR CAUTION The current sample comprised only Dutch speaking Caucasians , hence conclusions should be drawn cautiously . Future research should include larger groups , prematures , multiples and children from different cultural background s. WIDER IMPLICATION S OF THE FINDINGS This current research is the first to compare PGD preschoolers with matched controls . Concerns about the behavioural effects on the offspring should not inhibit the use of PGD . Furthermore , our findings suggest that on the long run ART procedures might enhance personal re sources of women to cope with family stress . These findings are reassuring for women who might feel insecure and anxious during their ART trajectory . STUDY FUNDING /COMPETING INTERESTS This research project gained funding from the OZR ( a grant by the Research group of the Vrije Universiteit Brussel ) , the FWO ( Fonds Wetenschappelijk Onderzoek ) and the Wetenschappelijk Fonds Willy Gepts . The UZ Brussel and the Centre of Medical Genetics received funding from pharmaceutical firms for data collection . UZ Brussel and the Centre for Medical Genetics have received many educational grants for organizing the data collection , from IBSA , Ferring , Organon , Shering-Plough , Merck and Merck Belgium . M.B. has received consultancy and speaker 's fees from Organon , Serono Symposia and Merck . The other authors have no competing interests . TRIAL REGISTRATION NUMBER not applicable OBJECTIVE To determine whether performing comprehensive chromosome screening ( CCS ) and transferring a single euploid blastocyst can result in an ongoing pregnancy rate that is equivalent to transferring two untested blastocysts while reducing the risk of multiple gestation . DESIGN R and omized , noninferiority trial . SETTING Academic center for reproductive medicine . PATIENT(S ) Infertile couples ( n = 205 ) with a female partner less than 43 years old having a serum anti-Müllerian hormone level ≥ 1.2 ng/mL and day 3 FSH < 12 IU/L. INTERVENTION(S ) R and omization occurred when at least two blastocysts were suitable for trophectoderm biopsy . The study group ( n = 89 ) had all viable blastocysts biopsied for real-time , polymerase chain reaction-based CCS and single euploid blastocyst transfer . The control group ( n = 86 ) had their two best- quality , untested blastocysts transferred . MAIN OUTCOME MEASURE(S ) The ongoing pregnancy rate to ≥ 24 weeks ( primary outcome ) and the multiple gestation rate . RESULT ( S ) The ongoing pregnancy rate per r and omized patient after the first ET was similar between groups ( 60.7 % after single euploid blastocyst transfer vs. 65.1 % after untested two-blastocyst transfer ; relative risk [ RR ] , 0.9 ; 95 % confidence interval [ CI ] , 0.7 - 1.2 ) . A difference of greater than 20 % in favor of two-blastocyst transfer was excluded . The risk of multiple gestation was reduced after single euploid blastocyst transfer ( 53.4 % to 0 % ) , and patients were nearly twice as likely to have an ongoing singleton pregnancy ( 60.7 % vs. 33.7 % ; RR , 1.8 ; 95 % CI , 1.3 - 2.5 ) . CONCLUSION ( S ) In women ≤ 42 years old , transferring a single euploid blastocyst results in ongoing pregnancy rates that are the same as transferring two untested blastocysts while dramatically reducing the risk of twins BACKGROUND Human preimplantation embryos generated through in vitro fertilization ( IVF ) or intracytoplasmic sperm injection ( ICSI ) treatments show a variable rate of numerical chromosome abnormalities or aneuploidies . Preimplantation genetic screening ( PGS ) has been design ed to screen for aneuploidies in high risk patients , with the aim of improving live birth rates in IVF/ICSI . We assessed whether the effect of PGS on live births rates differs in women of advanced maternal age with variable risks for embryonic aneuploidy , and weighed these effects against the results obtained after IVF/ICSI without PGS . METHODS The effect of PGS on live birth rates was compared between groups defined by maternal age , number of previous miscarriages , semen quality , total amount of recombinant FSH ( rFSH ) administered during ovarian stimulation and total number of top- quality embryos , using data from a r and omized controlled trial among women of advanced maternal age ( 35 - 41 years ) . RESULTS There was no significant differential effect of PGS in groups based on maternal age ( P-value of interaction 0.16 ) , the number of previous miscarriages ( P-value of interaction 0.93 ) , semen quality ( P-value of interaction 0.26 ) , rFSH dose ( P-value of interaction 0.15 ) or the number of top- quality embryos ( P-value of interaction 0.59 ) . Live birth rates after IVF/ICSI with PGS were lower in all groups when compared with live birth rates after IVF/ICSI without PGS . CONCLUSIONS The paradigm that the effect of PGS is determined by a woman 's risk for embryonic aneuploidy seems incorrect . In fact , PGS has no clinical benefit over st and ard IVF/ICSI in women of advanced maternal age regardless of their risk for embryonic aneuploidy OBJECTIVE The aim of this study was to evaluate the efficacy of preimplantation genetic screening ( PGS ) in women younger than 38 years and who had recurrent implantation failure ( RIF ) . STUDY DESIGN A prospect i ve nonr and omized parallel group study was performed in the assisted reproduction unit of a private tertiary care hospital . 140 infertile couples who had three or more previous failed cycles were included . Genetic counseling was given and couples who opted for another treatment cycle with PGS ( n=54 ) formed the PGS group whereas couples who declined PGS formed the control group ( n=86 ) . In the PGS group , following FISH analysis for the detection of chromosomes 13 , 16 , 18 , 21 , 22 , X and Y , only euploid embryos were transferred on day 5 . In the control group embryo transfer was performed on day 3 . Clinical pregnancy and live birth rates were compared . 95 % confidence intervals for differences between the groups were calculated . RESULTS Baseline and treatment cycle characteristics were similar in both groups . In the PGS group , a mean number of two embryos were transferred ; there were 8 clinical pregnancies ( 14.8 % ) . The implantation rate was 11.9 % . There were no miscarriages and the live birth rate was 14.8 % . In the control group , a mean number of 2.7 embryos were transferred result ing in 23 pregnancies ( 26.7 % ) . The implantation rate was 18.4 % . There were 2 miscarriages and the live birth rate was 24.4 % . The differences among the groups were not statistically significant . CONCLUSION The results suggest that this particular group of young patients with RIF may not benefit from PGS . However , PGS is a multistep procedure that is highly human dependent , and results may vary across laboratories |
12,740 | 31,447,571 | Conclusion We found that serum omentin level is significantly lower in T2DM and IGT patients but not in T1DM ones .
These data could be used by clinicians for early diagnosis and management of diabetes . | Aims A number of studies have examined the association between the serum levels of omentin and diabetes , but the findings have been inconclusive .
Herein , we systematic ally review ed available observational studies to eluci date the overall relationship between omentin and diabetes , including type 1 diabetes mellitus ( T1DM ) , type 2 diabetes mellitus ( T2DM ) , and impaired glucose tolerance ( IGT ) among adolescent and adult population . | Background Various adipokines are reported to be associated with the development of heart failure ( HF ) through insulin resistance and chronic inflammation . Omentin-1 is a novel adipokine and is associated with incident coronary artery disease . However , it remains unclear whether serum omentin-1 levels are associated with cardiac prognosis in patients with HF . Methods We measured serum omentin-1 levels at admission in 136 consecutive patients with HF , and 20 control subjects without signs of significant heart disease . We prospect ively followed patients with HF to endpoints of cardiac death or re-hospitalization for worsening HF . Results Serum omentin-1 levels were markedly lower in HF patients with cardiac events compared with to without . The patients who were in New York Heart Association ( NYHA ) functional class IV showed significantly lower serum omentin-1 levels compared to those in class II and III , whereas serum omentin-1 levels did not correlate with serum brain natriuretic peptide levels ( r = 0.217 , P = 0.011 ) . We divided the HF patients into three groups based on the tertiles of serum omentin-1 level ( low T1 , middle T2 , and high T3 ) . Multivariate Cox hazard analysis showed that the lowest serum omentin-1 level ( T1 ) was independently associated with cardiac events after adjustment for confounding factors ( hazard ratio 5.78 , 95 % confidence interval 1.20 - 12.79 ) . We divided the HF patients into two groups according to the median serum omentin-1 levels . Kaplan-Meier analysis revealed that the patients with low serum omentin-1 levels had a higher risk of cardiac events compared with those with high serum omentin-1 levels ( log-rank test p < 0.001 ) . Conclusion Decreased serum omentin-1 levels were associated with a poor cardiac outcome in patients with HF BACKGROUND Epidemiological studies have reported that patients with type 2 diabetes mellitus ( DM ) have increased mortality and morbidity from cardiovascular diseases , independent of other risk factors . However , most of these studies have been performed in selected patient groups . The purpose of the present study was prospect ively to assess the impact of type 2 DM on cardiovascular morbidity and mortality in an unselected population . METHODS A total of 13,105 subjects from the Copenhagen City Heart Study were followed up prospect ively for 20 years . Adjusted relative risks of first , incident , admission for , or death from ischemic heart disease , acute myocardial infa rct ion , or stroke , as well as total mortality in persons with type 2 DM compared with healthy controls , were estimated . RESULTS The relative risk of first , incident , and admission for myocardial infa rct ion was increased 1.5- to 4.5-fold in women and 1.5- to 2-fold in men , with a significant difference between sexes . The relative risk of first , incident , and admission for stroke was increased 2- to 6.5-fold in women and 1.5- to 2-fold in men , with a significant difference between sexes . In both women and men the relative risk of death was increased 1.5 to 2 times . CONCLUSIONS In persons with type 2 DM , the risk of having an incident myocardial infa rct ion or stroke is increased 2- to 3-fold and the risk of death is increased 2-fold , independent of other known risk factors for cardiovascular diseases OBJECTIVE Omentin is a protein expressed and secreted from visceral but not subcutaneous adipose tissue , which increases insulin sensitivity in human adipocytes . However , its pathophysiologic role in humans remains largely unknown . The objective of this study is to assess plasma omentin-1 levels in patients with type 2 diabetes mellitus ( T2DM ) and matched control subjects and to investigate the effects of liraglutide on plasma omentin-1 levels in patients with T2DM . PATIENTS AND METHODS Thirty T2DM patients with poor glycemic control after more than 3 months of treatment with one or two OHA(s ) ( T2DM ) , and 30 matched normal glycaemic controls ( NGT ) participated in the study . The T2DM group was given an injection of liraglutide once-daily for 16 weeks . Plasma omentin-1 levels were measured by enzyme-linked immunosorbent assay and the relationship between plasma omentin-1 levels and metabolic parameters was also analyzed . RESULTS Plasma omentin-1 levels were lower in T2DM than in the control ( 19.3 ± 4.0 μg/L vs. 26.4 ± 6.0 μg/L , P < 0.01 ) . Plasma omentin-1 levels increased significantly in T2DM patients after treatment with liraglutide compared with pre-treatment ( 19.3 ± 4.0 μg/L vs. 21.2 ± 3 . 9 μg/L , P < 0.01 ) . In all diabetic patients , multiple regression analysis showed that FINS and HOMA-IR were independently associated with plasma omentin-1 levels . CONCLUSIONS In T2DM patients , plasma omentin-1 levels decreased , but significantly increased after the treatment with liraglutide and metformin . These data suggest that liraglutide may play a role in increasing omentin-1 levels in T2DM patients |
12,741 | 19,588,316 | Monthly multidisciplinary team meetings improved prescribing of psychotropic drugs in nursing homes .
Videoconferencing compared to audioconferencing multidisciplinary case conferences showed mixed results ; there was a decreased number of case conferences per patient and shorter length of treatment , but no differences in occasions of service or the length of the conference .
There was also no difference between the groups in the number of communications between health professionals recorded in the notes .
Multidisciplinary meetings with an external facilitator , who used strategies to encourage collaborative working , was associated with increased audit activity and reported improvements to care . | BACKGROUND Poor interprofessional collaboration ( IPC ) can negatively affect the delivery of health services and patient care .
Interventions that address IPC problems have the potential to improve professional practice and healthcare outcomes .
OBJECTIVES To assess the impact of practice -based interventions design ed to change IPC , compared to no intervention or to an alternate intervention , on one or more of the following primary outcomes : patient satisfaction and /or the effectiveness and efficiency of the health care provided .
Secondary outcomes include the degree of IPC achieved . | 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 Sc and J Prim Health Care 2003;21:00 - 00 . ISSN 0281 - 3432 Objective r - r To investigate general practitioner ( GP ) assessment of a structured oncology information pack sent to GPs when newly referred patients had visited a department of oncology for the first time , and to compare their assessment of this material with their assessment of traditional information provided by the department . Design r - r R and omised , unblinded clinical trial . Setting r - r Patients and GPs in the catchment area of a regional oncology department . Subjects / patients r - r 248 cancer patients and their 199 GPs . Main outcome measures r - r GP assessment of the quality of the information material received for each patient . Results r - r 88.3 % of the 248 question naires were returned . The structured information pack improved GP knowledge of oncology ; GPs found themselves better equipped to support and counsel patients during the course of their illness , and practitioner satisfaction with the department rose . Conclusion r - r Intervention , though reasonably simple , inexpensive and not particularly time-consuming , improved cooperation between the specialist department and the GP . While this is a small step in the right direction , the need remains for new initiatives and further studies into how to improve cooperation and communication between the primary and secondary healthcare sectors OBJECTIVE To test the effectiveness of a nursing-centered intervention to prevent functional decline among hospitalized elderly medical patients . DESIGN Prospect i ve cohort study with stratified and matched cohort analyses . SETTING General medicine wards of a university teaching hospital . PATIENTS Two hundred sixteen patients aged > or = 70 years ( 85 intervention and 131 control patients ) . INTERVENTION The intervention included identification and surveillance of frail older patients , twice-weekly rounds of the Geriatric Care Team , and a nursing-centered educational program . MAIN OUTCOME MEASURE Functional decline , defined as a net decline in five activities of daily living ( ADLs ) . RESULTS In stratified analyses , the intervention result ed in a beneficial effect with a relative risk of 0.82 ( 95 % confidence interval [ CI ] 0.54 to 1.24 ) in patients ( n = 106 ) with one of four geriatric target conditions at baseline ( eg , delirium , functional impairment , incontinence , and pressure sores ) . The intervention had no effect in patients without target conditions at baseline ( n = 110 ) ; thus , this subgroup was excluded from further analyses . When patients were matched on number of target conditions and risk for functional decline at baseline ( n = 66 ) , the intervention result ed in a significant beneficial effect , with a reduction in functional decline from 64 % in controls to 41 % in the intervention group , for a relative risk of 0.64 ( 95 % CI , 0.43 to 0.96 ) . The intervention group had significantly less decline in ADL score and in individual ADLs than control subjects . Specific interventions aim ed at maximizing function , such as physical therapy , were received more often by intervention patients ; however , the beneficial effects of the intervention were achieved without increasing per-day hospital costs . CONCLUSIONS The intervention appears effective to decrease functional decline in targeted elderly hospitalized medical patients BACKGROUND Patients with cardiac arrests or who die in general wards have often received delayed or inadequate care . We investigated whether the medical emergency team ( MET ) system could reduce the incidence of cardiac arrests , unplanned admissions to intensive care units ( ICU ) , and deaths . METHODS We r and omised 23 hospitals in Australia to continue functioning as usual ( n=11 ) or to introduce a MET system ( n=12 ) . The primary outcome was the composite of cardiac arrest , unexpected death , or unplanned ICU admission during the 6-month study period after MET activation . Analysis was by intention to treat . FINDINGS Introduction of the MET increased the overall calling incidence for an emergency team ( 3.1 vs 8.7 per 1000 admissions , p=0.0001 ) . The MET was called to 30 % of patients who fulfilled the calling criteria and who were subsequently admitted to the ICU . During the study , we recorded similar incidence of the composite primary outcome in the control and MET hospitals ( 5.86 vs 5.31 per 1000 admissions , p=0.640 ) , as well as of the individual secondary outcomes ( cardiac arrests , 1.64 vs 1.31 , p=0.736 ; unplanned ICU admissions , 4.68 vs 4.19 , p=0.599 ; and unexpected deaths , 1.18 vs 1.06 , p=0.752 ) . A reduction in the rate of cardiac arrests ( p=0.003 ) and unexpected deaths ( p=0.01 ) was seen from baseline to the study period for both groups combined . INTERPRETATION The MET system greatly increases emergency team calling , but does not substantially affect the incidence of cardiac arrest , unplanned ICU admissions , or unexpected death OBJECTIVES To determine the effect of collaborative care management for depression on physical functioning in older adults . DESIGN Multisite r and omized clinical trial . SETTING Eighteen primary care clinics from eight healthcare organizations . PARTICIPANTS One thous and eight hundred one patients aged 60 and older with major depressive disorder . INTERVENTION Patients were r and omized to the Improving Mood : Promoting Access to Collaborative Treatment ( IMPACT ) intervention ( n=906 ) or to a control group receiving usual care ( n=895 ) . Control patients had access to all health services available as part of usual care . Intervention patients had access for 12 months to a depression clinical specialist who coordinated depression care with their primary care physician . MEASUREMENTS The 12-item short form Physical Component Summary ( PCS ) score ( range 0 - 100 ) and instrumental activities of daily living ( IADLs ) ( range 0 - 7 ) . RESULTS The mean patient age was 71.2 , 65 % were women , and 77 % were white . At baseline , the mean PCS was 40.2 , and the mean number of IADL dependencies was 0.7 ; 45 % of participants rated their health as fair or poor . Intervention patients experienced significantly better physical functioning at 1 year than usual-care patients as measured using between-group differences on the PCS of 1.71 ( 95 % confidence interval (CI)=0.96 - 2.46 ) and IADLs of -0.15 ( 95 % CI=-0.29 to -0.01 ) . Intervention patients were also less likely to rate their health as fair or poor ( 37.3 % vs 52.4 % , P<.001 ) . Combining both study groups , patients whose depression improved were more likely to experience improvement in physical functioning . CONCLUSION The IMPACT collaborative care model for late-life depression improves physical function more than usual care OBJECTIVE To test a quality improvement intervention , a learning collaborative based on the Institute for Healthcare Improvement 's Breakthrough Series methodology , specifically intended to improve care and outcomes for patients with childhood asthma . DESIGN R and omized trial in primary care practice s. SETTING Practice s in greater Boston , Mass , and greater Detroit , Mich. PARTICIPANTS Forty-three practice s , with 13 878 pediatric patients with asthma , r and omized to intervention and control groups . Intervention Participation in a learning collaborative project based on the Breakthrough Series methodology of continuous quality improvement . MAIN OUTCOME MEASURES Change from baseline in the proportion of children with persistent asthma who received appropriate medication therapy for asthma , and in the proportion of children whose parent received a written management plan for their child 's asthma , as determined by telephone interviews with parents of 631 children . RESULTS After adjusting for state , practice size , child age , sex , and within- practice clustering , no overall effect of the intervention was found . CONCLUSIONS This method ologically rigorous assessment of a widely used quality improvement technique did not demonstrate a significant effect on processes or outcomes of care for children with asthma . Potential deficiencies in program implementation , project duration , sample selection , and data sources preclude making the general inference that this type of improvement program is ineffective . Additional rigorous studies should be undertaken under more optimal setting s to assess the efficacy of this method for improving care AIM To study the effects of a team-based model for continuous quality improvement ( CQI ) on primary care practice management . DESIGN OF STUDY R and omised controlled trial . SETTING Twenty-six intervention and 23 control primary care practice s in the Netherl and s. METHOD Practice s interested in taking part in the CQI project were , after assessment of their practice organisation , r and omly assigned to the intervention or control groups . During a total of five meetings , a facilitator helped the teams in the intervention group select suitable topics for quality improvement and follow a structured approach to achieve improvement objectives . Checklists completed by an outreach visitor , question naires for the GPs , staff and patients were used to assemble data on the number and quality of improvement activities undertaken and on practice management prior to the start of the intervention and 1 year later . RESULTS Pre-test and post-test data were compared for the 26 intervention and 23 control practice s. A significant intervention effect was found for the number of improvement objectives actually defined ( 93 versus 54 , P<0.001 ) and successfully completed ( 80 versus 69 % of the projects , P<0.001 ) . The intervention group also improved on more aspects of practice management , as measured by our practice visit method , than the control group but none of these differences proved statistically significant . CONCLUSION The intervention exerted a significant effect on the number and quality of improvement projects undertaken and self-defined objectives met . Failure of the effects of the intervention on the other dimensions of practice management to achieve significance may be due to the topics selected for some of the improvement projects being only partly covered by the assessment instrument 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 Acute hospital general medicine services care for ageing complex patients , using the skills of a range of health-care providers . Evidence suggests that comprehensive early assessment and discharge planning may improve efficiency and outcomes of care in older medical patients . AIM To enhance assessment , communication , care and discharge planning by restructuring consistent , patient-centred multidisciplinary teams in a general medicine service . METHODS Prospect i ve controlled trial enrolling 1538 consecutive medical in patients . Intervention units with additional allied health staff formed consistent multidisciplinary teams aligned with inpatient admitting units rather than wards ; implemented improved communication processes for early information collection and sharing between disciplines ; and specified shared explicit discharge goals . Control units continued traditional , referral-based multidisciplinary models with existing staffing levels . RESULTS Access to allied health services was significantly enhanced . There was a trend to reduced index length of stay in the intervention units ( 7.3 days vs 7.8 days in control units , P = 0.18 ) , with no change in 6-month readmissions . In-hospital mortality was reduced from 6.4 to 3.9 % ( P = 0.03 ) ; less patients experienced functional decline in hospital ( P = 0.04 ) and patients ' ratings of health status improved ( P = 0.02 ) . Additional staffing costs were balanced by potential bed-day savings . CONCLUSION This model of enhanced multidisciplinary inpatient care has provided sustainable efficiency gains for the hospital and improved patient outcomes 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 Despite the widespread use of home based child health records of varying complexity in Engl and , there is a notable absence of their evaluation . Such a record booklet developed in the West Lambeth Health Authority has been used by parents , doctors , and community nurses to build up an independent chronological record of a child 's birth statistics , health , growth , immunisation , development checks , and contacts with health services . A r and omised controlled evaluation of the record , analyses of entries in it , and a survey of the views of mothers and health professionals using the record have been carried out . The need for such a record was confirmed by those question ed and analyses of entries in the booklet helped to modify and improve it . The evaluation was unable to show , however , any effect of the record on immunisation and developmental assessment service uptake . Its value in improving communication between the numerous health and other care agencies was dependent on its proper use BACKGROUND The need for training to equip primary care staff with the knowledge and skills to provide dietary advice to the public has been acknowledged . Little is known about the effectiveness of such training at improving the dietary counselling skills of multidisciplinary practice teams . AIM To evaluate the effectiveness of a nutrition training programme , delivered to primary care teams by a dietitian . DESIGN OF STUDY A paired-cluster r and omised trial . SETTING Twelve general practice s in Sunderl and , in the United Kingdom . METHOD A nutrition training programme , aim ed at improving the quality of dietary consultations , was developed and delivered to six primary care teams by a dietitian . Main outcome measures were patients ' recall of seven key consulting behaviours . Data were collected from patients in intervention and control practice s , pre- and post-intervention . Change in knowledge and attitude of practitioners was also measured . RESULTS All 12 practice s completed the trial . Data were collected from 251 patients pre-intervention and 228 patients post-intervention . Of the seven consulting behaviours targeted in the training , only the proportion of consultations where written information ( diet sheets ) was provided to patients was significantly higher ( 13 % higher , 95 % confidence interval [ CI = 4 to 21 , P = 0.004 ) in the intervention practice s post-training . Some evidence of improved practitioner knowledge and attitude was detected . CONCLUSION This evaluation of a nutrition training intervention detected only a limited impact on the behaviour , knowledge , and attitudes of primary care practitioners in dietary consultations PURPOSE Several r and omized trials have found that discharge planning improves outcomes for hospitalized patients . We do not know if adding a clinical nurse specialist ( CNS ) to physician teams in hospitals that already have discharge planning services makes a difference . METHODS In 2 teaching hospitals , patients were r and omly assigned to regular hospital care or care with a clinical nurse specialist . The clinical nurse specialist facilitated hospital care by retrieving preadmission information , arranging in-hospital consultations and investigations , organizing postdischarge follow-up visits , and checking up on patients postdischarge with a telephone call . In-hospital outcomes included mortality and length of stay . Postdischarge outcomes included time to readmission or death , patient satisfaction , and the risk of adverse event . Adverse events were poor outcomes due to medical care rather than the natural history of disease . RESULTS A total of 620 sequential patients were r and omized ( CNS n = 307 , control n = 313 ) , of which 361 were followed after discharge from hospital ( CNS n = 175 , control n = 186 ) . The groups were similar for the probability of in-hospital death ( CNS 9.3 % vs control 9.7 % ) or being discharged to the community ( 58.0 % vs 60.0 % ) . The groups did not differ for postdischarge outcomes including readmission or death ( 21.6 % vs 15.6 % ; P = 0.16 ) or risk of adverse event ( 23.6 % vs 22.8 % ) . Mean [ SD ] patient ratings of overall quality of care on a scale of 10 was higher in the clinical nurse specialist group ( 8.2 [ 2.2 ] vs 7.6 [ 2.4 ] ; P = 0.052 ) . CONCLUSION The addition of a clinical nurse specialist to a medical team improved patient satisfaction but did not impact hospital efficiency or patient safety Objective : To add a team training and human error curriculum to the Neonatal Resuscitation Program ( NRP ) and measure its effect on teamwork . We hypothesized that teams that received the new course would exhibit more teamwork behaviors than those in the st and ard NRP course . Study design : Interns were r and omized to receive NRP with team training or st and ard NRP , then video recorded when they performed simulated resuscitations at the end of the day-long course . Outcomes were assessed by observers blinded to study arm allocation and included the frequency or duration of six team behaviors : inquiry , information sharing , assertion , evaluation of plans , workload management and vigilance . Result : The interns in the NRP with team training group exhibited more frequent team behaviors ( number of episodes per minute ( 95 % CI ) ) than interns in the control group : information sharing 1.06 ( 0.24 , 1.17 ) vs 0.13 ( 0.00 , 0.43 ) ; inquiry 0.35 ( 0.11 , 0.42 ) vs 0.09 ( 0.00 , 0.10 ) ; assertion 1.80 ( 1.21 , 2.25 ) vs 0.64 ( 0.26 , 0.91 ) ; and any team behavior 3.34 ( 2.26 , 4.11 ) vs 1.03 ( 0.48 , 1.30 ) ( P-values < 0.008 for all comparisons ) . Vigilance and workload management were practice d throughout the entire simulated code by nearly all the teams in the NRP with team training group ( 100 % for vigilance and 88 % for workload management ) vs only 53 and 20 % of the teams in the st and ard NRP . No difference was detected in the frequency of evaluation of plans . Conclusion : Compared with the st and ard NRP , NRP with a teamwork and human error curriculum led interns to exhibit more team behaviors during simulated resuscitations OBJECTIVE : To assess the effect of a physician and pharmacist teamwork approach to uncontrolled hypertension in a medical resident teaching clinic , for patients who failed to meet the recommended goals of the fifth Joint National Commission on Detection , Evaluation and Treatment of High Blood Pressure . HYPOTHESIS : Physician and pharmacist teamwork can improve the rate of meeting national blood pressure goals in patients with previously uncontrolled hypertension . DESIGN : A single-blinded r and omized controlled trial lasting 6 months . SETTING : A primary care outpatient teaching clinic . PATIENTS : A sample of 95 adult hypertensive patients who failed to meet national blood pressure goals based on three consecutive visits over a 6-month period . INTERVENTION : Patients were r and omly assigned to a control arm of st and ard medical care or to an intervention arm in which a physician and pharmacist worked together as a team . MAIN RESULTS : At study completion , the percentage of patients achieving national goals due to intervention was more than double the percentage in the control arm ( 55 % vs 20 % , p < .001 ) . Systolic blood pressure declined 23 mm Hg in the intervention arm versus 11 mm Hg in the control arm ( p < .01 ) . Diastolic blood pressure declined 14 and 3 mm Hg in the intervention and control arms , respectively ( p < .001 ) . The intervention worked equally as well in men and women and demonstrated noticeable promise in a minority of mixed-ancestry Hawaiians in whom hypertension is of special concern . CONCLUSIONS : Patients who fail to achieve national blood pressure goals under st and ard outpatient medical care may benefit from a program that includes a physician and pharmacist teamwork approach OBJECTIVE to evaluate whether integrated care pathways improve the processes of care in stroke rehabilitation . DESIGN comparison of processes of care data collected in a r and omized controlled trial . PARTICIPANTS acute stroke patients undergoing rehabilitation r and omized to receive integrated care pathways management ( n=76 ) or conventional multidisciplinary care ( n=76 ) . MEASUREMENTS proportion of patients meeting recommended st and ards for processes of care using a vali date d stroke audit tool . RESULTS integrated care pathways methodology was associated with higher frequency of stroke specific assessment s , notably testing for inattention ( 84 % versus 60 % ; P=0.015 ) and nutritional assessment ( 74 % versus 22 % , P<0.001 ) . Documentation of provision of certain information to patients /carers ( 89 % versus 70 % ; P=0.024 ) and early discharge notification to general practitioners ( 80 % versus 45 % ; P<0.001 ) were also more common in this group . There were no significant differences in the processes of interdisciplinary co-ordination and patient management between the integrated care pathways group and the control group . CONCLUSION integrated care pathways may improve assessment and communication , even in specialist stroke setting 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 Background and Purpose — To compare a community-based multidisciplinary stroke team ( CST ) approach with hospital-based rehabilitation in terms of hospital stay , functioning , quality of life , and service use and costs . Methods — Stroke patients who met pre-agreed criteria were allocated r and omly to the CST service ( n=59 ) or to usual inpatient rehabilitation and follow-up care ( n=54 ) . Assessment s were completed at r and omization and 12 months later . Caregiver strain and satisfaction ( n=55 ) were also assessed . Cost data were collected for a sub sample of 38 patients . Results — Almost 80 % of surviving patients ( n=691 ) were discharged home and a small number ( n=55 ) were readmitted . Approximately 17 % ( 113/649 ) were r and omized . There were no statistically significant differences in hospital duration , costs , or outcome measures at baseline and 12 months except for higher satisfaction reported by CST patients . Overall , both groups recorded improvement in most domains over time . Carers reported a high level of satisfaction although the level of strain among carers is cause for concern . The community group ( n=18 ) cost less than the hospital group ( n=20 ) . Conclusions — A mixed model of hospital-based and community-based rehabilitation services is likely to lead to increased patient choice and satisfaction and a potential reduction in bed pressures for less severe stroke patients BACKGROUND AND PURPOSE Integrated Care Pathway ( ICP ) is an organized , goal -defined , and time-managed plan that has the potential of facilitating timely interdisciplinary coordination , improving discharge planning , and reducing length of hospital stay . METHODS An ICP for stroke rehabilitation based on evidence of best practice , professional st and ards , and existing infrastructure was developed . Its effectiveness was tested in 152 stroke patients undergoing rehabilitation who were r and omized to receive ICP care coordinated by an experienced nurse ( n=76 ) or conventional multidisciplinary care ( n=76 ) . RESULTS The age , sex , premorbid functional ability , and stroke characteristics of the 2 groups were comparable . There were no differences in mortality rates ( 10 [ 13 % ] versus 6 [ 8 % ] ) , institutionalization ( 10 [ 13 % ] versus 16 [ 21 % ] ) , or length of hospital stay ( 50+/-19 versus 45+/-23 days ) between patients receiving ICP or multidisciplinary care . Patients receiving conventional multidisciplinary care improved significantly faster between 4 and 12 weeks ( median change in Barthel Activities of Daily Living Index 6 versus 2 ; P<0.01 ) and had higher Quality of Life scores at 12 weeks ( 65 versus 59 ; P=0.07 ) and 6 months ( 72 versus 63 ; P<0.005 ) . There were no significant differences in the mean duration of physiotherapy ( 42.8+/-41.2 versus 39.4+/-36.4 hours ) or occupational therapy ( 8.5+/-7.5 versus 8.0+/-7.5 hours ) received between the 2 groups . CONCLUSIONS ICP management offered no benefit over conventional multidisciplinary care on a stroke rehabilitation unit . Functional recovery was faster and Quality of Life outcomes better in patients receiving conventional multidisciplinary care BACKGROUND Traditional primary care practice change approaches have not led to full implementation of national asthma guidelines . OBJECTIVE To evaluate the effectiveness of 2 asthma care improvement strategies in primary care . DESIGN Two-year r and omized controlled clinical trial . SETTING Forty-two primary care pediatric practice s affiliated with 4 managed care organizations . PARTICIPANTS Children aged 3 to 17 years with mild to moderate persistent asthma enrolled in primary care practice s affiliated with managed care organizations . INTERVENTIONS Peer leader education consisted of training 1 physician per practice in asthma guidelines and peer teaching methods . Planned care combined the peer leader program with nurse-mediated organizational change through planned visits with assessment s , care planning , and self-management support , in collaboration with physicians . Analyses compared each intervention with usual care . MAIN OUTCOME MEASURES Annualized asthma symptom days , asthma-specific functional health status ( Children 's Health Survey for Asthma ) , and frequency of brief oral steroid courses ( bursts ) . RESULTS Six hundred thirty-eight children completed baseline evaluations , representing 64 % of those screened and eligible . Mean + /- SD age was 9.4 + /- 3.5 years ; 60 % were boys . Three hundred fifty ( 55 % ) were taking controller medication . Mean + /- SD annualized asthma symptom days was 107.4 + /- 122 days . Children in the peer leader arm had 6.5 fewer symptom days per year ( 95 % confidence interval [ CI ] , - 16.9 to 3.6 ) , a nonsignificant difference , but had a 36 % ( 95 % CI , 11 % to 54 % ) lower oral steroid burst rate per year compared with children receiving usual care . Children in the planned care arm had 13.3 ( 95 % CI , - 24.7 to -2.1 ) fewer symptom days annually ( -12 % from baseline ; P = .02 ) and a 39 % ( 95 % CI , 11 % to 58 % ) lower oral steroid burst rate per year relative to usual care . Both interventions showed small , statistically significant effects for 2 of 5 Children 's Health Survey for Asthma scales . Planned care subjects had greater controller adherence ( parent report ) compared with usual care subjects ( rate ratio , 1.05 [ 95 % CI , 1.00 to 1.09 ] ) . CONCLUSIONS Planned care ( nurse-mediated organizational change plus peer leader education ) is an effective model for improving asthma care in the primary care setting . Peer leader education on its own may also serve as a useful model for improving asthma care , although it is less comprehensive and the treatment effect less pronounced Background Despite a burgeoning interest in using interprofessional approaches to promote effective collaboration in health care , systematic review s find scant evidence of benefit . This protocol describes the first cluster r and omized controlled trial ( RCT ) to design and evaluate an intervention intended to improve interprofessional collaborative communication and patient-centred care . Objectives The objective is to evaluate the effects of a four-component , hospital-based staff communication protocol design ed to promote collaborative communication between healthcare professionals and enhance patient-centred care . Methods The study is a multi-centre mixed- methods cluster r and omized controlled trial involving twenty clinical teaching teams ( CTTs ) in general internal medicine ( GIM ) divisions of five Toronto tertiary-care hospitals . CTTs will be r and omly assigned either to receive an intervention design ed to improve interprofessional collaborative communication , or to continue usual communication practice s . Non-participant naturalistic observation , shadowing , and semi-structured , qualitative interviews were conducted to explore existing patterns of interprofessional collaboration in the CTTs , and to support intervention development . Interviews and shadowing will continue during intervention delivery in order to document interactions between the intervention setting s and adopters , and changes in interprofessional communication . The primary outcome is the rate of unplanned hospital readmission . Secondary outcomes are length of stay ( LOS ) ; adherence to evidence -based prescription drug therapy ; patients ' satisfaction with care ; self-report surveys of CTT staff perceptions of interprofessional collaboration ; and frequency of calls to paging devices . Outcomes will be compared on an intention-to-treat basis using adjustment methods appropriate for data from a cluster r and omized design . Discussion Pre-intervention qualitative analysis revealed that a substantial amount of interprofessional interaction lacks key core elements of collaborative communication such as self- introduction , description of professional role , and solicitation of other professional perspectives . Incorporating these findings , a four-component intervention was design ed with a goal of creating a culture of communication in which the fundamentals of collaboration become a routine part of interprofessional interactions during unstructured work periods on GIM wards . Trial registration Registered with National Institutes of Health as NCT00466297 Outcome for bipolar disorder remains suboptimal despite the availability of efficacious treatments . To improve treatment effectiveness in clinical practice , a Veterans Affairs study team created a care model conceptually similar to the lithium clinics of the 1970s but augmented by principles of more recent collaborative care models for chronic medical illnesses . This intervention consists of improving patients ' self-management skills through psychoeducation ; supporting providers ' decision making through simplified practice guidelines ; and enhancing access to care , continuity of care , and information flow through the use of a nurse care coordinator . In this article , which is part I of a two-part report , the authors summarize the conceptual background and development of the intervention , describe the design of a three-year , 11-site r and omized effectiveness trial , and report data describing its successful implementation . Trial design emphasized aspects of effectiveness to support generalizability of the findings and eventual dissemination of the intervention . Part II ( see companion article , this issue ) reports clinical , functional , and overall cost outcomes of the trial Background Despite much interest in the development of liaison psychiatry in general practice there is no clear evidence that any form of intervention is effective . We carried out a pilot r and omised controlled trial , the first we believe into this type of care , of one such model ; enhanced liaison with individual patients by key workers , in general practice s in Paddington and North Kensington in London . Methods All patients referred from primary to secondary psychiatric care from four general practice s over a 10-month period , and still in contact with services , were eligible to be included in the study . The practice s were allocated in a constrained r and omised procedure to either normal care or enhanced key-worker liaison . The latter involved encouraging individual key workers to adopt improved communication between primary and secondary care . Baseline assessment s of symptomatology and social functioning were made before r and omisation and after 6 months by an independent research er . Results Of the 84 eligible patients , 43 were seen at baseline and 34 re-assessed after 6 months . There was no difference between the clinical outcomes in the two groups but self-rated social function was significantly improved in the enhanced liaison service compared with st and ard care ( adjusted P = 0.05 ) . Costs were similar but somewhat more expensive for enhanced liaison . Less than half ( 42 % ) of all key workers in the enhanced liaison arm felt they had involved the primary health care team more in the care of their patient , with 21 % of these altering their practice markedly during the study . Conclusions It is concluded that without additional re sources enhanced key-worker liaison for psychiatry in primary and secondary care has limited benefits although this does not necessarily apply to other forms of liaison practice A small , controlled trial of joint treatment of childhood asthma by a doctor , a physiotherapist , a psychologist , and a social worker , working together in the family setting , demonstrated an improvement in ventilatory capacity . The limited scope of this trial does not permit more general conclusions as to the effect of such treatment on the severity and frequency of attacks , but the observation that some measurable physiological improvement occurred suggests that the place of multidisciplinary nonpharmaceutical management of childhood asthma should be investigated in more detail Primary objective : Thirteen ( 10 males ) participants with severe acquired brain injuries ( ABI ) were r and omly assigned to two treatments , A or B ( ABAB , BABA ) in a crossover study to determine which treatment approach elicited more consistent and reliable yes/no responses . Research design : Treatment A consisted of an enriched stimulus environment , collaborative multidisciplinary interventions and additional yes/no response training , while Treatment B consisted of the st and ard hospital environment and interventions . Main outcomes : An ANOVA showed no order effect ( AB vs BA ; p ¼ 0:60 ) , but a trend ( A vs B ; p ¼ 0:07 ) towards statistical significance for increased responsiveness with treatment A. Inter-rater reliability ( n ¼ 10 ) ranged from fair-to-good , intra class correlation ( ICC ) 0.51 ; 95 % confidence interval ( CI ) ( 0.29–0.93 ) . Post-hoc analyses showed statistically significant increased responsiveness for four participants with treatment A ( p < 0:001 ) . Conclusion : Evidence is provided that enhanced communication strategies can improve responsiveness in a sub-group of participants with severe acquired brain injuries This report describes the findings of a r and omized study of a new team approach to home care for homebound chronically or terminally ill elderly . The team includes a physician , nurse practitioner , and social worker delivering primary health care in the patient 's home , including physician house calls . Weekly team conferences assure coordination of patient care . The team is available for emergency consultation through a 24-hour telephone service . The team physician attends to the patient during necessary hospitalizations . This approach was evaluated in a r and omized experimental design study measuring its impact on health care utilization , functional changes in patients , and patient and caretaker satisfaction . The team patients had fewer hospitalizations , nursing home admissions , and outpatient visits than the controls . They were more often able to die at home , if this was their wish . As expected , they used more in-home services , measured in weighted cost figures ; their overall cost was lower than their controls , but the difference was not statistically significant . Their functional abilities did not change differently from the controls , but they , and especially their informal caretakers in the home , expressed significantly higher satisfaction with the care received BACKGROUND Hospitalization often marks the beginning , and may be partially responsible for , a downward trajectory characterized by declining function , worsening quality of life , placement in a long term care facility , and death . At the University Hospitals of Clevel and , an Acute Care for Elders ( ACE ) unit that reengineered the process of caring for older patients ( > or = 70 years of age ) to improve functional outcomes was established in September 1990 . DESCRIPTION OF INTERVENTION The general principles of ACE included an approach to care guided by the biopsychosocial model and recognition of the importance of fitting the hospital environment to the patient 's needs . The design of the intervention was consistent with principles of comprehensive geriatric assessment and continuous quality improvement . Care , which focused on maintaining function , was directed by an interdisciplinary team that considered the patient 's needs both at home and in the hospital . The major components of the ACE Unit intervention included patient-centered nursing care ( daily assessment of functional needs by nursing , nursing-based protocol s to improve outcomes , daily rounds by a multidisciplinary team ) , a prepared environment , planning for discharge , and medical care review . RESULTS In a r and omized trial comparing ACE with usual care , patients receiving ACE had improved functional outcomes at discharge . The costs to the hospital for ACE unit care were less than for usual care . The functional status of ACE and usual care patients was similar 90 days after discharge . FUTURE DIRECTIONS The ACE unit intervention is being exp and ed to preserve the improvements observed during the hospitalization in the outpatient setting . In addition , needs other than function which are critical to patients ' long-term quality of life are being considered OBJECTIVE : To evaluate the effect of teamwork training on the occurrence of adverse outcomes and process of care in labor and delivery . METHODS : A cluster-r and omized controlled trial was conducted at seven intervention and eight control hospitals . The intervention was a st and ardized teamwork training curriculum based on crew re source management that emphasized communication and team structure . The primary outcome was the proportion of deliveries at 20 weeks or more of gestation in which one or more adverse maternal or neonatal outcomes or both occurred ( Adverse Outcome Index ) . Additional outcomes included 11 clinical process measures . RESULTS : A total of 1,307 personnel were trained and 28,536 deliveries analyzed . At baseline , there were no differences in demographic or delivery characteristics between the groups . The mean Adverse Outcome Index prevalence was similar in the control and intervention groups , both at baseline and after implementation of teamwork training ( 9.4 % versus 9.0 % and 7.2 % versus 8.3 % , respectively ) . The intracluster correlation coefficient was 0.015 , with a result ant wide confidence interval for the difference in mean Adverse Outcome Index between groups ( –5.6 % to 3.2 % ) . One process measure , the time from the decision to perform an immediate cesarean delivery to the incision , differed significantly after team training ( 33.3 minutes versus 21.2 minutes , P=.03 ) . CONCLUSION : Training , as was conducted and implemented , did not transfer to a detectable impact in this study . The Adverse Outcome Index could be an important tool for comparing obstetric outcomes within and between institutions to help guide quality improvement . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00381056 LEVEL OF EVIDENCE : BACKGROUND This r and omized controlled trial tested the effectiveness of comprehensive , interdisciplinary postdischarge care management in improving a profile of indicators of health recovery and secondary prevention ( profile of health and prevention ) in stroke and transient ischemic attack ( TIA ) patients . METHODS Ninety-six stroke/TIA patients were r and omized to usual care or intervention at discharge from our acute stroke unit . The intervention group received an in-home biopsychosocial assessment by an advanced practice nurse at 1 month . A care plan was developed by an interdisciplinary team and implemented in collaboration with the patient 's primary care physician . The profile of health and prevention , measured at 3 months , was comprised of 5 domains : ( 1 ) Neuromotor Function , ( 2 ) Severe Complications , ( 3 ) Quality of Life , ( 4 ) Management of Risk for common poststroke complications and recurrent stroke , and ( 5 ) Stroke Knowledge . A single global hypothesis test across multiple end points was used to compare the 2 groups . RESULTS The intervention significantly improved the profile of health and prevention ( P < .0001 ) . In addition , each domain showed a positive effect of the intervention . Effect sizes ( in st and ard deviation units ) of the intervention on domains were .1 for Neuromotor Function ( 90 % confidence interval [ CI ] = -.3 to .5 ) ; .4 for Severe Complications ( 90 % CI = .1 to .8 ) ; .5 for Quality of Life ( 90 % CI = .1 to .9 ) ; .6 for Management of Risk for common poststroke complications and recurrent stroke ( 90 % CI = .3 to 1 . ) ; and 1.0 for Stroke Knowledge ( 90 % CI = .6 to 1.4 ) . CONCLUSIONS This model of care management result ed in a significantly better profile of health and prevention for stroke/TIA patients 3 months postdischarge To measure the effects of a collaborative care model that emphasized the role of clinical pharmacists in providing drug therapy management and treatment follow-up to patients with depression , we conducted a r and omized controlled trial at a staff model health maintenance organization . We compared the outcomes of subjects treated in this collaborative care model ( 75 patients , intervention group ) with subjects receiving usual care ( 50 patients , control group ) . After 6 months , the intervention group demonstrated a significantly higher drug adherence rate than that of the control group ( 67 % vs 48 % , odds ratio 2.17 , 95 % confidence interval 1.04 - 4.51 , p=0.038 ) . Patient satisfaction was significantly greater among members r and omly assigned to pharmacists ' services than among controls , and provider satisfaction surveys revealed high approval rates as well . Changes in re source utilization were favorable for the intervention group , but differences from the control group did not achieve statistical significance . Clinical improvement was noted in both groups , but the difference was not significant . Clinical pharmacists had a favorable effect on multiple aspects of patient care . Future studies of this model in other health care setting s appear warranted PURPOSE The purpose of this study was to demonstrate the potential value of close collaboration at the office level of a nurse care manager with community-based primary care physicians in the care of adult patients with type 2 diabetes , particularly those physicians not affiliated with an integrated care system that some managed care organizations provide . METHODS Patients with type 2 diabetes were recruited from the general population of a large metropolitan area . Each received a comprehensive evaluation of his or her diabetes with results reported to patients and their physicians ( basic intervention ) . A r and om one-half of patients were additionally assigned to individual counseling , problem identification , care planning , and management recommendations by a nurse care manager ( individualized intervention ) . The patients receiving only the basic intervention served as the control group to those receiving the individualized intervention . Re-evaluation of all patients at 6 months after their entry into the study determined the effectiveness of the nurse-directed individualized intervention using A1C , blood pressure , and cholesterol as outcome measures . RESULTS Of 220 patients recruited , 197 had type 2 diabetes , r and omly assigned only the basic intervention ( 102 patients ) or individualized intervention ( 95 patients ) . Postintervention data were obtained on 164 patients ( 83 % ) . Significant improvement occurred in mean systolic blood pressure and A1C of all patients in the individualized but not the basic intervention only group . Patients with a systolic blood pressure > or=130 mm Hg at baseline showed improvement if they had more than 2 contacts with the study nurse but not if they had less than 2 contacts . CONCLUSIONS A nurse care manager collaborating at the office level with community-based primary care physicians can enhance the care provided to adult patients with type 2 diabetes . For those many physicians not affiliated with an integrated care system featured by some managed care organizations , this collaboration could underlie a team approach ( nurse/patient/physician ) for the ambulatory patient with diabetes that would be an essential element in a chronic disease model of care for diabetes at the community level OBJECTIVE : To develop a pharmacist intervention to improve depression care and outcomes within a primary care setting . METHODS : Pragmatic , r and omized trial of a clinical pharmacist collaborative care intervention versus usual care in a busy , academic family practice clinic . RESULTS : Seventy-four patients diagnosed with a new episode of major depression and started on antidepressant medications were r and omized to enhanced care ( EC ) or usual care ( UC ) groups . EC consists of a clinical pharmacist collaborating with primary care providers ( PCPs ) to facilitate education , initiation , and titration of acute-phase antidepressant treatment to monitor treatment adherence and to prevent relapse . Control patients receive UC by their PCP . The main end point is reduction of depression symptoms over time as measured by the Hopkins Symptom Checklist ( SCL-20 ) . Other outcomes include the Diagnostic and Statistical Manual of Mental Disorders , ( DSM-IV ) criteria for major depression , health-related quality of life measured by the Medical Outcomes Study Short Form 12 ( SF-12 ) , medication adherence , patient satisfaction , and healthcare utilization . The main end point and the cost of treating major depression will be used to estimate the cost-effectiveness of the collaborative care model . CONCLUSIONS : The study is a unique , ongoing trial that may have important implication s for the treatment of depression in primary care setting s as well as new roles for clinical pharmacists Objective : Few older minorities receive adequate treatment of depression in primary care . This study examines whether a collaborative care model for depression in primary care is as effective in older minorities as it is in nonminority elderly patients in improving depression treatment and outcomes . Study Design : A multisite r and omized clinical trial of 1801 older adults comparing collaborative care for depression with treatment as usual in primary care . Twelve percent of the sample were black ( n = 222 ) , 8 % were Latino ( n = 138 ) , and 3 % ( n = 53 ) were from other minority groups . We compared the 3 largest ethnic groups ( non-Latino white , black , and Latino ) on depression severity , quality of life , and mental health service use at baseline , 3 , 6 , and 12 months after r and omization to collaborative care or usual care . Principal Findings : Compared with care as usual , collaborative care significantly improved rates and outcomes of depression care in older adults from ethnic minority groups and in older whites . At 12 months , intervention patients from ethnic minorities ( blacks and Latinos ) had significantly greater rates of depression care for both antidepressant medication and psychotherapy , lower depression severity , and less health-related functional impairment than usual care participants ( 64 % , 95 % confidence interval [ CI ] 55–72 versus 45 % , CI 36–55 , P = 0.003 for antidepressant medication ; 37 % , CI 28–47 versus 13 % , CI 6–19 , P = 0.002 for psychotherapy ; mean = 0.9 , CI 0.8–1.1 versus mean = 1.4 , CI 1.3–1.5 , P < 0.001 for depression severity , range 0–4 ; mean = 3.7 , CI 3.2–4.1 , versus mean = 4.7 , CI 4.3–5.1 , P < 0.0001 for functional impairment , range 0–10 ) . Conclusions : Collaborative Care is significantly more effective than usual care for depressed older adults , regardless of their ethnicity . Intervention effects in ethnic minority participants were similar to those observed in whites The purpose of this study is to examine effects of a nurse-physician collaborative approach to care of patients with type 2 diabetes and to determine possible effect sizes for use in computing sample sizes for a larger study . Forty patients from a family practice clinic with type 2 diabetes were r and omly assigned to control or experimental groups . The control group received st and ard care , whereas the experimental group received st and ard care plus home visits from a nurse , as well as consultation with an exercise specialist and /or nutritionist . Follow-up continued for 3 months . Clinical end points included st and ard measures of diabetes activity as well as quality -of-life indicators . Focus group interviews were used to explore patients ’ responses to the program . Although findings were not statistically significant , a trend toward small to moderate positive effect sizes was found in glycosylated hemoglobin and blood pressure . Quality oflife measures also showed a trend toward small to moderate , but nonsignificant , improvements in physical functioning , bodily pain , vitality , social and global functioning , energy , impact of diabetes , and health distress . Focus group interviews indicated a very positive response from patients , who expressed feelings of empowerment . In this study , patients treated with nurse-physician collaboration demonstrated small , but nonsignificant , improvements in blood chemistry after only 3 months . Physical and social functioning , energy , and bodily pain also showed a small improvement . Changes in awareness of effects of diabetes on health and an expressed sense of self-efficacy suggest that effects could be sustainable over the longer term Purpose To describe how communication failures contribute to many medical mishaps . Method In late 1999 , a sample of 26 residents stratified by medical specialty , year of residency , and gender was r and omly selected from a population of 85 residents at a 600-bed U.S. teaching hospital . The study design involved semistructured face-to-face interviews with the residents about their routine work environments and activities , the medical mishaps in which they recently had been involved , and a description of both the individual and organizational contributory factors . The themes reported here emerged from inductive analyses of the data . Results Residents reported a total of 70 mishap incidents . Aspects of “ communication ” and “ patient management ” were the two most commonly cited contributing factors . Residents described themselves as embedded in a complex network of relationships , playing a pivotal role in patient management vis-à-vis other medical staff and health care providers from within the hospital and from the community . Recurring patterns of communication difficulties occur within these relationships and appear to be associated with the occurrence of medical mishaps . Conclusion The occurrence of everyday medical mishaps in this study is associated with faulty communication ; but , poor communication is not simply the result of poor transmission or exchange of information . Communication failures are far more complex and relate to hierarchical differences , concerns with upward influence , conflicting roles and role ambiguity , and interpersonal power and conflict . A clearer underst and ing of these dynamics highlights possibilities for appropriate interventions in medical education and in health care organizations aim ed at improving patient safety Admitting patients with fractured neck of femur using fast tracking procedure is well established in over 75 % of hospitals in the United Kingdom . A retrospective study on 143 patients admitted using such procedure revealed inadequacies in the system . Although the waiting time in the Accident and Emergency Department ( A&E ) was reduced , it did not contribute much to the other aspects of patients outcome . We conducted a prospect i ve trial using a multidisciplinary integrated care pathway ( ICP ) for the management of patients with fractured neck of femur . The objective of this study was to assess the effect of this protocol on the outcome compared to the earlier findings . The outcomes measured were admission time , time to surgery , length of in-hospital stay , cancellations , and 30-day mortality . The results showed a significant reduction in the length of hospital stay ( P = 0.001 ) . The 30-day mortality ( P = 0.056 ) and number of patients operated within 24 h of admission were better ( P = 0.048 ) but not significant . There was no difference in the time to admission to orthopaedic ward and other related complications between the two groups . This study has shown that a multidisciplinary care pathway for management of patients with fractured neck of femur has potential benefits Background : There is evidence to support both the use of intravenous methylprednisolone ( IVMP ) in multiple sclerosis ( MS ) relapse and physiotherapy in the management of MS , but no studies have investigated the combination of steroids and rehabilitation together . Objectives : To evaluate the benefits of IVMP with planned , comprehensive multidisciplinary team ( MDT ) care compared to IVMP with st and ard care . Methods : In this r and omised controlled trial , patients confirmed to have had a definite MS relapse severe enough to warrant IVMP ( 1 g daily for three days ) were r and omised to two groups . The control group was managed according to the st and ard ward routine ; the treatment group received planned coordinated multidisciplinary team assessment and treatment . Baseline assessment s , including demographics and Exp and ed Disability Status Scale ( EDSS ) were carried out on both groups . The primary outcome measures were Guy ’s Neurological Disability Scale ( GNDS ) , and Amended Motor Club Assessment ( AMCA ) . The secondary measures were the Barthel Index ( BI ) , Human Activity Profile ( HAP ) , and Short Form Item 36 Health Survey ( SF-36 ) . All measures have published data on reliability and validity . Measures were administered at one and three months . Results : Forty subjects , including 27 females , completed data collection . There were no significant differences between the two groups at baseline . Results showed statistically significant differences in GNDS ( p = 0.03 ) , AMCA ( p = 0.03 ) , HAPM ( p < 0.01 ) , HAPA ( p = 0.02 ) , and BI ( p = 0.02 ) at three months in favour of planned MDT care . Conclusion : This study indicates that combining steroids with planned MDT care is superior to administering them in a st and ard neurology or day ward setting . Further research is necessary in order to confirm this finding OBJECTIVE To assess the effect of a total quality management ( TQM ) approach on the appropriateness of clinical laboratory testing of patients with acute myocardial infa rct ion . DESIGN Retrospective , control-group , quasi-experimental study . SETTING Two metropolitan teaching hospitals : one involved in the intervention ( TQM experimental group ) ; the other had no intervention ( control group ) . INTERVENTION A multidisciplinary team involved in the development of improvement strategies , including laboratory testing guidelines , education programs , data collection , monitoring and feedback . OUTCOME MEASURES Total number of requested clinical ly indicated and non- clinical ly indicated tests . RESULTS The proportion of clinical ly indicated tests that were requested increased from 77.5 % to 88.2 % ( P < 0.01 ) and the number of non- clinical ly indicated tests was reduced by 81.7 % with the introduction of the TQM strategies ( P < 0.01 ) . CONCLUSIONS The introduction of a TQM approach has improved the appropriateness of test ordering in acute myocardial infa rct ion . The reduction in non- clinical ly indicated tests could produce substantial savings in hospital pathology costs , and the increase in clinical ly indicated tests provides better patient care Multidisciplinary case conferencing using a video-link was compared with multidisciplinary case conferencing by telephone . One hundred patients were r and omized to either videoconferencing ( intervention group , 50 patients ) or audioconferencing ( control group , 50 patients ) . The effectiveness of the intervention compared with the control was evaluated in terms of : the number of conferences per patient , average length of conference , length of treatment , number of occasions of service , degree of multidisciplinary team involvement , recorded level of communication , quality of the management plan ( in terms of the number of points contained in it ) and staff satisfaction . The intervention and control groups showed significant differences on only two of the outcome measures : the mean number of case conferences per patient was less for the intervention group , and the intervention group had a shorter length of treatment ( 6 days ) than the control group ( 10 days ) . The study did not demonstrate any significant differences in occasions of service or time commitment , which might have result ed in lower costs . However , the introduction of case conferencing by video-link was accompanied by a high level of satisfaction on the part of the 14 team members who were interviewed This 24-month exploratory study evaluated whether a 6-month programme supported by a trained external facilitator was feasible , acceptable and led to the adoption of a multidisciplinary approach to audit by secondary care staff . Undertaken in five acute hospital sites in the East Midl and s UK , 22 multidisciplinary teams were r and omised to either an intervention or control arm . Employing mixed methods , a range of outcomes , including collaborative behaviour , was measured . The intervention was feasible and acceptable to staff . Involvement in the facilitated programme had a positive impact on self-reported knowledge ( P=0.000 post-intervention and at 4-months follow-up ) , skills ( P=0.000 post-intervention and P=0.02 at 4-months follow-up ) and attitudes ( P<0.01 post-intervention ) , appeared to have some influence on improving self-reported ( P<0.05 post-intervention ) and observed collaborative behaviour ( P=0.01 ) and led to better quality audit result ing in measurable improvements to care . Improved collaborative behaviour may have result ed from an increase in assertive behaviour by nurses . Research to test approaches to support teams to work effectively together is currently hampered by a lack of suitable research instruments and needs addressing before main ( phase 111 ) trials are undertaken OBJECTIVE The objective of this study was to determine the effectiveness of a training to increase collaboration between general practitioners and occupational health physicians in the treatment of patients with low back pain ( LBP ) because more collaboration might improve a patient 's recovery and shorten sick leave . METHODS In a controlled trial , the intervention in one region was compared with usual care in a control region . Participating physicians enrolled patients with LBP on sick leave for 3 - 12 weeks . Patients filled out three question naires : at inclusion , at 3 months , and at 6 months . Information on sick leave was gathered from occupational health services . All analyses were performed on an intention-to-treat basis . RESULTS Fifty-six patients with LBP were enrolled in each region . There was little collaboration between physicians during the project . Patients in the intervention region returned to work significantly later ( P=.005 ) but were significantly more satisfied with their occupational health physician ( P=.01 ) . No differences were found between the intervention and control patients for pain , disability , quality of life , and medical consumption . CONCLUSION Our study does not show a positive effect of the training to increase collaboration between general practitioners and occupational health physicians . The training may not have improved collaboration enough to influence the prognosis of LBP OBJECTIVES To compare outcomes between stroke patients managed on the stroke unit , on general wards with stroke team support or at home by specialist domiciliary team and to derive prognostic variables that will identify patients most suitable for management by each strategy . To describe organisational aspects of individual strategies of stroke care and to evaluate cost-effectiveness of each strategy and its acceptability to patients , carers and professionals . DESIGN Prospect i ve single-blind r and omised controlled trial undertaken in patients recruited from a community-based stroke register . SETTING Suburban district in south-east Engl and . PARTICIPANTS Patients with disabling stroke who could be supported at home . INTERVENTIONS The stroke unit gave 24-hour care provided by specialist multidisciplinary team based on clear guidelines for acute care , prevention of complications , rehabilitation and secondary prevention . The stroke team provided management on general wards with specialist team support . The team undertook stroke assessment s and advised ward-based nursing and therapy staff on acute care , secondary prevention and rehabilitation aspects . Domiciliary care involved management at home under the supervision of a GP and stroke specialist with support from specialist team and community services . Support was provided for a maximum of 3 months . MAIN OUTCOME MEASURES The primary measure was death or institutionalisation at 1 year . Secondary measures were dependence , functional abilities , mood , quality of life , re source use , length of hospital stay , and patient , carer and professional satisfaction . RESULTS Of the 457 patients r and omised , 152 patients were allocated to the stroke unit ; 152 patients to stroke team and 153 patients to domiciliary stroke care ( average age 76 years , 48 % women ) . The groups were well matched for baseline characteristics , stroke type and severity , level of impairment and initial disability . Fifty-one ( 34 % ) patients in the domiciliary group were admitted to hospital after r and omisation . Mortality and institutionalisation at 1 year were lower on stroke unit compared with stroke team or domiciliary care . Significantly fewer patients on the stroke unit died compared with those managed by the stroke team . The proportion of patients alive without severe disability at 1 year was also significantly higher on the stroke unit compared with stroke team or domiciliary care . These differences were present at 3 and 6 months after stroke . Stroke survivors managed on the stroke unit showed greater improvement on basic activities of daily living compared with other strategies . Achievement of higher levels of function was not influenced by strategy of care . Quality of life at 3 months was significantly better in stroke unit and domiciliary care patients . There was greater dissatisfaction with care on general wards compared with stroke unit or domiciliary care . Poor outcome with domiciliary care and on general wards was associated with Barthel Index < 5 , incontinence and , on general wards , age over 75 years . The total costs of stroke per patient over the 12-month period were pound 11,450 for stroke unit , pound 9527 for stroke team and pound 6840 for home care . However , the mean costs per day alive for the stroke unit were significantly less than those for the specialist stroke team patients , but no different from domiciliary care patients . Costs for the domiciliary group were significantly less than for those managed by the specialist stroke team on general wards . CONCLUSIONS Stroke units were found to be more effective than a specialist stroke team or specialist domiciliary care in reducing mortality , institutionalisation and dependence after stroke . A role for specialist domiciliary services for acute stroke is not supported by this study . Management of patients with strokes on general medical wards , even with specialist team input , is not supported by this study . The stroke unit intervention was less costly per patient day alive and more effective than the stroke team intervention . The stroke unit was more effective and of equivalent cost when compared to home care . Hence , the stroke unit is a more cost-effective intervention than either stroke team or home care . Further research is needed to underst and processes contributing to the reduction in mortality on stroke units and to determine the generalisability of these results and the factors that will influence the implementation of the findings of this study in clinical practice In a rheumatology department , 2 r and omized groups of female out patients with rheumatoid arthritis were studied prospect ively for 1 year . The outcome of multidisciplinary team care ( T group , 31 patients ) was compared with that of regular outpatient clinic care ( NT group , 28 patients ) . Pharmacologic treatment and orthopedic specialist consultations were similar in both groups , but use of paramedical care was higher in the T group . Outcome measures of disease activity , specific joint function , and self-rated physical discomfort disclosed no significant differences between the 2 groups . Mental well-being increased in the T group . Overall health , measured by the Sickness Impact Profile , improved significantly only in the T group . This improvement was also significant compared with the NT group OBJECTIVES To measure the effects of outpatient geriatric evaluation and management ( GEM ) on high-risk older persons ' functional ability and use of health services . DESIGN R and omized clinical trial . SETTING Ambulatory clinic in a community hospital . PARTICIPANTS A population -based sample of community-dwelling Medicare beneficiaries age 70 and older who were at high risk for hospital admission in the future ( N = 568 ) . INTERVENTION Comprehensive assessment followed by interdisciplinary primary care . MEASUREMENTS Functional ability , restricted activity days , bed disability days , depressive symptoms , mortality , Medicare payments , and use of health services . Interviewers were blinded to participants ' group status . RESULTS Intention-to-treat analysis showed that the experimental participants were significantly less likely than the controls to lose functional ability ( adjusted odds ratio ( aOR ) = 0.67 , 95 % confidence interval ( CI ) = 0.47 - 0.99 ) , to experience increased health-related restrictions in their daily activities ( aOR = 0.60 , 95 % CI = 0.37 - 0.96 ) , to have possible depression ( aOR = 0.44 , 95 % CI = 0.20 - 0.94 ) , or to use home healthcare services ( aOR = 0.60 , 95 % CI = 0.37 - 0.92 ) during the 12 to 18 months after r and omization . Mortality , use of most health services , and total Medicare payments did not differ significantly between the two groups . The intervention cost $ 1,350 per person . CONCLUSION Targeted outpatient GEM slows functional decline BACKGROUND Over the past 20 years , both inpatient units and outpatient clinics have developed programs for geriatric evaluation and management . However , the effects of these interventions on survival and functional status remain uncertain . METHODS We conducted a r and omized trial involving frail patients 65 years of age or older who were hospitalized at 11 Veterans Affairs medical centers . After their condition had been stabilized , patients were r and omly assigned , according to a two-by-two factorial design , to receive either care in an inpatient geriatric unit or usual inpatient care , followed by either care at an outpatient geriatric clinic or usual outpatient care . The interventions involved teams that provided geriatric assessment and management according to Veterans Affairs st and ards and published guidelines . The primary outcomes were survival and health-related quality of life , measured with the use of the Medical Outcomes Study 36-Item Short-Form General Health Survey ( SF-36 ) , one year after r and omization . Secondary outcomes were the ability to perform activities of daily living , physical performance , utilization of health services , and costs . RESULTS A total of 1388 patients were enrolled and followed . Neither the inpatient nor the outpatient intervention had a significant effect on mortality ( 21 percent at one year overall ) , nor were there any synergistic effects between the two interventions . At discharge , patients assigned to the inpatient geriatric units had significantly greater improvements in the scores for four of the eight SF-36 subscales , activities of daily living , and physical performance than did those assigned to usual inpatient care . At one year , patients assigned to the outpatient geriatric clinics had better scores on the SF-36 mental health subscale , even after adjustment for the score at discharge , than those assigned to usual outpatient care . Total costs at one year were similar for the intervention and usual-care groups . CONCLUSIONS In this controlled trial , care provided in inpatient geriatric units and outpatient geriatric clinics had no significant effects on survival . There were significant reductions in functional decline with inpatient geriatric evaluation and management and improvements in mental health with outpatient geriatric evaluation and management , with no increase in costs OBJECTIVES To study the effects of comprehensive geriatric assessment ( CGA ) and multidisciplinary intervention on elderly patients sent home from the emergency department ( ED ) . DESIGN Prospect i ve , r and omized , controlled trial with 18 months of follow-up . SETTING Large medical school-affiliated public hospital in an urban setting in Sydney , Australia . PARTICIPANTS A total of 739 patients aged 75 and older discharged home from the ED were r and omized into two groups . INTERVENTION Patients r and omized to the treatment group underwent initial CGA and were followed at home for up to 28 days by a hospital-based multidisciplinary outreach team . The team implemented or coordinated recommendations . The control group received usual care . MEASUREMENTS The primary outcome measure was all admissions , to the hospital within 30 days of the initial ED visit . Secondary outcome measures were elective and emergency admissions , and nursing home admissions and mortality . Additional outcomes included physical function ( Barthel Index ( total possible score=20 ) and instrumental activities of daily living ( /12 ) and cognitive function ( mental status question naire ( /10 ) ) . RESULTS Intervention patients had a lower rate of all admissions to the hospital during the first 30 days after the initial ED visit ( 16.5 % vs 22.2 % ; P=.048 ) , a lower rate of emergency admissions during the 18-month follow-up ( 44.4 % vs 54.3 % ; P=.007 ) , and longer time to first emergency admission ( 382 vs 348 days ; P=.011 ) . There was no difference in admission to nursing homes or mortality . Patients r and omized to the intervention group maintained a greater degree of physical and mental function ( Barthel Index change from baseline at 6 months : -0.25 vs -0.75 ; P<.001 ; mental status question naire change from baseline at 12 months : -0.21 vs -0.64 ; P<.001 ) . CONCLUSION CGA and multidisciplinary intervention can improve health outcomes of older people at risk of deteriorating health and admission to hospital . Patients aged 75 and older should be referred for CGA after an ED visit BACKGROUND There is a lack of evidence on the most effective primary care management of older people with minor depression . AIM To evaluate a follow-up assessment by the community mental health team ( CMHT ) for older people with depressive symptoms identified by practice nurses at a health check for people over the age of 75 years . DESIGN OF STUDY A pragmatic r and omised controlled trial . SETTING A single large general practice in Leicestershire . METHOD Patients receiving a health check administered by a practice nurse and scoring 5 or more on the 15-item Geriatric Depression Scale ( GDS15 ) were r and omised to either follow-up by the CMHT or routine general practitioner ( GP ) care . The GDS15 score was measured at the subsequent health check 18 months later . RESULTS Forty-seven patients were r and omised to CMHT assessment and 46 to routine GP care . Uptake of the intervention was 72 % ( n = 34 ) . At the follow-up health check a greater proportion of the control group had improved GDS15 scores ( P = 0.08 ) . Following assessment , the CMHT recommended their further involvement in the care of 12 patients and this was authorised by patients ' GPs in six cases . CONCLUSIONS A follow-up mental health assessment by a member of the local CMHT was not effective in improving outcomes for mildly depressed older people . Other than r and om error possible reasons for this include the length of follow-up and a failure to meet raised expectations among the intervention group . If complex referral procedures do not improve outcomes for this group , then specialist community services should play a more prominent part in the training of practice staff to care for their depressed older patients OBJECTIVE To evaluate the impact of regular multidisciplinary team interventions on the quantity and quality of psychotropic drug prescribing in Swedish nursing homes . DESIGN A r and omized controlled trial . SETTING A sample of 33 nursing homes : 15 experimental homes and 18 control homes representing 5 % of all Swedish nursing homes . PARTICIPANTS The sample consisted of 1854 long-term care residents with an average age of 83 years . Seventy percent of the residents were women , and 42 % had a documented diagnosis of dementia . An additional 5 % had a psychotic disorder , and 7 % had a diagnosis of depression . INTERVENTION Experimental homes participated in an outreach program that was design ed to influence drug use through improved teamwork among physicians , pharmacists , nurses , and nurses ' assistants . Multidisciplinary team meetings were held on a regular basis throughout the 12-month study period . MEASUREMENTS Lists of each resident 's prescriptions were collected 1 month before and 1 month after the 12-month intervention . Measures included the proportion of residents with any psychotropic drug , polymedicine , and therapeutic duplication and proportion of residents with nonrecommended and acceptable drugs in each psychotropic drug class , as defined by current Swedish guidelines . RESULTS Baseline results show extensive psychotropic drug prescribing , with the most commonly prescribed drugs being hypnotics ( 40 % ) , anxiolytics ( 40 % ) , and antipsychotics ( 38 % ) . After 12 months of team meetings in the experimental homes , there was a significant decrease in the prescribing of psychotics ( -19 % ) , benzodiazepine hypnotics ( -37 % ) , and antidepressants ( -59 % ) . Orders for more acceptable antidepressants also increased in the experimental homes . In the control homes there was increased use of acceptable antidepressants , but there were no significant reductions in other drug classes . CONCLUSIONS There is excessive prescription of psychotropic drugs in Swedish nursing homes . Improved teamwork among caregivers can improve prescribing as defined by clinical guidelines BACKGROUND The release of the Agency for Health Care Policy and Research ( AHCPR ) 's Guideline for the Detection and Treatment of Depression in Primary Care created an opportunity to evaluate under naturalistic conditions the effectiveness of two clinical practice guideline implementation methods : continuous quality improvement ( CQI ) and academic detailing . A study conducted in 1993 - 1994 at Kaiser Permanente Northwest Division , a large , not-for-profit prepaid group practice ( group-model ) HMO , tested the hypotheses that each method would increase the number of members receiving depression treatment and would relieve depressive symptoms . METHODS Two trials were conducted simultaneously among adult primary care physicians , physician assistants , and nurse practitioners , using the same guideline document , measurement methods , and one-year follow-up period . The academic detailing trial was r and omized at the clinician level . CQI was assigned to one of the setting 's two geographic areas . To account for intraclinician correlation , both trials were evaluated using generalized equations analysis . RESULTS Most of the CQI team 's recommendations were not implemented . Academic detailing increased treatment rates , but -- in a cohort of patients with probable chronic depressive disorder -- it failed to improve symptoms and reduced measures of overall functional status . CONCLUSIONS New organizational structures may be necessary before CQI teams and academic detailing can substantially change complex processes such as the primary care of depression . New research and treatment guidelines are needed to improve the management of persons with chronic or recurring major depressive disorder OBJECTIVE The study addressed whether a collaborative model for chronic care , described in part I ( this issue ) , improves outcome for bipolar disorder . METHODS The intervention was design ed to improve outcome by enhancing patient self-management skills with group psychoeducation ; providing clinician decision support with simplified practice guidelines ; and improving access to care , continuity of care , and information flow via nurse care coordinators . In an effectiveness design veterans with bipolar disorder at 11 Veterans Affairs hospitals were r and omly assigned to three years of care in the intervention or continued usual care . Blinded clinical and functional measures were obtained every eight weeks . Intention-to-treat analysis ( N=306 ) with mixed-effects models addressed the hypothesis that improvements would accrue over three years , consistent with social learning theory . RESULTS The intervention significantly reduced weeks in affective episode , primarily mania . Broad-based improvements were demonstrated in social role function , mental quality of life , and treatment satisfaction . Reductions in mean manic and depressive symptoms were not significant . The intervention was cost-neutral while achieving a net reduction of 6.2 weeks in affective episode . CONCLUSIONS Collaborative chronic care models can improve some long-term clinical outcomes for bipolar disorder . Functional and quality -of-life benefits also were demonstrated , with most benefits accruing in years 2 and 3 BACKGROUND In 1996 a new model of maternity care characterized by continuity of midwifery care from early pregnancy through the postpartum period was implemented for women attending Monash Medical Centre , a tertiary level obstetric service , in Melbourne , Australia . This study 's purpose was to assess the impact of this model on women 's views and experiences of care during the antenatal , intrapartum , and postpartum periods compared with views of women receiving st and ard maternity care . METHODS One thous and low- and high-risk women who booked at the antenatal clinic and met the eligibility criteria were r and omly allocated to continuity of midwifery care from a group of seven midwives in collaboration with medical staff , or to st and ard care from a variety of midwives and medical staff . Women 's views of care were measured by means of a postal question naire at four months after the birth . RESULTS Team midwifery care was associated with increased satisfaction with antenatal , intrapartum , and some aspects of postpartum care . The differences were most obvious for antenatal care . CONCLUSIONS Continuity of midwifery care is realistically achievable in a tertiary obstetric referral service and is associated with increased satisfaction OBJECTIVES To determine whether an in-home palliative care intervention for terminally ill patients can improve patient satisfaction , reduce medical care costs , and increase the proportion of patients dying at home . DESIGN A r and omized , controlled trial . SETTING Two health maintenance organizations in two states . PARTICIPANTS Homebound , terminally ill patients ( N=298 ) with a prognosis of approximately 1 year or less to live plus one or more hospital or emergency department visits in the previous 12 months . INTERVENTION Usual versus in-home palliative care plus usual care delivered by an interdisciplinary team providing pain and symptom relief , patient and family education and training , and an array of medical and social support services . MEASUREMENTS Measured outcomes were satisfaction with care , use of medical services , site of death , and costs of care . RESULTS Patients r and omized to in-home palliative care reported greater improvement in satisfaction with care at 30 and 90 days after enrollment ( P<.05 ) and were more likely to die at home than those receiving usual care ( P<.001 ) . In addition , in-home palliative care subjects were less likely to visit the emergency department ( P=.01 ) or be admitted to the hospital than those receiving usual care ( P<.001 ) , result ing in significantly lower costs of care for intervention patients ( P=.03 ) . CONCLUSION In-home palliative care significantly increased patient satisfaction while reducing use of medical services and costs of medical care at the end of life . This study , although modest in scope , presents strong evidence for reforming end-of-life care BACKGROUND efficient strategies are needed to provide specialist advice in nursing homes to ensure quality medical care . We describe a case conference intervention involving a multidisciplinary team of health professionals . OBJECTIVES to evaluate the impact of multidisciplinary case conferences on the appropriateness of medications and on patient behaviours in high-level residential aged care facilities . DESIGN cluster-r and omised controlled trial . SETTING ten high-level aged care facilities . PARTICIPANTS 154 residents with medication problems and /or challenging behaviours were selected for case conference by residential care staff . INTERVENTION two multidisciplinary case conferences involving the resident 's general practitioner , a geriatrician , a pharmacist and residential care staff were held at the nursing home for each resident . MEASUREMENTS outcomes were assessed at baseline and 3 months . The primary outcome was the Medication Appropriateness Index ( MAI ) . The behaviour of each resident was assessed via the Nursing Home Behaviour Problem Scale . RESULTS 45 residents died before follow-up . Medication appropriateness improved in the intervention group [ MAI mean change 4.1 , 95 % confidence interval ( CI ) 2.1 - 6.1 ] compared with the control group ( MAI mean change 0.4 , 95 % CI -0.4 - 1.2 ; P < 0.001 ) . There was a significant reduction in the MAI for benzodiazepines ( mean change control -0.38 , 95 % CI -1.02 - 0.27 versus intervention 0.73 , 95 % CI 0.16 - 1.30 ; P = 0.017 ) . Resident behaviours were unchanged after the intervention and the improved medication appropriateness did not extend to other residents in the facility . CONCLUSION multidisciplinary case conferences in nursing homes can improve care . Outreach specialist services can be delivered without direct patient contact and achieve improvements in prescribing BACKGROUND In 2003 , through the Greater Cincinnati Health Council nine health care systems agreed to participate and fund 50 % of a two-year project to reduce hospital-acquired infections among patients in intensive care units ( ICU ) and following surgery ( SIP ) . METHODS Hospitals were r and omized to either the CR-BSI or SIP project in the first year , adding the alternative project in year 2 . Project leaders , often the infection control professionals , implemented evidence -based practice s to reduce catheter-related blood stream infections ( CR-BSIs ; maximal sterile barriers , chlorhexidine ) at their hospitals using a collaborative approach . Team leaders entered process information in a secure deidentifled Web-based data base . RESULTS Of the four initial sites r and omized to CR-BSI reduction , all reduced central line infections by 50 % ( CR-BSI , 1.7 to 0.4/1000 line days , p < .05 ) . At the project midpoint ( 3 quarters of 2004 ) , adherence to evidence -based practice s increased from 30 % to nearly 95 % . DISCUSSION The direct role of hospital leadership and development of a local community of practice , facilitated cooperation of physicians , problem solving , and success . Use of forcing functions ( removal of betadine in kits , creation of an accessory pack and a checklist for line insertion ) improved reliability . The appropriate floor for central line infections in ICUs is < 1 infection /1,000 line days UNLABELLED Interdisciplinary rounds ( IRs ) have been proposed to improve staff communication and reduce LOS . There have been no studies of IRs on an inpatient telemetry ward . Patients on a telemetry unit of a community hospital were r and omly assigned to either an IR intervention or st and ard care . Charts were review ed to determine LOS , patient characteristics , and indirect indices of quality of care . INTERVENTION Daily work rounds , in which resident physicians , nurses , and ancillary staff meet to discuss patients on the team . RESULTS 84 patients were enrolled , 42 r and omized to the intervention and 42 to st and ard care . There was no significant difference in LOS . Indirect measures of quality of care ( dietician , pharmacist , or physical therapist visit ) did not differ . In a multiple linear regression model , only abnormal laboratory data , the presence of dementia , and the presence of a home health aid significantly predicted LOS . CONCLUSION IRs did not decrease LOS in a telemetry ward . Whereas a potential benefit of IRs in other setting s can not be ruled out , this study emphasizes the importance of rigorous testing of strategies to enhance the quality or reduce the costs of inpatient care BACKGROUND In 1996 a new model of maternity care characterized by continuity of midwifery care from early pregnancy through to the postpartum period was implemented for women attending Monash Medical Centre , a tertiary level obstetric service , in Melbourne , Australia . The objective of this study was to compare the new model of care with st and ard maternity care . METHODS In a r and omized controlled trial , 1000 women who booked at the antenatal clinic and met the eligibility criteria were r and omly allocated to receive continuity of midwifery care ( team care ) from a group of seven midwives in collaboration with obstetric staff , or care from a variety of midwives and obstetric staff ( st and ard care ) . The primary outcome measures were procedures in labor , maternal outcomes , neonatal outcomes , and length of hospital stay . RESULTS Women assigned to the team care group experienced less augmentation of labor , less electronic fetal monitoring , less use of narcotic and epidural analgesia , and fewer episiotomies but more unsutured tears . Team care women stayed in hospital 7 hours less than women in st and ard care . More babies of st and ard care mothers were admitted to the special care nurseries for more than 5 days because of preterm birth , and more babies of team care mothers were admitted to the nurseries for more than 5 days with intrauterine growth retardation . No differences occurred in perinatal mortality between the two groups . CONCLUSIONS Continuity of midwifery care was associated with a reduction in medical procedures in labor and a shorter length of stay without compromising maternal and perinatal safety . Continuity of midwifery care is realistically achievable in a tertiary obstetric referral service Objective : This article uses data from two studies that have demonstrated the overall effectiveness of Collaborative Care interventions to evaluate factors associated with poor outcomes overall ( general prognostic factors ) and factors associated with greater or lesser effects of treatment ( differential treatment effects ) . Methods : Adult primary care patients initiating antidepressant treatment for major depression were r and omized to usual care or to Collaborative Care , a structured depression treatment program that included planned , proactive and coordinated care with a health care team and informed , activated patients ( n = 156 , mean age = 43 , 85 % white ) . Response to treatment was defined as a 50 % or greater reduction in depression at four months . Results : High neuroticism and a history of recurrent major depression ( 3 + episodes ) or dysthymia predicted poor outcomes in general . While the magnitude of the intervention effects differed , frequently cited predictors of persistence of depression ( age , gender , depression severity , medical and psychiatric comorbidity ) were not significantly associated with greater or lesser benefit from Collaborative Care ( no differential treatment effects ) . Results demonstrate the robustness of intervention effects across numerous groups at risk for persistence of depression . Conclusions : These findings suggest that at the time of diagnosis it is not possible to predict who is most likely to benefit from Collaborative Care . Instead , outcomes of treatment should be routinely monitored among depressed patients to ensure optimal response A r and omized and prospect i ve study examined the effects of intensive communication between treatment providers on physician behavior and patient care using a representative sample of patients referred to a German psychosomatic consultation-liaison ( C-L ) service ( 1998 - 1999 ) . Sixty-seven patients were grouped ( ICD-10 ) and r and omized into intervention ( n=33 ) and control groups ( n=34 ) . In the control group ( CG ) , only the inpatient referring physicians were informed of consultation findings , as is st and ard practice in Germany . In the IG , the consultant directly reported the consultation findings to the general practitioner ( GP ) . Patients were examined at 6-month ( T2 ) and 3.5-year ( T3 ) follow-up . Physician feedback and requests regarding the nature of communication were also assessed at T2 . A significant reduction in symptoms was revealed at both follow-ups for the IG and CG . No significant group differences were found for acceptance of psychotherapy ( 59.1 % IG and 42.3 % CG at T3 ) . The utilization of medical services remained stable across time . Patients who began psychotherapy were shown to have greater baseline symptom levels and " openness for new experiences " ( NEO Five-Factor Inventory , NEO-FFi ) . Regular GP integration of psychosocial aspects into primary care differed between IG ( 44.0 % ) and CG ( 25.0 % ) . Ninety-one percent of the GPs requested the option for a telephone conversation with the consultant or a case conference involving the patient at either their practice ( 37.7 % ) or the clinic ( 24.5 % ) . We conclude that GPs are interested in a differentiated and more intensive cooperation concerning the integration of psychosocial aspects in their outpatient treatment . The patient 's acceptance to follow a recommendation for psychotherapy , however , is related to the level of symptom severity and openness for new experiences Objective . Hospitals adapt to changing market conditions by exploring new care models that allow them to maintain high quality while containing costs . The authors examined the net cost savings associated with care management by teams of physicians and nurse practitioners , along with daily multidisciplinary rounds and postdischarge patient follow-up . Methods . One thous and two hundred and seven general medicine in patients in an academic medical center were r and omized to the intervention versus usual care . Intervention costs were compared to the difference in nonintervention costs , estimated by comparing changes between preadmission and postadmission in regression-adjusted costs for intervention versus usual care patients . Intervention costs were calculated by assigning hourly costs to the time spent by different providers on the intervention . Patient costs during the index hospital stay were estimated from administrative records and during the 4-month follow-up by weighting selfreported utilization by unit costs . Results . Intervention costs were $ 1187 per patient and associated with a significant $ 3331 reduction in nonintervention costs . About $ 1947 of the savings were realized during the initial hospital stay , with the remainder attributable to reductions in postdischarge service use . After adjustment for possible attrition bias , a reasonable estimate of the cost offset was $ 2165 , for a net cost savings of $ 978 per patient . Because health outcomes were comparable for the 2 groups , the intervention was cost-effective . Conclusions . Wider adoption of multidisciplinary interventions in similar setting s might be considered . The savings previously reported with hospitalist models may also be achievable with other models that focus on efficient inpatient care and appropriate postdischarge care OBJECTIVE To make measurable improvements in the quality and cost of neonatal intensive care using a multidisciplinary collaborative quality improvement model . DESIGN Interventional study . Data on treatment costs were collected for infants with birth weight 501 to 1500 g for the period of January 1 , 1994 to December 31 , 1997 . Data on re sources expended by hospitals to conduct this project were collected in a survey for the period January 1 , 1995 to December 31 , 1996 . SETTING Ten self-selected neonatal intensive care units ( NICUs ) received the intervention . They formed 2 subgroups ( 6 NICUs working on infection , 4 NICUs working on chronic lung disease ) . Nine other NICUs served as a contemporaneous comparison group . PATIENTS Infants with birth weight 501 to 1500 g born at or admitted within 28 days of birth between 1994 and 1997 to the 6 study NICUs in the infection group ( N = 2993 ) and the 9 comparison NICUs ( N = 2203 ) ; infants with birth weight 501 to 1000 g at the 4 study NICUs in the chronic lung disease group ( N = 663 ) and the 9 comparison NICUs ( N = 1007 ) . INTERVENTIONS NICUs formed multidisciplinary teams which worked together to undertake a collaborative quality improvement effort between January 1995 and December 1996 . They received instruction in quality improvement , review ed performance data , identified common improvement goals , and implemented " potentially better practice s " developed through analysis of the processes of care , literature review , and site visits . MAIN OUTCOME MEASURES Treatment cost per infant is the primary economic outcome measure . In addition , the re sources spent by hospitals in undertaking the collaborative quality improvement effort were determined . RESULTS Between 1994 and 1996 , the median treatment cost per infant with birth weight 501 to 1500 g at the 6 project NICUs in the infection group decreased from $ 57 606 to $ 46 674 ( a statistical decline ) ; at the 4 chronic lung disease hospitals , for infants with birth weights 501 to 1000 g , it decreased from $ 85 959 to $ 77 250 . Treatment costs at hospitals in the control group rose over the same period . There was heterogeneity in the effects among the NICUs in both project groups . Cost savings were maintained in the year following the intervention . On average , hospitals spent $ 68 206 in re sources to undertake the collaborative quality improvement effort between 1995 and 1996 . Two thirds of these costs were incurred in the first year , with the remaining third in the second year . The average savings per hospital in patient care costs for very low birth weight infants in the infection group was $ 2.3 million in the post-intervention year ( 1996 ) . There was considerable heterogeneity in the cost savings across hospitals associated with participation in the collaborative quality improvement project . CONCLUSION Cost savings may be achieved as a result of collaborative quality improvement efforts and when they occur , they appear to be sustainable , at least in the short run . In high-cost patient population s , such as infants with very low birth weights , cost savings can quickly offset institutional expenditures for quality improvement efforts Objectives : To compare the costs to the health service , women and their families of routine antenatal care provided by either traditional obstetrician-led shared care or general practitioner (GP)/community midwife care . Method : A multicentre r and omized controlled trial in 51 general practice s linked to nine maternity hospitals in Scotl and : 1667 low-risk pregnant women provided information on costs to the health service . 704 of these women provided information on non-health service costs . Results : GP/midwife antenatal care was found to cost statistically significantly less than shared care . This was the case for investigations carried out at routine antenatal visits ( GP/midwife = £ 87.25 , shared care = £ 91.15 , P = 0.05 ) , staffing costs at routine antenatal visits ( GP/midwife = £ 127.76 , shared care = £ 131.09 , P = 0.001 ) , and non-health service costs incurred by women and their companions ( GP/midwife = £ 118.53 , shared care = £ 133.49 , P = 0.001 ) . While non-routine care in the GP/midwife arm of the trial costs less than in the shared care arm , the difference was not statistically significant ( GP/midwife = £ 83.74 , shared care = £ 94.43 , P = 0.46 ) . The total societal cost of antenatal care was £ 417.28 per woman in the GP/midwife arm of the trial and £ 450.19 in the shared care arm of the trial . This difference was statistically significant ( P < 0.001 ) . The application of sensitivity analysis did not change these results . Conclusions : GP/midwife antenatal care is a satisfactory option for low-risk pregnant women in Scotl and provided that clinical outcomes and women 's satisfaction are at least the same as those of women with shared care Background : Patients with persistent medically unexplained symptoms often exhibit general dysfunction and psychiatric comorbidity and frequently resist psychiatric referral . The aim of this study was to evaluate the efficacy of a collaborative care model including training for general practitioners ( GPs ) and a psychiatric consultation model for patients with persistent medically unexplained symptoms in general practice . Method : R and omised controlled trial . Cluster r and omisation at GP practice s and multilevel analysis were performed . A total of 81 patients from 36 general practice s completed the study . A collaborative care model of training and psychiatric consultation in general practice in the presence of the GP was compared with training plus care as usual by the GP . Outcome assessment on the patients ’ well-being , functioning and utilisation of health care services was performed 6 weeks and 6 months later . Results : All the patients had somatoform disorders ( Whitely Index 7.46 ) , and 86 % had comorbid psychiatric disorders . In the intervention group , the severity of the main medically unexplained symptoms decreased by 58 % . The patients ’ social functioning improved . The utilization of health care was lower than in the care as usual group . Conclusions : A collaborative care model combining training with psychiatric consultation in the general practice setting is an effective intervention in the treatment of persistent medically unexplained symptoms . Anxiety and depressive disorders are highly comorbid in this group . The findings warrant a larger study |
12,742 | 28,745,394 | There was no evidence from r and omised controlled trials to support or refute the use of opioids to treat chronic non-cancer pain in children and adolescents .
We are unable to comment about efficacy or harm from the use of opioids to treat chronic non-cancer pain in children and adolescents .
We know from adult r and omised controlled trials that some opioids , such as morphine and codeine , can be effective in certain chronic pain conditions .
This means that no conclusions could be made about efficacy or harm in the use of opioids to treat chronic non-cancer pain in children and adolescents | BACKGROUND Pain is a common feature of childhood and adolescence around the world , and for many young people , that pain is chronic .
The World Health Organization guidelines for pharmacological treatments for children 's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world .
While in the past , pain was largely dismissed and was frequently left untreated , views on children 's pain have changed over time , and relief of pain is now seen as importantWe design ed a suite of seven review s on chronic non-cancer pain and cancer pain ( looking at antidepressants , antiepileptic drugs , non-steroidal anti-inflammatory drugs , opioids , and paracetamol as priority areas ) in order to review the evidence for children 's pain utilising pharmacological interventions in children and adolescents .
As the leading cause of morbidity in children and adolescents in the world today , chronic disease ( and its associated pain ) is a major health concern .
Chronic pain ( lasting three months or longer ) can arise in the paediatric population in a variety of pathophysiological classifications : nociceptive , neuropathic , idiopathic , visceral , nerve damage pain , chronic musculoskeletal pain , and chronic abdominal pain , and other unknown reasons .Opioids are used worldwide for the treatment of pain .
They bind to opioid receptors in the central nervous system ( mu , kappa , delta , and sigma ) and can be agonists , antagonists , mixed agonist-antagonists , or partial agonists .
Opioids are used in varying doses ( generally based on body weight for paediatric patients ) by means of parenteral , transmucosal , transdermal , or oral administration ( immediate release or modified release ) .
To achieve adequate pain relief in children using opioids , with an acceptable grade of adverse effects , the recommended method is a lower dose gradually titrated to effect in the child .
OBJECTIVES To assess the analgesic efficacy and adverse events of opioids used to treat chronic non-cancer pain in children and adolescents aged between birth and 17 years , in any setting . | Butorphanol tartrate ( 4 mg and 8 mg ) was compared to codeine phosphate ( 60 mg ) and placebo for oral analgesic activity and side-effects employing a double-blind design in ninety-three out- patients suffering from moderate to very severe musculoskeletal pain . The study duration was 72 hours with medication administered every 4 to 6 hours ( four times daily ) for a total of twelve doses per patient . The results demonstrate that both the 4 mg and 8 mg doses of butorphanol were significantly better ( p<0.05 ) than placebo . While codeine 60 mg also proved active , it appears to be less efficacious than the high dose of butorphanol . The peak effect appeared to be evident in 1 to 2 hours . Butorphanol may be at least seven times more potent than codeine on a milligram basis . Although no serious side-effects were observed , butorphanol appeared to present a greater incidence of side-effects than codeine and placebo in this study Short-term and long-term effects of neonatal pain and its analgesic treatment have been topics of translational research over the years . This study aim ed to identify the long-term effects of continuous morphine infusion in the neonatal period on thermal pain sensitivity , the incidence of chronic pain , and neurological functioning . Eighty-nine of the 150 participants of a neonatal r and omized controlled trial on continuous morphine infusion versus placebo during mechanical ventilation underwent quantitative sensory testing and neurological examination at the age of 8 or 9 years . Forty-three children from the morphine group and 46 children from the placebo group participated in this follow-up study . Thermal detection and pain thresholds were compared with data from 28 healthy controls . Multivariate analyses revealed no statistically significant differences in thermal detection thresholds and pain thresholds between the morphine and placebo groups . The incidence of chronic pain was comparable between both groups . The neurological examination was normal in 29 ( 76 % ) of the children in the morphine group and 25 ( 61 % ) of the children in the control group ( P = .14 ) . We found that neonatal continuous morphine infusion ( 10 μg/kg/h ) has no adverse effects on thermal detection and pain thresholds , the incidence of chronic pain , or overall neurological functioning 8 to 9 years later . Perspective : This unique long-term follow-up study shows that neonatal continuous morphine infusion ( 10 μg/kg/h ) has no long-term adverse effects on thermal detection and pain thresholds or overall neurological functioning . These findings will help clinicians to find the most adequate and safe analgesic dosing regimens for neonates and infants & NA ; The current analysis compares changes in pain with changes in function and health status in individuals with painful diabetic peripheral neuropathy ( DPN ) . The post hoc analysis is based on a 12 week , multinational , placebo‐controlled trial of pregabalin in which 401 patients were r and omized to treatment . Study measures included the Brief Pain Inventory short‐form ( BPI‐sf ) , EQ‐5D and other patient‐reported outcomes . Cutpoints were derived on the BPI‐sf 0–10 average pain numeric rating scale [ NRS ] to classify pain grade s of “ mild ” ( 1–3 ) , moderate ( 4–6 ) and severe ( 7–10 ) , adjusting for geographical regions where data were collected . Two different metrics were used to classify the importance of change in pain severity from baseline to 12 weeks : changes in pain severity grade s ( defined by cutpoint categories ) and percent reduction in the NRS ( categories ranging from 0–9 % to ≥50 % ) . An improvement in one pain grade or a ≥30 % reduction in the NRS served as determinants of a clinical ly important difference . Patients with a one‐ grade reduction in pain severity , either from “ severe‐to‐moderate ” or “ moderate‐to‐mild , ” had a 3‐point improvement the BPI‐sf Pain Interference Index ( PII ; a composite measure of function ) ; a reduction from “ severe‐to‐mild ” pain corresponded to a 6‐point improvement in the PII . Similarly , a reduction in the NRS of ≥30 % and ≥50 % corresponded to a 3‐point and a 5‐point improvement in the PII , respectively . Changes in pain were also associated with changes in health status . Results suggest that patients whose pain is not reduced to a mild level of severity can still experience clinical ly important changes in function and health status & NA ; Chronic pain is associated with a range of other problems , including disturbed sleep , depression , anxiety , fatigue , reduced quality of life , and an inability to work or socialise . We investigated whether good symptom control of pain ( using definitions of moderate and substantial benefit ) is associated with improvement in other symptoms . Individual patient data from four r and omised trials in fibromyalgia ( 2575 patients ) lasting 8–14 weeks were used to calculate percentage pain reduction for each completing patient ( 1858 ) , divided into one of five groups according to pain reduction , irrespective of treatment : substantial benefit – ≥50 % pain reduction ; moderate – 30 % to < 50 % ; minimal – 15 % to < 30 % ; marginal – 0 % to < 15 % ; worse – < 0 % ( increased pain intensity ) . We then calculated change from baseline to end of trial for measures of fatigue , function , sleep , depression , anxiety , ability to work , general health status , and quality ‐adjusted life year ( QALY ) gain over a 12‐month period . Substantial and moderate pain intensity reductions were associated with statistically significant reduction from baseline by end of trial in all measures , with values by trial end at or approaching normative values . Substantial pain intensity reduction result ed in 0.11 QALYs gained , and moderate pain intensity reduction in 0.07 QALYs gained over a 12‐month period . Substantial and moderate pain intensity reduction predicts broad beneficial outcomes and improved quality of life that do not occur without pain relief . Pain intensity reduction is a simple and effective predictor of which patients should continue treatment , and which should discontinue and try an alternative therapy Background : Recent warnings from Health Canada regarding codeine for children have led to increased use of nonsteroidal anti-inflammatory drugs and morphine for common injuries such as fractures . Our objective was to determine whether morphine administered orally has superior efficacy to ibuprofen in fracture-related pain . Methods : We used a parallel group , r and omized , blinded superiority design . Children who presented to the emergency department with an uncomplicated extremity fracture were r and omly assigned to receive either morphine ( 0.5 mg/kg orally ) or ibuprofen ( 10 mg/kg ) for 24 hours after discharge . Our primary outcome was the change in pain score using the Faces Pain Scale — Revised ( FPS-R ) . Participants were asked to record pain scores immediately before and 30 minutes after receiving each dose . Results : We analyzed data from 66 participants in the morphine group and 68 participants in the ibuprofen group . For both morphine and ibuprofen , we found a reduction in pain scores ( mean pre – post difference ± st and ard deviation for dose 1 : morphine 1.5 ± 1.2 , ibuprofen 1.3 ± 1.0 , between-group difference [ δ ] 0.2 [ 95 % confidence interval ( CI ) −0.2 to 0.6 ] ; dose 2 : morphine 1.3 ± 1.3 , ibuprofen 1.3 ± 0.9 , δ 0 [ 95 % CI −0.4 to 0.4 ] ; dose 3 : morphine 1.3 ± 1.4 , ibuprofen 1.4 ± 1.1 , δ −0.1 [ 95 % CI −0.7 to 0.4 ] ; and dose 4 : morphine 1.5 ± 1.4 , ibuprofen 1.1 ± 1.2 , δ 0.4 [ 95 % CI −0.2 to 1.1 ] ) . We found no significant differences in the change in pain scores between morphine and ibuprofen between groups at any of the 4 time points ( p = 0.6 ) . Participants in the morphine group had significantly more adverse effects than those in the ibuprofen group ( 56.1 % v. 30.9 % , p < 0.01 ) . Interpretation : We found no significant difference in analgesic efficacy between orally administered morphine and ibuprofen . However , morphine was associated with a significantly greater number of adverse effects . Our results suggest that ibuprofen remains safe and effective for outpatient pain management in children with uncomplicated fractures . Trial registration : Clinical Trials.gov , no. NCT01690780 SUMMARY Two double-blind between-patient comparisons of the analgesic activity of orally administered pentazocine 50 mg , dihydrocodeine 60 mg and placebo are described , which involved 99 patients in " severe " or " moderate " pain , mainly of skeletal origin , and 103 patients in " severe " or " moderate " pain predominatly of postoperative origin . In both studies pain was assessed by a single observer prior to and 1 hour after the administration of a single dose of one of the test preparations . Both active drugs were significantly superior to placebo , and in both studies a firm trend showed pentazocine to be more effective than dihydrocodeine which was in turn more effective than placebo . Drowsiness more commonly followed pentazocine administration , but nausea and vomiting more commonly followed dihydrocodeine Background : The aim was to compare the efficacy and safety of a combination of intramuscular ketorolac and chlorpromazine for the treatment of acute exacerbations of chronic pain with the more commonly used regimen of intramuscular meperidine and promethazine . Methods : Use-effective case series were drawn from a real-life , rural emergency department practice , in which 200 consecutive patients coming to a rural emergency department with acute exacerbations of chronic pain syndromes were assigned on an every-other basis in a single-blind fashion to one of the two treatment conditions . Patients were given intramuscular doses of either 60 mg of ketorolac plus 50 mg of chlorpromazine ( 75 mg of chlorpromazine for patients weighing more than 100 kg ) , or 50 mg of meperidine plus 25 mg of promethazine ( 50 mg of promethazine for patients weighing more than 75 kg ) ; patients weighing more than 100 kg were given 1.5 doses . Patients older than 65 years or whose blood pressure at the time of injection was less than 110/70 mmHg were given half-doses . Patients could receive one additional half-dose injection if they had no results within 30 to 60 minutes after the first injection . Patients were assessed on self-report and on a verbal and visual analog scale of pain rating . Temperature , blood pressure , heart rate , and respirations were monitored every 15 minutes . Results : Both regimens performed well , with more than 90 percent of patients reporting good or excellent improvement on acute exacerbations of chronic pain . Ketorolac-chlorpromazine offered significant advantages compared with meperidine-promethazine when patients rated their pain on a visual analog pain scale ( P < 0.05 ) but not on a verbal scale . Adverse reactions were minimal and consisted of more respiratory tract depression with meperidine and more vertigo or dizziness with chlorpromazine . There was no difference in incidence of hypotension between the two groups . Conclusions : The combination of ketorolac and chlorpromazine is a safe and efficacious alternative to meperidine plus promethazine for the treatment of exacerbations of chronic pain in the rural emergency department setting BACKGROUND Gastrointestinal ( GI ) adverse effects are common with oral opioid treatments ; their impact on health-related quality of life ( HRQoL ) is poorly understood . OBJECTIVES To estimate the extent to which GI adverse effects impact HRQoL. DESIGN 28-day prospect i ve , multicenter , observational registry . SETTING Outpatient setting s. PARTICIPANTS Six hundred thirty-nine patients with acute pain ( AP ; n = 243 ) and acute episodes of chronic pain ( CP ; pain ≥3 months ; n = 396 ) requiring treatment with a prescription medication containing oxycodone immediate-release on an as-needed basis for ≥5 days . MEASUREMENTS Modified Memorial Symptom Assessment Scale ; 12-item Short Form Health Survey ( SF-12 ) Physical ( PCS ) ; and Mental Component Scales ( MCS ) on days 3 , 7 , 14 , 21 , and 28 . Repeated measures mixed models provided estimates of impact of GI events on HRQoL. RESULTS Forty-seven percent of AP patients and 24 percent of CP patients developed constipation . More AP patients than CP developed nausea ( 31 percent vs 19 percent ) . After adjustment for confounders , constipation was associated with a 3.9-point reduction in PCS and a 2.3-point reduction in MCS among AP patients ( p < 0.0001 ) . Among AP patients , nausea/vomiting was associated with a reduction in PCS ( PCS = 3.2 ; p < 0.0001 ) and MCS ( MCS = 2.2 ; p = 0.0042 ) . Among CP patients , constipation was not associated with reductions in HRQoL , and nausea/vomiting was associated with a reduction in MCS but not PCS ( MCS = 2.4 ; p ≤ 0.0001 ) . CONCLUSION GI symptoms accompanying oral opioid treatment are common and negatively affect HRQoL differentially for those with AP and CP . Effective approaches for managing opioid-induced GI symptoms are warranted |
12,743 | 26,879,746 | This review found that pre-operative physiotherapy rehabilitation is effective for improving the outcomes of treatment following anterior cruciate ligament injury , including increasing knee-related function and improving muscle strength .
However , whilst there was a significant improvement in quality of life from baseline following intervention , no significant difference in quality of life was found between the control and intervention groups .
Conclusions : There is evidence to suggest that pre-operative physiotherapy rehabilitation is beneficial to patients with anterior cruciate ligament injury | Objective : To evaluate the effectiveness of pre-operative exercise physiotherapy rehabilitation on the outcomes of treatment following anterior cruciate ligament injury . | Objective To compare , in young active adults with an acute anterior cruciate ligament ( ACL ) tear , the mid-term ( five year ) patient reported and radiographic outcomes between those treated with rehabilitation plus early ACL reconstruction and those treated with rehabilitation and optional delayed ACL reconstruction . Design Extended follow-up of prospect i ve r and omised controlled trial . Setting Orthopaedic departments at two hospitals in Sweden . Participants 121 young , active adults ( mean age 26 years ) with acute ACL injury to a previously uninjured knee . One patient was lost to five year follow-up . Intervention All patients received similar structured rehabilitation . In addition to rehabilitation , 62 patients were assigned to early ACL reconstruction and 59 were assigned to the option of having a delayed ACL reconstruction if needed . Main outcome measure The main outcome was the change from baseline to five years in the mean value of four of the five subscales of the knee injury and osteoarthritis outcome score ( KOOS4 ) . Other outcomes included the absolute KOOS4 score , all five KOOS subscale scores , SF-36 , Tegner activity scale , meniscal surgery , and radiographic osteoarthritis at five years . Results Thirty ( 51 % ) patients assigned to optional delayed ACL reconstruction had delayed ACL reconstruction ( seven between two and five years ) . The mean change in KOOS4 score from baseline to five years was 42.9 points for those assigned to rehabilitation plus early ACL reconstruction and 44.9 for those assigned to rehabilitation plus optional delayed reconstruction ( between group difference 2.0 points , 95 % confidence interval −8.5 to 4.5 ; P=0.54 after adjustment for baseline score ) . At five years , no significant between group differences were seen in KOOS4 ( P=0.45 ) , any of the KOOS subscales ( P≥0.12 ) , SF-36 ( P≥0.34 ) , Tegner activity scale ( P=0.74 ) , or incident radiographic osteoarthritis of the index knee ( P=0.17 ) . No between group differences were seen in the number of knees having meniscus surgery ( P=0.48 ) or in a time to event analysis of the proportion of meniscuses operated on ( P=0.77 ) . The results were similar when analysed by treatment actually received . Conclusion In this first high quality r and omised controlled trial with minimal loss to follow-up , a strategy of rehabilitation plus early ACL reconstruction did not provide better results at five years than a strategy of initial rehabilitation with the option of having a later ACL reconstruction . Results did not differ between knees surgically reconstructed early or late and those treated with rehabilitation alone . These results should encourage clinicians and young active adult patients to consider rehabilitation as a primary treatment option after an acute ACL tear . Trial registration Current Controlled Trials IS RCT N84752559 We performed a prospect i ve , double-blind , r and omised , clinical trial to investigate the efficacy of two regimes of rehabilitation for knees with anterior cruciate ligament deficiency ( ACLD ) . Fifty ACLD patients were r and omly allocated to one of two treatment groups : a programme of muscle strengthening ( T ) or a programme design ed to enhance proprioception and improve hamstring contraction reflexes ( P ) . An indirect measure of proprioception , the reflex hamstring contraction latency ( RHCL ) , and a functional scoring system were used to record the status of the knee before and after the 12-week course of physiotherapy . Sagittal knee laxity was also measured . There was improvement in mean RHCL and in the mean functional score in both groups after treatment . The improvement in group P was significantly greater than that in group T. There was no significant change in joint laxity after treatment in either group . In both groups there was a positive correlation between improvement in RHCL and functional gain BACKGROUND The optimal management of a torn anterior cruciate ligament ( ACL ) of the knee is unknown . METHODS We conducted a r and omized , controlled trial involving 121 young , active adults with acute ACL injury in which we compared two strategies : structured rehabilitation plus early ACL reconstruction and structured rehabilitation with the option of later ACL reconstruction if needed . The primary outcome was the change from baseline to 2 years in the average score on four subscales of the Knee Injury and Osteoarthritis Outcome Score (KOOS)--pain , symptoms , function in sports and recreation , and knee-related quality of life ( KOOS(4 ) ; range of scores , 0 [ worst ] to 100 [ best ] ) . Secondary outcomes included results on all five KOOS subscales , the Medical Outcomes Study 36-Item Short-Form Health Survey , and the score on the Tegner Activity Scale . RESULTS Of 62 subjects assigned to rehabilitation plus early ACL reconstruction , 1 did not undergo surgery . Of 59 assigned to rehabilitation plus optional delayed ACL reconstruction , 23 underwent delayed ACL reconstruction ; the other 36 underwent rehabilitation alone . The absolute change in the mean KOOS(4 ) score from baseline to 2 years was 39.2 points for those assigned to rehabilitation plus early ACL reconstruction and 39.4 for those assigned to rehabilitation plus optional delayed reconstruction ( absolute between-group difference , 0.2 points ; 95 % confidence interval , -6.5 to 6.8 ; P=0.96 after adjustment for the baseline score ) . There were no significant differences between the two treatment groups with respect to secondary outcomes . Adverse events were common in both groups . The results were similar when the data were analyzed according to the treatment actually received . CONCLUSIONS In young , active adults with acute ACL tears , a strategy of rehabilitation plus early ACL reconstruction was not superior to a strategy of rehabilitation plus optional delayed ACL reconstruction . The latter strategy substantially reduced the frequency of surgical reconstructions . ( Funded by the Swedish Research Council and the Medical Faculty of Lund University and others ; Current Controlled Trials number , IS RCT N84752559 . BACKGROUND AND PURPOSE Treatment techniques involving perturbations of support surfaces may induce compensatory muscle activity that could improve knee stability and increase the likelihood of returning patients to high-level physical activity . The purpose of this study was to determine the efficacy of augmenting st and ard nonoperative anterior cruciate ligament ( ACL ) rehabilitation programs with a perturbation training program . SUBJECTS Twenty-six patients with acute ACL injury or ruptures of ACL grafts participated in the study . Subjects had to have a unilateral ACL injury , be free of concomitant multiple ligament or meniscal damage requiring surgical repair , and pass a screening examination design ed to identify patients who had the potential to return to high-level physical activity with nonoperative treatments . Subjects also had to be regular participants in level I activities ( eg , soccer , football , basketball ) or level II activities ( eg , racquet sports , skiing , construction work ) . METHODS Subjects were r and omly assigned to either a group that received a st and ard rehabilitation program ( st and ard group ) or a group that received the st and ard program augmented with a perturbation training program ( perturbation group ) . Treatment outcome was determined from scores on the Knee Outcome Survey 's Activities of Daily Living Scale ( ADLS ) and Sports Activity Scale , a global rating of knee function , scores on a series of single-limb hop tests , measurements of maximum isometric quadriceps femoris muscle force output , and the group frequency of unsuccessful rehabilitation . Unsuccessful rehabilitation was defined as the occurrence of an episode of giving way of the knee or failure to maintain the functional status of a rehabilitation c and i date on retesting . RESULTS More subjects had unsuccessful rehabilitation in the st and ard group compared with the perturbation group . There was a within-group x time interaction for the ADLS , global rating of knee function , and crossover hop test scores . These scores decreased from posttraining to the 6-month follow-up for the st and ard group . CONCLUSION AND DISCUSSION Although both the st and ard program and the perturbation training program may allow subjects to return to high-level physical activity , the perturbation training program appears to reduce the risk of continued episodes of giving way of the knee during athletic participation and allows subjects to maintain their functional status for longer periods We investigated whether preoperative perturbation training would help anterior cruciate ligament ( ACL ) deficient individuals who complain of knee instability ( " non-copers " ) regain quadriceps strength and walk normally after ACL reconstruction . Nineteen non-copers with acute ACL injury were r and omly assigned into a perturbation group ( PERT ) or a strengthening group ( STR ) . The PERT group received specialized neuromuscular training and progressive quadriceps strength training , whereas the STR group received progressive quadriceps strength training only . We compared quadriceps strength indexes and knee excursions during the mid-stance phase of gait preoperatively to data collected 6 months after ACL reconstruction . Analyses of Variance with repeated measures ( time/limb ) were conducted to compare quadriceps strength index values over time ( time x group ) and differences in knee excursions in limbs between groups over time ( limb x time x group ) . If significance was found , post hoc analyses were performed using paired and independent t-tests . Quadriceps strength indexes before intervention ( Pert : 87.2 % ; Str : 75.8 % ) improved 6 months after ACL reconstruction in both groups ( Pert : 97.1 % ; Str : 94.4 % ) . Non-copers who received perturbation training preoperatively had no differences in knee excursions between their limbs 6 months after ACL reconstruction ( p = 0.14 ) , whereas those who received just strength training continued to have smaller knee excursions during the mid-stance phase of gait ( p = 0.007 ) . Non-copers strength and knee excursions were more symmetrical 6 months postoperatively in the group that received perturbation training and progressive quadriceps strength training than the group who received strength training alone Abstract . Rehabilitation after anterior cruciate ligament ( ACL ) reconstruction has focused over the past decade on closed kinetic chain ( CKC ) exercises due to presumably less strain on the graft than with isokinetic open kinetic chain exercises ( OKC ) ; however , recent reports suggest that there are only minor differences in ACL strain values between some CKC and OKC exercises . We studied anterior knee laxity , thigh muscle torque , and return to preinjury sports level in 44 patients with unilateral ACL ; group 1 carried out quadriceps strengthening only with CKC while group 2 trained with CKC plus OKC exercises starting from week 6 after surgery . Anterior knee laxity was determined with a KT-1000 arthrometer ; isokinetic concentric and eccentric quadriceps and hamstring muscle torque were studied with a Kin-Com dynamometer before and 6 months after surgery . At an average of 31 months after surgery the patients answered a question naire regarding their current knee function and physical activity/sports to determine the extent and timing of their recovery . No significant differences in anterior knee laxity were noted between the groups 6 months postsurgery . Patients in group 2 increased their quadriceps torque significantly more than those in group 1 , but no differences were found in hamstring torque between the groups . A significantly higher number of patients in group 2 ( n=12 ) than in group 1 ( n=5 ) returned to sports at the same level as before the injury ( P<0.05 ) . Patients from group 2 who returned to sports at the same level did so 2 months earlier than those in group 1 . Thus the addition of OKC quadriceps training after ACL reconstruction results in a significantly better improvement in quadriceps torque without reducing knee joint stability at 6 months and also leads to a significantly higher number of athletes returning to their previous activity earlier and at the same level as before injury 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 . Background There is no consensus regarding the optimal rehabilitation regimen for increasing quadriceps strength after anterior cruciate ligament ( ACL ) injury . Hypothesis A comprehensive rehabilitation program supplemented with quadriceps strengthening in open kinetic chain ( OKC ) exercise will increase quadriceps strength and improve knee function without increasing static or dynamic sagittal tibial translation , compared with the same comprehensive rehabilitation program supplemented with quadriceps strengthening in closed kinetic chain ( CKC ) exercise , in patients with acute ACL deficiency . Study Design R and omized controlled trial ; Level of evidence , 1 . Methods Forty-two patients were tested a mean of 43 days ( range , 20–96 days ) after an ACL injury . Patients were r and omized to rehabilitation with CKC quadriceps strengthening ( 11 men and 9 women ) or OKC quadriceps strengthening ( 13 men and 9 women ) . Aside from these quadriceps exercises , the 2 rehabilitation programs were identical . Patients were assessed after 4 months of rehabilitation . Sagittal static translation and dynamic tibial translation were evaluated with a CA-4000 electrogoniometer . Muscle strength , jump performance , and muscle activation were also assessed . Functional outcome was evaluated by determining the Lysholm score and the Knee Injury and Osteoarthritis Outcome Score . Results There were no group differences in static or dynamic translation after rehabilitation . The OKC group had significantly greater isokinetic quadriceps strength after rehabilitation ( P = .009 ) . The hamstring strength , performance on the 1-repetition-maximum squat test , muscle activation , jump performance , and functional outcome did not differ between groups . Conclusions Rehabilitation with OKC quadriceps exercise led to significantly greater quadriceps strength compared with rehabilitation with CKC quadriceps exercise . Hamstring strength , static and dynamic translation , and functional outcome were similar between groups . Patients with ACL deficiency may need OKC quadriceps strengthening to regain good muscle torque Background : Prehabilitation is defined as preparing an individual to withst and a stressful event through enhancement of functional capacity . Hypothesis : We hypothesized that a preoperative exercise program would enhance postoperative outcomes after anterior cruciate ligament reconstruction ( ACLR ) . Study Design : R and omized controlled clinical trial ; Level of evidence , 1 . Methods : Twenty volunteers awaiting ACLR were r and omly assigned to a control or exercise intervention group . The exercise group completed a 6-week gym- and home-based exercise program . Assessment s include single-legged hop test ; quadriceps and hamstring peak torque and magnetic resonance imaging cross-sectional area ( CSA ) ; Modified Cincinnati Knee Rating System score ; and muscle biopsy of the vastus lateralis muscle completed at baseline , preoperatively , and 12 weeks postoperatively . Myosin heavy chain ( MHC ) isoforms protein and messenger RNA ( mRNA ) expression were determined with SDS-PAGE ( sodium dodecyl sulfate polyacrylamide gel electrophoresis ) and RT-PCR ( real-time polymerase chain reaction ) , respectively ; IGF-1 ( insulin-like growth factor 1 ) , MuRF-1 ( muscle RING-finger protein-1 ) , and MAFbx ( muscle atrophy f-box ) mRNA expression were determined with quantitative RT-PCR . Results : Following 6 weeks of exercise intervention , the single-legged hop test results improved significantly in the exercise-injured limb compared with baseline ( P = .001 ) . Quadriceps peak torque in the injured limb improved with similar gains in CSA compared with baseline ( P = .001 ) . However , this was not significantly increased compared with the control group . Quadriceps and vastus medialis CSA were also larger in the exercise group than in controls ( P = .0024 and P = .015 , respectively ) . The modified Cincinnati score was better in the exercise-injured limb compared with baseline . At 12 weeks postoperatively , the rate of decline in the single-legged hop test was reduced in the exercise group compared with controls ( P = .001 ) . Similar trends were not seen for quadriceps peak torque and CSA . The vastus medialis CSA had regressed to similar levels as the control group ( P = .008 ) . The modified Cincinnati score continued to increase in the exercise group compared with controls ( P = .004 ) . The expression of the hypertrophic IGF-1 gene was significantly increased after the exercise intervention ( P = .028 ) , with a decrease back to baseline 12 weeks postoperatively ( P = .012 ) . Atrophic MuRF-1 gene expression was decreased after intervention compared with baseline ( P = .05 ) but increased again at 12 weeks postoperatively ( P = .03 ) . The MAFbx levels did not change significantly in either group and within each time point . On the mRNA level , there was a shift from MHC-IIx isoform to MHC-IIa after exercise , with significant changes compared with control preoperatively ( P = .028 ) . Protein testing was able to reproduce this increase for MHC-IIa isoform expression only . Conclusion : The 6-week progressive prehabilitation program for subjects undergoing ACLR led to improved knee function based on the single-legged hop test and self-reported assessment using the modified Cincinnati score . These effects were sustained at 12 weeks postoperatively . This study supports prehabilitation as a consideration for patients awaiting ACLR ; however , further studies are warranted CONTEXT The Knee Self-Efficacy Scale ( K-SES ) has good reliability , validity , and responsiveness for patients ' perceived knee-function self-efficacy during rehabilitation after an anterior cruciate ligament ( ACL ) injury . Preoperative knee-function self-efficacy has also been shown to have a predictive ability in terms of outcome 1 y after ACL reconstruction . OBJECTIVE To evaluate a new clinical rehabilitation model containing strategies to enhance knee-function self-efficacy . DESIGN A r and omized , controlled study . SETTING Rehabilitation clinic and laboratory . PATIENTS 40 patients with ACL injuries . INTERVENTION All patients followed a st and ardized rehabilitation protocol . Patients in the experimental group were treated by 1 of 3 physiotherapists who had received specific training in a clinical rehabilitation model . These physiotherapists were also given their patients ' self-efficacy scores after the initial and 4- , 6- , and 12-mo follow-ups , whereas the 5 physiotherapists treating the patients in the control group were not given their patients ' self-efficacy scores . MAIN OUTCOME MEASURES The K-SES , the Tegner Activity Scale , the Physical Activity Scale , the Knee Injury and Osteoarthritis Outcome Score , and the Multidimensional Health Locus of Control . RESULTS Twenty-four patients ( 12 in each group ) completed all follow-ups . Current knee-function self-efficacy , knee symptoms in sports , and knee quality of life improved significantly ( P = .05 ) in both groups during rehabilitation . Both groups had a significantly ( P = .05 ) lower physical activity level at 12 mo than preinjury . No significant differences were found between groups . CONCLUSION In this study there was no evidence that the clinical rehabilitation model with strategies to enhance self-efficacy result ed in a better outcome than the rehabilitation protocol used for the control group |
12,744 | 32,013,061 | This is the first systematic review that has attempted to evaluate the effects of antioxidants on MMP and sperm motility .
Although results are not conclusive due to the dearth of studies , the close relationship between mitochondria and sperm motility is clear .
The investigation of this correlation could provide valuable information to be exploited in clinical practice for the treatment of male infertility | INTRODUCTION The role of nutraceuticals in the treatment of male infertility , especially in the " idiopathic form " , remains the subject of significant debate .
Many antioxidants improve sperm motility but the exact mechanism by which they act is still unclear .
Although several studies have shown a correlation between sperm motility and mitochondrial function , the effects of antioxidant therapy on mitochondrial membrane potential ( MMP ) are poorly studied .
The first aim of this review was to evaluate the efficacy of antioxidants on mitochondrial function and , consequently , on sperm motility in male infertile patients . | Purpose To evaluate whether the in vitro incubation of spermatozoa with myoinositol may improve the fertilization rate in ICSI cycles . Methods This is a prospect i ve , bicentric , r and omized study on 500 MII sibling oocytes injected in 78 ICSI cycles performed between March and October 2013 . R and omization of the oocytes into two groups was performed at the time of the denudation . Fertilization rates ( per oocyte injected with spermatozoa treated with myoinositol versus per oocyte injected with spermatozoa treated with placebo ) were measured as primary outcome and embryo morphology as secondary outcome . Clinical outcomes were also documented . Result (s)Fertilization rate ( 78.9 ± 28.6 % vs 63.2 ± 36.7 , P = 0.002 ) and percentage of grade A embryos on day 3 ( 59.8 ± 35.6 % vs 43.5 ± 41.5 , P = 0.019 ) were significantly higher when spermatozoa were treated in vitro with myoinositol versus placebo . No differences were found for the exp and ed blastocyst formation rate . Conclusion (s)In vitro treatment of spermatozoa with myoinositol may optimize ICSI outcomes by improving the fertilization rate and embryo quality on day 3 . The improvement of the number and the quality of embryos available in an ICSI cycle may have clinical utility if these findings can be confirmed OBJECTIVE To evaluate the mitochondrial membrane potential ( MMP ) of spermatozoa and its correlation with semen parameters and production of reactive oxygen species ( ROS ) in infertile men and healthy donors . DESIGN Controlled prospect i ve study . SETTING Male infertility clinic , Glickman Urological Institute , The Clevel and Clinic Foundation , Clevel and , Ohio . PATIENT(S ) Nineteen infertile men and 7 healthy volunteers . INTERVENTION(S ) St and ard semen analysis , assessment of MMP and ROS production in spermatozoa . The MMP was assessed by flow cytometry using the probe carbocyanine DiOC(6)(3 ) and ROS was measured with chemiluminescence assay using luminol . MAIN OUTCOME MEASURE(S ) The results of MMP are reported as the median interquartile range ( IQR ) number of cells counted in different areas of fluorescence . Results of ROS measurement are expressed as x10(6 ) counted photons per minute per 20 million sperm ( cpm ) . RESULT ( S ) The patients with abnormal semen parameters had a significantly lower MMP [ 1337.7 ( 1066.38 , 1879.2 ) ] , and higher ROS [ 1.12 ( 0.26 , 3.86 ) ] than the donors [ MMP : 2482.9 ( 2162.5 , 3520.6 ) ] and [ ROS : 0.10 ( 0.01 , 0.14 ) ] . The MMP was positively correlated with sperm concentration ( r = 0.62 ) and negatively correlated with the ROS produced ( r = -0.45 ) . CONCLUSION ( S ) Measuring MMP in spermatozoa provides useful information about a man 's fertility potential . Increased ROS production by spermatozoa is associated with a decreased MMP We investigated the effects of folic acid and zinc sulphate supplementation on the improvement of sperm function in subfertile oligoasthenoteratozoospermic ( OAT ) men . Eighty‐three OAT men participated in a 16‐week intervention r and omised , double‐blind clinical trial with daily treatment of folic acid ( 5 mg day−1 ) and zinc sulphate ( 220 mg day−1 ) , or placebo . Before and after treatment , semen and blood sample s were obtained for determining sperm concentration , motility , and morphology , sperm viability , sperm mitochondrial function , sperm chromatin status using toluidine blue , aniline blue , acridine orange and chromomycin A3 staining ; and semen and blood folate , zinc , B12 , total antioxidant capacity ( TAC ) and malondialdehyde ( MDA ) concentrations . Sperm concentration ( ×106 ml−1 ) increased in subfertile men receiving the combined treatment of folic acid and zinc sulphate and also in the group receiving only folic acid treatment ; however , it was not statistically significant ( P = 0.056 and P = 0.05 , respectively ) . Sperm chromatin integrity ( % ) increased significantly in subfertile men receiving only zinc sulphate treatment ( P = 0.048 ) . However , this improvement in sperm quality was not significant after adjusting placebo effect . This study showed that zinc sulphate and folic acid supplementation did not ameliorate sperm quality in infertile men with severely compromised sperm parameters , OAT . Male infertility is a multifactorial disorder , and also nutritional factors play an important role in results of administration of supplementation on sperm parameters . However , these results should be confirmed by multiple studies in larger population s of OAT men Introduction Infertility affects 50 to 80 million ( between 8 and 12 % of couples ) . Male factor is a cause of infertility in almost half of the cases , mainly due to oligoasthenoteratozoospermia . DNA fragmentation is now considered an important factor in the aetiology of male infertility . We studied the effects on semen analysis and on DNA fragmentation of in vivo admnistration of Myo-Inositol and Tribulus Terrestris plus Alga Ecklonia plus Biovis ( Tradafertil ; Tradapharma Sagl , Swizerl and ) in men with previously diagnosed male infertility . Material s and Methods Sixty patients were enrolled in the present study and were r and omized into two subgroups : the group A who received Myo-inositol 1000 mg , Tribulus Terrestris 300 mg , Alga Ecklonia Bicyclis 200 mg and Biovis one tablet a day for 90 days , and the group B ( placebo group ) who received one placebo tablet a day for 90 days . The primary efficacy outcome was the improvement of semen characteristics after 3 months ’ therapy and the secondary outcome was the reduction of the DNA fragmentation after treatment . Results The groups were homogenous for age , hormonal levels , sperm concentration and all parameters of sperm analysis . Sperm concentration and progressive motility improved after treatment with Tradafertil ( 3.82 Mil/ml vs. 1.71 Mil/ml ; p<0.05 ; 4.86 % vs. 1.00 % ; p<0.05 ) as well as the DNA fragmentation ( -1.64 % vs -0.39 % , p<0.001 ) . No side effects were revealed . Conclusions In conclusion , we can affirm that Tradafertil is safe and tolerable . It is a new phytotherapic approach to Oligoasthenoteratospermia ( OAT ) syndrome that could lead to good results without interacting with hypothalamic – pituitary – gonadal axis The aim of this study was to evaluate the possible beneficial effects of diet supplementation with a highly concentrated and purified docosahexaenoic acid ( DHA ) formula on human sperm function . We performed a prospect i ve , r and omized , double blind , placebo-controlled intervention study . One-hundred eighty human semen sample s from sixty infertile patients recruited in a private assisted reproduction center were included . All sample s were examined according to World Health Organization guidelines . We analyzed macroscopic and microscopic sperm parameters , oxidative stress , apoptosis , lipid peroxidation , mitochondrial membrane potential and DNA fragmentation before and after supplementation with different DHA daily doses ( 0.5 , 1 and 2 g ) or placebo for 1 and 3 months . No differences were found in traditional sperm parameters except for progressive sperm motility , with a significant increase after DHA ingestion after the first month with 1 or 2 g doses and after 3 months with 0.5 g of DHA . This effect was more evident in asthenozoospermic patients . No differences were found in any molecular semen parameter except oxidative stress , in which a slight benefit was observed after DHA treatment . In conclusion , this study support previous indications that highlight the importance of DHA supplementation as a means of improving sperm quality in asthenozoospermic men Male infertility is a multifactorial disorder that affects a significant percentage of couples . Its etiology and pathogenesis remain elusive in about one‐third of the cases ; this is referred to as idiopathic infertility . Inositols mediate the sperm processes involved into oocyte fertilization , such as penetration of the ovum cumulus oophorus , binding with the zona pellucida and the acrosome reaction . The aim of this double‐blind , r and omized , placebo‐controlled trial was to evaluate the efficacy and safety of myoinositol ( the most abundant form of inositols present in nature ) treatment in men with idiopathic infertility . To accomplish this , we evaluated the effects of myoinositol on sperm parameters and reproductive hormones at baseline and after 3 months of treatment in men with idiopathic infertility . No adverse reaction was observed . Myoinositol significantly increased the percentage of acrosome‐reacted spermatozoa , sperm concentration , and total count and progressive motility compared to placebo . In addition , myoinositol rebalanced serum luteinizing hormone , follicle‐stimulating hormone , and inhibin B concentrations . The clinical improvement of idiopathic infertile patients should encourage myoinositol use for the treatment of this disorder , even though its detailed mechanisms at the testicular level remain still unclear |
12,745 | 26,563,338 | There is limited evidence evaluating the effect of MDT care on disability , disease activity or QoL in people with RA .
There is likely to be no effect of MDT care on disability at 12 months or other time points | Abstract The objective of this study was to systematic ally review the evidence from r and omised controlled trials ( RCTs ) evaluating the effectiveness of multidisciplinary team ( MDT ) care for the management of disability , disease activity and quality of life ( QoL ) in adults with rheumatoid arthritis ( RA ) . | Objective To determine the clinical effectiveness and cost-effectiveness of nurse-led care ( NLC ) for people with rheumatoid arthritis ( RA ) . Methods In a multicentre pragmatic r and omised controlled trial , the assessment of clinical effects followed a non-inferiority design , while patient satisfaction and cost assessment s followed a superiority design . Participants were 181 adults with RA r and omly assigned to either NLC or rheumatologist-led care ( RLC ) , both arms carrying out their normal practice . The primary outcome was the disease activity score ( DAS28 ) assessed at baseline , weeks 13 , 26 , 39 and 52 ; the non-inferiority margin being DAS28 change of 0.6 . Mean differences between the groups were estimated controlling for covariates following per- protocol ( PP ) and intention-to-treat ( ITT ) strategies . The economic evaluation ( NHS and healthcare perspectives ) estimated cost relative to change in DAS28 and quality -adjusted life-years ( QALY ) derived from EQ5D . Results Demographics and baseline characteristics of patients under NLC ( n=91 ) were comparable to those under RLC ( n=90 ) . Overall baseline-adjusted difference in DAS28 mean change ( 95 % CI ) for RLC minus NLC was −0.31 ( −0.63 to 0.02 ) for PP and -0.15 ( −0.45 to 0.14 ) for ITT analyses . Mean difference in healthcare cost ( RLC minus NLC ) was £ 710 ( −£352 , £ 1773 ) and −£128 ( −£1263 , £ 1006 ) for PP and ITT analyses , respectively . NLC was more cost-effective with respect to cost and DAS28 , but not in relation to QALY utility scores . In all secondary outcomes , significance was met for non-inferiority of NLC . NLC had higher ‘ general satisfaction ’ scores than RLC in week 26 . Conclusions The results provide robust evidence to support non-inferiority of NLC in the management of RA . Trial registration IS RCT Background Workers with rheumatoid arthritis ( RA ) often experience restrictions in functioning at work and participation in employment . Strategies to maintain work productivity exist , but these interventions do not involve the actual workplace . Therefore the aim of this study is to investigate the (cost)effectiveness of an intervention program at the workplace on work productivity for workers with RA . Methods / design This study is a r and omized controlled trial ( RCT ) in specialized rheumatology treatment centers in or near Amsterdam , the Netherl and s. R and omisation to either the control or the intervention group is performed at patient level . Both groups will receive care as usual by the rheumatologist , and patients in the intervention group will also take part in the intervention program . The intervention program consists of two components ; integrated care , including a participatory workplace intervention . Integrated care involves a clinical occupational physician , who will act as care manager , to coordinate the care . The care manager has an intermediate role between clinical and occupational care . The participatory workplace intervention will be guided by an occupational therapist , and involves problem solving by the patient and the patients ’ supervisor . The aim of the workplace intervention is to achieve consensus between patient and supervisor concerning feasible solutions for the obstacles for functioning at work . Data collection will take place at baseline and after 6 and 12 months by means of a question naire . The primary outcome measure is work productivity , measured by hours lost from work due to presenteeism . Secondary outcome measures include sick leave , quality of life , pain and fatigue . Cost-effectiveness of the intervention program will be evaluated from the societal perspective . Discussion Usual care of primary and outpatient health services is not aim ed at improving work productivity . Therefore it is desirable to develop interventions aim ed at improving functioning at work . If the intervention program will be (cost)effective , substantial improvements in work productivity might be obtained among workers with RA at lower costs . Results are expected in 2015.Trial registration Background Comprehensive rehabilitation , involving health professionals from various disciplines , is widely used as an adjunct to pharmacological and surgical treatment in people with rheumatic diseases . However , the evidence for the clinical - and cost-effectiveness of such interventions is limited , and the majority of those who receive rehabilitation are back to their initial health status six to 12 months after discharge . Methods / design To evaluate the goal attainment , health effects and cost-effectiveness of a new rehabilitation programme compared to current traditional rehabilitation programmes for people with rheumatic diseases , a stepped-wedge cluster r and omized trial will be performed . Patients admitted for rehabilitation at six centres in the south-eastern part of Norway will be invited to participate . In the trial , six participating centres will switch from a control ( current rehabilitation programme ) to an intervention phase ( the new rehabilitation programme ) in a r and omized order . Supported by recent research , the new programme will be a supplement to the existing programme at each centre , and will comprise four elements design ed to enhance and support lifestyle changes introduced in the rehabilitation period : structured goal -planning , motivational interviewing , a self-help booklet and four follow-up telephone calls during the first five months following discharge . The primary outcome will be health-related quality of life and goal attainment , as measured by the Patient Generated Index directly before and after the rehabilitation stay , as well as after six and 12 months . Secondary outcomes will include self-reported pain , fatigue , a global assessment of disease activity and motivation for change ( measured on 11-point numeric ratings scales ) , health-related quality of life as measured by the Short Form 36 Health Survey ( SF-36 ) and utility assessed by the SF6D utility index . The main analysis will be on an intention to treat basis and will assess the clinical - and cost-effectiveness of the structured goal planning and tailored follow-up rehabilitation programme for patients with rheumatic diseases . Discussion The findings will constitute an important contribution to more cost-effective- and evidence -based rehabilitation services for people with rheumatic diseases . Trial registration IS RCT N91433175 AIM To compare the long-term effectiveness of care delivered by a clinical nurse specialist ( CNS ) with inpatient team care and day patient team care in patients with rheumatoid arthritis and increasing functional limitations . Background . The role of CNSs in the management of patients with rheumatoid arthritis ( RA ) is evolving , and their effectiveness in comparison with care provided by a rheumatologist alone has been established . However , long-term controlled studies showing how the effectiveness of CNSs compares with that of other forms of co-ordinated care , such as multidisciplinary team care , are lacking . METHODS Two hundred and ten patients rheumatoid arthritis patients were r and omized to care delivered by a CNS in a rheumatology outpatient clinic ( 12 weeks ) , inpatient team care ( 2 weeks ) and day patient team care ( 3 weeks ) . Clinical assessment s recorded on study entry , weeks 12 , 26 , 52 , 78 and 104 comprised the health assessment question naire ( HAQ ) and MacMaster Toronto Arthritis ( MACTAR ) patient preference interview as primary outcome measures . Grip strength , walk test , R AND -36 , Rheumatoid Arthritis Quality of Life question naire and disease activity score ( DAS ) were applied as secondary outcome measures . RESULTS No significant differences in medical treatment , use of services of other health professionals , introduction of adaptive equipment or number of hospitalizations were observed between the three treatment groups during 2 year follow-up , except that visits to nurse specialists were more frequent and home help was less frequent in the CNS group . A comparison of clinical outcomes among the three groups and a comparison between the nurse specialist and inpatient and day patient care groups together did not show any significant differences . Within all three groups functional status , quality of life and disease activity improved significantly ( P < 0.05 ) . In general , the results obtained after 12 weeks remained stable until 104 weeks after the start of the study . CONCLUSION Care provided by a CNS in an outpatient rheumatology clinic has a similar long-term clinical outcome to inpatient and day patient team care in patients with rheumatoid arthritis . A CNS intervention appears to be an effective innovation in the care for patients with rheumatoid arthritis Objective Multidisciplinary team ( MDT ) meetings are assumed to produce better decisions and are extensively used to manage chronic disease in the National Health Service ( NHS ) . However , evidence for their effectiveness is mixed . Our objective was to investigate determinants of MDT effectiveness by examining factors influencing the implementation of MDT treatment plans . This is a proxy measure of effectiveness , because it lies on the pathway to improvements in health , and reflects team decision making which has taken account of clinical and non- clinical information . Additionally , this measure can be compared across MDTs for different conditions . Methods We undertook a prospect i ve mixed- methods study of 12 MDTs in London and North Thames . Data were collected by observation of 370 MDT meetings , interviews with 53 MDT members , and from 2654 patient medical records . We examined the influence of patient-related factors ( disease , age , sex , deprivation , whether their preferences and other clinical /health behaviours were mentioned ) and MDT features ( as measured using the ‘ Team Climate Inventory ’ and skill mix ) on the implementation of MDT treatment plans . Results The adjusted odds ( or likelihood ) of implementation was reduced by 25 % for each additional professional group represented at the MDT meeting . Implementation was more likely in MDTs with clear goals and processes and a good ‘ Team Climate ’ ( adjusted OR 1.96 ; 95 % CI 1.15 to 3.31 for a unit increase in Team Climate Inventory ( TCI ) score ) . Implementation varied by disease category , with the lowest adjusted odds of implementation in mental health teams . Implementation was also lower for patients living in more deprived areas ( adjusted odds of implementation for patients in the most compared with least deprived areas was 0.60 , 95 % CI 0.39 to 0.91 ) . Conclusions Greater multidisciplinarity is not necessarily associated with more effective decision making . Explicit goals and procedures are also crucial . Decision implementation should be routinely monitored to ensure the equitable provision of care Purpose . To examine the effect of an interdisciplinary , out-patient rehabilitation programme for patients with chronic inflammatory arthritis on aerobic capacity and health-related quality of life ( HRQOL ) . Method . One hundred and seventy-four patients , 115 with peripheral arthritis ( PA ) ( 91 women , mean age 53 years , disease duration 16 years ) and 59 with spondylarthropathies ( SpA ) , ( 27 women , mean age 46 years , disease duration 14 years ) were consecutively enrolled in 18 days of interdisciplinary rehabilitation . We report data from evaluations at inclusion , at discharge , and at 4 and 12 months using a sub-maximal treadmill test of aerobic capacity and the Nottingham Health Profile ( NHP ) ( t-test ) . Results . At inclusion , less than 20 % of all patients tested had aerobic capacity classified as ‘ average ’ or better . At discharge , 41 % ( PA ) and 54 % ( SpA ) reached the ‘ average ’ level or better with improvements maintained for 12 months . The total NHP scores improved in both groups ( mean change −12 ( 99%CI –15 , –9 ) for PA ; mean change –13 ( 99%CI –19 , –8 ) for SpA ) and were maintained . Conclusion . Aerobic capacity and HRQOL improved significantly in this interdisciplinary out-patient rehabilitation study , and improvements were maintained for 12 months . The preserved level of aerobic capacity after 12 months indicated a change to a more physically active lifestyle among the participants Background Evidence supports the use of educational and physical training programs for people with rheumatoid arthritis ( RA ) . Objective The purpose of this study was to evaluate the effects of a group-based exercise and educational program on the physical performance and disease self-management of people with RA . Design This was a r and omized controlled trial . Setting The study was conducted at a rehabilitation center in the Netherl and s. Participants Thirty-four people diagnosed with RA participated in the study . Participants were r and omly assigned to either an intervention group ( n=19 ) or a waiting list control group ( n=15 ) . Intervention The intervention in this study was an 8-week , multidisciplinary , group therapy program for people with RA , consisting of physical exercise design ed to increase aerobic capacity and muscle strength ( force-generating capacity ) together with an educational program to improve health status and self-efficacy for disease-self-management . Measurements The main outcome measures were maximum oxygen uptake ( V̇o2max ) , muscle strength of the elbow and knee flexors and extensors , health status , and perceived self-efficacy . All data were recorded before intervention in week 1 , after intervention in week 9 , and at follow-up in week 22 . Results The intervention group showed significant improvement ( 12.1 % ) in V̇o2max at week 9 compared with the control group ( −1.7 % ) . Although significant within-group changes were found over time for muscle strength of the upper and lower extremities and health status that favored the intervention group , no between-group changes were found regarding these outcomes . Limitations An important limitation was the small number of participants included in our study , which may have result ed in a lack of power . Conclusions The present group-based exercise and educational program for people with RA had a beneficial effect on aerobic capacity but not on muscle strength , health status , or self-efficacy OBJECTIVE To study health-related quality of life ( HRQoL ) in arthritis rehabilitation performed by multidisciplinary teams in patients with chronic inflammatory arthritis . Predictors of change in health-related quality of life and the proportion of patients with clinical improvement were investigated . DESIGN Multicentre prospect i ve observational study in 4 European countries . METHODS HRQoL was measured with the European Quality 5 Dimensions ( EQ-5D ) and the Short Form 36 Health Survey ( SF-36 ) in 731 patients who underwent multidisciplinary rehabilitation . Potential predictors were physical functioning ( Health Assessment Question naire ( HAQ ) ) , self-efficacy ( Arthritis Self Efficacy Scale ( ASES ) ) , psychological health ( Hopkins Symptom Check List ( HSCL-25 ) ) , pain/fatigue ( numeric rating scales ( NRS ) ) , age , sex , diagnosis , comorbidity , education , clinical setting and change of medication during rehabilitation . Analysis of covariance ( ANCOVA ) was used to assess for potential predictors and interactions . The minimal important differences for HRQoL were analysed . RESULTS Reporting worse function ( b 0.05 , p = 0.01 ) , less psychological well-being ( b 0.09 , p = 0.000 ) , and experiencing more pain ( b 0.03 , p = 0.000 ) or fatigue ( b 0.02 , p = 0.000 ) at admission predicted improved HRQoL. Change in medication during rehabilitation ( b 0.08 , p = 0.013 ) was associated with greater improvement in HRQoL. These EQ-5D findings were supported by SF-36 findings . Positive minimal important differences were noted in 46 % ( EQ-5D ) and 23 - 47 % ( SF-36 subscales ) of the patients . CONCLUSION Patients with more severe symptoms experienced the largest gain in HRQoL post-intervention . The results of this study are of value for selecting the right patients for rheumatological team rehabilitation The aim of the present study was to compare the effects of in-patient multidisciplinary treatment with st and ard out-patient care in patients with active rheumatoid arthritis ( RA ) . Eighty patients with active RA were r and omized to receive 11 days of in-patient multidisciplinary treatment followed by st and ard out-patient care ( n = 39 ) , or to st and ard out-patient care only ( n = 41 ) . Patients were assessed at baseline , and after 2 , 4 , 12 and 52 weeks . In the in- patients , the improvement in variables of disease activity ( weeks 2 and 4 ) and emotional status ( weeks 4 and 12 ) was greater when compared with the out- patients ( P < 0.05 ) . The improvement in laboratory and functional measures did not differ between the groups . In the in-patient group , the percentage of patients responding to the American College of Rheumatology criteria for improvement was significantly greater at any time point during follow-up than in the out-patient group . A short period of in-patient multidisciplinary treatment for active RA has a direct beneficial effect on disease activity and emotional status with the favourable effect on disease activity remaining after 52 weeks OBJECTIVE To determine whether an outpatient team management program for persons with early chronic inflammatory arthritis would produce improved clinical outcomes and lower costs than traditional , nonteam outpatient rheumatologic care in a clinic setting . METHODS One hundred eighteen patients with chronic inflammatory arthritis were r and omly assigned to a team managed outpatient care program ( TEAMCARE ) or to traditional , one on one , nonteam managed rheumatologic care ( TRADCARE ) . The TEAMCARE program consisted of a half day educational program , a needs assessment intake interview , and quarterly telephone calls , monthly team meetings , and routine rheumatologic care . TRADCARE patient received unconstrained , routine primary and specialty outpatient care as practised typically by rheumatologists at this large multi-specialty clinic . All patients had numerous physical and laboratory outcome assessment s by rheumatologists at office visit . Every 6 months , patients completed several self-report measures of functional status , pain , psychosocial status , and costs . RESULTS One hundred seven patients completed one year of study participation . No significant differences were found between groups in measures of physical status , physical functioning , psychosocial status , or pain . There were no differences between groups in economic or utilization measures . CONCLUSION This team managed outpatient program for persons with recent onset chronic inflammatory arthritis afforded no advantage to routine outpatient care , characterized mainly by one on one relationships between patients and primary care doctors and rheumatologists , in our active outpatient clinical environment 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 The long-term effects of a period of 11 days of in-patient multidisciplinary team care were compared with routine out-patient care in 80 patients with active rheumatoid arthritis ( RA ) . Endpoint measures included swollen and tender joint counts , the patient 's assessment of pain , the patient 's and the physician 's assessment s of disease activity , the ESR and the Health Assessment Question naire ( HAQ ) . Two years after hospitalization , all 39 patients r and omized to the in-patient group and 39 out of 41 patients r and omized to the out-patient group were evaluable . At 2 yr , in the in-patient group the improvement according to mean changes from baseline was greater than that in the out-patient group for all endpoint measures except for the HAQ score , the differences not reaching statistical significance . Averaged over the time points 2 , 52 and 104 weeks , the improvement was significantly greater in the in-patient group than in the out-patient group , except for the ESR and HAQ score . In conclusion , a short period of in-patient multidisciplinary team care has a beneficial effect on disease activity over a period of 2 yr and should be considered as a useful treatment modality in patients with active RA Objectives : To provide a thorough description of team rehabilitation care and compare the structure , process , and outcomes in two specialized arthritis rehabilitation setting s. Methods : Patients with inflammatory arthritis scheduled for inpatient rehabilitation in seven specialized rehabilitation centres and three rheumatology hospital departments in Norway were included consecutively in a prospect i ve cohort study . Patients completed question naires at admission , at discharge , and at a 6-month follow-up , and kept a diary regarding structure and process variables during the rehabilitation stay . Results : Eighty patients in rehabilitation centres and 73 in hospital departments were included and 80 % responded to the 6-month follow-up question naire . The two clinical setting s differed significantly with regard to structure variables such as cost , referral of patients , length of stay , and number of health professionals involved , and most process variables reflecting treatment modalities . The most remarkable difference was in the amount of individual intervention compared with group intervention . Despite significant improvements in most outcomes at discharge , the scores deteriorated towards baseline level 6 months later . There was a trend towards more significant improvement during rehabilitation for patients at rehabilitation centres whereas patients at hospitals had more prolonged improvement . Conclusions : Team rehabilitation for inflammatory arthritis in two different clinical setting s differed across most variables for structure and process , but few significant differences in outcome were found . Considering the substantial differences in cost , there is an urgent need for consensus concerning which patients should receive rehabilitation in which setting . Future research on the development and evaluation of methods for prolonging the beneficial effects of rehabilitation is needed THE R AND OMIZED controlled trial ( RCT ) , more than any other methodology , can have a powerful and immediate impact on patient care . Ideally , the report of such an evaluation needs to convey to the reader relevant information concerning the design , conduct , analysis , and generalizability of the trial . This information should provide the reader with the ability to make informed judgments regarding the internal and external validity of the trial . Accurate and complete reporting also benefits editors and review ers in their deliberations regarding su bmi tted manuscripts . For RCTs to ultimately benefit patients , the published report should be of the highest possible st and ard OBJECTIVES To compare in a r and omized , controlled trial the clinical effectiveness of care delivered by a clinical nurse specialist , inpatient team care , and day patient team care in patients with rheumatoid arthritis ( RA ) who have increasing functional limitations . METHODS Between December 1996 and January 1999 , 210 patients with RA were recruited in the outpatient clinic of the rheumatology department of 6 academic and nonacademic hospitals . Clinical assessment s recorded on study entry and weeks 6 , 12 , 26 , and 52 included the Health Assessment Question naire ( HAQ ) and the McMaster Toronto Arthritis Patient Preference Disability Question naire as primary outcome measures , and the R AND -36 Item Health Survey , the Rheumatoid Arthritis Quality of Life question naire , the Health Utility Rating Scale , and the Disease Activity Score as secondary outcome measures . Patient satisfaction with care was measured on a visual analog scale in week 6 in all 3 groups and again in week 12 in the nurse specialist group . RESULTS Within all 3 groups , functional status , quality of life , health utility , and disease activity improved significantly over time ( P < 0.05 ) . However , a comparison of clinical outcome among the 3 groups and a comparison between the nurse specialist group and the inpatient and day patient care groups together did not show any sustained significant differences . Subgroup analysis showed that age had a significant impact on differences between the 3 treatment groups with respect to functional outcome as measured with the HAQ ( P < 0.001 ) . With increasing age , the most favorable outcome shifted from care provided by a clinical nurse specialist and inpatient care to day patient care . Patients ' satisfaction with care was significantly lower in the nurse specialist group than in the inpatient and day patient care groups ( P < 0.001 ) . CONCLUSION Care provided by a clinical nurse specialist appears to have a similar clinical outcome in comparison with inpatient and day patient team care . Although all patients were highly satisfied with multidisciplinary care , patients who received care provided by a clinical nurse specialist were slightly less satisfied than those who received inpatient or day patient team care . Age appeared to be the only factor related to differences in functional outcome between the 3 treatment groups . The choice of management strategy may , apart from age , further be dependent on the availability of facilities , the preferences of patients and health care providers , and economic considerations In a rheumatology department , 2 r and omized groups of female out patients with rheumatoid arthritis were studied prospect ively for 1 year . The outcome of multidisciplinary team care ( T group , 31 patients ) was compared with that of regular outpatient clinic care ( NT group , 28 patients ) . Pharmacologic treatment and orthopedic specialist consultations were similar in both groups , but use of paramedical care was higher in the T group . Outcome measures of disease activity , specific joint function , and self-rated physical discomfort disclosed no significant differences between the 2 groups . Mental well-being increased in the T group . Overall health , measured by the Sickness Impact Profile , improved significantly only in the T group . This improvement was also significant compared with the NT group OBJECTIVE To assess the sustainable benefits of a professional , multidisciplinary training program for patients with rheumatoid arthritis . DESIGN Two studies with different observation periods . Study I was a prospect i ve , r and omized trial for 1 year . Study II was a noncontrolled observation over 5 years . SETTING The 9-day program for eight patient groups encompassed a multidisciplinary cooperation between rheumatologists , orthopedists , physicotherapists , psychologists and social workers . PATIENTS Sixty-eight consecutive patients with rheumatoid arthritis participated in an arthritis training program either immediately after enrollment in the program or after 1 year . INTERVENTIONS The program covered the following fields : pathogenesis of rheumatoid arthritis , drug therapy , physicotherapy , practical exercise in remedial gymnastics , use of joint protection devices , orthopedic perspectives , psychological counseling , dietetics , information about unproven cures and social assistance . MAIN OUTCOME MEASURES Clinical outcome was assessed by self-report question naires : ( 1 ) Stanford Health Assessment Question naire , ( 2 ) Freiburg Question naire of Coping with Illness , ( 3 ) Beck Depression Inventory , and ( 4 ) a 21-point scale to evaluate cognitive-behavioral and environmental impact . RESULTS A significant and persistent improvement of all investigated parameters was demonstrated in the 1-year controlled trial . Between the end-point of the 1-year study and the 5-year evaluation , this improvement increased even more for functional status and coping with illness , whereas depression returned to baseline values . These effects were seen even without reinforcement of the training . CONCLUSION A professional , multidisciplinary approach to educate patients with rheumatoid arthritis leads to a significant and sustained improvement of the clinical outcome and is an approach that should be established as a part of conventional therapy OBJECTIVE To evaluate the effects of a program for individual education in combination with the use of an arthritis passport . METHODS We studied 3 groups of patients with rheumatoid arthritis . The first experimental group received educational material s and followed the program under the guidance of their regular providers of health care whose activities were coordinated through arthritis passports . The second experimental group only received education material s ; the control group received only usual care . RESULTS There were no effects on self-efficacy expectations , knowledge , health status , or behavior in either experimental group . Opinions of general practitioners , physiotherapists , and visiting nurses concerning the arthritis passport were very positive , but rheumatologists ' opinions were not . Opinions on coordination of care were more positive among the physiotherapists of the experimental group . CONCLUSIONS Individual education for patients with rheumatoid arthritis by health care providers during routine consultations , as implemented in this program , had no effect on self-efficacy expectations , knowledge , health status , or health behavior . Likewise , the distribution of educational material s by itself without the involvement of health care providers had no effect . The use of the arthritis passport improved coordination of care , especially for physiotherapists OBJECTIVE To develop and evaluate the effect of a new arthritis education program based on a previous study . METHODS One hundred individuals with established rheumatoid arthritis r and omized to an intervention group or a control group completed self-report question naires . RESULTS Three months after the education program the patients in the intervention group had increased their knowledge about their disease . They reported increased practice of exercise and joint protection and reduction of disability and pain . After 12 months , increased knowledge and practice of joint protection was maintained . However , there was no longer any difference between the intervention group and the control group regarding reported pain , disability , and practice of exercise . At both intervals the individuals in the intervention group reported an increased ability to h and le their pain and a reduction of problems with their disease . The control group remained stable except for a slight increase in pain . CONCLUSION A structured patient education program had positive impact for 3 months , and some improvements were maintained for 12 months . We suggest that patient education should become an integrated part of the total management of rheumatoid arthritis OBJECTIVE To evaluate the effect on health and functional status of an 8-week group-education program for rheumatoid arthritis ( RA ) in addition to usual medical care . METHODS All consecutive in patients and out patients with RA ( ACR criteria ) were asked to participate in this r and omized , prospect i ve , controlled trial . The educational intervention consisted of 8 weekly ambulatory sessions , each lasting 6 hours . Followup was undertaken after 1 year . The primary criterion for judging effectiveness was the Health Assessment Question naire ( HAQ ) score ; secondary criteria consisted of coping , medical knowledge , patient global satisfaction , and quality of life scores before the intervention and after 1 year . RESULTS We asked 1242 in patients and out patients to participate in the study : 208 ( 16.75 % ) agreed ( 104 in each group ) . At baseline , there was no statistically significant difference between the 2 groups . After 1 year , no statistically significant difference was observed between the 2 groups in change in HAQ score : -0.04 + /- 0.46 ( education group ) vs -0.06 + /- 0.47 ( control group ) ( p = 0.79 ) . Statistically significant differences were found in 3 domains : patient coping ( -1.22 + /- 5.55 vs -0.22 + /- 3.81 ; p = 0.03 ) , knowledge ( 3.42 + /- 4.73 vs 0.73 + /- 3.78 ; p < 0.0001 ) , and satisfaction ( 10.07 + /- 11.70 vs 5.72 + /- 13.77 ; p = 0.02 ) , all of which were better for the group attending the education sessions . CONCLUSION Despite improvements in patient coping , knowledge , and satisfaction , the education program was not found to be effective at 1 year . There may have been method ological problems relating to the sensitivity of question naires and patient selection , and tailored educational interventions should be considered Patients with rheumatoid arthritis must learn to adjust their exercise , rest and medication to the varying activity of the disease . Patient education can help patients in making the right decisions about adjustments in their treatment regimen and in attaining " self-management " behaviors . We developed a group education program based on social learning theory and the ' Arthritis Self-Management Course ' developed in the USA by Lorig . Goal of the program is the strengthening of self-efficacy , outcome expectations and self-management behaviors of RA patients which may lead to better health status . The program has been evaluated in an experimental design . We established significant positive effects of the group training on functional disability , joint tenderness , practice of relaxation and physical exercises , self-management behavior , outcome expectations , self-efficacy function and knowledge . After 14 months we still found effects on practice of physical exercises , self-efficacy function and knowledge |
12,746 | 27,306,751 | Site of underlying infection and illness severity may have favored overweight and obese BMI s. Conclusions This is the first meta- analysis to show that overweight or obese BMI s reduce adjusted mortality in adults admitted to the ICU with sepsis , severe sepsis , or septic shock . | Background At least 25 % of adults admitted to intensive care units ( ICU ) in the United States have an overweight , obese or morbidly obese body mass index ( BMI ) .
The effect of BMI on adjusted mortality in adults requiring ICU treatment for sepsis is unclear .
We performed a systematic review of adjusted all-cause mortality for underweight , overweight , obese and morbidly obese BMI s relative to normal BMI for adults admitted to the ICU with sepsis , severe sepsis , and septic shock . | Objectives : To examine the incidence of infections and to describe them and their outcome in intensive care unit ( ICU ) patients . Design and setting : International prospect i ve cohort study in which all patients admitted to the 28 participating units in eight countries between May 1997 and May 1998 were followed until hospital discharge . Patients : A total of 14,364 patients were admitted to the ICUs , 6011 of whom stayed less than 24 h and 8353 more than 24 h. Results : Overall 3034 infectious episodes were recorded at ICU admission ( crude incidence : 21.1 % ) . In ICU patients hospitalised longer than 24 h there were 1581 infectious episodes ( crude incidence : 18.9 % ) including 713 ( 45 % ) in patients already infected at ICU admission . These rates varied between ICUs . Respiratory , digestive , urinary tracts , and primary bloodstream infections represented about 80 % of all sites . Hospital-acquired and ICU-acquired infections were documented more frequently microbiologically than community-acquired infections ( 71 % and 86 % , respectively vs. 55 % ) . About 28 % of infections were associated with sepsis , 24 % with severe sepsis and 30 % with septic shock , and 18 % were not classified . Crude hospital mortality rates ranged from 16.9 % in non-infected patients to 53.6 % in patients with hospital-acquired infections at the time of ICU admission and acquiring infection during the ICU stay . Conclusions : The crude incidence of ICU infections remains high , although the rate varies between ICUs and patient subsets , illustrating the added burden of nosocomial infections in the use of ICU re sources OBJECTIVE The aim of the study was to evaluate the expression of tumor necrosis factor (TNF)-alpha protein in the subcutaneous and visceral adipose tIssue in correlation with adipocyte cell Volume , serum TNF-alpha , soluble TNF-receptor-2 ( sTNFR-2 ) and indirect parameters of insulin resistance in overweight/obese and lean healthy persons . DESIGN A cross-sectional case-control study was used . PATIENTS Twenty-eight overweight/obese prob and s with normal glucose tolerance ( BMI > 27 kg/m(2 ) ) and 15 lean people ( BMI < 25 kg/m(2 ) ) , all of them undergoing planned surgical operation , participated in the study . METHODS Two to four grams of subcutaneous and visceral adipose tIssue were removed and studied using semi-quantitative immunohistochemical staining of the TNF-alpha protein . Serum TNF-alpha , sTNFR-2 ( ELISA ) and fasting C-peptide ( RIA ) were measured . RESULTS TNF-alpha protein was expressed in adipocytes of both depots . The expression was evaluated visually and found to be greater in the obese patients . Significantly higher serum TNF-alpha ( 5.58+/-0.87 pg/ml vs 4.21+/-0.55 , mean+/-s.d . , P<0.01 , Mann-Whitney ) and sTNFR-2 levels ( 7.84+/-3.56 ng/ml vs 4.59+/-1.35 , P=0.005 ) were found in the obese subgroup in correlation with the fasting C-peptide level ( r=0.49 , P=0.003 ; and r=0.74 , P=0.001 ) and the C-peptide/ blood glucose ratio ( r=0.47 , Spearman , P=0.005 ; and r=0.70 , P=0.001 ) . The cell Volume of both adipocyte depots was found to have a significant positive correlation with serum TNF-alpha and sTNFR-2 levels in the total group of patients ( subcutaneous : r=0.52 , P=0.0003 ; r=0.69 , P<0.0001 ; visceral : r=0.65 , P<0.0001 ; r=0.63 , P<0.0001 ) and in both subgroups . CONCLUSIONS Adipocyte cell Volume of both the subcutaneous and visceral fat depots may be determinants of TNF-alpha , sTNFR-2 production and obesity-linked insulin resistance 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 . ) We report the findings from a prospect i ve study determining the magnitude of errors in the visual estimation of weight and height of critically ill patients . Forty-two consecutive patients were weighed by a physician with a calibrated stretcher scale and length measured with a steel measuring tape . The predicted body weight was calculated using the ARDSnet formulae . Attending physicians and nurses were asked to estimate patient 's actual weight , predicted weight and height . The average percent errors in estimation of actual and predicted weight were 11.4 and 14.6 % , respectively . Errors greater than 20 % in patient 's actual and predicted weight were observed in 15 and 24 % of cases , respectively . The majority of height estimations ( 86 % ) had an error < 10 % . There were non-significant differences between the estimations made by intensive care unit physicians and nurses . Our study shows that estimations of patient 's weight made by intensive care unit staff are often inaccurate . In contrast , estimations of height made by intensive care unit staff are usually adequate . Estimated body weight of critically ill patients has implication s for drug and respiratory therapy and should be used with caution Purpose . Data suggest that obesity in critical illness is associated with improved outcomes . We postulate that these findings may be influenced by preillness comorbidities . We sought to determine if critically ill obese patients without significant comorbidity had improved mortality compared to obese patients with multiple comorbidities . Material s and Methods . We analyzed data from a prospect i ve observational study conducted in 3 tertiary ICUs . Severely obese ( body mass index ≥30 ) adults in the ICU for ≥24 hours were identified and classified into limited comorbid illnesses ( 0 - 1 ) or multiple comorbidities ( ≥2 ) . The primary outcome was the odds ratio ( OR ) of mortality at day 28 . Important secondary outcomes were ICU length of stay and ICU free days in the first 28 days . Results . 598 patients were enrolled ; 183 had BMI ≥30 . Of these , 38 had limited comorbidities and 145 had multiple comorbidities . In unadjusted analyses , obese patients with multiple comorbidities were 4.70 times ( 95 % CI 1.07–20.6 ) as likely to die by day 28 compared to patients with limited comorbidities ( P = 0.04 ) . After stratifying by admission diagnosis and adjusting for APACHE II score , the influence of comorbidities remained large and trended toward significance ( OR 4.28 , 95 % CI 0.92–20.02 , P = 0.06 ) . In adjusted analyses , obese patients with multiple comorbidities tended to have longer ICU duration ( 3.06 days , SE 2.28 , P = 0.18 ) and had significantly fewer ICU free days in the first 28 days ( −3.92 days , SE 1.83 , P = 0.03 ) . Conclusions . Not all critically ill obese patients are the same . Those with less comorbidity may have better outcomes than those with multiple comorbidities . This may be important when considering prognosis and discussing care with patients and families Background Recent sepsis guidelines have focused on the early identification and risk stratification of patients on presentation . Obesity is associated with alterations in multiple inflammatory regulators similar to changes seen in sepsis , suggesting a potential interaction between the presence of obesity and the severity of illness in sepsis . Methods We performed a retrospective chart review of patients admitted with a primary billing diagnosis of sepsis at a single United States university hospital from 2007 to 2010 . Seven hundred and ninety-two charts were identified meeting inclusion criteria . Obesity was defined as a body mass index ( BMI ) ≥ 30 kg/m2 . The data recorded included age , race , sex , vital signs , laboratory values , length of stay , comorbidities , weight , height , and survival to discharge . A modified APACHE II score was calculated to estimate disease severity . The primary outcome variable was inpatient mortality . Results Survivors had higher average BMI than nonsurvivors ( 27.6 vs. 26.3 kg/m2 , p = 0.03 ) in unadjusted analysis . Severity of illness and comorbid conditions including cancer were similar across BMI categories . Increased incidence of diabetes mellitus type 2 was associated with increasing BMI ( p < 0.01 ) and was associated with decreased mortality , with an odds ratio of 0.53 compared with nondiabetic patients . After adjusting for age , gender , race , severity of illness , length of stay , and comorbid conditions , the trend of decreased mortality for increased BMI was no longer statistically significant , however diabetes continued to be strongly protective ( odds ratio 0.52 , p = 0.03 ) . Conclusions This retrospective analysis suggests obesity may be protective against mortality in septic in patients . The protective effect of obesity may be dependent on diabetes , possibly through an unidentified hormonal intermediary . Further prospect i ve studies are necessary to elaborate the specific mechanism of this protective effect Objective : To better define the incidence of sepsis and the characteristics of critically ill patients in European intensive care units . Design : Cohort , multiple-center , observational study . Setting : One hundred and ninety-eight intensive care units in 24 European countries . Patients : All new adult admissions to a participating intensive care unit between May 1 and 15 , 2002 . Interventions : None . Measurements and Main Results : Demographic data , comorbid diseases , and clinical and laboratory data were collected prospect ively . Patients were followed up until death , until hospital discharge , or for 60 days . Of 3,147 adult patients , with a median age of 64 yrs , 1,177 ( 37.4 % ) had sepsis ; 777 ( 24.7 % ) of these patients had sepsis on admission . In patients with sepsis , the lung was the most common site of infection ( 68 % ) , followed by the abdomen ( 22 % ) . Cultures were positive in 60 % of the patients with sepsis . The most common organisms were Staphylococcus aureus ( 30 % , including 14 % methicillin-resistant ) , Pseudomonas species ( 14 % ) , and Escherichia coli ( 13 % ) . Pseudomonas species was the only microorganism independently associated with increased mortality rates . Patients with sepsis had more severe organ dysfunction , longer intensive care unit and hospital lengths of stay , and higher mortality rate than patients without sepsis . In patients with sepsis , age , positive fluid balance , septic shock , cancer , and medical admission were the important prognostic variables for intensive care unit mortality . There was considerable variation between countries , with a strong correlation between the frequency of sepsis and the intensive care unit mortality rates in each of these countries . Conclusions : This large pan-European study documents the high frequency of sepsis in critically ill patients and shows a close relationship between the proportion of patients with sepsis and the intensive care unit mortality in the various countries . In addition to age , a positive fluid balance was among the strongest prognostic factors for death . Patients with intensive care unit acquired sepsis have a worse outcome despite similar severity scores on intensive care unit admission OBJECTIVES This study sought to define the relationship between body mass index ( BMI ) and mortality in heart failure ( HF ) across the world and to identify specific groups in whom BMI may differentially mediate risk . BACKGROUND Obesity is associated with incident HF , but it is paradoxically associated with better prognosis during chronic HF . METHODS We studied 6,142 patients with acute decompensated HF from 12 prospect i ve observational cohorts followed-up across 4 continents . Primary outcome was all-cause mortality . Cox proportional hazards models and net reclassification index described associations of BMI with all-cause mortality . RESULTS Normal-weight patients ( BMI 18.5 to 25 kg/m(2 ) ) were older with more advanced HF and lower cardiometabolic risk . Despite worldwide heterogeneity in clinical features across obesity categories , a higher BMI remained associated with decreased 30-day and 1-year mortality ( 11 % decrease at 30 days ; 9 % decrease at 1 year per 5 kg/m(2 ) ; p < 0.05 ) , after adjustment for clinical risk . The BMI obtained at index admission provided effective 1-year risk reclassification beyond current markers of clinical risk ( net reclassification index 0.119 , p < 0.001 ) . Notably , the " protective " association of BMI with mortality was confined to persons with older age ( > 75 years ; hazard ratio [ HR ] : 0.82 ; p = 0.006 ) , decreased cardiac function ( ejection fraction < 50 % ; HR : 0.85 ; p < 0.001 ) , no diabetes ( HR : 0.86 ; p < 0.001 ) , and de novo HF ( HR : 0.89 ; p = 0.004 ) . CONCLUSIONS A lower BMI is associated with age , disease severity , and a higher risk of death in acute decompensated HF . The " obesity paradox " is confined to older persons , with decreased cardiac function , less cardiometabolic illness , and recent-onset HF , suggesting that aging , HF severity/chronicity , and metabolism may explain the obesity paradox RATIONALE Difficult intubation in the intensive care unit ( ICU ) is a challenging issue . OBJECTIVES To develop and vali date a simplified score for identifying patients with difficult intubation in the ICU and to report related complications . METHODS Data collected in a prospect i ve multicenter study from 1,000 consecutive intubations from 42 ICUs were used to develop a simplified score of difficult intubation , which was then vali date d externally in 400 consecutive intubation procedures from 18 other ICUs and internally by bootstrap on 1,000 iterations . MEASUREMENTS AND MAIN RESULTS In multivariate analysis , the main predictors of difficult intubation ( incidence = 11.3 % ) were related to patient ( Mallampati score III or IV , obstructive sleep apnea syndrome , reduced mobility of cervical spine , limited mouth opening ) ; pathology ( severe hypoxia , coma ) ; and operator ( nonanesthesiologist ) . From the β parameter , a seven-item simplified score ( MACOCHA score ) was built , with an area under the curve ( AUC ) of 0.89 ( 95 % confidence interval [ CI ] , 0.85 - 0.94 ) . In the validation cohort ( prevalence of difficult intubation = 8 % ) , the AUC was 0.86 ( 95 % CI , 0.76 - 0.96 ) , with a sensitivity of 73 % , a specificity of 89 % , a negative predictive value of 98 % , and a positive predictive value of 36 % . After internal validation by bootstrap , the AUC was 0.89 ( 95 % CI , 0.86 - 0.93 ) . Severe life-threatening events ( severe hypoxia , collapse , cardiac arrest , or death ) occurred in 38 % of the 1,000 cases . Patients with difficult intubation ( n = 113 ) had significantly higher severe life-threatening complications than those who had a nondifficult intubation ( 51 % vs. 36 % ; P < 0.0001 ) . CONCLUSIONS Difficult intubation in the ICU is strongly associated with severe life-threatening complications . A simple score including seven clinical items discriminates difficult and nondifficult intubation in the ICU . Clinical trial registered with www . clinical trials.gov ( NCT 01532063 ) Purpose To investigate the possible impact of obesity , as assessed by body mass index ( BMI ) , on outcome in surgical intensive care unit ( ICU ) patients . Methods Prospect ively collected data from all consecutive adult patients admitted to our ICU between January 2004 and January 2009 were analysed retrospectively . BMI was calculated using the formula : BMI = body weight/height2 ( kg/m2 ) , and patients were grouped as underweight ( < 18.5 kg/m2 ) , normal weight ( 18.5–24.9 kg/m2 ) , overweight ( 25–29.9 kg/m2 ) , obese ( 30–39.9 kg/m2 ) and very obese ( ≥40 kg/m2 ) . Results Among the 12,938 patients who were admitted to our ICU during the study period , 9,935 ( 76.8 % ) had complete height and weight data and constituted the study group . The mean BMI was 27.1 ± 5.0 kg/m2 . Overall , 34.4 % of the study population had normal BMI , 1.8 % were underweight , 41.2 % were overweight , 20.8 % were obese and 1.8 % were very obese . The ICU mortality rate was similar among BMI subgroups , but hospital mortality was higher in underweight patients than in patients with normal BMI ( 17.8 % versus 11.1 % , P = 0.006 ) . On multivariate Cox regression analysis , being overweight [ hazard ratio ( HR ) 0.86 , 95 % confidence interval ( CI ) 0.74–0.99 , P = 0.047 ] or obese ( HR = 0.83 , 95 % CI = 0.69–0.99 , P = 0.047 ) was independently associated with lower 60-day in-hospital mortality , with normal BMI as the reference category . Risk of death increased in very obese patients , especially after neurosurgical procedures ( HR = 0.3 , 95 % CI = 1.06–8.48 , P = 0.039 ) . Conclusion In this cohort of surgical ICU patients , being overweight or obese was associated with decreased risk of 60-day in-hospital mortality Objective To investigate the numbers , clinical characteristics , re source use , and outcomes of admissions who met precise clinical and physiologic criteria for severe sepsis ( as defined in the PROWESS trial ) in the first 24 hrs in the intensive care unit . Design Observational cohort study , with retrospective analysis of prospect ively collected data . Setting Ninety-one adult general intensive care units in Engl and , Wales , and Northern Irel and between 1995 and 2000 . Patients Patients were 56,673 adult admissions . Interventions None . Measurements and Main Results We found that 27.1 % of adult intensive care unit admissions met severe sepsis criteria in the first 24 hrs in the intensive care unit . Most were nonsurgical ( 67 % ) , and the most common organ system dysfunctions were seen in the cardiovascular ( 88 % ) and respiratory ( 81 % ) systems . Modeling the data for Engl and and Wales for 1997 suggested that 51 ( 95 % confidence interval , 46–58 ) per 100,000 population per year were admitted to intensive care units and met severe sepsis criteria in the first 24 hrs . Of the intensive care unit admissions who met severe sepsis criteria in the first 24 hrs , 35 % died before intensive care unit discharge and 47 % died during their hospital stay . Hospital mortality rate ranged from 17 % in the 16–19 age group to 64 % in those > 85 yrs . In Engl and and Wales in 1997 , an estimated 24 ( 95 % confidence interval , 21–28 ) per 100,000 population per year died after intensive care unit admissions with severe sepsis in the first 24 hrs . For intensive care unit admissions who met severe sepsis criteria in the first 24 hrs , median intensive care unit length of stay was 3.56 days ( interquartile range , 1.50–9.32 ) and median hospital length of stay was 18 days ( interquartile range , 8–36 days ) . These admissions used 45 % of the intensive care unit and 33 % of the hospital bed days used by all intensive care unit admissions . Conclusions Severe sepsis is common and presents a major challenge for clinicians , managers , and healthcare policymakers . Intensive care unit admissions meeting severe sepsis criteria have a high mortality rate and high re source use BACKGROUND Sarcopenia is prevalent in older population s with many causes and varying outcomes however information for use in clinical practice is still lacking . AIMS The aim of this report is to identify the clinical determinants and prognostic significance of sarcopenia in a cohort of hospitalized acutely ill older patients . METHODS Four hundred and thirty two r and omly selected patients had their baseline clinical characteristic data assessed within 72 h of admission , at 6 weeks and at 6 months . Nutritional status was assessed from anthropometric and biochemical data . Sarcopenia was diagnosed from low muscle mass and low muscle strength-h and grip using anthropometric measures based on the European Working Group criteria . RESULTS Compared with patients without sarcopenia , those diagnosed with sarcopenia 44 ( 10 % ) were more likely to be older , have more depression symptoms and lower serum albumin concentration . The length of hospital stay ( LOS ) was significantly longer in patients diagnosed with sarcopenia compared with patients without sarcopenia [ mean ( SD ) LOS 13.4 ( 8.8 ) versus 9.4 ( 7 ) days respectively , p = 0.003 ] . The risk of non-elective readmission in the 6 months follow up period was significantly lower in patients without sarcopenia compared with those diagnosed with sarcopenia ( adjusted hazard ratio .53 ( 95 % CI : .32 to .87 , p = 0.013 ) . The death rate was also lower in patients without sarcopenia 38/388 ( 10 % ) , compared with those with sarcopenia 12/44 ( 27 % ) , p-value = .001 . CONCLUSION Older people with sarcopenia have poor clinical outcome following acute illness compared with those without sarcopenia Background Following publication of the PRISMA statement , the UK Centre for Review s and Dissemination ( CRD ) at the University of York in Engl and began to develop an international prospect i ve register of systematic review s with health-related outcomes . The objectives were to reduce unplanned duplication of review s and provide transparency in the review process , with the aim of minimizing reporting bias . Methods An international advisory group was formed and a consultation undertaken to establish the key items necessary for inclusion in the register and to gather views on various aspects of functionality . This article describes the development of the register , now called PROSPERO , and the process of registration . Results PROSPERO offers free registration and free public access to a unique prospect i ve register of systematic review s across all areas of health from all around the world . The dedicated web-based interface is electronically search able and available to all prospect i ve registrants . At the moment , inclusion in PROSPERO is restricted to systematic review s of the effects of interventions and strategies to prevent , diagnose , treat , and monitor health conditions , for which there is a health-related outcome .Ideally , registration should take place before the research ers have started formal screening against inclusion criteria but review s are eligible as long as they have not progressed beyond the point of completing data extraction .The required data set captures the key attributes of review design as well as the administrative details necessary for registration .Su bmi tted registration forms are checked against the scope for inclusion in PROSPERO and for clarity of content before being made publicly available on the register , rejected , or returned to the applicant for clarification . The public records include an audit trail of major changes to planned methods , details of when the review has been completed , and links to result ing publications when provided by the authors . Conclusions There has been international support and an enthusiastic response to the principle of prospect i ve registration of protocol s for systematic review s and to the development of PROSPERO .In October 2011 , PROSPERO contained 200 records of systematic review s being undertaken in 26 countries around the world on a diverse range of interventions Background : Because the aquaporin ( AQP ) 5 promoter −1364A/C polymorphism is associated with altered AQP5 expression , this association could have an impact on key mechanisms in sepsis , such as cell migration , activity of the rennin-angiotensin- aldosterone system ( RAAS ) , and water transport across biologic membranes . Therefore , we tested the hypothesis that the AQP5 promoter −1364A/C polymorphism is associated with increased 30-day survival in severe sepsis . Methods : In a prospect i ve study , adults with severe sepsis ( N = 154 ) were genotyped for the AQP5 promoter −1364A/C polymorphism . The clinical endpoint was 30-day survival . Kaplan – Meier plots and multivariate proportional hazard analyses were used to evaluate the relationship between genotypes and clinical outcomes . Results : Thirty-day survival was significantly associated with AQP5 −1364A/C genotypes ( P = 0.001 ) . Survival rates were 57 % for AA genotypes ( n = 90 ) but 83 % for combined AC/CC genotypes ( 56 vs. 8 , respectively ) . Multivariate proportional hazard analysis including sex , age , Simplified Acute Physiology Score II , Sequential Organ Failure Assessment score , body mass index , necessity for continuous hemofiltration/dialysis , concentrations of plasma angiotensin II , serum aldosterone , C-reactive protein , and interleukin 6 as covariates revealed the AQP5 −1364A/C polymorphism as a strong and independent prognostic factor for 30-day survival . In this analysis , homozygous AA subjects were at high risk for death within 30 days ( hazard ratio , 3.59 ; 95 % CI , 1.47–8.80 ; P = 0.005 ) compared with AC/CC genotypes . Conclusion : The C-allele of the AQP5 −1364A/C polymorphism is associated with increased 30-day survival in patients with severe sepsis . This finding suggests the importance of variations in expression of AQP5 channels in severe sepsis BACKGROUND Intubation procedure in obese patients is a challenging issue both in the intensive care unit ( ICU ) and in the operating theatre ( OT ) . The objectives of the study were ( i ) to compare the incidence of difficult intubation and ( ii ) its related complications in obese patients admitted to ICU and OT . METHODS We conducted a multicentre prospect i ve observational cohort study in ICU and OT in obese ( BMI ≥30 kg m(-2 ) ) patients . The primary endpoint was the incidence of difficult intubation . Secondary endpoints were the risk factors for difficult intubation , the use of difficult airway management techniques , and severe life-threatening complications related to intubation ( death , cardiac arrest , severe hypoxaemia , severe cardiovascular collapse ) . RESULTS In cohorts of 1400 and 11 035 consecutive patients intubated in ICU and in the OT , 282 ( 20 % ) and 2103 ( 19 % ) were obese . In obese patients , the incidence of difficult intubation was twice more frequent in ICU than in the OT ( 16.3 % vs 8.2 % , P<0.01 ) . In both cohorts , risk factors for difficult intubation were Mallampati score III/IV , obstructive sleep apnoea syndrome , and reduced mobility of cervical spine , while limited mouth opening , severe hypoxaemia , and coma appeared only in ICU . Specific difficult airway management techniques were used in 66 ( 36 % ) cases of difficult intubation in obese patients in the OT and in 10 ( 22 % ) cases in ICU ( P=0.04 ) . Severe life-threatening complications were significantly more frequent in ICU than in the OT ( 41.1 % vs 1.9 % , relative risk 21.6 , 95 % confidence interval 15.4 - 30.3 , P<0.01 ) . CONCLUSIONS In obese patients , the incidence of difficult intubation was twice more frequent in ICU than in the OT and severe life-threatening complications related to intubation occurred 20-fold more often in ICU . CLINICAL TRIAL REGISTRATION Current controlled trials . Identifier : NCT01532063 Objective : Numerous calculations routinely used in the intensive care require the knowledge of patients ’ weight and height , although these measurements are not always made . Estimates by doctors or nurses are often substituted . This study sought to ascertain the accuracy of estimates of weight and height of patients made by intensive care unit ( ICU ) staff . Design : Prospect i ve clinical study . Setting : Sixteen-bed mixed medical and surgical ICU in a university teaching hospital . Patients : Fourteen patients had their height and weight estimated by 20 members of the medical and nursing staff . Measurements : After all estimates had been recorded , measurements of weight and height were obtained . Weight was measured by means of a patient hoist with a calibrated weighing facility and height using a steel tape measure . Main Results : Estimation of weight was poor , with 47 % of estimates at least 10 % different and 19 % of estimates at least 20 % different from the measured values . The majority of height estimates were within 10 % of the measured values . Conclusions : Individual estimates of weight and height are frequently inaccurate . These errors of estimation could compromise application of effective therapies , as well as contribute to a reduction in design sensitivity of clinical trials |
12,747 | 26,993,844 | Among them , the ChronIc Venous Insufficiency Question naire ( CIVIQ ) , Aberdeen Varicose Vein Question naire ( AVVQ ) , and VEnous INsufficiency Epidemiological and Economic Study on Quality of Life ( VEINES-QOL ) scales were the most highly used according to the literature , and CIVIQ and VEINES-QOL were the most extensively vali date d scales and had the longest iterative validation process .
This systematic review confirmed that CVDs have an important effect on QOL .
Two scales , CIVIQ and VEINES-QOL , emerged as being thoroughly vali date d instruments , although factorial stability was not demonstrated for the VEINES-QOL . | OBJECTIVE We conducted a systematic review of the literature about quality -of-life ( QOL ) scales in chronic venous disorders ( CVDs ) comprising leg ulcers to identify the respective advantages and deficits of existing tools . | Endovenous laser ablation ( EVLA ) and radiofrequency ablation ( RFA ) are both associated with excellent technical , clinical and patient‐reported outcomes for the treatment of varicose veins . The aim of this study was to compare the techniques in a r and omized clinical trial Quality of life may be considerably reduced in patients who are suffering from chronic lower limb venous insufficiency , although existing generic quality of life instruments ( NHP , SF-36 or SIP ) can not completely identify their specific complaints . The Chronic Venous Insufficiency Question naire ( CIVIQ ) has been developed by iterative process . First , a pilot group of 20 patients was used to identify a number of important features of quality of life affected by venous insufficiency , other than physical symptoms of discomfort . A second study involving 2,001 subjects was used to reduce the number of items . Subjects were asked to score both the severity of their problems and the importance they attributed to each problem on a 5-point Likert scale . The importance items found in patients with venous insufficiency were subjected to factorial analyses ( PCA , PAF ) . The final version is a 20-item self-administered question naire which explores four dimensions : psychological , physical and social functioning and pain . Internal consistency of the question naire was vali date d for each dimension ( Cronbach 's alpha > 0.820 for three out of four factors ) . Reproducibility was confirmed in a 60 patient test-retest study . Pearson 's correlation coefficients for both the four dimension subscales and for the global score at 2-week intervals were greater than 0.940 . Finally , the question naire was tested in a r and omized clinical trial of 934 patients in order to assess responsiveness and the convergent validity of the instrument , together with the patient 's own quality of life . This study demonstrated that convergence was valid : Pearson 's correlation coefficients between clinical score differences and quality of life score differences were small ( from 0.199–0.564 ) but were statistically different from 0 ( p<0.001 ) . St and ardized response mean ( SRM ) and effect size ( ES ) were calculated to assess sensitivity to change . SRM and ES both demonstrated considerble responsiveness to change ( > 0.80 ) . Reliability , face , content , construct validity and responsiveness were also determined for this specific quality of life question naire relating to venous insufficiency . Results suggest that this question naire may be used with confidence to assess quality of life in clinical trials on chronic venous insufficiency OBJECTIVES This study aims to compare the efficacy and side effects of foam sclerotherapy of the saphenous veins with or without post-treatment compression using graduated elastic stockings . DESIGN This is a prospect i ve open r and omised controlled trial conducted in two centres . PATIENTS AND METHODS Sixty patients with incompetent great ( GSV ) or small saphenous veins ( SSV ) underwent ultrasound-guided foam sclerotherapy . R and omisation was conducted immediately after sclerotherapy to two parallel groups , one ( CG ) with compression stockings ( 15 - 20 mmHg worn during the day , for 3 weeks ) and the other ( WCG ) without compression . Efficacy of sclerotherapy and all of the side effects were assessed , including side effects in the treated region . On days 14 and 28 , clinical and duplex ultrasound ( DUS ) assessment s were performed by independent experts . Patients also completed quality of life ( QOL ) , symptom question naires and provided satisfaction scores . RESULTS Five men and 55 women ranging in age from 32 to 78 ( mean 57 years ) years were included : 29 in the WCG and 31 in the CG group . On day 28 , abolition of venous reflux and occlusion of the vein was obtained in 100 % of the cases in both groups . The length of the occluded vein was the same in both groups ( mean 36 cm for the GSV and 30 cm for the SSV ) as was the mean diameter of the occluded vein ( 5 mm ) . Symptoms and QOL question naires showed equivalent improvement in both groups on day 28 compared to pre-treatment assessment s. Side effects were few with no statistical difference between the two groups . Patient satisfaction scores were high in both groups for the outcome of sclerotherapy results , and good or very good for compression in 50 % of the CG cases . CONCLUSION We found no difference between compression and control groups when comparing efficacy , side effects , satisfaction scores , symptoms and QOL . Further studies are required to establish the role of compression in sclerotherapy and to evaluate other compression strategies BACKGROUND / OBJECTIVES We prospect ively measured change in quality of life ( QOL ) during the 2 years after a diagnosis of deep vein thrombosis ( DVT ) and evaluated determinants of QOL , including development of the post-thrombotic syndrome ( PTS ) . PATIENTS / METHODS Consecutive patients with acute DVT were recruited from 2001 to 2004 at eight hospitals in Canada . At study visits at baseline , and 1 , 4 , 8 , 12 and 24 months , clinical data were collected , st and ardized PTS assessment s were performed , and QOL question naires were self-completed . Generic QOL was measured using the Short-Form Health Survey-36 ( SF-36 ) question naire . Venous disease-specific QOL was measured using the Venous Insufficiency Epidemiological and Economic Study (VEINES)-QOL/Sym question naire . The change in QOL scores over a 2-year follow-up was assessed . The influence of PTS and other characteristics on QOL at 2 years was evaluated using multivariable regression analyses . RESULTS Among the 387 patients recruited , the average age was 56 years , two-thirds were out patients , and 60 % had proximal DVT . The cumulative incidence of PTS was 47 % . On average , QOL scores improved during follow-up . However , patients who developed PTS had lower scores at all visits and significantly less improvement in QOL over time ( P-values for PTS*time interaction were 0.001 , 0.012 , 0.014 and 0.006 for PCS , MCS , VEINES-QOL and VEINES-Sym ) . Multivariable regression analyses showed that PTS ( P < 0.0001 ) , age ( P = 0.0009 ) , proximal DVT ( P = 0.01 ) and inpatient status ( P = 0.04 ) independently predicted 2-year SF-36 PCS scores . PTS alone independently predicted 2-year VEINES-QOL ( P < 0.0001 ) and VEINES-Sym ( P < 0.0001 ) scores . CONCLUSIONS Development of PTS is the principal determinant of health-related QOL 2 years after DVT . Our study provides prognostic information on patient-reported outcomes after DVT and emphasizes the need for effective prevention and treatment of the PTS BACKGROUND Great saphenous vein ( GSV ) incompetence is the most common cause of superficial venous insufficiency . Radiofrequency catheter ablation ( RFA ) is superior to conventional ligation and stripping , and endovenous laser treatment ( EVL ) has emerged as an effective alternative to RFA . This r and omized study evaluated RFA and EVL for superficial venous insufficiency due to GSV incompetence and compared early and 1-year results . METHODS Between June 2006 and May 2008 , patients with symptomatic primary venous insufficiency due to GSV incompetence were r and omized to RFA or EVL . Patients with bilateral disease were r and omized for treatment of the first leg and received the alternative method on the other . Pretreatment examination included a leg assessment using the Venous Clinical Severity Score ( VCSS ) and CEAP classification . Patients completed the Chronic Venous Insufficiency Question naire 2 ( CIVIQ2 ) . RFA was performed with the ClosurePlus system ( VNUS Medical Technologies , Sunnyvale , Calif ) . EVL was performed with the EVLT system ( AngioDynamics Inc , Queensbury , NY ) . Early ( 1-week and 1-month ) postoperative results of pain , bruising , erythema , and hematoma were recorded . Duplex ultrasound ( DU ) imaging was used at 1 week and 1 year to evaluate vein status . VCSS scores and CEAP clinical class were recorded at each postoperative visit , and quality of life ( QOL ) using CIVIQ2 was assessed at 1 month and 1 year . RESULTS The study enrolled 118 patients ( 141 limbs ) : 46 ( 39 % ) were r and omized to RFA and 48 ( 40 % ) to EVL , and 24 ( 20 % ) had bilateral GSV incompetence . At 1 week , one patient in the RFA group had an open GSV and was deemed a failure . More bruising occurred in the EVL group ( P = .01 ) at 1 week , but at 1 month , there was no difference in bruising between groups . At 1 year , DU imaging showed evidence of recanalization with reflux in 11 RFA and 2 EVL patients ( P = .002 ) . The mean VCSS score change from baseline to 1 week postprocedure was higher for RFA than EVL ( P = .002 ) , but there was no difference between groups at 1 month ( P = .07 ) and 1 year ( P = .9 ) . Overall QOL mean score improved over time for all patients ( P < .001 ) . CEAP clinical class scores of > or=3 were recorded in 21 RFA ( 44 % ) and 24 EVL patients ( 44 % ) pretreatment , but at 1-year , 9 RFA ( 19 % ) and 12 EVL patients ( 24 % ) had scores of > or=3 ( P < .001 ) . This represented a significant improvement in all patients compared with baseline . CONCLUSION Both methods of endovenous ablation effectively reduce symptoms of superficial venous insufficiency . EVL is associated with greater bruising and discomfort in the perioperative period but may provide a more secure closure over the long-term than RFA Objectives To investigate whether additional catheter-directed thrombolysis ( CDT ) improves long-term quality of life ( QOL ) compared with st and ard treatment with anticoagulation and compression stockings alone in patients with proximal deep vein thrombosis ( DVT ) . Design Open-label r and omised controlled trial . Setting 19 Hospitals in the Norwegian southeastern health region . Participants Patients ( 18–75 years ) with a high proximal DVT , symptoms < 21 days and no increased risk of bleeding were eligible . 189 of 209 recruited patients completed 24 months of follow-up . Interventions Participants were r and omised to additional CDT with alteplase for 1–4 days or to st and ard treatment only with 6 months of anticoagulation and 24 months of compression stockings . Primary and secondary outcome measures Planned secondary outcome measures included QOL as assessed with the generic instrument EQ-5D and the disease-specific instrument VEINES-QOL/Sym . Primary outcome measure was post-thrombotic syndrome ( PTS ) after 24 months . Results After 24 months there were no differences in QOL between the additional CDT and st and ard treatment arms ; mean difference for the EQ-5D index was 0.04 ( 95 % CI −0.10 to 0.17 ) , for the VEINES-QOL score 0.2 ( 95 % CI −2.8 to 3.0 ) and for the VEINES-Sym score 0.5 ( 95 % CI −2.4 to 3.4 ; p values>0.37 ) . Independent of treatment arms , patients with PTS had poorer outcomes than patient without PTS ; mean difference for EQ-5D was 0.09 ( 95 % CI 0.03 to 0.15 ) , for VEINES-QOL score 8.6 ( 95 % CI 5.9 to 11.2 ) and for VEINES-Sym score 9.8 ( 95 % CI 7.3 to 12.3 ; p values<0.001 ) . Conclusions QOL did not differ between patients treated with additional CDT compared with st and ard treatment alone . Patients who developed PTS reported poorer QOL and more symptoms than patients without PTS . QOL should be included as an outcome measure in clinical studies on patients at risk of PTS . Trial registration AIM The early results of a r and omised clinical trial comparing local anaesthesia endovenous laser ablation ( EVLA ) with concurrent phlebectomies versus ultrasound-guided foam sclerotherapy ( UGFS ) into the great saphenous vein ( GSV ) revealed that laser was more expensive but the results on abolition of reflux were similar . The interim results at 15 month follow-up are reported . METHODS Evaluations included ultrasound , the venous clinical severity score ( VCSS ) , the Aberdeen varicose vein question naire ( AVVQ ) and the saphenous treatment score ( STS ) . The global absence of reflux defined technical success . Adjuvant sclerotherapy to areas of reflux was administered on patient choice . RESULTS Occlusion of the GSV was more effective with EVLA at 42/44 ( 95.5 % ) versus 31/46 ( 67.4 % ) for UGFS . However both techniques were equally effective at abolishing global venous reflux . The number of legs ( N.=100 ) with total reflux abolition , above-knee , below-knee or combined reflux and loss to follow-up was 18 , 6 , 12 , 8 , 6 with EVLA and 20 , 8 , 11 , 7 , 4 with UGFS , respectively . The VCSS , AVVQ and STS reduced compared to baseline ( P<0.0005 ) , but there was no statistical difference between the groups . The AVVQ remained unchanged between 3 - 15 months ( P=0.601 ) . Also during this time , 19/46(41 % ) UGFS versus 9/44(20 % ) EVLA legs received adjuvant treatment ( 2.1 times increase ) . However , overall , adjuvant foam was given 4.7 times more frequently in the UGFS patients . CONCLUSION EVLA and UGFS are equally effective at abolishing global venous reflux with overall success of 41 % and 43 % , respectively . The high reflux rate was not related to deterioration in quality of life indicating that this reflux was largely asymptomatic OBJECTIVE To assess the efficacy of calcium dobesilate on the quality -of-life ( QoL ) of patients with chronic venous disease ( CVD ) . DESIGN R and omised , parallel , double blind , placebo-controlled clinical trial . METHODS Patients were recruited from vascular surgery clinics and r and omised to 500 mg capsules of calcium dobesilate twice a day for 3 months or placebo . The primary outcome measure was ' QoL after 3 months ' treatment measured by the specific Chronic Insufficiency Venous International Question naire ( CIVIQ ) . Secondary outcomes were QoL at 12 months and assessment of the CVD signs and symptoms . The principal analysis was undertaken on the intention-to-treat ( ITT ) data . RESULTS Five hundred and nine patients were recruited ( 246 to calcium dobesilate and 263 to placebo ) . The analysis of the ' QoL after 3 months ' showed no significant differences between groups ( p=0.07 ) . For secondary outcomes , oedema and symptoms of CVD , there were no significant differences between groups . In a multi-factorial analysis , the ' QoL at 12 months ' was better in the calcium dobesilate group than in placebo group ( p=0.02 ) . CONCLUSIONS Treatment with calcium dobesilate was not found to be superior to placebo on the QoL of CVD patients . The sustained effect of calcium dobesilate observed after treatment should be confirmed in future studies Objective : We aim ed to assess the evolution of an endovenous laser ablation ( EVLA ) practice in the management of varicose veins in a university teaching hospital vascular surgical unit , over five years . Methods : This was a retrospective review of a prospect ively collected data base of patients undergoing EVLA for great saphenous vein incompetence and followed up for a year . For inter- and intragroup comparison , patients were divided into three groups : group A : endovenous access generally established at the perigenicular level ( n = 105 ) ; group B : when practice changed to gain access at lowest point of demonstrable reflux ( n = 70 ) ; and group C : when tumescence delivery changed from manual injections to delivery via peristaltic pump ( n = 49 ) . Outcomes including pain scores , time taken to return to normal functioning , quality of life ( QoL ) , venous clinical severity scores ( VCSS ) and complication rates were evaluated . Results : Intergroup analysis : increase in the length of vein treated and laser density delivered was observed over time , even as median procedure duration decreased ( P < 0.001 ) . An increase in sensory disturbance was noticed in group C ( P = 0.047 ) while better Aberdeen Varicose Vein Question naire ( AVVQ ) ( P = 0.004 ) , SF-36 ® physical domains ( P < 0.05 ) and patient satisfaction with treatment ( P = 0.025 ) were recorded in the same group at 52 weeks . No significant difference was observed in technical failure , pain scores , return to normal functioning , VCSS and recurrence rates post-intervention . Intragroup analysis : QoL measures ( AVVQ , SF-36 ® , EQ-5D ) and VCSS scores demonstrated significant improvement at 12 and 52 weeks compared with baseline ( P < 0.05 ) . Conclusions : Increase in length of vein treated and energy delivery seems to improve short-term outcomes ; however , operators need to be wary of a possible concurrent increase in paraesthetic complications OBJECTIVE --To develop a valid and reliable outcome measure for patients with varicose veins . DESIGN --Postal question naire survey of patients with varicose veins . SETTING --Surgical outpatient departments and training general practice s in Grampian region . SUBJECTS--373 patients , 287 of whom had just been referred to hospital for their varicose veins and 86 who had just consulted a general practitioner for this condition and , for comparison , a r and om sample of 900 members of the general population . MAIN MEASURES --Content validity , internal consistency , and criterion validity . RESULTS --281(76 % ) patients ( mean age 45.8 ; 76 % female ) and 542(60 % ) of the general population ( mean age 47.9 ; 54 % female ) responded . The question naire had good internal consistency as measured by item-total correlations . Factor analysis identified four important health factors : pain and dysfunction , cosmetic appearance , extent of varicosity and complications . The validity of the question naire was demonstrated by a high correlation with the SF-36 health profile , which is a general measure of patients ' health . The perceived health of patients with varicose veins , as measured by the SF-36 , was significantly lower than that of the sample of the general population adjusted for age and a lower proportion of women . CONCLUSION --A clinical ly derived question naire can provide a valid and reliable tool to assess the perceived health of patients with varicose veins . IMPLICATION S -- The question naire may be used to justify surgical treatment of varicose veins Aims On the one h and , the survey aims at the development and validation of an auto-administered question naire design ed to measure the everyday burden caused by chronic venous disorders ( CVDs ) . On the other h and , it aims at reporting initial epidemiological and demographic data in CVD patients and their correlations . Material s and methods After identification of 66 possible items , the elimination of redundant and less relevant questions left a question naire of 36 simple items , the Assessment of Burden in Chronic – Venous Disease ( ABC-V ) that has been applied prospect ively and consecutively to a population of 328 actual chronic venous disorder ( CVD ) patients in eight vein-specialized centres in France . Question naires were completed by patients at home and returned by mail ( free return envelopes ) . Results Significant correlation has been found between ABC-V , the Specific Quality of life & Outcomes Response – Venous ( SQOR-V ) and the Centre for Epidemiologic Studies Depression Scale ( CES-D ) , demonstrating the validity of the concept . ABC-V has been found increased by age ( P = 0.0127 ) and body mass index ( P < 0.001 ) , not by gender ( P = 0.8758 ) . Conclusion ABC-V is a first tool to assess the burden of CVDs , it provides with individual data and will help , for instance , determining the weight of the coefficient used in the disability-adjusted life year and quality -adjusted life year formulas , thus ensuring an accurate evaluation of the Global Burden of Chronic Venous Disorders OBJECTIVE To assess the validity of VEINES-QOL/Sym , a patient-reported question naire to evaluate quality of life and symptoms in patients with deep venous thrombosis ( DVT ) . STUDY DESIGN AND SETTING Psychometric study within the Venous Thrombosis Outcomes ( VETO ) Study , a prospect i ve cohort study of long-term outcomes after DVT . A total of 359 English- and French-speaking patients with acute , objective ly diagnosed DVT were recruited at seven hospitals in Quebec , Canada . The VEINES-QOL/Sym question naire , a 26-item patient-reported measure that generates separate summary scores for symptoms ( VEINES-Sym ) and quality of life ( VEINES-QOL ) was evaluated for acceptability , reliability , validity , and responsiveness in VETO Study subjects . RESULTS St and ard psychometric tests confirmed the acceptability ( missing data , item endorsement frequencies , floor and ceiling effects ) , reliability ( internal consistency , item-total and inter-item correlations , test-retest ) , validity ( content , construct , convergent , discriminant , known groups ) , and responsiveness to clinical change of the VEINES-QOL/Sym in patients with DVT . CONCLUSION The VEINES-QOL/Sym is a practical and scientifically sound patient-reported measure of outcomes that was developed using gold-st and ard methods . VEINES-QOL/Sym is valid and reliable for use as a measure of quality of life and symptoms in patients with acute DVT and provides a rigorous tool to allow more comprehensive evaluation of outcomes in clinical trials and epidemiological studies of patients with DVT Objective Previous reparative valvular surgical options directed at reconstructing damaged common femoral vein ( CFV ) valves associated with pathological chronic venous insufficiency ( CVI ) have not succeeded in reliably managing CVI . In consequence , venous valvuloplasty is rare and most patients are managed conservatively . As a result , monocusp surgery was identified as an optional surgical solution for this large underserved patient group . Methods Ulcer patients appear at wound clinics and often experience disappointing results . Monocusp valves were constructed utilizing viable vein wall in 14 operations on 11 patients . These patients were observed for four years to see if such an autogenous vein wall valve might control aggressive symptomatic CVI when faced with unusable valves . Results Long-term follow-up showed that the monocusp valves remained competent at four years . Symptomatic failures have not appeared at this time . Pain , swelling , ulcers and leg congestion were reliably reversed . VEnous INsufficiency Epidemiologic and Economic Study ( VEINES ) classification ( see Abenh aim L , Krux X , VIENES Study collaborators . Angiology 1997;48:59 and Kurz X , Kahn SR , Abenh aim L , et al. Int Angiol 1999;18:83–102 ) improved over four years from 2.7 ± 0.9 to 0 ( P < 0.001 ) ; CEAP classifications ( see Kistner RL , Eklof B , Masuda EM . Mayo Clin Proc 1996;71:338–45 ) improved from grade 4–6 to 0–1 ( CEAP is not generally a postoperative grading system , but it can be used to develop some form of qualitative analyses as to intervention effectiveness , i.e. what existed preoperatively no longer exists postoperatively . Its postsurgery use is limited by ( C5 ) classification – history of ulcer , which by definition can not go below that with a history of ulcer even if the ulcer has been cured ) . Mean venous reflux scores decreased from 3.8 ± 0.4 to 0.3 ± 0.5 ( P < 0.001 ) . Conclusion Monocusp implantation reliably resolved patient symptoms when unusable CFV valves were encountered . Postoperative CFV reflux is usually undetectable . The monocusp valve exhibits minimal thrombogenicity related to its viability with attendant antithrombotic hormone production capacity and has markedly improved the patient 's quality of life . Full thickness monocusp surgery could become widespread with the difficult dysplastic/aplastic CVI patient subset because of its simplicity , repeatability , durability , low complication rate , effectiveness , persistent availability and viability providing nitric oxide synthase and thymomodulin hormone production capacity . The full thickness of vein wall has distinct advantages over other partial thickness valve creation methods because of its long-term vitality . Postoperative coumadin is recommended for six months to minimize risks of deep vein thrombosis and /or pulmonary embolism BACKGROUND In Hong Kong , at the time of the study , compression treatment was not considered usual care for venous leg ulcer patients . AIM This r and omized controlled trial compared quality of life ( QOL ) aspects in venous leg ulcer patients of over 55-years of age , of short-stretch compression ( SSB ) , four-layer compression b and aging ( 4LB ) and usual care ( UC ) ( moist wound healing dressing , no compression ) . METHOD Study period was 24-weeks , the primary outcome was the patient functional status , disease-specific and generic health-related QOL measures and ulcer healing rates , comparing week 1 vs. week 24 ( end ) results . Assessment s included photogrammetry , Brief Pain Inventory , SF-12 Health Survey , Charing Cross Venous Ulcer Question naire and Frenchay Activity Index . Data analysis was performed using , where appropriate ; Kaplan Meier and log rank chi-square and the repeated measures analysis of variance test . RESULTS A total of 321 patients participated in the study , 45 ( 14 % ) withdrew for various reasons . Compression b and aging in both groups significantly reduced pain ( P < 0.0001 ) and improved functional status and QOL . Healing rate at 24 weeks for both compression groups was significant ( P < 0.001 ) ; for SSB this was 72.0 % ( 77/107 ) vs. 67.3 % in the 4LB group ( 72/107 ) and 29.0 % ( 31/107 ) with usual care . The reduction in ulcer area from weeks 12 to 24 was significant only for SSB ( P < 0.047 ) . CONCLUSION Compression was shown to be feasible for elderly community care patients in Hong Kong and is currently implemented as part of st and ard venous leg ulcer treatment Introduction Manual lymphatic drainage ( MLD ) is an adjunctive method of chronic venous disease ( CVD ) therapy . Evaluation of the change at the clinical stage , hemodynamic parameters and quality of life ( QoL ) following venous system surgery in CVD patients undergoing MLD preoperatively are the most interesting aspects of the study . Material and methods The CVD patients qualified for elective surgery of the venous system were r and omly divided into 2 groups : the MLD group ( n = 38 ) and the control group ( n = 32 ) . In the preoperative period , the MLD group underwent a series of MLD through a period of 2 weeks . The control group did not undergo MLD preoperatively . Both groups were evaluated for CVD staging on the day of qualification for surgery and between 25 and 30 days post-operatively . Additionally , the MLD group was evaluated after the series of MLD . The CVD staging was evaluated in both groups with a QoL question naire ( CIVIQ ) , CEAP classification , foot volumetry ( FV ) and venous refilling time ( VRT ) . Results Parameter values obtained in the MLD group ( before treatment/after MLD/after surgery ) : CEAP 2.23/2.15/2.10 , VRT 15/13/15.6 , FV 3625/3472/3418 , CIVIQ-complaints : 54.4/43.8/38.2 and CIVIQ-meaning : 57.3/49.3/43.1 . Parameter values obtained in control group ( before surgery/after surgery ) : CEAP 2.4/2.12 , VRT 13/14.9 , FV 3581/3559 , CIVIQ-complaints : 51.9/38.7 and CIVIQ-meaning : 53.7/40.6 . The CVD patients statistically improved in CEAP staging , FV and QoL in both groups ( p < 0.05 ) . Conclusions The MLD alone significantly reduced FV in patients with CVD , also improving their QoL. The MLD applied in CVD patients at the preoperative stage results in better surgical outcome , which is demonstrated by reduced disease progression , FV reduction and improvement in the OBJECTIVE To review the psychometric validation of the Chronic Venous dIsease quality of life Question naire ( CIVIQ-20 ) in the countries that have used it since 1996 . DESIGN Prospect i ve , clinical , international study in 18 countries . PATIENTS Patients with venous disease of the lower limb in the clinical , aetiological , anatomical and pathophysiological ( CEAP ) clinical stages C0s to C4 presenting to surgical outpatient departments and general practice s and receiving drug treatment for 6 months . METHODS Quantification of symptoms on a four-point scale and pain on a visual analogue scale , and self-administration of CIVIQ-20 to patients before visit ( baseline , 2 , 4 and 6 months ) . RESULTS In 3956 patients , CIVIQ-20 showed good internal consistency and reliability ( above 0.80 ) through test-retest correlations . The discriminating power of items was good in known groups of patients . Factor analysis identified physical , psychological and pain factors as important , but revealed instability of the social factor . CIVIQ-20 was highly sensitive to changes in the quality of life of patients clinical ly improved after drug treatment . CONCLUSION CIVIQ-20 is valuable in assessing treatment effects in longitudinal , multinational studies , but comparisons of different population s should use the global score rather than scores per dimension This report describes the clinical effectiveness and recurrence rates from a r and omized trial of endovenous laser ablation ( EVLA ) and surgery for varicose veins AIM The aim of this paper was to evaluate the efficacy of the concomitant use of endovenous laser treatment ( ELT ) and ultrasound-guided foam sclerotherapy ( USGFS ) in the management of chronic venous disorder and to objective ly analyze the influence of the combination therapy on the Health Related Quality of Life ( HRQL ) of the treated patients . METHODS In this prospect i ve series , 1 114 varicose veins in 924 consecutive subjects were treated either with a 980 nm ( 7 - 15W ) or a 1320 nm ( 3 - 10W ) endovenous laser . INCLUSION CRITERIA informed consent , clinical , etiologic , anatomical , and pathophysiological ( CEAP ) clinical class > or=2 , and an accessible vein . EXCLUSION CRITERIA coagulation disorder , pregnancy , lactation , current thrombosis , systemic disease , poor general health , or allergy to sodium tetradecyl sulfate ( STS ) . ELT was performed on refluxing saphenous truncal and non-saphenous veins , including incompetent perforators . USGFS was utilized to treat selective refluxing , symptomatic varicose tributaries that were not amenable to ELT alone . The Venous Dysfunction Score ( VDS ) and Health Related Quality of Life ( HRQL ) were assessed . All of the patients were strictly monitored and had Duplex ultrasound scanning to evaluate for deep vein thrombosis ( DVT ) at 24 - 72 hours . Thorough Duplex scanning was done at 1 week , 1 month , 3 months , 6 months , 12 months , and 24 months . RESULTS At 1 month , there was continued reflux ( > 0.5 seconds ) in 26 SFJs ( 3.0 % , N=824 ) and 4 SPJ s ( 2.5 % , N=155 ) and at 3 months in 15 SFJs ( 1.8 % ) , 5 SPJ s ( 3.7 % ) . At 6 months , reflux was present in 10 SFJs ( 1.2 % ) and 4 SPJs ( 2.5 % ) . At a mean of 12+/-10 months of post-treatment follow-up , 4 SFJ ( 1.9 % , N=207 ) and 1 SPJ ( 1.9 % , N=52 ) had reflux . Overall , there was elimination of reflux in 98 % of junctions . The posterior accessory saphenous veins ( PAV : N=117 ) had 100 % elimination of reflux at 1 month , a result that remained unchanged for more than a year ( P<0.001 ) . Similarly , anterior accessory saphenous veins ( AAV : N=56 ) , cranial , caudal , or thigh , extensions of the small saphenous vein ( CESSV : N=31 ) , and non-saphenous veins and incompetent perforators ( NSV , IP : N=31 ) all had sustained and statistically significant response ( P<0.001 ) . Sequentially assessed VDS showed significant improvement ( P<0.001 ) . The Aberdeen Varicose Vein Question naire ( AVVQ ) revealed significant improvement in HRQL at 1 - 2 year ( P<0.001 ) . Failed ELT attempts occurred in six cases due to vein spasm ( N=4 , 0.36 % ) or fiber/laser machine malfunction ( N=2 , 0.18 % ) . These veins were successfully treated with ultrasound-guided foam sclerotherapy . Thirty-two patients ( 2.9 % ) complained of a small area of numbness at one month . There was complete resolution in 6 ( 18.8 % ) of the patients by 6 months . There were four cases of a localized cellulitis at laser venous access sites . These resolved uneventfully with oral antibiotics . There were also two skin reactions , with localized urticaria , due to dressing tape . These required no additional treatment . There were two cases of superficial phlebitis that resolved with continued compression and NSAIDs . There was one asymptomatic popliteal DVT and one uncomplicated superficial skin burn that both resolved uneventfully with no treatment other than observation . No pulmonary embolism ( PE ) , thrombophlebitis , or visual disturbance occurred . CONCLUSIONS Ultrasound-guided foam sclerotherapy given concomitantly with ELT is safe and highly efficacious in the management of GSV , SSV reflux and in their tributaries or in non-saphenous veins . CVD patients treated with combination therapy given in this manner demonstrated significant improvement in their HRQL AIM The present study assessed the effect of Ruscus aculeatus , hesperidin methyl-chalcone and ascorbic acid ( HMC-AA ) , in the treatment of chronic venous disorders ( CVD ) in Latin American patients . METHODS This study is an observational , single arm , multicentric and prospect i ve trial . Patients suffering from CVD and belonging to C0s-C3 Clinical Etiological Anatomical and Physiopathological ( CEAP ) classes were included . Patient profiles , risk factors , clinical symptomatology and quality of life ( QoL ) assessed by SF-12 and CIVIQ question naires were evaluated at inclusion and after 12-week treatment . RESULTS The main factors influencing the previous management of patients were age , gender , body mass index ( BMI ) , familial history , physical activity , exposure to heat , heavy loads lifting , profession and clinical characteristics . All clinical symptoms significantly improved with treatment and , as BMI and CEAP classes increased . Ankle circumferences decreased over time , correlating with BMI and CEAP classes . The physical and psychological dimensions of the SF-12 score significantly increased over time and improved within each CEAP class . The CIVIQ score significantly improved over time , correlating with age and CEAP classes . CONCLUSION A 12-week treatment with Ruscus aculeatus HMC-AA showed a significant decrease in the clinical symptoms and a significant improvement in the QoL of patients with CVD PURPOSE To determine whether increased physical activity 1 month after deep vein thrombosis ( DVT ) led to worsening of venous symptoms and signs within the subsequent 3 months . METHODS By a multicenter prospect i ve cohort study of patients with acute DVT , we used vali date d question naires at baseline , 1 month , and 4 months post-DVT for each exposure , using the Godin Question naire to measure physical activity , the VEINES-QOL to measure disease severity , and the postthrombotic syndrome ( PTS ) scale to measure symptoms and signs usually attributed to sequelae of DVT . RESULTS Of 301 patients followed for 4 months , 25 % were inactive and 25 % were only mildly active before their DVT . In univariate analysis , physical activity at 1 month was not associated with a change in PTS score between 1 month and 4 months ( P=0.42 ) . After adjusting for the potential confounders of age , sex , pre-DVT physical activity , and disease severity at 1 month , the results suggested that higher physical activity levels at 1 month may be protective against worsening of the PTS score over the subsequent 3 months . Compared with those who were inactive at 1 month , the adjusted OR was 0.93 ( 95%CI : 0.47 , 1.87 ) for mildly to moderately active persons , and 0.52 ( 95%CI : 0.24 , 1.15 ) for highly active persons . Among patients who were active pre-DVT ( N=220 ) , 55.5 % had returned to their previous levels of physical activity or greater within 4 months . CONCLUSIONS For most persons , exercise at 1 month post-DVT does not appear to worsen venous symptoms and signs over the subsequent 3 months , and more than 50 % resume their usual level of activity within 4 months OBJECTIVE This multicenter r and omized clinical trial compared cryo stripping of the great saphenous vein ( GSV ) with conventional stripping . METHODS The study r and omized 494 patients with symptomatic ( CEAP ) clinical severity class 2 to 4 to cryo stripping ( n = 249 ) or conventional stripping ( n = 245 ) . The primary outcome was residual GSV 6 months after surgery measured by venous duplex ultrasound imaging . Secondary outcomes were quality of life , operation time , and postoperative neural damage . Duration of follow-up was 6 months . Quality of life was measured at 6 and 26 weeks postoperatively with the Aberdeen Varicose Vein Question naire ( AVVQ ) and Medical Outcomes Study Short-Form 36 ( SF-36 ) Health Survey . RESULTS The two groups were well matched at baseline . The percentage of patients with residual GSV at 6 months ( primary outcome ) was 44 % ( 102 of 230 ) in the cryo group and 15 % ( 33 of 215 ) in the conventional group ( difference 29 % ; 95 % confidence interval [ CI ] , 21%-37 % , P < .001 ) . Median operation time was significantly shorter in the cryo group ( 30 minutes ) compared with the conventional group ( 39 minutes ) . Neural damage was 12 % in both groups , and thus not significantly different . Scores on the subdomains of the SF-36 showed no significant change between the groups . The AVVQ after conventional stripping was 8.0 , which was a better result than the 11.7 result after cryo stripping ( difference 2.6 points ; 95 % CI , 1.0 - 4.2 ; P = .001 , repeated measurements analysis of variance with adjustment for baseline scores ) . CONCLUSIONS Cryo stripping accounts for numerous procedural failures and hence residual GSV in patients . The AVVQ showed small but significantly better results for patients after a conventional stripping . Cryo stripping has no benefits over conventional stripping Introduction : Endovenous laser ablation ( EVLA ) has been demonstrated to be an effective treatment for lower limb varicose veins in the short and midterm results . This study reports the 5-year outcomes of EVLA technique at different power setting s. Methods : Patients with primary symptomatic , unilateral varicose veins secondary to saphenofemoral junction ( SFJ ) incompetence and great saphenous vein ( GSV ) reflux were recruited and r and omized to either 12W ( intermittent laser withdrawal ) or 14W ( continuous laser withdrawal ) . They were assessed at baseline , 1 , 6 , 12 , 52 , 104 weeks , and 5 years . Outcome measures included : Venous Clinical Severity Score ( VCSS ) , pain scores , time taken to return to normal functions , complications , recurrence , quality of life ( QoL ) , and duplex ultrasound findings . Results : 76 consecutive patients , M : F 30:46 , median age 54(IQR : 37.3 - 59 ) years were r and omized . Intragroup analysis : Significant improvement was seen in both groups in VCSS , pain scores , Aberdeen varicose vein question naire ( AVVQ ) scores , Shortform-36 ( SF-36 ) and Euroqol ( EQ-5D ) domains over the follow-up period ( P < 0.05 ) . Intergroup analysis : Over 5 years , clinical ly recurrent varicosities and duplex detected SFJ incompetence was less frequent and patient satisfaction with cosmetic outcome significantly higher in the 14W group ( P < 0.05 ) . There was no significant difference between the groups in duration of procedure , postoperative pain scores , return to normal functioning , complications , VCSS , disease specific ( AVVQ ) and generic ( SF36 , EQ-5D ) QoL measures ( P > 0.05 ) . Conclusion : Late outcomes following EVLA were superior for the 14W continuous power setting s achieving better long term venous occlusion and lowered recurrence rates without increasing post-operative morbidity . Hence 14W continuous setting should be the energy delivery mode of choice BACKGROUND AND OBJECTIVE Superficial venous surgery for CEAP 2 disease leads to an improvement in disease-specific quality of life ( QoL ) in the short term . However , which factors influence the magnitude of this improvement , how surgery affects QoL in patients with CEAP 4 to 6 disease , and whether this improvement is durable are not known . The objective of this study was to identify patient , operative , and surgeon factors that might influence the change in disease-specific QoL in the 2 years after superficial venous surgery . METHODS This prospect i ve study was comprised of 203 unselected , consecutive patients with CEAP 2 to 6 disease who underwent saphenous with or without subfascial endoscopic perforator surgery and who completed the Aberdeen Varicose Vein Symptoms Severity Score ( AVVSSS ) before surgery and at 4 weeks , 6 months , and 2 years after surgery . Univariate and multivariate analyses were performed . RESULTS At baseline , recurrent and ulcer ( CEAP 5 and 6 ) diseases were associated with a higher ( worse ) AVVSSS . Surgery was associated with a significant improvement in median ( interquartile range [ IQR ] ) AVVSSS : baseline , 17.8 ( 11.8 to 27.2 ) ; 4 weeks , 13.8 ( 7.9 to 21.3 ) ; 6 months , 9.6 ( 4.2 to 15.8 ) ; and 2 years , 8.1 ( 4.0 to 14.7 ) . One hundred seventy-five patients ( 86 % ) at 6 months and 177 patients ( 87 % ) at 2 years reported an improvement in AVVSSS . Postoperative AVVSSS at both 6 months and 2 years was most significantly influenced by preoperative score ( P < .0001 ) . After adjustment for baseline AVVSSS , the following factors were identified in multivariate analysis as having a significant and independent positive ( + ) or negative ( - ) impact on AVVSSS : at 6 months , ( - ) recurrent disease ( P = .009 ) , ( - ) CEAP 4 disease ( P = .026 ) ; and at 2 years , ( + ) long saphenous surgery ( P = .02 ) , ( - ) CEAP 5 disease ( P = .030 ) . CONCLUSION In this unselected series , saphenous surgery with or without subfascial endoscopic perforator surgery led to an improvement in disease-specific QoL in 87 % of patients out to 2 years . Although univariate analysis results suggested that many baseline factors might be associated with outcome , multivariate analysis results suggested that only surgery for recurrent disease and for CEAP 4/5 disease remained as significant negative , and only long saphenous surgery as significant positive , independent prognostic factors . These data provide evidence of the medium-term clinical effectiveness of venous surgery across the full spectrum of CEAP clinical grade s , show the importance of multivariate analysis , and reemphasize the importance of minimization of recurrence BACKGROUND Clinical classification ( C ) of patients suffering from chronic venous disorders according to the Clinical , Etiology , Anatomy , and Pathophysiology Classification takes into account signs and symptoms , but the C3 ( venous edema ) class has been identified as poorly specific . Patients in whom physicians fail to observe significant edema ( sign ) frequently report a feeling of swelling ( symptom ) . Previous studies of venoactive drugs have demonstrated significant reduction in leg volume , but the correlation with a clinical improvement was lacking . OBJECTIVE To describe the clinical status of a sample of Argentinean patients presenting with venous symptoms and signs . To demonstrate the relationship between the reduction of leg swelling and the improvement of symptoms of chronic venous disorders ( CVDs ) and quality of life ( QoL ) in patients with CVD . MATERIAL S AND METHODS One thous and thirty-six patients were included prospect ively and su bmi tted to medical interrogation and examination and specific and generic self- question naires . Patients included were reassessed using the same tools after phlebotropic treatment ( Ruscus+hesperidin+ascorbic acid ) , the prescription of which was expected to induce variations in clinical status . RESULTS Significant correlations were observed between ankle circumference reduction and improvement of all symptoms in C2 to C3 patients : heaviness , pain , paraesthesia , and cramps . Such correlations were found in C0 to C1 patients . There was a correlation between improvement attained in QoL and the physical dimension of the Chronic Venous Insufficiency Question naire . CONCLUSIONS Our results demonstrate the relevance of moderate ankle swelling , which is not usually described clinical ly as edema and is probably a typical symptom of chronic venous disorders . Future studies should focus on this insufficiently analyzed clinical feature and put to better use more specific QoL question naires Background : Endovenous ablation of varicose veins using radiofrequency ablation ( RFA ) and endovenous laser therapy ( EVLT ) has reported advantages over traditional open surgical treatment . There is little evidence comparing the efficacy and patient-reported outcomes between the 2 endovenous solutions . This study compares the RFA and EVLT strategies in a prospect i ve double-blind clinical trial . Methods : Consecutive patients with primary unilateral great saphenous vein ( GSV ) reflux undergoing endovenous treatment were r and omized to RFA ( VNUS ClosureFAST ) or EVLT ( 810-nm diode laser ) . The primary outcome measure was GSV occlusion at 3 months after treatment . Secondary outcome measures were occlusion at 7 days , postoperative pain , analgesic requirement , and bruising , assessed at day 7 after surgery . Quality of life ( QoL ) was assessed preoperatively and 3 months after surgery using the Aberdeen Varicose Vein Question naire ( AVVQ ) and EQ-5D . Results : A total of 159 patients were r and omized to RFA ( 79 patients ) or EVLT ( 80 patients ) . Groups were well matched for demographics , disease extent , severity , and preoperative QoL. Duplex scanning confirmed 100 % vein occlusion at 1 week in both groups . At 3 months , occlusion was 97 % for RFA and 96 % for EVLT ; P = 0.67 . Median ( interquartile range ) percentage above-knee bruise area was greater after EVLT 3.85 % ( 6.1 ) than after RFA 0.6 % ( 2 ) ; P = 0.0001 . Postoperative pain assessed at each of the first 7 postoperative days was less after RFA ( P = 0.001 ) . Changes in the AVVQ ( P = 0.12 ) and EQ-5D ( P = 0.66 ) at 3 months were similar in both groups . Conclusions : RFA and EVLT offer comparable venous occlusion rates at 3 months after treatment of primary GSV varices ; with neither modality proving superior . RFA is associated with less periprocedural pain , analgesic requirement , and bruising . Registration number : IS RCT N63135694 ( http://www.controlled-trials.com Many patients with chronic wounds suffer not only directly from their wounds but also from high financial , social and psychological impairments , significantly reducing their quality of life . In order to provide an instrument both applicable to different patient population s and sensitive to areas of impact specific to certain skin diseases , the modular instrument ' Freiburg Life Quality Assessment ' has been developed . Each disease-specific version of the instrument consists of a core module of generic items and items specific for a distinct skin disease . Objective of the study was to assess reliability , sensitivity to change , and validity of the module for chronic ulcers . The instrument was implemented in a longitudinal observational study on vacuum-seal therapy ( n = 175 ) , in a cross-sectional observational study involving patients with chronic leg ulcers ( n = 384 ) and in a r and omised clinical trial on keratinocyte transplantation ( n = 198 ) . The instrument showed good internal consistency ( Cronbach 's alpha ≥0·85 ) . There were minor floor effects ≤4·3 % , but no ceiling effects . Retest-reliability and convergent validity with the EuroQol quality of life question naire ( EQ-5D ) ( visual analogue scale ) were satisfactory . Change scores correlated with change in other quality -of-life instruments ( r = 0·59 - 0·61 ) , but not with change in wound status OBJECTIVE This study compared postoperative patient comfort and the surgical outcome of endovenous laser ablation ( EVLA ) or stripping of the great saphenous vein , both performed in conjunction with high ligation . METHODS The study r and omized 100 patients with primary trunk varicosities of the great saphenous vein ( CEAP clinical class II to IV ) to EVLA or stripping . The success of surgery was followed-up by duplex ultrasound imaging at 1 , 4 , and 16 weeks . Primary end points were the size of the hematoma 1 week after the operation and the preoperative disease-specific Chronic Venous Insufficiency Question naire ( CIVIQ ) quality of life score compared with 4 weeks postoperatively . Secondary end points were postoperative symptoms ( pain , use of analgesics , paresthesia at the ankle , residual hematoma ) , complications , time taken to resume work , the patient 's satisfaction with the cosmetic outcome , and the CIVIQ quality of life score at 16 weeks . RESULTS The groups were well matched at baseline . In all , 95 patients could be followed up in accordance with the protocol . The treatment was successful in all patients . Endovenous laser ablation was associated with an occlusion rate of 100 % . Hematomas were significantly smaller after EVLA ( median [ quartiles ] ) at 125 ( 55 - 180 ) cm(2 ) vs stripping 200 ( 123 - 269 ) cm(2 ) ( P = .001 ) . No difference was registered between groups for the CIVIQ quality of life score , with EVLA at -1.25 ( -7.5 - 11.25 ) vs stripping at 4.38 ( -5.94 - 14.38 ; P = .34 ) . Several postoperative symptoms favored EVLA , but the only significant differences were seen in the minor side effects of surgery at 1 and 4 weeks and discomfort due to paresthesia at the ankle in the first postoperative week . EVLA was associated with a longer period of time until return to work ( median [ quartiles ] ) of 20 ( 14 - 25.5 ) days vs 14 ( 12.8 - 25 ) days ( P = .054 ) . CONCLUSION Endovenous laser ablation combined with high ligation is safe and effective . Postoperative hematomas are significantly smaller than those after stripping . Short-term quality of life is at least as good as that after stripping . The long-term results warrant further investigation Severe post-thrombotic syndrome ( PTS ) is responsible for considerable disability , reduced quality of life and increased health care costs . Current therapies are limited and often ineffective . We performed a two-centre , r and omized , cross-over controlled trial to evaluate Venowave , a novel lower-limb venous-return assist device , for the treatment of severe PTS . Eligible subjects were allocated to receive , in r and omized order , Venowave for eight weeks and a control device for eight weeks . The eight-week treatment periods were separated by a four-week period when no device was used ( i.e. wash-out period ) . The primary outcome measure was a ' clinical success ' defined as : i ) reported benefit from the device ; and ii ) moderate or greater improvement in symptoms of PTS ; and iii ) willingness to continue using the device . Secondary outcome measures included quality of life ( QOL ) as measured by VEINES-QOL question naire ( higher scores indicate better QOL ) , and PTS severity as measured by the Villalta PTS scale ( higher scores indicate more severe PTS ) . The study was registered with Clinical Trials . gov ( NCT00182208 ) . Thirty-two patients were enrolled . Of these , 26 ( 80 % ) were also using graduated compression stockings . Twenty-six participants completed both trial periods . Clinical success occurred in 10 ( 31 % ) participants receiving Venowave and four ( 13 % ) participants receiving the control device , with two ( 6 % ) participants reporting a clinical success with both devices ( P = 0.11 ) . Mean VEINES-QOL score at the end of study period was significantly greater ( P = 0.004 ) for Venowave ( 52.5 ; SD 5.8 ) compared to control ( 50.2 ; SD 6.2 ) . Mean Villalta scale score at the end of study period was significantly decreased ( P = 0.004 ) for Venowave ( 12.2 ; SD 6.3 ) compared to control ( 15.0 ; SD 6.1 ) . In conclusion , Venowave appears to be a very promising new therapy for patients with severe PTS , which may be used alone or in combination with graduated compression stockings OBJECTIVES To determine the feasibility and reliability of an online patient completed Aberdeen Varicose Vein Question naire ( AVVQ ) as a tool to guide specialist referral . METHODS This was a prospect i ve qualitative and quantitative study . One hundred and six patients completed an online question naire . Some 43 ( 40 % ) completed the AVVQ question naire at home and 63 ( 60 % ) did it immediately before their appointment . Venous Clinical Severity Score ( VCSS ) and CEAP grade s were assigned by a consultant vascular surgeon . In 11 patients , the question naire was repeated at the time of surgery to assess reproducibility and bias . RESULTS The AVVQ correlated with the specialist 's VCSS scores ( Spearman coefficient 0.795 ; p < 0.01 ) and similarly with CEAP grade ( P < 0.01 , ANOVA test ) . AVVQ was reproducible with close agreement ( Spearman coefficient 0.89 ; p < 0.01 ) between both 1st AVVQ score of 21.61 ( sd 10.26 ; range 6.12 - 40.14 ) and 2nd AVVQ score of 21.03 ( sd 10.50 range 4.51 - 42.57 ) . Patients ' feedback about the online AVVQ was positive . CONCLUSIONS An online question naire is acceptable to patients , correlates with clinical findings and using a threshold value could be used by healthcare Commissioners to guide varicose vein referrals Background The factorial instability of the CIVIQ-20 social dimension in different population s has necessitated the development of a new stable question naire to interpret results from international studies . Objective Construction of a stable and psychometrically vali date d question naire from CIVIQ-20 . Methods and major findings A prospect i ve , international study was used to construct a stable CIVIQ scale and to vali date its psychometric properties . An iterative process was implemented to eliminate the more unstable items ( six ) , and the social and physical dimensions were combined . The result ing instrument comprised 14 items , split into three dimensions ( pain , physical , and psychological ) , and was named CIVIQ-14 . The stability of the CIVIQ-14 factorial structure was confirmed in Polish , Czech , Spanish , and French population s using principal component analysis and multitrait/multi method analysis . Psychometric assessment demonstrated that CIVIQ-14 was reliable ( intra-class coefficient > 0.8 ; weighted kappa > 0.8 ) , valid ( correlation coefficients between dimension scores and clinical severity scores between 0.3 and 0.6 ) , and sensitive ( effect sizes > 0.6 for psychological dimension ; > 0.8 for the other dimensions ) . Conclusion CIVIQ-14 is a reliable , valid , and sensitive instrument applicable to international studies of patients with chronic venous disease BACKGROUND Endovenous laser ablation ( EVLA ) is an improved method to treat varicose great saphenous veins ( GSV ) with a high satisfactory rate . This study aim ed to evaluate the efficiency and safety of treatment by EVLA procedures with ultrasound-guided perivenous tumescence . METHODS Thirty-one patients ( 31 limbs ) with symptomatic varicose vein primary to chronic venous insufficiency ( CVI ) treated with EVLA were prospect ively studied . The entire procedure was performed under ultrasound-guided tumescent local anesthesia . The patients were evaluated with a 18 month follow-up postoperation using clinical examination and venous duplex ultrasonography . Pain scores and quality of life ( QOL ) were recorded using visual analog scale ( VAS ) and the chronic venous insufficiency question naire ( CIVIQ ) at 1 week , 1 month , and 12 months after operation . RESULTS All patients tolerated EVLA procedure well . The overall success occlusion rates of GSV were 92 % , 94 % , and 94 % at 1 , 12 , and 18 months follow-up , respectively . The score of CIVIQ one week preoperation was 69.14 ± 11.44 while that of CIVIQ one month postoperation was 85.32 ± 4.89 . The life quality has significantly improved after the operation of EVLA ( t = 12.71 , P < 0.05 ) . The VAS one month after treatment was lower than 1 week before therapy ( t = 8.048 , P < 0.05 ) . Major complications such as deep vein thrombosis and skin burns were not found . Most of the complications were minor and improved quickly . CONCLUSIONS This refinement type of EVLA procedure is a safe and effective treatment with a high satisfaction rate ; it displayed noteworthy features including shortening hospitalization , early ambulant activity , and preferable occlusion rates BACKGROUND The long-term results of a prospect i ve , r and omized controlled trial in patients with primary varicose veins are reported . METHODS Saphenofemoral ligation ( SFL ) was done in 73 patients ( 82 legs ) . In addition , 43 ( 23 women ; age , 47 ) underwent stripping and multiple phlebectomies under general anesthesia ( group S ) , and 39 ( 32 women ; age , 49 ) had concurrent sclerotherapy under local anesthesia ( group F ) . Assessment s included CEAP C status , Venous Clinical Severity Score ( VCSS ) , Venous Segmental Disease Score ( VSDS ) , Aberdeen Varicose Vein Question naire ( AVVQ ) , and 36-Item Short-Form ( SF-36 ) scores . RESULTS CEAP C was similar between groups ( C(2 - 6 ) ) . In group S , 40 % of legs required 25 additional foam sessions ( mean volume , 11 mL ) . In group F , 47.5 % of legs required 33 sessions ( mean volume , 9 mL ) The groups had equivalent preoperative VCSS scores and similar changes at 3 ( P = .504 ) and 5 years ( P = .484 ) , as were the absolute VCSS scores at 3 ( P = .313 ) and 5 years ( P = .104 ; Mann-Whitney U ) . The VSDS score improved ( median [ interquartile range ] ) preoperatively vs 3 years ( group S , 16.32 [ 14.7 ] vs 8.94 [ 11.51 ] , P = .003 ; group F , 12.28 [ 10.37 ] vs 4.97 [ 6.19 ] ; P < .0005 , Wilcoxon ) . Above knee obliteration occurred in 17 of 26 ( 65.4 % ) for group S and in 16 of 33 ( 48.5 % ) for group F at 3 years , and in 14 ( 53.8 % ) and 19 ( 57.6 % ) at 5 years . AVVQ scores were similar before and at 3 years ( P = .703 ) but significantly favored group S at 5 years ( P = .015 ; Mann-Whitney U ) . The AVVQ also improved within both groups . The SF-36 mental summary score over 3 years deteriorated in group S ( P = .04 ) . However , the physical summary scores did not change between groups ( S , P = .361 ; F , P = .889 ) or the mental score in group F ( P = .285 ) . Changes in the physical ( P = .724 ) and mental ( P = .354 , Mann-Whitney U ) scores did not differ between the groups due to treatment . CONCLUSION At 3 and 5 years of follow-up , the treatment was equally effective in the surgical and foam groups , as demonstrated with VCSS , VSDS , and the SF-36 physical component score . At 5 years , the AVVQ was significantly better in the surgical group . The additional foam sessions were also similar . Because traditional surgery for varicose veins does not provide a definitive treatment , foam sclerotherapy could be offered as in a dental care treatment model : " treat as and when the problem appears . AIM This study is a prospect i ve r and omized controlled trial comparing ultrasound-guided foam sclerotherapy of the great saphenous vein ( GSV ) combined with sapheno-femoral junction ( SFJ ) ligation to st and ard stripping surgery . Primary endpoints were patient recovery period , postoperative pain , quality of life and recurrence rate and secondary end points were frequency of complications on the two arms of the trial . METHODS Sixty consecutive patients with incompetence of the GSV result ing in varicose veins were prospect ively r and omized into 2 groups of 30 , treated by SFJ ligation and either ultrasound-guided foam sclerotherapy or st and ard stripping of the GSV . The study protocol included history , physical examination , assignment of CEAP class , assessment of the Aberdeen varicose vein question naire ( AVVQ ) and colour Duplex ultrasound . RESULTS All treatments were completed as intended . The time taken to complete treatment was shorter in the foam sclerotherapy plus SFJ ligation group as compared to st and ard stripping : 43 min vs. 65 min ( P<0.01 , Mann-Whitney ) . Less analgesic use postoperatively was recorded in the foam sclerotherapy group . Median time to return to normal activities was significantly reduced in the foam sclerotherapy group ( 3 days ) compared to the surgical group ( 6 days ) ( P<0.01 , Mann-Whitney ) . The median overall cost of the procedure in the sclerotherapy group was 3143RMB , and was 3638RMB in the conventional surgery ( P=0.235 , Mann-Whitney ) . At 3 months , median CEAP class dropped from four preoperatively to one following treatment in both groups ( p<0.01 , Wilcoxon test ) . After 6 months , in the foam sclerotherapy group five patients ( 20 % ) needed further sessions of foam sclerotherapy , result ing in a short-term closure rate of 80 % . And the short-term obliteration rate was 89.5 % in the conventional surgery group . CONCLUSION Ultrasound guided sclerotherapy combined with sapheno-femoral ligation involved a shorter treatment time , less postoperative discomfort and result ed in more rapid recovery compared to conventional GSV stripping OBJECTIVE To compare the proportion and rate of healing , pain , and quality of life of low-strength medical compression stockings ( MCS ) with traditional b and ages applied for the treatment of recalcitrant venous leg ulcers . METHODS A single-center , r and omized , open-label study was performed with consecutive patients . Sigvaris prototype MCS providing 15 mm Hg-25 mm Hg at the ankle were compared with multi-layer short-stretch b and ages . In both groups , pads were placed above incompetent perforating veins in the ulcer area . The initial static pressure between the dressing-covered ulcer and the pad was 29 mm Hg and 49 mm Hg with MCS and b and ages , respectively . Dynamic pressure measurements showed no difference . Compression was maintained day and night and changed every week . The primary endpoint was healing within 90 days . Secondary endpoints were healing within 180 days , time to healing , pain ( weekly Likert scales ) , and monthly quality of life ( ChronIc Venous Insufficiency Quality of Life [ CIVIQ ] question naire ) . RESULTS Of 74 patients screened , 60 fulfilled the selection criteria and 55 completed the study ; 28 in the MCS and 27 in the b and age group . Ulcers were recurrent ( 48 % ) , long lasting ( mean , 27 months ) , and large ( mean , 13 cm2 ) . All but one patient had deep venous reflux and /or incompetent perforating veins in addition to trunk varices . Characteristics of patients and ulcers were evenly distributed ( exception : more edema in the MCS group ; P = .019 ) . Healing within 90 days was observed in 36 % with MCS and in 48 % with b and ages ( P = .350 ) . Healing within 180 days was documented in 50 % with MCS and in 67 % with b and ages ( P = .210 ) . Time to healing was identical . Pain scored 44 and 46 initially ( on a scale in which 100 referred to maximum and 0 to no pain ) and decreased within the first week to 20 and 28 in the MCS and b and age groups , respectively ( P < .001 vs .010 ) . Quality of life showed no difference between the treatment groups . In both groups , pain at 90 days had decreased by half , independent of completion of healing . Physical , social , and psychic impairment improved significantly in patients with healed ulcers only . CONCLUSION Our study illustrates the difficulty of bringing large and long-st and ing venous ulcers to heal . The effect of compression with MCS was not different from that of compression with b and ages . Both treatments alleviated pain promptly . Quality of life was improved only in patients whose ulcers had healed Endovenous laser therapy ( EVLT ) is a minimally invasive treatment for varicose veins . This study compares early quality -of-life ( QoL ) outcomes following EVLT and surgery . Two nonr and omized groups were studied : an EVLT group with 70 patients , median age 49 ( interquartile range [ IQR ] 35 - 58 ) years , and a surgery group with 62 patients , median age 49 ( IQR 35 - 61 ) years . Patients were assessed prior to and at 1 , 6 , and 12 weeks following the procedure using the Short Form 36 ( SF-36 ) , the Aberdeen Varicose Veins Question naire ( AVVQ ) , and the Venous Clinical Severity Score ( VCSS ) . Follow-up at 1 , 6 , and 12 weeks was 100 % , 77 % , and 70 % following EVLT and 100 % , 85 % , and 47 % following surgery . SF-36 scores were significantly better in the EVLT group at 1 week ( Physical Functioning , Role Physical , Bodily Pain , Vitality , and Social Functioning domains ) and at 6 weeks ( Physical Functioning and Role Physical ) . At 12 weeks , no significant differences were evident between the groups . AVVQ scores were significantly better in the EVLT group at 6 and 12 weeks . VCSS scores were significantly improved in both groups at 12 weeks . EVLT and surgery provide similar QoL improvements in patients with varicose veins . EVLT , however , removes the QoL limitations experienced by patients in the early postoperative period OBJECTIVE Previous studies have correlated increasing great saphenous vein ( GSV ) diameter with increasing CEAP clinical classification . Some insurance carriers are currently using specific GSV diameters to determine coverage for treatment of axial venous insufficiency . The aim of this study was to investigate the correlation of patient quality of life ( QOL ) measures with GSV diameters in varicose vein patients with GSV reflux . METHODS Data were collected from the records of 91 patients prospect ively enrolled in two varicose vein trials . The patients had symptomatic varicose veins with saphenofemoral junction and proximal GSV reflux . Maximum GSV diameter was measured on duplex ultrasound imaging , with the patient st and ing , within 5 cm of the saphenofemoral junction . Chronic Venous Insufficiency Question naire 2 ( CIVIQ-2 ; Servier , Neuilly-sur-Seine , France ) , Venous Insufficiency Epidemiological and Economic Study ( VEINES ) Symptom ( Sym ) and QOL assessment s , and the Venous Clinical Severity Score ( VCSS ) assessment were completed before treatment of GSV insufficiency . Demographic information , patient weight , height , and body mass index were collected . Correlations between pairs of data were done using Pearson product-moment and Spearman correlation coefficients . RESULTS The 91 study patients ( 19 men , 72 women ) were a mean age of 45 years ( range , 18 - 65 years ) . The mean GSV diameter was 6.7 mm ( range , 2.2 - 14.1 mm ) . The mean VCSS score was 7.8 ( range , 3 - 12 ) . There was a weak correlation between increasing GSV diameter and VCSS ( r=0.23 ; P=.03 ) and no correlation between GSV diameter and the CIVIQ-2 score ( r=0.01 ) , VEINES-QOL ( r=-0.07 ) , and VEINES-Sym ( r=-0.1 ) . CONCLUSIONS GSV diameter is a poor surrogate marker for assessing the effect of varicose veins on a patient 's QOL ; thus , using GSV diameter as a sole criterion for determining medical necessity for the treatment of GSV reflux is inappropriate . Further correlations between QOL measures and duplex-derived objective findings are warranted BACKGROUND Endovenous laser therapy ( EVLT ) for ablation of the great saphenous vein ( GSV ) is thought to minimize postoperative morbidity compared with high ligation and stripping ( HL/S ) . Only a few r and omized trials have reported early results . This prospect i ve r and omized trial compared EVLT ( 980 nm ) and HL/S results at 1 and 2 years after the intervention . METHOD Patients with symptomatic varicose veins due to GSV insufficiency were r and omized to HL/S ( 100 limbs ) or EVLT ( 104 limbs ) . Four EVLT procedures failed primarily and were excluded . Phlebectomy and ligature of incompetent perforators were performed whenever indicated in both groups . Patients were re-examined clinical ly and by duplex ultrasound imaging preoperatively and at 12 days and at 1 and 2 years after treatment . Closure rate , complication rate , time to return to normal activity , the Aberdeen Varicose Vein Symptom Severity Score ( AVVSS ) , the Varicose Venous Clinical Severity Score ( VVCSS ) , and the Medical Outcome Study Short Form-36 scores were also recorded . RESULTS There were no differences in patient demographics , CEAP class , Widmer class , or severity scores between the groups . Simultaneous interventions did not differ between the groups . Similar times for the return to normal activity and scores for postoperative pain were reported . No major complications after treatment were recorded . HL/S limbs had significantly more postoperative hematomas than EVLT limbs , and EVLT patients reported more bruising . Follow-up at 1 year was 100 % for HL/S and 99 % for EVLT . Two GSVs in the EVLT group reopened and three partially reopened . No open GSVs occurred in HL/S limbs . Ninety-eight percent of the limbs in both groups were free of symptoms . VCSS , AVVSS , and Short Form-36 scores did not reveal any group differences . At 2 years , no differences compared with 1-year results were observed , except that two more GSVs in the EVLT group were partially reopened . CONCLUSIONS Abolition of GSV reflux and improvement in quality of life was similar after HL/S and EVLT . After EVLT , however , two GSVs were found completely reopened and five were partially reopened , which was significantly higher than after HL/S. A prolonged follow-up is ongoing BACKGROUND Apart from compression therapy , physical therapy has scarcely been evaluated in the treatment of chronic venous disorders ( CVDs ) . Spa treatment is a popular way to administer physical therapy for CVDs in France , but its efficacy has not yet been assessed in a large trial . The objective was to assess the efficacy of spa therapy for patients with advanced CVD ( CEAP clinical classes C4-C5 ) . METHODS This was a single-blind ( treatment concealed to the investigators ) r and omized , multicenter , controlled trial ( French spa resorts ) . Inclusion criteria were primary or post-thrombotic CVD with skin changes but no active ulcer ( C4a , C4b , or C5 ) . The treated group had the usual 3-week spa treatment course soon after r and omization ; the control group had spa treatment after the 1-year comparison period . All patients continued their usual medical care including wearing compression stockings . Treatment consisted of four balneotherapy sessions per day for 6 days a week . Follow-up was performed at 6 , 12 and 18 months by independent blinded investigators . The main outcome criterion was the incidence of leg ulcers at 12 months . Secondary criteria were a modified version of the Venous Clinical Severity Score , a visual analog scale for leg symptoms , and the Chronic Venous Insufficiency Question naire 2 and EuroQol 5D quality -of-life auto question naires . RESULTS Four hundred twenty-five subjects were enrolled : 214 in the treatment group ( Spa ) and 211 in the control group ( Ctr ) ; they were similar at baseline regarding their demographic characteristics , the severity of the CVD , and the outcome variables . At 1 year , the incidence of leg ulcers was not statistically different ( Spa : + 9.3 % ; 95 % confidence interval [ CI ] , + 5.6 - + 14.3 ; Ctr : + 6.1 % ; 95 % CI , + 3.2 - + 10.4 ) , whereas the Venous Clinical Severity Score improved significantly in the treatment group ( Spa : -1.2 ; 95 % CI , -1.6 - -0.8 ; Ctr : -0.6 ; 95 % CI , -1.0 - -0.2 ; P = .04 ) . A significant difference favoring spa treatment was found regarding symptoms after 1 year ( Spa : -0.03 ; 95 % CI , -0.57 - + 0.51 ; Ctr : + 0.87 ; 95 % CI,+0.46 - + 1.26 ; P = .009 ) . EuroQol 5D improved in the treatment group ( Spa : + 0.01 ; 95 % CI , -0.02 - + 0.04 ) while it worsened ( Ctr : -0.07 ; 95 % CI , -0.10 - -0.04 ) in the control group ( P < .001 ) . A similar pattern was found for the Chronic Venous Insufficiency Question naire 2 scale ( Spa : -2.0 ; 95 % CI , -4.4 - + 0.4 ; Ctr : + 2.4 ; 95 % CI , + 0.2 - + 4.7 ; P = .008 ) . The control patients showed similar improvements in clinical severity , symptoms , and quality of life after their own spa treatment ( day 547 ) . CONCLUSIONS In this study , the incidence of leg ulcers was not reduced after a 3-week spa therapy course . Nevertheless , our study demonstrates that spa therapy provides a significant and substantial improvement in clinical status , symptoms , and quality of life of patients with advanced venous insufficiency for at least 1 year OBJECTIVE To evaluate the efficacy of endovenous microwave ablation ( EMA ) in treatment of varicose veins ( VVS ) . METHODS The patients were r and omly divided into EMA and high ligation and stripping ( HLS ) groups . Clinical outcomes and complications were assessed at 1 , 3 , 6 , 12 , and 24 months after surgery , and the effect on quality of life was also assessed using the Aberdeen Varicose Vein Question naire ( AVVQ ) and Venous Clinical Severity Score ( VCSS ) respectively . RESULTS EMA occluded VVS completely , with a shorter operative time , less bleeding and smaller incisions than the HLS procedure . In the EMA group , skin burns were found on 11 limbs ( 10.2 % ) ; sensory alteration and ecchymosis were less ; and the recurrence rate of VVS was relatively lower compared with the HLS group . Both groups had significant improvement in VCSS and disease-specific quality of life ( AVVQ ) postoperatively . There was no significant difference in AVVQ and VCSS scores between the groups . CONCLUSION EMA is an effective new technique for the treatment of VVS , and had a more satisfactory clinical outcome than HLS in the short term Purpose Catheter-directed thrombolysis ( CDT ) is effective for acute iliofemoral deep venous thrombosis ( DVT ) , but CDT remains partially effective for subacute DVT . The aim of this study was to conduct a prospect i ve r and omized controlled single-centre clinical trial to compare CDT alone with CDT with additional balloon dilatation for the treatment of iliofemoral DVT . Methods The trial was performed between February 2007 and January 2011 . Iliofemoral DVT patients lacking effective therapy before enrollment were r and omly assigned either to CDT ( control group ) or to CDT with additional balloon dilatation ( intervention group ) . Insufficiency Epidemiological and Economic Study - Quality of Life ( VEINES-QOL ) , Severity of Venous Lower Limb Symptoms ( VEINES-Sym ) , 36-Item Short-Form Health Survey ( SF-36 ) , and Villalta scores were obtained at scheduled follow-up . Results Seven hundred twenty-two patients were screened , and 386 eligible patients were r and omized . No significant difference for mean total Villalta score was observed between the intervention group ( 4.20 ± 3.05 ) and the control group ( 4.89 ± 3.45 ) . However , post hoc analysis of the scores in subacute patients showed significant differences between the intervention group and the control group from 1 month ( 6.79 ± 4.23 , 8.28 ± 5.03 , P = 0.02 ) to 24 months ( 4.21 ± 3.08 , 5.67 ± 3.71 , P = 0.006 ) . A significant difference was also observed in subacute patients at the end of follow-up for VEINES-QOL/Sym ( 52.87 ± 6.52 , 50.31 ± 6.07 , P = 0.009 ; 51.87 ± 6.37 , 49.72 ± 5.96 , P = 0.02 ) and SF-36 PCS/MCS ( 45.02 ± 12.07 , 41.13 ± 11.68 , P = 0.03 ; 53.26 ± 11.43 , 49.50 ± 11.06 , P = 0.03 ) . ConclusionS ubacute iliofemoral DVT patients lacking effective therapy during acute phase , might receive more benefits from CDT with additional balloon dilatation . However , CDT alone is highly effective for acute patients Background Catheter‐directed thrombolysis ( CDT ) for deep venous thrombosis ( DVT ) of the lower extremity has good effect , but whether iliac vein stent placement after thrombolytic therapy is still controversial . The goal of this study was to evaluate the efficacy of stent placement in the iliac vein following CDT in lower extremity DVT . Methods This was a single‐center , prospect i ve , r and omized controlled clinical trial . After receiving CDT , the major branch of the distal iliac vein was completely patent in 155 patients with lower extremity DVT , and 74 of these patients with iliac vein residual stenosis of > 50 % were r and omly divided into a control group ( n=29 ) and a test group ( n=45 ) . In the test group , stents were implanted in the iliac vein , whereas no stents were implanted in the control group . We evaluated the clinical indicators , including patency of the deep vein , C in CEAP classification , Venous Clinical Severity Score ( VCSS ) , and Chronic Venous Insufficiency Question naire ( CIVIQ ) Score . Results All patients had postoperative follow‐up visits for a period of 6–24 months . Venography or color ultrasound was conducted in subjects . There was a significant difference between the patency rate at the last follow‐up visit ( 87.5 % vs. 29.6 % ) and the 1‐year patency rate ( 86.0 % vs. 54.8 % ) between the test and control groups . The change in the C in CEAP classification pre‐ and post‐procedure was significantly different between the test and control groups ( 1.61±0.21 vs. 0.69±0.23 ) . In addition , at the last follow‐up visit , VCSS and CIVIQ Score were both significantly different between the test and control groups ( 7.57±0.27 vs. 0.69±0.23 ; 22.67±3.01 vs. 39.34±6.66 , respectively ) . Conclusion The stenting of iliac vein obstruction following CDT in lower extremity DVT may increase the patency of the deep vein , and thus provides better efficacy and quality of life OBJECTIVES The aim of this study was to compare the efficacy and side effects of ultrasound-guided foam sclerotherapy of the great saphenous vein using 1 % and 3 % polidocanol foam with a 3-year follow-up . DESIGN A multicentre prospect i ve double-blind r and omised clinical trial comparing the efficacy of 1 % vs. 3 % polidocanol sclerosant foam . MATERIAL S AND METHODS Patients with incompetence of the great saphenous vein ( GSV ) in CEAP clinical classes C2 - 5 ( CEAP , Clinical -Etiology-Anatomy-Pathophysiology ) , with or without incompetence of the sapheno-femoral junction , were included . The Turbofoam method was used to create 1 % and 3 % polidocanol foam , which was injected into the GSV under ultrasound guidance , with a volume not exceeding 10 ml . Further foam sclerotherapy was carried out at 6 weeks , 3 and 6 months if required to abolish persistent venous reflux . The main outcome measure was the absence of saphenous reflux as assessed by ultrasound imaging at 6 months , 1 , 2 and 3 years . Clinical severity ( Venous Clinical Severity score ( VCSS ) ) and quality of life ( the Chronic Venous Insufficiency Question naire ( CIVIQ ) ) scores were assessed . RESULTS A total of 143 patients were included ; 1 % group men = 18 , women = 55 , 3 % group men = 19 , women = 51 . The abolition of venous reflux was : 1 % group , 69 % and 3 % group , 85 % at 6 months ; 1 % group , 79 % and 3 % group , 78 % at 3 years ( including additional injections at 6 months ) . Three asymptomatic thrombo-embolic events ( 2 % ) occurred . Local side effects ( principally pigmentation and matting ) were 9 % in the 3 % group and 6 % in the 1 % group at 3 years ( N.S. ) . Clinical severity and quality of life scores improved by more than 20 % at 6 months in both the groups , with no difference between the groups . CONCLUSIONS This is the first r and omised clinical trial of ultrasound-guided foam sclerotherapy which is a 3-year follow-up and shows equivalent efficacy of 1 % and 3 % sclerosant foam . CLINICAL TRIAL REGISTRATION NUMBER 2006 - 07 - 05 AIM This study is a prospect i ve r and omised controlled trial comparing sapheno-femoral ligation , great saphenous stripping and multiple avulsions with sapheno-femoral ligation and ultrasound guided foam sclerotherapy to the saphenous vein . Primary end points were patient recovery period and quality of life and secondary end points frequency of complications on the two arms of the trial and the cost of the treatment . MATERIAL AND METHOD Sixty patients with primary varicose veins due to GSV incompetence and suitable for day case surgery were r and omly allocated to undergo ultrasound-guided sclerotherapy with sapheno-femoral ligation under local anaesthesia ( n=30 ) or sapheno-femoral ligation , stripping and multiple avulsions under general anaesthesia ( n=30 ) . The study protocol included history , physical examination , assignment of CEAP class and assessment venous clinical severity score ( VCSS ) , completion of the aberdeen vein question naire ( AVQ ) and colour duplex ultrasound . RESULTS All treatments were completed as intended . Median time to return to normal activities was significantly reduced in the foam sclerotherapy group ( 2 days ) compared to the surgical group ( 8 days ) ( p<0.001 , Mann-Whitney ) . AVQ score was also significantly reduced at 3 months by 46 % in the sclerotherapy group , and by 40 % in the conventional surgery group ( p<0.001 , Wilcoxon ) . The time taken to complete treatment was shorter in the foam sclerotherapy plus SFJ ligation group : 45 vs. 85 min ( p<0.001 , Mann-Whitney ) . The overall cost of the procedure in the sclerotherapy group ( 672.97 pounds ) was significantly less compared to conventional surgery ( 1120.64 pounds ) . At 3 weeks , there was no statistical difference in the complication rate between the two groups . At 3 months , median CEAP class dropped from four pre-operatively to one following treatment in both groups and the median VCSS score dropped from five to one in group one and from seven to three in group two ( p<0.001 , Wilcoxon test ) . In group one four patients ( 13 % ) had a recanalised vein which needed further sessions of foam sclerotherapy , result ing in a short-term closure rate of 87 % . CONCLUSION Ultrasound guided sclerotherapy combined with sapheno-femoral ligation was less expensive , involved a shorter treatment time and result ed in more rapid recovery compared to sapheno-femoral ligation , saphenous stripping and phlebectomies BACKGROUND The addition of long saphenous vein ( LSV ) stripping to sapheno-femoral junction ( SFJ ) disconnection and multiple stab avulsions ( MSAs ) in the course of varicose vein ( VV ) surgery is associated with a significant reduction in recurrence , and a significant improvement in quality of life . It is hypothesised that these benefits relate , at least in part , to a favourable effect of stripping on deep venous reflux . OBJECTIVE To examine the effect of long saphenous vein ( LSV ) stripping on deep venous reflux ( DVR ) . METHODS This was prospect i ve study of 62 consecutive patients ( 77 limbs ) CEAP class 2 - 6 , undergoing SFJ disconnection and MSAs , with and without successful stripping of the LSV to the knee . A duplex ultrasound examination was performed pre-operatively and at a median ( IQR ) of 24 ( 23 - 25 ) months post-operatively . Completely stripped limbs were defined as those in whom complete stripping of the LSV to the knee was confirmed on post-operative duplex . Reflux > /=0.5 s. was considered pathological . RESULTS Pre-operatively , 32 ( 42 % ) limbs had deep venous reflux ( DVR ) . Post-operative duplex at 24 months revealed that the LSV had been completely stripped in 29 ( 38 % ) limbs . In patients with pre-operative DVR , complete stripping was associated with a significant reduction in the prevalence of superficial femoral vein ( SFV ) ( p<0.001 ) and popliteal vein ( PV ) ( p=0.016 ) , McNemar test ) on post-operative duplex . By contrast , in patients without pre-operative DVR , incomplete stripping was associated the development of SFV ( p=0.031 ) and PV ( p=0.008 ) reflux . CONCLUSIONS Complete LSV stripping abolishes DVR in a significant proportion of limbs , whereas failure to strip is frequently associated with the development of new DVR . These data support for routine stripping and suggest that the benefits of stripping may relate , at least in part , to a favourable impact on deep venous function OBJECTIVE The purpose of this study was to develop a practical and scientifically rigorous , patient-reported outcome measure to evaluate quality of life and symptoms across the range of conditions ( eg , telangiectasias , varicose veins , edema , skin changes , leg ulcers ) in chronic venous disorders of the leg ( CVDL ) . METHODS This study was a psychometric study within the VEnous INsufficiency Epidemiological and Economic Study ( VEINES ) , an international , prospect i ve cohort study to evaluate clinical outcomes , quality of life , costs , and use of health services in CVDL . The study was set in the 166 general practice s and 116 specialist clinics in Belgium , France , Italy , and Canada ( Quebec ) that participated in the VEINES study plus in additional specialist clinics in Ottawa and Montreal . Field testing was carried out in three sample s of patients in four countries ( Belgium , France , Italy , Canada ) , including participants in the VEINES study ( n dagger 1531 ) and patients recruited in additional sample s of 88 English-speaking patients ( Canada ) and 53 French-speaking patients ( Belgium , France ) . The reliability and validity sample ( n = 615 ) included 527 VEINES patients and 88 patients from the supplementary English-speaking sample . The test-retest sample ( n = 135 ) included 53 French-speaking and 82 English-speaking patients from the supplementary sample s. The responsiveness sample included 1516 VEINES patients . The 26-item VEINES-QOL/Sym is a new , patient-reported question naire to evaluate symptoms and quality of life and is available in four language versions ( English , French , Italian , French Canadian ) . RESULTS St and ard psychometric tests confirmed the acceptability ( missing data , item endorsement frequencies , floor and ceiling effects ) , reliability ( internal consistency , item-total , inter-item correlations ) and validity ( content , construct , convergent , discriminant , known groups ) of the four language versions of the VEINES-QOL/Sym and the test-retest reliability of the English and French versions and provided preliminary evidence of responsiveness in a pooled language sample . CONCLUSION The VEINES-QOL/Sym is a practical and scientifically sound , patient-reported measure of outcomes in CVDL that has been developed with rigorous methods . As the only fully vali date d measure of quality of life and symptoms that is appropriate for use across the full spectrum of CVDL-related conditions , that is quick and easy to administer , and that is available in four language s , the VEINES-QOL/Sym provides a rigorous tool for improving the evaluation of outcomes in clinical trials , epidemiologic studies , and audit PURPOSE This prospect i ve study aim ed to vali date a newly design ed specific measure of quality of life for patients with venous ulcers . METHODS The study was set in a London teaching hospital and surrounding community clinics . Items for the question naire were selected by means of patient interviews , a literature review , and expert opinion . The question naire and the Short Form 36-item ( SF-36 ) Health Survey were given to a prospect i ve consecutive cohort of 98 patients with proven venous ulcers that were diagnosed by means of clinical and color duplex examination . Fifty-eight of the patients were women ( 60 % ) , and the median age of patients was 76 years . The question naire was assessed for reliability , validity , and responsiveness . RESULTS The ulcer-specific question naire showed good reliability , as assessed by means of the internal consistency ( Cronbach alpha = 0.93 ) and test-retest analysis ( r = 0.84 ) . Factor analysis identified four important health factors : social function , domestic activities , cosmesis , and emotional status . Validity was demonstrated by means of a high correlation with all eight domains of the SF-36 general health measure ( r > 0.55 , P < .001 ) . Responsiveness was demonstrated by means of a significant reduction in the score on the ulcer question naire as ulcers healed at 6 and 11 weeks ( P < .05 ) . CONCLUSION Good evidence exists that a clinical ly derived measure for patients with venous ulcers has validity to measure the quality of life OBJECTIVE This clinical trial aim ed to evaluate the clinical results of the use of a tulip fibre versus the use of a bare fibre for endovenous laser ablation . METHODS In a multicentre prospect i ve r and omised trial 174 patients were r and omised for the treatment of great saphenous vein reflux . A duplex scan was scheduled 1 month , 6 months and 1 year postoperatively . Ecchymosis was measured on the 5th postoperative day . In addition , pain , analgesics requirement , postoperative quality of life ( CIVIQ 2 ) and patient satisfaction rate were noted . RESULTS Patients treated with a tulip fibre had significantly less postoperative ecchymosis ( 0.04 vs. 0.21 ; p < 0.001 ) and pain ( 5th day ) ( 1.00 vs. 2.00 ; p < 0.001 ) and had a better postoperative quality of life ( 27 vs. 32 ; p = 0.023 ) . There was no difference in analgesic intake ( p = 0.11 ) and patient satisfaction rate ( p = 0.564 ) . The total occlusion rate at 1 year was 97.02 % and there was no significant difference between the two groups ( p = 0.309 ) . CONCLUSION Using a tulip fibre for EVLA of the great saphenous vein results , when compared with the use of a bare fibre , in equal occlusion rates at 1 year but causes less postoperative ecchymosis and pain and in a better postoperative quality of life |
12,748 | 22,967,716 | Conclusions Overall , BASICS lowered both alcohol consumption and negative consequences in college students .
Gender and peer factors seem to play an important role as moderators of behavior change in college drinking .
Characteristics of BASICS procedure have been evaluated as more favorable and acceptable by students in comparison with others interventions or control conditions . | Background Many studies reported that brief interventions are effective in reducing excessive drinking .
This study aim ed to assess the efficacy of a protocol of brief intervention for college students ( BASICS ) , delivered face-to-face , to reduce risky alcohol consumption and negative consequences . | This study evaluated the efficacy of two brief personalized feedback interventions ( PFIs ) using identical feedback and motivational interviewing strategies aim ed at reducing alcohol consumption and alcohol-related problems to two control conditions among a sample of high-risk drinking college students . Students ( N = 152 ) were r and omly assigned to a computer-delivered PFI with a video interviewer , a face-to-face PFI with a live interviewer , a comprehensive assessment condition , or a minimal assessment -only condition . At 10 weeks posttreatment , the face-to-face PFI significantly reduced weekly drinking quantity and peak and typical blood alcohol concentration compared with the comprehensive assessment and minimal assessment -only conditions ( d values ranged from 0.32 to 0.61 ) . No significant between-group differences were evidence d for the computer-delivered PFI condition , although effect sizes were comparable to other college drinking studies using computer-delivered interventions ( d values ranged from 0.20 to 0.27 ) . Results provide further support for the use of a face-to-face PFI to help reduce college students ' alcohol consumption and suggest that a video interviewer in the context of a computer-delivered PFI is likely a helpful but not necessarily a complete substitute for a live interviewer In this study , the authors evaluated the efficacy of a brief motivational intervention ( BMI ) and a computerized program for reducing drinking and related problems among college students sanctioned for alcohol violations . Referred students ( N = 198 , 46 % women ) , stratified by gender , were r and omly assigned to a BMI or to the Alcohol 101 Plus computer program . Data obtained at baseline , 1 , 6 , and 12 months were used to evaluate intervention efficacy . Planned analyses revealed 3 primary findings . First , women who received the BMI reduced drinking more than did women who received the computer intervention ; in contrast , men 's drinking reductions did not differ by condition . Second , readiness to change and hazardous drinking status predicted drinking reductions at 1 month postintervention , regardless of intervention . Third , by 1 year , drinking returned to presanction ( baseline ) levels , with no differences in recidivism between groups . Exploratory analyses revealed an overall mean reduction in drinking immediately after the sanction event and before taking part in an intervention . Furthermore , after the self-initiated reductions prompted by the sanction were accounted for , participation in the BMI but not the computer intervention was found to produce additional reduction in drinking and related consequences This study tested 3 forms of alcohol risk reduction programming for young adults . Volunteers were r and omly assigned to receive a 6-week class and discussion group , a 6-unit self-help manual , or a single 1-hr feedback and advice session with professional staff . Results reveal significant reductions in self-reported drinking at the end of the intervention phase and maintenance of drinking changes throughout a 2-year follow-up period . Comparable drinking reductions were rated across treatments ; however , noncompliance with the self-help reading program suggested limited utility . Treatment response was related to subject age , as subjects showed increased drinking during the year they reached legal drinking status . The efficacy of brief motivational interventions and client matching in prevention programs is discussed OBJECTIVE This study tested the effectiveness of brief primary care provider interventions delivered in a college student health center to a sample of college students who screened positive for high-risk drinking . METHOD Between November 2005 and August 2006 , 8,753 students who presented as new patients to the health service at a large public university were screened for high-risk drinking , and 2,484 students ( 28 % ) screened positive on the 5/4 gender-specific high-risk drinking question ( i.e. , five or more drinks per occasion for men and four or more for women ) . Students who screened positive for high-risk drinking and consented to participate ( N= 363 ; 52 % female ) were r and omly assigned either to a control group ( n = 182 ) or to an experimental group ( n = 181 ) . Participants in the experimental group received two brief intervention sessions that were founded in motivational interviewing techniques and delivered by four specially trained providers within the student health center . Data on alcohol use and related harms were obtained from a Web-based Healthy Lifestyle Question naire , 30-day Timeline Followback alcohol-use diaries , the Rutgers Alcohol Problem Index ( RAPI ) , and eight items from the Drinker Inventory of Consequences-2L . RESULTS Repeated measures analysis showed that , compared with the control group ( C ) , the intervention group ( I ) had significant reductions in typical estimated blood alcohol concentration ( BAC ) ( C = .071 vs I = .057 at 3 months ; C = .073 vs I = .057 at 6 months ) , peak BAC ( C = . 142 vs I = .112 at 3 months ; C = .145 vs I = .108 at 6 months ) , peak number of drinks per sitting ( C = 8.03 vs I = 6.87 at 3 months ; C = 7.98 vs I = 6.52 at 6 months ) , average number of drinks per week ( C = 9.47 vs I = 7.33 at 3 months ; C = 8.90 vs I = 6.16 at 6 months ) , number of drunk episodes in a typical week ( C = 1.24 vs I = 0.85 at 3 months ; C = 1.10 vs I = 0.71 at 6 months ) , number of times taken foolish risks ( C = 2.24 vs I = 1.12 at 3 months ) , and RAPI sum scores ( C = 6.55 vs I = 4.96 at 6 months ; C = 6.17 vs I = 4.58 at 9 months ) . CONCLUSIONS Brief interventions delivered by primary care providers in a student health center to high-risk-drinking students may result in significantly decreased alcohol consumption , high-risk drinking , and alcohol-related harms The authors evaluated the efficacy of Brief Alcohol Screening and Intervention for College Students ( BASICS - L. A. Dimeff , J. S. Baer , D. R. Kivlahan , & G. A. Marlatt , 1999 ) , a single session of drinking-related feedback intended to reduce heavy drinking and related harm . College student drinkers ( N = 99 ) were assigned to BASICS , an educational intervention , or an assessment -only control group . At 3 months postintervention . there were no overall significant group differences , but heavier drinking BASICS participants showed greater reductions in weekly alcohol consumption and binge drinking than did heavier drinking control and education participants . At 9 months , heavier drinking BASICS participants again showed the largest effect sizes . BASICS participants evaluated the intervention more favorably than did education participants . This study suggests that BASICS may be more efficacious than educational interventions for heavier drinking college students Background Matriculation from high school to college is typified by an increase in alcohol use and related harm for many students . Therefore , this transition period is an ideal time for preventive interventions to target alcohol use and related problems . Purpose The purpose of this report is to describe the design and methods used in the Transitions Project , a r and omized controlled trial of two interventions design ed to prevent and reduce heavy episodic drinking and alcohol-related negative consequences among incoming college students . Methods This study used a 2 × 2 factorial design to investigate the effects of a two-session brief motivational intervention delivered to students and a h and book-based parent intervention . Interventions were administered to students and parents . Follow-up assessment took place at 10- and 22-months post-baseline . Results The Transitions Project successfully recruited and retained participants across a major transition period ( i.e. , entering college ) , administered and compared two distinct but complementary interventions , and collected and analyzed highly skewed data . The application of a factorial design and two-part latent growth curve modeling allowed us to examine main and interactive intervention effects in terms of both initiation and growth in heavy drinking and alcohol-related problems . Limitations While we conducted successful tests of our primary and secondary study hypotheses over a lengthy follow-up period , our study design did not permit full interpretation of null findings . We suggest that research ers carefully consider assessment timing , tests of assessment reactivity , and ensure objective tests of intervention efficacy when conducting clinical trials of motivational interventions . Conclusions The lessons we learned while conducting this trial have the potential to assist other research ers design ing and conducting future preventive interventions targeting parents and college students . The data analytic procedures presented can also help guide trials that plan to analyze zero-inflated non-normal outcome data This r and omized controlled trial evaluated the efficacy of a brief intervention design ed to reduce the harmful consequences of heavy drinking among high-risk college students . Students screened for risk while in their senior year of high school ( 188 women and 160 men ) were r and omly assigned to receive an individualized motivational brief intervention in their freshman year of college or to a no-treatment control condition . A normative group selected from the entire screening pool provided a natural history comparison . Follow-up assessment s over a 2-year period showed significant reductions in both drinking rates and harmful consequences , favoring students receiving the intervention . Although high-risk students continued to experience more alcohol problems than the natural history comparison group over the 2-year period , most showed a decline in problems over time , suggesting a developmental maturational effect This study consisted of a r and omized controlled trial of a 1-session motivational intervention for college student binge drinkers . Sixty students who reported binge drinking 2 or more times in the past 30 days were r and omly assigned to either a no-treatment control or a brief intervention group . The intervention provided students with feedback regarding personal consumption , perceived drinking norms , alcohol-related problems , situations associated with heavy drinking , and alcohol expectancies . At 6-week follow-up , the brief intervention group exhibited significant reductions on number of drinks consumed per week , number of times drinking alcohol in the past month , and frequency of binge drinking in the past month . Estimates of typical student drinking mediated these reductions . This study replicates earlier research on the efficacy of brief interventions with college students and extends previous work regarding potential mechanisms of change OBJECTIVE This study evaluated the relative efficacy of personalized drinking feedback ( PDF ) delivered with and without a motivational interview ( MI ) for college student drinkers . METHOD Heavy-drinking college students ( N = 54 ; 691 % female ) were identified from a large screening sample and r and omly assigned either to receive PDF during a single MI session or to receive PDF without an MI . Of these participants , 51 ( 94 % ) completed a 6-month follow-up assessment that included measures of alcohol consumption and alcohol-related problems . RESULTS At 6-months postintervention , participants in both groups showed significant , small to moderate reductions in alcohol consumption , but the groups did not differ . Women showed larger reductions than men . Rates of alcohol-related problems remained relatively unchanged . CONCLUSIONS The hypothesis that an MI would enhance the efficacy of PDF was not supported This study is the first reported test of the unique and combined effects of Brief Motivational Intervention ( BMI ) and Alcohol Expectancy Challenge ( AEC ) with heavy drinking college students . Three hundred and thirty-five participants were r and omly assigned in a 2x2 factorial design to either : BMI , AEC , BMI and AEC , and assessment only conditions . Follow-ups occurred at 1 , 3 , and 6 months . Unconditional latent curve analyses suggested that alcohol use ( Q-F ) , heavy episodic drinking , and alcohol problems were best modeled as quadratic effects . BMI produced significant decreases in Q-F , heavy drinking , and problems , while AEC produced significant decreases in Q-F and heavy drinking . There was no evidence of an additive effect of combining the interventions . Intervention effects decayed somewhat for BMI and completely for AEC over 6 months . Multi-group analyses suggested similar intervention effects for men and women . BMI effects on alcohol problems were mediated by perceived norms . These findings extend previous research with BMI and AEC but do not support their utility as a combined preventive intervention to reduce collegiate alcohol abuse The Lifestyle Management Class ( LMC ) was evaluated as a universal and targeted alcohol prevention program among voluntary and m and ated college students . The relative efficacy of peer- and professional-led group interventions was also tested in this r and omized , controlled design . LMC participants showed decreases in driving after drinking relative to control participants . Changes in heavy drinking varied as a function of treatment condition , readiness to change , and gender , with a trend toward larger decreases among voluntary LMC participants high in readiness to change and a comparable though nonsignificant advantage for male LMC participants in the m and ated sample . The LMC was comparably effective for m and ated and voluntary students , with no clear advantage for peer- or professional-led groups OBJECTIVE The current study tested the efficacy of a brief intervention design ed to reduce drinking and drinking-related consequences among first-year fraternity members . METHOD Twelve fraternities were r and omly assigned to receive either a motivational enhancement intervention with individual and housewide feedback components ( n = 6 houses ) or a treatment-as-usual control condition ( n = 6 houses ) . Individual feedback was delivered either by peer interviewers or professional research staff . Participants were assessed during their pledge ( first ) year of house membership and during a follow-up period 1 year later . RESULTS Of the participants who completed follow-up ( N = 120 ) , fraternity members who received the brief intervention reported significant reductions in alcohol use ( total average consumption ) and typical peak blood alcohol concentrations when compared with fraternity members in the control condition . No differences in drinking-related consequences were observed . Fraternity members who received their individualized feedback from peer interviewers and professional members of the research staff reported similar outcomes . CONCLUSIONS Results provide support for the efficacy of a brief motivational enhancement intervention in reducing drinking within this high-risk population . The cost-effective use of peer interviewers appears to be a promising strategy for delivering individualized prevention programming in college population OBJECTIVE The current study is a multisite r and omized alcohol prevention trial to evaluate the efficacy of both a parenting h and book intervention and the Brief Alcohol Screening and Intervention for College Students ( BASICS ) intervention , alone and in combination , in reducing alcohol use and consequences among a high-risk population of matriculating college students ( i.e. , former high school athletes ) . METHOD Students ( n = 1,275 ) completed a series of Web-administered measures at baseline ( in the summer before starting college ) and follow-up ( after 10 months ) . Students were r and omized to one of four conditions : parent intervention only , BASICS only , combined ( parent and BASICS ) , and assessment -only control . Intervention efficacy was tested on a number of outcome measures , including peak blood alcohol concentration , weekly and weekend drinking , and negative consequences . Hypothesized mediators and moderators of intervention effect were tested . RESULTS The overall results revealed that the combined-intervention group had significantly lower alcohol consumption , high-risk drinking , and consequences at 10-month follow-up , compared with the control group , with changes in descriptive and injunctive peer norms mediating intervention effects . CONCLUSIONS The findings of the present study suggest that the parent intervention delivered to students before they begin college serves to enhance the efficacy of the BASICS intervention , potentially priming students to respond to the subsequent BASICS session OBJECTIVES This study examined long-term response to an individual preventive intervention for high-risk college drinkers relative to the natural history of college drinking . METHODS A single-session , individualized preventive intervention was evaluated within a r and omized controlled trial with college freshmen who reported drinking heavily while in high school . An additional group r and omly selected from the entire screening pool provided a normative comparison . Participant self-report was assessed annually for 4 years . RESULTS High-risk controls showed secular trends for reduced drinking quantity and negative consequences without changes in drinking frequency . Those receiving the brief preventive intervention reported significant additional reductions , particularly with respect to negative consequences . Categorical individual change analyses show that remission is normative , and they suggest that participants receiving the brief intervention are more likely to improve and less likely to worsen regarding negative drinking consequences . CONCLUSIONS Brief individual preventive interventions for high-risk college drinkers can achieve long-term benefits even in the context of maturational trends AIM The aim of this paper was to compare the quantity and frequency of alcohol use and its associated negative consequences between two groups of college students who were identified as being " risky drinkers . " Subjects were r and omly allocated in a clinical trial to intervention or control groups . METHODS Risky drinking use was defined as Alcohol Use Disorders Identification Test ( AUDIT ) > or=8 and /or Rutgers Alcohol Problem Index ( RAPI ) > or=5 problems in the previous year . Students who had undergone the Brief Alcohol Screening and Intervention for College Students ( BASICS ) ( N = 145 at baseline ; 142 at 12 months , and 103 at 24 months , loss of 29.7 % ) were compared with a control group ( N = 121 at baseline ; 121 at 12 months and 113 at 24 months , loss of 9.3 % ) , the nonintervention group . Variables included drinking frequency , quantity and peak consumption , dependence assessment , and family and friends ' abuse assessment . RESULTS Treated students at a 24-month follow-up decreased quantity of alcohol use per occasion and lowered AUDIT and RAPI scores . CONCLUSIONS This is the first brief intervention work on risky drinking with college students in Brazil and the results are encouraging . However , it is difficult to conduct individual prevention strategies in a country where culture fosters heavy drinking through poor public policy on alcohol and lack of law enforcement The authors conducted two r and omized clinical trials with ethnically diverse sample s of college student drinkers in order to determine ( a ) the relative efficacy of two popular computerized interventions versus a more comprehensive motivational interview approach ( BASICS ) and ( b ) the mechanisms of change associated with these interventions . In Study 1 , heavy drinking participants recruited from a student health center ( N = 74 , 59 % women , 23 % African American ) were r and omly assigned to receive BASICS or the Alcohol 101 CD-ROM program . BASICS was associated with greater post-session motivation to change and self-ideal and normative discrepancy relative to Alcohol 101 , but there were no group differences in the primary drinking outcomes at 1-month follow-up . Pre to post session increases in motivation predicted lower follow-up drinking across both conditions . In Study 2 , heavy drinking freshman recruited from a core university course ( N = 133 , 50 % women , 30 % African American ) were r and omly assigned to BASICS , a web-based feedback program ( e-CHUG ) , or assessment -only . BASICS was associated with greater post-session self-ideal discrepancy than e-CHUG , but there were no differences in motivation or normative discrepancy . There was a significant treatment effect on typical weekly and heavy drinking , with participants in BASICS reporting significantly lower follow-up drinking relative to assessment only participants . In Study 2 , change in the motivation or discrepancy did not predict drinking outcomes . Across both studies , African American students assigned to BASICS reported medium effect size reductions in drinking whereas African American students assigned to Alcohol 101 , e-CHUG , or assessment did not reduce their drinking In this r and omized controlled trial , the authors evaluated brief motivational interventions ( BMI s ) for at-risk college drinkers . Heavy drinking students ( N = 509 ; 65 % women , 35 % men ) were r and omized into 1 of 6 intervention conditions formed by crossing the baseline Timeline Followback ( TLFB ) interview ( present versus absent ) and intervention type ( basic BMI , BMI enhanced with a decisional balance module , or none ) . Assessment s completed at baseline , 1 , 6 , and 12 months measured typical and risky drinking as well as drinking-related problems . Relative to controls , the TLFB interview reduced consumption but not problems at 1 month . The basic BMI improved all drinking outcomes beyond the effects of the TLFB interview at 1 month , whereas the enhanced BMI did not . Risk reduction achieved by brief interventions maintained throughout the follow-up year This study investigated the clinical significance of previously reported statistically significant mean reductions in drinking and related problems among college students in a r and omized trial of a brief indicated preventive intervention ( G. A. Marlatt et al. , 1998 ) . Data were analyzed over a 2-year follow-up for participants from a high-risk intervention group ( n = 153 ) , a high-risk control group ( n = 160 ) , and a functional comparison group ( n = 77 ) . A risk cutpoint for each dependent measure was based on the functional comparison group distribution . Compared with the high-risk controls , more individuals in the high-risk intervention group improved and fewer worsened , especially on alcohol-related problems and , to a lesser extent , on drinking pattern variables . These data from a prevention context clarify the magnitude and direction of individual change obscured by group means Importance of peer counselor posttraining supervision on motivational interviewing ( MI ) microskills and postintervention drinking outcomes were evaluated in a sample of heavy-drinking undergraduate students completing Brief Alcohol Screening and Intervention for College Students ( BASICS ; L.A. Dimeff , J.S. Baer , D.R. Kivlahan , & G.A. Marlatt , 1999 ) . Two peer counselor groups were trained using identical protocol s. Posttraining , one group was r and omized to receive supervision , whereas the other received no supervision . Groups were subsequently compared on MI microskills . College students ( n = 122 ) were r and omly assigned to either assessment -only control , supervision , or no supervision groups and completed a BASICS intervention . Postintervention drinking outcomes were examined . Results suggested supervision aided peer counselors in reducing use of closed-ended questions . Both treatment groups reduced total drinks per week and heavy-drinking behaviors compared to control . No differences on peak blood alcohol concentration ( BAC ) or alcohol-related consequences were observed . Differences in supervision did not influence drinking outcomes ; however , posttraining supervision for peer counselors deficient in MI microskills may be needed to improve BASICS fidelity |
12,749 | 27,317,475 | The ELAPE was associated with a significantly lower intraoperative perforation rate .
There were no differences regarding the circumferential margin involvement , R0 resections , and local recurrence rate .
There was less blood loss in ELAPE patients .
The ELAPE significantly lowered the intraoperative perforation rate , with no benefits regarding circumferential resection margin involvement and local recurrence rate | BACKGROUND The aim of this study was to compare the short-term morbidity and long-term oncologic benefits of extralevator abdominoperineal excision ( ELAPE ) with conventional abdominoperineal resection ( CAPR ) for patients with rectal cancer . | Objectives : The aim of this prospect i ve registry-based population study was to investigate the efficacy of extralevator abdominoperineal excision ( ELAPE ) regarding local recurrence rates within 3 years after surgery . Background : Local recurrence of rectal cancer is more common after abdominoperineal excision ( APE ) than after anterior resection . Extralevator abdominoperineal excision was introduced to address this problem . No large-scale studies with long-term oncological outcomes have been published . Methods : All Swedish patients operated on with an APE and registered in the Swedish ColoRectal Cancer Registry 2007 to 2009 were included ( n = 1397 ) and analyzed with emphasis on the perineal part of the operation . Local recurrence at 3 years was collected from the registry . Results : The local recurrence rates at 3 years [ median follow-up , 3.43 years ( APE , 3.37 years ; ELAPE , 3.41 years ; not stated : 3.43 years ) ] were significantly higher for ELAPE compared with APE ( relative risk , 4.91 ) . Perioperative perforation was also associated with an increased risk of local recurrence ( relative risk , 3.62 ) . There was no difference in 3-year overall survival between APE and ELAPE . In the subgroup of patients with very low tumors ( ⩽4 cm from the anal verge ) , no significant difference in the local recurrence rate could be observed . Conclusions : Extralevator abdominoperineal excision results in a significantly increased 3-year local recurrence rate as compared with st and ard APE . Intraoperative perforation seems to be an important risk factor for local recurrence . In addition to significantly increased 3-year local recurrence rates , the significantly increased incidence of wound complications leads to the conclusion that ELAPE should only be considered in selected patients at risk of intraoperative perforation PURPOSE Despite the major improvements that have been made due to total mesorectal excision ( TME ) , low rectal cancer still remains a challenge . METHODS By investigating a prospect i ve r and omized rectal cancer trial in which surgeons had undergone training in TME the factors responsible for the poor outcome were determined and a new method for assessing the quality of surgery was tested . RESULTS Survival differed greatly between abdominoperineal resection ( APR ) and anterior resection ( AR ; 38.5 % v 57.6 % , P = .008 ) . Low rectal carcinomas have a higher frequency of circumferential margin involvement ( 26.5 % v 12.6 % , P < .001 ) . More positive margins were present in the patients operated with APR ( 30.4 % ) compared to AR ( 10.7 % , P = .002 ) . Furthermore , more perforations were present in these specimens ( 13.7 % v 2.5 % , P < .001 ) . The plane of resection lies within the sphincteric muscle , the submucosa or lumen in more than 1/3 of the APR cases , and in the remainder lay on the sphincteric muscles . CONCLUSION We systematic ally described and investigated the pathologic properties of low rectal cancer in general , and APR in particular , in a prospect i ve r and omized trial including surgeons who had been trained in TME . The poor prognosis of the patients with an APR is ascribed to the resection plane of the operation leading to a high frequency of margin involvement by tumor and perforation with this current surgical technique . The clinical results of this operation could be greatly improved by adopting different surgical techniques and possibly greater use of radiochemotherapy Summary Background Local recurrence rates in operable rectal cancer are improved by radiotherapy ( with or without chemotherapy ) and surgical techniques such as total mesorectal excision . However , the contributions of surgery and radiotherapy to outcomes are unclear . We assessed the effect of the involvement of the circumferential resection margin and the plane of surgery achieved . Methods In this prospect i ve study , the plane of surgery achieved and the involvement of the circumferential resection margin were assessed by local pathologists , using a st and ard pathological protocol in 1156 patients with operable rectal cancer from the CR07 and NCIC-CTG CO16 trial , which compared short-course ( 5 days ) preoperative radiotherapy and selective postoperative chemoradiotherapy , between March , 1998 , and August , 2005 . All analyses were by intention to treat . This trial is registered , number IS RCT N 28785842 . Findings 128 patients ( 11 % ) had involvement of the circumferential resection margin , and the plane of surgery achieved was classified as good ( mesorectal ) in 604 ( 52 % ) , intermediate ( intramesorectal ) in 398 ( 34 % ) , and poor ( muscularis propria plane ) in 154 ( 13 % ) . We found that both a negative circumferential resection margin and a superior plane of surgery achieved were associated with low local recurrence rates . Hazard ratio ( HR ) was 0·32 ( 95 % CI 0·16–0·63 , p=0·0011 ) with 3-year local recurrence rates of 6 % ( 5–8 % ) and 17 % ( 10–26 % ) for patients who were negative and positive for circumferential resection margin , respectively . For plane of surgery achieved , HRs for mesorectal and intramesorectal groups compared with the muscularis propria group were 0·32 ( 0·16–0·64 ) and 0·48 ( 0·25–0·93 ) , respectively . At 3 years , the estimated local recurrence rates were 4 % ( 3–6 % ) for mesorectal , 7 % ( 5–11 % ) for intramesorectal , and 13 % ( 8–21 % ) for muscularis propria groups . The benefit of short-course preoperative radiotherapy did not differ in the three plane of surgery groups ( p=0·30 for trend ) . Patients in the short-course preoperative radiotherapy group who had a resection in the mesorectal plane had a 3-year local recurrence rate of only 1 % . Interpretation In rectal cancer , the plane of surgery achieved is an important prognostic factor for local recurrence . Short-course preoperative radiotherapy reduced the rate of local recurrence for all three plane of surgery groups , almost abolishing local recurrence in short-course preoperative radiotherapy patients who had a resection in the mesorectal plane . The plane of surgery achieved should therefore be assessed and reported routinely . Funding Medical Research Council ( UK ) and the National Cancer Institute of Canada Purpose Local recurrences are more common after abdominoperineal excision ( APE ) than after anterior resection of rectal cancer . Extralevator APE was introduced to address this problem . This prospect i ve registry-based population study aims to investigate the efficacy of extralevator APE ( ELAPE ) in improving short-term oncological outcome . Methods All Swedish patients operated with any kind of abdominoperineal excision and registered in the Swedish Rectal Cancer Registry 2007–2009 were included ( n = 1,397 ) and analyzed with emphasis on the perineal part of the operation . Short-term perioperative and oncological results were collected from the registry . Results Extralevator APE did not result in fewer intraoperative perforations or involved circumferential resection margins as compared to st and ard APE for the entire group . Intraoperative perforations were significantly fewer for patients with low tumours ( ≤4 cm ) ( ELAPE : n = 28/386 versus APE : n = 9/58 ) ( p = 0.043 ) and for early ( T0–T2 ) T-stages ( ELAPE : n = 3/172 versus APE : n = 6/75 ) ( p = 0.025 ) . There were significantly more post-operative wound infections for ELAPE than for APE ( n = 106 ( 20.4 % ) versus n = 25 ( 12.0 % ) , p = 0.011 ) . Conclusions The short-term results indicate that selective use of extralevator APE can be warranted , for example , for subgroups with low tumours . In conclusion , selective use of the extralevator APE is advocated as not all patients seem to benefit from the technique , and there are significantly more short-term complications after extralevator APE Background The extralevator abdominoperineal excision ( ELAPE ) has been proposed as oncologically superior to st and ard abdominoperineal excision ( SAPE ) . However , little is known regarding comparative margins achieved in ELAPE and SAPE . The purpose of this study was to compare patterns of tissue removal between these two groups that can aid patient selection . Methods Twenty APE specimens , comprising 10 SAPEs and 10 ELAPEs , were selected r and omly from a single UK centre . Transverse slices of pathological specimens were matched to corresponding axial MRI images obtained from conventional pelvic MRI imaging . Measurements from the muscularis propria to the resection margin [ muscularis to margin ( MTM ) distance ] were recorded by height ( from anal verge ) and quadrant for each surgical group . MTM distances achieved on histopathological assessment were also compared to MRI assessed distances necessary to achieve a clear CRM . Results ELAPE specimens had a greater mean MTM distance than for SAPE ( 7.75 vs. 5.61 mm , p = 0.02 ) . ELAPE had significantly greater MTM distances in lateral and posterior quadrants ( p < 0.05 ) than SAPE at 30–49 mm . There was no significant difference in mean anterior distances ( 1.57 vs. 1.16 mm , p = 0.507 ) with the smallest difference at a height of 60–69 mm . Two ( 2 % ) of pathological MTM distances within ELAPE group failed to achieve the minimum MRI assessed distance compared with 30 ( 23 % ) in the SAPE group , which had higher CRM positivity . Conclusions ELAPE appears to confer oncological benefit over SAPE but with notable exceptions , including tumours located above and below the puborectalis sling and anteriorly at the level of prostate where exenteration may be more appropriate OBJECTIVE To evaluate the oncological results and possible benefits associated with extralevatory abdominoperineal excision ( ELAPE ) when compared with conventional abdominoperineal excision ( APE ) . BACKGROUND ELAPE was introduced in 2007 with the purpose of reducing the rate of positive resection margins after resection of low rectal cancers . Preliminary studies have shown promising results . No large-scale or nationwide data have been presented . METHODS Data base study based on data from the Danish Colorectal Cancer Group 's prospect i ve data base . Data on all ELAPEs and APEs performed in Denmark in the period January 1 , 2009 , through August 2012 were retrieved and evaluated for differences in demography , tumor characteristics , and oncological results . Uni- and multivariate logistic regression analyses were performed to identify risk factors for resection with a positive circumferential resection margin ( CRM+ ) . RESULTS A total of 554 patients were included , 301(54 % ) were operated by ELAPE ; 253(46 % ) by APE . Sixty-three percent were men , median ( interquartile range ) age was 69 ( 61 - 76 years ) years , and tumors removed had predominantly T-stages T2 and T3 ( 32 % and 45 % , respectively ) . Overall , CRM+ was found in 13 % of patients . When divided according to type of procedure , we found no significant differences in demography and tumor T- and N-stages . Resections with a CRM+ were more common after ELAPE ( 16 % vs 7 % ; P = 0.006 ) . After uni- and multivariate logistic regression analyses , surgery by ELAPE remained a risk factor for a CRM+ [ odds ratio , 2.59 ( 95 % confidence interval , 1.31 - 5.12 ) ; P = 0.006 ) . CONCLUSIONS In this nationwide study , resection of low rectal cancers by ELAPE did not improve short-term oncological results , when compared with conventional APE BACKGROUND : There is debate whether performing the perineal part of the abdominoperineal resection in a prone position in comparison with a lithotomy position optimizes circumferential resection margins and , subsequently , cancer outcomes . OBJECTIVE : The aim of this study was to compare outcomes of patients undergoing abdominoperineal in a prone vs a lithotomy position . DESIGN : A single-center , prospect ively maintained colorectal cancer data base was queried for patients with stages I to III rectal cancer undergoing abdominoperineal resection in a prone vs a lithotomy position from 1997 to 2007 . Patients were compared with respect to demographics , tumor and treatment characteristics , perioperative morbidity , and oncologic outcomes . Oncologic outcomes were adjusted for age , ASA class , tumor stage , and use of adjuvant treatments . & khgr;2 , Fisher exact probability test , Wilcoxon rank-sum test , Kaplan-Meier estimates , log-rank sum test , and Cox regression models were used for the analysis . P < .05 was considered significant . RESULTS : The query returned 168 patients ( 81 prone and 87 lithotomy ) , with a median age of 63 ( interquartile range , 52–74 ) years and a median follow-up of 42 ( interquartile range , 23–69 ) months . Prone and lithotomy patients were not statistically different regarding demographics , tumor stage , rates of R0 resection , number of harvested nodes , perioperative morbidity , follow-up time , and oncologic outcomes . CONCLUSIONS : Surgical positioning during the perineal part of the abdominoperineal resection does not affect perioperative morbidity or oncologic outcomes and should be left to the surgeon 's discretion BACKGROUND An alternative treatment for low rectal cancer is the cylindrical technique . We aim to compare the outcomes of patients undergoing conventional abdominoperineal resection ( APR ) versus cylindrical APR . METHODS A prospect i ve , r and omized , open-label , parallel controlled trial was conducted between January 2008 and December 2010 . Sixty-seven patients with T3-T4 low rectal cancer were identified during the study period ( conventional n = 32 , cylindrical n = 35 ) . RESULTS Patients who received cylindrical APR had less operative time for the perineal portion ( P < .001 ) , larger perineal defect ( P < .001 ) , less intraoperative blood loss ( P = .001 ) , larger total cross-sectional tissue area ( P < .001 ) , similar total operative time ( P = .096 ) , and more incidence of perineal pain ( P < .001 ) . The local recurrence of the cylindrical APR group was improved statistically ( P = .048 ) . CONCLUSIONS Cylindrical APR in the prone jackknife position has the potential to reduce the risk of local recurrence without increased complications when compared with conventional APR in the lithotomy position for the treatment of low rectal cancer BACKGROUND The use of extra-levator abdominoperineal resection ( ELAPE ) procedure for lower rectal cancer is controversial . It is unclear whether the ELAPE procedure could improve surgical safety and lead to better oncological outcomes . METHODS Sixty-nine lower rectal cancer patients who underwent ELAPE ( 36 cases ) or conventional abdominoperineal resection ( APE ; 33 cases ) between June 2011 and February 2013 were prospect ively investigated . Clinicopathological variables including blood loss , intraoperative perforation ( IOP ) rate , circumferential resection margin ( CRM ) involvement , lymph node harvest , the postoperative complications , urinary and sexual function , quality of life ( QOL ) , local recurrence rate and survival were recorded and compared . RESULTS Blood loss ( P = 0.021 ) , perineal wound complication ( P = 0.039 ) , IOP rate ( P = 0.028 ) , local recurrence ( P = 0.034 ) were significantly less frequent in the ELAPE group . There was greater CRM involvement in the conventional APE group but no statistical difference between the two groups . Urinary function , sexual function and QOL were not significantly different between the two groups . Overall survival and progression-free survival were not significantly different between two groups , even when survival was analyzed according to TNM stage , T stage , N stage , and with or without neoadjuvant chemoradiotherapy . In patients who underwent ELAPE there was no statistical difference in postoperative complications between younger and elderly patients ( age ≥60 ) . CONCLUSIONS ELAPE procedure with definitive anatomic l and marks demonstrated surgical safety and decreased local recurrence for lower rectal cancer patients including the elderly , but there were no survival improvements in compared to conventional APE procedure |
12,750 | 29,312,640 | Conclusions Compared with HAS-BLED , the ORBIT score does not perform better in predicting major bleeding events in anticoagulated atrial fibrillation patients .
More anticoagulated AF patients and major bleeding events were categorized as low risk when using ORBIT | Background The HAS-BLED and ORBIT scores have been proposed to assess bleeding risk in anticoagulated atrial fibrillation patients .
We performed a systematic review and meta- analysis to compare the predictive ability by using these two scores . | Background Therapeutic decisions in atrial fibrillation ( AF ) are often influenced by assessment of bleeding risk . However , existing bleeding risk scores have limitations . Objectives We sought to develop and vali date a novel bleeding risk score using routinely available clinical information to predict major bleeding in a large , community-based AF population . Methods We analysed data from Outcomes Registry for Better Informed Treatment of Atrial Fibrillation ( ORBIT-AF ) , a prospect i ve registry that enrolled incident and prevalent AF patients at 176 US sites . Using Cox proportional hazards regression , we identified factors independently associated with major bleeding among patients taking oral anticoagulation ( OAC ) over a median follow-up of 2 years ( interquartile range = 1.6–2.5 ) . We also created a numerical bedside risk score that included the five most predictive risk factors weighted according to their strength of association with major bleeding . The predictive performance of the full model , the simple five-item score , and two existing risk scores ( hypertension , abnormal renal/liver function , stroke , bleeding history or predisposition , labile INR , elderly , drugs/alcohol concomitantly , HAS-BLED , and anticoagulation and risk factors in atrial fibrillation , ATRIA ) were then assessed in both the ORBIT-AF cohort and a separate clinical trial population , Rivaroxaban Once-daily oral direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation ( ROCKET-AF ) . Results Among 7411 ORBIT-AF patients taking OAC , the rate of major bleeding was 4.0/100 person-years . The full continuous model ( 12 variables ) and five-factor ORBIT risk score ( older age [ 75 + years ] , reduced haemoglobin/haematocrit/history of anaemia , bleeding history , insufficient kidney function , and treatment with antiplatelet ) both had good ability to identify those who bled vs. not ( C-index 0.69 and 0.67 , respectively ) . These scores both had similar discrimination , but markedly better calibration when compared with the HAS-BLED and ATRIA scores in an external validation population from the ROCKET-AF trial . Conclusions The five-element ORBIT bleeding risk score had better ability to predict major bleeding in AF patients when compared with HAS-BLED and ATRIA risk scores . The ORBIT risk score can provide a simple , easily remembered tool to support clinical decision making OBJECTIVES The objective of this study was to compare the predictive performance of bleeding risk-estimation tools in a cohort of patients with atrial fibrillation ( AF ) undergoing anticoagulation . BACKGROUND Three bleeding risk-prediction schemes have been derived for and vali date d in patients with AF : HEMORR(2)HAGES ( Hepatic or Renal Disease , Ethanol Abuse , Malignancy , Older Age , Reduced Platelet Count or Function , Re-Bleeding , Hypertension , Anemia , Genetic Factors , Excessive Fall Risk and Stroke ) , ATRIA ( Anticoagulation and Risk Factors in Atrial Fibrillation ) , and HAS-BLED ( Hypertension , Abnormal Renal/Liver Function , Stroke , Bleeding History or Predisposition , Labile International Normalized Ratio , Elderly , Drugs/Alcohol ) . Τhe relative predictive values of these bleeding scores have not previously been compared . METHODS We analyzed the data set from the AMADEUS ( Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation ) trial , a multicenter , r and omized , open-label noninferiority study that compared fixed-dose idraparinux with adjustable-dose oral vitamin K antagonist therapy in patients with AF . The principal safety outcome was any clinical ly relevant bleeding event , which was a composite of major bleeding plus clinical ly relevant nonmajor bleeding . RESULTS The HAS-BLED score performed best in predicting any clinical ly relevant bleeding , reflected both in net reclassification improvement ( 10.3 % and 13 % improvement compared with HEMORR(2)HAGES and ATRIA , respectively ) and receiver-operating characteristic ( ROC ) analyses ( c-indexes : 0.60 vs. 0.55 and 0.50 for HAS-BLED vs. HEMORR(2)AGES and ATRIA , respectively ) . Using decision-curve analysis , the HAS-BLED score demonstrated superior performance compared with ATRIA and HEMORR(2)HAGES at any threshold probability for clinical ly relevant bleeding . HAS-BLED was the only score that demonstrated a significant predictive performance for intracranial hemorrhage ( c-index : 0.75 ; p = 0.03 ) . An ATRIA score > 3 was not significantly associated with the risk for any clinical ly relevant bleeding on Cox regression or on ROC analysis ( c-index : 0.50 ; p = 0.87 ) . CONCLUSIONS All 3 tested bleeding risk-prediction scores demonstrated only modest performance in predicting any clinical ly relevant bleeding , although the HAS-BLED score performed better than the HEMORR(2)HAGES and ATRIA scores , as reflected by ROC analysis , reclassification analysis , and decision-curve analysis . Only HAS-BLED demonstrated a significant predictive performance for intracranial hemorrhage . Given its simplicity , the HAS-BLED score may be an attractive method for the estimation of oral anticoagulant-related bleeding risk for use in clinical practice , supporting recommendations in international guidelines Context Guidelines for prescribing anticoagulants in atrial fibrillation do not use contemporary stroke rates or account for intracranial bleeding risk . Contribution The authors studied 6-year rates of ischemic stroke and intracranial hemorrhage in 13559 adults with nonvalvular atrial fibrillation . They calculated ischemic stroke rates in patients receiving and not receiving warfarin ( treatment benefit ) and intracranial hemorrhage rates ( treatment harm ) . Benefit minus harm ( net treatment benefit ) was highest in patients with previous stroke , age older than 84 years , and others with high stroke risk . Caution Patients received warfarin according to clinical judgment , not r and omly . Implication Age and other stroke risk factors should drive the decision to use warfarin in atrial fibrillation . The Editors Warfarin anticoagulation is very efficacious in preventing thromboembolism ( primarily ischemic stroke but also systemic thromboembolism ) in patients with atrial fibrillation and is highly effective in practice ( 1 , 2 ) . Nonetheless , warfarin therapy increases the risk for major hemorrhage and is burdensome for both physicians and patients . Therefore , clinical guidelines ( 3 , 4 ) recommend warfarin only for patients with atrial fibrillation who are considered to be at intermediate or high risk for ischemic stroke . However , these risk-based anticoagulation guidelines have substantial limitations . First , they do not explicitly account for the risk for fatal and disabling hemorrhage due to warfarin . Second , they are primarily based on studies conducted more than 15 years ago . Recent studies ( 2 , 5 , 6 ) of patients with atrial fibrillation suggest a lower absolute risk for stroke while not receiving warfarin therapy , perhaps reflecting better treatment of hypertension or other risk factors . Finally , the net clinical benefit of risk-based recommendations for anticoagulation in patients with atrial fibrillation has not been demonstrated in large population s followed for long periods . In our observational study , we quantify the net clinical benefit of warfarin anticoagulation , defined as the estimated reduction in rate of thromboembolism , mainly ischemic stroke , minus 1.5 times the estimated increase in rate of intracranial hemorrhage attributable to warfarin therapy in st and ard stroke risk subgroups in the community-based cohort of patients in the ATRIA ( AnTicoagulation and Risk Factors In Atrial Fibrillation ) Study . Methods Study Population The ATRIA Study cohort consists of 13559 adults with diagnosed nonvalvular atrial fibrillation who received care within Kaiser Permanente of Northern California , a large integrated health care delivery system . Cohort assembly is described in detail elsewhere ( 2 , 7 ) . In brief , we identified patients with a diagnosis of atrial fibrillation between 1 July 1996 and 31 December 1997 by search ing outpatient data bases for internal medicine or cardiology visits in which an International Classification of Diseases , Ninth Revision , Clinical Modification ( ICD-9-CM ) , diagnosis of atrial fibrillation ( 427.31 ) was assigned and by search ing electrocardiographic data bases for a diagnosis of atrial fibrillation . The date of the first diagnosis of atrial fibrillation during the period of cohort assembly was considered the patient 's index date . Cohort assembly was finalized by November 1998 , and the cohort was followed through 30 September 2003 with a combination of retrospective ( back to July 1996 ) and prospect i ve ( through September 2003 ) review of health plan data bases and medical records . Patients who died or withdrew from the health plan during follow-up were censored at their date of death or on the last day of the month in which they terminated their membership . Date of death was ascertained from health plan clinical or administrative files , the California Automated Mortality Linkage System , or the Social Security Administration Death Master File . The institutional review boards at Massachusetts General Hospital and the Kaiser Foundation Research Institute approved the research . Patient Characteristics We search ed data bases of clinical inpatient and ambulatory visits ( outpatient clinic and emergency department ) during the 5 years before each patient 's index date to identify previously diagnosed ischemic stroke , heart failure , coronary heart disease , and hypertension by using relevant ICD-9-CM codes ( 2 ) . We used a vali date d , comprehensive health plan diabetes registry to identify patients with diabetes mellitus . Ascertainment of these stroke risk factors was vali date d against review of sample s of outpatient medical records ; crude agreement was high ( 78 % to 96 % ) , and corresponding statistics ranged from 0.51 to 0.89 . Of note , stroke risk prediction based on risk factors ascertained in the ATRIA Study was in good agreement with risk schemes generated by pooled r and omized trial and chart-based cohort study data ( 2 , 810 ) . Information from medical care received at both health plan and nonhealth plan facilities was obtained through these data bases . Data on age and sex were obtained from administrative data bases . Warfarin Exposure We determined warfarin exposure on the basis of information from automated clinical , pharmacy , and laboratory data bases by using methods described elsewhere ( 2 ) . We vali date d this computerized approach in 1207 patients by comparing it with warfarin status documented in their medical record at the time of an outcome event ; the result ing statistic was 0.84 . Nearly all discrepancies were due to transient discontinuation of warfarin treatment . If medical chart review of an outcome event showed that the patient stopped receiving warfarin within 5 days before the event , the event was considered to take place while the patient was receiving warfarin . For patients considered to be receiving warfarin , an adapted linear interpolation method was used to determine the person-time spent in the therapeutic international normalized ratio ( INR ) range of 2.0 to 3.0 ( 11 ) . If the interval between consecutive INR measurements was greater than 8 weeks , the INR person-time for this period was considered not available . Outcome Assessment Thromboembolic Events We search ed hospitalization and billing cl aims data bases through 30 September 2003 for primary ICD-9-CM discharge diagnoses that indicated potential thromboembolism , including ischemic stroke and other systemic embolism ( ICD-9-CM codes available on request ) ( 2 ) . For both potential thromboembolic events and hemorrhagic events , medical record analysts obtained the relevant medical records by using a structured protocol . We did not investigate hospitalizations with the selected discharge diagnosis codes in a secondary position , because such hospitalizations rarely were prompted by new thromboembolic events . We estimate that our rates of ischemic stroke would have been increased relatively by 6 % had we review ed all such hospitalizations ( 2 ) . We defined a vali date d ischemic stroke as a sudden neurologic deficit lasting more than 24 hours , corresponding to a vascular territory in the absence of primary hemorrhage , that was not explained by other causes ( for example , trauma or infection ) . We defined a valid peripheral embolism as being identified by radiographic imaging , intraoperative examination , or pathologic findings ( with no atherosclerotic disease in the affected artery ) . Thromboembolic events occurring after hospital admission , generally as a complication of medical care , were not included as outcome events . Two members of the physician outcomes review committee review ed all potential thromboembolic events by using a formal protocol . Disagreements were resolved by a third committee member or by a consulting neurologist , if needed . Intracranial Hemorrhage We search ed hospitalization and billing data bases for primary and secondary discharge diagnoses of intracranial hemorrhage , including intraparenchymal , subdural , subarachnoid , and other hemorrhage ( ICD-9-CM codes available on request ) . We excluded intracranial hemorrhage associated with a concomitant discharge diagnosis of major trauma ( ICD-9-CM codes 852.1 , 852.3 , 852.5 , and 853.1 ) and events not leading to hospitalization or those that occurred as a complication of a hospitalization for another problem . Net Clinical Benefit We defined the core net clinical benefit of warfarin therapy in atrial fibrillation as the annualized rate of thromboembolic events ( TE rate ) prevented minus the annualized rate of intracranial hemorrhages ( ICH rate ) induced , multiplied by a weighting factor . The following equation illustrates this definition : The weighting factor reflects the relative impact , in terms of death and disability , of an intracranial hemorrhage ( including intracerebral , subdural , subarachnoid , and other hemorrhages ) while receiving warfarin versus experiencing an ischemic stroke while not receiving warfarin ( 12 ) . We assigned our base case a weighting factor of 1.5 , reflecting outcomes in the ATRIA Study cohort ( 13 , 14 ) . We also provide additional sensitivity analyses by using weighting factors of 1.0 and 2.0 . For 10 % of potential thromboembolic events and intracranial hemorrhages identified by ICD-9-CM codes , the patients ' medical records were unavailable or contained insufficient information to determine whether a valid event had occurred . We did not include these events . For events with missing clinical information , the ratio of patients receiving warfarin to those not receiving warfarin was similar to the ratio for vali date d events . Making the improbable assumption that all such potential events met our validity criteria increased our estimate of unadjusted overall net clinical benefit by only 0.07 % per year . Statistical Analysis We calculated incidence rates of thromboembolism and intracranial hemorrhage as the number of events per 100 person-years of follow-up . Because individual participants in the ATRIA Study cohort could have alternating periods of receiving and not receiving warfarin , we BACKGROUND The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation ( ARISTOTLE ) trial showed that apixaban is better than warfarin at prevention of stroke or systemic embolism , causes less bleeding , and results in lower mortality . We assessed in this trial 's participants how results differed according to patients ' CHADS(2 ) , CHA(2)DS(2)VASc , and HAS-BLED scores , used to predict the risk of stroke and bleeding . METHODS ARISTOTLE was a double-blind , r and omised trial that enrolled 18,201 patients with atrial fibrillation in 39 countries . Patients were r and omly assigned apixaban 5 mg twice daily ( n=9120 ) or warfarin ( target international normalised ratio 2·0 - 3·0 ; n=9081 ) . The primary endpoint was stroke or systemic embolism . The primary safety outcome was major bleeding . We calculated CHADS(2 ) , CHA(2)DS(2)VASc , and HAS-BLED scores of patients at r and omisation . Efficacy analyses were by intention to treat , and safety analyses were of the population who received the study drug . ARISTOTLE is registered with Clinical Trials.gov , number NCT00412984 . FINDINGS Apixaban significantly reduced stroke or systemic embolism with no evidence of a differential effect by risk of stroke ( CHADS(2 ) 1 , 2 , or ≥3 , p for interaction=0·4457 ; or CHA(2)DS(2)VASc 1 , 2 , or ≥3 , p for interaction=0·1210 ) or bleeding ( HAS-BLED 0 - 1 , 2 , or ≥3 , p for interaction=0·9422 ) . Patients who received apixaban had lower rates of major bleeding than did those who received warfarin , with no difference across all score categories ( CHADS(2 ) , p for interaction=0·4018 ; CHA(2)DS(2)VASc , p for interaction=0·2059 ; HAS-BLED , p for interaction=0·7127 ) . The relative risk reduction in intracranial bleeding tended to be greater in patients with HAS-BLED scores of 3 or higher ( hazard ratio [ HR ] 0·22 , 95 % CI 0·10 - 0·48 ) than in those with HAS-BLED scores of 0 - 1 ( HR 0·66 , 0·39 - 1·12 ; p for interaction=0·0604 ) . INTERPRETATION Because apixaban has benefits over warfarin that are consistent across patient risk of stroke and bleeding as assessed by the CHADS2 , CHA2DS2VASc , and HAS-BLED scores , these scores might be less relevant when used to tailor apixaban treatment to individual patients than they are for warfarin . Further improvement in risk stratification for both stroke and bleeding is needed , particularly for patients with atrial fibrillation at low risk for these events . FUNDING Bristol-Myers Squibb and Pfizer |
12,751 | 26,446,908 | Targeted drugs with companion diagnostics are associated with improved safety , and tolerability .
Differences were most marked for gastrointestinal , cutaneous and neurological toxicity | BACKGROUND Companion diagnostics aim to identify patients that will respond to targeted therapies , therefore increasing the clinical efficacy of such drugs .
Less is known about their influence on safety and tolerability of targeted anti-cancer agents . | BACKGROUND The treatment of advanced renal cell carcinoma has been revolutionised by targeted therapy with drugs that block angiogenesis . So far , no phase 3 r and omised trials comparing the effectiveness of one targeted agent against another have been reported . We did a r and omised phase 3 study comparing axitinib , a potent and selective second-generation inhibitor of vascular endothelial growth factor ( VEGF ) receptors , with sorafenib , an approved VEGF receptor inhibitor , as second-line therapy in patients with metastatic renal cell cancer . METHODS We included patients coming from 175 sites ( hospitals and outpatient clinics ) in 22 countries aged 18 years or older with confirmed renal clear-cell carcinoma who progressed despite first-line therapy containing sunitinib , bevacizumab plus interferon-alfa , temsirolimus , or cytokines . Patients were stratified according to Eastern Cooperative Oncology Group performance status and type of previous treatment and then r and omly assigned ( 1:1 ) to either axitinib ( 5 mg twice daily ) or sorafenib ( 400 mg twice daily ) . Axitinib dose increases to 7 mg and then to 10 mg , twice daily , were allowed for those patients without hypertension or adverse reactions above grade 2 . Participants were not masked to study treatment . The primary endpoint was progression-free survival ( PFS ) and was assessed by a masked , independent radiology review and analysed by intention to treat . This trial was registered on Clinical Trials.gov , number NCT00678392 . FINDINGS A total of 723 patients were enrolled and r and omly assigned to receive axitinib ( n=361 ) or sorafenib ( n=362 ) . The median PFS was 6·7 months with axitinib compared to 4·7 months with sorafenib ( hazard ratio 0·665 ; 95 % CI 0·544 - 0·812 ; one-sided p<0·0001 ) . Treatment was discontinued because of toxic effects in 14 ( 4 % ) of 359 patients treated with axitinib and 29 ( 8 % ) of 355 patients treated with sorafenib . The most common adverse events were diarrhoea , hypertension , and fatigue in the axitinib arm , and diarrhoea , palmar-plantar erythrodysaesthesia , and alopecia in the sorafenib arm . INTERPRETATION Axitinib result ed in significantly longer PFS compared with sorafenib . Axitinib is a treatment option for second-line therapy of advanced renal cell carcinoma . FUNDING Pfizer BACKGROUND We conducted a multinational , r and omized study to compare radiotherapy alone with radiotherapy plus cetuximab , a monoclonal antibody against the epidermal growth factor receptor , in the treatment of locoregionally advanced squamous-cell carcinoma of the head and neck . METHODS Patients with locoregionally advanced head and neck cancer were r and omly assigned to treatment with high-dose radiotherapy alone ( 213 patients ) or high-dose radiotherapy plus weekly cetuximab ( 211 patients ) at an initial dose of 400 mg per square meter of body-surface area , followed by 250 mg per square meter weekly for the duration of radiotherapy . The primary end point was the duration of control of locoregional disease ; secondary end points were overall survival , progression-free survival , the response rate , and safety . RESULTS The median duration of locoregional control was 24.4 months among patients treated with cetuximab plus radiotherapy and 14.9 months among those given radiotherapy alone ( hazard ratio for locoregional progression or death , 0.68 ; P=0.005 ) . With a median follow-up of 54.0 months , the median duration of overall survival was 49.0 months among patients treated with combined therapy and 29.3 months among those treated with radiotherapy alone ( hazard ratio for death , 0.74 ; P=0.03 ) . Radiotherapy plus cetuximab significantly prolonged progression-free survival ( hazard ratio for disease progression or death , 0.70 ; P=0.006 ) . With the exception of acneiform rash and infusion reactions , the incidence of grade 3 or greater toxic effects , including mucositis , did not differ significantly between the two groups . CONCLUSIONS Treatment of locoregionally advanced head and neck cancer with concomitant high-dose radiotherapy plus cetuximab improves locoregional control and reduces mortality without increasing the common toxic effects associated with radiotherapy to the head and neck . ( Clinical Trials.gov number , NCT00004227 . BACKGROUND Trastuzumab , a monoclonal antibody against human epidermal growth factor receptor 2 ( HER2 ; also known as ERBB2 ) , was investigated in combination with chemotherapy for first-line treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer . METHODS ToGA ( Trastuzumab for Gastric Cancer ) was an open-label , international , phase 3 , r and omised controlled trial undertaken in 122 centres in 24 countries . Patients with gastric or gastro-oesophageal junction cancer were eligible for inclusion if their tumours showed overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation . Participants were r and omly assigned in a 1:1 ratio to receive a chemotherapy regimen consisting of capecitabine plus cisplatin or fluorouracil plus cisplatin given every 3 weeks for six cycles or chemotherapy in combination with intravenous trastuzumab . Allocation was by block r and omisation stratified by Eastern Cooperative Oncology Group performance status , chemotherapy regimen , extent of disease , primary cancer site , and measurability of disease , implemented with a central interactive voice recognition system . The primary endpoint was overall survival in all r and omised patients who received study medication at least once . This trial is registered with Clinical Trials.gov , number NCT01041404 . FINDINGS 594 patients were r and omly assigned to study treatment ( trastuzumab plus chemotherapy , n=298 ; chemotherapy alone , n=296 ) , of whom 584 were included in the primary analysis ( n=294 ; n=290 ) . Median follow-up was 18.6 months ( IQR 11 - 25 ) in the trastuzumab plus chemotherapy group and 17.1 months ( 9 - 25 ) in the chemotherapy alone group . Median overall survival was 13.8 months ( 95 % CI 12 - 16 ) in those assigned to trastuzumab plus chemotherapy compared with 11.1 months ( 10 - 13 ) in those assigned to chemotherapy alone ( hazard ratio 0.74 ; 95 % CI 0.60 - 0.91 ; p=0.0046 ) . The most common adverse events in both groups were nausea ( trastuzumab plus chemotherapy , 197 [ 67 % ] vs chemotherapy alone , 184 [ 63 % ] ) , vomiting ( 147 [ 50 % ] vs 134 [ 46 % ] ) , and neutropenia ( 157 [ 53 % ] vs 165 [ 57 % ] ) . Rates of overall grade 3 or 4 adverse events ( 201 [ 68 % ] vs 198 [ 68 % ] ) and cardiac adverse events ( 17 [ 6 % ] vs 18 [ 6 % ] ) did not differ between groups . INTERPRETATION Trastuzumab in combination with chemotherapy can be considered as a new st and ard option for patients with HER2-positive advanced gastric or gastro-oesophageal junction cancer . FUNDING F Hoffmann-La Roche BACKGROUND Treatment with cetuximab , a monoclonal antibody directed against the epidermal growth factor receptor , improves overall and progression-free survival and preserves the quality of life in patients with colorectal cancer that has not responded to chemotherapy . The mutation status of the K-ras gene in the tumor may affect the response to cetuximab and have treatment-independent prognostic value . METHODS We analyzed tumor sample s , obtained from 394 of 572 patients ( 68.9 % ) with colorectal cancer who were r and omly assigned to receive cetuximab plus best supportive care or best supportive care alone , to look for activating mutations in exon 2 of the K-ras gene . We assessed whether the mutation status of the K-ras gene was associated with survival in the cetuximab and supportive-care groups . RESULTS Of the tumors evaluated for K-ras mutations , 42.3 % had at least one mutation in exon 2 of the gene . The effectiveness of cetuximab was significantly associated with K-ras mutation status ( P=0.01 and P<0.001 for the interaction of K-ras mutation status with overall survival and progression-free survival , respectively ) . In patients with wild-type K-ras tumors , treatment with cetuximab as compared with supportive care alone significantly improved overall survival ( median , 9.5 vs. 4.8 months ; hazard ratio for death , 0.55 ; 95 % confidence interval [ CI ] , 0.41 to 0.74 ; P<0.001 ) and progression-free survival ( median , 3.7 months vs. 1.9 months ; hazard ratio for progression or death , 0.40 ; 95 % CI , 0.30 to 0.54 ; P<0.001 ) . Among patients with mutated K-ras tumors , there was no significant difference between those who were treated with cetuximab and those who received supportive care alone with respect to overall survival ( hazard ratio , 0.98 ; P=0.89 ) or progression-free survival ( hazard ratio , 0.99 ; P=0.96 ) . In the group of patients receiving best supportive care alone , the mutation status of the K-ras gene was not significantly associated with overall survival ( hazard ratio for death , 1.01 ; P=0.97 ) . CONCLUSIONS Patients with a colorectal tumor bearing mutated K-ras did not benefit from cetuximab , whereas patients with a tumor bearing wild-type K-ras did benefit from cetuximab . The mutation status of the K-ras gene had no influence on survival among patients treated with best supportive care alone . ( Clinical Trials.gov number , NCT00079066 . BACKGROUND Cetuximab , an IgG1 chimeric monoclonal antibody against epidermal growth factor receptor ( EGFR ) , has activity against colorectal cancers that express EGFR . METHODS From December 2003 to August 2005 , 572 patients who had colorectal cancer expressing immunohistochemically detectable EGFR and who had been previously treated with a fluoropyrimidine , irinotecan , and oxaliplatin or had contraindications to treatment with these drugs underwent r and omization to an initial dose of 400 mg of cetuximab per square meter of body-surface area followed by a weekly infusion of 250 mg per square meter plus best supportive care ( 287 patients ) or best supportive care alone ( 285 patients ) . The primary end point was overall survival . RESULTS In comparison with best supportive care alone , cetuximab treatment was associated with a significant improvement in overall survival ( hazard ratio for death , 0.77 ; 95 % confidence interval [ CI ] , 0.64 to 0.92 ; P=0.005 ) and in progression-free survival ( hazard ratio for disease progression or death , 0.68 ; 95 % CI , 0.57 to 0.80 ; P<0.001 ) . These benefits were robust after adjustment in a multivariable Cox proportional-hazards model . The median overall survival was 6.1 months in the cetuximab group and 4.6 months in the group assigned to supportive care alone . Partial responses occurred in 23 patients ( 8.0 % ) in the cetuximab group but in none in the group assigned to supportive care alone ( P<0.001 ) ; the disease was stable in an additional 31.4 % of patients assigned to cetuximab and in 10.9 % of patients assigned to supportive care alone ( P<0.001 ) . Quality of life was better preserved in the cetuximab group , with less deterioration in physical function and global health status scores ( both P<0.05 ) . Cetuximab treatment was associated with a characteristic rash ; a rash of grade 2 or higher was strongly associated with improved survival ( hazard ratio for death , 0.33 ; 95 % CI , 0.22 to 0.50 ; P<0.001 ) . The incidence of any adverse event of grade 3 or higher was 78.5 % in the cetuximab group and 59.1 % in the group assigned to supportive care alone ( P<0.001 ) . CONCLUSIONS Cetuximab improves overall survival and progression-free survival and preserves quality -of-life measures in patients with colorectal cancer in whom other treatments have failed . ( Clinical Trials.gov number , NCT00079066 [ Clinical Trials.gov ] . ) BACKGROUND Bevacizumab , a monoclonal antibody against vascular endothelial growth factor , has been shown to benefit patients with a variety of cancers . METHODS Between July 2001 and April 2004 , the Eastern Cooperative Oncology Group ( ECOG ) conducted a r and omized study in which 878 patients with recurrent or advanced non-small-cell lung cancer ( stage IIIB or IV ) were assigned to chemotherapy with paclitaxel and carboplatin alone ( 444 ) or paclitaxel and carboplatin plus bevacizumab ( 434 ) . Chemotherapy was administered every 3 weeks for six cycles , and bevacizumab was administered every 3 weeks until disease progression was evident or toxic effects were intolerable . Patients with squamous-cell tumors , brain metastases , clinical ly significant hemoptysis , or inadequate organ function or performance status ( ECOG performance status , > 1 ) were excluded . The primary end point was overall survival . RESULTS The median survival was 12.3 months in the group assigned to chemotherapy plus bevacizumab , as compared with 10.3 months in the chemotherapy-alone group ( hazard ratio for death , 0.79 ; P=0.003 ) . The median progression-free survival in the two groups was 6.2 and 4.5 months , respectively ( hazard ratio for disease progression , 0.66 ; P<0.001 ) , with corresponding response rates of 35 % and 15 % ( P<0.001 ) . Rates of clinical ly significant bleeding were 4.4 % and 0.7 % , respectively ( P<0.001 ) . There were 15 treatment-related deaths in the chemotherapy-plus-bevacizumab group , including 5 from pulmonary hemorrhage . CONCLUSIONS The addition of bevacizumab to paclitaxel plus carboplatin in the treatment of selected patients with non-small-cell lung cancer has a significant survival benefit with the risk of increased treatment-related deaths . ( Clinical Trials.gov number , NCT00021060 . BACKGROUND In single-group studies , chromosomal rearrangements of the anaplastic lymphoma kinase gene ( ALK ) have been associated with marked clinical responses to crizotinib , an oral tyrosine kinase inhibitor targeting ALK . Whether crizotinib is superior to st and ard chemotherapy with respect to efficacy is unknown . METHODS We conducted a phase 3 , open-label trial comparing crizotinib with chemotherapy in 347 patients with locally advanced or metastatic ALK-positive lung cancer who had received one prior platinum-based regimen . Patients were r and omly assigned to receive oral treatment with crizotinib ( 250 mg ) twice daily or intravenous chemotherapy with either pemetrexed ( 500 mg per square meter of body-surface area ) or docetaxel ( 75 mg per square meter ) every 3 weeks . Patients in the chemotherapy group who had disease progression were permitted to cross over to crizotinib as part of a separate study . The primary end point was progression-free survival . RESULTS The median progression-free survival was 7.7 months in the crizotinib group and 3.0 months in the chemotherapy group ( hazard ratio for progression or death with crizotinib , 0.49 ; 95 % confidence interval [ CI ] , 0.37 to 0.64 ; P<0.001 ) . The response rates were 65 % ( 95 % CI , 58 to 72 ) with crizotinib , as compared with 20 % ( 95 % CI , 14 to 26 ) with chemotherapy ( P<0.001 ) . An interim analysis of overall survival showed no significant improvement with crizotinib as compared with chemotherapy ( hazard ratio for death in the crizotinib group , 1.02 ; 95 % CI , 0.68 to 1.54 ; P=0.54 ) . Common adverse events associated with crizotinib were visual disorder , gastrointestinal side effects , and elevated liver aminotransferase levels , whereas common adverse events with chemotherapy were fatigue , alopecia , and dyspnea . Patients reported greater reductions in symptoms of lung cancer and greater improvement in global quality of life with crizotinib than with chemotherapy . CONCLUSIONS Crizotinib is superior to st and ard chemotherapy in patients with previously treated , advanced non-small-cell lung cancer with ALK rearrangement . ( Funded by Pfizer ; Clinical Trials.gov number , NCT00932893 . ) BACKGROUND The multitargeted tyrosine kinase inhibitor sunitinib has shown activity against pancreatic neuroendocrine tumors in pre clinical models and phase 1 and 2 trials . METHODS We conducted a multinational , r and omized , double-blind , placebo-controlled phase 3 trial of sunitinib in patients with advanced , well-differentiated pancreatic neuroendocrine tumors . All patients had Response Evaluation Criteria in Solid Tumors-defined disease progression documented within 12 months before baseline . A total of 171 patients were r and omly assigned ( in a 1:1 ratio ) to receive best supportive care with either sunitinib at a dose of 37.5 mg per day or placebo . The primary end point was progression-free survival ; secondary end points included the objective response rate , overall survival , and safety . RESULTS The study was discontinued early , after the independent data and safety monitoring committee observed more serious adverse events and deaths in the placebo group as well as a difference in progression-free survival favoring sunitinib . Median progression-free survival was 11.4 months in the sunitinib group as compared with 5.5 months in the placebo group ( hazard ratio for progression or death , 0.42 ; 95 % confidence interval [ CI ] , 0.26 to 0.66 ; P<0.001 ) . A Cox proportional-hazards analysis of progression-free survival according to baseline characteristics favored sunitinib in all subgroups studied . The objective response rate was 9.3 % in the sunitinib group versus 0 % in the placebo group . At the data cutoff point , 9 deaths were reported in the sunitinib group ( 10 % ) versus 21 deaths in the placebo group ( 25 % ) ( hazard ratio for death , 0.41 ; 95 % CI , 0.19 to 0.89 ; P=0.02 ) . The most frequent adverse events in the sunitinib group were diarrhea , nausea , vomiting , asthenia , and fatigue . CONCLUSIONS Continuous daily administration of sunitinib at a dose of 37.5 mg improved progression-free survival , overall survival , and the objective response rate as compared with placebo among patients with advanced pancreatic neuroendocrine tumors . ( Funded by Pfizer ; Clinical Trials.gov number , NCT00428597 . ) BACKGROUND We conducted a phase 3 , r and omized , double-blind , placebo-controlled trial of sorafenib , a multikinase inhibitor of tumor-cell proliferation and angiogenesis , in patients with advanced clear-cell renal-cell carcinoma . METHODS From November 2003 to March 2005 , we r and omly assigned 903 patients with renal-cell carcinoma that was resistant to st and ard therapy to receive either continuous treatment with oral sorafenib ( at a dose of 400 mg twice daily ) or placebo ; 451 patients received sorafenib and 452 received placebo . The primary end point was overall survival . A single planned analysis of progression-free survival in January 2005 showed a statistically significant benefit of sorafenib over placebo . Consequently , crossover was permitted from placebo to sorafenib , beginning in May 2005 . RESULTS At the January 2005 cutoff , the median progression-free survival was 5.5 months in the sorafenib group and 2.8 months in the placebo group ( hazard ratio for disease progression in the sorafenib group , 0.44 ; 95 % confidence interval [ CI ] , 0.35 to 0.55 ; P<0.01 ) . The first interim analysis of overall survival in May 2005 showed that sorafenib reduced the risk of death , as compared with placebo ( hazard ratio , 0.72 ; 95 % CI , 0.54 to 0.94 ; P=0.02 ) , although this benefit was not statistically significant according to the O'Brien-Fleming threshold . Partial responses were reported as the best response in 10 % of patients receiving sorafenib and in 2 % of those receiving placebo ( P<0.001 ) . Diarrhea , rash , fatigue , and h and -foot skin reactions were the most common adverse events associated with sorafenib . Hypertension and cardiac ischemia were rare serious adverse events that were more common in patients receiving sorafenib than in those receiving placebo . CONCLUSIONS As compared with placebo , treatment with sorafenib prolongs progression-free survival in patients with advanced clear-cell renal-cell carcinoma in whom previous therapy has failed ; however , treatment is associated with increased toxic effects . ( Clinical Trials.gov number , NCT00073307 [ Clinical Trials.gov ] . ) BACKGROUND Everolimus ( RAD001 ) is an orally administered inhibitor of the mammalian target of rapamycin ( mTOR ) , a therapeutic target for metastatic renal cell carcinoma . We did a phase III , r and omised , double-blind , placebo-controlled trial of everolimus in patients with metastatic renal cell carcinoma whose disease had progressed on vascular endothelial growth factor-targeted therapy . METHODS Patients with metastatic renal cell carcinoma which had progressed on sunitinib , sorafenib , or both , were r and omly assigned in a two to one ratio to receive everolimus 10 mg once daily ( n=272 ) or placebo ( n=138 ) , in conjunction with best supportive care . R and omisation was done central ly via an interactive voice response system using a vali date d computer system , and was stratified by Memorial Sloan-Kettering Cancer Center prognostic score and previous anticancer therapy , with a permuted block size of six . The primary endpoint was progression-free survival , assessed via a blinded , independent central review . The study was design ed to be terminated after 290 events of progression . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00410124 . FINDINGS All r and omised patients were included in efficacy analyses . The results of the second interim analysis indicated a significant difference in efficacy between arms and the trial was thus halted early after 191 progression events had been observed ( 101 [ 37 % ] events in the everolimus group , 90 [ 65 % ] in the placebo group ; hazard ratio 0.30 , 95 % CI 0.22 - 0.40 , p<0.0001 ; median progression-free survival 4.0 [ 95 % CI 3.7 - 5.5 ] vs 1.9 [ 1.8 - 1.9 ] months ) . Stomatitis ( 107 [ 40 % ] patients in the everolimus group vs 11 [ 8 % ] in the placebo group ) , rash ( 66 [ 25 % ] vs six [ 4 % ] ) , and fatigue ( 53 [ 20 % ] vs 22 [ 16 % ] ) were the most commonly reported adverse events , but were mostly mild or moderate in severity . Pneumonitis ( any grade ) was detected in 22 ( 8 % ) patients in the everolimus group , of whom eight had pneumonitis of grade 3 severity . INTERPRETATION Treatment with everolimus prolongs progression-free survival relative to placebo in patients with metastatic renal cell carcinoma that had progressed on other targeted therapies BACKGROUND Reports of clinical trials usually emphasize efficacy results , especially when results are statistically significant . Poor safety reporting can lead to misinterpretation and inadequate conclusions about the interventions assessed . Our aim was to describe the reporting of harm-related results from r and omized controlled trials ( RCTs ) . METHODS We search ed the MEDLINE data base for reports of RCTs published from January 1 , 2006 , through January 1 , 2007 , in 6 general medical journals with a high impact factor . Data were extracted by use of a st and ardized form to appraise the presentation of safety results in text and tables . RESULTS Adverse events were mentioned in 88.7 % of the 133 reports . No information on severe adverse events and withdrawal of patients owing to an adverse event was given in 27.1 % and 47.4 % of articles , respectively . Restrictions in the reporting of harm-related data were noted in 43 articles ( 32.3 % ) with a description of the most common adverse events only ( n = 17 ) , severe adverse events only ( n = 16 ) , statistically significant events only ( n = 5 ) , and a combination of restrictions ( n = 5 ) . The population considered for safety analysis was clearly reported in 65.6 % of articles . CONCLUSION Our review reveals important heterogeneity and variability in the reporting of harm-related results in publications of RCTs BACKGROUND Interferon alfa is widely used for metastatic renal-cell carcinoma but has limited efficacy and tolerability . Temsirolimus , a specific inhibitor of the mammalian target of rapamycin kinase , may benefit patients with this disease . METHODS In this multicenter , phase 3 trial , we r and omly assigned 626 patients with previously untreated , poor-prognosis metastatic renal-cell carcinoma to receive 25 mg of intravenous temsirolimus weekly , 3 million U of interferon alfa ( with an increase to 18 million U ) subcutaneously three times weekly , or combination therapy with 15 mg of temsirolimus weekly plus 6 million U of interferon alfa three times weekly . The primary end point was overall survival in comparisons of the temsirolimus group and the combination-therapy group with the interferon group . RESULTS Patients who received temsirolimus alone had longer overall survival ( hazard ratio for death , 0.73 ; 95 % confidence interval [ CI ] , 0.58 to 0.92 ; P=0.008 ) and progression-free survival ( P<0.001 ) than did patients who received interferon alone . Overall survival in the combination-therapy group did not differ significantly from that in the interferon group ( hazard ratio , 0.96 ; 95 % CI , 0.76 to 1.20 ; P=0.70 ) . Median overall survival times in the interferon group , the temsirolimus group , and the combination-therapy group were 7.3 , 10.9 , and 8.4 months , respectively . Rash , peripheral edema , hyperglycemia , and hyperlipidemia were more common in the temsirolimus group , whereas asthenia was more common in the interferon group . There were fewer patients with serious adverse events in the temsirolimus group than in the interferon group ( P=0.02 ) . CONCLUSIONS As compared with interferon alfa , temsirolimus improved overall survival among patients with metastatic renal-cell carcinoma and a poor prognosis . The addition of temsirolimus to interferon did not improve survival . ( Clinical Trials.gov number , NCT00065468 [ Clinical Trials.gov ] . ) PURPOSE Cabozantinib , a tyrosine kinase inhibitor ( TKI ) of hepatocyte growth factor receptor ( MET ) , vascular endothelial growth factor receptor 2 , and rearranged during transfection ( RET ) , demonstrated clinical activity in patients with medullary thyroid cancer ( MTC ) in phase I. PATIENTS AND METHODS We conducted a double-blind , phase III trial comparing cabozantinib with placebo in 330 patients with documented radiographic progression of metastatic MTC . Patients were r and omly assigned ( 2:1 ) to cabozantinib ( 140 mg per day ) or placebo . The primary end point was progression-free survival ( PFS ) . Additional outcome measures included tumor response rate , overall survival , and safety . RESULTS The estimated median PFS was 11.2 months for cabozantinib versus 4.0 months for placebo ( hazard ratio , 0.28 ; 95 % CI , 0.19 to 0.40 ; P < .001 ) . Prolonged PFS with cabozantinib was observed across all subgroups including by age , prior TKI treatment , and RET mutation status ( hereditary or sporadic ) . Response rate was 28 % for cabozantinib and 0 % for placebo ; responses were seen regardless of RET mutation status . Kaplan-Meier estimates of patients alive and progression-free at 1 year are 47.3 % for cabozantinib and 7.2 % for placebo . Common cabozantinib-associated adverse events included diarrhea , palmar-plantar erythrodysesthesia , decreased weight and appetite , nausea , and fatigue and result ed in dose reductions in 79 % and holds in 65 % of patients . Adverse events led to treatment discontinuation in 16 % of cabozantinib-treated patients and in 8 % of placebo-treated patients . CONCLUSION Cabozantinib ( 140 mg per day ) achieved a statistically significant improvement of PFS in patients with progressive metastatic MTC and represents an important new treatment option for patients with this rare disease . This dose of cabozantinib was associated with significant but manageable toxicity BACKGROUND No effective therapeutic options for patients with unresectable imatinib-resistant gastrointestinal stromal tumour are available . We did a r and omised , double-blind , placebo-controlled , multicentre , international trial to assess tolerability and anticancer efficacy of sunitinib , a multitargeted tyrosine kinase inhibitor , in patients with advanced gastrointestinal stromal tumour who were resistant to or intolerant of previous treatment with imatinib . METHODS Blinded sunitinib or placebo was given orally once daily at a 50-mg starting dose in 6-week cycles with 4 weeks on and 2 weeks off treatment . The primary endpoint was time to tumour progression . Intention-to-treat , modified intention-to-treat , and per- protocol analyses were done . This study is registered at Clinical Trials.gov , number NCT00075218 . FINDINGS 312 patients were r and omised in a 2:1 ratio to receive sunitinib ( n=207 ) or placebo ( n=105 ) ; the trial was unblinded early when a planned interim analysis showed significantly longer time to tumour progression with sunitinib . Median time to tumour progression was 27.3 weeks ( 95 % CI 16.0 - 32.1 ) in patients receiving sunitinib and 6.4 weeks ( 4.4 - 10.0 ) in those on placebo ( hazard ratio 0.33 ; p<0.0001 ) . Therapy was reasonably well tolerated ; the most common treatment-related adverse events were fatigue , diarrhoea , skin discolouration , and nausea . INTERPRETATION We noted significant clinical benefit , including disease control and superior survival , with sunitinib compared with placebo in patients with advanced gastrointestinal stromal tumour after failure and discontinuation of imatinab . Tolerability was acceptable BACKGROUND Until now , only imatinib and sunitinib have proven clinical benefit in patients with gastrointestinal stromal tumours ( GIST ) , but almost all metastatic GIST eventually develop resistance to these agents , result ing in fatal disease progression . We aim ed to assess efficacy and safety of regorafenib in patients with metastatic or unresectable GIST progressing after failure of at least imatinib and sunitinib . METHODS We did this phase 3 trial at 57 hospitals in 17 countries . Patients with histologically confirmed , metastatic or unresectable GIST , with failure of at least previous imatinib and sunitinib were r and omised in a 2:1 ratio ( by computer-generated r and omisation list and interactive voice response system ; preallocated block design ( block size 12 ) ; stratified by treatment line and geographical region ) to receive either oral regorafenib 160 mg daily or placebo , plus best supportive care in both groups , for the first 3 weeks of each 4 week cycle . The study sponsor , participants , and investigators were masked to treatment assignment . The primary endpoint was progression-free survival ( PFS ) . At disease progression , patients assigned placebo could crossover to open-label regorafenib . Analyses were by intention to treat . This trial is registered with Clinical Trials.gov , number NCT01271712 . RESULTS From Jan 4 , to Aug 18 , 2011 , 240 patients were screened and 199 were r and omised to receive regorafenib ( n=133 ) or matching placebo ( n=66 ) . Data cutoff was Jan 26 , 2012 . Median PFS per independent blinded central review was 4·8 months ( IQR 1·4 - 9·2 ) for regorafenib and 0·9 months ( 0·9 - 1·8 ) for placebo ( hazard ratio [ HR ] 0·27 , 95 % CI 0·19 - 0·39 ; p<0·0001 ) . After progression , 56 patients ( 85 % ) assigned placebo crossed over to regorafenib . Drug-related adverse events were reported in 130 ( 98 % ) patients assigned regorafenib and 45 ( 68 % ) patients assigned placebo . The most common regorafenib-related adverse events of grade 3 or higher were hypertension ( 31 of 132 , 23 % ) , h and -foot skin reaction ( 26 of 132 , 20 % ) , and diarrhoea ( seven of 132 , 5 % ) . INTERPRETATION The results of this study show that oral regorafenib can provide a significant improvement in progression-free survival compared with placebo in patients with metastatic GIST after progression on st and ard treatments . As far as we are aware , this is the first clinical trial to show benefit from a kinase inhibitor in this highly refractory population of patients . FUNDING Bayer HealthCare Pharmaceuticals Purpose : We sought to evaluate the activity and tolerance of the rationally design ed sequence of paclitaxel – topotecan – etoposide , a nonplatinum regimen , as induction therapy for limited-stage small-cell lung cancer before combined chemo- and radiotherapy . Patients and Methods : Patients with measurable disease , performance status 0 to 2 , no prior therapy , and adequate organ function were eligible . Paclitaxel ( 110 mg/m2 , administered intravenously on day 1 ) , topotecan ( 1.5 mg/m2 , administered orally on days 2 to 4 ) , and etoposide ( 160 mg/m2 , administered orally on days 5 to 7 every 21 days ) , with filgrastim for two cycles , were followed by chest irradiation to 70 Gy ( to postinduction tumor volume ) concurrent with carboplatin ( area under the curve of 5 , administered intravenously on day 1 ) and etoposide ( 100 mg/m2 on days 1 to 3 every 21 days ) without filgrastim for three cycles ( five chemotherapy cycles total ) . We aim ed to determine the response rates to induction and overall therapy , overall and failure-free survival , and toxicity . The primary statistical endpoint was to differentiate between complete response rates of 50 and 70 % for the overall treatment program . Results : Between June 2001 and January 2003 , 65 patients were enrolled , but one never started therapy , and one was ineligible . Patient characteristics included male/female , 27/36 ; white/black/other/unknown , 58/3/1/1 ; median age 62 ( range , 38–78 ) ; performance status 0/1/2 , 27/33/3 . Induction chemotherapy result ed in six ( 10 % ) complete responses and 35 ( 56 % ) partial responses . Overall response to chemoradiotherapy included 27 ( 43 % ; 95 % confidence interval [ CI ] 30–56 % ) complete responses and 24 ( 38 % ) partial responses . Median progression-free survival is 12 months ( 95 % CI , 9–15 months ) . Median overall survival is 20 months ( 95 % CI , 16–24 months ) . Frequent ( > 20 % ) grade 3/4 toxicities during all therapy included neutropenia , febrile neutropenia , anemia , thrombocytopenia , fatigue , and dysphagia . One patient died of febrile neutropenia , one died of febrile neutropenia and typhlitis , and one patient who declined transfusion for anemia died of cardiac ischemia . Conclusions : This treatment regimen has significant activity in limited-stage small-cell lung cancer but did not meet our prospect ively defined criteria for further investigation in this setting . The addition of etoposide and the use of a sequenced administration schedule did not seem to improve overall activity beyond our prior experience with a topotecan – paclitaxel doublet PURPOSE Patients with advanced pancreatic cancer have a poor prognosis and there have been no improvements in survival since the introduction of gemcitabine in 1996 . Pancreatic tumors often overexpress human epidermal growth factor receptor type 1 ( HER1/EGFR ) and this is associated with a worse prognosis . We studied the effects of adding the HER1/EGFR-targeted agent erlotinib to gemcitabine in patients with unresectable , locally advanced , or metastatic pancreatic cancer . PATIENTS AND METHODS Patients were r and omly assigned 1:1 to receive st and ard gemcitabine plus erlotinib ( 100 or 150 mg/d orally ) or gemcitabine plus placebo in a double-blind , international phase III trial . The primary end point was overall survival . RESULTS A total of 569 patients were r and omly assigned . Overall survival based on an intent-to-treat analysis was significantly prolonged on the erlotinib/gemcitabine arm with a hazard ratio ( HR ) of 0.82 ( 95 % CI , 0.69 to 0.99 ; P = .038 , adjusted for stratification factors ; median 6.24 months v 5.91 months ) . One-year survival was also greater with erlotinib plus gemcitabine ( 23 % v 17 % ; P = .023 ) . Progression-free survival was significantly longer with erlotinib plus gemcitabine with an estimated HR of 0.77 ( 95 % CI , 0.64 to 0.92 ; P = .004 ) . Objective response rates were not significantly different between the arms , although more patients on erlotinib had disease stabilization . There was a higher incidence of some adverse events with erlotinib plus gemcitabine , but most were grade 1 or 2 . CONCLUSION To our knowledge , this r and omized phase III trial is the first to demonstrate statistically significantly improved survival in advanced pancreatic cancer by adding any agent to gemcitabine . The recommended dose of erlotinib with gemcitabine for this indication is 100 mg/d BACKGROUND Vascular endothelial growth factor ( VEGF ) and VEGF receptor-2 (VEGFR-2)-mediated signalling and angiogenesis can contribute to the pathogenesis and progression of gastric cancer . We aim ed to assess whether ramucirumab , a monoclonal antibody VEGFR-2 antagonist , prolonged survival in patients with advanced gastric cancer . METHODS We did an international , r and omised , double-blind , placebo-controlled , phase 3 trial between Oct 6 , 2009 , and Jan 26 , 2012 , at 119 centres in 29 countries in North America , Central and South America , Europe , Asia , Australia , and Africa . Patients aged 24 - 87 years with advanced gastric or gastro-oesophageal junction adenocarcinoma and disease progression after first-line platinum-containing or fluoropyrimidine-containing chemotherapy were r and omly assigned ( 2:1 ) , via a central interactive voice-response system , to receive best supportive care plus either ramucirumab 8 mg/kg or placebo , intravenously once every 2 weeks . The study sponsor , participants , and investigators were masked to treatment assignment . The primary endpoint was overall survival . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00917384 . FINDINGS 355 patients were assigned to receive ramucirumab ( n=238 ) or placebo ( n=117 ) . Median overall survival was 5·2 months ( IQR 2·3 - 9·9 ) in patients in the ramucirumab group and 3·8 months ( 1·7 - 7·1 ) in those in the placebo group ( hazard ratio [ HR ] 0·776 , 95 % CI 0·603 - 0·998 ; p=0·047 ) . The survival benefit with ramucirumab remained unchanged after multivariable adjustment for other prognostic factors ( multivariable HR 0·774 , 0·605 - 0·991 ; p=0·042 ) . Rates of hypertension were higher in the ramucirumab group than in the placebo group ( 38 [ 16 % ] vs nine [ 8 % ] ) , whereas rates of other adverse events were mostly similar between groups ( 223 [ 94 % ] vs 101 [ 88 % ] ) . Five ( 2 % ) deaths in the ramucirumab group and two ( 2 % ) in the placebo group were considered to be related to study drug . INTERPRETATION Ramucirumab is the first biological treatment given as a single drug that has survival benefits in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma progressing after first-line chemotherapy . Our findings vali date VEGFR-2 signalling as an important therapeutic target in advanced gastric cancer . FUNDING ImClone Systems BACKGROUND Lapatinib , a tyrosine kinase inhibitor of human epidermal growth factor receptor type 2 ( HER2 , also referred to as HER2/neu ) and epidermal growth factor receptor ( EGFR ) , is active in combination with capecitabine in women with HER2-positive metastatic breast cancer that has progressed after trastuzumab-based therapy . In this trial , we compared lapatinib plus capecitabine with capecitabine alone in such patients . METHODS Women with HER2-positive , locally advanced or metastatic breast cancer that had progressed after treatment with regimens that included an anthracycline , a taxane , and trastuzumab were r and omly assigned to receive either combination therapy ( lapatinib at a dose of 1250 mg per day continuously plus capecitabine at a dose of 2000 mg per square meter of body-surface area on days 1 through 14 of a 21-day cycle ) or monotherapy ( capecitabine alone at a dose of 2500 mg per square meter on days 1 through 14 of a 21-day cycle ) . The primary end point was time to progression , based on an evaluation by independent review ers under blinded conditions . RESULTS The interim analysis of time to progression met specified criteria for early reporting on the basis of superiority in the combination-therapy group . The hazard ratio for the independently assessed time to progression was 0.49 ( 95 % confidence interval , 0.34 to 0.71 ; P<0.001 ) , with 49 events in the combination-therapy group and 72 events in the monotherapy group . The median time to progression was 8.4 months in the combination-therapy group as compared with 4.4 months in the monotherapy group . This improvement was achieved without an increase in serious toxic effects or symptomatic cardiac events . CONCLUSIONS Lapatinib plus capecitabine is superior to capecitabine alone in women with HER2-positive advanced breast cancer that has progressed after treatment with regimens that included an anthracycline , a taxane , and trastuzumab . ( Clinical Trials.gov number , NCT00078572 [ Clinical Trials.gov ] . ) BACKGROUND Trastuzumab emtansine ( T-DM1 ) is an antibody-drug conjugate incorporating the human epidermal growth factor receptor 2 (HER2)-targeted antitumor properties of trastuzumab with the cytotoxic activity of the microtubule-inhibitory agent DM1 . The antibody and the cytotoxic agent are conjugated by means of a stable linker . METHODS We r and omly assigned patients with HER2-positive advanced breast cancer , who had previously been treated with trastuzumab and a taxane , to T-DM1 or lapatinib plus capecitabine . The primary end points were progression-free survival ( as assessed by independent review ) , overall survival , and safety . Secondary end points included progression-free survival ( investigator-assessed ) , the objective response rate , and the time to symptom progression . Two interim analyses of overall survival were conducted . RESULTS Among 991 r and omly assigned patients , median progression-free survival as assessed by independent review was 9.6 months with T-DM1 versus 6.4 months with lapatinib plus capecitabine ( hazard ratio for progression or death from any cause , 0.65 ; 95 % confidence interval [ CI ] , 0.55 to 0.77 ; P<0.001 ) , and median overall survival at the second interim analysis crossed the stopping boundary for efficacy ( 30.9 months vs. 25.1 months ; hazard ratio for death from any cause , 0.68 ; 95 % CI , 0.55 to 0.85 ; P<0.001 ) . The objective response rate was higher with T-DM1 ( 43.6 % , vs. 30.8 % with lapatinib plus capecitabine ; P<0.001 ) ; results for all additional secondary end points favored T-DM1 . Rates of grade 3 or 4 adverse events were higher with lapatinib plus capecitabine than with T-DM1 ( 57 % vs. 41 % ) . The incidences of thrombocytopenia and increased serum aminotransferase levels were higher with T-DM1 , whereas the incidences of diarrhea , nausea , vomiting , and palmar-plantar erythrodysesthesia were higher with lapatinib plus capecitabine . CONCLUSIONS T-DM1 significantly prolonged progression-free and overall survival with less toxicity than lapatinib plus capecitabine in patients with HER2-positive advanced breast cancer previously treated with trastuzumab and a taxane . ( Funded by F. Hoffmann-La Roche/Genentech ; EMILIA Clinical Trials.gov number , NCT00829166 . ) IMPORTANCE Targeting oncogenic drivers ( genomic alterations critical to cancer development and maintenance ) has transformed the care of patients with lung adenocarcinomas . The Lung Cancer Mutation Consortium was formed to perform multiplexed assays testing adenocarcinomas of the lung for drivers in 10 genes to enable clinicians to select targeted treatments and enroll patients into clinical trials . OBJECTIVES To determine the frequency of oncogenic drivers in patients with lung adenocarcinomas and to use the data to select treatments targeting the identified driver(s ) and measure survival . DESIGN , SETTING , AND PARTICIPANTS From 2009 through 2012 , 14 sites in the United States enrolled patients with metastatic lung adenocarcinomas and a performance status of 0 through 2 and tested their tumors for 10 drivers . Information was collected on patients , therapies , and survival . INTERVENTIONS Tumors were tested for 10 oncogenic drivers , and results were used to select matched targeted therapies . MAIN OUTCOMES AND MEASURES Determination of the frequency of oncogenic drivers , the proportion of patients treated with genotype-directed therapy , and survival . RESULTS From 2009 through 2012 , tumors from 1007 patients were tested for at least 1 gene and 733 for 10 genes ( patients with full genotyping ) . An oncogenic driver was found in 466 of 733 patients ( 64 % ) . Among these 733 tumors , 182 tumors ( 25 % ) had the KRAS driver ; sensitizing EGFR , 122 ( 17 % ) ; ALK rearrangements , 57 ( 8 % ) ; other EGFR , 29 ( 4 % ) ; 2 or more genes , 24 ( 3 % ) ; ERBB2 ( formerly HER2 ) , 19 ( 3 % ) ; BRAF , 16 ( 2 % ) ; PIK3CA , 6 ( < 1 % ) ; MET amplification , 5 ( < 1 % ) ; NRAS , 5 ( < 1 % ) ; MEK1 , 1 ( < 1 % ) ; AKT1 , 0 . Results were used to select a targeted therapy or trial in 275 of 1007 patients ( 28 % ) . The median survival was 3.5 years ( interquartile range [ IQR ] , 1.96 - 7.70 ) for the 260 patients with an oncogenic driver and genotype-directed therapy compared with 2.4 years ( IQR , 0.88 - 6.20 ) for the 318 patients with any oncogenic driver(s ) who did not receive genotype-directed therapy ( propensity score-adjusted hazard ratio , 0.69 [ 95 % CI , 0.53 - 0.9 ] , P = .006 ) . CONCLUSIONS AND RELEVANCE Actionable drivers were detected in 64 % of lung adenocarcinomas . Multiplexed testing aided physicians in selecting therapies . Although individuals with drivers receiving a matched targeted agent lived longer , r and omized trials are required to determine if targeting therapy based on oncogenic drivers improves survival . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01014286 PURPOSE Oncologists prescribe anticancer drugs based on results of phase III r and omized clinical trials ( RCTs ) , but some safety concerns appear only later in up date d drug labels . Here , we analyze adverse drug reactions ( ADRs ) of targeted anticancer agents from up date d drug labels and their reporting in corresponding pivotal RCTs . METHODS We search ed the US Food and Drug Administration ( FDA ) Web site for approved targeted anticancer drugs with up date s of their labels related to safety in 2008 and 2009 and at least one RCT referenced in the up date d drug label . For each drug , serious ADRs , including potentially fatal ADRs , were identified from the up date d label . Published reports of RCTs referenced in the label were search ed to determine whether they described these ADRs . RESULTS We identified 12 eligible targeted anticancer agents with 36 corresponding RCTs referenced in up date d drug labels . There were 76 serious ADRs reported in up date d drug labels , and 50 % ( n = 38 ) were potentially fatal . Of these , 39 % ( n = 30 ) of all serious ADRs and 39 % ( n = 15 ) of potentially fatal ADRs were not described in any published report of RCTs , whereas 49 % and 58 % , respectively , were not described in initial drug labels . After a median 4.3 years between initial approval and up date of drug labels , 42 % ( n = 5 ) of targeted cancer agents acquired one or more boxed warnings ( the highest level of FDA alert ) . CONCLUSION Published reports of pivotal RCTs and initial drug labels contain limited information about serious ADRs of targeted anticancer agents . Rare but serious ADRs may be important causes of morbidity and mortality in general oncologic practice |
12,752 | 28,872,667 | RESULTS Behavioural data from 91 studies showed a broad cluster of deficits in the anticipatory control of movement , basic processes of motor learning , and cognitive control .
Importantly , however , performance issues in DCD were often shown to be moderated by task type and difficulty .
As well , we saw new evidence of compensatory processes and strategies in several studies .
Data from diffusion-weighted magnetic resonance imaging suggested reduced white matter organization involving sensorimotor structures and altered structural connectivity across the whole brain network .
INTERPRETATION Taken together , results support the hypothesis that children with DCD show differences in brain structure and function compared with typically developing children .
Behaviourally , these differences may affect anticipatory planning and reduce automatization of movement skill , prompting greater reliance on slower feedback-based control and compensatory strategies . | AIM To better underst and the neural and performance factors that may underlie developmental coordination disorder ( DCD ) , and implication s for a multi-component account . | We assessed the non-academic and academic functioning of young adults with DCD , and investigated the emotional influences and the role of strategy use within this population . A r and om sample of 2379 adolescents and young adults aged 19 - 25 ( 1081 males [ 45.4 % ] ; mean age=20.68 , SD=3.42 ) was used to develop the instruments . From this sample , three study groups were identified ( n=429 ) based on the Adolescents & Adults Coordination Question naire : probable DCD ( n=135 ; 67.2 % males ) , suspected borderline DCD ( n=149 ; 51.4 % males ) and control ( 145 ; 70.5 % males ) . Participants completed the Daily Life Functions Question naire ( assessing non-academic and academic functioning ) , the Recent Emotional State Test ( assessing feelings result ing from task performance ) , the Internal Factors Attributed to Success Question naire and the Problem Solving Question naire to assess strategy and executive strategy use . A MANOVA revealed statistically significant differences between-groups ( F[7,422]=16.19 ; p<.001 ; η=.197 ) ; post hoc analyses revealed differences for all measures ( except the Problem Solving Question naire ) , with the probable DCD and suspected borderline DCD groups performing worse than controls . Severity of motor deficits was correlated with all outcomes except strategy use . Logistic regression revealed that non-academic functioning was the most significant predictor of group placement ( B=-1.32 ; p<.001 ) ; academic functioning/h and writing was the second most significant predictor ( B=0.44 ; p=.047 ) . Deficits in motor coordination continue into adulthood and have an effect on academic and non-academic function , as well as on the emotional state of the individual Timing ability is essential for common everyday performance . The aim of the study was to compare timing abilities and temporal aspects of h and writing performance and relationships between these two components among children with Developmental Coordination Disorders ( DCD ) and a control group . Forty two children , 21 diagnosed as DCD and 21 with typical development , aged 7 - 12 , were matched for age , gender and school performed 14 tasks of the interactive metronome ( IM ) and three functional h and writing tasks on an electronic tablet that was part of a computerized system ( ComPET -- computerized penmanship evaluation tool ) . The IM supplies response time , while on-paper and in-air time per written stroke is received from the ComPET . Results indicated significant differences between the groups for both IM and h and writing tasks ( ComPET ) . Linear regression indicated that the mean IM response time explained 37 % of variance of the in-air time per stroke during a paragraph-copying task . Furthermore , based on one discriminate function including two measures reflected timing ability , 81 % of all participants were correctly classified into groups . Study results strongly recommend consideration of the IM as an evaluation and intervention tool for children with DCD who are faced with timing deficits in their everyday functioning The current research aim ed at examining the executive function ( EF ) of young adults with Developmental Coordination Disorder ( DCD ) in comparison to young adults without DCD . The study used a r and omized cohort ( N=429 ) of young adults with DCD ( n=135 ) , borderline DCD ( n=149 ) and control ( n=145 ) , from a previous study . This initial cohort was asked to participate in the current study three to four years later . Twenty-five individuals with DCD ( mean age=24 years , 1 month [ SD=0.88 ] ; 18 males ) , 30 with borderline DCD ( mean age=24 years , 2 month [ SD=0.98 ] ; 18 males ) and 41 without DCD ( mean age=25 years , 2 months [ SD=1.91 ] ; 20 males ) participated in this study . Participants completed the BRIEF-A question naire , assessing EF abilities and the WURS question naire , assessing attention abilities . The DCD and borderline DCD groups had significantly lower EF profiles in comparison with the control group but no significant differences were found between the DCD and borderline DCD groups . While a high percentage of attention problems were found in both DCD groups , the executive functioning profiles remained consistent even when using the attention component as a covariate . The study results suggest that young adults with DCD have EF problems which remain consistent with or without attention difficulties UNLABELLED Children with developmental coordination disorder ( DCD ) struggle to learn new motor skills . It is unknown whether children with DCD learn motor skills more effectively with an external focus of attention ( focusing on impact of movement on the environment ) or an internal focus of attention ( focusing on one 's body movements ) during implicit ( unconscious ) and explicit ( conscious ) motor learning . PURPOSE This paper aims to determine the trends of implicit motor learning in children with DCD , and how focus of attention influences motor learning in children with DCD in comparison with typically developing children . METHODS 25 children , aged 8 - 12 , with ( n=12 ) and without ( n=13 ) DCD were r and omly assigned to receive instructions that focused attention externally or internally while completing a computer tracking task during acquisition , retention , and transfer phases . The motor task involved tracking both repeated and r and om patterns , with the repeated pattern indicative of implicit learning . RESULTS Children with DCD scored lower on the motor task in all three phases of the study , demonstrating poorer implicit learning . Furthermore , graphical data showed that for the children with DCD , there was no apparent difference between internal and external focus of attention during retention and transfer , while there was an advantage to the external focus of attention group for typically developing children . CONCLUSION Children with DCD demonstrate less accuracy than typically developing children in learning a motor task . Also , the effect of focus of attention on motor performance is different in children with DCD versus their typically developing counterparts during the three phases of motor learning . IMPLICATION S Results may inform clinicians how to facilitate motor learning in children with DCD by incorporating explicit learning with either internal or external focus of attention within interventions OBJECTIVE To assess executive function in children with developmental dyspraxia . PATIENTS AND METHOD INCLUSION CRITERIA children aged 8 years to 12 years 5 months at the time of the study , diagnosed with developmental dyspraxia between January , 2008 and August , 2009 by a multidisciplinary team in one single center . ASSESSMENT TOOLS ( 1 ) Paper- and -pencil neuropsychological and ecological tests to assess flexibility , planning , inhibition and prospect i ve memory ; ( 2 ) two question naires answered by parents ; ( 3 ) the ' Children 's Cooking Task ' ( CCT ) , an ecological task performed in a real environment ( Chevignard et al. , 2009 [ 15 ] ) . In this last test , children were compared to matched controls . Non-parametric statistical tests were used . RESULTS Thirteen patients participated in the study ( 11 boys-2 girls ; mean age 10.3 years [ SD=1.3 ] ) . Neuropsychological tests highlighted planning and inhibition disorders , but no impaired flexibility . For more than half of the children , the question naires indicated impaired executive functions in daily life tasks . Finally , patients showed a significantly increased rate of errors during the CCT , compared with the control group ( P<0.001 ) . CONCLUSION Overall results suggest that some children diagnosed with developmental dyspraxia also exhibit executive function disorders . Ecological tests seem more sensitive for identifying executive function disorders than conventional tests Background Children with Developmental Coordination Disorder ( DCD ) have multiple impairments in movement , in learning , and in the activities of daily living . Studies from other countries have associated these impairments with cognitive function , particularly executive functioning , but these findings have not been confirmed in China . Aim Compare the executive functioning of children with DCD with that of normal children . Methods The Wisconsin Card Sorting Test ( WCST ) was administered to 39 children who met DSM-IV criteria of DCD identified at the Seventh People 's Hospital of Hangzhou from March 2008 through March 2010 . The WCST was also administered to a control group of 39 r and omly selected children from one elementary school in Hangzhou . Results The total responses on the WCST and the number of non-perseverative errors for cases and controls were similar , but cases had significantly more errors , more perseverative responses and more perseverative errors ; moreover , they completed fewer categories than controls and required more trials to complete the first category . Conclusion Our study confirms previous studies which show significantly impaired executive functioning in patients with DCD . Collectively , these studies suggest that the deficits in executive functioning of children with DCD significantly impair their intellectual and social development |
12,753 | 30,083,701 | Conclusions and Relevance Early detection strategies focused on women with PMB have the potential to capture as many as 90 % of endometrial cancers ; however , most women with PMB will not be diagnosed with endometrial cancer . | Importance As the worldwide burden of endometrial cancer continues to rise , interest is growing in the evaluation of early detection and prevention strategies among women at increased risk .
Focusing efforts on women with postmenopausal bleeding ( PMB ) , a common symptom of endometrial cancer , may be a useful strategy ; however , PMB is not specific for endometrial cancer and is often caused by benign conditions .
Objective To provide a reference of the prevalence of PMB in endometrial cancers and the risk of endometrial cancer in women with PMB . | A study was conducted to compare transvaginal ultrasound ( TVS ) , saline infusion sonography ( SIS ) and outpatient hysteroscopy for examining the uterine cavity in women with postmenopausal bleeding and unscheduled bleeding on hormone replacement therapy ( HRT ) . Fourty Subjects agreed to undergo TVS , SIS and hysteroscopy in addition to endometrial sampling . The abnormalities detected by each imaging method were recorded together with the discomfort ( visual analogue scale ) . Thirty women completed all three imaging procedures . In 18 cases TVS suggested an abnormal cavity . SIS and hysteroscopy were of similar efficacy in clarifying the nature of this , and confirmed an abnormality in 12 cases ( 40 % ) . TVS was significantly less painful than the other procedures ( p < 0.001 ) . SIS and hysteroscopy were associated with pain scores similar to endometrial sampling . These findings justify the need for a large r and omised trial of TVS , SIS , hysteroscopy and endometrial sampling , in order to develop the most appropriate strategy for investigating postmenopausal bleeding and unscheduled bleeding on HRT Women with postmenopausal bleeding should be evaluated efficiently to exclude endometrial carcinoma Objective . To develop and test a risk-scoring model for the prediction of endometrial cancer among symptomatic postmenopausal women at risk of intrauterine malignancy . Methods . We prospect ively studied 624 postmenopausal women with vaginal bleeding and endometrial thickness > 4 mm undergoing diagnostic hysteroscopy . Patient characteristics and endometrial assessment of women with or without endometrial cancer were compared . Then , a risk-scoring model , including the best predictors of endometrial cancer , was tested . Univariate , multivariate , and ROC curve analysis were performed . Finally , a split-sampling internal validation was also performed . Results . The best predictors of endometrial cancer were recurrent vaginal bleeding ( odds ratio ( OR ) = 2.96 ) , the presence of hypertension ( OR = 2.01 ) endometrial thickness > 8 mm ( OR = 1.31 ) , and age > 65 years ( OR = 1.11 ) . These variables were used to create a risk-scoring model ( RHEA risk-model ) for the prediction of intrauterine malignancy , with an area under the curve of 0.878 ( 95 % CI 0.842 to 0.908 ; P < 0.0001 ) . At the best cut-off value ( score ≥ 4 ) , sensitivity and specificity were 87.5 % and 80.1 % , respectively . Conclusion . Among symptomatic postmenopausal women with endometrial thickness > 4 mm , a risk-scoring model including patient characteristics and endometrial thickness showed a moderate diagnostic accuracy in discriminating women with or without endometrial cancer . Based on this model , a decision algorithm was developed for the management of such a population We conducted this study to test the hypothesis that transvaginal ultrasonography and color Doppler imaging of the uterine arteries are complementary methods in the assessment of patients with postmenopausal bleeding . Sixty-seven patients were studied . Seventeen suffered from endometrial carcinoma , 12 from benign endometrial lesions ( six polyp , six hyperplasia ) and 38 had no organic pathology . Transvaginal ultrasonography was found to be superior to CDI in the detection of pathologic conditions of the endometrium , but neither method can distinguish benign lesions from their malignant counterparts . CDI does not give additional information over that obtained by transvaginal ultrasonography in the assessment of patients with postmenopausal bleeding , and the limitations of both methods in the differentiation of endometrial carcinoma from benign lesions need to be recognized In this prospect i ve study , 139 patients , 83 premenopausal patients with abnormal uterine bleeding and 56 postmenopausal patients either with metrorrhagia ( 33 ) or a suspect sonographic finding ( 23 ) , were examined preoperatively with transvaginal sonography ( TVS ) and saline contrast hysterosonography ( SCHS ) . The histological results , obtained by hysteroscopy , were compared with the preoperative findings . Uterine pathology ( benign polyps , submucous fibroids , endometrial hyperplasia and carcinoma ) was found in 74.7 % and 76.8 % of the pre- and postmenopausal patients , respectively . TVS and SCHS are very sensitive at diagnosing uterine pathology , the latter being more specific and enabling better surgical management and a reduction in unnecessary interventions OBJECTIVE To evaluate the role of one-stop clinic for early diagnosis and management of women with postmenopausal bleeding by means of transvaginal ultrasonography , outpatient hysteroscopy and endometrial biopsy . STUDY DESIGN A prospect i ve analysis was performed on 522 women with postmenopausal bleeding who were referred directly to the gynecology outpatient clinic for evaluation of postmenopausal bleeding . Endometrial thickness of 6 mm , as measured by a transvaginal scan , was considered the cutoff limit for further investigation by hysteroscopy and endometrial biopsy . RESULTS One hundred ninety-one women were using hormone replacement therapy . Thirty-two were taking tamoxifen . Outpatient hysteroscpoy was performed in 157 ( 71.3 % ) cases . Thirty-seven ( 16.8 % ) cases had general anesthesia for hysteroscopy . Twenty-four ( 11 % ) cases had only an endometrial sample obtained . Twenty-one cases of endometrial carcinoma , 20 of endometrial hyperplasia , 4 of cervical carcinoma and 5 of other genital tract malignancies along with several benign pathologies , including submucosal myomas , were detected . Seven ( 2.3 % ) cases of endometrial thickness below the cutoff limit had recurrent bleeding due to benign conditions . CONCLUSION A one-stop clinic is effective for early diagnosis of genital tract malignancy in a majority of patients with postmenopausal bleeding and significantly help in reducing the hospital waiting list PURPOSE To assess the accuracy of hysterosonography ( HSG ) and its role in diagnostic confidence and therapeutic clinical decision making among referring physicians caring for patients with postmenopausal bleeding ( PMB ) . MATERIAL S AND METHODS One hundred twenty-three patients with PMB underwent transvaginal ultrasonography ( US ) and HSG . They were examined for cancer , polyp , leiomyoma , and hyperplasia . Physicians assessed the effect of the studies on diagnostic confidence and care , including biopsy , dilation and curettage , hysteroscopy , hormone manipulation , and /or patient reassurance . Abnormality was proved with histopathologic evaluation , and normality , with 6-month follow-up . RESULTS In 10 patients , HSG was unsuccessful , and in 15 , follow-up was incomplete ; this left 98 patients . Endometrial polyps were seen in 46 ( 47 % ) patients ; leiomyoma , in 11 ( 11 % ) ; cancer , in four ( 4 % ) ; hyperplasia , in eight ( 8 % ) ; and normal findings , in 29 ( 30 % ) . Our calculations yielded a sensitivity of 98 % and a specificity of 88 % . In 86 ( 88 % ) patients , US added certainty to the diagnosis ; in 78 ( 80 % ) , it result ed in a change in patient treatment . CONCLUSION HSG and transvaginal US in patients with PMB improves diagnostic accuracy , clinical decision making , and the clinician 's diagnostic certainty . In patients with benign causes of PMB , the absence of abnormality at HSG and a normal endometrial biopsy result may eliminate the need for further studies OBJECTIVE The purpose of this study was to use transvaginal ultrasonographic measurements to find the thickness of the endometrium below which the risk of endometrial abnormality in women with postmenopausal bleeding is low . STUDY DESIGN This multicenter study was carried out at eight clinics in four Nordic countries . The study included 1168 women with postmenopausal bleeding scheduled for curettage Before the curettage was performed , the thickness of the endometrium was measured with transvaginal ultrasonography . The measurement included both endometrial layers ( double-layer technique ) . The transvaginal ultrasonographic measurement was compared with the histopathologic diagnosis of the curettage specimens . RESULTS In women with atrophic endometrium the mean endometrial thickness ( + /- SD ) was 3.9 + /- 2.5 mm . The corresponding figures for women with endometrial cancer were 21.1 + /- 11.8 mm . No malignant endometrium was thinner than 5 mm . In 30 women ( 2.8 % ) it was not possible to measure the thickness of the endometrium ; one of these women had endometrial cancer . The 95 % confidence limit for the probability of excluding endometrial abnormality was 5.5 % when the endometrial thickness was < or = 4 mm as measured by transvaginal ultrasonography . CONCLUSION The risk of finding pathologic endometrium at curettage when the endometrium is < or = 4 mm as measured by transvaginal ultrasonography is 5.5 % . Thus in women with postmenopausal bleeding and an endometrium < or = 4 mm it would seem justified to refrain from curettage OBJECTIVE This study was undertaken to evaluate whether it was possible to abstain from performing an endometrial biopsy when endometrial thickness according to transvaginal ultrasonography was < /=4 mm in women with postmenopausal bleeding or irregular bleeding during hormone replacement therapy . STUDY DESIGN Transvaginal ultrasonography was performed in 361 women aged > /=50 years who were referred because of postmenopausal bleeding or irregular bleeding during hormone replacement therapy . If endometrial thickness was < /=4 mm , a Papanicolaou cervical smear was performed and the woman was reexamined with transvaginal ultrasonography after 4 and 12 months . Subjects were also instructed to return if they had recurrent bleeding , in which case transvaginal ultrasonography was performed and an endometrial biopsy specimen was obtained . Women with an endometrial thickness > /=5 mm underwent either curettage or endometrial biopsy . RESULTS One hundred sixty-three women had an endometrial thickness < /=4 mm . In this group one endometrial cancer that was missed by ultrasonography was diagnosed by cervical cytologic examination and two adnexal malignancies were diagnosed by ultrasonography . Endometrial malignancy was diagnosed in 0.6 % of the women with an endometrial thickness < /=4 mm . Endometrial biopsy was performed because of recurrent bleeding in 6.1 % of cases and because of endometrial thickening in 8.1 % . No cancer or hyperplasia was subsequently diagnosed among the women with an endometrial thickness < /=4 mm . Endometrial cancer was diagnosed in 18.7 % of the women with an endometrial thickness > /=5 mm . The corresponding figure when atypical hyperplasia and endometrial metastases were included was 20 . 2 % . CONCLUSION If the false-negative rate of endometrial biopsy techniques is taken into account , then the combination of transvaginal ultrasonography and cervical cytologic examination is an adequate form of management for women with postmenopausal bleeding or irregular bleeding during hormone replacement therapy as long as endometrial thickness is < /=4 mm . A r and omized prospect i ve study is necessary to verify this finding Background Abnormal uterine bleeding ( AUB ) is one of the most common debilitating menstrual problems and has remained one of the most frequent indications for hysterectomy in developing countries . Approximately in 40 % of hysterectomy specimens , no definite organic pathology could be established . The problem is common worldwide but causes may vary from one region to another . This study may help gynecologists in our population to improve their therapeutic strategies by promoting minimally invasive uterus sparing modalities such as endometrial ablation and hysteroscopic resection of early proliferative lesions . Methods It was a prospect i ve , cross-sectional study conducted at Liaquat National Hospital from 15th January 2010 till 14th July 2011 over a period of 18 months . Women who underwent dilatation and curettage for endometrial sampling with complaints of AUB were included in the study and histopathologic spectrum was determined . Results Polymenorrhea was the most common presenting pattern ( 30 % , 72/241 ) with reproductive age women being the most susceptible ( 49.3%,119/241 ) . The commonest histopathological spectrum was normal menstrual pattern ( 34 % , 82/241 ) and the commonest pathology was hormonal imbalance ( 27 % , 65/241 ) , followed by endometrial polyp ( 14 % , 34/241 ) , chronic endometritis ( 12 % , 28/241 ) , atrophic endometrium ( 6 % , 15/241 ) , endometrial hyperplasia ( 5 % , 12/241 ) , and endometrial carcinoma ( 2 % , 5/241 ) . Chronic endometritis was commonly seen in reproductive age ( 18 % , 21/119 ) ; hormonal imbalance ( 45 % , 35/77 ) and endometrial hyperplasia ( 6.5 % , 5/77 ) in perimenopausal age ; endometrial polyp ( 35.5 % , 16/45 ) and endometrial carcinoma ( 9 % , 4/45 ) in postmenopausal age . Conclusion Frequency of benign endometrial pathology is quite high in AUB , 236 participants ( 98 % , 236/241 ) . Histopathological spectrum in patients with AUB is quite variable with respect to age . The most common pattern of AUB was polymenorrhea . The most common pathology was hormonal imbalance . It is suggested that age was associated with more progressive lesions found in peri and postmenopausal age group such as endometrial hyperplasia and endometrial carcinoma . Yet endometrial polyp was the most common pathology found in postmenopausal women . Therefore , the management strategy should be individualized , as in most cases a restrictive approach is appropriate in order to avoid unnecessary hysterectomies OBJECTIVES To compare three outpatient methods of endometrial evaluation in terms of performance , patient acceptability and cost-effectiveness . DESIGN Pragmatic unblinded trial r and omised separately within three groups determined by risk of endometrial cancer . SETTING The gynaecology outpatient clinic of a large city hospital in Edinburgh , Scotl and . PARTICIPANTS Women referred for investigation and management of abnormal bleeding between January 1999 and May 2001 . INTERVENTIONS Investigations were : blind biopsy alone , hysteroscopy with biopsy , ultrasound evaluation including transvaginal ultrasound , and , in the low-risk group , the option of no investigation . Within this design , two devices for obtaining endometrial biopsy were compared , the Pipelle sample r and the Tao brush . MAIN OUTCOME MEASURES Successful ( informative ) completion of the investigation , acceptability of the investigation method to women , women 's satisfaction with clinic care in the short term and at 10 months and 2 years of follow-up , and cost-effectiveness to the end of investigation . RESULTS Minor adverse events ( e.g. shock , patient distress ) did not occur for ultrasound , but occurred in 16 % and 10 % of women for hysteroscopy and biopsy procedures respectively . Pipelle biopsy provided an acceptable endometrial sample for 79 % of moderate-risk women , but only 43 % of high-risk women . The Tao brush gave similar performance in moderate-risk women ( 77 % ) , but was more successful than the Pipelle sample r in postmenopausal ( high-risk ) women ( 72 % ) . There were significantly more successful visualizations for ultrasound than for hysteroscopy in both the low-risk and the moderate-risk group , and a similar but non-significant trend in the high-risk group . Ultrasound was significantly better than hysteroscopy at detecting fibroids , but hysteroscopy significantly better for polyps . At the 10-month follow-up , high-risk women who had been investigated by hysteroscopy ( with biopsy ) had the most positive views of their clinic experience , but this effect had largely disappeared by 24 months . In the moderate-risk group , the subgroup r and omised to biopsy alone gave the most negative responses about their clinic experience and health now . Women wishing they had more investigation comprised 22 % of moderate-risk women and 38 % of low-risk women , but only 14 % of postmenopausal women . At follow-up the moderate-risk women ( with menstrual bleeding problems ) , compared with postmenopausal women , had much worse ratings for clinic experience and health now . Re source use tended to be higher in the moderate- and low-risk women . There was minimal difference in cost-effectiveness between investigation options in the high-risk group , with the option involving hysteroscopy being marginally better than ultrasound . The most cost-effective investigation in the moderate-risk group was biopsy alone and in the low-risk group ultrasound . CONCLUSIONS Decision-making about investigation would be clarified if postmenopausal women were studied separately from premenopausal women with menstrual bleeding problems . For postmenopausal women exclusion of cancer is a main objective , so once investigation has been completed discharge follows , but in the woman with abnormal menstrual bleeding , even if serious pathology is excluded , the original presenting symptoms require management . About 60 % of premenopausal women with abnormal bleeding reported that their symptoms were not ' much improved ' at 10 months . Research is needed to underst and this phenomenon , and to explore ways to integrate patient factors into optimising evaluation and treatment . The significance of benign pathologies in this group also requires clarification . Given the relatively small differences observed in cost-effectiveness , there is justification for allowing other issues ( such as clinician preferences and women 's perspectives ) to influence decisions as to the investigation method . There is scope to make better use of patient factors to inform decisions as to the most efficient and acceptable method of investigation for an individual woman . Additional analyses , using data available as a result of this study , will contribute to this agenda Endometrial sampling is the mainstay of management of the postmenopausal patient with uterine bleeding . Thirty women with postmenopausal bleeding were studied prospect ively . Before endometrial sampling , a vaginal probe ultrasonographic examination was performed . Eleven patients demonstrated a thin " pencil line " endometrial echo in which the maximum anteroposterior thickness on the long axis view was less than or equal to 5 mm . All eleven patients had minimal tissue obtained on biopsy and a pathology report of " tissue insufficient for diagnosis . " Seventeen patients had an echogenic endometrium greater than or equal to 6 mm . Pathology reports of their sample s revealed tissue insufficient for diagnosis ( two cases ) , proliferative endometrium ( six ) , secretory endometrium ( three ) , hyperplastic endometrium ( three ) , polyp ( two ) , and endometrial cancer ( one case ) . Two additional patients had no endometrial echo visualized because of associated myomas . These findings suggest ( 1 ) that the absence of significant endometrial tissue ( echo less than or equal to 5 mm ) on vaginal ultrasonography in cases with postmenopausal bleeding is uniformly associated with tissue insufficient for diagnosis , and ( 2 ) when endometrial thickness is greater than or equal to 6 mm the histologic diagnosis should be determined in the pathology laboratory OBJECTIVE To compare the diagnostic accuracy of ultrasonographic endometrial thickness and outpatient hysteroscopy , to establish the most appropriate exam for the diagnosis of endometrial cancer in postmenopausal women with abnormal uterine bleeding ( AUB ) . The secondary aim was to develop a multivariable approach considering clinical history as an added value for these diagnostic procedures . METHODS This prospect i ve study was conducted on 220 consecutive postmenopausal patients with AUB , who underwent ultrasonographic evaluation of endometrial thickness , outpatient hysteroscopy and endometrial biopsy . Evaluation of sensitivity , specificity , positive and negative predictive value was performed . Receiver operator characteristic curve ( ROC ) was calculated to assess the global performance of ultrasonographic measurement of endometrial thickness and diagnostic hysteroscopy as tests for detecting endometrial cancer and atrophy . RESULTS Histological findings for < 4 mm level revealed that atrophy was present in 48 ( 65 % ) and in 2 cases ( 2.7 % ) endometrial cancer was found ; for > or = 4 mm values polyps and myomas were present in 86 ( 59 % ) and there were 11 ( 7.5 % ) endometrial cancer . Sensibility and specificity for trans-vaginal ultrasound , with a cut-off value > or = 4 mm , was 55.6 % and 49.7 % while positive predictive value was 83.3 % and negative predictive value 98.1 % ( ROC curve 0.597 ) . Hysteroscopy revealed sensitivity 100 % , specificity 49.6 % , positive predictive value 81.3 % and negative predictive value 100 % ( ROC curve 0.993 ) . CONCLUSIONS In conclusion , endometrial thickness < 4 mm can miss malignancies but trans-vaginal ultrasound remains the first line diagnostic procedure in postmenopausal women without AUB , because it is not invasive and has high sensitivity for detecting endometrial cancer and other endometrial disease ; according to our experience , outpatient hysteroscopy with biopsy is m and atory in all postmenopausal women with AUB OBJECTIVES We evaluated the role of three-dimensional power Doppler ultrasound ( 3D PD-US ) to detect endometrial lesions in women with postmenopausal endometrial bleeding . MATERIAL S AND METHODS In this prospect i ve observational study , from January 2009 to November 2012 , we recruited 225 postmenopausal women with postmenopausal uterine bleeding who met the study criteria . Women who had hematologic disease , chronic medical diseases , or nonuterine pelvic diseases were excluded . Prior to endometrial biopsy , the patients underwent a baseline transvaginal ultrasound screening . The vascular indices and endometrial volumes were calculated with 3D PD-US and compared with the endometrial histopathology . RESULTS Among the endometrial histopathologic findings of 174 women , atrophic endometrium was the most common finding ( 30.5 % ) . Endometrial malignancy was confirmed in 28 cases ( 16.1 % ) , and endometrial hyperplasia was diagnosed in 17 cases ( 9.8 % ) . The prevalence of endometrial cancer was high in patients who had endometrial thickness > 9.5 mm ( p < 0.001 ) and volume greater than 4.05 mL ( p < 0.001 ) . For the endometrial carcinoma only , the cutoff values of vascular index , flow index , and vascular flow index for predicting malignancy were 13.070 , 12.610 , and 3.764 , respectively . For endometrial hyperplasia , endometrial thickness and vascular flow index were significant findings . CONCLUSION Endometrial vasculature and volume can be obtained using 3D PD-US . The diagnostic usefulness of 3D PD-US for endometrial diseases is promising in women with postmenopausal endometrial bleeding BACKGROUND The purpose of this study was to assess the utility of transvaginal ultrasonography in the evaluation of endometrial morphology in addition to the st and ard criterion of endometrial thickness for selecting patients for endometrial sampling . METHODS Two hundred and seven consecutive cases of postmenopausal bleeding were evaluated by transvaginal ultrasound . Endometrial thickness was measured as the maximum anteroposterior thickness of the endometrium including both the anterior and posterior layers , in the sagittal long axis view . The morphology of the endometrium was studied and categorized as homogeneous , focally increased echogenecity , diffusely increased echogenecity or diffusely inhomogeneous . Patients were followed up for clinical course and endometrial histopathology . RESULTS Textural inhomogeneity was observed in all the three cases of endometrial cancers with endometrial thickness of less than 6 mm , and , in ten out of 11 cases of a more than 6 mm thick endometrium . On the other h and the endometrial texture was homogeneous in all cases of endometrial atrophy/tissue inadequate for diagnosis , with thickness of less than 6 mm . CONCLUSION This study adds the dimension of abnormal echogenecity of the endometrium to the currently followed criterion of endometrial thickness with a view to enhance accuracy , both for a better prediction of atrophy and a higher prediction for endometrial cancer . Expectant management can be offered to patients with a homogeneous endometrium which is 6 mm thick or less . Aggressive evaluation for a malignancy must be made if there is a focal increased echogenecity or a diffuse increased echogenecity even in a thin endometrium Endometrial sample s were obtained with the Accurette and the Vabra aspirator and were compared with sample s obtained by dilation and curettage in 40 patients with postmenopausal bleeding . The degree of discomfort and patient acceptability of the two outpatient procedures , the adequacy of the sample s for cytological and histological examination , and the cytological and histological diagnosis were compared . The Accurette and the Vabra aspirator could not be inserted in 5 out of 40 patients because of cervical stenosis . From approximately 30 of the remaining 35 patients , adequate sample s were obtained . Six cases of endometrial hyperplasia and 3 of endometrial carcinoma were diagnosed by all the methods employed , except for 1 case of endometrial hyperplasia in which the sample obtained with the Accurette was inadequate for histological examination but was nevertheless adequate for cytological examination . Of the 5 patients in whom endometrial sampling by both the Accurette and the Vabra aspirator could not be performed because of cervical stenosis , 2 cases of endometrial carcinoma were found on uterine curettage . In patients with cervical stenosis , however , dilatation and curettage under general anaesthesia is m and atory . The Accurette has the advantage of being less expensive and more suitable for routine endometrial sampling for the detection of endometrial hyperplasia or carcinoma and dating of the endometrium in cases of infertility . Both the Accurette procedure and Vabra aspiration appeared to be reliable methods of obtaining endometrial sample BACKGROUND AND OBJECTIVES In postmenopausal women , ovarian stromal hyperplasia and endometrial cancer are often identified concurrently . The aim of the present study was to verify the association of ovarian volume with histologic findings and sex hormones levels in women with postmenopausal bleeding and thickened endometrium . DESIGN AND SETTING Prospect i ve observational study conducted in a teaching hospital between March 2008 and February 2010 PATIENTS AND METHODS Ninety women with postmenopausal bleeding and thickened endometrium ( ≥5 mm ) were enrolled . They underwent vaginal sonography for ovarian volume measurement . Blood sample s were collected for sex steroid hormones assay . In addition , endometrial sampling was done for definitive histologic diagnosis . RESULTS According to histologic results , 18 cases ( 20 % ) had endometrial adenocarcinoma , 24 cases ( 26.7 % ) had endometrial hyperplasia with or without atypia and 48 cases ( 53.3 % ) had benign histologic findings . Large ovaries were significantly associated with higher body mass index ( BMI ≥30 ) ( P=.002 ) and endometrial adenocarcinoma ( P<.001 ) . After adjustment for age and BMI , increased ovarian volume in adenocarcinoma was associated with high serum level of estradiol ( P<.001 ) , serum total testosterone ( P=.04 ) and serum free testosterone ( P<.01 ) compared with other histologic findings . CONCLUSIONS Large ovaries among women with postmenopausal bleeding and thick endometrium were associated with elevated serum sex steroid hormones and represent a marker of risk for endometrial adenocarcinoma OBJECTIVE To propose a scoring system to predict endometrial cancer using different ultrasound image characteristics at gray-scale , with and without enhancement by gel infusion , and Doppler transvaginal sonography ( TVS ) and to evaluate intra- and interobserver variability in assessment of these characteristics . METHOD Unenhanced TVS , Doppler examinations and gel infusion sonography ( GIS ) were performed prospect ively in 174 consecutive postmenopausal women with endometrial thickness ≥ 5 mm . The reference st and ard in all women was hysteroscopy or hysterectomy with pathological evaluation of the malignancy . The presence of various ultrasound pattern characteristics indicative of endometrial malignancy and intra- and interobserver variability in their assessment were evaluated . Multivariate logistic regression was used to correlate image and clinical parameters to presence of endometrial cancer . RESULTS A simple Doppler flow score ( which considered only presence of vascularity and not presence of single/double dominant vessel , multiple vessels , large vessels , color splash or densely packed vessels ) had an area under the receiver-operating characteristics curve ( AUC ) of 0.83 in the prediction of endometrial cancer . Models including endometrial thickness , Doppler score and interrupted endomyometrial junction on unenhanced TVS predicted endometrial cancer with an AUC of 0.95 ( 95 % CI , 0.92 - 0.99 ) and , with addition of irregular surface on GIS , the AUC was 0.97 ( 95 % CI , 0.94 - 0.99 ) . A risk of endometrial cancer ( REC ) scoring system based on body mass index , Doppler score , endometrial thickness and interrupted endomyometrial junction on unenhanced TVS and irregular surface at GIS performed very well at identifying endometrial cancer ; at a REC-score of ≥ 4 the sensitivity for detection of endometrial cancer was 91 % and specificity was 94 % . Observers agreed in 82.3 % of cases ( kappa , 0.63 ( 0.48 - 0.78 ) ) when subjective parameters were analyzed in stored videoclips . CONCLUSION Our observer-dependent proposed scoring system seems to perform well in the prediction of endometrial cancer and should be tested in future studies BACKGROUND Postmenopausal bleeding is a clinical ly important complaint in general gynecologic practice . The incidence of spontaneous postmenopausal bleeding in the general population is approximately 10 % immediately after menopause , and 5 % in all menopausal women . OBJECTIVES The study was aim ed to reveal the histopathologic diagnosis of postmenopausal uterine bleeding , and to investigate the correlation between various clinical factors and endometrial carcinoma . We also evaluated the role of endometrial volume calculation in the clinical use for the endometrial histopathologic findings . MATERIAL S AND METHODS In this prospect i ve observational study , we recruited 163 postmenopausal women with abnormal uterine bleeding from January 2008 through December 2010 . Women who had hematologic disease , or had nonuterine pelvic diseases were excluded . Clinical characteristics such as age , body mass index ( BMI ) , associated diseases , and previous postmenopausal hormone therapy were checked . They were evaluated by transvaginal ultrasonography and underwent endometrial biopsy for the endometrial histopathologic examination . RESULTS Among the endometrial histopathologic findings , atrophic endometrium was the most common finding ( 32.7 % ) , followed by hyperplastic endometrium ( 10.4 % ) , endometrial carcinoma ( 10.4 % ) , and endometrial polyp ( 9.2 % ) . The prevalence of endometrial hyperplasia and cancer was not significantly different at the 5 mm cut-off thickness of the endometrium , but significantly higher in women with ≥ 3 mL of endometrial volume . However , the incidence of endometrial cancer and hyperplasia in women with endometrial bleeding was not significantly different with or without previous or current hormone therapy . CONCLUSIONS Endometrial biopsy should be performed to exclude endometrial hyperplasia and carcinoma in postmenopausal women with endometrial bleeding to perform proper and prompt treatment , especially in old aged women ( > 60 years ) and in patients with endometrial volume ≥ 3 The objective of the present study was to evaluate the usefulness of transvaginal ultrasonography in assessment of the endometrial thickness in patients with postmenopausal uterine bleeding in relation to the histopathological results of the endometrial biopsy . A total of 118 women with postmenopausal uterine bleeding were studied prospect ively . Thirty postmenopausal women without vaginal bleeding and without gynaecological complaints served as a control group . In women with histopathological diagnosis of atrophic endometrium the mean endometrial thickness was 3.1 + /- 1.7 mm whereas the corresponding value for patients with endometrial carcinoma was 18.4 + /- 8.2 mm ( P < 0.001 ) . No endometrial carcinoma was diagnosed in endometrial thickness < or = 6 mm . The sensitivity was 100 % and specificity 64 % if a 6-mm cutoff limit was used . We consider that transvaginal ultrasonographic investigation for post-menopausal bleeding may provide useful information for selection of those patients who are under higher risk of endometrial abnormalities . When using vaginal sonography for measuring the endometrial thickness in women with postmenopausal bleeding , it is reasonable not to perform a dilatation and curettage if the endometrial thickness is < or = 6 mm The prognosis of endometrial cancer is strongly associated with stage at diagnosis , suggesting that early detection may reduce mortality . Women who are diagnosed with endometrial carcinoma often have a lengthy history of vaginal bleeding , which offers an opportunity for early diagnosis and curative treatment . We performed DNA methylation profiling on population -based endometrial cancers to identify early detection biomarkers and replicated top c and i date s in two independent studies . We compared DNA methylation values of 1,500 probes representing 807 genes in 148 population -based endometrial carcinoma sample s and 23 benign endometrial tissues . Markers were replicated in another set of 69 carcinomas and 40 benign tissues profiled on the same platform . Further replication was conducted in The Cancer Genome Atlas and in prospect ively collected endometrial brushings from women with and without endometrial carcinomas . We identified 114 CpG sites showing methylation differences with p values of ≤ 10(-7 ) between endometrial carcinoma and normal endometrium . Eight genes ( ADCYAP1 , ASCL2 , HS3ST2 , HTR1B , MME , NPY and SOX1 ) were selected for further replication . Age-adjusted odds ratios for endometrial cancer ranged from 3.44 ( 95%-CI : 1.33 - 8.91 ) for ASCL2 to 18.61 ( 95%-CI : 5.50 - 62.97 ) for HTR1B . An area under the curve ( AUC ) of 0.93 was achieved for discriminating carcinoma from benign endometrium . Replication in The Cancer Genome Atlas and in endometrial brushings from an independent study confirmed the c and i date markers . This study demonstrates that methylation markers may be used to evaluate women with abnormal vaginal bleeding to distinguish women with endometrial carcinoma from the majority of women without malignancy OBJECTIVE To evaluate the sensitivity and specificity of vaginal sonography in the detection of endometrial abnormalities in patients with postmenopausal bleeding ( PMB ) . METHODS In a prospect i ve study , 54 patients with PMB were examined with vaginal ultrasonography prior to dilatation and curettage . The mean endometrial thickness was compared with the histopathological results . A cutoff value of 5 mm was prospect ively chosen to evaluate the sensitivity and specificity of this method . RESULTS The calculated sensitivity for the measurement of endometrial thickness as a predictor of endometrial pathology was 89 % , and the specificity was 83 % . We found carcinoma associated with an endometrial thickness of 6 mm . CONCLUSIONS Although its sensitivity was high , we feel that an endometrial thickness > 5 mm should constitute a cause for concern but not a definitive indication of pathology . Thus we believe that , at this point , the role of vaginal sonography as an aid in determining which women with PMB should undergo curettage has yet to be determined We compared transvaginal ultrasonography ( TVS ) and endometrial cytology by the Endocyte method for endometrial cancer screening . A total of 600 postmenopausal women who hoped for endometrial cancer screening ( mean age , 61.1 + /- 8.8 years ; range , 44 - 87 years ) underwent TVS , endometrial cytology ( Endocyte method ) , and endometrial histology . The endometrial borders could be visualized by TVS in all women studied . However , cytology could not be performed in 59 women ( 9.8 % ) due to cervical stenosis . These 59 women were excluded from further study . Of the 541 remaining women , 38 had pathologic conditions ( 16 had endometrial cancer and 22 had endometrial hyperplasia ) . One ( 6.3 % ) of the 16 endometrial cancer patients and 10 ( 45.5 % ) of the 22 hyperplasia patients were asymptomatic . One hundred thirty-nine ( 83.7 % ) of the 166 women with postmenopausal bleeding had no pathological condition . When the cutoff value of endometrial thickness was set at 4 mm for women < 5 years since menopause and 3 mm for those > or = 5 years since menopause , TVS showed a 97.4 % sensitivity , 75.7 % specificity , 23.8 % positive predictive value , and 99.7 % negative predictive value . Thirty-seven of the 38 patients with endometrial disease were detected by TVS . Eight patients with a benign Endocyte examination were found to have endometrial hyperplasia . However , all endometrial cancers were detected by cytological examination . The Endocyte method exhibited 78.9 % sensitivity , 95.4 % specificity , 56.6 % positive predictive value , and an 88.5 % negative predictive value . In conclusion , TVS is thought to be useful for identification of patients who required further diagnostic investigation including endometrial histology BACKGROUND Abnormal uterine bleeding is the Common presenting complaint in Gynaecology Outpatient Department in all age groups . It is due to the anovulatory cycles which are commonly seen in adolescent and peri-menopausal women . Abnormal uterine bleeding is caused by wide variety of organic or non-organic causes . Histopathological examination of endometrial sample remains the gold st and ard for diagnosis of endometrial pathology . AIM To study the clinicopathological spectrum of endometrium in abnormal uterine bleeding in peri-menopausal and post-menopausal age groups . MATERIAL AND METHODS The study included prospect i ve analysis of 119 cases of endometrial sample s in patients of abnormal uterine bleeding above 40 years of age . The specimens were routinely processed and H&E stained slides were studied . Patients were categorized into peri-menopausal ( 40 - 49 years ) and post-menopausal ( > 50 years ) age group . RESULTS A total of 119 specimens of endometrium were analyzed . Maximum number ( 73.94 % ) of cases were from peri-menopausal age group . The most common presenting complaint was menorrhagia ( 48.86 % ) followed by post-menopausal bleeding ( 26.05 % ) . In peri-menopausal age group proliferative endometrium ( 35.22 % ) was the predominant histopathological pattern followed by endometrial hyperplasia ( 23.86 % ) . Atrophic endometrium ( 25.80 % ) was the most frequent finding followed by endometrial hyperplasia ( 19.35 % ) in post-menopausal age group . Three cases of endometrial carcinoma were reported in post-menopausal age group only . CONCLUSION A thorough histopathological work up and clinical correlation is m and atory in cases of abnormal uterine bleeding above the age of 40 years to find out organic lesions . Careful screening can detect early cancer of endometrium which has excellent prognosis and it will help in further management OBJECTIVE To determine whether the accuracy of transvaginal sonography to detect endometrial pathology is enhanced by assessing endometrial morphology and the regularity of the endometrial border in addition to measurement of endometrial thickness in women with postmenopausal bleeding . DESIGN AND METHODS A total of 159 women with postmenopausal bleeding were included in a prospect i ve study performed at the Clinic of Obstetrics and Gynecology , University of Mainz . The results obtained on transvaginal sonographic assessment of the endometrium were compared with the histological evaluation of the operative endometrial specimen . RESULTS A cut-off level for endometrial thickness of 5 mm had a sensitivity of 94 % , specificity of 48 % and positive and negative predictive values of 69 % and 87 % , respectively for the presence of endometrial pathology . Assessment of the regularity of the endometrial border showed a sensitivity of 75 % , specificity of 66 % and positive and negative predictive values of 73 % and 69 % , respectively . For the third sonographic parameter , endometrial morphology , the sensitivity was 82 % , specificity 64 % , the positive predictive value 73 % and the negative predictive value 74 % . The combined consideration of the three sonographic parameters showed a sensitivity of 97 % , specificity of 65 % , and positive and negative predictive values of 80 % and 94 % , respectively . CONCLUSION The combined evaluation of endometrial thickness , endometrial morphology and the endometrial border enhances the accuracy of transvaginal sonography to detect endometrial pathology in women with postmenopausal bleeding , thus facilitating the decision regarding further diagnostic and therapeutic measures OBJECTIVE We sought to compare the combined diagnostic reliability of sonohysterography and endometrial biopsy with fractional curettage with hysteroscopy in the initial evaluation of postmenopausal women with abnormal uterine bleeding . STUDY DESIGN This year-long , prospect i ve , controlled , clinical investigation was initiated Sept. 1 , 1995 . All postmenopausal women with abnormal uterine bleeding were offered inclusion , with 104 enrolled . An endometrial biopsy was performed at the time of initial evaluation . Routine transvaginal ultrasonography was then used to measure the uterus , ovaries , and endometrial stripe thickness , followed immediately by sonohysterography to evaluate the symmetry of endometrial wall thickness and delineate any intraluminal masses . Definitive histopathologic sampling was obtained by fractional curettage with hysteroscopy and statistically compared with the diagnoses arrived at by endometrial biopsy and sonohysterography . RESULTS The combination of endometrial biopsy and transvaginal sonohysterography positively correlated with the surgical findings > 95 % of the time , with a sensitivity and specificity of 94 % and 96 % , respectively ( confidence interval 91 % to 99 % ) . No patients with endometrial hyperplasia or cancer were misdiagnosed . CONCLUSIONS Sonohysterography combined with endometrial biopsy is a reliable office tool for evaluating postmenopausal women with abnormal uterine bleeding . Medical management of those patients identified as having no endometrial abnormalities can be considered with confidence , while saving the cost and surgical risk of fractional curettage . Patients with intraluminal masses should be referred for surgical management in a timely fashion OBJECTIVES We have established a ' one stop ' clinic for the management of women with abnormal uterine bleeding based on transvaginal sonography and saline contrast sonohysterography . This report review s our experience with the first 93 patients attending the clinic . DESIGN AND METHODS Patients were seen with the intention of performing a transvaginal scan , saline contrast sonohysterography , endometrial biopsy , full blood count and thyroid function tests . The findings were prospect ively recorded on a computer data base and a management plan formulated . RESULTS A transvaginal scan was performed on 89 ( 95.7 % ) women , 70 ( 75.3 % ) also undergoing saline contrast sonohysterography . An endometrial biopsy was carried out in 67 ( 72 % ) women aged 40 years and above , and 79 ( 84.9 % ) had blood tests . The median age of patients was 44 ( range , 21 - 78 ) years . The majority of women presented with menstrual disorders . Uterine pathology was detected on transvaginal scan in 42 ( 47.2 % ) cases . Adnexal pathology was detected in 12 ( 13.5 % ) of the patients . Endometrial biopsy detected three ( 4.5 % ) cases of endometrial atypia , and three ( 4.5 % ) cases of adenocarcinoma . A hemoglobin level of < 10 g/dL was detected in 3 ( 3.4 % ) patients . A single clinic visit was thought sufficient for 83 ( 89.2 % ) women . Medical therapy was started in 47 ( 50.5 % ) patients , 15 ( 16.3 % ) were brought back for inpatient diagnostic hysteroscopy , and nine ( 9.7 % ) were booked for operative endoscopy , while six ( 6.5 % ) had conventional surgery ; the remainder were reassured . CONCLUSIONS This study demonstrates that a ' one stop ' management philosophy based on pelvic ultrasound is feasible . Our data suggest that diagnostic hysteroscopy can be decreased using this approach , and challenge the use of hysteroscopy as the first stage test Objective : To evaluate the diagnostic accuracy of power Doppler area ( PDA ) in the detection of endometrial cancer in women with postmenopausal bleeding . Design : Prospect i ve diagnostic study . Setting : University hospital . Population : Seventy-four consecutive women presenting with postmenopausal bleeding and a total endometrial thickness of more than 4 mm . Methods : The PDA was measured by pelvic ultrasound . Endometrial cancer and hyperplasia with complex atypia were considered abnormal . Main Outcome Measures : A receiver operating characteristic curve was constructed and area under curve ( AUC ) calculated as well as positive and negative likelihood ratios ( LR+ and LR− ) . Results : Eighteen women ( 24 % ) had abnormal results of their histological specimen . The AUC of the PDA was 0.88 ( 95 % confidence interval [ CI ] , 0.80 - 0.98 ) . The LR+ and LR− of the PDA were , respectively , 14.5 ( 95 % CI , 4.69 - 44.9 ) and 0.23 ( 95 % CI , 0.09 - 0.55 ) . In women with total endometrial thickness of 4 to 10 mm , the AUC , LR+ , and LR− were , respectively , 0.91 ( 95 % CI , 0.78 - 1.00 ) , 23.9 ( 95 % CI , 3.29 - 175.0 ) , and 0.34 ( 95 % CI , 0.13 - 0.86 ) . Conclusions : The PDA is an effective measure in the diagnosis and exclusion of endometrial cancer Eighteen centers took part in this prospect i ve study into which 930 eligible patients were recruited . The selection criteria for admission were atypical bleeding after at least 6 months of postmenopausal amenorrhea , and absence of hormonal therapies for at least 6 months . The sonographic measurement of the maximum bi-endometrial thickness was made in a longitudinal plane . Sonographic measurements were always performed within 3 days prior to histological evaluation . In these patients the mean number of years from menopause ( 25 - 75th centile ) was 6 ( range 2 - 16 ) . The prevalence of endometrial carcinoma was 11.5 % and the prevalence of atrophy was 49.2 % . The area under the receiver operator characteristic curves generated by sonographic thickness measurements reached the level of 85 % , both for cancer and atrophy . The likelihood ratio for cancer , yielded by an endometrial thickness of < or = 4.0 mm , was 0.05 , and for atrophy it was 7.1 . This cut-off of > 4.0 mm yielded a sensitivity for the detection of cancer of 98 % and a negative predictive value of 99 % . The overall sensitivity and positive predictive value for atrophy achieved by this cut-off were 57.2 % and 87.3 % , respectively . A multivariate logistic model showed that age and body mass index were independent variables associated with a significantly higher risk of endometrial cancer . The post-test probabilities for cancer and atrophy were recalculated on the basis of the integration of age , body mass index and endometrial thickness . The estimated reduction of invasive procedures on the basis of this integration was 31 % . Transvaginal sonographic measurement of endometrial thickness , integrated with individual risk factors , can help in the management of postmenopausal patients with atypical bleeding , with regard to either the need for histological evaluation in high risk cases , or the choice of possible expectant management . We have shown that an endometrial thickness of < or = 4.0 mm safely predicts endometrial atrophy and justifies expectant management when the patient underst and s the need for proper follow up . This could be achieved with a reduction in the use of invasive procedures without unwanted delay in cancer diagnosis Objective : To assess the optimal diagnostic approach to women with postmenopausal bleeding by comparing transvaginal ultrasound and endometrial sampling with office hysteroscopy . Methods : A prospect i ve collective study was performed on 102 consecutive patients with postmenopausal bleeding who were evaluated by ultrasound measurement of the endometrial thickness ( EL ) , endometrial sampling by Accurette ® and outpatient hysteroscopy and directed biopsy . Results : Accurette was inadequate for histological diagnosis in 65 of 136 sample s and many repeat investigations were required . In all 16 cases of endometrial polyps , ultrasound measurement of the EL was ≧4 mm and hysteroscopy confirmed the findings . Accurette detected only 5 polyps . All 7 cases of endometrial hyperplasia were detected using an EL of ≧4 mm and hysteroscopy confirmed the findings . Accurette failed to detect 5 out of 7 cases of endometrial hyperplasia . Five cases of endometrial cancer were diagnosed : all had an EL ≧4 mm but were inadequately sample d for diagnostic purpose s in 3 cases . A definitive diagnosis was made on hysteroscopy in 4 cases ( 1 patient did not have a hysteroscopy ) . Conclusion : Accurette is not a good sampling device for the diagnosis of postmenopausal bleeding . An ultrasound measurement of the EL ≧4 mm in patients with postmenopausal bleeding warrants further investigation . Outpatient office hysteroscopy is an accurate and sensitive modality to employ as a first line investigation for definitive diagnosis OBJECTIVE To evaluate the reproducibility of transvaginal three-dimensional ( 3D ) endometrial volume measurement in patients with postmenopausal bleeding and to compare the reproducibility of this technique to that of two-dimensional ( 2D ) endometrial thickness measurement . METHODS In a prospect i ve , blinded study , transvaginal ultrasound examinations were performed in 51 consecutive patients with postmenopausal bleeding . Three-dimensional volume and 2D thickness measurements were made and intraobserver and interobserver reproducibility of each technique were assessed . RESULTS The intraobserver correlation of 3D endometrial volume measurement of the first observer was 0.97 and that of the second observer was 0.99 . Thus , mean intraobserver correlation was 0.98 . The mean interobserver correlation was 0.95 ( 0.95 vs. 0.96 ) . There was no significant difference in reproducibility at different volume cut-offs . The mean intra- and interobserver correlation of endometrium volume measurements for five patients with endometrial carcinoma did not differ significantly from that for patients without carcinoma ( 0.98 , 0.98 vs. 0.98 , 0.95 ) . The intraobserver correlation of 2D endometrial thickness measurements from the first observer was 0.71 and that from second observer 0.87 . Thus , mean intraobserver correlation of the endometrial thickness measurements was 0.79 . The mean interobserver correlation was 0.76 ( 0.84 vs. 0.70 ) . CONCLUSIONS Endometrial volume and thickness measurements by 3D and 2D ultrasound , respectively , show good reproducibility but the reproducibility of 3D ultrasound is better OBJECTIVE To determine whether measurements of blood flow in endometrial and uterine vessels by transvaginal color Doppler ultrasonography was valuable in the diagnosis of a neoplastic endometrial pathology ( hyperplasia and carcinoma ) in women with abnormal bleeding . METHODS This is a prospect i ve study and included 105 post-menopausal women and 33 pre-menopausal women with abnormal uterine bleeding . All subjects underwent transvaginal color Doppler ultrasonography . We investigated whether obtained results were correlated with histopathological findings . RESULTS There was no significant difference in the mean+/-S.D. RI of the left and the right uterine arteries , intramyometrial arteries and endometrial arteries between patients with neoplastic and non-neoplastic endometrium on histopathological examination . Doppler 's velocity waveforms of small endometrial blood vessels could be detected in 9 % of the women with non-neoplastic endometrium and in 42 % of the women with neoplastic endometrium ( P<0.05 ) . The mean+/-S.D. of the endometrial thickness was significantly higher in the women with neoplastic endometrium than that of the women with non-neoplastic endometrium ( 16.6+/-6.1 mm vs. 9.5+/-4.7 mm , P<0.05 ) . CONCLUSION Doppler 's velocity waveforms of uterine vessels coupled with transvaginal ultrasonography are not valuable enough to replace histopathological examination in the diagnosis of a neoplastic endometrial pathology . However , it may be helpful in cases in which invasive techniques are difficult to perform and in the differentiation of a certain group of patients at little risk of endometrial carcinoma OBJECTIVE To make a prospect i ve comparison between endometrial thickness determined by transvaginal sonography ( TVS ) and hysteroscopic findings in women with postmenopausal bleeding with histologic findings obtained by dilatation and curettage ( D&C ) . METHODS Eighty-one patients who had not received hormonal replacement therapy were scanned by transvaginal probe , and double-layer endometrial thickness was measured 1 day before hysterectomy and D&C. RESULTS The histologic diagnosis was atrophy in 12 cases , irregular proliferative changes in 21 , endometrial polyps in 16 hyperplasia in 16 and endometrial carcinoma in 16 . TVS detected 46 of 48 pathologic conditions , including all cases of endometrial carcinoma if the endometrial thickness ( both layers ) was > or = 5 mm ( sensitivity 95.8 % , specificity 4.5 % ) . Hysteroscopy also detected the endometrial pathology in 46 of 48 cases but with a higher specificity ( sensitivity 95.3 % , specificity 93.9 % ) . CONCLUSION TVS and hysteroscopy are complementary diagnostic methods and could be accurately used to discriminate normal and pathologic conditions in patients with postmenopausal bleeding Postmenopausal bleeding is traditionally investigated with invasive procedures . Recent studies in white population s have suggested that these procedures can be avoided , as ultrasonographic endometrial thickness of < 5 mm is not associated with malignancy . We performed a prospect i ve study in 75 Jamaican Afro-Caribbean women with postmenopausal bleeding to determine whether an endometrial thickness of < 5 mm excluded endometrial cancer . We also examined the aetiology of postmenopausal bleeding and looked for possible risk factors . Double-layer transvaginal ultrasonographic measurement of the endometrial thickness was followed by hysteroscopy , suction curettage and histopathological confirmation . Correlation between imaging and pathology was not reliable . Half the patients with endometrial cancer had an endometrial thickness of between 3 mm and 4 mm . Seventy per cent of the women with endometrial thickness of greater than 5 mm had benign pathology . Additionally , the following characteristics were found to be more strongly associated with women with endometrial cancer : age over 65 years and 5 or more years since menopause . However parity < 2 appeared not to have a significant effect OBJECTIVE This study was performed to examine whether an improvement in the transvaginal sonographic evaluation of the endometrium is possible by the addition of sonomorphological criteria to the measurement of endometrial thickness in women with postmenopausal bleeding . METHODS Various sonomorphological criteria were analyzed prospect ively in 321 patients with postmenopausal bleeding . In a logistic regression model relevant criteria were selected and a diagnostic formula for differentiation of endometrial sonographic findings was derived . RESULTS The criteria of endometrial structure , endometrial-myometrial border and endometrial thickness were significant for the differentiation of malignancy . These results allowed an estimation of the probability of malignancy for each sonographic endometrial finding . Using the cut-off point of 0.1 for the probability of malignancy , the sensitivity and specificity were 96.8 % and 61.9 % , respectively , with an accuracy of 72.3 % . In contrast , the differentiation by endometrial thickness as the sole criterion ( cut-off point > or = 5 mm ) achieved a sensitivity of 97.9 % and a specificity of 33.2 % , with an accuracy of 52.3 % . CONCLUSION A useful diagnostic formula based on sonomorphological and metric criteria for endometrial differentiation was obtained . The specificity and accuracy increased with a minimal loss of sensitivity . However , estimates for sensitivity , specificity , and accuracy may be overoptimistic because they were derived from the same data used for development of the model OBJECTIVE To determine the accuracy of ultrasound scan in the diagnosis of endometrial hyperplasia and cancer in postmenopausal bleeding . DESIGN A prospect i ve diagnostic accuracy study ( 1996 - 97 ) . SETTING Minimal access surgical training centers in two large teaching hospitals . METHODS Ultrasound scan and outpatient endometrial sampling were performed on 96 patients with postmenopausal bleeding . Patients unable to have these outpatient procedures had a formal inpatient hysteroscopy and curettage . Test performance characteristics were computed for ultrasound scan comparing its estimate of endometrial thickness with histologic diagnosis that served as a ' gold ' st and ard . OUTCOME MEASURES Accuracy of the ultrasonic endometrial thickness was estimated using sensitivity , specificity and predictive values for binary data . For multilevel data , the diagnostic accuracy was computed using likelihood ratios ( LRs ) . An LR < decreased the probability that endometrial hyperplasia/cancer was present , whereas an LR > 1 increased the probability that such lesion was present . RESULTS Using endometrial thickness > or = 4 mm , the sensitivity of ultrasound to detect the endometrial malignancy was 92.9 % , the specificity was 500 % , and the positive and negative predictive values were 24.1 % and 97.6 % respectively . Analysis using likelihood ratio ( LR ) revealed that LR was 0.14 for endometrial thickness > or = 4.0 mm , 0.94 for endometrial thickness 4.1 - 9.0 mm , and 3.3 for endometrial thickness > 9.0 mm . CONCLUSION In women with postmenopausal bleeding , malignancy can probably be safely excluded if sonographic endometrial thickness is < or = 4.0 mm . However , the probability of endometrial hyperplasia/cancer is not particularly altered by the knowledge that endometrial thickness on scan is > 4.0 mm Objective : To determine the diagnostic accuracy of transvaginal ultrasonography ( TVS ) and hysteroscopy for the diagnosis of endometrial pathology in postmenopausal women with abnormal uterine bleeding ( AUB ) . Design : This prospect i ve nonr and omized study was conducted on 752 postmenopausal women with AUB who underwent TVS and outpatient hysteroscopy with eye-directed biopsy . Histologic diagnoses were compared with the ultrasonographic and hysteroscopic findings , and the sensitivity , specificity , positive predictive value , negative predictive value , and diagnostic accuracy were determined . Results : In three cases of atrophic endometrium on hysteroscopy , histologic examination revealed endometrial carcinoma . TVS using an endometrial thickness of less than 4 mm as the cutoff showed sensitivity of 89 % , specificity of 86 % , a positive predictive value of 82 % , a negative predictive value of 92 % , and diagnostic accuracy of 87 % . Hysteroscopy was technically successful in all women and revealed sensitivity of 98 % , specificity of 91 % , a positive predictive value of 88 % , a negative predictive value of 98 % , and diagnostic accuracy of 94 % . Conclusions : Hysteroscopy is a significantly more accurate diagnostic method for the detection of endometrial pathology than TVS , has better specificity , and should be considered for all patients with AUB with an endometrial thickness of more than 4 mm . Hysteroscopy shows great efficiency in the diagnosis of focal abnormalities of the endometrium , which are unlikely recognized by ultrasonography and should be indicated in cases of AUB with an endometrial thickness less than 4 mm on ultrasonography because of the possibility of missing infrequent ( 0.8 % ) but relevant endometrial pathologies . Among such women showing abnormal or suspicious lesions , it is necessary to perform hysteroscopy with eye-directed biopsy because some cases of endometrial carcinoma could be missed |
12,754 | 30,646,955 | Conclusion Available data consistently show that risk of progression increases across the pre clinical AD stages , where Stage 3 shows a risk of progression comparable to MCI due to AD .
The possibility to define , in the clinical routine , a patient as “ pre-MCI due to AD ” could offer these subjects the opportunity to use disease-modifying drugs at best | Background Alzheimer ’s disease ( AD ) pathology begins several years before the clinical onset .
The long pre clinical phase is composed of three stages according to the 2011National Institute on Aging and Alzheimer ’s Association ( NIA-AA ) criteria , followed by mild cognitive impairment ( MCI ) , a featured clinical entity defined as “ due to AD ” , or “ prodromal AD ” , when pathophysiological biomarkers ( i.e. , cerebrospinal fluid or positron emission tomography with amyloid tracer ) are positive .
In the clinical setting , there is a clear need to detect the earliest symptoms not yet fulfilling MCI criteria , in order to proceed to biomarker assessment for diagnostic definition , thus offering treatment with disease-modifying drugs to patients as early as possible .
According to the available evidence , we thus estimated the prevalence and risk of progression at each pre clinical AD stage , with special interest in Stage 3 . | Objective : To compare the diagnostic accuracy of CSF biomarkers and amyloid PET for diagnosing early-stage Alzheimer disease ( AD ) . Methods : From the prospect i ve , longitudinal BioFINDER study , we included 122 healthy elderly and 34 patients with mild cognitive impairment who developed AD dementia within 3 years ( MCI-AD ) . β-Amyloid ( Aβ ) deposition in 9 brain regions was examined with [18F]-flutemetamol PET . CSF was analyzed with INNOTEST and EUROIMMUN ELISAs . The results were replicated in 146 controls and 64 patients with MCI-AD from the Alzheimer 's Disease Neuroimaging Initiative study . Results : The best CSF measures for identifying MCI-AD were Aβ42/total tau ( t-tau ) and Aβ42/hyperphosphorylated tau ( p-tau ) ( area under the curve [ AUC ] 0.93–0.94 ) . The best PET measures performed similarly ( AUC 0.92–0.93 ; anterior cingulate , posterior cingulate/precuneus , and global neocortical uptake ) . CSF Aβ42/t-tau and Aβ42/p-tau performed better than CSF Aβ42 and Aβ42/40 ( AUC difference 0.03–0.12 , p < 0.05 ) . Using nonoptimized cutoffs , CSF Aβ42/t-tau had the highest accuracy of all CSF/PET biomarkers ( sensitivity 97 % , specificity 83 % ) . The combination of CSF and PET was not better than using either biomarker separately . Conclusions : Amyloid PET and CSF biomarkers can identify early AD with high accuracy . There were no differences between the best CSF and PET measures and no improvement when combining them . Regional PET measures were not better than assessing the global Aβ deposition . The results were replicated in an independent cohort using another CSF assay and PET tracer . The choice between CSF and amyloid PET biomarkers for identifying early AD can be based on availability , costs , and doctor/patient preferences since both have equally high diagnostic accuracy . Classification of evidence : This study provides Class III evidence that amyloid PET and CSF biomarkers identify early-stage AD equally accurately BACKGROUND Brain amyloid deposition is one of the key pathological hallmarks underlying the cognitive changes associated with Alzheimer 's disease . Growing interest has been given to the earliest clinical manifestations of amyloid plaques . However , the relationship between amyloid status and activities of everyday function remains largely unknown . In the present study , we examined the relationship between instrumental activities of daily living performance ( using the ADL-PI score ) and amyloid status in older adults . METHODS Cross-sectional analyses of data from the Multidomain Alzheimer Preventive Trial ( MAPT ) were performed . Volunteers underwent a brain 18F-AV45 positron emission tomography examination . Bivariate analysis and regression models were conducted to study the relationships between brain amyloid deposition and the total ADL-PI score . RESULTS We included 271 participants ( women = 60 % ; age = 76±4 years ) . Amyloid positron emission tomography was positive ( st and ard uptake value ≥1.17 ) for 103 participants ( 38 % ) . The ADL-PI score was lower in amyloid positive participants than in their amyloid negative counterparts ( 38.8 vs 40.3 , p = .007 ) . This association was also confirmed in regression models adjusted for age , gender , and familial history of Alzheimer 's disease ( odds ratio = 0.94 ; 95 % confidence interval 0.89 - 0.99 ; p = .02 ) . This finding was consistent in cognitively normal individuals and in those with mild cognitive impairment , using the clinical dementia rating scale . CONCLUSIONS This study highlighted an association between early functional limitations and brain amyloid deposition in elderly subjects . These symptoms could be the clinical manifestations of amyloid plaques even in the absence of overt dementia . Further prospect i ve studies are warranted for examining the evolution of ADL-PI score over the course of Alzheimer 's disease BACKGROUND Alzheimer 's disease ( AD ) pathology is common in patients with amnestic mild cognitive impairment ( aMCI ) without dementia , but the prevalence of AD pathology in patients with subjective cognitive impairment ( SCI ) and non-amnestic mild cognitive impairment ( naMCI ) is unknown . AD is characterised by decreased CSF concentrations of Abeta(42 ) and increased concentrations of tau . We investigated the prevalence of a CSF AD profile in patients with SCI , naMCI , or aMCI and the association of this profile with cognitive outcome in each group . METHODS Patients with SCI , naMCI , aMCI , and neurologically healthy controls were recruited from 20 memory clinics across Europe , between January , 2003 , and June , 2005 , into this prospect i ve cohort study . A CSF AD profile was defined as an abnormal ratio of Abeta(42):tau . Patients were assessed annually up to 3 years . Outcome measures were changes in memory , overall cognition , mini-mental state examination ( MMSE ) score , daily function , and progression to AD-type dementia . FINDINGS The CSF AD profile was more common in patients with SCI ( 31 of 60 [ 52 % ] ) , naMCI ( 25 of 37 [ 68 % ] ) , and aMCI ( 56 of 71 [ 79 % ] ) than in healthy controls ( 28 of 89 [ 31 % ] ) . The profile was associated with cognitive decline in patients with naMCI ( memory , MMSE , and daily function ) and in patients with aMCI ( MMSE and daily function ) . In patients with aMCI , a CSF AD profile was predictive of AD-type dementia ( OR 26.8 , 95 % CI 1.6 - 456.4 ) . INTERPRETATION AD is a common cause of SCI , naMCI , and aMCI and is associated with cognitive decline in patients with naMCI or aMCI . Patients with SCI might be in the early stages of AD , and cognitive decline might become apparent only after longer follow-up . FUNDING European Commission ; Ana Aslan International Foundation OBJECTIVE In the course of performing systematic review s on the prevalence of low back and neck pain , we required a tool to assess the risk of study bias . Our objectives were to ( 1 ) modify an existing checklist and ( 2 ) test the final tool for interrater agreement . STUDY DESIGN AND SETTING The final tool consists of 10 items addressing four domains of bias plus a summary risk of bias assessment . Two research ers tested the interrater agreement of the tool by independently assessing 54 r and omly selected studies . Interrater agreement overall and for each individual item was assessed using the proportion of agreement and Kappa statistic . RESULTS Raters found the tool easy to use , and there was high interrater agreement : overall agreement was 91 % and the Kappa statistic was 0.82 ( 95 % confidence interval : 0.76 , 0.86 ) . Agreement was almost perfect for the individual items on the tool and moderate for the summary assessment . CONCLUSION We have addressed a research gap by modifying and testing a tool to assess risk of study bias . Further research may be useful for assessing the applicability of the tool across different conditions Our objectives were ( 1 ) to test the association between the report of subjective cognitive decline ( SCD ) and prospect i ve objective cognitive performance in high age individuals and ( 2 ) to study the course of longitudinal cognitive performance before and after the first report of SCD The objective is to evaluate the prognosis of subjective cognitive complaints ( SCC ) patients during 4-year follow-up . A prospect i ve study on 92 SCC patients investigating their cognitive , affective and behavioural aspects . SCC patients were classified as having no objective cognitive impairment ( NOCI ) , mild cognitive impairment ( MCI ) , or subtypes of MCI . Results : 43 patients were found to have NOCI and 49 MCI . During the follow-up , 45.5 % of NOCI patients remained unchanged , 13.9 % were diagnosed as MCI and only one progressed to dementia . Of the MCI patients , 32.3 % remained stable , 18.4 % became demented and 4 % reverted to NOCI . Visual attention , behavioural memory , long-term verbal memory , apathy and caregiver distress , provided independent predictors of progression to dementia BACKGROUND Imaging with amyloid-β PET can potentially aid the early and accurate diagnosis of Alzheimer 's disease . Florbetaben ( ¹⁸F ) is a promising ¹⁸F-labelled amyloid-β-targeted PET tracer in clinical development . We aim ed to assess the sensitivity and specificity of florbetaben ( ¹⁸F ) PET in discriminating between patients with probable Alzheimer 's disease and elderly healthy controls . METHODS We did a multicentre , open-label , non-r and omised phase 2 study in 18 centres in Australia , Germany , Switzerl and , and the USA . Imaging with florbetaben ( ¹⁸F ) PET was done on patients with probable Alzheimer 's disease ( age 55 years or older , mini-mental state examination [ MMSE ] score=18 - 26 , clinical dementia rating [CDR]=0·5 - 2·0 ) and age-matched healthy controls ( MMSE ≥ 28 , CDR=0 ) . Our primary objective was to establish the diagnostic efficacy of the scans in differentiating between patients with probable disease and age-matched healthy controls on the basis of neocortical tracer uptake pattern 90 - 110 min post-injection . PET images were assessed visually by three readers masked to the clinical diagnosis and all other clinical findings , and quantitatively by use of pre-established brain volumes of interest to obtain st and ard uptake value ratios ( SUVRs ) , taking the cerebellar cortex as the reference region . This study is registered with Clinical Trials.gov , number NCT00750282 . FINDINGS 81 participants with probable Alzheimer 's disease and 69 healthy controls were assessed . Independent visual assessment of the PET scans showed a sensitivity of 80 % ( 95 % CI 71 - 89 ) and a specificity of 91 % ( 84 - 98 ) for discriminating participants with Alzheimer 's disease from healthy controls . The SUVRs in all neocortical grey-matter regions in participants with Alzheimer 's disease were significantly higher ( p < 0·0001 ) compared with the healthy controls , with the posterior cingulate being the best discriminator . Linear discriminant analysis of regional SUVRs yielded a sensitivity of 85 % and a specificity of 91 % . Regional SUVRs also correlated well with scores of cognitive impairment such as the MMSE and the word-list memory and word-list recall scores ( r -0·27 to -0·33 , p ≤ 0·021 ) . APOE ɛ4 was more common in participants with positive PET images compared with those with negative scans ( 65%vs 22 % [ p=0·027 ] in patients with Alzheimer 's disease ; 50%vs 16 % [ p = 0·074 ] in healthy controls ) . No safety concerns were noted . INTERPRETATION We provide verification of the efficacy , safety , and biological relevance of florbetaben ( ¹⁸F ) amyloid-β PET and suggest its potential as a visual adjunct in the diagnostic algorithm of dementia . FUNDING Bayer Schering Pharma AG BACKGROUND There is very limited data on the prevalence of abnormal cerebrospinal fluid ( CSF ) biomarkers of Alzheimer 's disease ( AD ) and their predictive value for clinical progression in memory clinic patients with subjective cognitive decline ( SCD ) . OBJECTIVE To assess the frequency of abnormal CSF biomarkers of AD and their predictive value for clinical progression in memory clinic patients with SCD in comparison to patients with mild cognitive impairment ( MCI ) from the same cohort . METHODS We analyzed prospect i ve data from memory clinic patients of the German Competence Network Dementia cohort with a baseline diagnosis of SCD ( n = 82 ) or MCI ( n = 134 ) , distinguished by actuarial neuropsychological MCI criteria ( " Jak-Bondi criteria ") . Risk of clinical progression during 3-year follow-up was evaluated with Cox-Proportional-Hazard models . RESULTS Prevalence of abnormal values in CSF markers of tau-mediated neurodegeneration ( 67.8 % versus 46.3 % ) but not of amyloid deposition ( 40.3 % versus 35.4 % ) was significantly higher in MCI compared to SCD . The rate of incident AD dementia ( 26.1 % versus 12.2 % ) was also significantly higher in MCI . In SCD , additional 22 % progressed to MCI during follow-up . Combined amyloid/tau abnormality was the strongest predictor of clinical progression in both groups . CONCLUSION High prevalence of biomarker abnormality and clinical progression , together with the predictive value of CSF biomarkers , in memory clinic patients with SCD support the validity and usefulness of this condition as a " pre-MCI " at risk stage of AD |
12,755 | 31,392,721 | Limited evidence was found for pre-operative gabapentin , perineural adjuncts ( opioids , glucocorticoids , or α-2-adrenoceptor agonists added to the local anaesthetic solution ) or postoperative transcutaneous electrical nerve stimulation .
Inconsistent evidence was found for subacromial/intra-articular injection , and for surgical technique-linked interventions , such as platelet-rich plasma .
No evidence was found for stellate ganglion block , cervical epidural block , specific postoperative rehabilitation protocol s or postoperative compressive cryotherapy . | Rotator cuff repair can be associated with significant and difficult to treat postoperative pain .
We aim ed to evaluate the available literature and develop recommendations for optimal pain management after rotator cuff repair . | Abstract Purpose The goal of the study was to evaluate the efficacy of additional axillary nerve block ( ANB ) with suprascapular nerve block ( SSNB ) and patient-controlled anaesthesia ( PCA ) with no device assistance after arthroscopic rotator cuff repair . The hypothesis is that patients with intravenous ( IV ) PCA and the blockade of the two main nerves ( SSNB + ANB ) experienced lesser pain than patients with IV PCA or IV PCA + SSNB . Methods The 114 patients undergoing arthroscopic rotator cuff repair were allocated r and omly to three groups as follows : group I , intravenous PCA pumps ( only PCA ) ; group II , IV PCA + SSNB using a blind technique ( PCA + SSNB ) ; and group III , IV PCA + SSNB + ANB using a blind technique ( PCA + SSNB + ANB ) . Pain visual analogue scale ( VAS ) scores were evaluated at 1 , 6 , 12 , 24 , 36 , and 48 post-operative hours . Furthermore , the degree of pain was compared according to cuff tear size . Results The pain VAS score of group III was lower than that of the other two groups and was significantly lower at post-operative hours 1 , 6 , and 12 . In addition , the larger cuff tear tended to be indicative of greater pain . However , all groups experienced rebound pain . Conclusion PCA + SSNB + ANB using a blind technique is a better pain control method than PCA + SSNB and only PCA during the initial 12 post-operative hours . PCA + SSNB + ANB is a cost-effective , time-saving , and easily performed method for post-operative pain control as an axis of multimodal pain control strategy .Level of evidence II BACKGROUND Local analgesic injections are commonly used for pain relief after shoulder surgery . The aim of this study was to compare the efficacy of local injections administered in the glenohumeral joint , the subacromial space , or both locations after arthroscopic rotator cuff repair . METHODS Between March 2011 and December 2011 , 121 consecutive patients who had undergone arthroscopic rotator cuff repair surgery were enrolled in the study and all patients were r and omly allocated to 3 groups . In group 1 , 40 patients received a postoperative glenohumeral injection of bupivacaine ( 20 mL ) and lidocaine ( 10 mL ) . In group 2 , 42 patients received the same postoperative injection , but it was administered in the subacromial space . In group 3 , 39 patients received the same amount of local anesthesia but with half injected in the glenohumeral joint and half in the subacromial space . The visual analog scale was used to assess pain intensity before surgery and at postoperative hours 1 , 2 , 6 , 12 , and 24 . Demerol was used as a postinjection rescue analgesic , and the total number of administrations was recorded at each time point . RESULTS There were no significant differences between groups in patient age , sex , or rotator cuff tear size ( P > .05 ) . The visual analog scale scores for pain between each group were not significantly different at any time point , including before surgery ( P > .05 ) . In addition , the amount of supplementary analgesic administered was not significantly different between the groups ( P > .05 ) . CONCLUSION Injection of local analgesics after arthroscopic rotator cuff repair relieves postoperative pain regardless of the injection location Purpose This prospect i ve study was undertaken to compare the effectiveness and safety of a multimodal pain control protocol with those of intravenous patient-controlled analgesia in rotator cuff repair . Methods Seventy patients scheduled for rotator cuff repair were r and omized to either a multimodal pain control group ( group 1 , 40 patients ) or an intravenous patient-controlled analgesia group ( group 2 , 30 patients ) . We compared these two groups with respect to level of pain before surgery to the fifth postoperative day , duration of postoperative rehabilitation , consumption of additional analgesics , and adverse effects . Results Mean visual analogue scale scores immediately after surgery ( day 0 ) and on postoperative days 1–5 were 6.9 , 5.5 , 4.3 , 3.3 , 3.0 , and 2.6 in group 1 and 7.8 , 5.9 , 4.4 , 4.7 , 4.3 , and 3.7 in group 2 . Pain relief was significantly better in group 1 on days 0 , 3 , 4 , and 5 ( P = 0.026 , 0.006 , 0.010 , and 0.009 , respectively ) . Furthermore , functional recovery occurred earlier in group 1 . No significant differences were observed between the two groups with respect to nausea , vomiting , urinary retention , and headache ( n.s . ) , but group 1 was found to be significantly less likely to experience dizziness or urticaria ( P = 0.007 , 0.017 , respectively ) . One other significant difference was observed : 1 patient ( 2.5 % ) in group 1 and 6 patients ( 20 % ) in group 2 discontinued regimen because of medication-related adverse effects ( P = 0.016 ) . Conclusion The multimodal pain control protocol was found to offer more effective postoperative pain control with fewer adverse effects than intravenous patient-controlled analgesia . However , achieving adequate pain control within the first 48 h of surgery remains challenging , and thus , the developments of more effective and safer multimodal pain control protocol s are required BACKGROUND : Early mobilization after shoulder surgery plays a vital role in successful functional rehabilitation . However , postoperative pain often reduces , or even prevents , effective physiotherapy . We investigated the effect of analgesia via patient-controlled interscalene technique on early functional rehabilitation after open shoulder surgery . METHODS : Eighty-seven patients were r and omly assigned to one of two groups : patient-controlled continuous interscalene block ( PCISB ) and patient-controlled IV ( opioid ) analgesia ( PCA ) . Interscalene block was performed preoperatively ; otherwise analgesic protocol s were started in the postanesthesia care unit and were continued for 72 h. Physiotherapy was performed for 60 min a day on day 2 and 3 after surgery according to a st and ardized protocol . Maximum mobility was defined as the range of motion that could be achieved with pain as the limiting factor . Efficiency of functional rehabilitation was evaluated 1 day before and 3 days after surgery with the help of a multimodal scoring system ( Constant-Score ) that evaluates pain , daily life activity , strength and range of motion . Maximum intensity of pain was also monitored via Visual Analog Scales for the first 72 h after surgery and during in-hospital physiotherapy . RESULTS : Constant-Score rates were significantly improved by the interscalene block . However , no significant differences in mobility and strength sub-scores were observed between the groups . Compared with PCA , PCISB proved to be beneficial concerning pain at rest at 6 h ( P < 0.001 ) , 24 h ( P = 0.044 ) , and 72 h ( P = 0.013 ) and for pain during physiotherapy at 48 h after surgery ( P = 0.016 ) . CONCLUSION : Compared with opioid-based PCA , PCISB improved analgesia , but not function , during early rehabilitation of the shoulder joint PURPOSE To compare the effect of early versus delayed motion protocol s on quality of life , clinical outcomes , and repair integrity in patients who have undergone arthroscopic single-tendon rotator cuff repair . METHODS This was a prospect i ve , r and omized , investigator-blinded clinical trial . Seventy-three patients from a single surgeon 's practice who underwent arthroscopic repair of a single-tendon rotator cuff tear were r and omized to either an early motion protocol ( starting 2 to 3 days after surgery ) or a delayed motion protocol ( starting 28 days after surgery ) . The primary outcome measure was the Western Ontario Rotator Cuff index ( WORC ) . Secondary outcome measures included clinical outcome scores , integrity of the repair on 6-month magnetic resonance imaging scans , pain scores , physical examination data , and ultrasonography . Study participants were followed up at 3 , 6 , and 12 weeks ; 6 months ; and 1 year postoperatively . RESULTS There was no statistically significant difference in WORC scores at 6 months ( 529 ± 472 in delayed group vs 325 ± 400 in early group , P = .08 ) . Mixed-effects analysis indicated the early group maintained lower WORC scores throughout the postoperative period ( estimated difference of 191 , P = .04 ) . The proportions of patients with tears on the 6-month postoperative magnetic resonance imaging scan were comparable ( 31 % in delayed group vs 34 % in early group , P = .78 ) . CONCLUSIONS There was no difference between the delayed and early motion groups in WORC scores at 6 months after surgery . Early motion was associated with lower WORC scores throughout the postoperative period ; however , both groups had a similar trajectory of improvement , suggesting both protocol s have the same effect on patient-reported improvement . Although failure rates were similar between the groups , the sample size was not sufficient to support a statement regarding the relation between tear morphology and the rehabilitation protocol . LEVEL OF EVIDENCE Level II , lesser- quality r and omized controlled trial Purpose The aim of this study was to compare the pain relieving effect of ultrasound-guided interscalene brachial plexus block ( ISB ) combined with arthroscopy-guided suprascapular nerve block ( SSNB ) with that of ultrasound-guided ISB alone within the first 48 h after arthroscopic rotator cuff repair . Methods Forty-eight patients with rotator cuff tears who had undergone arthroscopic rotator cuff repair were enrolled . The 24 patients in group 1 received ultrasound-guided ISB and arthroscopy-guided SSNB ; the remaining 24 patients in group 2 underwent ultrasound-guided ISB alone . Visual analogue scale pain score and patient satisfaction score were checked at 1 , 3 , 6 , 12 , 18 , 24 , and 48 h post-operatively . Results Group 1 had a lower visual analogue scale pain score at 3 , 6 , 12 , 18 , 24 , and 48 h post-operatively ( 1.7 < 2.6 , 1.6 < 4.0 , 3.5 < 5.8 , 3.6 < 5.2 , 3.2 < 4.2 , 1.3 < 2.0 ) , and a higher patient satisfaction score at 6 , 12 , 18 , 24 , and 36 h post-operatively than group 2 ( 7.8 > 6.0 , 6.2 > 4.3 , 6.4 > 5.1 , 6.9 > 5.9 , 7.9 > 7.1 ) . Six patients in group 1 developed rebound pain twice , and the others in group 1 developed it once . All of the patients in group 2 had one rebound phenomenon each ( p = 0.010 ) . The mean timing of rebound pain in group 1 was later than that in group 2 ( 15.5 > 9.3 h , p < 0.001 ) , and the mean size of rebound pain was smaller in group 1 than that in group 2 ( 2.5 > 4.0 , p = 0.001 ) . Conclusion Arthroscopy-guided SSNB combined with ultrasound-guided ISB result ed in lower visual analogue scale pain scores at 3–24 and 48 h post-operatively , and higher patient satisfaction scores at 6–36 h post-operatively with the attenuated rebound pain compared to scores in patients who received ultrasound-guided ISB alone after arthroscopic rotator cuff repair . The combined blocks may relieve post-operative pain more effectively than the single block within 48 h after arthroscopic cuff repair . Level of evidence R and omized controlled trial , Level I. Clinical Trials.gov Identifier : NCT02424630 BACKGROUND Arthroscopic rotator cuff repair ( ARCR ) can be associated with significant postoperative pain . Concern for opioid abuse has led surgeons to identify alternative , efficacious methods of postoperative analgesia . To determine whether transcutaneous electrical nerve stimulation ( TENS ) can have a similarly beneficial effect after shoulder procedures , we conducted a prospect i ve double-blinded r and omized trial in patients undergoing outpatient ARCR . METHODS All patients undergoing ARCR of a full-thickness rotator cuff tear by the senior authors were identified . Patients with a history of recent narcotic use or prior narcotic abuse and those under management of a pain control specialist were excluded . Patients were r and omized into 2 groups , active or placebo TENS , and used the device for 4 sessions/day for 45 minutes/session for the first postoperative week . All patients received Percocet 5/325 mg ( oxycodone/acetaminophen ) for use as rescue pain pills . One-week narcotic consumption and visual analog scale pain scores were compared between groups . RESULTS The final analysis included 37 patients ( 21 active,16 placebo ) . Baseline and procedural differences were not different between groups . At 1 week postoperatively , patients in the active group had significantly lower pain scores ( 3.6 ± 2.1 vs. 5.8 ± 1.2 ; P= .008 ) . Postoperative Percocet consumption during the initial 48 hours ( 12.8 ± 4.7 vs. 17.2 ± 6.3 ; P = .020 ) and during the first week ( 25.2 ± 9.9 vs. 33.8 ± 14.3 ; P = .037 ) was also significantly lower in the active group . CONCLUSION Results from this prospect i ve double-blinded r and omized trial demonstrate that compared with placebo TENS , active TENS can result in significantly less pain and reduced opioid use in the immediate postoperative period after ARCR , suggesting that TENS may be potentially useful in a multimodal approach to managing postoperative pain BACKGROUND Beach chair positioning for shoulder surgery is associated with measurable cerebral desaturation events ( CDEs ) in up to 80 % of patients . Near-infrared spectroscopy ( NIRS ) technology allows real-time measurement of cerebral oxygenation and may minimize the frequency of CDEs . The purpose of this study was to investigate the incidence of CDEs when anesthetists were aware of and blinded to NIRS monitoring and to determine the short-term cognitive effects of surgery in the beach chair position . METHODS NIRS was used to monitor cerebral oxygenation saturation in 41 consecutive patients undergoing arthroscopic shoulder surgery in the beach chair position . Patients were r and omized to 2 groups , anesthetists aware of or blinded to NIRS data . The Montreal Cognitive Assessment ( MoCA ) was used to assess cognitive function preoperatively , immediately postoperatively , and at 2 and 6 weeks postoperatively . RESULTS Overall , 7 ( 17.5 % ) patients experienced a CDE , 5 ( 25 % ) in the aware group and 2 ( 10 % ) in the blinded group . There was no significant difference in MoCA scores between the aware and blinded groups preoperatively ( 27.9.1 vs. 28.2 ; P = .436 ) , immediately postoperatively ( 26.1 vs. 26.2 ; P = .778 ) , 2 weeks postoperatively ( 28.0 vs. 28.1 ; P = .737 ) , or 6 weeks postoperatively ( 28.5 vs. 28.4 ; P = .779 ) . There was a correlation of NIRS with systolic blood pressure ( r = 0.448 ) , diastolic blood pressure ( r = 0.708 ) , and mean arterial pressure ( r = 0.608 ) . CONCLUSION In our series , the incidence of CDEs was much lower than previously reported and was not lowered by use of NIRS . Patients did not have significant cognitive deficits after arthroscopic surgery in the beach chair position , and there was a correlation between NIRS and intraoperative brachial blood pressure BACKGROUND We sought to compare the efficacy of interscalene brachial plexus bolus blockade ( IBPBB ) and patient-controlled interscalene indwelling catheter analgesia ( PCIA ) for postoperative pain management within 48 hours postoperatively in patients undergoing arthroscopic rotator cuff repairs ( ARCR ) . METHODS Patients undergoing ARCR were r and omized into 3 groups by postoperative analgesia method . The IBPBB group received a mixed solution of 16 mL of 0.75 % ropivacaine and 4 mL of 2 % lidocaine as a bolus postoperatively . The PCIA group received a 10-mL bolus solution of 0.75 % ropivacaine ( 4 mL ) and 5 % dextrose water ( 6 mL ) just after the operation and continuous infusion of this solution . The control received only meperidine as needed , 12.5 mg , intravenously . Visual analog scale ( VAS ) pain scores were evaluated for the first 48 hours postoperatively . RESULTS For the first 2 hours postoperatively , VAS scores in the IBPBB group were significantly lower than in the PCIA group and control group , but at 12 and 24 hours postoperatively , VAS scores of the IBPBB group were significantly higher than the PCIA group ( P < .05 ) . At 48 hours postoperatively , there was no significant difference in VAS scores among the 3 groups ( P = .169 ) . The method of analgesia was the only factor affecting pain scores at 24 hours postoperatively ( P < .05 ) . CONCLUSIONS IBPBB provided effective immediate postoperative analgesia until 6 hours postoperatively . Especially until postoperative 2 hours , the VAS pain score was less than 1 point in the IBPBB group ; however , there was significant rebound pain at 12 hours after surgery . During the first 24 hours postoperatively , PCIA reduced postoperative pain without rebound pain . Surgeons should choose methods for control of postoperative pain considering the advantages and disadvantages of each analgesic method PURPOSE To study the effects on pain as the main outcome parameter and on function and cuff integrity as the secondary outcome parameters after arthroscopic rotator cuff repair in the short term comparing the abduction brace with an antirotation sling for postoperative shoulder immobilization . METHODS Eligible patients were between the ages of 18 and 75 years who were diagnosed with a traumatic or degenerative tear of the supraspinatus and /or infraspinatus tendon , confirmed by magnetic resonance imaging , for which an arthroscopic footprint repair was indicated and performed . Patients were r and omly allocated to the antirotation sling or abduction brace group . Postoperative pain and use of analgesics were accurately registered up to 3 months after surgery using a patient diary . Follow-up examinations including the Constant-Murley score , Western Ontario Rotator Cuff index , and glenohumeral range of motion were scheduled 6 weeks , 3 and 6 months , and 1 year after surgery . RESULTS The average level of pain measured directly postoperation up to 1 year after surgery was not significant different between groups . Postoperatively , function scores and glenohumeral range of motion improved significantly for both groups ; however , no differences were observed between groups . No retears were observed on ultrasonograph 3 months after surgery . CONCLUSIONS In the short term , the level of pain , function , and quality of life were not significantly different between the use of an abduction brace and that of an antirotation sling after arthroscopic rotator cuff repair . Based on these findings , the abduction brace used in this study does not seem to be the solution for decreasing the pain experienced in the first postoperative weeks after arthroscopic rotator cuff repair , and both are recommendable . LEVEL OF EVIDENCE Level I , r and omized controlled trial Background : The interscalene nerve block provides analgesia for shoulder surgery , but is associated with diaphragm paralysis . One solution may be performing brachial plexus blocks more distally . This noninferiority study evaluated analgesia for blocks at the supraclavicular and anterior suprascapular levels , comparing them individually to the interscalene approach . Methods : One hundred-eighty-nine subjects undergoing arthroscopic shoulder surgery were recruited to this double-blind trial and r and omized to interscalene , supraclavicular , or anterior suprascapular block using 15 ml , 0.5 % ropivacaine . The primary outcome was numeric rating scale pain scores analyzed using noninferiority testing . The predefined noninferiority margin was one point on the 11-point pain scale . Secondary outcomes included opioid consumption and pulmonary assessment s. Results : All subjects completed the study through the primary outcome analysis . Mean pain after surgery was : interscalene = 1.9 ( 95 % CI , 1.3 to 2.5 ) , supraclavicular = 2.3 ( 1.7 to 2.9 ) , suprascapular = 2.0 ( 1.4 to 2.6 ) . The primary outcome , mean pain score difference of supraclavicular – interscalene was 0.4 ( –0.4 to 1.2 ; P = 0.088 for noninferiority ) and of suprascapular – interscalene was 0.1 ( –0.7 to 0.9 ; P = 0.012 for noninferiority ) . Secondary outcomes showed similar opioid consumption with better preservation of vital capacity in the anterior suprascapular group ( 90 % baseline [ P < 0.001 ] ) and the supraclavicular group ( 76 % [ P = 0.002 ] ) when compared to the interscalene group ( 67 % ) . Conclusions : The anterior suprascapular block , but not the supraclavicular , provides noninferior analgesia compared to the interscalene approach for major arthroscopic shoulder surgery . Pulmonary function is best preserved with the anterior suprascapular nerve block BACKGROUND AND HYPOTHESIS Arthroscopic rotator cuff repair can be a painful outpatient procedure . The purpose of this study was to evaluate the efficacy of continuous subacromial bupivacaine infusion to relieve pain after arthroscopic rotator cuff repair . We hypothesized that patients receiving continuous subacromial bupivacaine infusions after arthroscopic rotator cuff repair will have less postoperative pain in the early postoperative period than placebo and control groups . MATERIAL S AND METHODS Eighty-eight patients undergoing arthroscopic rotator cuff repair were r and omized in a blinded fashion into 1 of 3 groups . Group 1 received no postoperative subacromial infusion catheter . Group 2 received a postoperative subacromial infusion catheter filled with saline solution . Group 3 received a postoperative subacromial infusion catheter filled with 0.5 % bupivacaine without epinephrine . Infusion catheters were scheduled to infuse at 4 mL/h for 50 hours . Postoperative pain levels were assessed with visual analog scale scores hourly for the first 6 postoperative hours , every 6 hours for the next 2 days , and then every 12 hours for the next 3 days . Patients recorded daily oxycodone consumption for the first 5 postoperative days . RESULTS Immediately postoperative , the group with no catheter had significantly lower visual analog scale scores ( P = .04 ) . There were no significant differences in visual analog scale scores among the groups at any other time point . There were no differences found among the groups regarding mean daily oxycodone consumption . CONCLUSION The use of continuous bupivacaine subacromial infusion catheters result ed in no detectable pain reduction after arthroscopic rotator cuff repair based on visual analog scale scores and narcotic medication consumption BACKGROUND The aim of this study was to evaluate the efficacy of tramadol as an adjuvant to the local anaesthetic solution in patients undergoing shoulder arthroscopy for rotator cuff tear after middle interscalene block ( MIB ) . METHODS We enrolled 120 patients ( ASA I-II ) , scheduled for arthroscopic surgery for rotator cuff tear . The patients were se date d with midazolam 0.02 mg/kg and haloperidol 2 mg i.v . before performing MIB . All subjects underwent a MIB with 0.4 mL/kg of 0.5 % levobupivacaine . After computerized r and omization , all patients were allocated in 1 of 3 groups , each including 40 subjects . Group Placebo ( Group P ) received 0.4 mL/kg of 0.5 % levobupivacaine plus isotonic sodium chloride for MIB and isotonic sodium chloride i.m . Group " Perineural Tramadol " ( Group TPN ) received 0.4 ml/Kg of 0.5 % levobupivacaine plus 1.5 mg/kg of tramadol perineurally and isotonic sodium chloride i.m . Group " Intramuscular Tramadol " ( Group TIM ) received 0.4 ml/Kg of 0.5 % levobupivacaine plus isotonic sodium chloride perineurally and 1.5 mg/kg of tramadol i.m . RESULTS The MIB onset times were not statistically different in the three groups . The duration of analgesia was significantly longer in Groups TPN and TIM , where tramadol was administered , either i.m . or perineurally , compared with the placebo group . A significant statistical difference was found in the duration of analgesia between the group TPN and TIM . CONCLUSION The addition of tramadol to the local anaesthetic solution administered for MIB provided a longer duration of analgesia compared with placebo and i.m tramadol administration in patients undergoing arthroscopic surgery for rotator cuff tear Purpose The aim of this study was to assess whether addition of epineural buprenorphine prolonged postoperative analgesia of middle interscalene brachial plexus block ( MIB ) with levobupivacaine . Methods One hundred and fifty consenting adult patients , scheduled for shoulder arthroscopic surgery for a rotator cuff tear under MIB with 29.5 ml of 0.75 % levobupivacaine , were r and omized to receive additionally either saline or intramuscular buprenorphine 0.15 mg or epineural buprenorphine 0.15 mg . Onset of sensory and motor blocks , duration of postoperative analgesia , and consumption of postoperative analgesics were compared among the groups . Results There were significant ( P < 0.05 ) differences in the onset and the duration of the sensory block and in the duration of postoperative analgesia . Duration of both sensory block and postoperative analgesia was longer ( P < 0.05 ) in patients who had received epineural buprenorphine ( 856.1 ± 215.2 and 1,049.7 ± 242.2 min ) than in patients who had received intramuscular buprenorphine ( 693.6 ± 143.4 and 820.3 ± 335.3 min ) or saline ( 488.3 ± 137.6 and 637.5 ± 72.1 min ) . Requirement of postoperative rescue analgesics was lower in the epineural buprenorphine group than in the other two groups . Few complications occurred from MIB ( < 1 % ) and none from buprenorphine . Conclusions Epineural buprenorphine prolonged postoperative analgesia of MIB more effectively than intramuscular buprenorphine , which suggests that buprenorphine acts at a peripheral nervous system site of action Purpose The purpose of this study was to evaluate the outcomes of arthroscopy-guided direct suprascapular nerve block performed after arthroscopic rotator cuff repair . Methods In the present prospect i ve , r and omized , double-blinded clinical study , 30 patients were divided into two groups : 15 patients ( group I ) were treated with arthroscopy-guided suprascapular nerve block using 10 mL 0.5 % ropivacaine with 1:200,000 epinephrine , and 15 patients ( group II ) were treated with placebo using 10 mL 0.9 % saline after arthroscopic rotator cuff repair . Patient pain levels were measured using the visual analog scale ( VAS ) at 1 , 3 , 6 , 12 , 18 , and 24 h post-operatively . Additionally , the number of boluses and total amount of fentanyl dispensed by patient-controlled analgesia administration during the 24-h post-operative period were evaluated . Results VAS scores did not differ significantly between groups I and II during the 24-h post-operative period , but mean fentanyl bolus consumption was significantly less in group I compared with group II ( p = 0.015 ) . Conclusion Arthroscopy-guided suprascapular nerve block at the end of a rotator cuff repair was safe and less time-consuming than expected . Although this procedure did not significantly reduce the post-operative pain , the post-operative need for fentanyl boluses as analgesia was reduced significantly , and it would be beneficial if this procedure involved a sensory branch of axillary nerve block or was performed at the beginning of the arthroscopic procedure . Level of evidence Prospect i ve , r and omized , double-blinded clinical trial , Level Background : Arthroscopic rotator cuff repair has a high rate of patient satisfaction . However , multiple studies have shown significant rates of anatomic failure . Biological augmentation would seem to be a reasonable technique to improve clinical outcomes and healing rates . Purpose : To represent a prospect i ve , double-blinded , r and omized study to assess the use of platelet-rich fibrin matrix ( PRFM ) in rotator cuff surgery . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : Pre study power analysis demonstrated that a sample size of 30 patients in each group ( PRFM vs control ) would allow recognition of a 20 % difference in perioperative pain scores . Sixty consecutive patients were r and omized to either receive a commercially available PRFM product or not . Preoperative and postoperative range of motion ( ROM ) , University of California – Los Angeles ( UCLA ) , and Simple Shoulder Test ( SST ) scores were recorded . Surgery was performed using an arthroscopic single-row technique . Visual analog scale ( VAS ) pain scores were obtained upon arrival to the recovery room and 1 hour postoperatively , and narcotic consumption was recorded and converted to st and ard narcotic equivalents . The SST and ROM measurements were taken at 3 , 6 , 9 , and 12 weeks postoperatively , and final ( 1 year ) American Shoulder and Elbow Surgeons ( ASES ) shoulder and UCLA shoulder scores were assessed . Results : There were no complications . R and omization created comparable groups except that the PRFM group was younger than the control group ( mean ± SD , 59.67 ± 8.16 y vs 64.50 ± 8.59 y , respectively ; P < .05 ) . Mean surgery time was longer for the PRFM group than for the control group ( 83.28 ± 17.13 min vs 73.28 ± 17.18 min , respectively ; P < .02 ) . There was no significant difference in VAS scores or narcotic use between groups and no statistically significant differences in recovery of motion , SST , or ASES scores . Mean ASES scores were 82.48 ± 8.77 ( PRFM group ) and 82.52 ± 12.45 ( controls ) ( F1,56 = 0.00 , P > .98 ) . Mean UCLA shoulder scores were 27.94 ± 4.98 for the PRFM group versus 29.59 ± 1.68 for the controls ( P < .046 ) . Structural results correlated with age and size of the tear and did not differ between the groups . Conclusion : Platelet-rich fibrin matrix was not shown to significantly improve perioperative morbidity , clinical outcomes , or structural integrity . While longer term follow-up or different platelet-rich plasma formulations may show differences , early follow-up does not show significant improvement in perioperative morbidity , structural integrity , or clinical outcome BACKGROUND : Interscalene analgesia is a recognized technique for the management of postoperative pain after major shoulder surgery . The most effective local anesthetic concentration in this setting is still controversial . In this study , we compared the analgesia and side effects of a continuous infusion of ropivacaine 0.2 % and 0.3 % administered through an interscalene catheter for the first 48 hours after surgery . METHODS : Eighty consecutive patients scheduled for elective open rotator cuff repair were r and omized into 2 groups to receive a continuous infusion of either ropivacaine 0.2 % or ropivacaine 0.3 % for 48 hours at a rate of 14 mL/h through an interscalene catheter after a preoperative bolus of 40 mL ropivacaine 0.5 % in all patients . Pain score ( visual analog scale 0–100 ) , intensity of motor block , quality of sleep during the first postoperative night , morphine consumption , side effects , and patient satisfaction were assessed by an anesthesiologist masked to treatment group . RESULTS : Total morphine consumption was significantly reduced in group 0.3 % ( 12 vs 30 mg ) . Quality of sleep was significantly better in group 0.3 % ( 4 % vs 27 % of awakening during the first postoperative night ) . H and grip strength , visual analog scale scores , and side effects were similar in both groups . CONCLUSION : The use of ropivacaine 0.3 % through an interscalene catheter for the first 48 hours after open rotator cuff repair provided a significant reduction of morphine consumption and a better sleep quality for the first postoperative night without increasing the intensity of motor block or side effects Background Dexamethasone added to local anesthetic for brachial plexus block improves postoperative pain after arthroscopic rotator cuff repair , as compared with the use of local anesthetic alone . Dexamethasone is present in non-particulate form in local anesthetic solution , while betamethasone is partially present in particulate form . The particulate betamethasone gradually decays and is expected to cause its longer-lasting effect . This study investigated the postoperative analgesic effect of betamethasone added to ropivacaine for brachial plexus block in patients who underwent arthroscopic rotator cuff repair . Methods This was a prospect i ve , r and omized , triple-blind study of 44 patients undergoing arthroscopic rotator cuff repair surgery . Ultrasound-guided interscalene brachial plexus block , involving 20 mL of 0.375 % ropivacaine ( group R ) or 19 mL of 0.375 % ropivacaine with 4 mg ( 1 mL ) of betamethasone ( group BR ) , was administered and surgery was performed under general anesthesia . After surgery , the pain score was recorded at 12 h after surgery , and on the first , second , and seventh postoperative day . Analgesia duration , offset time of motor block , frequency of rescue analgesic administration , postoperative nausea/vomiting , and sleep disturbance during the night after surgery were recorded . The numerical values were expressed as median [ interquartile range ] . P values < 0.05 were considered statistically significant . Results The duration of analgesia was significantly prolonged in group BR ( group BR : 19.1 h [ 16.6 , 20.9 h ] , group R : 13.3 h [ 11.6 , 16.5 h ] , p < 0.001 ) . The pain scores at 12 h after surgery and on the first and seventh day after surgery were significantly lower in group BR than in group R. The duration of motor block was significantly prolonged in group BR . The frequency of rescue analgesic administration and the sleep disturbance rate were significantly lower in group BR . There was no difference in postoperative nausea/vomiting between the two groups . Conclusions Betamethasone added to local anesthetic in interscalene brachial plexus block improved postoperative pain after arthroscopic rotator cuff repair , and betamethasone prolonged the duration of analgesia by almost 6 h . Trial registration University Hospital Medical Information Network Center Clinical Trials Registration System ( UMIN000012899 ) BACKGROUND Interscalene brachial plexus block ( ISB ) provides excellent , but time-limited analgesia . Dexamethasone added to local anaesthetics prolongs the duration of a single-shot ISB . However , systemic glucocorticoids also improve postoperative analgesia . The hypothesis was tested that perineural and i.v . dexamethasone would have an equivalent effect on prolonging analgesic duration of an ISB . METHODS We performed a prospect i ve , double blind , r and omized , placebo-controlled study . Patients presenting for arthroscopic shoulder surgery with an ISB were r and omized into three groups : ropivacaine 0.5 % ( R ) ; ropivacaine 0.5 % and dexamethasone 10 mg ( RD ) ; and ropivacaine 0.5 % with i.v . dexamethasone 10 mg ( RDiv ) . The primary outcome was the duration of analgesia , defined as the time between performance of the block and the first analgesic request . St and ard hypothesis tests ( t-test , Mann-Whitney U-test ) were used to compare treatment groups . The primary outcome was analysed by Kaplan-Meier survival analysis with a log-rank test and Cox 's proportional hazards regression . RESULTS One hundred and fifty patients were included after obtaining ethical committee approval and patient informed consent . The median time of a sensory block was equivalent for perineural and i.v . dexamethasone : 1405 min ( IQR 1015 - 1710 ) and 1275 min ( IQR 1095 - 2035 ) for RD and RDiv , respectively . There was a significant difference between the ropivacaine group : 757 min ( IQR 635 - 910 ) and the dexamethasone groups ( P<0.0001 ) . CONCLUSIONS I.V. dexamethasone is equivalent to perineural dexamethasone in prolonging the analgesic duration of a single-shot ISB with ropivacaine . As dexamethasone is not licensed for perineural use , clinicians should consider i.v . administration of dexamethasone to achieve an increased duration of ISB Purpose The aim of this study was to evaluate the effects and safety of a sleep aid for postoperative analgesia in patients undergoing arthroscopic rotator cuff repair . Material s and Methods Seventy-eight patients were prospect ively assigned to either the zolpidem group ( multimodal analgesia+zolpidem ; 39 patients ) or the control group ( multimodal analgesia ; 39 patients ) . Self-rated pain levels were assessed twice a day using a visual analog scale ( VAS ) . The need for additional rescue analgesic , duration of functional recovery , and adverse effects were assessed for the first 5 days after surgery . Results The mean number of times that additional rescue analgesic was required during 5 days after surgery was 2.1±2.0 in the zolpidem group and 3.3±2.8 in the control group , a significant difference . There were no significant differences between the two groups in mean VAS pain scores during the first 5 days after surgery , although the zolpidem group had lower VAS pain scores than the control group . Additionally , there were no significant differences in duration of functional recovery and adverse effects between the two groups . Conclusion The use of zolpidem for analgesia after arthroscopic rotator cuff repair provided a significant reduction in the need for rescue analgesic without increasing adverse effects . Nevertheless , mean VAS pain scores during the first 5 days after surgery did not differ between the zolpidem group and the control group BACKGROUND This prospect i ve , r and omized study tested the hypothesis that a reduced dose continuous interscalene regimen incorporating a low background infusion with m and atory boluses would provide similar shoulder surgery analgesia compared with a dose regimen incorporating a conventional higher background infusion . METHODS After rotator cuff surgery , patients received via an interscalene catheter , one of two elastomeric pumps , each having a 5 ml per 60 min bolus function and a 2 ml h⁻¹ ( n=38 ) or 5 ml h⁻¹ ( n=43 ) ropivacaine 2 mg ml⁻¹ infusion . Boluses commenced from the onset of pain and continued for > 48 h as required ( pro re nata , PRN ) up to every hour for a numerical rating pain score ( NRPS , 0 - 10 ) > 2 . Group 2 ml h⁻¹ received m and atory 6 hourly boluses irrespective of the NRPS . Rescue tramadol was available . Patients were question ed on postoperative days 1 and 2 for treatment effectiveness and side-effects . RESULTS Postoperative pain was similar between the groups [ Group 2 ml h⁻¹ day 2 median ( IQR ) ( 95 % confidence interval of the mean ) worst movement pain=4 ( 1 - 5 ) ( 2.8 - 4.7 ) vs 4 ( 2 - 5 ) ( 3.1 - 4.6 ) , P=0.99 ] , as were night awakenings and tramadol consumption . Numerically rated numbness and weakness were similar between the groups ; however , nine patients ( 21 % ) in the 5 ml h⁻¹ group vs one ( 3 % ) in the 2 ml h⁻¹ group required a temporary infusion cessation due to side-effects ( predominantly h and numbness ) ( P=0.02 ) . CONCLUSIONS Continuous interscalene ropivacaine 0.2 % 2 ml h⁻¹ with m and atory 6 hourly ( and PRN ) boluses provides similar analgesia after rotator cuff repair but with reduced side-effects compared with 5 ml h⁻¹ with PRN only boluses BACKGROUND The influence of the muscular response elicited by neurostimulation on the success rate of interscalene block using a catheter ( ISC ) is unknown . In this investigation , we compared the success rate of ISC placement as indicated by biceps or deltoid , triceps , or both twitches . METHODS Three hundred ( ASA I-II ) patients presenting for elective arthroscopic rotator cuff repair were prospect ively r and omized to assessment by biceps ( Group B ) or deltoid , triceps , or both twitches ( Group DT ) . All ISCs were placed with the aid of neurostimulation . The tip of the stimulating needle was placed after disappearance of either biceps or deltoid , triceps , or both twitches at 0.3 mA. The catheter was advanced 2 - 3 cm past the tip of the needle and the block was performed using 40 ml ropivacaine 0.5 % . Successful block was defined as sensory block of the supraclavicular nerve and sensory and motor block involving the axillary , radial , median , and musculocutaneous nerves within 30 min . RESULTS Success rate was 98.6 % in Group DT compared with 92.5 % in Group B ( 95 % confidence interval 0.01 - 0.11 ; P<0.02 ) . Supplemental analgesics during h and ling of the posterior part of the shoulder capsule were needed in two patients in Group DT and seven patients in Group B. Three patients in Group B had an incomplete radial nerve distribution anaesthesia necessitating general anaesthesia . One patient in Group B had an incomplete posterior block extension of the supraclavicular nerve . No acute or late complications were observed . CONCLUSIONS Eliciting deltoid , triceps , or both twitches was associated with a higher success rate compared with eliciting biceps twitches during continuous interscalene block BACKGROUND A hyperosmolar irrigation solution has been reported to be safe and have potential benefits for use during shoulder arthroscopy in an animal model study . In this study , the clinical effects of a hyperosmolar solution were compared with a st and ard isotonic solution when used for shoulder arthroscopy . METHODS A prospect i ve , double-blind , r and omized controlled trial was performed to compare isotonic ( 273 mOsm/L ) and hyperosmolar ( 593 mOsm/L ) irrigation solutions used for arthroscopic rotator cuff repair . Primary outcomes focused on the amount of periarticular fluid retention based on net weight gain , change in shoulder girth , and pain . All patients were tracked through st and ard postsurgical follow-up to ensure no additional complications arose . Patients were contacted at 1 year to assess American Shoulder and Elbow Surgeon score , visual analog scale pain score , and the Single Assessment Numeric Evaluation shoulder scores RESULTS : Fifty patients ( n = 25/group ) were enrolled and completed the study . No statistically significant differences were noted between cohorts in demographics or surgical variables . The hyperosmolar group experienced significantly less mean weight gain ( 1.6 ± 0.82 kg vs. 2.25 ± 0.77 kg ; P = .005 ) , significantly less change in shoulder girth ( P < .05 ) , and a significantly lower immediate postoperative visual analog scale pain score ( P = .036 ) . At 1 year postoperatively , the differences between groups for American Shoulder and Elbow Surgeons , visual analog scale pain , and Single Assessment Numeric Evaluation were not significant ( P > .2 ) . CONCLUSION A hyperosmolar irrigation solution provides a safe and effective way to decrease periarticular fluid retention associated with arthroscopic rotator cuff surgery without any adverse long-term effects . Use of a hyperosmolar irrigation solution for shoulder arthroscopy has potential clinical benefits to surgeons and patients PURPOSE To compare the analgesic efficacy of 3-day continuous interscalene brachial plexus block versus a single-shot block for arthroscopic rotator cuff repair . METHODS Eighty-five patients scheduled for arthroscopic rotator cuff repair were r and omly assigned to either the single-shot group ( SSG ) or continuous interscalene brachial block group ( CG ) . Patients in the SSG received 2.5 mg/kg of 0.5 % bupivacaine up to 25 mL ; the CG received the same dose as a loading dose via catheter followed by an infusion of 0.125 % bupivacaine at 5 mL/h and a patient-controlled bolus of 5 mL hourly for 72 hours . Follow-up after discharge was with telephone calls over the next 3 days . Pain was measured on a visual analog scale . Also measured were sleep disturbance , number of opioid doses taken , adverse effects , and level of patient satisfaction . RESULTS The median rest pain scores on the 3 days of follow-up measured on a scale of 0 to 10 ( with 10 equal to greatest pain ) were 0 , 0 , and 3 in the CG compared with 4 , 4 , and 3 in the SSG ( P < .001 ) for days 1 , 2 , and 3 , respectively . The median maximum scores were 2 , 2 , and 4 in the CG compared with 8 , 7 , and 6 in the SSG ( P < .001 ) for the same time period . CONCLUSIONS A 3-day continuous interscalene brachial plexus block provides better analgesia than a single-shot block . Sleep patterns were better , and less opioid was needed after arthroscopic rotator cuff repair in patients given a continuous plexus block . LEVEL OF EVIDENCE Level I , prospect i ve r and omized study Purpose The aim of this study was to compare the effect of postoperative pain control and adverse effects of intravenous patient-controlled analgesia ( IV PCA ) and multimodal shoulder injection after arthroscopic rotator cuff repair . Methods Seventy patients scheduled for elective arthroscopic rotator cuff repair were prospect ively r and omized to receive either IV PCA or multimodal shoulder injections . Postoperative pain , nausea , vomiting , and other adverse effects were assessed at 2 , 6 , 12 , 24 , and 48 h after surgery . Use of rescue analgesics and antiemetics , level of satisfaction , and cost for both modalities were recorded . Results Pain was better controlled in the multimodal shoulder injection group at 2 h postoperatively ( P = 0.001 ) . However , the use of additional analgesics was greater in the multimodal shoulder injection group during 12–48 h after surgery ( P < 0.001 ) . The incidence of nausea within 12–24 h after surgery in the multimodal shoulder injection group ( 5.7 % ) was less significant compared with that in the IV PCA group ( 31.4 % , P = 0.012 ) , but no difference in overall incidence of the use of rescue antiemetics was observed between the groups ( n.s . ) . No differences in adverse effects were noted between the groups . Patient satisfaction also showed no differences ( n.s . ) . Costs required for both modalities were $ 20.3 for the multimodal shoulder injection and $ 157.8 for the IV PCA . Conclusions Multimodal shoulder injection is a safe and effective modality for management of pain after arthroscopic rotator cuff repair . Considering the expense and need of special devices for IV PCA , multimodal shoulder injection may be an effective and safe alternative to IV PCA for postoperative analgesia after arthroscopic rotator cuff repair . Level of evidence R and omized , controlled trial , Level Purpose : Hypotensive anesthesia is crucial during arthroscopic shoulder surgery to reduce bleeding and allow for clear visibility . The aim of this study was to compare the clinical efficacy of continuous infusion of remifentanil , nicardipine , and remifentanil plus nicardipine to control hypotensive anesthesia in arthroscopic shoulder surgery . Methods : For this study , we enrolled 45 consecutive patients who were scheduled to have arthroscopic rotator cuff repair surgery and r and omly allocated them into remifentanil ( group R , n = 15 ) , nicardipine ( group N , n = 15 ) , and remifentanil plus nicardipine ( group RN , n = 15 ) groups . During the surgeries , these drugs were administered with continuous infusion . We analyzed the mean arterial pressure ( MAP ) and heart rate during surgery , stay time in the recovery room , visual analogue scale ( VAS ) scores , use of antiemetics in the recovery room , and postoperative blood urea nitrogen and creatinine changes . Results : The VAS score in the recovery room was higher for group R ( mean 5.6 , SD 1.4 ) than for groups N ( mean 3.9 , SD 0.9 ) and RN ( mean 4.0 , SD 1.1 ; p = 0.000 ) . There were no statistical differences regarding other clinical variables among the three groups ( all p > 0.05 ) except for MAP at 120 min of surgery between groups N and RN ( N : 84.67 ( SD 10.7 ) mmHg , RN : 65.4 ( SD 9.2 ) mmHg , p = 0.027 ) . Conclusion : The continuous infusion of remifentanil plus nicardipine appeared to be advantageous for maintaining hypotensive anesthesia until 120 min of arthroscopic shoulder surgery without rebound pain in a postanesthesia care unit Purpose This study was carried out to evaluate the postoperative analgesic effects of preoperative intravenous flurbiprofen in patients undergoing arthroscopic rotator cuff repair under general anesthesia . Methods We studied 44 patients who underwent an elective arthroscopic rotator cuff repair in a prospect i ve , r and omized , and double-blind fashion . The patients were divided into two groups . Group A ( n = 22 ) received lipid emulsion 0.1 ml·kg−1 as a placebo , and group B ( n = 22 ) received flurbiprofen 1 mg·kg−1 before the surgery . Intralipid or flurbiprofen was given intravenously 5 min before the surgery . General anesthesia was maintained with sevoflurane and nitrous oxide , and 10 ml of 0.75 % ropivacaine was administered intraarticularly at the end of the surgery . Postoperative analgesia was supplied with intravenous 0.1 mg buprenorphine according to the patient ’s dem and . The effectiveness of flurbiprofen ’s analgesic effect was measured by a visual analog scale ( VAS ) and by the amount of buprenorphine consumption at 0.5 , 1 , 2 , 4 , 6 , 12 , and 24 h after the surgery . Time to the first analgesic was also recorded . Results VAS in group B was significantly ( P < 0.01 ) lower than that in group A during the first 6 h postoperatively . The amount of buprenorphine consumption in group B was also significantly ( P < 0.01 ) less than that in group A within the first 2 h postoperatively . The time to first analgesic request in group B was significantly ( P < 0.01 ) longer than that in group A. Conclusion These results show that preoperative intravenous flurbiprofen facilitates the analgesic effect in the early postoperative period after arthroscopic rotator cuff repair BACKGROUND : We performed this r and omized trial to compare the recovery profile of patients receiving single injection ( SISB ) and continuous interscalene brachial plexus block ( CISB ) or general anesthesia ( GA ) for arthroscopic rotator cuff repair surgery through the first postoperative week . Our primary hypothesis was that the highest pain numeric rating scale ( NRS ) ( worst pain score ) at the end of the study week would be lower for patients in the CISB group than for patients in the SISB or GA groups . METHODS : Seventy-one patients scheduled for elective outpatient arthroscopic rotator cuff repair were enrolled . CISB patients received 20 mL of 0.5 % ropivacaine as a bolus through a catheter , whereas SISB patients received the same injection volume through a needle . CISB patients received an infusion of 0.2 % ropivacaine at 5 mL/h with a patient-controlled bolus of 5 mL hourly for 48 hours . GA-only patients received a st and ardized general anesthetic . Postoperative highest NRS pain scores through the first postoperative week , time-to-first pain , analgesic consumption , fast-tracked postoperative anesthesia care unit ( PACU ) bypass rate , length of PACU stay , time-to-discharge home , total hours of sleep , and related adverse effects were recorded in the PACU and at home on postoperative days 1 , 2 , 3 , and 7 . RESULTS : No patient in the CISB or SISB groups reported a NRS ≥1 or required analgesics while in the PACU . While most patients in the CISB and SISB groups were fast-tracked to PACU discharge , no patient in the GA group was fast-tracked ( & KHgr;2 P = 0.003 ) . Length of stay in the PACU was significantly shorter for the CISB and SISB groups than for the GA group ( 20 ± 31 , 30 ± 42 , and 165 ± 118 minutes , respectively ( CISB vs GA , P < 0.001 ; SISB vs GA , P < 0.001 ) , and time-to-discharge home was significantly shorter when compared with the GA group . Time to first pain report was longer in the CISB group . Mean NRS scores were lower for patients in the CISB group than in the SISB and GA groups on postoperative days 1 and 2 , and use of narcotics ( doses ≥1 ) was lower until postoperative day 3 . Patients who received CISB slept significantly longer than patients who received SISB or GA ( P < 0.01 ) during the first 48 hours postoperatively . By the end of the study week , 26 % of patients in the CISB group , 83 % in the SISB group , and 58 % of GA patients reported NRS ≥4 ( both P-values ⩽ 0.05 ) . CONCLUSION : The analgesic benefits of CISB found in the PACU and immediately after discharge extend through the intermediate recovery period ending on postoperative day 7 Background : The exact role of platelet-rich plasma ( PRP ) in rotator cuff tendon reconstruction remains unclear . Purpose /Hypothesis : This study investigated whether an intraoperative pure PRP injection , compared with a local anesthetic injection , improves patient-reported outcomes at 3 and 6 months after arthroscopic rotator cuff repair . The hypothesis was that pure PRP improves patient-reported outcomes ( Oxford Shoulder Score [ OSS ] ) at 3 and 6 months after surgery and has the same pain-reducing effect compared with a postoperative subacromial local anesthetic ( ropivacaine ) injection . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : Between January 2011 and November 2012 , a total of 120 patients who underwent arthroscopic double-row repair of a supraspinatus tendon rupture were r and omized to receive either pure PRP by an injection at the footprint ( PRP group ; n = 60 ) or ropivacaine injected in the subacromial region ( control group ; n = 60 ) . Seventy-eight percent of patients had other concomitant tears . All patients , surgeons , and follow-up investigators were blinded . Clinical parameters and various outcome scores ( Constant-Murley shoulder score ; OSS ; patient American Shoulder and Elbow Surgeons score ; quick Disabilities of the Arm , Shoulder and H and score ; EuroQol 5 dimensions ) were documented preoperatively and at 3 , 6 , and 24 months postoperatively . The repair integrity was assessed by magnetic resonance imaging or ultrasound at 24 months . Furthermore , a pain diary was completed within the first 10 postoperative days , and adverse events were recorded . Group outcome differences were analyzed using t tests , Fisher exact tests , and mixed models . Results : The final follow-up rate was 91 % . An associated tear of the subscapularis tendon was diagnosed in 23 % of PRP-treated patients and 36 % of control patients . Three months after surgery , the mean ( ±SD ) OSS was 32.9 ± 8.6 in PRP-treated patients and 30.7 ± 10.0 in control patients ( P = .221 ) . No significant differences were noted for other outcome parameters as well as at 6 and 24 months postoperatively . Smoking was a significant effect modifier . Pain for both groups decreased from postoperative day 1 to 10 without any significant group difference ( P = .864 ) . Six ( 12.2 % ) and 11 ( 20.8 % ) patients were diagnosed with a recurrent supraspinatus tendon defect in the PRP and control groups , respectively ( P = .295 ) . Twenty-two ( 40.7 % ) and 18 ( 30.5 % ) PRP-treated and control patients , respectively , experienced a local adverse event within 24 months ( P = .325 ) . Conclusion : Patients treated with pure PRP showed no significantly improved function at 3 , 6 , and 24 months after arthroscopic repair compared with control patients receiving ropivacaine ; however , a similar pain reduction was documented in both groups . The negative influence of smoking on the effect of pure PRP requires further investigation . Registration : NCT01266226 ( Clinical Trials.gov ) Background The aim of the study was to investigate whether a multimodal analgesia ( MMA ) protocol reduces postoperative pain and opioids consumption in patients undergoing arthroscopic rotator cuff repair . Methods Fifty-four patients scheduled for arthroscopic rotator cuff repair were r and omly assigned to either the MMA group or the control group . The primary outcome was visual analog scale ( VAS ) for pain . Secondary outcome measures included the time required for the VAS pain to reduce to that of a blood draw , ( PCA ) consumption , rescue morphine consumption , night awakening , and opioid-related side effects . Results The MMA group showed significantly less postoperative pain at postoperative 5 h , and 9 a.m. and 5 p.m. at 4th postoperative day ( P < 0.001 , = 0.040 , and 0.013 , respectively ) . MMA also shortened the time for postoperative pain to reduce down to the blood draw pain level from 5 days in the control group to 2 days in the MMA group . MMA also significantly reduced PCA consumption for up to 24 h postoperatively ( P = 0.038 ) and rescue morphine consumption during the first 6 h and between 48 and 60 h postoperatively ( P = 0.036 and 0.044 , respectively ) . No significant differences were observed between the MMA and control groups with respect to side effects . Conclusion The MMA protocol used in this study was found to reduce postoperative pain and opioid consumption during the acute postoperative period after arthroscopic rotator cuff repair without increasing side effects after arthroscopic rotator cuff repair Purpose Despite its effectiveness in other surgeries , studies on continuous epidural block in upper-extremity surgery are rare because of technical difficulties and potential complications . This study compared postoperative analgesic efficacy and safety of ultrasound-guided continuous interscalene brachial plexus block ( UCISB ) and fluoroscopy-guided targeted continuous cervical epidural block ( FCCEB ) in arthroscopic rotator cuff repair ( ARCR ) . Methods Seventy-five patients were r and omly and equally assigned to groups FCCEB ( 0.2 % ) , UCISB75 ( 0.75 % ) , and UCISB20 ( 0.2 % ) according to the initial ropivacaine dose ( 8 ml ) . The background infusion ( 0.2 % ropivacaine at 5 ml/h ) , bolus ( 3 ml of 0.2 % ropivacaine ) , and lockout time ( 20 min ) were consistent . Respiratory effects [ respiratory discomfort ( modified Borg scale ) , ventilatory function , and hemidiaphragmatic excursion ( ultrasound ) ] , analgesic quality [ pain severity at rest and motion attempt ( VAS-R and -M ) , number of boluses , analgesic supplements , and sleep disturbance ] , neurologic effects , procedural discomfort , satisfaction , and adverse effects were evaluated preprocedurally and up to 72 h postoperatively . Results FCCEB caused less respiratory depression and sensorimotor block , but had less analgesic efficacy than UCISBs ( P < 0.05 ) . FCCEB caused nausea , vomiting , and dizziness more frequently ( P < 0.05 ) and had lower patient satisfaction than UCISBs ( P < 0.05 ) . UCISB75 can cause severe respiratory distress in patients with lung disorders . Other variables were not significantly different between the groups . Conclusions UCISB20 may provide superior postoperative analgesia and is the most recommendable postoperative analgesic method in ARCR.Level of evidence R and omized controlled trials , Therapeutic study , Level The purpose of this study was to compare early postoperative outcomes between arthroscopic and mini-open repair for rotator cuff tears smaller than 3 cm to determine whether arthroscopic repair causes less postoperative pain and allows for faster recovery of range of motion . Sixty patients scheduled for rotator cuff repair were r and omized to either an arthroscopic repair group ( 30 patients ) or a mini-open repair group ( 30 patients ) . Pain level , range of motion , shoulder stiffness , and complications were compared between the 2 groups from immediately postoperatively to 6 months postoperatively . Although no statistically significant difference was found in mean visual analog scale pain scores between the 2 groups during the 6 months postoperatively , mean visual analog scale pain score was significantly lower in the arthroscopic repair group compared with the mini-open repair group at postoperative days 1 and 2 ( P=.02 and P=.04 , respectively ) . No significant difference existed in postoperative range of motion , duration of rehabilitation , shoulder stiffness , or complications between the 2 groups ; however , the use of additional analgesics in the arthroscopic repair group was significantly lower than in the mini-open repair group ( P=.03 ) . Arthroscopic and mini-open repair had equivalent clinical outcomes in the early postoperative period . The hypothesis that arthroscopic repair would cause less postoperative pain and allow faster recovery of range of motion in the early postoperative period compared with mini-open repair was not supported PURPOSE To compare the efficacy of suprascapular nerve block ( SSB ) and interscalene block ( ISB ) as postoperative analgesia within the first 24 hours after arthroscopic supraspinatus and /or infraspinatus tendon repair . METHODS A single-blind , r and omized controlled study was performed between 2013 and 2014 . The inclusion criteria were arthroscopic supraspinatus and /or infraspinatus tendon repair confirmed intraoperatively , with or without associated procedures , and informed consent . The exclusion criteria were a previously operated shoulder , repair of the subscapularis tendon , and an allergy to local anesthetics . ISB was performed under ultrasound guidance by an anesthesiologist , whereas SSB was performed based on specific anatomic l and marks by a surgeon . The primary evaluation criterion was mean shoulder pain score during the first postoperative 24 hours assessed on a visual analog scale by the patient . The secondary criteria were complications of locoregional anesthesia , the use of analgesics in the recovery room ( the first 2 hours ) until postoperative day 7 , and pain ( visual analog scale ) during the first week . Forty-four patients were needed for this noninferiority study . An institutional review board approved the study . RESULTS Seventy-four patients were r and omized , and 59 met the intraoperative inclusion criteria . Six patients were excluded ( 1 for pneumothorax after ISB , 1 for unsuccessful SSB , and 4 for incomplete question naires ) . None of the patients were lost to follow-up . There was no significant difference between the SSB and ISB groups in mean pain score for the first 24 hours ( P = .92 ) or the first 7 days ( P = .05 ) . However , there was significantly less pain in the ISB group in the recovery room ( P = .01 ) . Consumption of analgesics was comparable between the groups , but the SSB group took significantly more morphine in the recovery room . CONCLUSIONS In this prospect i ve , r and omized controlled study , SSB was as effective as ISB for mean pain control within the first 24 hours but ISB was more effective in relieving pain in the recovery room after arthroscopic supraspinatus and /or infraspinatus tendon repair . LEVEL OF EVIDENCE Level I , therapeutic , r and omized controlled study PURPOSE The purpose of our study was to compare the effectiveness of subacromial bupivacaine infusion and a transdermal fentanyl patch in the treatment of postoperative pain after arthroscopic shoulder surgery . METHODS Sixty patients with rotator cuff disease scheduled for elective arthroscopic shoulder surgery were enrolled in the study . For the treatment of postoperative pain , 30 patients constituted group F and received a 12.0-μg/h fentanyl patch for 72 hours and saline solution infusion in a subacromial manner at the rate of 4 mL/h . The remaining 30 patients constituted group B and received a placebo patch and an infusion of 2.5-mg/mL bupivacaine in a subacromial manner for 72 hours . The primary outcome measure was the postoperative numerical rating scale pain score . The consumption of opioids , ibuprofen , and acetaminophen was also recorded . The Constant scores and general recovery were followed up until the 90th postoperative day . RESULTS There was no statistically significant difference in the numerical rating scale scores ( P = .60 ) between the groups . No differences in the use of rescue analgesic were observed except that the patients receiving bupivacaine used more ibuprofen ( median , 1,200 mg v 600 mg ) during the day of surgery ( P = .042 ) . No difference was found in general recovery between the groups . CONCLUSIONS A fentanyl patch delivering 12-μg/h fentanyl offers an easy and safe treatment option as a part of multimodal analgesia with few adverse effects in the treatment of postoperative pain in a carefully selected patient group after arthroscopic shoulder surgery . LEVEL OF EVIDENCE Level I , r and omized controlled trial Purpose Ultrasound (US)-guided continuous interscalene brachial plexus block ( CBPB ) is known to provide effective pain relief for arthroscopic rotator cuff repair . This study was conducted to compare analgesic efficacy and forearm muscle tone of the basal infusion rate and bolus dose of 0.2 % ropivacaine for US-guided CBPB with intravenous patient-controlled analgesia ( IV-PCA ) . Methods In a prospect i ve trial , 99 patients scheduled to undergo arthroscopic rotator cuff repair were divided into three groups . In groups A and B , an US-guided 17-gauge Tuohy needle was inserted into the interscalene brachial plexus . A loading dose of 10 ml 0.2 % ropivacaine was administered via the needle . A 19-gauge perineural catheter was then inserted through the needle and advanced to a depth of 1.5 cm beyond the needle tip between the C5 and C6 nerve trunks . After surgery , groups A and B received a continuous infusion of 0.2 % ropivacaine at 4 or 0 ml/h , a bolus of 0 or 4 ml , and a lockout time of 60 min through the catheter , respectively . Group C received IV-PCA . Pain scores and the forearm muscle tone of patients were compared using a numeric rating scale ( NRS ) , rates of patients taking supplementary opioid analgesics , and manual muscle test ( MMT ) scoring . Results The NRS scores and rate of patients taking supplementary opioid analgesics in groups A and B were lower than those in group C after surgery . Groups A and B showed similar clinical efficacy . There were no significant differences in MMT scoring among the three groups . Conclusions The bolus dose of 0.2 % ropivacaine using US-guided CBPB would provide equivalent analgesic efficacy comparable with the basal infusion and motor weakness comparable with IV-PCA after arthroscopic rotator cuff repair INTRODUCTION Although arthroscopic rotator cuff repair is minimally invasive , there is still considerable postoperative pain , especially during the first 48 hours . The present study assessed the short-term efficacy and safety of multimodal analgesic ( MMA ) injection associated to corticosteroids in arthroscopic rotator cuff tear surgery . MATERIAL AND METHOD A single-center prospect i ve r and omized study included 50 patients undergoing arthroscopic rotator cuff tear surgery . The study group received subacromial injection of a mixture of morphine , ropivacaine and methylprednisolone associated to intra-articular injection of morphine plus methylprednisolone ; the control group received only isotonic saline . All patients had had 24 hours self-administered morphine associated to st and ard analgesia . Postoperative data were recorded at 30 minutes and 1 , 2 , 4 , 6 , 12 , 18 and 24 hours : pain intensity , morphine intake and side effects , and also time to first morphine bolus and additional analgesic intake . Constant , ASES and SST functional scores were recorded at 3 months . RESULTS Postoperative pain was significantly less intense in the MMA group than in controls at 30 min , H1 , H4 , H6 , H12 , H18 and H24 ( P<0.05 ) . A rebound at D10 occurred in both groups . During the first 24 hours , MMA significantly reduced cumulative resort to morphine ( P<0.05 at H1/2 , P<0.001 at H1 - 24 ) . Mean time to first bolus was significantly longer in the MMA group ( 71.6 vs. 33 min ; P<0.05 ) . The rate of opioid-related side effects was similar between groups . At last follow-up , functional scores were similar between groups . There were no cases of infection or delayed skin healing . CONCLUSION MMA associated to corticosteroids after arthroscopic rotator cuff tear surgery provided immediate benefit in terms of analgesia and morphine sparing , without apparent risk of infection . The practice is presently little known in France and deserves longer-term assessment , especially as regards functional rehabilitation and tendon healing . LEVEL OF EVIDENCE 2 BACKGROUND Interscalene brachial plexus block ( ISBPB ) provides excellent analgesia after rotator cuff surgery but is associated with diaphragm dysfunction . In this study , ISBPB with 20 mL of 0.125 % or 0.25 % bupivacaine were compared to assess the effect on diaphragm function , oxygen saturation , pain control , opioid requirements , and patient satisfaction . MATERIAL S AND METHODS In this prospect i ve , r and omized , double-blind study , 30 adults undergoing outpatient arthroscopic rotator cuff repair were enrolled to receive ultrasound-guided interscalene brachial plexus catheter placement with 20 mL of 0.125 % ( n = 15 ) or 0.25 % bupivacaine ( n = 15 ) . Diaphragm function and oxygen saturation were assessed before ISBPB placement and on discharge from the postanesthesia care unit . Postoperative pain scores , opioid requirements , and patient satisfaction were compared . RESULTS Diaphragm function and oxygen saturation were superior in the low concentration group . Absent or paradoxic motion of the diaphragm was present in 78 % of the 0.25 % group compared with 21 % of patients in the 0.125 % group ( P = .008 ) . Oxygen saturation decreased 4.3 % in the 0.25 % group compared with a decrease of 2.6 % in the 0.125 % group ( P = .04 ) . Pain scores averaged 1 of 10 in the 0.25 % group and 0 of 10 in the 0.125 % group ( P = .02 ) . Opioid requirements and patient satisfaction were not different between the two groups . CONCLUSIONS In this r and omized , double-blind comparison of ISBPB performed with 20 mL of 0.125 % or 0.25 % bupivacaine , diaphragm function and oxygen saturation were superior in patients treated with more dilute bupivacaine . Furthermore , there were no clinical ly significant differences in pain scores , and no statistically significant differences in opioid requirements and patient satisfaction BACKGROUND Local anesthetic administered directly to the operative site by slow infusion has become a popular supplementary pain management strategy following rotator cuff surgery , but it is expensive and there is little conclusive evidence that it provides additional benefits . The purpose of this study was to determine the effectiveness and safety of ropivacaine infusion following arthroscopic or mini-incision rotator cuff surgery . METHODS We performed a r and omized , participant and outcome assessor-blinded , placebo-controlled trial . Participants , stratified by operative procedure ( either arthroscopic decompression or rotator cuff repair ) , were given preemptive 1 % ropivacaine ( 20 mL ) and intraoperative intravenous parecoxib ( 40 mg ) and were r and omly assigned to 0.75 % ropivacaine or placebo by elastomeric pump at 5 mL/hr . Pain at rest was reported on a verbal analogue scale at fifteen , thirty , and sixty minutes and at two , four , eight , twelve , eighteen , and twenty-four hours . The use of alternative analgesia , delay in discharge , and adverse events , including development of stiff painful shoulder , infection , and leakage , were also assessed . RESULTS Eighty-eight participants received arthroscopic decompression ( forty-three in the placebo arm and forty-five in the ropivacaine arm ) and seventy received rotator cuff repair ( thirty-five participants in each treatment arm ) . Compared with placebo , ropivacaine infusion result ed in a significant but clinical ly unimportant improvement in average pain in the first twelve hours following both procedures ( the average pain score was 1.62 and 2.16 for the ropivacaine and placebo arms , respectively , in the arthroscopic decompression group and 2.12 and 2.82 in the rotator cuff repair group , with a pooled difference between groups of 0.61 ; 95 % confidence interval , 0.22 to 1.01 ; p = 0.003 ) . When adjusted for opioid use , the pooled difference between groups was 0.49 ( 95 % confidence interval , 0.12 to 0.86 ; p = 0.009 ) . No difference was detected between groups with regard to the maximum pain in the first twelve hours or the average or maximum pain in the second twelve hours , with or without adjustment for opioid use , and no difference was found between groups with regard to the amount of oral analgesia used . No difference was detected between groups with regard to the prevalence of nausea and vomiting , catheter leakage , delayed discharge , or stiff painful shoulder , and no participant in either group had a postoperative infection develop . CONCLUSIONS We found minimal evidence to support the use of ropivacaine infusion for improving outcomes following rotator cuff surgery in the setting of preemptive ropivacaine and intraoperative parecoxib OBJECTIVES Arthroscopic rotator cuff surgery can result in severe postoperative pain . We compared a continuous subacromial infusion to a continuous interscalene block with levobupivacaine for patients undergoing arthroscopic rotator cuff surgery . METHODS Sixty patients were r and omized to two groups : 1 ) interscalene block with 0.5 % levobupivacaine ( 30 mL ) followed by a postoperative subacromial infusion : 0.125 % levobupivacaine 5 mL/h basal infusion , 5 mL bolus dose and a 20 min lockout time or ; 2 ) interscalene block with 0.5 % levobupivacaine ( 30 mL ) followed by a postoperative interscalene infusion : 0.125 % levobupivacaine 5 mL/h basal infusion , 5 mL bolus dose and a 20 min lockout time . Infusions were maintained for 48 hours . RESULTS The VAS scores in the postanesthesia care unit and at 4 h were not different . The VAS scores at 8 , 12 , 24 , 36 and 48 h were lower than 4 in both groups ; but they were significantly lower in the interscalene group . Additional analgesic requirements were lower in the interscalene group ( 16.6 % vs 53.3 % , p<0.05 ) . Patients ' satisfaction was higher in the interscalene group ( 9.4±0.8 vs 8±1.2 , p<0.01 ) . One patient had a toxicity related to interscalene block but ; there was no complication related to subacromial catheters . CONCLUSION This study demonstrates that subacromial infusions , although provided good postoperative analgesia , are not as effective as interscalene infusions and additional analgesics should be prescribed when subacromial infusions are started . Subacromial infusions could be considered as an alternative in case of any contraindication to interscalene block PURPOSE The aim of this study was to compare the results of ultrasonographically guided axillary nerve block ( ANB ) combined with suprascapular nerve block ( SSNB ) with those of SSNB alone on postoperative pain and satisfaction within the first 48 hours after arthroscopic rotator cuff repair . METHODS Forty-two patients with rotator cuff tears who had undergone arthroscopic rotator cuff repair were enrolled in this study . Among them , 21 patients were r and omly allocated to group 1 and received both SSNB and ANB with 10 mL ropivacaine . The other 21 patients were allocated to group 2 and received SSNB with 10 mL 0.75 % ropivacaine and ANB with 10 mL saline . Visual analog scale ( VAS ) pain score , patient satisfaction ( SAT ) , and lateral pain index ( LPI ) was checked at 1 , 3 , 6 , 12 , 18 , 24 , 36 , and 48 hours postoperatively . RESULTS Group 1 showed a significantly lower mean VAS score at postoperative 1 , 3 , 6 , 12 , 18 , and 24 hours compared with group 2 ( 5.1 < 7.6 , 4.4 < 6.3 , 3.7 < 5.3 , 3.2 < 4.5 , 2.7 < 4.0 , and 2.7 < 3.4 , respectively ) . A significantly high mean SAT and low mean LPI was observed in group 1 at postoperative 1 , 3 , 6 , 12 , 18 , 24 , and 36 hours ( 4.9 > 2.4 , 5.9 > 3.7 , 6.3 > 5.0 , 6.8 > 5.7 , 7.3 > 6.2 , 7.5 > 6.6 , and 7.7 > 7.0 , respectively ) , ( 1.1 < 3.0 , 0.8 < 2.5 , 0.7 < 2.0 , 0.7 < 1.6 , 0.6 < 1.3 , 0.6 < 1.0 , and 0.4 < 0.7 , respectively ) . The frequency of rebound pain decreased in group 1 compared with group 2 ( P = .032 ) . In addition , rebound phenomenon showed a correlation with ANB on univariate logistic regression ( P = .034 ; odds ratio , 0.246 ) . CONCLUSIONS Ultrasonographically guided ANB combined with SSNB in arthroscopic rotator cuff repair showed an improved mean VAS in the first 24 hours after surgery compared with SSNB alone . The mean SAT and LPI of the combined blocks were better than those of the single block within the first 36 hours . Ultrasonographically guided ANB combined with SSNB also decreased the rebound phenomenon . LEVEL OF EVIDENCE Level I , r and omized controlled trial OBJECTIVE This study aims to assess diaphragmatic excursion and measure pulmonary functions as measures of the degree to which the phrenic nerve is blocked after ISB with two different concentrations of ropivacaine : 0.2 % and 0.1 % . DESIGN R and omized , double-blinded study . SETTING AND PATIENTS Ambulatory surgical facility . SUBJECTS Fifty patients undergoing shoulder arthroscopy for rotator cuff repair . METHODS Patients were r and omized to receive ultrasound-guided ISB with 20 mL of either 0.2 % or 0.1 % ropivacaine . Diaphragmatic excursion was measured using M-mode ultrasound . Pulmonary functions were assessed by portable spirometer . Additional outcome data included oxygen saturation in post-anesthesia care unit ( PACU ) , pain scores , quality of recovery scores ( QOR ) , and opioid consumption over 72 hour period after surgery . RESULTS Forced vital capacity ( FVC ) was significantly reduced 30 minutes after block placement and in PACU in the 0.2 % group when compared with the 0.1 % group ( P = 0.04,P = 0.03 , respectively ) . Forced expiratory volume ( FEV1 ) was also significantly decreased in the 0.2 % group in PACU when compared with the 0.1 % group ( P = 0.04 ) . There were no significant differences in pain scores , length of stay , and total opioid consumption in PACU . Patients who received 0.2 % ropivacaine had a longer block duration ( 18 vs 11.9 hours , P = 0.04 ) and used less opioid in the 72 hours after surgery ( 55 mg vs 102 mg codeine equivalents , P = 0.02 ) , when they were compared to their counterparts who received 0.1 % for their block . CONCLUSION 0.1 % ropivacaine may impair pulmonary function less than 0.2 % ropivacaine . The clinical significance of these differences needs to be further studied Background Results on the effectiveness of PRP supplementation in arthroscopic rotator cuff repair are conflicting , making it difficult to draw definitive conclusions . Methods This was a prospect i ve , r and omized , and double-blind study with two groups of 20 patients each ( PRP group and control group ) . Degenerative supraspinatus full-thickness tears grade C2–C3 were subjected to arthroscopic repair ; PRP supplementation was given to patients in the PRP group . The outcomes were assessed by DASH , Constant scales , and ultrasound before and 6 months after surgery . Pain measured by VAS was evaluated preoperatively and 7 and 30 days after surgery . Results The two groups did not differ significantly by age , sex , and dominance of the affected side . In all surgical procedures , a long head of the biceps tenotomy and single-row repair were performed . The preoperative VAS was 5.6 ± 2.4 in PRP group and 6.4 ± 1.5 in the control group ( p > 0.05 ) . The group supplemented with PRP reported a VAS significantly better in the first week ( 2.5 ± 1.9 vs 5.3 ± 2.1 , p < 0.05 ) and during the first month after surgery ( 1.5 ± 1.0 vs 3.2 ± 1.7 , p < 0.05 ) compared to the control group . The preoperative Constant and DASH scores were 39.95 ± 12 and 51 ± 15.2 , respectively , in the PRP group and 41 ± 11 ( p > 0.05 ) and 45 ± 12.6 ( p > 0.05 ) in the control group . The average Constant score improved significantly after 6 months to 81 ± 11.2 ( p < 0.05 ) in the PRP group and 78.5 ± 9 ( p < 0.05 ) in the control group . No differences were noted between the two groups ( p > 0.05 ) . The DASH score after 6 months was 17.4 ± 8 ( p < 0.05 ) for the treatment group ( the PRP group ) and 21 ± 8.4 ( p < 0.05 ) for the control group . No statistically significant differences were found as regards the DASH score in the two groups after 6 months ( p > 0.05 ) . The two groups showed no differences in the ultrasound evaluation after 6 months either . No re-ruptures occurred in either group . Conclusions PRP leads to a reduction in pain during a short-term follow-up . Pain reduction allows for a more rapid recovery of mobilization and improvement in functionality . Level of evidence R and omized controlled trial , Level of evidence , 1 Purpose To investigate the postoperative analgesic effect of subacromial patient-controlled analgesia ( SA-PCA ) with ropivacaine in comparison with intravenous patient-controlled analgesia ( IV-PCA ) after arthroscopic rotator cuff repair . Methods Sixty patients were prospect ively r and omized into one of the two types of analgesics for 48 h after the operation . In the SA-PCA group , patients received 0.5 % ropivacaine at a rate of 2 ml/h with a patient-controlled bolus dose of 2 ml . In the IV-PCA group , patients received intravenous patient-controlled analgesia . Pain relief was regularly assessed using visual analog scale ( VAS ) for 48 h , and side effects were noted . Results The postoperative pain VAS at 1 h after the operation was lower for the SA-PCA group ( 4.3 ± 2.7 ) than for the IV-PCA group ( 6.3 ± 2.6 , P = 0.009 ) . The frequency of requested bolus doses by patients in the IV-PCA ( 19 ± 19 ) was higher than in the SA-PCA ( 7 ± 10 , P = 0.04 ) . Rescue opioid or NSAID requirements were not different . More patients in the IV-PCA ( 17/30 ) experienced nausea than in the SA-PCA ( 7/30 , P = 0.03 ) . Patient satisfaction was higher in the SA-PCA than in the IV-PCA [ 6.7 ( 3–10 ) vs. 5.6 ( 0–8 ) , P = 0.04 ] . The mean total venous plasma concentration of ropivacaine at 8 and 24 h was below the maximum tolerated venous plasma concentration , and symptoms of systemic toxicity were not noted during 48 h in the SA-PCA . Conclusions The analgesic effect of subacromial patient-controlled analgesia with ropivacaine was better than intravenous analgesia during the immediate postoperative period with fewer side effects . Level of evidence Therapeutic study , Level Background : Rotator cuff tear is a common finding in patients with painful , poorly functioning shoulders . The surgical management of this disorder has improved greatly and can now be fully arthroscopic . Purpose : To evaluate clinical and radiological results of arthroscopic rotator cuff repair using 2 different techniques : single-row anchor fixation versus transosseous hardware-free suture repair . Study Design : R and omized controlled trial ; Level of evidence , 1 . Methods : Sixty-nine patients with rotator cuff tears were enrolled : 35 patients were operated with metal anchors and 34 with st and ardized transosseous repair . The patients were clinical ly evaluated before surgery , during the 28 days after surgery , and at least 1 year after the operation by the use of vali date d rating scores ( Constant score , QuickDASH , and numerical rating scale [ NRS ] ) . Final follow-up was obtained at more than 3 years by a QuickDASH evaluation to detect any difference from the previous follow-up . During the follow-up , rotator cuff integrity was determined through magnetic resonance imaging and was classified according to the 5 Sugaya categories . Results : Patients operated with the transosseous technique had significantly less pain , especially from the 15th postoperative day : In the third week , the mean NRS value for the anchor group was 3.00 while that for transosseous group was 2.46 ( P = .02 ) ; in the fourth week , the values were 2.44 and 1.76 , respectively ( P < .01 ) . No differences in functional outcome were noted between the 2 groups at the final evaluation . In the evaluation of rotator cuff repair integrity , based on Sugaya magnetic resonance imaging classification , no significant difference was found between the 2 techniques in terms of retear rate ( P = .81 ) . Conclusion : No significant differences were found between the 2 arthroscopic repair techniques in terms of functional and radiological results . However , postoperative pain decreased more quickly after the transosseous procedure , which therefore emerges as a possible improvement in the surgical repair of the rotator cuff . Registration : NCT01815177 ( Clinical Trials.gov identifier ) PURPOSE To compare the effects of a single-dose interscalene block and general anesthesia ( SISB/GA ) with the effects of GA only in the early postoperative period after arthroscopic rotator cuff repair by evaluating subjective pain visual analog scale scores and objective pain-related stress biomarkers . METHODS Patients refractory to conservative treatment of the affected shoulder were enrolled in this prospect i ve , r and omized endpoint study . Patients diagnosed with a rotator cuff tear ( 1 - 4 cm ) based on magnetic resonance imaging were included . Exclusion criteria were small ( < 1 cm ) and massive ( > 4 cm ) rotator cuff tears . Thirty-one patients each were r and omized into the SISB/GA and GA treatment groups . Preoperative pain scores were measured at 6:00 AM on the day of surgery , measured again at 1 and 6 hours postoperatively , and then every 6 hours until 3 days postoperatively . Blood sampling was performed to evaluate the stress biomarkers insulin , dehydroepi and rosterone sulfate , and fibrinogen preoperatively at 6:00 AM on the day of surgery and postoperatively at 18 , 42 , and 66 hours ( 6:00 AM on postoperative days 1 - 3 ) . RESULTS Pain scores were significantly decreased in the SISB/GA group ( 2.50 ± 0.94 ) versus the GA group ( 3.82 ± 1.31 ) on the day of surgery ( P < .001 ) , and especially at 6 hours postoperatively ( SISB/GA : 2.42 ± 1.43 ; GA : 4.23 ± 2.17 ; P < .001 ) . Insulin was decreased significantly in the SISB/GA group ( 10.55 ± 7.92 μU/mL ) versus the GA group ( 20.39 ± 25.60 μU/mL ) at 42 hours postoperatively ( P = .048 ) . There was no significant change in dehydroepi and rosterone sulfate or fibrinogen over time ( P > .05 ) . CONCLUSIONS After arthroscopic rotator cuff repair , an SISB effectively relieved pain on the day of surgery without any complications . In addition , insulin levels were significantly reduced at 42 hours postoperatively . LEVEL OF EVIDENCE Level I , prospect i ve r and omized controlled trial BACKGROUND The purpose of this study was to compare the effect of compressive cryotherapy ( CC ) vs. ice on postoperative pain in patients undergoing shoulder arthroscopy for rotator cuff repair or subacromial decompression . A commercial device was used for postoperative CC . A st and ard ice wrap ( IW ) was used for postoperative cryotherapy alone . METHODS Patients scheduled for rotator cuff repair or subacromial decompression were consented and r and omized to 1 of 2 groups ; patients were r and omized to use either CC or a st and ard IW for the first postoperative week . All patients were asked to complete a " diary " each day , which included visual analog scale scores based on average daily pain and worst daily pain as well as total pain medication usage . Pain medications were then converted to a morphine equivalent dosage . RESULTS Forty-six patients completed the study and were available for analysis ; 25 patients were r and omized to CC and 21 patients were r and omized to st and ard IW . No significant differences were found in average pain , worst pain , or morphine equivalent dosage on any day . CONCLUSION There does not appear to be a significant benefit to use of CC over st and ard IW in patients undergoing shoulder arthroscopy for rotator cuff repair or subacromial decompression . Further study is needed to determine if CC devices are a cost-effective option for postoperative pain management in this population of patients Objective This trial investigated postoperative analgesia in arthroscopic rotator cuff repair surgery patients under general anesthesia , associated with ultrasound-guided peri-plexus interscalene brachial plexus block ( US-IBPB ) , and compared single injection to elastomeric pump continuous infusion of local anesthetics . Complications associated to both techniques are described . Methods In this prospect i ve , quasi-r and omized controlled clinical trial , 68 adults scheduled for elective arthroscopic rotator cuff repair were assigned to receive Group 1 ( G1 = 41 ) US-IBPB with a 20 mL injection of 0.5 % peri-plexus ropivacaine , introduction of catheter , injection of 20 mL of 0.5 % ropivacaine through continuous catheter infusion of local anesthetic by elastomeric pump ( ropivacaine 0.2 % , infusion of 5 mL/h ) . In Group 2 ( G2 = 27 ) , US-IBPB , with a single peri-plexus injection of 40 mL ropivacaine 0.5 % . In both groups oral analgesics were prescribed , paracetamol 500 mg associated to codeine 30 mg for patients with VAS between 3 and 5 , and also oxycodone 20 mg for VAS ≥ 6 . The anesthesiology team was available through contact telephones and the patients received a table to complete in order to report pain intensity according to VAS , use of oral medication , and complications related to the catheter and pump , until the third postoperative day . Results The intensity of pain was higher on second day after surgery than on days 1 and 3 , in both groups confirmed by the ANOVA test ( p = 0.00006 ) Among the groups , G1 patients had lower pain intensity than G2 , ( p = 0.000197 ) . G2 patients presented greater pain intensity during all periods studied ( days 1 , 2 , and 3 ) than G1 patients . Postoperatively , G2 patients had higher consumption of rescue analgesics , nausea , and vomiting ( 40.74 % ) vs. G1 ( 5 % ) and dizziness ( 25.92 % ) . No patient with catheter and elastomeric pump ( G1 ) had complications regarding its insertion and maintenance during postoperative period . Conclusion The quality of analgesia for arthroscopic rotator cuff repair with peri-plexus US-IBPB and continuous infusion with elastomeric pump presented superior postoperative analgesia quality to single puncture IBPB on postoperative days 2 and 3 , with lower consumption of rescue opioids in this period BACKGROUND Arthroscopic rotator cuff repair ( ARCR ) provides excellent clinical outcomes but is often associated with significant postoperative pain . The use of intraoperative anesthesia in conjunction with multimodal pharmacologic strategies is a widely accepted approach for managing surgical pain and reducing opiate use . The purpose of this study was to determine whether using a combined field and suprascapular nerve block with liposomal bupivacaine ( LB ) in addition to an interscalene block would provide greater pain relief and a reduction in opiate consumption compared with an interscalene block alone . METHODS The study enrolled 50 patients with full-thickness rotator cuff tears undergoing primary ARCR surgery . Patients were r and omized to receive intraoperative LB ( n = 25 ) or not ( n = 25 ) and given postoperative " pain journals " to document visual analog scale pain scores and to track their daily opioid consumption during the first 5 postoperative days . RESULTS Patients in the LB group reported statistically and clinical ly lower pain scores during postoperative days 1 and 2 ( P < .0001 and P = .03 , respectively ) . In addition , patients in the LB group consumed significantly fewer narcotics than the control group during the 5-day period , demonstrating a 64 % reduction in total narcotic consumption ( P = .002 ) . CONCLUSION The findings of this study suggest that the addition of LB to multimodal anesthetic protocol s significantly reduces the acute perioperative pain experienced following rotator cuff repair and the number of narcotic pills consumed in the first 5 days after ARCR . Furthermore , the findings provide guidelines for postoperative narcotic prescribing to reduce the quantity of opiates prescribed PURPOSE The aim of the study was to determine the effect of low-dose gabapentin on postoperative pain management in patients undergoing arthroscopic rotator cuff repair . METHODS This r and omized , double-blinded , placebo-controlled study included 46 patients . The patients were divided into 2 groups according to the drug administered 2 hours before surgery , either 300 mg of gabapentin or placebo . The primary outcome measure was the visual analog scale ( VAS ) score at 2 , 6 , 12 , and 24 hours postoperatively . The secondary outcome measures were fentanyl consumption and side effects during the first 2 hours in the postanesthesia care unit and then at 6 and 24 hours postoperatively . The patients were evaluated for side effects including nausea , vomiting , respiratory depression , dizziness , drowsiness , voiding difficulty , and pruritus . RESULTS The VAS scores at 2 , 6 , and 12 hours postoperatively were significantly lower in the gabapentin group than in the placebo group ( P = .023 , P = .019 , and P = .022 , respectively ) . The consumption of fentanyl , over a period of 24 hours , was not different in the comparisons between the groups ( P = .686 ) . The incidence of side effects was similar in the 2 groups . CONCLUSIONS A single dose of 300 mg of gabapentin reduced the VAS score during the first 24 hours postoperatively in patients undergoing shoulder arthroscopic rotator cuff repair , without significant side effects when compared with placebo . However , the fentanyl consumption did not differ between the gabapentin and placebo groups . LEVEL OF EVIDENCE Level I , r and omized controlled trial BACKGROUND AND OBJECTIVES Arthroscopy for shoulder disorders is associated with severe and difficult to control pain , postoperatively . The addition of clonidine to local anesthetics for peripheral nerve block has become increasingly common , thanks to the potential ability of this drug to reduce the mass of local anesthetic required and to prolonging analgesia postoperatively . The present study aim ed to evaluate the success of brachial plexus block for arthroscopic rotator cuff surgery using local anesthetic with or without clonidine . METHOD 53 patients of both genders , between 18 and 70 years old , American Society of Anesthesiologists I or II , who were scheduled to undergo arthroscopic shoulder surgery were selected . Patients were then r and omized into two groups . The verbal numerical pain scale and the presence of motor block were obtained in the post-anesthetic recovery room and 6 , 12 , 18 and 24h postoperatively . RESULTS The association of clonidine ( 0.15 mg ) to a solution of 0.33 % ropivacaine ( 30mL ) in brachial plexus block for shoulder arthroscopy has not diminished the visual numeric pain scale values , nor the need for opioid rescue postoperatively . There was a lower incidence of nausea/vomiting postoperatively and a significant motor block time prolongation in the group of patients who received clonidine as adjuvant . CONCLUSIONS The use of brachial plexus block with local anesthetic for analgesic postoperative control is well established in the literature . The addition of clonidine in the dose proposed for prolongation of the analgesic effect and reduction of opioid rescue proved unhelpful |
12,756 | 25,790,086 | CONCLUSIONS The results suggest that not all children with mild or moderate TBI recover without long-term problems .
Few studies followed children and adolescents with mild TBIs for extended periods of time , although it is clinical ly important to monitor patients over time | AIM To systematic ally review existing empirical evidence concerning neuropsychological , psychosocial and academic outcomes following mild and moderate TBI during childhood and adolescence . | OBJECTIVE . We examined whether mild traumatic brain injuries in children and adolescents , especially when associated with acute clinical features reflecting more severe injury , result in different postinjury trajectories of postconcussive symptoms compared with mild orthopedic injuries . PARTICIPANTS AND METHODS . Participants in this prospect i ve and longitudinal cohort study were 8- to 15-year-old children , 186 with mild traumatic brain injuries and 99 with mild orthopedic injuries , who were recruited from consecutive admissions to emergency departments in 2 large children 's hospitals . Parents rated current postconcussive symptoms within 3 weeks of injury and at 1 , 3 , and 12 months after injury . At the initial assessment , parents also provided retrospective ratings of preinjury symptoms , and children with mild traumatic brain injuries received MRI of the brain . Clinical features examined as predictors of postconcussive symptoms included loss of consciousness , Glasgow Coma Scale score below 15 , other injuries , acute symptoms of concussion , and intracranial abnormalities on the MRI . RESULTS . Finite mixture modeling identified 4 longitudinal trajectories of postconcussive symptoms ( ie , no postconcussive symptoms , moderate persistent postconcussive symptoms , high acute/resolved postconcussive symptoms , high acute/persistent postconcussive symptoms ) . The mild traumatic brain injuries and orthopedic injuries groups demonstrated a different distribution of trajectories . Children with mild traumatic brain injuries were more likely than those with orthopedic injuries to demonstrate high acute/resolved and high acute/persistent trajectories relative to the no postconcussive symptoms group . The 2 trajectories with high acute levels of postconcussive symptoms were especially likely among children with mild traumatic brain injuries whose acute clinical presentation reflected more severe injury . CONCLUSIONS . Mild traumatic brain injuries , particularly those that are more severe , are more likely than orthopedic injuries to result in transient or persistent increases in postconcussive symptoms in the first year after injury . Additional research is needed to eluci date the range of factors , both injury related and non – injury related , that place some children with mild traumatic brain injuries at risk for postconcussive symptoms OBJECTIVES This study of concussed adolescents sought to determine if a computer-based neurocognitive assessment ( Immediate Postconcussion Assessment and Cognitive Test [ ImPACT ] ) performed on patients who present to the emergency department ( ED ) immediately following head injury would correlate with assessment s performed 3 to 10 days postinjury and if ED neurocognitive testing would detect differences in concussion severity that clinical grading scales could not . METHODS A prospect i ve cohort sample of patients 11 to 17 years of age presenting to the ED within 12 hours of a head injury were evaluated using two traditional concussion grading scales and neurocognitive testing . ED neurocognitive scores were compared to follow-up scores obtained at least 3 days postinjury . Postconcussive symptoms , outcomes , and complications were assessed via telephone follow-up for all subjects . RESULTS Sixty patients completed phone follow-up . Thirty-six patients ( 60 % ) completed follow-up testing a median of 6 days postinjury . Traditional concussion grading did not correlate with neurocognitive deficits detected in the ED or at follow-up . For the neurocognitive domains of verbal memory , processing speed , and reaction time , there was a significant correlation between ED and follow-up scores trending toward clinical improvement . By 2 weeks postinjury , 23 patients ( 41 % ) had not returned to normal activity . At 6 weeks , six patients ( 10 % ) still had not returned to normal activity . CONCLUSIONS Immediate assessment in the ED can predict neurocognitive deficits seen in follow-up and may be potentially useful to individualize management or test therapeutic interventions . Neurocognitive assessment in the ED detected deficits that clinical grading could not and correlated with deficits at follow-up Childhood traumatic brain injury ( TBI ) is a common , acquired disability , which has significant implication s for subsequent development , and for later quality of life . To date few studies have documented outcomes in these children into adolescence , when academic , social and personal dem and s increase . The objective of this study was to document functional outcomes at 10 years post-injury , and to identify predictors of outcome including injury , socio-demographic and pre-injury characteristics . The study employed consecutive recruitment to a prospect i ve , longitudinal study . Children with a diagnosis of TBI between 2 and 12 years were initially recruited and divided according to injury severity ( mild , moderate , severe ) . The sample was review ed at 10 years post-injury and intellectual , adaptive , executive and social domains were investigated . Results indicated that , at 10 years post child TBI , survivors ' functional abilities fell overall within the low average to average range regardless of injury severity , suggesting no extreme impairments at a group level for any of the domains under investigation . Significant group differences were identified , though , for adaptive abilities and for speed of processing , with more severe injury associated with poorer performances in each instance . Further , a similar trend was identified for measures of intellectual ability and executive functions . Individual rates of impairment were considerably higher than population expectations across all severity groups for these domains . Although rates of social impairment were also elevated , they were less related to injury factors , suggesting that cognitive/adaptive outcomes and social consequences of TBI may have different bases Primary objective : Comparison of healthcare costs for youth with mild traumatic brain injuries ( TBIs ) to costs in a matched cohort of children without TBI in the 3 years following injury . Research design : This study used a prospect i ve cohort design with 3-year follow-up . Costs were examined using the well-established two-step model and controlling for potential confounding variables . Methods and procedures : Four-hundred and ninety subjects from a large health maintenance organization , 14 years old or younger , who sustained a mild TBI in 1993 , were identified using computerized records . For each youth with mild TBI , three control subjects were selected ( n = 1470 ) , matched on age , sex and enrolment at the time of injury . Experimental interventions : Not applicable . Main outcomes and results : TBI exposure was associated with an increase in the proportion of subjects who had non-zero medical costs in all categories examined and a 75 % increase in mean total costs . Presence of psychological distress was also associated with increased proportion of subjects with costs in all categories examined and was associated with an approximate doubling of mean total costs . Conclusions : Mild TBI and psychological distress were each associated with significant increases in healthcare costs in an HMO setting Objective : To test the feasibility of inpatient neurocognitive testing and measure the degree of disability in children hospitalized with mild traumatic brain injury ( MTBI ) . Summary Background Data : MTBI is common in the pediatric population . A st and ardized approach to identify neurocognitive impairment and determine optimal time to return to exertional activities ( eg , school , sports ) is lacking . Methods : For a 2-year period , children ( age : 11–17 years ) hospitalized at a level 1 urban Pediatric Trauma Center with MTBI were prospect ively enrolled . Neurocognitive performance was assessed utilizing previously vali date d computer-based tests ( Immediate Postconcussion Assessment and Cognitive Testing ) as inpatient and in follow-up clinic after discharge . The feasibility of inpatient testing and the degree neurocognitive impairment and symptomatology were assessed . This study was approved by the IRB and registered with clinical trials.gov ( NCT00715949 ) . Results : For the 2 years of study , 116 subjects were prospect ively enrolled and tested . The population had a mean age of 14 years and 69.8 % were male . On initial in-hospital testing , the overall population demonstrated considerable neurocognitive deficits ( mean values for all 4 subtests below 25th percentile , norm 50 % ) with at least one subtest score below 25 % in 95.7 % and an abnormal symptom score in 83.4 % of patients . In comparing initial testing to follow-up testing ( N = 63 ) , significant improvements were noted for all subtests ( verbal memory : 28.0 % vs. 37.5 % , respectively , norm 50 % , P = 0.02 ; visual memory : 24.9 % vs. 38.1 % , respectively , norm 50 % , P < 0.01 ; visual motor : 21.8 % vs. 31.1 % , respectively , norm 50 % , P = 0.01 ; reaction time : 21.8 % vs. 30.3 % , respectively , norm 50 % , P = 0.05 ) , with a decline in the symptom score ( 26.9 vs. 9.2 , respectively , norm 0 - 8 , P < 0.01 ) as well . Patients not seen in follow-up ( N = 53 ) did not differ demographically from those seen in clinic . Conclusions : Inpatient neurocognitive testing was feasible in pediatric MTBI patients . Neurocognitive abnormalities were nearly universally present on initial evaluation with significant improvements demonstrated at the time of outpatient follow-up . Return to activity recommendations are thus best deferred for most hospitalized MTBI children until formal assessment can be performed after discharge The degree to which postinjury posttraumatic stress disorder ( PTSD ) and /or depressive symptoms in adolescents are associated with cognitive and functional impairments at 12 and 24 months after traumatic brain injury ( TBI ) is not yet known . The current study used a prospect i ve cohort design , with baseline assessment and 3- , 12- , and 24-month followup , and recruited a cohort of 228 adolescents ages 14 - 17 years who sustained either a TBI ( n = 189 ) or an isolated arm injury ( n = 39 ) . Linear mixed-effects regression was used to assess differences in depressive and PTSD symptoms between TBI and arm-injured patients and to assess the association between 3-month PTSD and depressive symptoms and cognitive and functional outcomes . Results indicated that patients who sustained a mild TBI without intracranial hemorrhage reported significantly worse PTSD ( Hedges g = 0.49 , p = .01 ; Model R(2 ) = .38 ) symptoms across time as compared to the arm injured control group . Greater levels of PTSD symptoms were associated with poorer school ( η(2 ) = .07 , p = .03 ; Model R(2 ) = .36 ) and physical ( η(2 ) = .11 , p = .01 ; Model R(2 ) = .23 ) functioning , whereas greater depressive symptoms were associated with poorer school ( η(2 ) = .06 , p = .05 ; Model R(2 ) = .39 ) functioning OBJECT The aim of this study was to determine whether the presence of intracranial pathophysiology on computed tomography ( CT ) scans obtained within 24 hours of mild traumatic brain injury ( MTBI ) in children adversely affects neuropsychological outcome during the 1st year postinjury . METHODS A prospect i ve longitudinal design was used to examine the neuropsychological outcomes in children ( ages 5 - 15 years ) who had been treated for MTBI , which was defined as a loss of consciousness for up to 30 minutes and a lowest Glasgow Coma Scale ( GCS ) score of 13 - 15 . Exclusion criteria included any preinjury neurological disorder . Outcome assessment s were performed within 2 weeks and at 3 , 6 , and 12 months postinjury . Outcomes were compared between patients with MTBI whose postinjury CT scans revealed complications of brain pathophysiology ( 32 patients , CMTBI group ) and those with MTBI but without complications ( 48 patients , MTBI group ) . RESULTS Significant interactions confirmed that the pattern of recovery over 12 months after injury differed depending on the intracranial pathology , presence and severity of injuries to body regions other than the head , preinjury attention-deficit hyperactivity disorder ( ADHD ) , and socioeconomic status . Children in the CMTBI group had significantly poorer episodic memory , slower cognitive processing , diminished recovery in managing cognitive interference , and poorer performance in calculating and reading than patients in the MTBI group . Among the patients with mild or no extracranial injury , visuomotor speed was slower in those in the CMTBI group ; and among patients without preinjury ADHD , working memory was worse in those in the CMTBI group . CONCLUSIONS Neuropsychological recovery during the 1st year following MTBI is related to the presence of radiographically detectable intracranial pathology . Children with intracranial pathology on acute CT performed more poorly in several cognitive domains when compared with patients whose CT findings were normal or limited to a linear skull fracture . Depending on the presence of preinjury ADHD and concomitant extracranial injury , working memory and visuomotor speed were also diminished in patients whose CT findings revealed complications following MTBI . Computed tomography within 24 hours postinjury appears to be useful for identifying children with an elevated risk for residual neuropsychological changes The occurrence of postconcussive symptoms ( PCS ) following mild traumatic brain injury ( TBI ) in children may depend on cognitive reserve capacity . This prospect i ve , longitudinal study examined whether the relationship between mild TBI and PCS is moderated by cognitive ability , which served as a proxy for cognitive reserve . Participants included 182 children with mild TBI and 99 children with orthopedic injuries ( OI ) , ranging from 8 to 15 years of age when injured . Mild TBI were classified as complicated ( n = 32 ) or uncomplicated ( n = 150 ) depending on whether they were associated with trauma-related intracranial abnormalities on magnetic resonance imaging . PCS were assessed initially within 3 weeks of injury , and again at 1 , 3 , and 12 months post injury . The initial assessment also included st and ardized tests of children 's cognitive skills and retrospective parent ratings of pre-injury symptoms . Hierarchical linear modeling indicated that ratings of PCS were moderated jointly by cognitive ability and injury severity . Children of lower cognitive ability with a complicated mild TBI were especially prone to cognitive symptoms across time according to parents and to high acute levels of PCS according to children 's self-ratings . Cognitive reserve is an important moderator of the outcomes of mild TBI in children and adolescents Abstract Background Mild traumatic brain injury ( MTBI ) is a leading cause of injury for children during their pre-school years . However , there is little information regarding the long-term outcomes of these injuries . Method We used fully prospect i ve data from an epidemiological study of a birth cohort to examine behavioural effects associated with MTBI during the pre-school years . Cases of confirmed MTBI were divided into two groups , those that had received outpatient medical attention , and those that had been admitted to hospital for a brief period of observation ( inpatient cases ) . The remainder of the cohort served as a reference control group . Results Mother/teacher ratings for behaviours associated with attention deficit/hyperactivity disorder and oppositional defiant/conduct disorder , obtained yearly from age 7 to 13 , revealed evidence of deficits after inpatient MTBI ( n = 21 ) , relative to more minor outpatient injury MTBI ( n = 55 ) and the reference control group ( n = 852 ) . For the inpatient group there was evidence of increasing deficits over years 7 - 13 . Conclusions More severe pre-school MTBI may be associated with persistent negative effects in terms of psychosocial development . The vulnerability of pre-school children to MTBI signals a pressing need to identify high-risk cases that may benefit from monitoring and early intervention The level of parent-child agreement on post-concussive symptoms ( PCS ) was examined in children following mild traumatic brain injuries ( TBI ) . As part of a larger longitudinal study , 186 children with mild TBI and 99 with orthopedic injuries ( OI ) , from 8 to 15 years of age , were recruited prospect ively . Parents and children completed the PCS Interview ( PCS-I ) and the Health and Behavior Inventory ( HBI ) at 2 weeks , 1 month , 3 months , and 12 months postinjury . Item-level correlations between child and parent ratings on both measures of PCS were significant but modest in both groups . Parent-child correlations for composite scales on the HBI and the total score on the PCS-I were significant in both groups , but somewhat higher in the OI group than in the mild TBI group . Mean symptom ratings tended to be significantly higher for children as compared to parents , especially for somatic symptoms . Parents and children display modest agreement when reporting PCS ; their ratings correlate significantly , but children report higher mean levels of symptoms than parents BACKGROUND The Cochrane Collaboration is strongly encouraging the use of a newly developed tool , the Cochrane Collaboration Risk of Bias Tool ( CCRBT ) , for all review groups . However , the psychometric properties of this tool to date have yet to be described . Thus , the objective of this study was to add information about psychometric properties of the CCRBT including inter-rater reliability and concurrent validity , in comparison with the Effective Public Health Practice Project Quality Assessment Tool ( EPHPP ) . METHODS Both tools were used to assess the method ological quality of 20 r and omized controlled trials included in our systematic review of the effectiveness of knowledge translation interventions to improve the management of cancer pain . Each study assessment was completed independently by two review ers using each tool . We analysed the inter-rater reliability of each tool 's individual domains , as well as final grade assigned to each study . RESULTS The EPHPP had fair inter-rater agreement for individual domains and excellent agreement for the final grade . In contrast , the CCRBT had slight inter-rater agreement for individual domains and fair inter-rater agreement for final grade . Of interest , no agreement between the two tools was evident in their final grade assigned to each study . Although both tools were developed to assess ' quality of the evidence ' , they appear to measure different constructs . CONCLUSIONS Both tools performed quite differently when evaluating the risk of bias or method ological quality of studies in knowledge translation interventions for cancer pain . The newly introduced CCRBT assigned these studies a higher risk of bias . Its psychometric properties need to be more thoroughly vali date d , in a range of research fields , to underst and fully how to interpret results from its application OBJECTIVE To determine the acute predictors associated with the development of postconcussion syndrome ( PCS ) in children and adolescents after mild traumatic brain injury . DESIGN Retrospective analysis of a prospect i ve observational study . SETTING Pediatric emergency department ( ED ) in a children 's hospital . PARTICIPANTS Four hundred six children and adolescents aged 5 to 18 years . MAIN EXPOSURE Closed head trauma . MAIN OUTCOME MEASURES The Rivermead Post Concussion Symptoms Question naire administered 3 months after the injury . RESULTS Of the patients presenting to the ED with mild traumatic brain injury , 29.3 % developed PCS . The most frequent PCS symptom was headache . Predictors of PCS , while controlling for other factors , were being of adolescent age , headache on presentation to the ED , and admission to the hospital . Patients who developed PCS missed a mean ( SD ) of 7.4 ( 13.9 ) days of school . CONCLUSIONS Adolescents who have headache on ED presentation and require hospital admission at the ED encounter are at elevated risk for PCS after mild traumatic brain injury . Interventions to identify this population and begin early treatment may improve outcomes and reduce the burden of disease Objectives : To examine recovery of attention from 3 to 6 months postinjury ; to identify effects of injury severity and time since injury on performance ; to explore whether complex attention skills ( eg , shifting , divided attention , attentional control ) are more vulnerable to traumatic brain injury ( TBI ) , and slower to recover than simple attention skills ( eg , attentional capacity , selective attention , sustained attention ) . Design : Prospect i ve longitudinal investigation . Participants : A total of 205 school-aged children with TBI were divided into groups according to injury severity ( mild = 63 % , moderate = 27 % , severe = 10 % ) . Setting : Emergency departments of 3 metropolitan children 's hospitals across Australia . Main Measures : St and ardized clinical measures of both simple and complex attention were administered at 3 months and 6 months postinjury . Results : Attention skills were vulnerable to the impact of TBI . More severe injury affected attention skills most negatively . Significant recovery was observed over time . There were few interaction effects , with severity groups exhibiting similar levels of recovery over the 6 months post-TBI . No differences in recovery trajectories were detected for simple and complex attention . Conclusions : These findings have important clinical and educational implication s , suggesting that children with TBI , and particularly those with more serious injuries , are most vulnerable to attention deficits in the acute stages postinjury . It is important that schools and families are aware of these limitations and structure expectations accordingly . For example , gradual return to school should be considered , and in the early stages of recovery , children should be provided with sufficient rest time , with reduced expectations for tasks such as homework Objective : This study sought to examine the effects of mild traumatic brain injury ( TBI ) on executive functions in school-aged children . Participants and method : The prospect i ve , longitudinal study involved 8–15 year old children , 186 with mild TBI and 99 with mild orthopaedic injuries ( OI ) . They were administered the Stockings of Cambridge and Spatial Working Memory sub-tests from the Cambridge Neuropsychological Testing Automated Battery ( CANTAB ) ∼10 days , 3 months and 12 months post-injury . Parents completed the Behavior Rating Inventory of Executive Functions ( BRIEF ) on each occasion , with ratings at the initial assessment intended to assess pre-morbid functioning retrospectively . Results : On the CANTAB , the groups did not differ on the Stockings of Cambridge and the mild TBI group unexpectedly performed better than the OI group on Spatial Working Memory . On the BRIEF , children with mild TBI showed a marginally significant trend toward more problems than the OI group on the Metacognition Index composite . The only BRIEF sub-scale on which they demonstrated significantly more problems was Organization of Material s. The presence of intracranial abnormalities on MRI was associated with more problems on the BRIEF Organization of Material s sub-scale at 3 months , but other findings were not consistent with hypothesized effects of TBI severity . The CANTAB sub-tests were significant predictors of later ratings on the BRIEF , but accounted for modest variance . Discussion : Children with mild TBI show limited evidence of deficits in executive functions , either cognitively or behaviourally , irrespective of injury characteristics . Cognitive tests of executive functions are modest predictors of ratings of executive functions in everyday life , for children both with and without mild TBI BACKGROUND : Much disagreement exists as to whether postconcussion syndrome ( PCS ) is attributable to brain injury or to other factors such as trauma alone , preexisting psychosocial problems , or medicolegal issues . We investigated the epidemiology and natural history of PCS symptoms in a large cohort of children with a mild traumatic brain injury ( mTBI ) and compared them with children with an extracranial injury ( ECI ) . METHODS : This investigation was a prospect i ve , consecutive controlled-cohort study of 670 children who presented to a tertiary referral emergency department with mTBI and 197 children who presented with ECI . For all participants , data were collected by use of a telephone interview of a parent 7 to 10 days after injury . If a change from preinjury symptoms was reported by a parent , follow-up continued monthly until symptom resolution . Outcomes were measured by using the Post Concussion Symptom Inventory , Rivermead Postconcussion Symptom Question naire , Brief Symptom Inventory , and Family Assessment Device . RESULTS : There was a significant difference between the mTBI and ECI groups in their survival curves for time to symptom resolution ( log rank [ Mantel-Cox ] 11.15 , P < .001 ) . Three months after injury , 11 % of the children in the mTBI group were symptomatic ( 13.7 % of children older than 6 years ) compared with 0.5 % of the children in the ECI group . The prevalence of persistent symptoms at 1 year was 2.3 % in the mTBI group and 0.01 % in the ECI group . Family functioning and maternal adjustment did not differ between groups . CONCLUSIONS : Among school-aged children with mTBI , 13.7 % were symptomatic 3 months after injury . This finding could not be explained by trauma , family dysfunction , or maternal psychological adjustment . The results of this study provide clear support for the validity of the diagnosis of PCS in children STUDY AIM This study sought to determine whether premorbid child and family functioning accounts for or moderates group differences in post-concussive symptoms following mild traumatic brain injury ( TBI ) in childhood . METHODS This prospect i ve , longitudinal cohort study recruited 8- to 15-year-old children , 186 with mild TBI and 99 with orthopedic injuries ( OI ) , from consecutive emergency department admissions . Parents and children rated post-concussive symptoms within 3 weeks of injury and at 1 , 3 , and 12 months post injury . Parents also provided retrospective ratings of pre-injury symptoms , as well as of premorbid child behavioral adjustment , overall family functioning , and other stressors and re sources in the family environment . RESULTS Children with mild TBI reported more post-concussive symptoms than those with OI , as did their parents , although premorbid child behavioral adjustment and symptoms also were significant predictors of post-concussive symptoms . Group differences in somatic symptoms as reported by parents were more pronounced among children from families that were higher functioning and had more environmental re sources . DISCUSSION Mild TBI during childhood results in more post-concussive symptoms than OI , even after children 's premorbid adjustment is taken into account . Counter to expectations , post-concussive symptoms following mild TBI may actually be more apparent among children from higher-functioning families with greater re sources Objective : The purpose of this study was to examine family adaptation to a traumatic brain injury ( TBI ) in young children during the first 18-month postinjury , when compared with children who had an orthopedic injury . Methods : A concurrent cohort/ prospect i ve research design was used with repeated assessment s of children aged 3 to 6 years with TBI or orthopedic injury requiring hospitalization and their families . Shortly after injury and at 6- , 12- , and 18-month postinjury , parents of 99 children with TBI ( 20 severe , 64 moderate , 15 mild ) and 117 with orthopedic injury completed st and ardized assessment s of family functioning , parental distress and coping , injury-related burden , and noninjury-related parent stressors and re sources . Mixed models analyses examined group differences in parental burden and distress adjusted for race and social demographic factors . Results : Both moderate and severe TBI were associated with higher levels of injury-related stress than orthopedic injury , with stress levels diminishing over time in all groups . Severe TBI was also associated with greater psychological distress on the Brief Symptom Inventory but not with more depressive symptoms . Family functioning and social re sources moderated the relationship of TBI severity to injury-related burden and caregiver distress , respectively . Lower child adaptive skills were associated with poorer family outcome but group differences remained even when controlling for this effect . Conclusions : Severe TBI in young children has adverse consequences for parents and families during the first 18-month postinjury . The consequences lessen over time for many families and vary as a function of social re sources OBJECTIVE To examine reliable change in postconcussive symptoms and its functional consequences among children with mild traumatic brain injury ( TBI ) over the first year postinjury as compared with children with orthopedic injuries . DESIGN Prospect i ve , longitudinal cohort . SETTING Emergency departments at 2 children 's hospitals . PARTICIPANTS Eight- to 15-year-old children with mild TBI ( n = 186 ) or orthopedic injuries ( n = 99 ) . MAIN EXPOSURE Closed-head or orthopedic trauma . MAIN OUTCOME MEASURES Parents rated preinjury symptoms retrospectively shortly after injury and postconcussive symptoms at 2 weeks and 3 and 12 months postinjury . A regression-based approach was used to determine whether each child displayed reliable increases in postconcussive symptoms at each postinjury occasion . Health-related quality of life was assessed at 3 and 12 months postinjury . Information regarding children 's educational programming was collected at the initial and 12-month assessment s. RESULTS Children with mild TBI were significantly more likely than those with orthopedic injuries to show reliable increases in both cognitive and somatic symptoms . Group differences in the likelihood of reliable increases became less common with time for somatic symptoms but persisted to 12 months postinjury for cognitive symptoms . Among children with mild TBI , reliable increases in symptoms were more common among children with loss of consciousness or abnormalities on neuroimaging . Reliable increases in symptoms were associated with significant declines in health-related quality of life and an increased likelihood of educational intervention . CONCLUSION Many children with mild TBI show reliable increases in postconcussive symptoms that are associated with significant functional impairment in their daily lives Primary objective : Research suggest that post-concussive syndrome after mild traumatic brain injury ( mTBI ) is more common than chronic cognitive impairment . The aim of this study was to investigate very long-term outcome of subjective complaints after paediatric mTBI . Research design : The study was a follow-up 23 years after a prospect i ve head injury study at a general hospital in Norway . Methods and procedures : Forty-one patients were assessed with the Minnesota Multiphasic Personality Inventory-2 ( MMPI-2 ) 23 years after sustaining mTBI as children . Main outcomes and results : A good overall outcome was found with scores close to the normative mean , average length of education and normal employment rate . However , the children that sustained complicated mTBI showed slightly more pathological scores , typical for mild post-concussive syndrome . The most important predictors of poor outcome were skull fracture and a combination of post-traumatic amnesia > 30 minutes and EEG pathology within 24 hours after TBI . No influence of pre- and post-injury risk factors on current MMPI-2 profiles was evident . Conclusions : The results give support for the notion of potentially differential impact of uncomplicated vs complicated mTBI . The findings suggest that children and adolescents sustaining complicated mTBI may be at risk of developing subtle chronic symptoms typical of post-concussive syndrome This study aim ed to examine the prevalence and trajectory of sleep disturbances and their associated risk factors in children up to 24 months following a traumatic brain injury ( TBI ) . In addition , the longitudinal association between sleep disturbances and children 's functional outcomes was assessed . This was a prospect i ve study of a cohort of children with TBI and a comparison cohort of children with orthopedic injury ( OI ) . Parental reports of pre-injury sleep disturbances were compared to reports of post-injury changes at 3 , 12 , and 24 months . Risk factors for sleep disturbances were examined , including severity of TBI , presence of psychosocial problems , and pain . Sleep disturbances were also examined as a predictor of children 's functional outcomes in the areas of adaptive behavior skills and activity participation . Both cohorts ( children with TBI and OI ) displayed increased sleep disturbances after injury . However , children with TBI experienced higher severity and more prolonged duration of sleep disturbances compared to children with OI . Risk factors for disturbed sleep included mild TBI , psychosocial problems , and frequent pain . Sleep disturbances emerged as significant predictors of poorer functional outcomes in children with moderate or severe TBI . Children with TBI experienced persistent sleep disturbances over 24 months . Findings suggest a potential negative impact of disturbed sleep on children 's functional outcomes , highlighting the need for further research on sleep in children with TBI OBJECTIVE : To examine disability in children and adolescents after traumatic brain injury ( TBI ) across the spectrum of injury severity . METHODS : This was a prospect i ve cohort study of children younger than 18 years treated for a TBI ( n = 729 ) or an arm injury ( n = 197 ) between March 1 , 2007 , and September 30 , 2008 . The main outcome measures were disability in health-related quality of life , adaptive skills , and participation in social and community activities 3 , 12 , and 24 months after injury compared with preinjury functioning . RESULTS : The health-related quality of life for children with moderate or severe TBI was lower at all follow-up times compared with baseline , but there was some improvement during the first 2 years after injury . Three months after injury , there was a substantial decrease in the level of activities in which children with moderate and severe TBI were able to participate ; these activities improved at 12 and 24 months but were still significantly impaired . Communication and self-care abilities in children with moderate and severe TBI were lower at 3 months than at baseline and did not improve by 24 months . Children who met the definition of mild TBI but had an intracranial hemorrhage had lower quality -of-life scores at 3 months . CONCLUSIONS : Children with moderate or severe TBI and children with mild TBI who had intracranial hemorrhage had substantial long-term reduction in their quality of life , participation in activities with others , and ability to communicate and care for themselves Primary objective : To investigate the occurrence of post-concussive symptoms ( PCS ) and symptoms of post-traumatic stress disorder ( PTSD ) in children following mild traumatic brain injuries ( TBI ) . Research design : Longitudinal study comparing the outcomes of mild TBI and orthopaedic injuries ( OI ) in children aged 8–15 . Methods and procedures : One hundred and eighty-six children with mild TBI and 99 with OI were recruited prospect ively . Parents rated children 's PCS and symptoms of PTSD at 2 weeks , 3 months and 12 months post-injury . One hundred and sixty-seven with mild TBI and 84 with OI completed all assessment s. Main outcomes and results : Controlling for symptoms of PTSD , the mild TBI group demonstrated more PCS than the OI group , although the magnitude of group differences diminished with time . Controlling for PCS , the OI group displayed more symptoms of PTSD than the mild TBI group at baseline , but not thereafter . Symptoms of PTSD and PCS were correlated significantly , but more highly in the OI group than the mild TBI group . Conclusions : Although PCS and symptoms of PTSD are correlated , children with mild TBI are more distinguishable from children with OI based on PCS than on symptoms of PTSD . The latter symptoms , moreover , do not account for increased PCS following mild TBI in children Objective : The aim is to describe how children and youths perform leisure activities , 1 year after a mild traumatic brain injury ( MTBI ) . Methods : Basis is to compile previously collected material ; patients were extracted from a prospect i ve r and omized controlled trial of MTBI . A retrospective analysis was conducted among 73 children and youths between 16 and 18 years of age . The entire group administrated the Interest Checklist at baseline and at 1-year follow-up . Results : Statistical significant difference was found in 31 of 50 different activities . The result showed that children and youths did not return to perform leisure activities . Fewer returned in the intervention group than in the control group . Conclusion : An occupational therapist can help children and youths to have balance in their life and continue a functional life after a MTBI . Continued research is needed , how to prevent MTBI and how to support children and youths to continue with leisure activities |
12,757 | 31,978,257 | Based on very low-certainty evidence , there is considerable uncertainty about whether interventions for ascites in people with decompensated liver cirrhosis decrease mortality , adverse events , or liver transplantation compared to paracentesis plus fluid replacement in people with decompensated liver cirrhosis and ascites .
Based on very low-certainty evidence , transjugular intrahepatic portosystemic shunt and adding aldosterone antagonists to paracentesis plus fluid replacement may increase the resolution of ascites compared to paracentesis plus fluid replacement .
Based on very low-certainty evidence , aldosterone antagonists plus loop diuretics may increase the decompensation rate compared to paracentesis plus fluid replacement | BACKGROUND Approximately 20 % of people with cirrhosis develop ascites .
Several different treatments are available ; including , among others , paracentesis plus fluid replacement , transjugular intrahepatic portosystemic shunts , aldosterone antagonists , and loop diuretics .
However , there is uncertainty surrounding their relative efficacy .
OBJECTIVES To compare the benefits and harms of different treatments for ascites in people with decompensated liver cirrhosis through a network meta- analysis and to generate rankings of the different treatments for ascites according to their safety and efficacy . | Background : Patients with cirrhosis and tense ascites treated by paracentesis alone have a decrease in effective arterial blood volume after ascites removal . Although intravenous albumin is effective in preventing paracentesis induced decreased arterial blood volume , its clinical use is controversial . As paracentesis induces arteriolar vasodilation which plays a role in the development of decreased effective arterial blood volume , administration of a vasoconstrictor ( terlipressin ) could prevent circulatory alterations due to paracentesis . Aims : To perform a pilot study comparing the effects of terlipressin and albumin on effective arterial blood volume in patients with cirrhosis treated by paracentesis for tense ascites . Methods : Twenty patients with cirrhosis and tense ascites were r and omly assigned to be treated by either paracentesis and terlipressin or paracentesis and albumin . Terlipressin ( 3 mg ) or albumin ( 8 g/l of removed ascites ) were administered on the day of paracentesis . Effective arterial blood volume was assessed by measuring plasma renin concentrations at baseline and on the day of hospital discharge ( 4–6 days after treatment ) . Decreased effective arterial blood volume was defined as an increase in plasma renin concentrations on the day of hospital discharge of more than 50 % of baseline values . Results : Irrespective of the treatment group , mean values for plasma renin concentrations at hospital discharge did not differ from their respective baseline values ( p=0.10 ) . Baseline plasma levels of renin concentrations did not differ between the terlipressin and albumin groups ( p=0.61 ) . Changes from baseline in plasma renin concentrations did not differ between groups ( p=0.39 ) . Three patients in the terlipressin group and three in the albumin group developed decreased arterial blood volume . Conclusions : This r and omised pilot study suggests that terlipressin may be as effective as intravenous albumin in preventing a decrease in effective arterial blood volume in patients with cirrhosis treated by paracentesis for tense ascites OBJECTIVES : Intravenous albumin has been used to prevent paracentesis-induced circulatory dysfunction ( PICD ) in cirrhotics ; however , its use is costly and controversial . Splanchnic arterial vasodilatation is primarily responsible for PICD . There are no reports of use of midodrine in the prevention of PICD . In this pilot study , we evaluated midodrine and albumin in the prevention of PICD . METHODS : Forty patients with cirrhosis underwent therapeutic paracentesis with midodrine or albumin in a r and omized controlled trial at a tertiary center . Effective arterial blood volume was assessed by plasma renin activity . RESULTS : Plasma renin activity at baseline and at 6 days after paracentesis did not differ in the two groups ( 43.18 ± 10.73 to 45.90 ± 8.59 ng/mL/h , P= 0.273 in the albumin group and 44.44 ± 8.44 to 41.39 ± 10.21 ng/mL/h , P= 0.115 in the midodrine group ) . Two patients had an increase in plasma renin activity of more than 50 % from baseline in the albumin group , and none in the midodrine group . A significant increase in 24-h urine volume and urine sodium excretion was noted in the midodrine group . Midodrine therapy was cheaper than albumin therapy . CONCLUSIONS : The study suggests that midodrine may be as effective as albumin in preventing PICD in cirrhotics , but at a fraction of the cost , and can be administered orally . Midodrine also result ed in an increase in 24-h urine volume and sodium excretion AIM To investigate the effects of long-term albumin administration on survival , recurrence of ascites and onset of other complications . METHODS One hundred consecutive patients admitted for first-onset ascites were r and omized to receive diuretics plus human albumin 25 g/wk in the first year and 25 g every two wk thereafter ( group 1 ) or diuretics alone ( group 2 ) . The primary endpoint was survival without liver transplantation . Secondary endpoints were recurrence of ascites and occurrence of other complications . RESULTS Median follow-up was 84 ( 2 - 120 ) mo . Albumin-treated patients had significantly greater cumulative survival rate ( Breslow test=7.05 , P=0.0078 ) and lower probability of ascites recurrence ( 51 % versus 94 % , P<0.0001 ) . Chronic albumin infusion result ed in a mean increase in survival of 16 mo . CONCLUSION Long-term albumin administration after first-onset ascites significantly improves patients ' survival and decreases the risk of ascites recurrence Background Transjugular intrahepatic portosystemic shunt ( TIPS ) has recently been reported to be effective in the treatment of cirrhotic patients with refractory ascites . However , the clinical utility of TIPS in the subset of refractory ascitic patients with good hepatic and renal function is uncertain . The aim of this study was to compare the efficacy of TIPS to that of large-volume paracentesis in cirrhotic patients with refractory ascites who have good hepatic and renal function . Methods Sixty cirrhotic patients with refractory ascites who presented with a Child – Pugh score of < 11 , serum bilirubin of <3 mg/dl and creatinine of < 1.9 mg/dl were assigned r and omly to TIPS ( n = 30 ) or large-volume paracentesis plus albumin ( n = 30 ) . The primary endpoint was survival . The secondary endpoints were response to treatment and development of hepatic encephalopathy . Results The baseline characteristics were similar in the two groups . Seventeen patients treated with TIPS and 21 treated with paracentesis died during the study period . The cumulative probabilities of survival at 1 and 2 years were 80 and 64 % in the TIPS group and 49 and 35 % in the paracentesis group ( p < 0.005 ) . TIPS was significantly superior to paracentesis in the control of ascites ( p < 0.005 ) . Treatment failure was more frequent in the paracentesis group , whereas the frequency of hepatic encephalopathy was greater in the TIPS group . Conclusions In cirrhotic patients with refractory ascites who have good hepatic and renal function , TIPS improves survival and provides better control of ascites than large-volume paracentesis BACKGROUND AND AIMS The clinical utility of transjugular intrahepatic portosystemic shunts ( TIPS ) vis-à-vis total paracentesis in the management of refractory ascites is unclear . METHODS A multicenter , prospect i ve , r and omized clinical trial was performed in which 109 subjects with refractory ascites were r and omized to either medical therapy ( sodium restriction , diuretics , and total paracentesis ) ( n = 57 ) or medical therapy plus TIPS ( n = 52 ) . The principal end points were recurrence of tense symptomatic ascites and mortality . RESULTS A technically adequate shunt was created in 49 of 52 subjects . TIPS plus medical therapy was significantly superior to medical therapy alone in preventing recurrence of ascites ( P < 0.001 ) . The total number of deaths in the 2 groups was identical ( TIPS vs. medical therapy alone : 21 vs. 21 ) . There were no significant differences in the 2 arms with respect to overall and transplant-free survival . There was a higher incidence of moderate to severe encephalopathy in the TIPS group ( 20 of 52 vs. 12 of 57 ; P = 0.058 ) . There were no significant differences in the number of subjects who developed liver failure ( 7 vs. 3 ) , variceal hemorrhage ( 5 vs. 8) , or acute renal failure ( 3 vs. 2 ) . There were also no significant differences between the 2 groups in the frequency of emergency-department visits , medically indicated hospitalizations , or quality of life . CONCLUSIONS Although TIPS plus medical therapy is superior to medical therapy alone for the control of ascites , it does not improve survival , affect hospitalization rates , or improve quality of life BACKGROUND & AIMS Paracentesis associated with plasma exp and ers is widely used for the treatment of ascites in cirrhosis . This study investigated the clinical importance of paracentesis-induced-circulatory dysfunction and compared the efficacy of albumin , dextran 70 , and polygeline in preventing this complication . METHODS A total of 289 cirrhotic patients with ascites were r and omized to treatment by total paracentesis plus intravenous albumin ( 97 patients ) , dextran 70 ( 93 patients ) , or polygeline ( 99 patients ) . Postparacentesis circulatory dysfunction was defined as an increase in plasma renin activity on the sixth day after paracentesis of more than 50 % of the pretreatment value to a level > 4 ng.mL-1.h-1 . RESULTS Postparacentesis circulatory dysfunction occurred more frequently in patients treated with dextran 70 ( 34.4 % ; P = 0.018 ) or polygeline ( 37.8 % ; P = 0.004 ) than in those receiving albumin ( 18.5 % ) . The plasma exp and er used and the volume of ascites removed were independent predictors of this complication . Postparacentesis circulatory dysfunction persisted during follow-up and was associated with a shorter time to first readmission ( 1.3 + /- 0.5 vs. 3.5 + /- 0.8 months , median + /- SEM ; P = 0.03 ) and shorter survival ( 9.3 + /- 4.2 vs. 16.9 + /- 4.3 months ; P = 0.01 ) . Creatinine and sodium levels in serum , and Child-Pugh score at inclusion , and postparacentesis circulatory dysfunction were independent predictors of survival . CONCLUSIONS Postparacentesis circulatory dysfunction is not spontaneously reversible and is associated with a shorter time to first readmission and shorter survival . Albumin is the best plasma exp and er to prevent this complication Background Refractory ascites ( RA ) is a complication of cirrhosis which is treated with large volume paracentesis ( LVP ) as the st and ard of care . Alfapump ® system is a fully implantable pump system which reduces the need for LVP . The aim was to assess health-related quality of life ( HRQL ) in patients treated with alfapump ® versus LVP . Methods The data were collected in a multicenter open-label r and omized controlled trial ( clinical trials.gov # NCT01528410 ) . Subjects with cirrhosis Child – Pugh class B or C accompanied by RA were r and omized to receive alfapump ® or LVP . The SF-36v2 and CLDQ scores were compared between the two treatment arms at screening and monthly during treatment . Results Of 60 subjects r and omized , HRQL data were available for 58 ( N = 27 received alfapump ® and N = 31 received LVP only ) . At baseline , no differences were seen between the treatment arms ( all p > 0.05 ) : age 61.9 ± 8.4 , 79.3 % male , MELD scores 11.7 ± 3.3 , 85.2 % Child – Pugh class B , 70.7 % had alcoholic cirrhosis . The mean number of LVP events/subject was lower in alfapump ® than LVP ( 1.1 vs. 8.6 , p < 0.001 ) . The HRQL scores showed a moderate improvement from the baseline levels in subjects treated with alfapump ® ( p < 0.05 for abdominal and activity scores of CLDQ ) but not with LVP ( all one-sided p > 0.05 ) in the first 3 months . Multivariate analysis showed that treatment with alfapump ® was independently associated with better HRQL at 3 months ( total CLDQ score : beta = 0.67 ± 0.33 , p = 0.05 ) . Conclusion As compared to LVP , the use of alfapump ® system is associated with both a reduction in the number of LVP events and improvement of health-related quality of life The aim of the current study was to compare total paracentesis associated with dextran-40 infusion with diuretics in the treatment of tense ascites in patients with cirrhosis . Eighty patients were r and omly allocated to two groups : 40 patients were treated with paracentesis plus dextran-40 infusion ( 8 g per liter of ascitic fluid removed ) , and 40 patients with diuretics . After treatment patients were discharged with diuretics , and patients developing tense ascites during follow up ( 54 + /- 4 weeks ) were treated according to their initial schedule . Paracentesis was more effective than diuretics in mobilizing the ascitic fluid . The incidence of complications was significantly higher ( p < 0.05 ) in the diuretic group ( 38 % ) than in the paracentesis group ( 15 % ) . This difference was mainly due to a higher incidence of hepatic encephalopathy in the former group ( 30 % vs. 2.5 % ) . A significantly higher incidence of hepatic encephalopathy was also observed in the diuretic group during the follow-up readmissions for ascites recurrence . There were no significant differences between the two treatment groups in the probability of survival after inclusion . Plasma renin activity and plasma aldosterone concentration measured before and 2 and 6 days after paracentesis in 20 r and omly selected patients increased significantly ( p < 0.05 ) ( baseline values : 5.3 + /- 1.4 ng.ml-1.h-1 and 63 + /- 21 ng/dl ; 48 h after paracentesis : 11.7 + /- 3.9 ng.ml-1.h-1 and 99 + /- 31 ng/dl ; 6 days after paracentesis : 10.9 + /- 3 ng.ml-1.h-1 and 110 + /- 27 ng/dl ) . ( ABSTRACT TRUNCATED AT 250 WORDS A multi-centre r and om trial of 57 cases of alcoholic cirrhosis with refractory ascites was carried out ; 29 patients received a LeVeen shunt and 28 were treated by conventional medical therapy . The effectiveness of the LeVeen shunt in reducing ascites was good in the first month , but was not different from conventional medical therapy by the end of one year . Complications were significantly more frequent in the surgical group . Of the 29 patients fitted with a LeVeen shunt , 25 developed one or more complications . Of the 28 patients in the medical control group , only 8 developed complications . The mortality rate of the two groups also differed significantly . Twelve patients in the surgical group ( 41 % ) died in the course of the first month against only 5 ( 18 % ) in the medical control group . By the end of one year , the mortality rate of the two groups was almost identical : 23 ( 79 % ) and 21 ( 75 % ) respectively . These observations confirm the poor prognosis for refractory ascites in cases of alcoholic cirrhosis and the inadvisability of attempting to treat it by implanting a LeVeen shunt To investigate the usefulness of paracentesis as an alternative treatment for ascites , 41 cirrhotic patients with ' tense ' ascites were r and omly assigned to treatment with either repeated paracenteses plus i.v . albumin infusion ( n = 20 ) or diuretics ( n = 21 ) . Satisfactory mobilization of ascites was obtained with paracentesis in all but one case and with diuretics in all but two cases . Ascites disappeared within 3 or 4 days with paracentesis , but only after 15 days with diuretics . The rate of reaccumulation of ascites following paracentesis , without diuretic administration , exceeded 300 g/day in only 5 patients . The incidence of complications and the mortality rate were similar in both groups of patients during hospital stay and during follow-up . This was corroborated by the evidence that no negative changes were induced in clinical and laboratory parameters of hemodynamic , hepatic and renal function after evacuation of the ascites . These results confirm that repeated paracenteses combined with human albumin replacement are safe and effective for treating ' tense ' ascites , and more rapid than traditional diuretic therapy BACKGROUND / AIMS Diuretic requirements after mobilization of ascites by paracentesis have never been assessed in cirrhosis . It is also unknown whether diuretics increase the incidence of postparacentesis circulatory dysfunction . The aim of this study was to investigate these features and to assess whether measurement of plasma renin activity and aldosterone prior to paracentesis predicts diuretic response after this procedure . METHODS Thirty-six patients with non-azotemic cirrhosis and ascites treated by total paracentesis plus i.v . albumin were r and omly assigned to receive placebo ( n=17 ) or spironolactone 225 mg/day ( n=19 ) immediately after paracentesis and followed-up for 4 weeks . RESULTS Five patients ( three in the placebo and two in the spironolactone group ) ab and oned the treatment prior to ascites recurrence or the end of the study due to complications or lack of compliance . The analysis was performed in the remaining 31 patients . Ascites recurrence was more common in the placebo group ( 13 cases , 93 % ) than in the spironolactone group ( 3 cases , 18 % ) ( p<0.0001 ) and occurred within the first 2 weeks of follow-up in more than 50 % of patients . Patients developing ascites in the spironolactone group had higher levels of renin ( 14.1 , 20.6 , 32.4 ng/ml per h ) and aldosterone ( 120 , 149 , 288 ng/dl ) than those who did not develop ascites ( renin : 2.0+/-2.1 ng/ml per h ; range 0.1 - 6.8 ; aldosterone : 43+/-38 ng/dl ; range 4 - 116 ) . Three patients in the placebo group and two in the spironolactone group developed postparacentesis circulatory dysfunction ( defined as an increase in renin at the third day after paracentesis greater than 50 % over baseline levels up to a value higher than 4 ng/ml per h ) . CONCLUSIONS Patients with cirrhosis treated by paracentesis should receive diuretics immediately after this procedure to prevent early recurrence of ascites . The administration of 225 mg/day of spironolactone is a good empiric treatment for non-azotemic patients with cirrhosis , because it is effective in most cases and does not increase the incidence of postparacentesis circulatory dysfunction . The determination of plasma levels of renin or aldosterone prior to paracentesis predicts the efficacy of spironolactone in the prevention of ascites recurrence Aims This study aim ed to compare the change in health‐related quality of life of patients receiving a traditional cemented monoblock Thompson hemiarthroplasty compared with a modern cemented modular polished‐taper stemmed hemiarthroplasty for displaced intracapsular hip fractures . Patients and Methods This was a pragmatic , multicentre , multisurgeon , two‐arm , parallel group , r and omized st and ard‐of‐care controlled trial . It was embedded within the WHiTE Comprehensive Cohort Study . The sample size was 964 patients . The setting was five National Health Service Trauma Hospitals in Engl and . A total of 964 patients over 60 years of age who required hemiarthroplasty of the hip between February 2015 and March 2016 were included . A st and ardized measure of health outcome , the EuroQol ( EQ‐5D‐5L ) question naire , was carried out on admission and at four months following the operation . Results Of the 964 patients enrolled , 482 died or were lost to follow‐up ( 50 % ) . No significant differences were noted in EQ‐5D between groups , with a mean difference at four months of 0.037 in favour of the Exeter/Unitrax implant ( 95 % confidence interval ( CI ) 0.014 to 0.087 , p = 0.156 ) , rising to 0.045 ( 95 % CI 0.007 to 0.098 , p = 0.09 ) when patients who died were excluded . The minimum clinical ly important difference for EQ‐5D‐5L used in this study is 0.08 , therefore any benefit between implants is unlikely to be noticeable to the patient . There was no difference in mortality or mobility score . Conclusion Allowing for the high rate of loss to follow‐up , the use of the traditional Thompson hemiarthroplasty in the treatment of the displaced intracapsular hip fracture shows no difference in health outcome when compared with a modern cemented hemiarthroplasty Summary In a r and omized prospect i ve study the efficacy and side effects of xipamide versus the combination spironolactone/furosemide in the treatment of cirrhotic ascites were studied . Out of 27 patients four responded to a basic treatment consisting of salt and water restriction and one had to be excluded because of deterioration of kidney function . The remaining 22 patients were r and omized to additional treatment with either 20 mg xipamide/day ( group I ) or 200 mg spironolactone/ day combined with 40 mg of furosemide every other day ( group II ) . A response to treatment during the first 4 days was seen in 7 of 11 patients of group I versus only 3 of 11 patients in group II . In the latter group 7 of 11 patients finally responded after 8 days of treatment . Responsiveness to either diuretic treatment strongly depended on pretreatment fractional Na excretion , FENa . The resistance to diuretic treatment can be predicted by a FENa<0.2 % , and could be overcome by additional strategies known to reduce avid proximal Na reabsorption . Xipamide frequently induced hypokalemia , whereas hyperkalemia was seen following treatment with spironolactone/furosemide . Kidney function remained stable during either diuretic treatment Intravenous albumin infusion prevents complications after large-volume paracentesis ( LVP ) , particularly paracentesis-induced circulatory dysfunction ( PCD ) , and improves patient survival . However , albumin is expensive . We compared a low-molecular weight dextran ( Dextran-40 ) with albumin in treating LVP in cirrhotic patients with tense ascites . Sixty-nine cirrhotic patients were included and 96 LVPs were performed . Any repeat punctures on the same patient were at least three months apart . Patients were r and omized to receive either i.v . Dextran-40 infusion ( Group I , n = 48 ) or i.v . albumin infusion after LVP ( Group II , n = 48 ) . Clinical , biochemical , and hormonal evaluations were done before and after LVP . Patients were followed up for the detection of any recurrence of ascites or complications . The two groups were similar in age , sex , and etiology of cirrhosis , and in the volumes of ascites recovered . Significant decreases in mean arterial pressure were observed in both groups 24 and 48 h after LVP . Urine volumes increased significantly at 24 h in both groups ( p < 0.05 ) , but remained high only in Group I. Plasma renin activity and aldosterone concentrations increased in both groups 48 h after LVP , but they were more marked in Group I. Complications developed in 17 % of patients treated with Dextran-40 and in 23 % treated with albumin ( p > 0.05 ) . Ascites recurrence rates and survival were similar in the two groups . In conclusion , Dextran-40 was thus not as efficacious as albumin for preventing PCD Ascitic fluid opsonic activity and ascitic fluid C3 concentrations are important protective factors against spontaneous bacterial peritonitis . This r and omized controlled study was performed to compare the effect of diuretic administration alone vs. single large-volume therapeutic paracentesis followed by administration of diuretics on ascitic fluid opsonic activity and on ascites and serum immunoglobulin and complement concentrations in patients with alcoholic cirrhosis and tense ascites . Twenty-one patients were r and omly allocated to two groups : group 1 included 11 patients who were treated with diuretics alone , and group 2 included 10 patients who were treated with single large-volume therapeutic paracentesis ( 5 to 6 L of ascites removed ) followed by diuretics . Ascitic fluid opsonic activity and serum and ascites immunoglobulin and complement concentrations were measured at the beginning and at the end of treatment . The ascitic fluid opsonic activity increased significantly in patients treated with diuretics alone ( p < 0.05 ) , whereas in the group of patients treated with therapeutic paracentesis followed by diuretics , the ascites opsonic activity remained stable . Although ascitic fluid IgG , IgA and C3 concentrations increased significantly in patients treated with diuretics alone ( p < 0.05 ) , ascitic fluid C3 concentration significantly decreased in patients from group 2 ( p < 0.05 ) , whereas IgG and IgA concentrations remained unchanged . However , in both groups of patients serum immunoglobulin and complement concentrations remained unchanged . This study suggests that in cirrhotic patients with tense ascites , treatment with diuretics alone may have the potential advantage over single large-volume therapeutic paracentesis followed by the administration of diuretics of providing better protection from spontaneous bacterial peritonitis . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND AND AIMS Patients with refractory ascites ( RA ) require repeated large volume paracenteses ( LVP ) , which involves frequent hospital visits and is associated with a poor quality -of-life . This study assessed safety and efficacy of an automated , low-flow pump ( alfapump ® [ AP ] ) compared with LVP st and ard of care [ SoC ] . METHODS A r and omized controlled trial , in seven centers , with six month patient observation was conducted . Primary outcome was time to first LVP . Secondary outcomes included paracentesis requirement , safety , health-related quality -of-life ( HRQoL ) , and survival . Nutrition , hemodynamics , and renal injury biomarkers were assessed in a sub- study at three months . RESULTS Sixty patients were r and omized and 58 were analyzed ( 27 AP , 31 SoC , mean age 61.9years , mean MELD 11.7 ) . Eighteen patients were included in the sub- study . Compared with SoC , median time to first LVP was not reached after six months in the AP group , meaning a significant reduction in LVP requirement for the AP patients ( AP , median not reached ; SoC , 15.0days ( HR 0.13 ; 95%CI 13.0 - 22.0 ; p<0.001 ) , and AP patients also showed significantly improved Chronic Liver Disease Question naire ( CLDQ ) scores compared with SoC patients ( p<0.05 between treatment arms ) . Improvements in nutritional parameters were observed for h and -grip strength ( p=0.044 ) and body mass index ( p<0.001 ) in the sub- study . Compared with SoC , more AP patients reported adverse events ( AEs ; 96.3 % vs. 77.4 % , p=0.057 ) and serious AEs ( 85.2 vs. 45.2 % , p=0.002 ) . AEs consisted predominantly of acute kidney injury in the immediate post-operative period , and re-intervention for pump related issues , and were treatable in most cases . Survival was similar in AP and SoC. CONCLUSIONS The AP system is effective for reducing the need for paracentesis and improving quality of life in cirrhotic patients with RA . Although the frequency of SAEs ( and by inference hospitalizations ) was significantly higher in the AP group , they were generally limited and did not impact survival . Lay summary : The alfapump ® moves abdominal fluid into the bladder from where it is then removed by urination . Compared with st and ard treatment , the alfapump reduces the need for large volume paracentesis ( manual fluid removal by needle ) in patients with medically untreatable ascites . This can improve life quality for these patients . www . clinical trials.gov#NCT01528410 Uncontrolled studies suggest that transjugular intrahepatic portal‐systemic shunting ( TIPS ) may improve quality of life in patients with refractory ascites . We hypothesized that any improvement of quality of life in patients with TIPS would be matched in controls due to the competing effects of improved ascites and worsened hepatic encephalopathy . Thus , an analysis of quality of life was performed using original data from the North American Study for the Treatment of Refractory Ascites , a multicenter trial of 109 patients r and omized to TIPS or repeated large volume paracentesis ( LVP ) for refractory ascites . Short form 36 ( SF‐36 ) surveys were completed at baseline and at 6‐ and 12‐month follow‐up . Variables analyzed were : r and omization group , number of LVP performed , cumulative volume from LVP , shortness of breath , abdominal distention , abdominal pain , diuretic usage , confusion , hospitalizations , and emergency room visits . Outcomes were changes in physical component scale ( PCS ) and mental component scale ( MCS ) of SF‐36 results . We constructed multivariable , mixed effects models , including r and omization group and baseline MCS and PCS . Changes in PCS and MCS from baseline were similar between the two r and omization groups . In multivariate analysis , PCS improvement was associated with lack of confusion , improved ascites , and lack of hospitalizations , but not directly with r and omization group . Improvement in MCS was associated with r and omization to TIPS and lack of confusion . In conclusion , patients with refractory ascites r and omized to TIPS or repeated LVP had similar changes in quality of life . Competing effects of hepatic encephalopathy , requirement for repeated LVP , and need for hospitalizations explain similar changes in quality of life between the two groups . ( HEPATOLOGY 2005 . Forty-three patients with decompensated alcoholic liver disease and ascites of recent onset were r and omized to salt and water restriction alone ( control group ) or to salt and water restriction plus diuretics ( diuresis group ) . The two treatment groups were comparable in clinical findings and laboratory results . Seven patients in the control group and 5 patients in the diuresis group died during the acute illness . Weight loss was more marked and the disappearance of ascites more common in those given diuretics . A modest decrease in serum sodium and increase in serum potassium , and readily reversible elevations of blood urea nitrogen were noted in the diuresis group . Eight patients in each treatment group developed either the hepatorenal syndrome , marked electrolyte abnormalities , or encephalopathy . Diuresis can be accomplished in these critically ill patients without serious complications that can be attributed to the diuretic treatment OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials Dialytic ultrafiltration of ascites through a hemofilter associated with peritoneal reinfusion ( DUF ) of the concentrate has been proposed for the treatment of refractory ascites . In five cirrhotic patients , 18 ascites evacuation procedures were r and omized either to DUF ( n=8 ) or to large paranceteses ( LP ) ( n=10 ) . The effects of these two methods on hemodynamic and renal function were assessed . After DUF , the protein concentration in ascites increased transiently from 28±7 g/l to 64.8±8 g/l ( p<0.04 ) ; urinary output increased from day 1 to day 4 ( 1000±100 ) VS 1430±140 ml/24h ; p<0.02 ) . After LP , ascitic protein concentration and urinary output were unchanged . No side effects were observed with the two methods . The mean amount of albumin infused was 20±15 g after DUF and 15±5 after LP ( ns ) Objective Large-volume paracentesis associated with plasma volume expansion with albumin is an effective , safe , but costly therapy for ascites in patients with cirrhosis . The aim of this study was to compare the use of a synthetic plasma exp and er , hydroxyethyl starch ( HES ) , with that of albumin . Design Sixty cirrhotic patients with ascites were studied . Patients were r and omly assigned to be infused with either albumin ( 8 g/l of ascites removed , n = 33 ) or HES ( 200 ml/I of ascites removed , n = 27 ) . None of the patients was treated with diuretics or had renal impairment or hyponatremia at entry . Clinical and laboratory data were obtained before and 1 , 3 and 15 days after treatment Results There were no significant differences in clinical and laboratory parameters between the two groups at entry into the study . None of the patients developed renal impairment during the trial . One patient ( HES group ) presented with hyponatremia . Plasma atrial natriuretic factor and aldosterone levels did not differ between the two groups at baseline or at 1 and 3 days after paracentesis . The volume of ascites removed did not differ between the albumin ( 7.9 ± 4.41 ) and HES ( 6.9 ± 5.3 I ) groups . However , there was a significant difference in weight loss between the albumin and HES groups ( 7.9 ± 5.2 kg vs 4.7 ± 3.4 kg ; p = 0.01 ) . Clinical and laboratory parameters indicated that HES was well tolerated except for hypoalbuminemia . Conclusion HES is well tolerated in patients with cirrhosis . There is no difference between HES and albumin in the prevention of complications related to large-volume paracentesis . The lesser degree of weight loss observed with HES needs further study OBJECTIVES : Splanchnic arterial vasodilatation and subsequent activation of anti-natriuretic and vasoconstrictive mechanisms have an important role in cirrhotic ascites . The aim of this study was to evaluate the effects of midodrine , clonidine , and their combination on systemic hemodynamics , renal function , and control of ascites in patients with cirrhosis and refractory or recurrent ascites . METHODS : Sixty cirrhotic patients with refractory or recurrent ascites were prospect ively studied after long-term administration of clonidine ( n=15 ) or midodrine ( n=15 ) , or both ( n=15 ) plus st and ard medical therapy ( SMT ) , or SMT alone ( n=15 ) , in a r and omized controlled trial at a tertiary center . RESULTS : A significant increase in urinary volume , urinary sodium excretion , mean arterial pressure , and decrease in plasma renin activity ( P<0.05 ) was noted after 1 month . There was also a significant decrease in cardiac output ( P<0.05 ) and increase in systemic vascular resistance ( P<0.05 ) in all groups , except clonidine . There was no change in glomerular filtration rate and model for end-stage liver disease score . Midodrine and a combination of midodrine and clonidine plus SMT were superior to SMT alone in the control of ascites ( P=0.05 ) , and there was a trend towards better control of ascites in the clonidine group ( P=0.1 ) . The mortality and frequency of various complications were similar in all groups . CONCLUSIONS : These results suggest that midodrine , clonidine , and their combination plus SMT improves the systemic hemodynamics without any renal or hepatic dysfunction , and is superior to SMT alone for the control of ascites . However , the combination therapy was not superior to midodrine or clonidine alone A prospect i ve r and omized matched pair study was design ed to test the efficacy of the peritoneovenous ( LeVeen ) shunt as a treatment for massive cirrhotic ascites compared with traditional medical therapy . Patients who failed to lose weight while on a low salt diet and fluids restricted to 1000 ml daily were placed in the study group . Weight loss , decrease in abdominal girth and diuresis were significantly greater ( P < 0·01 ) for surgical patients than for their medically treated counterparts . The surgical technique is simple , quick and inexpensive . The surgical patients outlived their matched partners in 12 of 14 pairs where a definitive comparison was possible ( P < 0·02 ) . The median stay in hospital after r and omization was shortened from 32 days with medical therapy to 15 days for those undergoing the shunt operation . Those treated medically experienced a significant rise in mean blood urea nitrogen and K+ ( P < 0·02 ) . Patients with alcoholic hepatitis , hyperbilirubinaemia ( bilirubin > 154 m̈mol/l ) , peritoneal sepsis , severe coagulopathy and those who had recently bled from oesophageal varices are poor risks for the surgical procedure In patients with cirrhosis , ascites accumulates because of sodium retention , triggered by a reduction of the effective arterial blood volume , and imbalanced Starling forces in the splanchnic area due to portal hypertension and hypoalbuminemia . Albumin is the ideal plasma exp and er in this setting , since it ameliorates systemic and reneal haemodynamics , so reducing sodium retention , and increases oncotic pressure in the splanchnic compartment . In particular , albumin proved useful in patients treated with diuretics , as demonstrated by a r and omised study performed at our Instituition in which 126 ascitic in patients were treated according to a stepped-care diuretic regimen . In fact , patients receiving diuretics plus albumin ( n = 63 ) had a higher cummulative rate of response ( p < 0.05 ) and a shorter hospital stay ( 20 + /- 1 versus 24 + /- 2 days , p < 0.05 ) than those given diuretics alone . Treatment with albumin on an outpatient basis ( 25 g/week ) result ed in a lower probability of developing ascites ( p < 0.02 vs. patients not given albumin ) and a lower probability of readmission ( p < 0.02 ) . Patients given albumin also had a better quality of life . As discussed in another article , evidence also supports the use of albumin in patients treated for paracentesis , as well as in patients with spontaneous peritonitis or hepatorenal syndrome Although some clinical studies seem to prove the efficacy of nonantialdosteronic potassium-sparing diuretics in the treatment of ascites , no controlled study has compared the efficacy of these drugs with that of antialdosteronic diuretics . Forty nonazotemic cirrhotic patients were r and omized to receive amiloride ( group A , n = 20 ) or potassium canrenoate ( group B , n = 20 ) . The initial doses of amiloride and potassium canrenoate were 20 mg and 150 mg , respectively . The doses were increased in stepwise fashion to 60 and 500 mg/day , respectively , if no response ensued . Nonresponders to the highest doses of each drug were later treated with potassium canrenoate and amiloride , respectively . Seven of 20 group A patients responded to amiloride , whereas 14 of 20 group B patients responded to potassium canrenoate ( p < 0.025 ) . Seven of 13 nonresponders to amiloride later responded to potassium canrenoate , whereas only two of the nonresponders to potassium canrenoate later responded to amiloride . The diuretic responses to amiloride and potassium canrenoate were related to the activity of the renin-aldosterone system . All responders to amiloride ( n = 9 ) had normal values of plasma aldosterone . All nonresponders to amiloride who later responded to potassium canrenoate ( n = 7 ) had increased levels of plasma aldosterone . Moreover , on comparison of all responders ( n = 21 ) and nonresponders ( n = 12 ) to potassium canrenoate , a higher degree of renal proximal sodium reabsorption ( with consequent limitation of sodium delivery to the distal tubule ) was found to be the main difference . ( ABSTRACT TRUNCATED AT 250 WORDS Therapeutic paracentesis has recently been reported to eliminate ascites in patients with cirrhosis more rapidly than diuresis . However , diuresis has been shown to increase ascitic fluid opsonic activity . Patients with adequate ascitic fluid opsonic activity have been reported to be protected from spontaneous bacterial peritonitis . In this r and omized controlled trial , 19 patients with cirrhotic ascites were treated with diuresis versus daily therapeutic paracenteses during 20 hospitalizations . Serum and ascitic fluid complement concentrations and ascitic fluid opsonic activity were measured at the beginning and end of treatment . Although opsonic activity increased significantly ( p less than 0.01 ) in patients treated with diuresis , this parameter was stable in the paracentesis group . The stability of the ascitic fluid opsonic activity and complement concentration in the paracentesis group were maintained at the expense of a decrease in serum complement , whereas serum and ascitic fluid complement increased in the diuresis group . Diuresis may have the advantage over therapeutic paracentesis of providing better protection from spontaneous bacterial peritonitis . Study of larger numbers of patients will determine if these changes in complement concentrations and opsonic activity translate into an increased risk of spontaneous bacterial peritonitis in vivo The transjugular intrahepatic portosystemic shunt ( TIPS ) has been shown to be effective in the control of refractory or recidivant ascites . However , the effect of TIPS on survival as compared with that of large‐volume paracentesis plus albumin is uncertain . A multicenter , prospect i ve , clinical trial was performed in 66 patients with cirrhosis and refractory or recidivant ascites ( 16 Child‐Turcotte‐Pugh class B and 50 Child‐Turcotte‐Pugh class C ) r and omly assigned to treatment with TIPS ( n = 33 ) or with large‐volume paracentesis plus human albumin ( n = 33 ) . The primary endpoint was survival without liver transplantation . Secondary endpoints were treatment failure , rehospitalization , and occurrence of complications . Thirteen patients treated with TIPS and 20 patients treated with paracentesis died during the study period , 4 patients in each group underwent liver transplantation . The probability of survival without transplantation was 77 % at 1 year and 59 % at 2 years in the TIPS group as compared with 52 % and 29 % in the paracentesis group ( P = .021 ) . In a multivariate analysis , treatment with paracentesis and higher MELD score showed to independently predict death . Treatment failure was more frequent in patients assigned to paracentesis , whereas severe episodes of hepatic encephalopathy occurred more frequently in patients assigned to TIPS . The number and duration of rehospitalizations were similar in the two groups . In conclusion , compared to large‐volume paracentesis plus albumin , TIPS improves survival without liver transplantation in patients with refractory or recidivant ascites . ( HEPATOLOGY 2004;40:629–635 . This study was undertaken to investigate the role of increased renal thromboxane ( TX ) A2 production in modulating renal hemodynamics and sodium and water retention in cirrhotic patients with ascites . In a r and omized , double-blind , placebo-controlled , crossover trial , 15 nonazotemic cirrhotic patients with ascites and elevated urinary TXB2 excretion received the thromboxane-receptor antagonist ONO-3708 ( 3 micrograms.kg-1.min-1 ) in a 4-hour continuous infusion . Administration of ONO-3708 significantly blocked TXA2 receptors ; bleeding time showed a twofold increase ( 432 + /- 65 vs. 131 + /- 17 seconds ; P less than 0.005 ) , and platelet aggregation to U-46619 ( an agonist of TXA2 receptors ) was abolished in all patients studied . The drug induced a significant increase in free water clearance ( 3.06 + /- 0.70 vs. 1.72 + /- 0.57 mL/min ; P less than 0.001 ) and diuresis ( 4.74 + /- 0.79 vs. 3.94 + /- 0.66 mL/min ; P less than 0.05 ) compared with placebo , as well as a significant ( 14 % ) increase in renal plasma flow . The increases in both free water clearance and diuresis induced by ONO-3708 were directly related to basal urinary TXB2 excretion . These results suggest a role for renal TXA2 as a modulator of water h and ling in cirrhotic patients with ascites We studied 35 cirrhotic patients with tense ascites assigned at r and om into two groups : Group I consisted of 17 patients treated by total therapeutic paracentesis ( TTP ) ( 6 - 15 l ) plus i.v . albumin ( 5 g/l of fluid ) and Group II consisted of 18 patients treated by TTP ( 5.5 - 15.5 l ) without albumin . On 19 patients we performed a sequential assessment of cardiac output ( CO ) , plasma renin activity ( PRA ) and plasma aldosterone ( PA ) . Both groups were similar in age , sex , and etiology of cirrhosis . CO , PRA and PA values were expressed as mean changes occurring in relation to their respective baseline values . CO changes after TTP ( l/min ) : Group I : 2.5 after 6 h and 2.2 after 12 h ; Group II : 2.2 after 6 h and -0.4 after 12 h , ( p < 0.05 comparing values after 12 h between the two groups ) . PRA changes after TTP ( ng/dl/h ) : Group I : -7.4 after 1 h , -7.8 after 6 h and -3.2 after 24 h ; Group II : -2.4 after 1 h , -0.8 after 6 h and 3.9 after 24 h ( p < 0.05 comparing values between both groups after 6 and 24 h ) . PA changes after TTP ( ng/dl ) : Group I : -50.5 after 1 h , -36.7 after 6 h and -34.6 after 24 h ; Group II : -18.2 after 1 h , -2.2 after 6 h and 20 after 24 h , ( p < 0.05 comparing values between both groups after 1 and 6 h ) . Complications were minimal in both groups . ( ABSTRACT TRUNCATED AT 250 WORDS AIM There have been only a few trials demonstrating additional effects of human serum albumin ( HSA ) on diuretic therapy in patients with cirrhotic ascites . We aim ed to evaluate the safety and efficacy of recombinant HSA , KD-294 , treatment in patients with cirrhotic ascites . METHODS The inclusion criteria were patients 20 - 75 years of age , with cirrhotic ascites and a serum albumin concentration of less than 3.0 g/dL. Eighty-five patients were registered and 71 patients underwent r and omization . Enrolled patients received oral spironolactone at 50 mg/day and i.v . furosemide at 20 mg/day in addition to low-sodium diet . They were divided r and omly into a KD-294 treatment group ( n = 35 ) or non-treatment control group ( n = 36 ) . Patients in the KD-294 group received KD-294 at 25 g/day for up to 5 days and those in the control group continued the diuretic therapy . They were followed up for 5 weeks . RESULTS KD-294 was well tolerated . A correlation between the increases in serum albumin and decreases in bodyweight was not shown . However , changes of plasma renin concentration ( PRC ) showed a significant decrease in the KD-294 group compared with the control group . As a result of this exploratory analysis , patients with high PRC showed a significant correlation between increases in serum albumin and decreases in bodyweight . CONCLUSION The present data do not show efficacy in all patients with cirrhotic ascites , however , they suggest that additional effects of HSA on diuretic therapy are expected in high PRC patients OBJECTIVE Therapeutic paracentesis in patients with cirrhosis is associated with a circulatory dysfunction . Intravenous albumin has been used to prevent the circulatory dysfunction ; however , the use of albumin is controversial and costly . Splanchnic vasodilation is mainly responsible for circulatory dysfunction in these patients . There are no reports of use of noradrenaline , a vasoconstrictor , on the prevention of paracentesis-induced circulatory dysfunction in patients with cirrhosis . Therefore , we studied the preventive effect of noradrenaline on paracentesis-induced circulatory dysfunction in patients with cirrhosis after therapeutic paracentesis and compared it with that of intravenous albumin in a r and omized pilot study . METHODS Forty patients with cirrhosis and tense ascites underwent therapeutic paracentesis with albumin or noradrenaline in a r and omized controlled trial at a tertiary centre . Effective arterial blood volume was assessed by measuring plasma renin activity at baseline and at 6 days after treatment . RESULTS Effective arterial blood volume as indicated by plasma renin activity before and 6 days after paracentesis did not differ in the two groups ( 20.62 + /- 10.27 - 22.02 + /- 10.15 ng mL(-1 ) h(-1 ) ; P = 0.11 in the albumin group and 19.66 + /- 8.91 - 20.78 + /- 9.41 ng mL(-1 ) h(-1 ) ; P = 0.37 in the noradrenaline group ) . Plasma aldosterone concentration before and 6 days after paracentesis were also similar in both groups ( 1196.5 + /- 434.2 - 1217.0 + /- 405.7 pg mL(-1 ) ; P = 0.7 in the albumin group and 1206.0 + /- 522.5 - 1273.5 + /- 444.8 pg mL(-1 ) ; P = 0.22 in the noradrenaline group ) . The cost of noradrenaline treatment was significantly lower when compared with that of albumin ( P < 0.001 ) . CONCLUSIONS Noradrenaline is as effective as albumin in preventing paracentesis-induced circulatory dysfunction in patients with cirrhosis after therapeutic paracentesis , but at a fraction of the cost To investigate whether paracentesis could be an alternative therapy for ascites , 117 cirrhotics with tense ascites were r and omly allocated into two groups . Fifty-eight patients ( group 1 ) were treated with paracentesis ( 4 - 6 L/day until disappearance of ascites ) and intravenous albumin infusion ( 40 g after each tap ) . Fifty-nine patients ( group 2 ) were treated with spironolactone ( 200 - 400 mg/day ) plus furosemide ( 40 - 240 mg/day ) . Patients from group 2 not responding to diuretics were treated with a LeVeen shunt . After disappearance of ascites , patients from both groups were discharged from hospital and were instructed to take diuretics . Patients developing tense ascites during follow-up were readmitted to hospital and treated according to their initial schedule . Paracentesis was effective in eliminating the ascites in 56 patients from group 1 ( 96.5 % ) and did not induce significant changes in renal and hepatic function , plasma volume , cardiac index , peripheral resistance , plasma renin activity , plasma norepinephrine and antidiuretic hormone concentration , and urinary excretion of prostagl and in E2 and 6-keto-prostagl and in F1 alpha . Diuretics were effective in eliminating the ascites in 43 patients from group 2 ( 72.8 % ) ( p less than 0.05 ) . Ten patients in group 1 and 36 in group 2 developed complications during their first hospital stay ( p less than 0.001 ) . This difference was due to the significantly higher incidence of hepatic encephalopathy , renal impairment , and electrolyte disturbances occurring in patients treated with diuretics . The duration of hospital stay was 11.7 + /- 1.5 days for patients from group 1 and 31 + /- 2.8 days for patients from group 2 ( p less than 0.001 ) . The two groups did not differ significantly with respect to the probability of requiring readmission to hospital during follow-up , reasons for readmission , survival probability after entry into the study , and causes of death . These results indicate that paracentesis associated with intravenous albumin infusion is a fast , effective , and safe therapy for ascites in patients with cirrhosis 72 cirrhotics with tense ascites were r and omly assigned to treatment with either paracentesis plus intravenous albumin infusion ( 38 patients ) or diuretics ( 34 patients ) . Paracentesis was not associated with significant changes in renal function . The clinical course of the disease was similar in the two groups of patients , both during their hospital stay and during follow-up BACKGROUND & AIMS Splanchnic arterial vasodilatation plays an important role in cirrhotic ascites . The aim of this study was to evaluate the effects of long term administration of midodrine on systemic hemodynamics , renal function , and control of ascites in patients with cirrhosis and refractory or recurrent ascites . METHODS Forty cirrhotic patients with refractory or recurrent ascites were prospect ively studied after long term administration of midodrine plus st and ard medical therapy ( n=20 ) or st and ard medical therapy alone ( n=20 ) in a r and omized controlled trial at a tertiary centre . RESULTS A significant increase in urinary volume , urinary sodium excretion , mean arterial pressure , and decrease in plasma renin activity ( p<0.05 ) was noted after 1 month of midodrine administration . There was also a significant decrease in cardiac output and an increase in systemic vascular resistance after midodrine therapy at 3 months ( p<0.05 ) . There was no change in glomerular filtration rate and model for end-stage liver disease ( MELD ) score . Midodrine plus st and ard medical therapy was significantly superior to st and ard medical therapy alone in the control of ascites ( p=0.013 ) at 3 months . The mortality rate in the st and ard medical therapy group was significantly higher than the midodrine group ( p<0.046 ) . There was no significant difference in the frequency of various complications at the end of follow-up . CONCLUSIONS The results of this r and omized pilot study suggest that midodrine plus st and ard medical therapy improves the systemic hemodynamics without any renal or hepatic dysfunction in these patients and is superior to st and ard medical therapy alone for the control of ascites BACKGROUND / AIMS Diuretic treatment of ascites could result in intravascular volume depletion , electrolyte imbalance and renal impairment . We investigated whether intravascular volume expansion with albumin exert beneficial effects in cirrhosis with ascites . METHODS In protocol 1 , 126 cirrhotic in patients in whom ascites was not relieved following bed rest and a low-sodium diet , were r and omly assigned to receive diuretics ( group A ) or diuretics plus albumin , 12.5 g/day ( group B ) . In protocol 2 , group A patients continued to receive diuretics and group B diuretics plus albumin ( 25 g/week ) as out patients and were followed up for 3 years . End points were : disappearance of ascites , duration of hospital stay ( protocol 1 ) , recurrence of ascites , hospital readmission and survival ( protocol 2 ) . RESULTS The cumulative rate of response to diuretic treatment of ascites was higher ( p < 0.05 ) and hospital stay was shorter ( 20 + /- 1 versus 24 + /- 2 days , p < 0.05 ) in group B than in group A patients . After discharge , group B patients had a lower cumulative probability of developing ascites ( 19 % , 56 % , 69 % versus 30 % , 79 % and 82 % at 12 , 24 and 36 months , p < 0.02 ) and a lower probability of readmission to the hospital ( 15 % , 56 % , 69 % versus 27 % , 74 % and 79 % , respectively , p < 0.02 ) . Survival was similar in the two groups . CONCLUSIONS Albumin is effective in improving the rate of response and preventing recurrence of ascites in cirrhotic patients with ascites receiving diuretics . However , the cost/benefit ratio was favorable to albumin in protocol 1 but not in protocol 2 BACKGROUND There is no satisfactory treatment for refractory ascites in patients with cirrhosis . Both peritoneovenous shunts and paracentesis have been used , but there is uncertainty about their relative merits . METHODS We studied 89 patients with cirrhosis and refractory ascites who were r and omly assigned to receive either repeated large-volume paracentesis plus intravenous albumin or a LeVeen peritoneovenous shunt . Patients in the paracentesis group in whom recurrent tense ascites developed during follow-up were treated with paracentesis , and those in the peritoneovenous-shunt group with diuretic agents or by the insertion of a new shunt if there was shunt obstruction . RESULTS During the first hospitalization , ascites was removed in all 41 patients in the paracentesis group and in 44 of the 48 patients in the peritoneovenous-shunt group . The mean ( + /- SD ) duration of hospitalization in the two groups was 11 + /- 5 and 19 + /- 9 days , respectively ( P less than 0.01 ) . There were no significant differences in the number of patients who had complications or died . During follow-up , 37 patients in each group were hospitalized again . In the paracentesis group , the number of rehospitalizations for any reason ( 174 vs. 97 in the peritoneovenous-shunt group ) or for ascites ( 125 vs. 38 ) was significantly higher , and the median time to a first readmission for any reason ( 1 + /- 1 vs. 2 + /- 2 months ) or for ascites ( 2 + /- 2 vs. 8 + /- 17 months ) was significantly shorter than in the peritoneovenous-shunt group . The total times in the hospital during follow-up , however , were similar in the two groups ( 48 + /- 49 and 44 + /- 39 days , respectively ) . Three patients had obstructions of their peritoneovenous shunts during their first hospitalizations , and 15 patients had a total of 20 obstructions during follow-up . Survival was similar in both groups . CONCLUSIONS The LeVeen shunt and paracentesis are equally effective in relieving refractory ascites . The former may provide better long-term control of ascites , but shunt occlusion is common and survival is not improved Previous studies have suggested that treatment of ascites in cirrhotic patients by repeated paracenteses and albumin infusion is fast , effective and safe . In one of these studies including patients with hyponatremia or renal impairment , this treatment was associated with a reduction of duration of hospital stay in comparison with large dose diuretics . The aim of this r and omized study was to compare paracentesis with albumin perfusion and low dose diuretics in cirrhotic patients with ascites , but without hyponatremia or renal impairment . Twenty-six patients ( group 1 ) were treated with paracentesis ( 4 L/day ) and 27 patients ( group 2 ) were treated with spironolactone ( 225 to 300 mg/day ) , associated with furosemide ( 40 to 80 mg/day ) , when inefficient alone . Ascites and peripheric edema disappeared more rapidly in group 1 than in group 2 , 8.6 + /- 9.6 vs 13.5 + /- 6.7 days ( P = 0.001 ) and 4.1 + /- 2.6 vs 10.5 + /- 6.5 days ( P = 0.001 ) respectively . During hospitalisation , the incidence of complications was higher in group 2 than in group 1 : 56 vs 26 % ( P = 0.03 ) . Hyponatremia occurred in 30 % of patients in group 2 and 4 % of patients in group 1 ( P = 0.04 ) . The duration of hospital stay was shorter in group 1 ( 15.0 + /- 10.4 days ) than in group 2 ( 21.0 + /- 11.7 days ) ( P = 0.007 ) . During follow-up , ascites reappeared in 32 % of patients in group 1 and 57 % of patients in group 2 ( P = 0.09 ) . At 3 months , one patient in group 1 and 2 patients in group 2 developed spontaneous peritonitis whereas survival was similar in both groups . ( ABSTRACT TRUNCATED AT 250 WORDS It has recently been suggested that insertion of a titanium tip at the venous end of the LeVeen shunt drastically reduces the rate of shunt obstruction . To assess whether the LeVeen shunt with titanium tip improves the results obtained with therapeutic paracentesis , 81 patients with cirrhosis and refractory ascites were r and omly assigned to therapy with paracentesis plus intravenous albumin ( 42 patients ) or LeVeen shunt with titanium tip ( 39 patients ) . If patients were readmitted for ascites during follow-up , those in the first group were treated with paracentesis , and those in the LeVeen shunt group by the insertion of a new valve or a new shunt if obstruction was demonstrated . During first hospitalization , both treatments were equally effective in removing ascites . Complications were similar in both groups except for a higher rate of severe bacterial infection in the LeVeen shunt group . The mean duration of hospitalization was shorter in the paracentesis group than in the shunt group . During follow-up , the total number of readmissions and the number of readmissions for ascites were higher in the paracentesis group than in the shunt group ( 252 vs. 99 , P < .001 ; and 193 vs. 43 , P < .001 , respectively ) . The total time in hospital , however , was similar ( 38 + /- 38 vs. 39 + /- 43 days , P = NS ) . Three patients had obstruction of the shunt during first hospitalization and 14 patients had a total of 22 obstructions during follow-up . Long-term survival was similar in both groups . The insertion of a titanium tip at the venous end of the LeVeen shunt does not prevent obstruction . ( ABSTRACT TRUNCATED AT 250 WORDS Paracentesis‐induced circulatory dysfunction ( PICD ) is a recently described complication that can be prevented with the administration of plasma exp and ers . The aim of this study was to compare the efficacy of saline versus albumin in the prevention of PICD . Patients were r and omized to receive albumin or saline after total paracentesis . Patients readmitted as a consequence of a second episode of tense ascites were treated with total paracentesis and the alternative plasma exp and er . After r and omization , 35 patients received saline and 37 received albumin . Twenty‐one patients were readmitted for tense ascites and treated with the alternative exp and er . Significant increases in plasma renin activity ( PRA ) were found 24 hours and 6 days after paracentesis when saline was used ( baseline , 5.6 ± 5.7 ; 24 hours , 7.6 ± 6.9 ; 6 days , 8.5 ± 8.0 ng · mL−1 · hr−1 ; P < .05 and P < .01 vs. baseline , respectively ) , whereas no significant changes were observed with albumin . The incidence of PICD was significantly higher in the saline group versus the albumin group ( 33.3 % vs. 11.4 % , respectively ; P = .03 ) . However , no significant differences were found when less than 6 L of ascitic fluid was evacuated ( 6.7 % vs. 5.6 % in the saline and albumin groups , respectively ; P = .9 ) . Similar results were observed when analyzing patients who received 2 consecutive paracentesis ( i.e. , a significant increase in PRA after saline [ P < .01 ] without significant variations after albumin ) . In conclusion , albumin is more effective than saline in the prevention of PICD . Saline is a valid alternative to albumin when less than 6 L of ascitic fluid is evacuated Fifty-four cirrhotic patients with refractory ascites were treated with one-session large-volume paracentesis and r and omly assigned to two groups . The first group was infused with human albumin , and the second group was infused with hemaccel at doses with comparable oncotic power . The two groups were compared for incidence of complications , recurrence of massive ascites after hospital dismissal and survival rate . The incidence of complications traditionally related to paracentesis , the probability of requiring readmission to the hospital for ascites ( p = 0.48 ) and the probability of survival after entry into the study ( p = 0.85 ) were the same for the two groups . A multivariate analysis of 16 parameters , including treatment modality , identified absolute unresponsiveness to diuretics as the only independent predictor of mortality . These results indicate that hemaccel infusion may safely replace albumin infusion after total paracentesis for cirrhotic patients with refractory ascites It has recently been shown that repeated large-volume paracentesis associated with intravenous albumin infusion is a rapid , effective , and safe therapy of ascites in cirrhosis . To investigate whether intravenous albumin infusion is necessary in the treatment of cirrhotics with large-volume paracentesis , 105 patients with tense ascites were r and omly allocated into two groups . Fifty-two patients ( group 1 ) were treated with paracentesis ( 4 - 6 L/day until disappearance of ascites ) plus intravenous albumin infusion ( 40 g after each tap ) , and 53 ( group 2 ) with paracentesis without albumin infusion . After disappearance of ascites , patients were discharged from the hospital with diuretics . Patients developing tense ascites during follow-up were treated according to their initial schedule . Paracentesis was effective in eliminating the ascites in 50 patients from group 1 and in 48 from group 2 , with the duration of the hospital stay being approximately 11 days in both groups . Paracentesis plus intravenous albumin did not induce significant changes in st and ard renal function tests , plasma renin activity , and plasma aldosterone . In contrast , paracentesis without albumin was associated with a significant increase in blood urea nitrogen , a marked elevation in plasma renin activity and plasma aldosterone concentration , and a significant reduction in serum sodium concentration . One patient from group 1 and 11 from group 2 developed renal impairment or severe hyponatremia after treatment , or both ( chi 2 = 9.19 ; p less than 0.01 ) . The development of these complications could not be predicted by clinical and laboratory data before treatment . Although the probability of survival after entry into the study was similar in patients from both groups , a multivariate analysis identified the development of hyponatremia or renal impairment , or both , following the first paracentesis treatment and the occurrence of other complications during the first hospitalization ( encephalopathy , gastrointestinal bleeding , and severe infection ) as being the only independent predictors of mortality . These results indicate that intravenous albumin infusion is important in avoiding renal and electrolyte complications and activation of endogenous vasoactive systems in cirrhotics with ascites who are treated with repeated large-volume paracentesis . The development of such complications may impair survival in these patients BACKGROUND In patients with cirrhosis and ascites , creation of a transjugular intrahepatic portosystemic shunt may reduce the ascites and improve renal function . However , the benefit of this procedure as compared with that of large-volume paracentesis is uncertain . METHODS We r and omly assigned 60 patients with cirrhosis and refractory or recurrent ascites ( Child-Pugh class B in 42 patients and class C in 18 patients ) to treatment with a transjugular shunt ( 29 patients ) or large-volume paracentesis ( 31 patients ) . The mean ( + /-SD ) duration of follow-up was 45+/-16 months among those assigned to shunting and 44+/-18 months among those assigned to paracentesis . The primary outcome was survival without liver transplantation . RESULTS Among the patients in the shunt group , 15 died and 1 underwent liver transplantation during the study period , as compared with 23 patients and 2 patients , respectively , in the paracentesis group . The probability of survival without liver transplantation was 69 percent at one year and 58 percent at two years in the shunt group , as compared with 52 percent and 32 percent in the paracentesis group ( P=0.11 for the overall comparison , by the log-rank test ) . In a multivariate analysis , treatment with transjugular shunting was independently associated with survival without the need for transplantation ( P=0.02 ) . At three months , 61 percent of the patients in the shunt group and 18 percent of those in the paracentesis group had no ascites ( P=0.006 ) . The frequency of hepatic encephalopathy was similar in the two groups . Of the patients assigned to paracentesis in whom this procedure was unsuccessful , 10 received a transjugular shunt a mean of 5.5+/-4 months after r and omization ; 4 had a response to this rescue treatment . CONCLUSIONS In comparison with large-volume paracentesis , the creation of a transjugular intrahepatic portosystemic shunt can improve the chance of survival without liver transplantation in patients with refractory or recurrent ascites BACKGROUND / AIMS The most rational treatment of moderate ascites is spironolactone alone or in combination with furosemide . However , it is unknown which of these two treatment schedules is preferable . METHODS One hundred nonazotemic cirrhotic patients with moderate ascites were r and omly assigned to be treated with spironolactone and furosemide ( Group 1 : 50 patients ) or with spironolactone alone ( Group 2 : 50 patients ) . If no response was obtained , the doses of diuretics were increased up to 400 mg/day of spironolactone and 160 mg/day of furosemide . In patients of group 2 not responding to 400 mg/day of spironolactone , furosemide was added . In cases with an excessive response , the dosage of diuretics was reduced . RESULTS The response rate ( 98 % in Group 1 vs. 94 % in Group 2 ) , the rapidity of ascites mobilization and the incidence of complications induced by diuretic therapy was similar in both groups . The need to reduce the diuretic dosage was significantly higher in Group 1 than Group 2 ( 68 % vs. 34 % ; P=0.002 ) . CONCLUSIONS In the treatment of moderate ascites , spironolactone alone seems to be as safe and effective as spironolactone associated with furosemide . Since spironolactone alone requires less dose adjustment , it would be more suitable for treating ascites on an outpatient basis OBJECTIVE --To compare the effectiveness and safety of spontaneous ascites filtration and reinfusion and total paracentesis plus intravenous albumin infusion in cirrhotic patients with tense ascites . DESIGN --R and omised trial of the two treatments . SETTING --Teaching hospital and district general hospital in Milan . PATIENTS --45 consecutive cirrhotic patients with recurrent tense ascites and urinary sodium excretion rate less than 20 mmol/day . 35 fulfilled admission criteria and completed the study . 17 received spontaneous ascites filtration and 18 paracentesis plus albumin infusion . MAIN OUTCOME MEASURES --Body weight ; urinary volume ; serum and urinary electrolyte , serum fibrinogen , and plasma aldosterone concentrations ; and plasma renin activity before the procedure and 24 hours and eight days afterwards . RESULTS --Both procedures were effective in all patients . Weight decreased in both groups and showed no substantial increase after eight days . In patients receiving ascites filtration , values decreased significantly ( p less than 0.01 ) after 24 hours for platelet count ( mean relative change 0.92 ; 99 % confidence interval 0.86 to 0.98 ) and serum fibrinogen concentration ( 0.92 ; 0.88 to 0.98 ) but returned to pretreatment values after eight days ; no laboratory and clinical signs of disseminated intravascular coagulation were noted . Three patients in this group had fever , which receded spontaneously . One patient in each group had dilutional hyponatraemia . CONCLUSIONS --Spontaneous ascites filtration and reinfusion is an effective treatment for tense ascites . Reinfusion of the patient 's concentrated proteins provides savings without compromising safety Background In patients with cirrhosis , ascites is defined as refractory when it can not be mobilized or recurs early in st and ard diuretic therapy We compared the efficacy and safety of apheresis and reinfusion of concentrated ascites ( ARCA ) versustotal paracentesis plus intravenous albumin ( PARA ) in a prospect i ve trial on cirrhotic patients with tense ascites . Twenty-four patients werer and omized to either ARCA ( N = 12 ) or PARA ( N = 12 ) , and followed for two years . Sex , age , Child 's class , and renal and liver function were similar in the two groups . The times of the procedures were 2.7 ±1.0 ( ARCA ) vs 2.2 ± 1.1 ( PARA ) hr , with removalof 8.8 ± 3.5 ( ARCA ) and 6.9 ± 3.4 (PARA)liters of ascites and intravenous infusion of 59.8± 35.2 ( ARCA ) and 42.5 ± 20.5 ( PARA ) g of albumin . Both procedures were safe . Biochemical signs of coagulative disturbances having no clinical relevance were observed after ARCA , with anincrease in prothrombin time ( P = 0.005 ) and serum FSP ( P = 0.02 ) . No significant changes in renalfunction , serum albumin , or plasma and urinaryelectrolytes were shown . Plasma renin activity increasedafter PARA ( P = 0.02 ) and plasma atrial natriureticfactor increased after ARCA ( P = 0.008 ) , although nodifferences were observed in diuresis in the immediatefollow-up . During the long-term follow-up , patients urvival and recurrence of tense ascites were the same in both groups . We conclude that apheresis and reinfusion of concentrated ascites are as safe and effective as total paracentesis with albumin infusionfor the treatment of tense ascites in cirrhotic patients OBJECTIVE To investigate whether albumin can be substituted by mannitolum in cirrhotic patients with tense ascites treated by paracentesis . METHODS Sixty-eight patients admitted to this therapeutic procedure were r and omly assigned to receive intravenous albumin ( 36 patients ) and mannitolum ( 32 patients ) infusion . In repeated large-volume paracentesis ( 3 - 6 L/day ) , intravenous albumin 20 g or intravenous 20 % mannitolum 250 ml were added . RESULTS In 24 and 48 hours after paracentesis the mean value of electrolytes , liver and renal functions and various indicators of systemic circulation either in Group 1 or in Group 2 cases were found without changes ( P > 0.05 ) . As compared with that before paracentesis , the diameter of spleen vein was increased significantly ( P < 0.05 ) . The complications occurring after paracentesis were similar in both groups . CONCLUSIONS It was suggested that paracentesis with intravenous infusion of mannitolum is an effective and safe method in treating cirrhotic patients with tense ascites We compared the clinical efficacy and safety of large-volume paracentesis and dialytic ultrafiltration in the treatment of refractory ascites in cirrhotic patients . A group of cirrhotic subjects ( age 49 - 80 years ) were r and omly allocated to either continuous paracentesis ( 1 - 1.5 l/hour ) or dialytic ultrafiltration until disappearance of ascites . Each patient was maintained on bed rest , fluid restriction ( 1 l/day ) and a low ( 25 mmol/day ) sodium diet for 14 days . Five patients ( three in the paracentesis group and two in dialytic ultrafiltration group ) developed massive ascites 3 - 5 months later , and received the crossover treatment . The average volume of fluid removed was similar in the two groups ( 4.70 + /- 1.47 l for dialytic ultrafiltration versus 4.69 + /- 1.84 l for paracentesis ) , but the treatment period was significantly shorter with dialytic ultrafiltration . The plasma creatinine significantly increased three days after paracentesis but did not increase in patients treated with dialytic ultrafiltration . There was an initial fall in mean arterial pressure during the first two hours of either treatment ; a further fall in blood pressure was observed with paracentesis but not with dialytic ultrafiltration . Pretreatment plasma renin activity was elevated , but was not altered by either treatment . Plasma atrial natriuretic peptide levels were in the high-normal range before treatment . Paracentesis was associated with a delayed fall in plasma atrial natriuretic peptide , while dialytic ultrafiltration induced a modest but significant rise . No complication was experienced with dialytic ultrafiltration in the two weeks following treatment , but four of the eight patients who underwent paracentesis had developed severe complications . ( ABSTRACT TRUNCATED AT 250 WORDS The vasopressin analog terlipressin is believed to cause vasoconstriction selectively by V1 receptor stimulation . However , a possible antidiuretic effect by V2 receptor stimulation has never been ruled out . Twenty-two patients with ascites , including seven with refractory ascites , were included . The subjects were studied during a 400 ml/h oral water load before and after infusion of 2 mg of terlipressin ( 18 patients ) or placebo infusion ( 4 patients ) . Effects on the V2 receptors were assessed by evaluating aquaporin (AQP)2 excretion , free water clearance ( C(H2O ) ) , urine osmolality ( Uosm ) , and fractional distal water excretion ( DFeH2O ) . After terlipressin the excretion of AQP2 increased by 89 % [ 144 ng/mmol creatinine , 95 % confidence interval ( CI ) 73 - 214 ng/mmol creatinine , P = 0.001 ] . C(H2O ) decreased 1.05 ml/min ( from 0.17 to -0.89 ml/min , P = 0.001 ) , and DFeH2O decreased 37 % ( 19 vs. 12 ; 95 % CI 2 - 11 , P = 0.01 ) . Uosm increased by 27 % ( 93 mosmol/kgH2O , 95 % CI 23 - 164 mosmol/kgH2O , P = 0.02 ) . Plasma sodium decreased 1.1 mmol/l ( P < 0.01 ) . An increase in AQP2 excretion and a decrease in C(H2O ) and distal water excretion after terlipressin despite water loading is a clear indication of activation of the antidiuretic system ( V2 receptor effect ) Royal Free Hospital , London , UK Introduction Background of the European Liver Transplant RegistrySince 1968 the European Liver Transplant Registry ( ELTR ) collects prospect ively the data of liver transplantation ( LT ) in 145 centersall over Europe . It represents more than 95 % of the overallEuropean data compared to the published official figures [ 1 ] . This collection ismade prospect ivelythroughast and ardized question -naire . The first part of the question naire includes items regarding date and indicationfor LT , donor and recipient data , surgical tech-niqueofLT , and theimmediatepostoperativeimmunosuppressiontherapy . The second part concerns graft and patient outcome , and immunosuppressive regimen follow-up . Participation in the ELTRis voluntary and a st and ard computerized data base is provided tocontributing centers with detailed instructions for the collection of accurate and uniform information [2].Along with reports concerning LT for specific hepatic diseases[3–12],ELTRhasallowedthedevelopmentofriskmodelsforliver-transplantation mortality according to the characteristics of thedonor and recipient , and of the transplant procedure [ 13,14 ] . Quality ofthe data isassessedroutinely . Aregularauditingpro-cessisconductedeachyeartoensurethereliabilityofthescientific analysis of the data , a control of the good adequacy between ELTR question naire and patient charts is performed by r and omly con-ductedauditvisits . Results oftheseauditvisitshaveindicatedthatELTR data were reliable and the scientific results of ELTR can beconsidered credible and representative of LT in Europe [15–18].In addition , a control quality program has been developed inter-nally . The data are subjected to checks for completeness , consis-tency , and range . Comprehensive logical intra- and inter-up date sare performed . Moreover , the ELTR has established agreementswith the European Organ Sharing Organizations ( OSO ) : UnitedKingdom Transplant Service Support Authority (UKTransplant),Spanish Organizacion Nacional de Transplantes ( ONT ) , Sc and ina-vian Sc and itransplant ( SKT ) , Dutch Transplant Foundation (NTS),Eurotransplant ( ET ) , French Agence de la Biomedecine ( ABM ) toexchange data collectedfromEuropeanCenters and tocrosscheckcommon data between OSO and ELTR . Patients and methods We have first considered all data since 1968 to show the evolu-tion of results of LT in Europe since its initial development . Therest of the analysis has been undertaken during two differentperiods : ( a ) from January 1988 to December 2009 ( 89,865 LT –80,347 patients ) , where the date from January 1988 was chosenJournal of Hepatology 2012 vol . PURPOSE We aim ed to evaluate and compare the efficacy and safety of high-dose furosemide+salt orally by comparing HSS+ furosemide ( i.v . ) and repeated paracentesis in patients with RA . METHODS This was a prospect i ve study of 78 cirrhotic patients with RA , r and omized into three groups : Group A ( n= 25 ) i.v . furosemide ( 200 - 300 mg bid ) and 3 % hypotonic saline solution ( HSS ) ( once or twice a day ) ; Group B ( n= 26 ) oral furosemide tablets ( 360 - 520 mg bid ) and salt ( 2.5 g bid ) ; and , Group C ( n= 27 ) repeated large-volume-paracentesis ( RLVP ) with albumin infusion . Patients without hyperkalemia were administrated 100 mg of spironolactone/day . During the follow-up ; INR , creatinine , and total bilirubin levels were measured to determine the change in MELD ( model of end stage liver disease ) score . RESULTS Hepatic encephalopathy ( HE ) , severe episodes of spontaneous bacterial peritonitis ( SBP ) and pleural effusions ( PE ) occurred more frequently in Group C. Improvement in Child-Pugh and MELD score was better in Group A and B than Group C. In Group B , improvements were seen in the Child-Pugh and MELD score , reduction in body weight , duration and number of hospitalization . In Groups A and B , remarkable increases in diuresis were observed ( 706±116 to 2425±633 mL and 691±111 to 2405±772 mL ) and serum sodium levels also improved . HE and SBP were occurred more often in group C ( p<0.002 ) . Hospitalization decreased significantly in Group B ( p<0.001 ) . There was no significant difference in survival among groups . CONCLUSION High dose oral furosemide with salt ingestion may be an alternative , effective , safe and well-tolerated method of therapy for RA Surgicalorty patients with cirrhosis of the liver and tense ascites were r and omized to receive either aldactone 400 mg/day and furosemid 80 mg/day ( n = 20 ) or repeated large volume paracentesis ( LVP ) and infusion of low molecular weight dextran ( n = 20 ) . Both treatment groups were similar in clinical and laboratory parameters . Complete mobilization of the ascitic fluid was achieved in all receiving LVP and dextran therapy within 1 week of the treatment , in contrast to the minimal mobilization of the ascitic fluid in patients receiving diuretics even after 2 weeks of therapy . Renal function , the clinical parameters of systemic hemodynamics , serum electrolytes , and hepatic function remained stable in patients receiving LVP and dextran and were similar to those in the diuretictreated patients . We found no deterioration of these functions in the nonedematous patients treated by LVP and dextran even though the protective effect of edema against LVP was lacking in them . Plasma volume estimation in six nonedematous cirrhotic patients treated by LVP and dextran did not reveal any hypovolemia after complete mobilization of ascites . The frequency of complications and death were similar in the two groups . Dextran infusion is a safe , effective , and low-cost replacement therapy in patients with cirrhotic ascites treated by LVP In a three‐way erossover study , 23 patients with hepatic cirrhosis , ascites , and dependent edema received 40 mg/day of furosemide alone and combined with triamterene 50 mg/day and triamterine 100 mg/day . Baseline potassium exeretion did not increase when furosemide was given alone , but potassium excretion fell when 50 mg or 100 mg of triamterene was also given . Both doses of triamterene augmented the natriuretic effect of furosemide To compare the efficacy of three commonly used diuretic regimens in the treatment of ascites , we r and omized 90 patients to three treatment groups : Sequential Spironolactone ( spironolactone followed by furosemide if necessary ) , Combination ( spironolactone and furosemide in combination ) , and Furosemide ( furosemide given alone ) . Diuretics were begun at a low dose by mouth and the dosage increased until a 0.4 - 0.8 kg daily diuresis was achieved . The clinical and laboratory findings were comparable for the three experimental groups on admission to the study . All three regimens achieved a comparable rate of diuresis . To do so was far more difficult with furosemide alone , which required repetitious upward adjustments in dosage and massive KCl supplements . The incidence of encephalopathy , hepatorenal syndrome , and marked electrolyte abnormalities was similar for the three treatment groups except that severe hyperkalemia was more frequent on combination therapy . We conclude that diuresis should be initiated with one of the two spironolactone regimens and not with furosemide as the sole agent The new antikaluretic diuretic , amiloride ( MK-870 ) , was evaluated in 72 patients with cirrhosis and refractory ascites . When used alone in a daily dose of 15 to 30 mg , there was a satisfactory natriuresis in approximately 80 % of patients , a modest kaluresis in only 20 % , a consistent increase in urine pH , and a bicarbonate diuresis in one-third . There was no instances of hypokalemia or alkalosis ; however , hyperkalemia was an occasional problem , particularly in patients with decreased renal function . In a controlled trial amiloride proved somewhat more effective than spironolactone or triampterene when each was used with ethacrynic acid . The combination of amiloride and hydrochlorothiazide was usually effective and rarely caused electrolyte disturbance Introduction Cirrhotic ascites is conventionally treated with bed rest , salt restriction , and diuretics . In 20–30 % of patients it eventually became resistant to diuretic therapy partly because of reduced sodium excretion owingto the development of resistance against atrial natriuretic peptide . Diuretics resistance can be overcome partially by increasing distal tubular sodium delivery by atrial natriuretic peptide and mannitol administration . Objectives To determine the short-term response of intravenous mannitol administration on mobilization of resistant cirrhotic ascites in addition to conventional diuretic treatment . Study design It was an interventional , experimental ( double-blind r and omized controlled ) study conducted in the medical department of Jinnah Hospital , Lahore . A total of 60 patients meeting inclusion and exclusion criteria were included in the study , 30 each in mannitol and placebo groups . Patients were followed for 5 days after the administration with mannitol or placebo . Main outcome measures were increase in 24 h urinary sodium , increase in urinary volume , decrease in weight and abdominal girth . Results Data showed that all the parameters of response , that is increase in 24 h urinary sodium ( cases 34.09±16.71 vs. control 19.16±13.22 , P=0.000 ) , increase in urinary volume ( cases 260.00±73.58 vs. control 91.67±43.71 ) decrease in weight ( cases 3.07±1.14 vs. control 2.3±1.08 , P=0.010 ) and decrease in abdominal girth ( cases 4.70±2.86 vs. control 2.07±1.41 , P=0.000 ) on day 5 of treatment were in favor of mannitol administration . Conclusion This study shows that resistant ascites can be initially mobilized by infusion of mannitol . The long-term benefits of such therapy are unknown We r and omized 31 cirrhotic patients with tense ascites to a Group A receiving only diuretic therapy ( spironolactone , furosemide , n = 14 ) or a Group B treated with paracentesis and intravenous albumin infusion ( n = 17 ) . Ascites was eliminated in 88 % of patients in Group B compared to 57 % of patients in Group A ( p < 0.05 ) . Complications developed in 4 patients in Group A and 2 patients in Group B. Paracentesis was associated to a mild and transient reduction in mean arterial pressure and a significant rise in urinary output . Duration of hospital stay was 5 + /- 3 days in Group B and 22 + /- 6 in Group A ( p < 0.001 ) . Survival and likelihood of readmission for ascites was similar in both groups . Our results suggest that paracentesis plus intravenous albumin infusion is a fast , safe and effective therapy for tense ascites in cirrhotic patients UNLABELLED Patients with advanced cirrhosis and ascites are characterized by circulatory dysfunction with splanchnic vasodilatation and renal vasoconstriction , which often lead to ascites . The vasoconstrictor terlipressin improves renal function in hepatorenal syndrome ( HRS ) . The aim of this study was to evaluate if terlipressin also improves renal function in patients with ascites without HRS . Twenty-three patients with cirrhosis participated ; 15 with nonrefractory ascites were r and omized to either terlipressin ( N group , n = 11 ) or a placebo ( P group , n = 4 ) , and 8 had refractory ascites and received terlipressin ( R group ) . The glomerular filtration rate ( GFR ) , sodium clearance ( C(Na ) ) , lithium clearance ( C(Li ) ) , osmolal clearance ( C(Osm ) ) , and urine sodium concentration ( U(Na ) ) were assessed before and after the injection of 2 mg of terlipressin or the placebo . GFR increased in the N group ( 69 + /- 19 versus 92 + /- 25 mL/min , P < 0.005 ) and in the R group ( 31 + /- 19 versus 41 + /- 31 mL/min , P < 0.05 ) after terlipressin . In the N group , terlipressin induced an increase in C(Na ) ( 0.89 + /- 0.21 versus 1.52 + /- 1.45 mL/min , P < 0.05 ) , C(Li ) ( 17.3 + /- 8.9 versus 21.5 + /- 11.6 mL/min , P < 0.05 ) , and C(Osm ) ( 2.10 + /- 0.81 versus 3.06 + /- 2.0 mL/min , P < 0.05 ) . In the R group , terlipressin induced an increase in C(Na ) ( 0.11 + /- 0.18 versus 0.35 + /- 0.40 mL/min , P < 0.05 ) and C(Li ) ( 5.5 + /- 4.2 versus 9.5 + /- 8.55 mL/min , P < 0.05 ) . U(Na ) increased in both groups after terlipressin ( P < 0.005 ) . Plasma norepinephrine ( P < 0.05 ) and renin ( P < 0.05 ) decreased after terlipressin . All parameters remained unchanged after the placebo . CONCLUSION The vasopressin 1 receptor agonist terlipressin improves renal function and induces natriuresis in patients with cirrhosis and ascites without HRS . Vasoconstrictors may represent a novel future treatment modality for these patients BACKGROUND Patients with cirrhotic ascites have low serum albumin levels , and paracentesis of ascitic fluid could compromise them further . AIM We compared the therapeutic efficacy of ascitic fluid filtration and concentrate infusion ( AFI ) versus total-volume paracentesis ( TVP ) with colloid infusion in control of tense or intractable cirrhotic ascites . METHODS Ten patients underwent AFI ; their ascitic fluid was filtered repeatedly through hollow-fiber hemodialyzer , and the concentrate reinfused intravenously . In ten patients TVP was done with simultaneous intravenous colloid infusion . Follow-up was done weekly and the study terminated if the patient needed diuretics or developed complications . RESULTS Pre- study parameters were similar in the two groups . In the AFI and TVP groups , the duration of procedure was median 12 hours and 5.5 hours ; fluid removed by paracentesis was 10.2 L and 8.0 L , respectively ; and fluid infused intravenously was 0.5 L [ with mean ( SD ) protein content 5.7 ( 1.3 ) g/dl ] and 1.1 L , respectively . Glomerular filtration rates were lower than normal in the two groups but did not change significantly with the procedure ; body weight remained significantly lower up to week 3 and week 2 , respectively . The study was terminated at median week 3 ( range 1 - 8 ) and week 2 ( 1 - 4 ) , respectively . Fever was an accompaniment of AFI and one patient developed peritonitis . CONCLUSION Patients undergoing AFI remained diuretic-free longer ; the procedure is cost-effective but needs to be further evaluated to minimize the side-effects OBJECTIVE To explore the therapeutic schemes for refractory ascites of advanced schistosomiasis . METHODS The advanced schistosomiasis patients with refractory ascites were r and omly divided into 4 groups : a conventional group , high-dose albumin group , high-dose diuretic group , and comprehensive group , and the course of the treatment was 4 weeks . The abdominal circumference , urine volume , and weight changes were observed daily , and B-ultrasound , liver function , and renal function were performed weekly . RESULTS In the total effective rates , recurrence rates and A/G and renal function changes , the high-dose albumin group and comprehensive group were superior to the conventional group and high-dose diuretic group ( P < 0.01 ) . The death rate of the comprehensive group was the lowest among the 4 groups . CONCLUSION The therapeutic scheme of the comprehensive group is optimum BACKGROUND Therapeutic paracentesis in patients with cirrhosis induces arterial vasodilatation , causes a decrease in effective arterial blood volume and leads to circulatory dysfunction , which can be prevented by intravenous albumin . However , the use of albumin , being a blood product , is controversial . Recently , terlipressin , a vasoconstrictor , has been successfully used to combat this adverse effect of therapeutic paracentesis . Therefore , the aim of the present study was to investigate the preventive effect of terlipressin on paracentesis-induced circulatory dysfunction in patients with cirrhosis after therapeutic paracentesis and compared with that of intravenous albumin . METHODS Forty patients with cirrhosis and tense ascites underwent therapeutic paracentesis with albumin or terlipressin in a r and omized pilot study at a tertiary center . Effective arterial blood volume was assessed by measuring plasma renin activity at baseline and at 4 - 6 days after treatment . RESULTS Effective arterial blood volumes as indicated by plasma renin activity before and 4 - 6 days after paracentesis did not differ in the two groups ( 19.15 + /- 12.1 to 20.33 + /- 12.8 ng/mL per h , P = 0.46 in the albumin group ; and 20.11 + /- 10.6 to 21.08 + /- 10.52 ng/mL per h , P = 0.44 in the terlipressin group ) . Plasma aldosterone concentrations before and 4 - 6 days after paracentesis were also similar in both groups ( 1334.75 + /- 1058 to 1440.0 + /- 1161 pg/mL , P = 0.06 in the albumin group ; and 1473.0 + /- 1168 to 1572.29 + /- 1182 pg/mL , P = 0.24 in the terlipressin group ) . Both terlipressin and albumin prevented paracentesis-induced renal impairment in these patients . CONCLUSIONS Terlipressin may be as effective as intravenous albumin in preventing paracentesis-induced circulatory dysfunction in patients with cirrhosis after therapeutic paracentesis Previous studies demonstrated the effectiveness of diuretics in mobilizing fluid , but frequent complications occur with their use in treating ascites . To develop an effective but safe regimen for treatment of cirrhotic ascites , a two-part crossover study was done . Subjects with life-threatening complications of cirrhosis were excluded . In part one it was demonstrated that a six-day diuretic regimen with dietary sodium restriction of 10 mEq/day is safe and more effective than sodium restriction alone . In part two the duration of diuretic therapy was safely extended from six to nine days with mobilization of significantly more fluid . Careful selection of subjects , use of diuretics in modest dosages for brief periods of time , and daily monitoring of subjects were important for the success of this study BACKGROUND Midodrine is an α-agonist prodrug of desglymidodrine used for the management of hypotension . Midodrine has demonstrated usefulness in hepatorenal syndrome . OBJECTIVE The objective of the present work was to study the role of midodrine in patients with non-azotemic cirrhosis with tense ascites . METHODS This prospect i ve r and omized double blind placebo-controlled study was conducted on 67 non azotemic in patients with liver cirrhosis and tense ascites ( 52 men and 15 women ; age range , 45 - 72 ) . One patient declined to participate in the study , 33 patients were r and omly assigned to take midodrine hydrochloride , and 33 patients were r and omly assigned to take placebo . Out of 67 enrolled patients , 60 patients ( 30 : in midodrine group ; 30 : in placebo group ) completed the study and 6 patients lost to follow up . Patients were assessed for patients ’ characteristics , history of tapping their ascetic fluid , laboratory values , and Doppler parameters before and after the study . Average 24-h urine volume was assessed before and after the start of the study . RESULTS significant reduction in body weight and abdominal girth was observed after 2 weeks of midodrine therapy . CONCLUSION Midodrine appeared to be effective in lowering body weights and abdominal girths of non azotemic cirrhotic patients with tense ascites BACKGROUND / AIMS Postparacentesis circulatory dysfunction is the most severe complication of ascites paracentesis . The aim of our study was to compare the st and ard treatment with the administration of a vasoconstrictor terlipressin . METHODOLOGY Forty-nine patients treated by paracentesis due to tense ascites were r and omized for the treatment with albumin ( 8g/L of removed ascites ) or terlipressin ( 1 mg every four hours for 48 hours ) . The blood pressure , heart rate , diuresis , electrocardiograph , st and ard biochemical and hematological parameters , sodium , potassium and nitrogen urinary excretion , aldosterone and renin activity in the blood plasma were monitored for a period of 72 hours . RESULTS In any parameter of hemodynamic changes , no statistically significant difference was demonstrated between r and omized groups , in particular measurements as well as in the development in the course of the first three days after the intervention . The result suggests similar efficacy of the circulatory dysfunction prevention after the paracentesis in both treatment procedures . In both groups , on the first three days , there was a tendency to improve hemodynamics reflected by the renin-angiotensin-aldosteron system activity . In the terlipressin group , this tendency approached statistically significant levels . CONCLUSIONS The administration of terlipressin in a dose of 1 mg every fourth hour performed for a period of 48 hours was as effective as intravenous albumin in preventing hemodynamic changes in patients with tense ascites treated by paracentesis . The treatment was well tolerated BACKGROUND / AIMS Ascites may cause or aggravate pulmonary dysfunction in patients with liver cirrhosis . Diuretics and paracentesis are the main therapies for ascites . The aim of the present study was to evaluate and compare the therapeutic effects of diuretics and large-volume paracentesis on lung function in 26 male patients with non-alcoholic cirrhosis and tense ascites . METHODS The patients were divided into two groups . Group A was composed of 13 subjects who were treated with diuretics including spironolactone ( 100 - 400 mg/day ) and furosemide ( 80 - 320 mg/day ) . In group B , 13 subjects received large-volume paracentesis plus intravenous albumin ( 6 - 8 g/l ascites removed ) . Pulmonary function tests including spirometry , plethysmography , single-breath carbon-monoxide diffusing capacity ( DLco ) and arterial blood gases , were done 1 day before diuretic treatment and 1 day after termination of the study in group A patients , and 1 day before and after large-volume paracentesis in group B subjects . RESULTS Before treatment , the clinical and laboratory data were comparable between the two groups . After treatment , ventilatory function as evidence d by forced expiratory volume in 1 s , forced vital capacity , total lung capacity , functional residual capacity and expiratory reserve volume , and DLco increased significantly in both groups . Arterial PO2 and PCO2 increased significantly and AaPO2 ( alveolar-arterial PO2 difference ) decreased significantly in the subjects treated with diuretics . Nevertheless , paracentesis did not improve arterial blood gases . The changes in lung volumes , DLco and PaO2 after treatment ( the data after minus those before treatment ) were comparable , except that a significant decrease in AaPO2 was observed in the diuretic group . CONCLUSIONS Both diuretic therapy and large-volume paracentesis significantly improved the ventilatory function in patients with tense cirrhotic ascites . In terms of oxygenation improvement as evaluated by AaPO2 , diuretic treatment may be superior to large-volume paracentesis Although , total paracentesis associated with human albumin substitution has shown to be a rapid , effective and safe treatment of diuretic refractory ascites in advanced liver cirrhosis , it implies high costs and has a limited availability . Therefore an alternative procedure the reinfusion of concentrated ascites has gained popularity in recent years ( Smart et al. 1990 ; Grazioto et al. 1997 ) . It was the aim of the study to compare human albumin substitution vs. reinfusion of ascitic-ultrafiltrate after total paracentesis . 35 patients with cirrhosis and tense ascites received total paracentesis associated with either human albumin ( 5 - 8 g/l ascites ) (= group A ) or reinfusion of an ascitic-ultrafiltrate fluid by means of hemofiltration technique (= group B ) . The mean volume of ascites removed was 9.41 ( 2.1 - 20.0 ) in group A and 11.41 ( 6.5 - 21.0 ) in group B. No significant differences in serum electrolytes , liver and renal function , coagulation profiles and hormones of the renin-angiotensin-aldosterone system were observed during hospitalization . In both groups sodium excretion increased significantly . 43 % of the patients in group B developed pyrexia and chill after reinfusion of the ascitic-ultrafiltrate fluid . In one patient an anaphylactic bronchospasm occurred requiring IUC-treatment . The treatment cost in case of human albumin were 326.-DM vs. 290.-DM for each patient treated with ascitic-ultrafiltrate fluid reinfusion . The probabilities of hospital readmission and survival were similar in both groups during follow-up . The results indicate that i.v . infusion of ascitic-ultrafiltrate fluid is as effective as total paracentesis and albumin infusion in case of diuretic refractory ascites . However , according to the costs of instruments and staff and due to the significant allergic reactions caused by ascitic fluid it can not be considered as a real alternative to albumin substitution BACKGROUND / AIMS Large-volume paracentesis in patients with cirrhosis and ascites induces arterial vasodilatation and decreases effective arterial blood volume , termed paracentesis-induced circulatory dysfunction ( PICD ) , which can be prevented by costly intravenous albumin . Vasoconstrictors , e.g. terlipressin , may also prevent PICD . The aim was to compare the less expensive vasoconstrictor midodrine , an alpha-adrenoceptor agonist , with albumin in preventing PICD . METHODS Twenty-four patients with cirrhosis and ascites were r and omly assigned to be treated with either midodrine ( n=11 ) ( 12.5 mg three times per day ; over 2 days ) or albumin ( n=13 ) ( 8 g/L of removed ascites ) after large-volume paracentesis . Effective arterial blood volume was assessed indirectly by measuring plasma renin and aldosterone concentration on days 0 and 6 after paracentesis ; renal function and haemodynamic changes were also measured . PICD was defined as an increase in plasma renin concentration on day 6 by more than 50 % of the baseline value . RESULTS PICD developed in six patients of the midodrine group ( 60 % ) and in only four patients ( 31 % ) of the albumin group . Six days after paracentesis , the aldosterone concentration increased significantly in the midodrine group , but not in the albumin group . CONCLUSIONS This pilot study suggests that midodrine is not as effective as albumin in preventing circulatory dysfunction after large-volume paracentesis in patients with cirrhosis and ascites BACKGROUND & AIMS Large-volume paracentesis ( LVP ) is the treatment of choice for patients with cirrhosis and refractory ascites . However , LVP can lead to postparacentesis circulatory dysfunction ( PCD ) , which is associated with faster ascites recurrence and renal failure . PCD results from vasodilatation , which reduces effective blood volume , and is prevented by intravenous administration of albumin . Vasoconstrictors could be used instead of albumin and , with longer use , prevent PCD and delay ascites recurrence . METHODS We performed a multicenter , r and omized , double-blind , placebo-controlled trial to compare albumin with the vasoconstrictor combination of octreotide and midodrine in patients with refractory ascites who underwent LVP . Patients in the albumin group received a single intravenous dose of albumin at the time of LVP plus placebos for midodrine and octreotide ( n = 13 ) . Patients in the vasoconstrictor group received saline solution ( as a placebo for albumin ) , 10 mg of oral midodrine ( 3 times/day ) , and a monthly 20-mg intramuscular injection of long-acting octreotide ( n = 12 ) . Patients were followed up until recurrence of ascites . RESULTS The median times to recurrence of ascites were 10 days in the albumin group and 8 days in the vasoconstrictor group ( P = .318 ) . There were no significant differences in PCD between the albumin group ( 18 % ) and the vasoconstrictor group ( 25 % , P = .574 ) . When ascites recurred , serum levels of creatinine were higher in the vasoconstrictor group ( 1.2 vs 0.9 mg/dL in the albumin group ; P = .051 ) . CONCLUSIONS The combination of midodrine and octreotide after LVP is not superior to albumin in delaying recurrence of ascites or preventing PCD in patients with cirrhosis . Outcomes appear to be worse in patients given octreotide and midodrine . Clinical Trials.gov number , NCT00108355 BACKGROUND Evidence is scarce on the efficacy of long-term human albumin ( HA ) administration in patients with decompensated cirrhosis . The human Albumin for the treatmeNt of aScites in patients With hEpatic ciRrhosis ( ANSWER ) study was design ed to clarify this issue . METHODS We did an investigator-initiated multicentre r and omised , parallel , open-label , pragmatic trial in 33 academic and non-academic Italian hospitals . We r and omly assigned patients with cirrhosis and uncomplicated ascites who were treated with anti-aldosteronic drugs ( ≥200 mg/day ) and furosemide ( ≥25 mg/day ) to receive either st and ard medical treatment ( SMT ) or SMT plus HA ( 40 g twice weekly for 2 weeks , and then 40 g weekly ) for up to 18 months . The primary endpoint was 18-month mortality , evaluated as difference of events and analysis of survival time in patients included in the modified intention-to-treat and per- protocol population s. This study is registered with EudraCT , number 2008 - 000625 - 19 , and Clinical Trials.gov , number NCT01288794 . FINDINGS From April 2 , 2011 , to May 27 , 2015 , 440 patients were r and omly assigned and 431 were included in the modified intention-to-treat analysis . 38 of 218 patients died in the SMT plus HA group and 46 of 213 in the SMT group . Overall 18-month survival was significantly higher in the SMT plus HA than in the SMT group ( Kaplan-Meier estimates 77 % vs 66 % ; p=0·028 ) , result ing in a 38 % reduction in the mortality hazard ratio ( 0·62 [ 95 % CI 0·40 - 0·95 ] ) . 46 ( 22 % ) patients in the SMT group and 49 ( 22 % ) in the SMT plus HA group had grade 3 - 4 non-liver related adverse events . INTERPRETATION In this trial , long-term HA administration prolongs overall survival and might act as a disease modifying treatment in patients with decompensated cirrhosis . FUNDING Italian Medicine Agency UNLABELLED A national multicenter study ( 34 centers ) compared six treatments in 328 patients with cirrhotic ascites . Excluded were patients with g.i . bleeding within the last six months , chronic encephalopathy , cancer , tuberculosis or the following complications persisting after three weeks : acute encephalopythy , fever greater than 38 degrees C , infected ascites or biochemical abnormalities : blood urea greater than 8 mmol/l , natremia less than 130 mmol/l , kaliemia less than 2.5 or greater than 5.5 mmol/l , WBC greater than 12000 mm3 , total bilirubin greater than 85.5 mumol/l . In each center patients were r and omized into two treatment groups , each center using 2 of 6 proposed treatments : ( 1 ) Spironolactone and 500 mg Na p.d ( 77 patients ) , ( 2 ) Spironolactone + furosemide or Moduretic ( amiloride + hydrochlorothiazide ) and 500 mg Na p.d ( 80 patients ) , ( 3 ) Spironolactone + Furosemide or Moduretic and unrestricted sodium diet ( 86 patients ) , ( 4 ) Concentrated ascites reinfusion and 500 mg Na p.d . ( 36 patients ) , ( 5 ) Unmodified ascites reinfusion and 500 mg Na p.d . ( 23 patients ) , ( 6 ) Slow ascites drainage and 500 mg Na p.d . ( 31 patients ) . Statistical analysis methods were X2 , variance analysis and Spotvoll-Stoline and Dunn-Sidak tests . Before treatment , there was no significant difference between the 6 groups . RESULTS After one month of treatment , no difference was found in the frequency of total or partial regression of ascites , complications of cirrhosis , mortality , acceptability of treatment . Mechanical treatments induced more rapid weight loss but more frequent recurrence ; comparison of groups 2 and 3 did not confirm any benefit associated with unrestricted Na diet . Duration of treatment and hospitalization were shorter in group 4 than in groups 3 and 6 BACKGROUND / AIMS Refractory ascites , which occurs in certain patients with cirrhosis , is associated with a blunted natriuretic response to exogenous atrial natriuretic peptide ( ANP ) . Since this blunting seems to be related to ANP-induced arterial hypotension , a vasoconstrictor , such as terlipressin ( a vasopressin analogue ) , may restore natriuresis to exogenous ANP . Moreover , since cirrhosis-elicited vasodilation is thought to play a role in sodium retention , a vasoconstriction caused by terlipressin alone may lead to an increase in sodium excretion . This study aim ed to evaluate the natriuretic response to either a combination of ANP with terlipressin or terlipressin alone in patients with cirrhosis and refractory ascites . METHODS Sixteen consecutive patients with cirrhosis and refractory ascites were r and omly assigned to receive either a combination of terlipressin ( 1 - 2 mg , i.v . bolus ) with ANP ( 35 ng/kg , i.v . bolus followed by 15 ng x kg(-1 ) x min(-1 ) for 60 min ) ( n=8 ) or terlipressin alone ( 1 - 2 mg , i.v . bolus ) ( n=8 ) . Sodium excretion and urine output , systemic , splanchnic and renal hemodynamics and renal oxygen consumption were measured before and during treatments . RESULTS Combined therapy did not change arterial pressure but significantly increased urinary sodium excretion and urine output . These effects were associated with a significant increase in glomerular filtration rate and a decrease in renal oxygen consumption . Terlipressin alone significantly increased arterial pressure but did not change urinary sodium excretion or urine output . Moreover , terlipressin did not change either glomerular filtration rate or renal oxygen consumption . CONCLUSIONS The combination of exogenous ANP with terlipressin , but not terlipressin alone , increases sodium excretion in patients with cirrhosis and refractory ascites The optimal management of severe ascites in patients with alcoholic cirrhosis has not been defined . in a 5 1/2-year study , we r and omly assigned 299 men with alcoholic cirrhosis , who had persistent or recurrent severe ascites despite a st and ard medical regimen , to receive either intensive medical treatment or peritoneovenous ( LeVeen ) shunting . We identified three risk groups : Group 1 had normal or mildly abnormal results on liver-function tests , Group 2 had more severe liver dysfunction or previous complications , and Group 3 had severe prerenal azotemia without kidney disease . For the patients who received the medical treatment and those who received the surgical treatment combined , the median survival times were 1093 days in Group 1 , 222 days in Group 2 , and 37 days in Group 3 ( P less than or equal to 0.01 ) for all comparisons ) . For all the groups combined , the median time to the resolution of ascites was 5.4 weeks for medical patients and 3.0 weeks for surgical patients ( P less than 0.01 ) . Within each risk group , mortality during the initial hospitalization and median long-term survival were similar among patients receiving either treatment . However , the median time to the recurrence of ascites in Group 1 was 4 months in medical patients , as compared with 18 months in surgical patients ( P = 0.01 ) ; in Group 2 it was 3 months in medical patients as compared with 12 months in surgical patients ( P = 0.04 ) . The median duration of hospitalization was longer in medical patients than in surgical patients ( 6.1 vs. 2.4 weeks in Group 1 [ P less than 0.001 ] and 5.0 vs. 3.1 weeks in Group 2 [ P less than 0.01 ] ) . Group 3 was too small to permit a meaningful comparison . During the initial hospitalization , the incidence of infections , gastrointestinal bleeding , and encephalopathy was similar among the medical and surgical patients . We conclude that peritoneovenous shunting alleviated disabling ascites more rapidly than medical management . However , survival was closely related to the severity of the illness at the time of r and omization and was not altered by shunting In a prospect i ve r and omized short-term study , the efficacy and safety of xipamide and a combination of spironolactone and furosemide were compared in the treatment of hepatic cirrhotic ascites . Twenty-two patients were r and omized to either xipamide , 20 mg/day ( group I ) , or spironolactone , 200 mg/day , combined with furosemide , 40 mg on alternate days ( group II ) . During the first 4 days of treatment , adequate diuresis , measured as loss of body weight greater than 1.6 kg , occurred in 7 patients in group I and in 3 in group II . In the latter group , another 4 patients responded satisfactorily after a further 4 days of treatment . Four patients in group I who failed to respond to xipamide with an adequate loss of body weight were subsequently treated with the spironolactone-furosemide combination , but only one responded . Two patients in group II who failed to respond to the combination of spironolactone and furosemide also failed to respond to xipamide . In both groups , a positive diuretic response occurred only when the pretreatment fractional sodium excretion exceeded 0.2 % . Diuretic resistance was overcome only by additional treatments which reduced proximal tubular sodium reabsorption . Xipamide commonly induced hypokalaemia ; in contrast hyperkalaemia was seen following treatment with the spironolactone-furosemide combination . Renal function remained stable in all patients during both diuretic treatments . An open ongoing 6-month trial of torasemide , 10 - 40 mg/day , in combination with spironolactone , 50 - 400 mg/day , has also been undertaken in 117 patients with cirrhotic ascites who showed inadequate responses to salt and water restriction and spironolactone alone . Twenty-seven patients have been withdrawn from the study , 9 for the complications of hepatic coma , bleeding oesophageal varices , or hyponatraemia . Twenty-two patients are still being treated and 68 have completed the trial on a mean dose of torasemide , 15 mg/day . Body weight was reduced by a mean of 2.3 kg at 6 weeks , 2.6 kg at 14 weeks and 3.2 kg after 6 months . Loss of body weight was primarily associated with reduction of ascites and secondarily with reduction of peripheral oedema . There were no untoward adverse reactions with torasemide , and no significant changes in serum electrolytes , liver , renal , or haematological variables Background UK deaths due to chronic liver diseases such as cirrhosis have quadrupled over the last 40 years , making this condition now the third most common cause of premature death . Most patients with advanced cirrhosis ( end-stage liver disease [ ESLD ] ) develop ascites . This is often managed with diuretics , but if refractory , then the fluid is drained from the peritoneal cavity every 10–14 days by large volume paracentesis ( LVP ) , a procedure requiring hospital admissions . As the life expectancy of patients with ESLD and refractory ascites ( if ineligible for liver transplantation ) is on average ≤ 6 months , frequent hospital visits are inappropriate from a palliative perspective . One alternative is long-term abdominal drains ( LTADs ) , used successfully in patients whose ascites is due to malignancy . Although inserted in hospital , these drains allow ascites management outside of a hospital setting . LTADs have not been formally evaluated in patients with refractory ascites due to ESLD . Methods / design Due to uncertainty about appropriate outcome measures and whether patients with ESLD would wish or be able to participate in a study , a feasibility r and omised controlled trial ( RCT ) was design ed . Patients were consulted on trial design . We plan to recruit 48 patients with refractory ascites and r and omise them ( 1:1 ) to either ( 1 ) LTAD or ( 2 ) current st and ard of care ( LVP ) for 12 weeks . Outcomes of interest include acceptability of the LTAD to patients , carers and healthcare professionals as well as recruitment and retention rates . The Integrated Palliative care Outcome Scale , the Short Form Liver Disease Quality of Life question naire , the EuroQol 5 dimensions instrument and carer-reported ( Zarit Burden Interview ) outcomes will also be assessed . Preliminary data on cost-effectiveness will be collected , and patients and healthcare professionals will be interviewed about their experience of the trial with a view to identifying barriers to recruitment . Discussion LTADs could potentially improve end-of-life care in patients with refractory ascites due to ESLD by improving symptom control , reducing hospital visits and enabling some self-management . Our trial is design ed to see if such patients can be recruited , as well as to inform the design of a subsequent definitive trial . Trial registration IS RCT N , IS RCT N30697116 . Registered on 7 October 2015 BACKGROUND & AIMS Patients with decompensated cirrhosis on the waiting list for liver transplantation ( LT ) commonly develop complications that may preclude them from reaching LT . Circulatory dysfunction leading to effective arterial hypovolemia and activation of vasoconstrictor systems is a key factor in the pathophysiology of complications of cirrhosis . The aim of this study was to investigate whether treatment with midodrine , an alpha-adrenergic vasoconstrictor , together with intravenous albumin improves circulatory dysfunction and prevents complications of cirrhosis in patients awaiting LT . METHODS A multicenter , r and omized , double-blind , placebo-controlled trial ( NCT00839358 ) was conducted , including 196 consecutive patients with cirrhosis and ascites awaiting LT . Patients were r and omly assigned to receive midodrine ( 15 - 30 mg/day ) and albumin ( 40 g/15 days ) or matching placebos for one year , until LT or drop-off from inclusion on the waiting list . The primary endpoint was incidence of any complication ( renal failure , hyponatremia , infections , hepatic encephalopathy or gastrointestinal bleeding ) . Secondary endpoints were mortality , activity of endogenous vasoconstrictor systems and plasma cytokine levels . RESULTS There were no significant differences between both groups in the probability of developing complications of cirrhosis during follow-up ( p = 0.402 ) or one-year mortality ( p = 0.527 ) . Treatment with midodrine and albumin was associated with a slight but significant decrease in plasma renin activity and aldosterone compared to placebo ( renin -4.3 vs. 0.1 ng/ml.h , p < 0.001 ; aldosterone -38 vs. 6 ng/dl , p = 0.02 , at week 48 vs. baseline ) . Plasma norepinephrine only decreased slightly at week 4 . Neither arterial pressure nor plasma cytokine levels changed significantly . CONCLUSIONS In patients with cirrhosis awaiting LT , treatment with midodrine and albumin , at the doses used in this study , slightly suppressed the activity of vasoconstrictor systems , but did not prevent complications of cirrhosis or improve survival . LAY SUMMARY Patients with cirrhosis who are on the liver transplant waiting list often develop complications which prevent them from receiving a transplant . Circulatory dysfunction is a key factor behind a number of complications . This study was aim ed at investigating whether treating patients with midodrine ( a vasoconstrictor ) and albumin would improve circulatory dysfunction and prevent complications . This combined treatment , at least at the doses administered in this study , did not prevent the complications of cirrhosis or improve the survival of these patients BACKGROUND The 5-dimensional EuroQol question naire ( EQ-5D ) is vali date d to measure general health-related quality of life ( QOL ) . Our objective was to determine the responsiveness and minimal clinical ly important difference ( MCID ) of the EQ-5D health utility value ( EQ-5D HUV ) and visual analog scale ( EQ-5D VAS ) in chronic rhinosinusitis ( CRS ) . METHODS 203 adults undergoing medical management for CRS were prospect ively recruited . General health-related QOL ( using EQ-5D HUV and EQ-5D VAS ) and CRS-specific QOL ( using the 22-item Sinonasal Outcome Test [ SNOT-22 ] ) were measured at enrollment and a subsequent follow-up time point 2 - 12 months later . At follow-up , participants also rated change in general health as Much worse , A little worse , About the same , A little better or Much better compared to enrollment . The EQ-5D HUV and EQ-5D VAS MCIDs were calculated using distribution-based , anchor-based , and receiver operator characteristic ( ROC ) curve-based methods . RESULTS Change in SNOT-22 score was correlated with EQ-5D HUV and EQ-5D VAS change . Using the different methods of calculating MCID , we find the EQ-5D HUV MCID to be 0.04 and EQ-5D VAS MCID to be 8.0 . The calculated EQ-5D MCIDs had approximately a sensitivity of 40 - 50 % and specificity of 80 % in detecting patients experiencing noticeable improvement in general health . CONCLUSIONS The EQ-5D responds well to changing CRS symptomatology . We propose MCIDs for EQ-5D HUV of 0.04 and EQ-5D VAS of 8 in CRS patients , which although specific , are not sensitive for detecting patients experiencing improvement in general health Background and aims Albumin infusion reduces the incidence of postparacentesis circulatory dysfunction among patients with cirrhosis and tense ascites compared with no treatment . Less costly treatment alternatives such as vasoconstrictors have been investigated , but the results are controversial . Midodrine , an oral & agr;1-adrenergic agonist , increases effective circulating blood volume and renal perfusion by increasing systemic and splanchnic blood pressure . Our aim is to assess whether or not morbidity in terms of renal dysfunction , hyponatremia , systemic , or portal hemodynamics derangement or mortality differed in patients receiving albumin versus midodrine . Patients and methods Seventy-five patients with cirrhosis and refractory ascites were r and omized to receive albumin infusion , oral midodrine for 2 days , or oral midodrine for 30 days after therapeutic large volume paracentesis ( LVP ) . The primary endpoints were development of renal impairment or hyponatremia , change in systemic and portal hemodynamics , cost , and mortality in the short-term and long-term follow-up . Results No significant difference was found between groups in the development of renal impairment , hyponatremia , or mortality 6 and 30 days after LVP . A significant increase in 24-h urine sodium excretion was noted in the midodrine 30-day group . Renal perfusion improved significantly with the midodrine intake for 30 days only . The cost of midodrine therapy was significantly lower than albumin . Conclusion Midodrine is as effective as albumin in reducing morbidity and mortality among patients with refractory ascites undergoing LVP at a significantly lower cost . Long- duration midodrine intake can be more useful than shorter duration intake in terms of improvement of renal perfusion and sodium excretion Forty-one patients with cirrhosis and tense ascites were r and omized to receive daily paracentesis of 5 liters associated with Dextran 70 as volume exp and er ( 6 g for each 1000 ml of ascites removed ) ( group I = 20 patients ) or paracentesis with albumin ( 6 g for each 1000 ml of ascites ) ( group II = 21 patients ) . The basal clinical features , laboratory data , and plasma renin activity were similar in both groups . The volume of ascites removed was 12.9 + /- 4.4 and 10.9 + /- 3.7 liters in group I and II , respectively ( n.s . ) . No significant changes were observed in liver and renal function tests , KPTT , platelet count , factor VIII , serum electrolytes or plasma renin activity 24 and 96 h after the last paracentesis in both groups , except for a decrease in bilirubin in group I and a transient increase of serum albumin in group II . Four patients developed complications in each group , mainly hyponatremia , while one patient in each group developed renal impairment . One patient from group I died with hepatic encephalopathy . Moreover , the probability of survival and readmission to the hospital because of tense ascites were similar in both groups of patients during the follow-up . The treatment cost with Dextran 70 was 15.50 dollars vs. 364.30 dollars with albumin for each patient treated . These results indicate that repeated large volume paracentesis associated with Dextran 70 is as effective and safe as paracentesis associated with albumin in cirrhotic patients with tense ascites . However , due to its reduced cost , paracentesis with Dextran 70 may be considered the treatment of choice in cirrhotic patients with tense ascites without liver cancer and renal failure Goals : In this pilot study , we compared midodrine and albumin in the prevention of paracentesis-induced circulatory dysfunction ( PICD ) . Background : PICD with pronounced arterial vasodilatation in cirrhotics with tense ascites can be prevented by the infusion of albumin , which is an expensive treatment modality . Various vasoconstrictors have also been used to prevent PICD , but there are few studies about the usage of midodrine . Study : Fifty patients with cirrhosis and tense refractory ascites were r and omly assigned to be treated with either midodrine ( n=25 ) ( 12.5 mg 3 times/d ; over 3 d ) or albumin ( n=25 ) ( 8 g/L of removed ascites ) after a large-volume paracentesis . Effective arterial blood volume was assessed indirectly by measuring serum creatinine , serum sodium , plasma renin activity , and aldosterone concentration before and 6 days after paracentesis . Results : Midodrine therapy was cheaper compared with albumin therapy , but serum creatinine , serum sodium , plasma renin activity , and plasma aldosterone concentration values after treatment [ 0.99±0.19 to 3.02±2.58 mg/dL ( P=0.001 ) , 132.36±3.2 to 130.2±4.1 mEq/L ( P<0.001 ) , 3.03±0.33 to 4.2±0.76 ng/mL/h ( P<0.001 ) , and 166.72±64.26 to 298.64±130 pg/mL ( P<0.001 ) , respectively ] significantly differed in the midodrine group from that in the albumin group [ 1.10±0.22 to 1.11±0.161 mg/dL ( P=0.885 ) , 132.2±3.524 to 131.88±3.09 mEq/L ( P=0.246 ) , 4±0.91 to 4.11±0.74 ng/mL/h ( P=0.440 ) , and 204.88±115.9 to 177.08±100.5 pg/mL ( P<0.001 ) , respectively ] . Seven patients , among whom 6 were hepatocellular carcinoma ( HCC ) positive , in the midodrine group of our study died as a consequence of liver failure complicated by acute renal failure , followed by hepatic encephalopathy . Whereas in the albumin group , even among the 7 patients with HCC , no patient died or developed hepatorenal syndrome or developed hepatic encephalopathy . Conclusions : This pilot study suggests that midodrine is not as effective as intravenous albumin in preventing circulatory dysfunction after large-volume paracentesis in patients with cirrhosis and tense ascites , especially with HCC-positive patients BACKGROUND Splanchnic arterial vasodilatation and subsequent sodium and water retention play an important role in cirrhotic ascites . Midodrine and tolvaptan have been used separately in these patients . However , there are no reports on the use of combination of midodrine and tolvaptan in the control of ascites . The aim of this study was to evaluate the safety and efficacy of midodrine , tolvaptan and their combination in control of refractory or recurrent ascites in cirrhotics . METHODS Fifty cirrhotic patients with refractory or recurrent ascites were r and omised to receive midodrine ( n=13 ) , tolvaptan ( n=12 ) or both ( n=13 ) plus st and ard medical therapy ( SMT ) or SMT alone ( n=12 ) . RESULTS A significant increase in urinary volume and urinary sodium at 1 and 3 months ( P<.05 ) was observed in all groups except SMT . There was no worsening of renal or hepatic function in any group . There was deterioration of model for end-stage liver disease ( MELD ) in SMT . Midodrine as well as combination of midodrine and tolvaptan but not tolvaptan alone was superior to SMT in control of ascites at 3 months ( P<.05 ) . The combination therapy was also superior to midodrine in the control of ascites at 1 month . The morbidity and mortality were similar in all the groups except SMT . CONCLUSIONS The results of this pilot study suggest that midodrine and combination with tolvaptan better controls ascites without any renal or hepatic dysfunction . The combination therapy rapidly controls ascites as compared to midodrine or tolvaptan alone Published evidence suggests that aspects of trial design lead to biased intervention effect estimates , but findings from different studies are inconsistent . This study combined data from 7 meta-epidemiologic studies and removed overlaps to derive a final data set of 234 unique meta-analyses containing 1973 trials . Outcome measures were classified as " mortality , " " other objective , " " or subjective , " and Bayesian hierarchical models were used to estimate associations of trial characteristics with average bias and between-trial heterogeneity . Intervention effect estimates seemed to be exaggerated in trials with inadequate or unclear ( vs. adequate ) r and om-sequence generation ( ratio of odds ratios , 0.89 [ 95 % credible interval { CrI } , 0.82 to 0.96 ] ) and with inadequate or unclear ( vs. adequate ) allocation concealment ( ratio of odds ratios , 0.93 [ CrI , 0.87 to 0.99 ] ) . Lack of or unclear double-blinding ( vs. double-blinding ) was associated with an average of 13 % exaggeration of intervention effects ( ratio of odds ratios , 0.87 [ CrI , 0.79 to 0.96 ] ) , and between-trial heterogeneity was increased for such studies ( SD increase in heterogeneity , 0.14 [ CrI , 0.02 to 0.30 ] ) . For each characteristic , average bias and increases in between-trial heterogeneity were driven primarily by trials with subjective outcomes , with little evidence of bias in trials with objective and mortality outcomes . This study is limited by incomplete trial reporting , and findings may be confounded by other study design characteristics . Bias associated with study design characteristics may lead to exaggeration of intervention effect estimates and increases in between-trial heterogeneity in trials reporting subjectively assessed outcomes |
12,758 | 24,903,204 | But , as the critics rightfully point out , studies that include meta-analyses are often not without biases . | There seemsto be a growing negativity towardmeta-analyses .
Twoyears ago systematic review s and meta-analyses , and more specifically Cochrane review s , were critiqued ( Humaidan et al. , 2012 ; Humaidan and Polyzos , 2012 ) .
In the present issue of Human Reproduction another example of negative publicity toward meta-analyses is published in the form of an Opinion paper ( Simón and Bellver , 2014 ) .
Meta-analyses-attacking authors in essence argue that meta-analyses should be faultless while meta-analyses are considered to be highest in the evidence -based pyramid . | Aim : To evaluate the effect of local injury to the endometrium during spontaneous menstrual cycles before in vitro fertilization ( IVF ) treatment on implantation and pregnancy rates in women with recurrent implantation failure ( RIF ) . Methods : In a prospect i ve r and omized controlled trial ( RCT ) , a total of 36 patients , with RIF undergoing IVF , were r and omized to two groups . In 18 patients , endometrial biopsies were performed using a pipelle curette on days 9–12 and 21–24 of the menstrual cycle preceding IVF treatment . In 18 control patients , a cervical pipelle was performed . Results : The implantation rate ( 2.08 % versus 11.11 % ; p = 0.1 ) , clinical ( 0 % versus 31.25 % ; p < 0.05 ) and live births rates ( 0 % versus 25 % ; p = 0.1 ) were lower in the experimental group compared with controls . Conclusion : Our RCT did not find any benefit from local injury to the endometrium in women with a high number of RIFs . Further studies are warranted to better define the target population of patients who may benefit from this procedure OBJECTIVES To investigate the effect of endometrial scratching , performed during oral contraceptive pill ( OCP ) pretreatment , on reproductive outcome and on ultrasound markers of endometrial receptivity , and to assess the pain involved in the procedure , in unselected women undergoing assisted reproductive techniques ( ART ) . METHODS Women undergoing ART were r and omly allocated to undergo either endometrial scratching with a pipelle de Cornier or a sham procedure , 7 - 14 days before starting controlled ovarian stimulation ( COS ) . We evaluated subsequent rates of clinical pregnancy , live birth , implantation , miscarriage and multiple pregnancy . Pain during the procedure was evaluated using a 10-cm visual analog scale . Endometrial thickness and volume and three-dimensional power Doppler ( 3D-PD ) indices ( vascularization index ( VI ) , flow index ( FI ) and vascularization flow index ( VFI ) ) were assessed during COS when there was at least one follicle ≥ 17 mm in diameter . RESULTS We included 158 women . Endometrial scratching was associated with higher rates of live birth ( 41.8 % vs 22.8 % , P = 0.01 ) and clinical pregnancy ( 49.4 % vs 29.1 % , P = 0.01 ) and higher pain score ( 6.42 ± 2.35 cm vs 1.82 ± 1.52 cm , P < 0.001 ) , endometrial VI ( 3.71 ± 1.77 vs 2.95 ± 1.56 , P < 0.01 ) and VFI ( 0.97 ± 0.51 vs 0.76 ± 0.40 , P < 0.01 ) . There was no significant effect of endometrial scratching on rate of miscarriage ( 15.4 % vs 21.7 % , P = 0.53 ) or multiple pregnancy ( 22.5 % vs 25.0 % , P = 0.79 ) , or on endometrial thickness ( 10.12 ± 1.55 mm vs 9.98 ± 1.62 mm , P = 0.59 ) , endometrial volume ( 6.18 ± 1.63 cm(3 ) vs 6.01 ± 1.48 cm(3 ) , P = 0.51 ) or FI ( 26.12 ± 2.82 vs 25.91 ± 2.72 , P = 0.65 ) . CONCLUSIONS Endometrial scratching performed once , during OCP pretreatment 7 - 14 days before starting COS , increases the chance of live birth and clinical pregnancy , but might cause considerable pain OBJECTIVE To evaluate the effect of a single endometrial biopsy regimen ( S-EBR ) in the cycle preceding the ICSI cycle in patients with repeated implantation failure . STUDY DESIGN This was a prospect i ve r and omized controlled trial which included two-hundred infertile women with a history of repeated implantation failure . The subjects were r and omly divided into two groups . Group A subjects underwent hysteroscopy and endometrial scraping by Novak curette in the cycle preceding the ICSI cycle , while group B subjects underwent hysteroscopy without endometrial scraping . Implantation rate , clinical pregnancy rate , abortion rate and live birth rate were compared between both groups . RESULTS The number of retrieved oocytes in group A was 11.6 ± 3 and in group B was 11.6 ± 2.8 with no statistically significant difference ( p=0.787 ) . There were statistically significant differences regarding the implantation rate , the clinical pregnancy rate and live birth rate . The implantation rate in group A was 12 % while in group B it was 7 % ( p=0.015 ) , the clinical pregnancy rate was 32 % in group A while it was only 18 % in group B ( p=0.034 ) and the live birth rate was 28 % in group A while it was 14 % in group B ( p=0.024 ) . CONCLUSIONS The single endometrial biopsy regimen ( S-EBR ) performed during hysteroscopy has statistically significant higher implantation rate , clinical pregnancy rate and live birth rate than hysteroscopy without endometrial scraping |
12,759 | 29,498,128 | Based on the available evidence , it is not possible to define a precise threshold for the optimal horizontal distance between two adjacent implants | OBJECTIVES To address the following focused question : " Does the horizontal distance between two adjacent implants inserted in the anterior maxilla affect the inter-implant mucosa fill ? " . | PURPOSE To prospect ively evaluate peri-implant bone and soft tissue dimension changes around adjacent implants placed at different horizontal interimplant distances . MATERIAL S AND METHODS Thirty partially edentulous patients , who underwent rehabilitation with two adjacent implant-supported crowns as part of their treatment plan , were assigned to three groups based on their prosthetic needs . Patients in group A ( 10 patients , 20 implants ) were to have two implants placed at a 2-mm interimplant distance , patients in group B ( 10 patients , 20 implants ) were to have two implants placed at a 3-mm interimplant distance , and patients in group C ( 10 patients , 20 implants ) were to have two implants placed at an interimplant distance of > 4 mm according to their prosthetic needs . All patients received single-crown restorations after 3 months . Clinical examinations were performed at the time of crown placement ( T3 ) , and 6 months ( T6 ) , 12 months ( T12 ) , and 24 months ( T24 ) after implant placement . Peri-implant bone levels were assessed radiographically at the time of implant placement ( T0 ) , and at T3 , T12 , and T24 . RESULTS One patient from group C did not return for follow-up examinations after implant placement . The mean ( ± st and ard deviation ) horizontal interimplant distance was 1.97 ± 0.44 mm for implants in group A , 3.12 ± 0.15 mm for implants in group B , and 5.3 ± 0.64 mm for implants in group C. For group A , the mean marginal bone loss was 0.29 ± 0.51 mm at the T0-T3 interval , 0.31 ± 0.36 mm at the T0-T12 interval , and 0.27 ± 0.33 mm at the T0-T24 interval . For group B , the mean marginal bone loss was 0.16 ± 0.29 mm at the T0-T3 interval , 0.20 ± 0.28 mm at the T0-T12 interval , and 0.23 ± 0.28 mm at the T0-T24 interval . For group C , the mean marginal bone loss was 0.51 ± 0.84 mm at the T0-T3 interval , 0.45 ± 0.72 mm at the T0-T12 interval , and 0.44 ± 0.74 mm at the T0-T24 interval . For group A , the mean midproximal bone loss was 0.33 ± 0.50 mm at the T0-T3 interval , 0.45 ± 0.35 mm at the T0-T12 interval , and 0.40 ± 0.32 mm at the T0-T24 interval . For group B , the mean midproximal loss was 0.31 ± 0.37 mm at the T0-T3 interval , 0.32 ± 0.39 mm at the T0-T12 interval , and 0.33 ± 0.42 mm at the T0-T24 interval . For group C , the mean midproximal bone loss was 0.40 ± 0.44 mm at the T0-T3 interval and 0.41 ± 0.50 mm at both the T0-T12 and T0-T24 intervals . There were no statistically significant differences in marginal and midproximal bone crest loss between the different groups at any time point . CONCLUSION The study failed to support the hypothesis that horizontal interimplant distance has an effect on peri-implant bone and soft tissue dimension changes for implants with internal conical implant-abutment interface connection and platform-switching characteristics PURPOSE The aim of this pilot study was to determine what effect thin mucosal tissues can have on crestal bone stability around implants with platform switching . MATERIAL S AND METHODS Twelve 2-piece implants , consisting of 6 implants with horizontally matching implant-abutment connection ( control ) and 6 implants with platform switching ( test ) were placed in 4 patients . The mean age of the patients was 43 years ( range , 37 to 56 yrs ) . Mucosal tissue thickness at implant sites was measured to be 2 mm or less . Implants were restored with 5 splinted crowns and single 3-unit fixed partial denture . Intraoral radiographs were obtained and crestal bone changes were measured at implant placement and after a 1-year follow-up post-treatment . The statistical significance level was set to P less than .05 . RESULTS Bone loss around the test implants was 1.81 + /- 0.39 mm on the mesial site and 1.70 + /- 0.35 mm on the distal aspect . Control implants overcame marginal bone resorption equaling 1.60 + /- 0.46 mm on the mesial site and 1.76 + /- 0.45 mm on distal measurement . No statistically significant difference was found between control and test implants either mesially ( F([1,10 ] ) = 0.746 ; P = .408 ) or distally ( F([1,10 ] ) = 0.080 ; P = .783 ) . CONCLUSION Within the limitations of this pilot study it can be concluded that implants with platform switching did not preserve crestal bone better in comparison with implants with traditional implant-abutment connection if , at the time of implant placement , thin mucosal tissues were present AIM To evaluate the peri-implant tissues in patients with two adjacent implant crowns in the aesthetic zone , treated with either two adjacent implants with a scalloped platform or with a flat platform . MATERIAL AND METHODS Forty patients were r and omly allocated to : ( 1 ) a " scalloped implant group " : 20 patients treated with two adjacent implants with a scalloped platform , and ( 2 ) a " flat implant group " : 20 patients treated with two adjacent implants with a flat platform . Clinical and radiographic examinations were performed during a 1-year follow-up period to assess hard and soft tissue changes . RESULTS The scalloped implant group showed significantly more marginal bone loss ( scalloped : 2.7±1.4 mm , flat : 0.9±0.8 mm ) and more inter-implant bone crest loss ( scalloped : 1.8±1.4 , flat : 1.0±0.9 mm ) than the flat implant group . There was no significant difference between the groups with regard to the papilla index and patients ' satisfaction . CONCLUSION After 1 year of function , there was more bone loss around scalloped implants than around flat implants . With regard to the presence of papilla , there were no differences between the groups . With both applied implant design s , it is difficult to establish a predictable and harmonious aesthetic result , especially regarding the peri-implant mucosa . Patients were very satisfied with the aesthetic outcome of the adjacent implants irrespective of the treatment concept applied PURPOSE The aim of this clinical trial was to evaluate the influence of gingival tissue thickness on crestal bone loss around dental implants after a 1-year follow-up . MATERIAL S AND METHODS Forty-six implants ( 23 test and 23 control ) were placed in 19 patients . The test implants were placed about 2 mm supracrestally , whereas the control implants were positioned at the bone level . Before implant placement , the tissue thickness at implant sites was measured with a periodontal probe . After healing , metal-ceramic cement-retained prostheses were constructed . According to tissue thickness , the test implants were divided into A ( thin ) and B ( thick ) groups . Intraoral radiographs were performed and crestal bone changes were measured at implant placement and after 1 year . RESULTS Mean bone loss around the test implants in group A ( thin mucosa ) was 1.61 + /- 0.24 mm ( SE ; range , 0.9 to 3.3 mm ) on the mesial and 1.28 + /- 0.167 mm ( range , 0.8 to 2.1 mm ) on the distal . Mean bone loss in test group B ( thick mucosa ) implants was 0.26 + /- 0.08 mm ( range , 0.2 to 0.9 mm ) on the mesial aspect and 0.09 + /- 0.05 mm ( range , 0.2 to 0.6 mm ) on the distal aspect . Mean bone loss around control implants was 1.8 + /- 0.164 mm ( range , 0.6 to 4.0 mm ) and 1.87 + /- 0.166 mm ( range , 0.0 to 4.1 mm ) on the mesial and distal aspects , respectively . Analysis of variance revealed a significant difference in terms of bone loss between test A ( thin ) and B ( thick ) groups on both the mesial and the distal . CONCLUSION Initial gingival tissue thickness at the crest may be considered as a significant influence on marginal bone stability around implants . If the tissue thickness is 2.0 mm or less , crestal bone loss up to 1.45 mm may occur , despite a supracrestal position of the implant-abutment interface |
12,760 | 28,965,590 | Results of the current meta- analysis revealed that mercury is an important causal factor in the etiology of ASD .
It seems that the detoxification and excretory mechanisms are impaired in ASD patients which lead to accumulation of mercury in the body . | BACKGROUND & AIMS The relationship between mercury and autism spectrum disorders ( ASD ) has always been a topic of controversy among research ers .
This study aim ed to assess the relationship between ASD and mercury levels in hair , urine , blood , red blood cells ( RBC ) , and brain through a meta- analysis . | BACKGROUND Thimerosal is an organic-mercury (Hg)-containing compound ( 49.55 % Hg by weight ) historically added to many multi-dose vials of vaccine as a preservative and still added to some vaccines today . Concerns about the toxic effects from Thimerosal-containing childhood vaccines and the risk of an atypical autism diagnosis were evaluated in this study . METHODS A hypothesis-testing , prospect i ve longitudinal , case-control study assessed exposure to Hg from Thimerosal-containing hepatitis B vaccines ( TM-HepB ) among cases diagnosed with atypical autism ( n=164 ) and controls ( n=15,216 ) . Automated medical records for subjects born from 1991 to 2000 and continuously enrolled in the Vaccine Safety Data link ( VSD ) data base were examined . RESULTS Cases diagnosed with atypical autism were statistically significantly more likely to have received greater overall and dose-dependent exposures to Hg from TM-HepB vaccines administered within the first month of life , first two months of life , and first six months of life than the controls . Similar phenomena were observed when cases and controls were separated by gender . CONCLUSIONS Routine childhood vaccination is an important public health tool to reduce infectious diseases . The present study provides important epidemiological evidence significantly associating increasing Hg exposure from Thimerosal-containing childhood vaccines and the subsequent risk of atypical autism diagnosis , and suggests that Thimerosal should be eliminated from vaccines |
12,761 | 26,417,202 | Studies evaluating illicit opioid consumption using other measures demonstrate pain to increase the risk for opioid abuse .
Conclusion CNCP may increase risk for continued opioid abuse and poor psychiatric functioning . | Background While a number of pharmacological interventions exist for the treatment of opioid use disorder , evidence evaluating the effect of pain on substance use behavior , attrition rate , and physical or mental health among these therapies has not been well established .
We aim to evaluate these effects using evidence gathered from a systematic review of studies evaluating chronic non-cancer pain ( CNCP ) in patients with opioid use disorder . | Rationale Buprenorphine may be a useful alternative option to methadone in addicts . Opioids can produce severe changes in the immune system . Objectives The objectives of this study are to compare the effect of sublingual buprenorphine and methadone on the immune system and to compare the two substances on the drying-out program compliance . Methods We studied 62 r and omized out patients for a period of 12 months . Subjects ( 55 males and 7 females ; mean age 25±4 years ; average history of heroin abuse being 2 years ) on maintenance treatment were assigned in two groups ( A and B ) . Methadone chloride ( medium dose 100 mg/day ) was administered to group A , whereas group B received sublingual buprenorphine ( 32.40±2.8 mg/day ) . Urine toxicological screening , plasma levels of TNF-alpha interleukin-1 , interleukin-beta , lymphocyte CD14 and a self-rating depression question naire were measured . Results Urine screening was negative for opiates in 17.6 % of group A and in 10.7 % of group B ( p<0.001 ; r=0.62 ) . Depression score was 62±2 in group A and 55±3 in group B ( p<0.01 ) . Cytokine and CD14 revealed higher concentrations both in groups A and B without significant differences ( p>0.05 ) between the two groups . Conclusions The effects of buprenorphine and methadone tested on the immune system were overlapping in our patients . The elevated cytokine levels observed may suggest that the two drugs stimulate immunologic hyperactivation of an immune system that was formerly inhibited by heroin . Furthermore , our data suggest that buprenorphine can be a valid alternative to methadone in maintenance treatment of chronic heroin abuse and referred a marked decline in depression Patients on methadone maintenance therapy are relatively intolerant of pain , a finding hypothesized to reflect a hyperalgesic state induced by chronic opioid administration . To explore if the intrinsic activity of the opioid maintenance agent might affect expression of hyperalgesia in this population , withdrawal latency for cold-pressor ( CP ) pain was compared between small groups of methadone-maintained ( n = 18 ) , buprenorphine-maintained ( n = 18 ) , and matched control ( n = 18 ) subjects . The opioid-maintained groups had equal and significantly shorter withdrawal latencies than controls , however it is possible that high rates of continued illicit opioid use precluded finding differences between methadone and buprenorphine groups . Differential effects of maintenance agent were found for the few subjects without illicit opioid use , such that withdrawal latencies for methadone-maintained ( n = 5 ) were less than for buprenorphine-maintained ( n = 7 ) which were less than controls ( n = 18 ) . Diminished pain tolerance in patients receiving opioid maintenance treatment has significant clinical implication s. More research is needed to determine if buprenorphine offers advantages over methadone in this regard Methadone medical maintenance ( MMM ) reduces the reporting schedule for stable and well-functioning methadone maintenance patients to once a month , with counseling provided by medical staff . We report on the 12-month outcomes of 92 highly stable methadone maintenance patients r and omly assigned to one of three study conditions : routine care , MMM at the methadone maintenance program , and MMM at a physician 's office . Methadone medical maintenance patients received a 28-day supply of methadone , whereas routine care patients received five or six take-home methadone doses each week . All patients performed a medication recall once a month and su bmi tted two urine sample s each month . An adaptive stepped-care system of treatment intensification was used for patients who failed recall or who had drug-positive urine specimens . Seventy-seven patients completed the 12-month study period . Dropout was caused primarily by problems with h and ling methadone and disliking the recall frequency . There were low rates of drug use or failed medication recall . Treatment satisfaction was high in all groups , but the MMM patients initiated more new employment or family/social activities than did routine care patients over the study period . The stepped-care approach was well tolerated and matched patients to an appropriate step of service within a continuum of treatment intensity Abstract Background Buprenorphine dependence is a relatively novel addiction . Aims To compare the treatment outcome in three groups over 12-weeks of treatment . Methods Two hundred and four intravenous (IV)-buprenorphine-dependent patients were r and omised into three groups . Subjects received 50 mg oral methadone tablet , or 5 mg sublingual buprenorphine tablet , or 50 mg oral naltrexone , and a weekly 30-minute clinical counselling session . Results The majority ( 80 % ) had a history of opium or heroin dependency before they were introduced to IV buprenorphine . The main source of buprenorphine for misusers was street sale ( 91 % ) . The mean duration of buprenorphine dependence was 1.9 years and the mean dose per day was 3.9 ampoules ( 1 ampoule contains 0.3 mg of buprenorphine in 1ml ) . Overall 59 % of the patients completed the 12-week study . Retention in the 50 mg methadone group was significantly better than the 5 mg dose buprenorphine group ( p=0.001 ) and the 50 mg dose naltrexone group ( p=0.000 ) . Retention in the 5 mg buprenorphine group was significantly better than the 50 mg naltrexone dose group ( p=0.000 ) . Conclusions These results support the efficacy and safety of oral methadone and sublingual buprenorphine tablets for injection buprenorphine-dependent patients BACKGROUND The partial opiate-receptor agonist buprenorphine has been suggested for treatment of heroin dependence , but there are few long-term and placebo-controlled studies of its effectiveness . We aim ed to assess the 1-year efficacy of buprenorphine in combination with intensive psychosocial therapy for treatment of heroin dependence . METHODS 40 individuals aged older than 20 years , who met DSM-IV criteria for opiate dependence for at least 1 year , but did not fulfil Swedish legal criteria for methadone maintenance treatment were r and omly allocated either to daily buprenorphine ( fixed dose 16 mg sublingually for 12 months ; supervised daily administration for a least 6 months , possible take-home doses thereafter ) or a tapered 6 day regimen of buprenorphine , thereafter followed by placebo . All patients participated in cognitive-behavioural group therapy to prevent relapse , received weekly individual counselling sessions , and su bmi tted thrice weekly supervised urine sample s for analysis to detect illicit drug use . Our primary endpoint was 1-year retention in treatment and analysis was by intention to treat . FINDINGS 1-year retention in treatment was 75 % and 0 % in the buprenorphine and placebo groups , respectively ( p=0.0001 ; risk ratio 58.7 [ 95 % CI 7.4 - 467.4 ] ) . Urine screens were about 75 % negative for illicit opiates , central stimulants , cannabinoids , and benzodiazepines in the patients remaining in treatment . INTERPRETATION The combination of buprenorphine and intensive psychosocial treatment is safe and highly efficacious , and should be added to the treatment options available for individuals who are dependent on heroin AIMS To evaluate the effectiveness of buprenorphine compared with methadone maintenance therapy in opiate addicts over a treatment period of 24 weeks . DESIGN Subjects were r and omized to receive either buprenorphine or methadone in an open , comparative study . SETTING Subjects were recruited and treated at the drug addiction outpatient clinic at the University of Vienna . PARTICIPANTS Sixty subjects ( 19 females and 41 males ) who met DSM-IV criteria for opioid dependence and were seeking treatment . INTERVENTION Subjects received either sublingual buprenorphine ( 2-mg or 8-mg tablets ; maximum daily dose 8 mg ) or oral methadone ( racemic D -/+ L-methadone ; maximum daily dose 80 mg ) . A stable dose was maintained following the 6-day induction phase . MEASUREMENT Assessment of treatment retention and illicit substance use ( opiates , cocaine and benzodiazepines ) was made by urinalysis . FINDINGS The retention rate was significantly better in the methadone maintained group ( p < 0.05 ) but subjects completing the study in the buprenorphine group had significantly lower rates of illicit opiate consumption ( p = 0.04 ) . CONCLUSION The results support the superiority of methadone with respect to retention rate . However , they also confirm previous reports of buprenorphine use as an alternative in maintenance therapy for opiate addiction , suggesting that a specific subgroup may be benefiting from buprenorphine . This is the first comparative trial to use sublingual buprenorphine tablets : previously published comparison studies refer to 30 % solutions of buprenorphine in alcohol BACKGROUND Prescription opioid dependence is a growing problem , but little research exists on its treatment , including patient characteristics that predict treatment outcome . METHODS A secondary analysis of data from a large multisite , r and omized clinical trial , the National Drug Abuse Treatment Clinical Trials Network Prescription Opioid Addiction Treatment Study ( POATS ) was undertaken to examine baseline patient characteristics ( N=360 ) associated with success during 12-week buprenorphine/naloxone treatment for prescription opioid dependence . Baseline predictor variables included self-reported demographic and opioid use history information , diagnoses assessed via the Composite International Diagnostic Interview , and historical opioid use and related information from the Pain And Opiate Analgesic Use History . RESULTS In bivariate analyses , pre-treatment characteristics associated with successful opioid use outcome included older age , past-year or lifetime diagnosis of major depressive disorder , initially obtaining opioids with a medical prescription to relieve pain , having only used opioids by swallowing or sublingual administration , never having used heroin , using an opioid other than extended-release oxycodone most frequently , and no prior opioid dependence treatment . In multivariate analysis , age , lifetime major depressive disorder , having only used opioids by swallowing or sublingual administration , and receiving no prior opioid dependence treatment remained as significant predictors of successful outcome . CONCLUSIONS This is the first study to examine characteristics associated with treatment outcome in patients dependent exclusively on prescription opioids . Characteristics associated with successful outcome after 12 weeks of buprenorphine/naloxone treatment include some that have previously been found to predict heroin-dependent patients ' response to methadone treatment and some specific to prescription opioid-dependent patients receiving buprenorphine/naloxone Ninety-six confirmed heroin addicts requesting a heroin maintenance prescription were r and omly allocated to treatment with injectable heroin or oral methadone . Progress was monitored throughout the next 12 months by research workers operating independently of the clinic . Heroin can be seen as maintaining the status quo , with the majority continuing to inject heroin regularly and to supplement their maintenance prescription from other sources ; it was associated with a continuing intermediate level of involvement with the drug subculture and criminal activity . Refusal to prescribe heroin while offering oral methadone constituted a more confrontational response and result ed in a higher abstinence rate , but also a greater dependence on illegal sources of drugs for these who continued to inject . Those offered oral methadone tended to polarize toward high or low categories of illegal drug use and involvement with the drug subculture , and were more likely to be arrested during the 12-month follow-up . There was no difference between the two groups in terms of employment , health , or consumption of nonopiate drugs . Refusal to prescribe heroin result ed in a significantly greater drop out from regular treatment AIMS To evaluate the safety and efficacy of an 8 mg/day sublingual dose of buprenorphine in the maintenance treatment of heroin addicts by comparison with a 1 mg/day dose over a 16-week treatment period . As a secondary objective , outcomes were determined concurrently for patients treated with two other dose levels . DESIGN Patients were r and omized to four dosage groups and treated double-blind . SETTING Twelve outpatient opiate maintenance treatment centers throughout the United States . PARTICIPANTS Two hundred and thirty-nine women and 497 men who met the DSM-III-R criteria for opioid dependence and were seeking treatment . INTERVENTION Patients received either 1 , 4 , 8 or 16 mg/day of buprenorphine and were treated in the usual clinical context , including a 1-hour weekly clinical counseling session . MEASUREMENT Retention in treatment , illicit opioid use as determined by urine toxicology , opioid craving and global ratings by patient and staff . Safety outcome measures were provided by clinical monitoring and by analysis of the reported adverse events . FINDINGS Outcomes in the 8 mg group were significantly better than in the 1 mg group in all four efficacy domains . No deaths occurred in either group . The 8 mg group did not show an increase in the frequency of adverse events . Most reported adverse effects were those commonly seen in patients treated with opioids . CONCLUSIONS The findings support the safety and efficacy of buprenorphine and suggest that an adequate dose of buprenorphine will be a useful addition to pharmacotherapy Buprenorphine at 2 mg and 6 mg daily was compared with methadone at 35 mg and 65 mg during 24 weeks of maintenance among 125 opioid-dependent patients . As hypothesized , 6 mg of buprenorphine were superior to 2 mg of buprenorphine in reducing illicit opioid use , but higher dosage did not improve treatment retention . Self-reported illicit opioid use declined substantially in all groups , but by the third month , significantly more heroin abuse was reported at 2 mg than at 6 mg of buprenorphine or of methadone . From an initial average of $ 1860/month , month 3 usage dropped to $ 41 ( methadone 65 mg ) , $ 73 ( methadone 35 mg ) , $ 118 ( buprenorphine 6 mg ) , and $ 35I/month ( buprenorphine 2 mg ) . Days of use also dropped from 29 days to 1.7 ( methadone 65 mg ) , 2.8 ( methadone 35 mg ) , 4.0 ( buprenorphine 6 mg ) , and 6.6 days/month ( buprenorphine 2 mg ) . This relatively low efficacy for 2 mg of buprenorphine persisted through month 6 of the trial , with 7.2 days/month and $ 235/month of use for buprenorphine at 2 mg versus 1.9 days/month and $ 65/month for the other three groups . Increased opioid abuse also was associated with significantly greater and persistent opioid withdrawal symptoms . Our secondary hypothesis , that buprenorphine would be equivalent to methadone in efficacy , was not supported . Treatment retention was significantly better on methadone ( 20 us . 16 weeks ) , and methadone patients had significantly more opioid-free urines ( 51 % vs. 26 % ) . Abstinence for at least 3 weeks was also more common on methadone than buprenorphine ( 65 % vs. 27 % ) . Thus , methadone was clearly superior to these two buprenorphine doses , but illicit opioid use was reduced more by higher than lower buprenorphine dosage . Future studies need to examine higher sublingual buprenorphine doses of 12 mg to 20 mg daily for potential efficacy AIMS To assess the efficacy of buprenorphine compared with methadone maintenance therapy for opioid dependence in a large sample using a flexible dosing regime and the marketed buprenorphine tablet . DESIGN Patients were r and omized to receive buprenorphine or methadone over a 13-week treatment period in a double-blind , double-dummy trial . SETTING Three methadone clinics in Australia . PARTICIPANTS Four hundred and five opioid-dependent patients seeking treatment . INTERVENTION Patients received buprenorphine or methadone as indicated clinical ly using a flexible dosage regime . During weeks 1 - 6 , patients were dosed daily . From weeks 7 - 13 , buprenorphine patients received double their week 6 dose on alternate days . MEASUREMENTS Retention in treatment , and illicit opioid use as determined by urinalysis . Self-reported drug use , psychological functioning , HIV-risk behaviour , general health and subjective ratings were secondary outcomes . FINDINGS Intention-to-treat analyses revealed no significant difference in completion rates at 13 weeks . Methadone was superior to buprenorphine in time to termination over the 13-week period ( Wald chi 2 = 4.371 , df = 1 , P = 0.037 ) , but not separately for the single-day or alternate-day dosing phases . There were no significant between-group differences in morphine-positive urines , or in self-reported heroin or other illicit drug use . The majority ( 85 % ) of the buprenorphine patients transferred to alternate-day dosing were maintained in alternate-day dosing . CONCLUSIONS Buprenorphine did not differ from methadone in its ability to suppress heroin use , but retained approximately 10 % fewer patients . This poorer retention was due possibly to too-slow induction onto buprenorphine . For the majority of patients , buprenorphine can be administered on alternate days CONTEXT Sustained-release naltrexone implants may improve outcomes of nonagonist treatment of opioid addiction . OBJECTIVE To compare outcomes of naltrexone implants , oral naltrexone hydrochloride , and nonmedication treatment . DESIGN Six-month double-blind , double-dummy , r and omized trial . SETTING Addiction treatment programs in St Petersburg , Russia . PARTICIPANTS Three hundred six opioid-addicted patients recently undergoing detoxification . INTERVENTIONS Biweekly counseling and 1 of the following 3 treatments for 24 weeks : ( 1 ) 1000-mg naltrexone implant and oral placebo ( NI+OP group ; 102 patients ) ; ( 2 ) placebo implant and 50-mg oral naltrexone hydrochloride ( PI+ON group ; 102 patients ) ; or ( 3 ) placebo implant and oral placebo ( PI+OP group ; 102 patients ) . MAIN OUTCOME MEASURE Percentage of patients retained in treatment without relapse . RESULTS By month 6 , 54 of 102 patients in the NI+OP group ( 52.9 % ) remained in treatment without relapse compared with 16 of 102 patients in the PI+ON group ( 15.7 % ) ( survival analysis , log-rank test , P < .001 ) and 11 of 102 patients in the PI+OP group ( 10.8 % ) ( P < .001 ) . The PI+ON vs PI+OP comparison showed a nonsignificant trend favoring the PI+ON group ( P = .07 ) . Counting missing test results as positive , the proportion of urine screening tests yielding negative results for opiates was 63.6 % ( 95 % CI , 60%-66 % ) for the NI+OP group ; 42.7 % ( 40%-45 % ) for the PI+ON group ; and 34.1 % ( 32%-37 % ) for the PI+OP group ( P < .001 , Fisher exact test , compared with the NI+OP group ) . Twelve wound infections occurred among 244 implantations ( 4.9 % ) in the NI+OP group , 2 among 181 ( 1.1 % ) in the PI+ON group , and 1 among 148 ( 0.7 % ) in the PI+OP group ( P = .02 ) . All events were in the first 2 weeks after implantation and resolved with antibiotic therapy . Four local-site reactions ( redness and swelling ) occurred in the second month after implantation in the NI+OP group ( P = .12 ) , and all resolved with antiallergy medication treatment . Other nonlocal-site adverse effects were reported in 8 of 886 visits ( 0.9 % ) in the NI+OP group , 4 of 522 visits ( 0.8 % ) in the PI+ON group , and 3 of 394 visits ( 0.8 % ) in the PI+ON group ; all resolved and none were serious . No evidence of increased deaths from overdose after naltrexone treatment ended was found . CONCLUSIONS The implant is more effective than oral naltrexone or placebo . More patients in the NI+OP than in the other groups develop wound infections or local irritation , but none are serious and all resolve with treatment . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00678418 Buprenorphine was registered in Australia as a maintenance and detoxification agent for the management of opioid dependence in November , 2000 , and became widely available in August , 2001 . This paper provides an overview of key developments in the introduction of buprenorphine treatment in Australia , with an emphasis upon the delivery of services in community-based ( primary care ) setting s. A central study in this work was the Buprenorphine Implementation Trial ( BIT ) , a r and omized , controlled trial comparing buprenorphine and methadone maintenance treatment delivered under naturalistic conditions by specialist and community-based service providers ( general practitioners and community pharmacists ) in 139 subjects across nineteen treatment sites . In addition to conventional patient outcome measures ( treatment retention , drug use , psychosocial functioning , and cost effectiveness ) , the BIT study also involved the development and evaluation of clinical guidelines , training programs for clinicians , and client literature , which are described here . Integration of treatment systems ( methadone with buprenorphine , specialist and primary -care programs ) and factors thought to be important in the uptake of buprenorphine treatment in Australia since registration are discussed AIMS To evaluate the effect of a 4 mg/day sublingual dose of buprenorphine in the maintenance treatment of opium dependence in comparison with a 1 mg/day dose over an 18-week treatment period . As a secondary objective , the results were determined concurrently for subjects treated with a 2 mg/day dose . DESIGN Subjects were assigned r and omly to three dosage groups . PARTICIPANTS 330 consecutive ( 320 men and 10 women ) opium addicts who met the DSM-IV criteria for opioid dependence and were seeking treatment . INTERVENTION Subjects received a 1 , 2 or 4 mg/day dose of buprenorphine and were treated in an outpatient clinic where they also received a weekly 1-hour clinical counseling session . MEASUREMENTS Addiction Severity Index , retention in treatment , and illegal opioid use as determined by r and om urine testing . FINDINGS The mean age was 37.5 years ( SD=11.4 , range 19 - 72 ) . Overall , 194 ( 58.8 % ) of the patients completed the 18 week study . Completion rates by dosage groups were 47.3 % for the 1 mg group , 58.2 % for the 2 mg group and 70.9 % for the 4 mg group ( chi(2)=12.7 , df=2 , P=0.0017 ) . CONCLUSIONS The results support the efficacy and safety of buprenorphine for opium addiction and suggest that an adequate dose of buprenorphine would help to increase the success rate AIM This study aim ed to assess the efficacy of the prescription of intravenous diacetylmorphine ( DAM ) versus oral methadone with medical and psychosocial support , with a view of improving physical and mental health as well as social integration among socially excluded , opioid-dependent individuals for whom st and ard treatments have failed . DESIGN This study used an open , r and omized controlled trial . SETTING This study took place in Granada , Spain . PARTICIPANTS Sixty-two opioid-dependent participants were r and omized , 31 in each treatment group , and 50 of them were analyzed . The participants were recruited directly from the streets , through peer outreach , in well-known meeting places for drug-addicted individuals . INTERVENTIONS Participants in the experimental group received injected DAM , twice a day , plus oral methadone , once a day , for 9 months . The control group received only oral methadone , once a day . The two groups received an equivalent opioid dosage . The average DAM dosage was 274.5 mg/day ( range : 15 - 600 mg ) , and an average methadone dosage was 42.6 mg/day ( range : 18 - 124 mg ) . The daily methadone dosage in the control group was 105 mg/day ( range : 40 - 180 mg ) . Comprehensive clinical , psychological , social , and legal support was given to both groups . MEASUREMENTS The following were measured in this study : general health , quality of life , drug-addiction-related problems , nonmedical use of heroin , risk behavior for HIV and HCV , and psychological , family , and social status . FINDINGS Both groups improved with respect to the total domain assessed . Those in the experimental group showed greater improvement in terms of physical health ( the improvement was 2.5 times higher ; p = .034 ) and risk behavior for HIV infection ( the improvement was 1.6 times higher ; p = .012 ) . In addition , this group decreased its street heroin use from 25 days/month to 8 days/month as seen on the Addiction Severity Index ( p = .020 ) , as well as the number of days free from drug-related problems ( the improvement was 2.1 times higher ; p = .004 ) or involvement in crime ( from 11 days/month to < 1 day/month ; p = .096 between groups ) . CONCLUSIONS These findings support the hypothesis that , under the same conditions , DAM could be safely delivered , in our context . Also , in physical health , HIV risk behavior , street heroin use , and days involved in crime , DAM plus methadone was more efficacious than methadone alone . This implies that this treatment could provide an effective alternative for the treatment of socially excluded , opioid-dependent patients with severe physical and mental health problems because of drug addiction , when all available previous treatments have failed INTRODUCTION AND AIMS In 2003 , a r and omised controlled trial comparing injected diacetylmorphine and oral methadone was carried out in And alusia , Spain . The subsequent follow-up study evaluated the health and drug use status of participants , 2 years after the completion of the trial . DESIGN AND METHODS This follow-up cohort study was carried out between March and August 2006 . Data collected included information on socio-demographics , drug use , health and health-related quality of life . We compared data collected before r and omisation and at 2 years for the following three groups : those currently on heroin-assisted treatment ( C-HAT ) , those who have discontinued HAT ( D-HAT ) , and those who have never received HAT ( N-HAT ) . RESULTS From the total 62 r and omised participants in 2003 , 54 ( 87 % ) were interviewed for this study . Participants were distributed as follow : C-HAT 44.4 % ( 24 ) , N-HAT 22.2 % ( 12 ) and D-HAT 33.3 % ( 18 ) . Illicit heroin use had a statistically significant decrease in the three groups from baseline to 2 years post trial . Mean days of heroin use were 2.42 ( SD = 3.02 ) ; 6.56 ( SD = 9.48 ) and 13.92 ( SD = 12.59 ) for the C-HAT , D-HAT and N-HAT groups , respectively . Those currently on HAT were the only group that sustained at 2 years , their marked improvement in health after 9 months of treatment during the trial period . DISCUSSION AND CONCLUSIONS Patients who received HAT showed better outcomes compared with those not on HAT . The results of this study strengthen the evidence showing that HAT can improve and stabilise the health of long-term heroin users with severe comorbidities and high mortality BACKGROUND Buprenorphine is a partial agonist at the mu-opioid receptor that has been proposed as an alternative to traditional full agonist maintenance therapy for the treatment of opioid addiction . We report on a clinical trial in which the relative safety and efficacy of long-term fixed-dose buprenorphine maintenance was examined in comparison to low- and high-dose methadone maintenance . METHODS Two hundred twenty-five treatment-seeking opioid addicts ( 46 women , 179 men ) were r and omly assigned to receive , in a double-blind manner , either 8 mg/d of buprenorphine , 30 mg/d of methadone , or 80 mg/d of methadone maintenance over a 1-year period . Objective and subjective measures of efficacy ( urine toxicology , retention , craving , and withdrawal symptoms ) were examined at the study midpoint and at termination , and safety data were tabulated over the entire 52-week study period . RESULTS Patients assigned to high-dose methadone maintenance performed significantly better on measures of retention , opioid use , and opioid craving than either the low-dose methadone or the buprenorphine group at both 26-week and 52-week time points . Performance on these measures was virtually identical between the latter two groups . No serious adverse health effects attributable to buprenorphine were noted . CONCLUSIONS Buprenorphine maintenance at 8 mg/d appears to be less than optimally efficacious under the conditions of the present study . Continued research is needed to reconcile these findings with the more positive results reported by other investigative groups . There are no apparent health risks associated with long-term buprenorphine maintenance at this dosage Clinical trials carried out to compare methadone and buprenorphine in the treatment of opioid dependence have generally employed an alcoholic solution of buprenorphine , which has a bioavailability superior to that of the tablets . Since the product available for large scale use is in tablet form , one intended to verify the efficacy of this formulation . In a multicentre r and omised controlled double blind study , 72 opioid dependent patients were assigned to treatment with buprenorphine ( 8 mg/day ) or methadone ( 60 mg/day ) for a period of 6 months . The two compounds did not show any significant difference with regard to urinalyses : the average percentage of analyses proving negative was 60.4 % for patients assigned to buprenorphine , and 65.5 % for those assigned to methadone . With regard to retention , a non-significant trend in favour of methadone was observed . Patients completing the trial improved significantly in terms of psychosocial adjustment and global functioning , as ascertained by the DSM-IV-GAF and symptom checklist-90 ( SCL-90 ) scales , and this was independent of the treatment group . Finally , in the case of buprenorphine , patients who dropped out differed significantly from those who stayed , in terms of a higher level of psychopathological symptoms , and a lower level of psychosocial functioning . The results of the study further support the utility of buprenorphine for the treatment of opioid dependence CONTEXT Oral naltrexone can completely antagonize the effects produced by opioid agonists . However , poor compliance with naltrexone has been a major obstacle to the effective treatment of opioid dependence . OBJECTIVE To evaluate the safety and efficacy of a sustained-release depot formulation of naltrexone in treating opioid dependence . DESIGN AND SETTING R and omized , double-blind , placebo-controlled , 8-week trial conducted at 2 medical centers . PARTICIPANTS Sixty heroin-dependent adults . INTERVENTIONS Participants were stratified by sex and years of heroin use ( > or = 5 vs < 5 ) and then were r and omized to receive placebo or 192 or 384 mg of depot naltrexone . Doses were administered at the beginning of weeks 1 and 5 . All participants received twice-weekly relapse prevention therapy , provided observed urine sample s , and completed other assessment s at each visit . MAIN OUTCOME MEASURES Retention in treatment and percentage of opioid-negative urine sample s. RESULTS Retention in treatment was dose related , with 39 % , 60 % , and 68 % of patients in the placebo , 192 mg of naltrexone , and 384 mg of naltrexone groups , respectively , remaining in treatment at the end of 2 months . Time to dropout had a significant main effect of dose , with mean time to dropout of 27 , 36 , and 48 days for the placebo , 192 mg of naltrexone , and 384 mg of naltrexone groups , respectively . The percentage of urine sample s negative for opioids , methadone , cocaine , benzodiazepines , and amphetamine varied significantly as a function of dose . When the data were recalculated without the assumption that missing urine sample s were positive , a main effect of group was not found for any drugs tested except cocaine , where the percentage of cocaine-negative urine sample s was lower in the placebo group . Adverse events were minimal and generally mild . This formulation of naltrexone was well tolerated and produced a robust , dose-related increase in treatment retention . CONCLUSION These data provide new evidence of the feasibility , efficacy , and tolerability of long-lasting antagonist treatments for opioid dependence Large-scale placebo controlled clinical trials assessing the efficacy of medications for the treatment of drug dependence have generally been limited to alcohol , cocaine and nicotine dependent population s. The purpose of the present study was to assess the early ( 1 - 2 week ) clinical effectiveness of buprenorphine versus placebo in an opioid dependent population . The study used a parallel-group design with a behavioral choice component to compare buprenorphine ( a mu-opioid partial agonist ) to placebo for the treatment of opioid dependence . Opioid dependent volunteer patients participated in a 14-day study to assess the effectiveness and patient acceptance of this new pharmacotherapy for the treatment of opioid dependence . Patients were r and omly assigned to placebo ( n = 60 ) or 2 mg ( n = 60 ) or 8 mg ( n = 30 ) daily sublingual buprenorphine . All doses were administered double-blind . On days 6 - 13 all patients could request a dose change , knowing that their new dose would be r and omly chosen from the remaining 2 alternatives . Compared to placebo , patients given buprenorphine ( independent of dose ) showed greater time on initial dose , requested fewer dose changes , used less illicit opioids ( assessed by urinalysis ) , and rated dose adequacy higher . These results demonstrate that a placebo controlled study with a behavioral choice component is an effective means of assessing the potential efficacy and acceptability of new pharmacotherapies for opioid dependence AIMS To compare levo-alpha-acetylmethadol ( LAAM ) and methadone maintenance ( MM ) on treatment retention , drug use during treatment and at follow-up , and abstinence . DESIGN A two-group experimental design with patients assigned r and omly ( 2:1 ) to receive fully subsidized LAAM or MM for 52 weeks . SETTING A community clinic providing maintenance treatment in Los Angeles , California . PARTICIPANTS A total of 315 treatment-seeking patients willing to be assigned r and omly to treatment condition ; 289 ( 91.7 % ) were interviewed at 52 weeks . INTERVENTION LAAM or MM , plus ancillary services available to all patients . Medication dose varied according to clinical judgement . MEASUREMENTS Treatment retention and status at 52-week follow-up , weekly clinical urinalysis , self-reported drug use and research urinalysis on sample s collected at follow-up . FINDINGS LAAM participants were more likely to complete the planned 52 weeks ( 57.4 % ) than MM participants ( 46.2 % ) and were less likely to be discharged for arrest/incarceration . LAAM produced fewer during treatment clinic opiate-positive sample s ( M = 48.8 ) than MM ( M = 62.3 ) . Further , 24.4 % on LAAM compared to 11.8 % on MM were able to sustain at least 12 weeks of abstinence during the last 24 weeks of treatment . Opiate use at follow-up was lowest ( 50.9 % ) among LAAM participants in maintenance treatment . No adverse events , cardiological or otherwise , were observed with LAAM administration . CONCLUSIONS LAAM is an effective medication for the treatment of opiate dependence in community clinics with numerous behavioral and clinical advantages . LAAM is more effective than MM in promoting retention and extended reduction in and abstinence from opiate use while in treatment This was a double-blind comparison of methadyl acetate and two dose levels of methadone hydrochloride in the maintenance of 430 street heroin addicts from 12 Veterans Administration hospitals . The starting sample consisted of 146 patients receiving low-dose methadone , 142 patients receiving methadyl acetate . Patients were first given 30 mg of both drugs , and doses were incremented by 10 mg/week until they stabilized at methadyl acetate , 80 mg three times a week , and methadone hydrochloride , 50 mg daily or 100 mg daily . Dosage was fixed for the balance of the 40-week treatment period . Safety was evaluated by clinical and laboratory observations conducted at frequent intervals throughout the study . Relative efficacy was evaluated by illicit drug use , program retention and attendance , and global staff judgments . It is concluded that methadyl acetate is as safe a drug as methadone and that it compares favorably with highdose methoadone in terms of efficacy . Both methyadyl acetate and high-dose methadone appear to be better maintenance regimens than low-dose methadone under the conditions of this study OBJECTIVE To compare the clinical efficacy of different doses of levomethadyl acetate hydrochloride ( known as LAAM ) in the treatment of opioid dependence . DESIGN A r and omized controlled , double-blind , parallel group , 17-week study . SETTING Outpatient facilities at Johns Hopkins University Bayview Medical Center , Baltimore , Md. PATIENTS Opioid-dependent volunteers ( N=180 ) applying to a treatment- research clinic . INTERVENTION Thrice-weekly ( Monday/Wednesday/Friday ) oral LAAM dose conditions of 25/25/35 mg , 50/50/70 mg , and 100/100/140 mg and nonm and atory counseling . MAIN OUTCOME MEASURES Retention in treatment , self-reported heroin use , and opioid-positive urine specimens . RESULTS Retention was independent of subjects ' sex and dose . Self-reported heroin use decreased in a dose-related manner . At final assessment , patients in the high-dose condition reported using heroin 2.5 of 30 days as compared with 4.1 or 6.3 days for patients in the medium-dose and low-dose conditions , respectively ( high dose vs low dose , P<.05 ) ; urinalysis results were similarly dose related . Overall , 20 ( 34 % ) of 59 patients in the high-dose condition remained opioid-abstinent for 4 consecutive weeks , as compared with 8 ( 14 % ) of 59 in the medium-dose and 7 ( 11 % ) of 62 in the low-dose conditions ( P<.01 ) . Self-report and urinalysis data are consistent with a greater than 90 % reduction in illicit opioid use by the high-dose group relative to pretreatment levels . CONCLUSION Opioid substitution treatment with LAAM substantially reduces illicit opioid use . The clinical efficacy of LAAM is positively related to dose The aim of this study is to characterize patients with chronic pain in methadone maintenance treatment ( MMT ) . Between September and December , 2003 , 170 consecutive patients from an MMT clinic participated in a question naire survey on pain ( duration and severity ) . Chronic pain was defined as current pain lasting for ≥6 months . The patients ' maintenance methadone dosage and urine tests for drug abuse during the month before and of the survey were recorded . Of the 170 patients , 94 ( 55.3 % ) experienced chronic pain . They had a significantly higher proportion of chronic illness ( 74.5 % ) compared to non‐pain patients ( 44.7 % ) ( Fisher‘s Exact Test P<0.0005 ) . Twelve ( 12.8 % ) of the chronic pain patients scored their pain as mild , 38 ( 40.4 % ) as moderate , 22 ( 23.4 % ) as severe and 22 ( 23.4 % ) as very severe . Pain duration significantly correlated with pain severity ( Pearson R=0.3 , P>0.0005 ) and was significantly associated with methadone daily dosage : patients with pain duration of ≥10 years ( n=26 ) were receiving the highest methadone dosage ( 182.1±59.2 mg/day ) , those with pain duration from 1 to 10 years ( n=59 ) 160.9±56.2 mg/day , and those with pain duration of < 1 year ( n=9 ) 134.2±73.2 mg/day . Patients in the non‐pain group ( n=76 ) were receiving 147.1±52.8 mg/day of methadone ( ANOVA , F=3.1 , P=0.03 ) . We conclude that pain duration and severity significantly correlated . Although methadone was not prescribed for the treatment of pain but rather for opiate addiction , the patients in the MMT clinic with prolonged pain were prescribed a significantly higher methadone dosage compared to patients with short pain duration , and non‐pain patients Patients with opioid addiction who receive prescription opioids for treatment of nonmalignant chronic pain present a therapeutic challenge . Fifty-four participants with chronic pain and opioid addiction were r and omized to receive methadone or buprenorphine/naloxone . At the 6-month follow-up examination , 26 ( 48.1 % ) participants who remained in the study noted a 12.75 % reduction in pain ( P = 0.043 ) , and no participants in the methadone group compared to 5 in the buprenorphine group reported illicit opioid use ( P = 0.039 ) . Other differences between the two conditions were not found . Long-term , low-dose methadone or buprenorphine/naloxone treatment produced analgesia in participants with chronic pain and opioid addiction OBJECTIVE To assess the efficacy of buprenorphine for short-term maintenance/detoxification . DESIGN A r and omized , double-blind , parallel group study comparing buprenorphine , 8 mg/d , methadone , 60 mg/d , and methadone , 20 mg/d , in a 17-week maintenance phase followed by an 8-week detoxification phase . SETTING Outpatient facilities at the Addiction Research Center , Baltimore , Md. PATIENTS One hundred sixty-two volunteers seeking treatment for opioid dependence . INTERVENTION In addition to the medication , counseling using a relapse prevention model was offered but not required . PRIMARY OUTCOME MEASURES Retention time in treatment , urine sample s negative for opioids , and failure to maintain abstinence . RESULTS Throughout the maintenance phase , retention rates were significantly greater for buprenorphine ( 42 % ) than for methadone , 20 mg/d ( 20 % , P less than .04 ) ; the percentage of urine sample s negative for opioids was significantly greater for buprenorphine ( 53 % , P less than .001 ) and methadone , 60 mg/d ( 44 % , P less than .04 ) , than for methadone , 20 mg/d ( 29 % ) . Failure to maintain abstinence during the maintenance phase was significantly greater for methadone , 20 mg/d , than for buprenorphine ( P less than .03 ) . During the detoxification phase , no differences were observed between groups with respect to urine sample s negative for opioids . For the entire 25 weeks , retention rates for buprenorphine ( 30 % , P less than .01 ) and methadone , 60 mg/d ( 20 % , P less than .05 ) , were significantly greater than for methadone , 20 mg/d ( 6 % ) . All treatments were well tolerated , with similar profiles of self-reported adverse effects . The percentages of patients who received counseling did not differ between groups . CONCLUSIONS Buprenorphine was as effective as methadone , 60 mg/d , and both were superior to methadone , 20 mg/d , in reducing illicit opioid use and maintaining patients in treatment for 25 weeks AIMS Slow-release morphine may represent a much-needed new pharmacological treatment for opioid dependence . DESIGN In a 14-week r and omized , double-blind , double-dummy , cross-over study oral slow-release morphine was compared with methadone as a treatment for opioid dependency . During two study periods , each consisting of a 1-week titration and a 6-week fixed-dose treatment phase , medication was administered daily under supervised conditions . SETTING The study was carried out at the Addiction Clinic , Department of Psychiatry , Medical University Vienna . PARTICIPANTS Sixty-four subjects ( 56 males , eight females ) with opioid dependence participated in the trial . MEASUREMENTS Efficacy was evaluated on the basis of retention , use of illicit substances based on urinalysis , extent of drug cravings , withdrawal symptoms and general wellbeing . Safety was assessed on the basis of adverse events and clinical and physical examination . Demographic and baseline characteristics were assessed using the European Addiction Severity Index . FINDINGS Fifty-five patients ( 86 % ) completed the study , with a mean methadone dose of 85 mg and a mean slow-release morphine dose of 680 mg . No significant differences in retention or use of illicit substances ( opioids , benzodiazepines , cocaine ) were observed , irrespective of treatment group or medication . However , patients receiving slow-release morphine had significantly lower depression ( P < 0.001 ) and anxiety scores ( P = 0.008 ) and fewer physical complaints ( P < 0.001 ) . CONCLUSIONS Oral slow-release morphine is as effective as methadone in the treatment of opioid dependency , with comparable safety and tolerability and a greater benefit on patient wellbeing . Greater pharmaceutical diversity represents a modern development in mainstream medicine . Slow-release morphine might represent a future treatment option that will improve long-term outcomes for this target group BACKGROUND Acute and chronic pains are reported to be highly prevalent in patients under opioid maintenance treatment ( OMT ) . Lack of knowledge concerning the complex relationship between pain , opioid use , and their impact on OMT efficacy can account for the barriers encountered for pain management . OBJECTIVES To assess the impact of acute pain exposure on long-term OMT retention in a cohort of patients under buprenorphine or methadone followed up during 12 months . STUDY DESIGN Prospect i ve , multi-center observational cohort clinical study . SETTING Emergency departments , surgery departments , and specialized addiction care centers in an outpatient setting in south-western France ( Midi-Pyrenees area ) , from April 2008 to January 2010 . METHODS Patients aged 18 or more under OMT for at least 3 months , and followed up by a physician were recruited . Acute pain was assessed using the Visual Analog Scale ( VAS ) or the Verbal Rating Scale ( VRS ) . Exposed patients were those with a pain score greater than 0 at the time of admission on any of the rating scales . The OMT rate after 12 months was compared among exposed and unexposed patients . OMT retention was also investigated after 3 and 6 months follow-up . RESULTS A total of 151 patients , 81 exposed and 70 unexposed , were recruited ; among them , respectively , 26 ( 32 % ) and 34 ( 49 % ) completed 12-months follow-up . Acute pain exposure appeared to be significantly and negatively associated with retention in treatment ( crude OR : 0.44 ; 95 % CI [ 0.22 - 0.87 ] ; adjusted OR : 0.46 ; 95 % CI [ 0.23 - 0.93 ] ) . Compared to methadone users , patients under buprenorphine were less likely to have their OMT maintained after 12 months ( OR 0.37 ; 95 % CI [ 0.18 - 0.75 ] ; adjusted OR 0.38 ; 95 % CI [ 0.18 - 0.80 ] ) . LIMITATIONS Follow-up rate was 40 % ( 60/151 ) . CONCLUSION This study demonstrates the strong negative impact of acute pain on OMT in a population mainly composed of patients under buprenorphine , as well as differential response depending on the OMT medication . The findings highlight the need to consider the characteristics of pain in the population under OMT and to develop evidence -based guidelines for pain management . TRIAL REGISTRATION The study was registered at www . clinical .trials.gov with the study identifier : NCT00738036 . Ethics Committee approval was received on February 11 , 2008 . Participants ' written consent was not required This r and omized placebo-controlled trial tested the efficacy of oral naltrexone with or without fluoxetine for preventing relapse to heroin addiction and for reducing HIV risk , psychiatric symptoms , and outcome . All patients received drug counseling with parental or significant-other involvement to encourage adherence . Patients totaling 414 were approached , 343 gave informed consent , and 280 were r and omized ( mean age , 23.6 + /- 0.4 years ) . At 6 months , two to three times as many naltrexone patients as naltrexone placebo patients remained in treatment and had not relapsed , odds ratio ( OR ) = 3.5 ( 1.96 - 6.12 ) , p < .0001 . Overall , adding fluoxetine did not improve outcomes , OR = 1.35 ( 0.68 - 2.66 ) , p = .49 ; however , women receiving naltrexone and fluoxetine showed a trend toward a statistically significant advantage when compared to women receiving naltrexone and fluoxetine placebo , OR = 2.4 ( 0.88 - 6.59 ) , p = .08 . HIV risk , psychiatric symptoms , and overall adjustment were markedly improved among all patients who remained on treatment and did not relapse , regardless of group assignment . More widespread use of naltrexone could be an important addition to addiction treatment and HIV prevention in Russia Background : We established a program of research to improve the development , reporting and evaluation of practice guidelines . We assessed the construct validity of the items and user ’s manual in the β version of the AGREE II . Methods : We design ed guideline excerpts reflecting high- and low- quality guideline content for 21 of the 23 items in the tool . We design ed two study packages so that one low- quality and one high- quality version of each item were r and omly assigned to each package . We r and omly assigned 30 participants to one of the two packages . Participants review ed and rated the guideline content according to the instructions of the user ’s manual and completed a survey assessing the manual . Results : In all cases , content design ed to be of high quality was rated higher than low- quality content ; in 18 of 21 cases , the differences were significant ( p < 0.05 ) . The manual was rated by participants as appropriate , easy to use , and helpful in differentiating guidelines of varying quality , with all scores above the mid-point of the seven-point scale . Considerable feedback was offered on how the items and manual of the β-AGREE II could be improved . Interpretation : The validity of the items was established and the user ’s manual was rated as highly useful by users . We used these results and those of our study presented in part 1 to modify the items and user ’s manual . We recommend AGREE II ( available at www.agreetrust.org ) as the revised st and ard for guideline development , reporting and evaluation AIMS To evaluate whether buprenorphine . even without additional control and psychosocial treatment and support , alleviates the problems faced by patients waiting for medication assisted rehabilitation ( MAR ) . DESIGN A r and omized , double-blind , 12-week study of Subutex versus placebo without additional support as an interim therapy . PARTICIPANTS One hundred and six patients , 70 males and 36 females , waiting for MAR in Oslo . The average age was 38 years with an average history of heroin use of 20 years . Fifty-five patients were assigned to buprenorphine and 51 to a placebo . INTERVENTION Subutex or placebo sublingual tablets were given under supervision in a daily dose of 16 mg with the exception of a double dose on Saturday and no dose on Sunday . MEASUREMENT Retention , compliance , self-reported drug-abuse , wellbeing and mental health . FINDINGS The average number of days of participation was significantly higher in the buprenorphine group , 42 ( median : 29 ) compared to 14 ( median : 11 ) for the placebo group ( P < 0.001 ) . The retention of patients after 12 weeks was 16 patients in the buprenorphine group and one patient in the placebo group . The buprenorphine group had a larger decrease in reported opioid use ( p < 0.001 ) and in reported use of other drugs , tablets and alcohol abuse ( p < 0.01 ) . The group also showed a stronger increase in wellbeing ( p < 0.01 ) and life satisfaction ( p < 0.05 ) . None of the participants died . CONCLUSION The patients waiting for MAR benefited significantly from the buprenorphine as an interim therapy according to retention , self-reported use of drugs and wellbeing . However , the patients had difficulties in remaining in treatment over time without psychosocial support BACKGROUND This analysis explored the prevalence and correlates of pain in patients enrolled in methadone maintenance treatment ( MMT ) . METHODS Patients in two MMT programs starting a hepatitis care coordination r and omized controlled trial completed the Brief Pain Inventory Short-Form and other question naires . Associations between clinical ly significant pain ( average daily pain≥5 or mean pain interference≥5 during the past week ) and sociodemographic data , medical status , depressive symptoms , and health-related quality of life , and current substance use were evaluated in multivariate analyses . RESULTS The 489 patients included 31.8 % women ; 30.3 % Hispanics , 29.4 % non-Hispanic Blacks , and 36.0 % non-Hispanic Whites ; 60.1 % had hepatitis C , 10.6 % had HIV , and 46.8 % had moderate or severe depressive symptomatology . Mean methadone dose was 95.7 mg ( SD 48.9 ) and urine drug screening ( UDS ) was positive for opiates , cocaine , and amphetamines in 32.9 % , 40.1 % , and 2.9 % , respectively . Overall , 237 ( 48.5 % ) reported clinical ly significant pain . Pain treatments included prescribed opioids ( 38.8 % ) and non-opioids ( 48.9 % ) , and self-management approaches ( 60.8 % ) , including prayer ( 33.8 % ) , vitamins ( 29.5 % ) , and distraction ( 12.7 % ) . Pain was associated with higher methadone dose , more medical comorbidities , prescribed opioid therapy , and more severe depressive symptomatology ; it was not associated with UDS or self-reported substance use . CONCLUSIONS Clinical ly significant pain was reported by almost half of the patients in MMT programs and was associated with medical and psychological comorbidity . Pain was often treated with opioids and was not associated with measures of drug use . Studies are needed to further clarify these associations and determine their importance for pain treatment strategies BACKGROUND Studies in Europe have suggested that injectable diacetylmorphine , the active ingredient in heroin , can be an effective adjunctive treatment for chronic , relapsing opioid dependence . METHODS In an open-label , phase 3 , r and omized , controlled trial in Canada , we compared injectable diacetylmorphine with oral methadone maintenance therapy in patients with opioid dependence that was refractory to treatment . Long-term users of injectable heroin who had not benefited from at least two previous attempts at treatment for addiction ( including at least one methadone treatment ) were r and omly assigned to receive methadone ( 111 patients ) or diacetylmorphine ( 115 patients ) . The primary outcomes , assessed at 12 months , were retention in addiction treatment or drug-free status and a reduction in illicit-drug use or other illegal activity according to the European Addiction Severity Index . RESULTS The primary outcomes were determined in 95.2 % of the participants . On the basis of an intention-to-treat analysis , the rate of retention in addiction treatment in the diacetylmorphine group was 87.8 % , as compared with 54.1 % in the methadone group ( rate ratio for retention , 1.62 ; 95 % confidence interval [ CI ] , 1.35 to 1.95 ; P<0.001 ) . The reduction in rates of illicit-drug use or other illegal activity was 67.0 % in the diacetylmorphine group and 47.7 % in the methadone group ( rate ratio , 1.40 ; 95 % CI , 1.11 to 1.77 ; P=0.004 ) . The most common serious adverse events associated with diacetylmorphine injections were overdoses ( in 10 patients ) and seizures ( in 6 patients ) . CONCLUSIONS Injectable diacetylmorphine was more effective than oral methadone . Because of a risk of overdoses and seizures , diacetylmorphine maintenance therapy should be delivered in setting s where prompt medical intervention is available . ( Clinical Trials.gov number , NCT00175357 . This study was conducted to compare long-term outcome effects on the quality of life ( QOL ) of oral methadone with sublingual buprenorphine maintenance treatment . The QOL status of opioid-dependent patients was assessed using the German version ( “ Berlin Quality of Life Profile ” ) of the Lancashire Quality of Life Profile . Physical symptoms were measured using the Opiate Withdrawal Scale ( OWS ) . Urine tests were carried out r and omly to detect additional consumption . In the first study period , 53 opioid-dependent subjects were enrolled and 25 could be reached after 3 years . The retention rate was 50 % for methadone and 45 % for buprenorphine ( p = 0.786 ) . Baseline values of the total sample ( completers and noncompleters ) QOL and somatic complaints did not show significant differences between the two treatment groups . QOL characteristics at 6 months of treatment of the buprenorphine completer and noncompleter groups differed significantly regarding job ( p = 0.013 ) , family , and total score of physical symptoms ( p = 0.002 ) , in which the completer group showed the more favorable values . Concerning physical symptoms at 36 months , logistic regression revealed significantly less stomach cramps ( p = 0.037 ) and fatigue and tiredness ( p = 0.034 ) in buprenorphine compared to the methadone . Moreover , the buprenorphine-maintained group showed significantly less additional consumption of benzodiazepines ( p = 0.015 ) compared with methadone participants . It is concluded that opioid addicts improved their QOL and health status when treated with methadone or buprenorphine . In summary , regarding QOL and health status , the present data indicate that buprenorphine is also a useful long-term alternative for maintenance treatment of opioid-dependent patients Naltrexone may be more effective for treating opioid ( heroin ) dependence in Russia than in the U.S. because patients are mostly young and living with their parents , who can control medication compliance . In this pilot study we r and omized 52 consenting patients who completed detoxification in St. Petersburg to a double blind , 6-month course of biweekly drug counseling and naltrexone , or counseling and placebo naltrexone . Significant differences in retention and relapse favoring naltrexone were seen beginning at 1 month and continuing throughout the study . At the end of 6 months , 12 of the 27 naltrexone patients ( 44.4 % ) remained in treatment and had not relapsed as compared to 4 of 25 placebo patients ( 16 % ; p<0.05 ) . Since heroin dependence is the main way HIV is being spread in Russia , naltrexone is likely to improve treatment outcome and help reduce the spread of HIV if it can be made more widely available BACKGROUND Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone has been proposed , but its efficacy and safety have not been well studied . METHODS We conducted a multicenter , r and omized , placebo-controlled trial involving 326 opiate-addicted persons who were assigned to office-based treatment with sublingual tablets consisting of buprenorphine ( 16 mg ) in combination with naloxone ( 4 mg ) , buprenorphine alone ( 16 mg ) , or placebo given daily for four weeks . The primary outcome measures were the percentage of urine sample s negative for opiates and the subjects ' self-reported craving for opiates . Safety data were obtained on 461 opiate-addicted persons who participated in an open-label study of buprenorphine and naloxone ( at daily doses of up to 24 mg and 6 mg , respectively ) and another 11 persons who received this combination only during the trial . RESULTS The double-blind trial was terminated early because buprenorphine and naloxone in combination and buprenorphine alone were found to have greater efficacy than placebo . The proportion of urine sample s that were negative for opiates was greater in the combined-treatment and buprenorphine groups ( 17.8 percent and 20.7 percent , respectively ) than in the placebo group ( 5.8 percent , P<0.001 for both comparisons ) ; the active-treatment groups also reported less opiate craving ( P<0.001 for both comparisons with placebo ) . Rates of adverse events were similar in the active-treatment and placebo groups . During the open-label phase , the percentage of urine sample s negative for opiates ranged from 35.2 percent to 67.4 percent . Results from the open-label follow-up study indicated that the combined treatment was safe and well tolerated . CONCLUSIONS Buprenorphine and naloxone in combination and buprenorphine alone are safe and reduce the use of opiates and the craving for opiates among opiate-addicted persons who receive these medications in an office-based setting Despite the high prevalence of prescription opioid dependence in the U.S. , little is known about the course of this disorder and long-term response to treatment . We therefore examined 18-month post-r and omization outcomes of participants in the Prescription Opioid Addiction Treatment Study , a multi-site , r and omized controlled trial examining varying duration s of buprenorphine-naloxone treatment and different intensities of counseling for prescription opioid dependence . Thus the current follow-up study provides a unique contribution to the field by reporting longer-term outcomes of a well-characterized population of treatment-seeking prescription opioid dependent patients . Participants from the treatment trial ( N=252/653 ) completed an 18-month follow-up telephone assessment . Multivariable analyses examined associations between participant characteristics and key indicators of month-18 status : opioid abstinence , DSM-IV opioid dependence , and opioid agonist treatment . Overall , participants showed improvement from baseline to month 18 : 49.6 % were abstinent in the previous 30 days , with only 16.3 % opioid-dependent . Some participants , however , had initiated past-year heroin use ( n=9 ) or opioid injection ( n=17 ) . Most participants ( 65.9 % ) engaged in substance use disorder treatment during the past year , most commonly opioid agonist therapy ( 48.8 % ) . Of particular interest in this population , multivariable analysis showed that greater pain severity at baseline was associated with opioid dependence at 18 months . In conclusion , although opioid use outcomes during the treatment trial were poor immediately following a buprenorphine-naloxone taper compared to those during 12 weeks of buprenorphine-naloxone stabilization , opioid use outcomes at 18-month follow-up showed substantial improvement over baseline and were comparable to the rate of successful outcomes during buprenorphine-naloxone stabilization in the treatment trial Physical pain is common among individuals seeking treatment for opioid dependence . Pain may negatively impact addiction treatment . The authors prospect ively studied opioid-dependent individuals initiating office-based buprenorphine treatment , comparing buprenorphine treatment outcomes ( treatment retention and opioid use ) among participants with and without pain ( baseline pain or persistent pain ) . Among 82 participants , 60 % reported baseline pain and 38 % reported persistent pain . Overall , treatment retention was 56 % and opioid use decreased from 89 % to 26 % over 6 months . In multivariable analyses , the authors found no association between pain and buprenorphine treatment outcomes . Opioid-dependent individuals with and without pain can achieve similar success with buprenorphine treatment INTRODUCTION The present investigation examines baseline patient characteristics to predict dosing of buprenorphine-naloxone , a promising treatment for opioid addiction in youths . METHODS This study of 69 opioid-dependent youths is a secondary analysis of data collected during a National Institute on Drug Abuse ( NIDA ) Clinical Trials Network study . Out patients aged 15 - 21 were r and omized to a 12-week buprenorphine-naloxone dosing condition ( including 4 weeks of taper ) . Predictors of dosing included sociodemographic characteristics ( gender , race , age , and education ) , substance use ( alcohol , cannabis , cocaine , and nicotine use ) , and clinical characteristics ( pain and withdrawal severity ) . RESULTS Most ( 75.4 % ) reported having either " some " ( n=40 , 58.0 % ) or " extreme " ( n=12 , 17.4 % ) pain on enrollment . Maximum daily dose of buprenorphine-naloxone ( 19.7 mg ) received by patients reporting " extreme " pain at baseline was significantly higher than the dose received by patients reporting " some " pain ( 15.0 mg ) and those without pain ( 12.8 mg ) . In the adjusted analysis , only severity of pain and withdrawal significantly predicted dose . During the dosing period , there were no significant differences in opioid use , as measured by urinalysis , by level of pain . CONCLUSION These data suggest that the presence of pain predicts buprenorphine-naloxone dose levels in opioid-dependent youth , and that patients with pain have comparable opioid use outcomes to those without pain , but require higher buprenorphine-naloxone doses Thirty-four long-term heroin addicts were treated with either methadone hydrochloride or methadyl acetate ( dl-methadyl acetate , acetylmethadol ) under double-blind conditions over 15 weeks . These drugs were not found to be significantly different with regard to acceptability to patients , reduction of illicit drug use , increase in legitimate employment , reduction of criminal activity , frequency of clinic attendance , and medical safety . These results suggest that the advantages of methadyl acetate , namely reduction in the frequency of clinic visits and the possibility of more effective control over administration and illegal redistribution , are not outweighed by any problems detectable under the conditions of the present study . However , in spite of these potential advantages , the unusual pharmacological actions of methadyl acetate could represent potential hazards |
12,762 | 27,008,687 | The main problem reported in many trials was a very slow recruitment rate , mainly due to the difficulty in finding eligible patients .
This review demonstrated that placebo-controlled surgical trials are feasible , at least for procedures with a lower level of invasiveness , but also that recruitment is difficult .
Many of the presumed challenges to undertaking such trials , for example , funding , anaesthesia or blinding of patients and assessors , were not reported as obstacles to completion in any of the review ed trials | OBJECTIVES To find evidence , either corroborating or refuting , for many persisting beliefs regarding the feasibility of carrying out surgical r and omised controlled trials with a placebo arm , with emphasis on the challenges related to recruitment , funding , anaesthesia or blinding . | Background : The BioEnterics ® Intragastric Balloon ( BIB ® ) System in association with restricted diet has been used for the short-term treatment of morbid obesity . Aim of this study was to evaluate the real , short term , efficacy of the BIB for weight reduction in morbidly obese patients by using a prospect i ve , double-blind , r and omised , sham-controlled , crossover study . Methods : Patients were recruited from January 2003 to December 2003 . After selection , they were r and omly allocated into two groups : BIB followed by sham procedure after 3 months ( Group A ) , and sham procedure followed by BIB after 3 months ( Group B ) . All endoscopic procedures were performed under unconscious intravenous sedation . The BioEnterics Intragastric Balloon ( Inamed Health ; Santa Barbara , CA , USA ) was filled by using saline ( 500 ml ) and methylene blue ( 10 ml ) . Patients were discharged with omeprazole therapy and diet ( 1000 kcal ) . Patients were followed up weekly by a physician blinded to r and omisation . In both groups mortality , complications , BMI , BMI reduction and % EWL were considered . Data were expressed as mean±s.d . , except as otherwise indicated . Statistical analysis was performed by means of Student 's t-test , Fisher 's exact test or χ 2 with Yates correction ; P<0.05 was considered significant . Results : A total of 32 patients were selected and entered the study ( 8M/24F ; mean age : 36.2±5.6 years , range 25–50 years ; mean BMI 43.7±1.5 kg/m2 , range 40–45 kg/m2 ; mean % EW : 43.1±13.1 , range : 35–65 ) . All patients completed the study . Mortality was absent . Complications related to endoscopy , balloon placement and removal were absent . Mean time of BIB positioning was 15±2 min , range 10–20 min . After the first 3 months of the study , in Group A patients the mean BMI significantly ( P<0.001 ) lowered from 43.5±1.1 to 38.0±2.6 kg/m2 , while in Group B patients the decrease was not significant ( from 43.6±1.8 to 43.1±2.8 kg/m2 ) . The mean % EWL was significantly higher in Group A than in Group B ( 34.0±4.8 vs 2.1±1 % ; P<0.001 ) . After crossover , at the end of the following 3 months , the BMI lowered from 38.0±2.6 to 37.1±3.4 kg/m2 and from 43.1±2.8 to 38.8±3.1 kg/m2 in Groups A and B , respectively . Conclusions : The results of this study show that treatment of obese patients with BioEnterics Intragastric Balloon is a safe and effective procedure . In association with appropriate diet it is significantly effective in weight reduction when compared to sham procedure plus diet . The BIB ® procedure can play a role in weight reduction in morbidly obese patients or in the preoperative treatment of bariatric patients OBJECTIVES We sought to evaluate the safety and efficacy of percutaneous transmyocardial revascularization ( PTMR ) in patients with refractory angina caused by one or more chronic total occlusions ( CTOs ) of a native coronary artery . BACKGROUND Previous unblinded , r and omized trials of PTMR in patients with end-stage coronary artery disease and refractory angina have demonstrated significant relief of angina and increased exercise duration . Whether such benefits would be realized in blinded patients with less extensive coronary artery disease is unknown . METHODS A total of 141 consecutive patients with class III or IV angina caused by one or more chronically occluded native coronary arteries in which a percutaneous coronary intervention ( PCI ) had failed were prospect ively r and omized , at 17 medical centers , in the same procedure , to PTMR plus maximal medical therapy ( MMT ) ( n = 71 ) or MMT only ( n = 70 ) . Blinding was achieved through heavy sedation , dark goggles and the concurrent performance of PCI in all patients . RESULTS Baseline characteristics were similar between the two groups . A median number of 20 laser channels were created in patients r and omized to PTMR . At six months , the anginal class improved by two or more classes in 49 % of patients assigned to PTMR and in 37 % of those assigned to MMT ( p = 0.33 ) . The median increase in exercise duration from baseline to six months was 64 s with PTMR versus 52 s with MMT ( p = 0.73 ) . There were no differences in the six-month rates of death ( 8.6 % vs. 8.8 % ) , myocardial infa rct ion ( 4.3 % vs. 2.9 % ) or any revascularization ( 4.3 % vs. 5.9 % ) in the PTMR and MMT groups , respectively ( p = NS for all ) . CONCLUSIONS In patients with class III or IV angina caused by nonrecanalizable CTOs , the performance of PTMR does not result in a greater reduction in angina , improvement in exercise duration or survival free of adverse cardiac events , as compared with MMT only Background Surgical placebos are controversial . This in-depth study explored the design , acceptability , and feasibility issues relevant to design ing a surgical placebo-controlled trial for the evaluation of the clinical and cost effectiveness of arthroscopic lavage for the management of people with osteoarthritis of the knee in the UK . Methods Two surgeon focus groups at a UK national meeting for orthopaedic surgeons and one regional surgeon focus group ( 41 surgeons ) ; plenary discussion at a UK national meeting for orthopaedic anaesthetists ( 130 anaesthetists ) ; three focus groups with anaesthetists ( one national , two regional ; 58 anaesthetists ) ; two focus groups with members of the patient organisation Arthritis Care ( 7 participants ) ; telephone interviews with people on consultant waiting lists from two UK regional centres ( 15 participants ) ; interviews with Chairs of UK ethics committees ( 6 individuals ) ; postal surveys of members of the British Association of Surgeons of the Knee ( 382 surgeons ) and members of the British Society of Orthopaedic Anaesthetists ( 398 anaesthetists ) ; two centre pilot ( 49 patients assessed ) . Results There was widespread acceptance that evaluation of arthroscopic lavage had to be conducted with a placebo control if scientific rigour was not to be compromised . The choice of placebo surgical procedure ( three small incisions ) proved easier than the method of anaesthesia ( general anaesthesia ) . General anaesthesia , while an excellent mimic , was more intrusive and raised concerns among some stakeholders and caused extensive discussion with local decision-makers when seeking formal approval for the pilot . Patients were willing to participate in a pilot with a placebo arm ; although some patients when allocated to surgery became apprehensive about the possibility of receiving placebo , and withdrew . Placebo surgery was undertaken successfully . Conclusions Our study illustrated the opposing and often strongly held opinions about surgical placebos , the ethical issues underpinning this controversy , and the challenges that exist even when ethics committee approval has been granted . It showed that a placebo-controlled trial could be conducted in principle , albeit with difficulty . It also highlighted that not only does a placebo-controlled trial in surgery have to be ethically and scientifically acceptable but that it also must be a feasible course of action . The place of placebo-controlled surgical trials more generally is likely to be limited and require specific circumstances to be met . Suggested criteria are presented . Trial registration numberThe trial was assigned IS RCT N02328576 through http://controlled-trials.com/ in June 2006 . The first patient was r and omised to the pilot in July 2007 BACKGROUND & AIMS Ablation of gastric inlet patches ( GIP ) in the cervical esophagus by argon plasma coagulation ( APC ) can alleviate chronic globus sensations in the throat . We investigated the efficacy of this therapy in a r and omized , controlled multicenter trial . METHODS Patients with chronic globus sensations and GIP were r and omly assigned 1:1 to groups that were treated with APC or a sham procedure ( controls ) . Patients and their referring physicians were blinded to therapy . All patients completed a st and ardized question naire about symptoms before and 3 months after the procedure . Thereafter , control patients were eligible for cross-over therapy . Long-term efficacy was assessed in all patients > or=6 months after APC . RESULTS Improvement of symptoms was reported in 9 ( 82 % ) of 11 patients who received APC , compared with 0 ( 0 % ) of 10 patients in the control group ( P = .002 ) . Nine ( 90 % ) of 10 patients treated with APC had per protocol healing , compared with 0 ( 0 % ) of 9 controls ( P < .001 ) . Scores for symptom/globus assessment significantly improved in patients in the APC group , whereas patients in the control group did not perceive any symptom relief . Eight of the 10 patients who started in the control group crossed over to the APC group . Long-term efficacy ( after a median follow-up of 17 months ) was documented in 13 ( 76 % ) of 17 treated patients . CONCLUSIONS Ablation of gastric inlet patches appears to be an effective therapy for alleviation of associated globus sensations . This new treatment modality might change the paradigm for treatment of these patients Background : Alzheimer disease ( AD ) has been associated with abnormal cerebral clearance of macromolecules , such as amyloid and microtubule-associated-protein tau ( MAP-τ ) . We hypothesized that improving clearance of macromolecules from the CNS might slow the progression of dementia . Objective : This prospect i ve , r and omized , double-blinded , placebo-controlled trial evaluated the safety and effectiveness of a surgically implanted shunt in subjects with probable AD . Methods : A total of 215 subjects with probable AD by National Institute of Neurological Disorders and Stroke – Alzheimer ’s Disease and Related Disorders Association criteria received either a low-flow ventriculoperitoneal shunt or a sham ( occluded ) shunt for 9 months . Longitudinal CSF sampling was performed in both active and control subjects . Primary outcome measures were the Mattis Dementia Rating Scale and the Global Deterioration Scale . CSF Aβ(1 - 42 ) and MAP-τ also were assayed . Results : After a planned interim analysis , the study was halted for futility . Using the intent-to-treat population , no between-group differences were observed in the primary outcome measures . The surgical procedure and device were associated with 12 CNS infections , some temporally associated with CSF sampling . All were treated successfully . Conclusions : We found no benefit to low-flow CSF shunting in subjects with mild to severe Alzheimer disease . CSF infections , while treatable , occurred more frequently than expected , in some cases likely related to CSF sampling . GLOSSARY : Aβ = amyloid beta-peptides ; AD = Alzheimer disease ; ADCS-ADL = AD Cooperative Study Activities of Daily Living ; BBB = blood – brain barrier ; CP = choroid plexus ; FDA = Food and Drug Administration ; GDS = Global Deterioration Scale ; GEE = Generalized Estimating Equations ; IA = interim analysis ; ISF = interstitial fluid ; ITT = intent-to-treat ; LRP-1 = lipoprotein receptor-related protein-1 ; MAP-τ = microtubule-associated-protein tau ; MDRS = Mattis Dementia Rating Scale ; MMSE = Mini-Mental State Examination ; NAART = North American Adult Reading Test ; NINCDS-ADRDA = National Institutes of Neurological and Communicative Diseases and Stroke – Alzheimer ’s Disease and Related Disorders Association ; NPH = normal-pressure hydrocephalus ; PHF = perihippocampal fissures ; RAGE = receptor for advanced glycation end-products ; SADAS-Cog = St and ardized AD Assessment Scale – Cognitive ; SAE = serious adverse events OBJECTIVE To examine the effect on pain and quality of life for women with all stages of endometriosis undergoing laparoscopic surgery compared with placebo surgery . DESIGN A r and omized , blinded , crossover study . SETTING A tertiary referral unit in a district general hospital . PATIENT(S ) Thirty-nine women with histologically proven endometriosis completed the 12-month study . INTERVENTION(S ) Women were r and omized to receive initially either a diagnostic procedure ( the delayed surgical group ) or full excisional surgery ( the immediate surgery group ) . After 6 months , repeat laparoscopy was performed , with removal of any pathology present . MAIN OUTCOME MEASURE(S ) The end points were changes from baseline values of visual analogue pain scores , vali date d quality -of-life instruments ( EQ-5D and SF-12 ) , and sexual activity question naire scores . Patients and assessors of outcomes were blinded to the treatment-group assignment . RESULT ( S ) Significantly more of the 39 women operated on according to protocol reported symptomatic improvement after excisional surgery than after placebo : 16 of 20 ( 80 % ) vs. 6 of 19 ( 32 % ) ; chi(2)(1 ) = 9.3 . Other aspects of quality of life were also significantly improved 6 months after excisional surgery but not after placebo . Progression of disease at second surgery was demonstrated for women having only an initial diagnostic procedure in 45 % of cases , with disease remaining static in 33 % and improving in 22 % of cases . Nonresponsiveness to surgery was reported in 20 % of cases . CONCLUSION ( S ) Laparoscopic excision of endometriosis is more effective than placebo at reducing pain and improving quality of life . Surgery is associated with a 30 % placebo response rate that is not dependent on severity of disease . Approximately 20 % of women do not report an improvement after surgery for endometriosis BACKGROUND Laparoscopic adhesiolysis for chronic abdominal pain is controversial and is not evidence based . We aim ed to test our hypothesis that laparoscopic adhesiolysis leads to substantial pain relief and improvement in quality of life in patients with adhesions and chronic abdominal pain . METHODS Patients had diagnostic laparoscopy for chronic abdominal pain attributed to adhesions ; other causes for their pain had been excluded . If adhesions were confirmed during diagnostic laparoscopy , patients were r and omly assigned either to laparoscopic adhesiolysis or no treatment . Treatment allocation was concealed from patients , and assessors were unaware of patients ' treatment and outcome . Pain was assessed for 1 year by visual analogue score ( VAS ) score ( scale 0 - 100 ) , pain change score , use of analgesics , and quality of life score . Analysis was by intention to treat . FINDINGS Of 116 patients enrolled for diagnostic laparoscopy , 100 were r and omly allocated either laparoscopic adhesiolysis ( 52 ) or no treatment ( 48 ) . Both groups reported substantial pain relief and a significantly improved quality of life , but there was no difference between the groups ( mean change from baseline of VAS score at 12 months : difference 3 points , p=0.53 ; 95 % CI -7 to 13 ) . INTERPRETATION Although laparoscopic adhesiolysis relieves chronic abdominal pain , it is not more beneficial than diagnostic laparoscopy alone . Therefore , laparoscopic adhesiolysis can not be recommended as a treatment for adhesions in patients with chronic abdominal pain A r and omized controlled double-blind study was undertaken to assess the efficacy and safety of endoscopic neodymium : yttrium aluminum garnet ( Nd : YAG ) laser therapy for active esophageal variceal bleeding . Ten patients were r and omized to the laser treatment group and 10 to a control group that received sham endoscopy and st and ard medical therapy . Initial hemostasis was achieved in seven laser-treated patients but in 0 of 10 controls receiving sham treatment ( p less than 0.002 ) . However , four of the seven who were initially controlled with laser therapy had rebleeding 12 to 48 hours later ; thus , three of 10 laser patients had lasting hemostasis . The mean blood transfusion requirements were similar in both groups ( laser = 7.3 units ; control = 7.8 units ) . Six of the 10 laser-treated patients were discharged from the hospital and four died . There were seven hospital deaths in the control group and three patients were discharged ( p = 0.22 ) . In two patients in the treatment group , laser therapy increased bleeding . There were no perforations Objective To determine the rate of early discontinuation and non-publication of r and omised controlled trials involving patients undergoing surgery . Design Cross sectional observational study of registered and published trials . Setting R and omised controlled trials of interventions in patients undergoing a surgical procedure . Data sources The Clinical Trials.gov data base was search ed for interventional trials registered between January 2008 and December 2009 using the keyword “ surgery ” . Recruitment status was extracted from the Clinical Trials.gov data base . A systematic search for studies published in peer review ed journals was performed ; if they were not found , results posted on the Clinical Trials.gov results data base were sought . Email queries were sent to trial investigators of discontinued and unpublished completed trials if no reason for the respective status was disclosed . Main outcome measures Trial discontinuation before completion and non-publication after completion . Logistic regression was used to determine the effect of funding source on publication status , with adjustment for intervention type and trial size . Results Of 818 registered trials found using the keyword “ surgery ” , 395 met the inclusion criteria . Of these , 21 % ( 81/395 ) were discontinued early , most commonly owing to poor recruitment ( 44 % , 36/81 ) . The remaining 314 ( 79 % ) trials proceeded to completion , with a publication rate of 66 % ( 208/314 ) at a median time of 4.9 ( interquartile range 4.0 - 6.0 ) years from study completion to publication search . A further 6 % ( 20/314 ) of studies presented results on Clinical Trials.gov without a corresponding peer review ed publication . Industry funding did not affect the rate of discontinuation ( adjusted odds ratio 0.91 , 95 % confidence interval 0.54 to 1.55 ) but was associated with a lower odds of publication for completed trials ( 0.43 , 0.26 to 0.72 ) . Investigators ’ email addresses for trials with an uncertain fate were identified for 71.4 % ( 10/14 ) of discontinued trials and 83 % ( 101/122 ) of unpublished studies . Only 43 % ( 6/14 ) and 20 % ( 25/122 ) replies were received . Email responses for completed trials indicated 11 trials in press , five published studies ( four in non-indexed peer review ed journals ) , and nine trials remaining unpublished . Conclusions One in five surgical r and omised controlled trials are discontinued early , one in three completed trials remain unpublished , and investigators of unpublished studies are frequently not contactable . This represents a waste of research re sources and raises ethical concerns regarding hidden clinical data and futile participation by patients with its attendant risks . To promote future efficiency and transparency , changes are proposed to research governance frameworks to overcome these concerns A prospect i ve single blind controlled trial was performed to assess the efficacy of the neodymium yttrium aluminium garnet laser in the management of patients bleeding from peptic ulcers and single vessels . Over 20 months 184 patients were found at endoscopy to be bleeding from peptic ulcers and single vessels ; 130 of these failed to meet the criteria for entry into the study , but their bleeding stopped with conservative management . Forty-five patients entered the study : in all 25 who were bleeding from ulcers with spots the bleeding stopped irrespective of the treatment allocated . Twenty patients were bleeding from arteries . Eight were allocated to placebo treatment , and all later underwent emergency surgery for further haemorrhage . Twelve were allocated to receive laser treatment , and only one of eight who actually received it required surgery ( p less than 0.002 ) . It is concluded that laser treatment reduces the incidence of further haemorrhage and the need for emergency surgery , but the technique is difficult and not always applicable Background : Endoscopic treatment for gastro-oesophageal reflux disease ( GORD ) is rapidly emerging , but there is a great need for r and omised controlled trials to evaluate the efficacy . Design and setting : A single-centre , double-blind , r and omised , sham-controlled trial of endoscopic gastroplication by the Endocinch suturing system . Patients and interventions : 60 patients with GORD were r and omly assigned to three endoscopic gastroplications ( n = 20 ) , a sham procedure ( n = 20 ) or observation ( n = 20 ) . The research nurse and patients in the active and sham groups were blinded to the procedure assignment . After 3 months , open-label active treatment was offered to all patients . Outcome measures : The primary outcome measures were proton pump inhibitor ( PPI ) use and GORD symptoms , and secondary measures were quality of life , 24-h oesophageal acid exposure , oesophageal manometry and adverse events . Follow-up assessment s were performed at 3 , 6 and 12 months . Results : At 3 months , the percentage of patients who had reduced drug use by ⩾50 % was greater in the active treatment group ( 65 % ) than in the sham ( 25 % ) or observation groups ( 0 % ) ( p<0.02 ) . Symptoms ( heartburn and to a lesser extent regurgitation ) improved more in the active group than in the sham group . Three Short Form-20 quality of life subscales ( role function , general health and bodily pain perception ) improved in the active group versus sham . Oesophageal acid exposure was modestly decreased after active treatment ( p<0.02 ) , but not significantly greater than after the sham procedure ( p = 0.61 ) . The active treatment effects on PPI use , symptoms and quality of life persisted after 6 and 12 months of open-label follow-up ( n = 41 ) , but 29 % of patients were retreated in this period . No serious adverse events occurred . Conclusions : Endoscopic gastroplication , using the Endocinch device , reduced acid-inhibitory drug use , improved GORD symptoms and improved the quality of life at 3 months compared with a sham procedure . The effects persisted up to 12 months . However , the reduction in oesophageal acid exposure was not greater after endoscopic treatment than after a sham procedure Background Poor recruitment and retention of participants in r and omised controlled trials ( RCTs ) is problematic but common . Clear and detailed reporting of participant flow is essential to assess the generalisability and comparability of RCTs . Despite improved reporting since the implementation of the CONSORT statement , important problems remain . This paper aims : ( i ) to up date and extend previous review s evaluating reporting of participant recruitment and retention in RCTs ; ( ii ) to quantify the level of participation throughout RCTs . Methods We review ed all reports of RCTs of health care interventions and /or processes with individual r and omisation , published July – December 2004 in six major journals . Short , secondary or interim reports , and Phase I/II trials were excluded . Data recorded were : general RCT details ; inclusion of flow diagram ; participant flow throughout trial ; reasons for non-participation/withdrawal ; target sample sizes . Results 133 reports were review ed . Overall , 79 % included a flow diagram , but over a third were incomplete . The majority reported the flow of participants at each stage of the trial after r and omisation . However , 40 % failed to report the numbers assessed for eligibility . Percentages of participants retained at each stage were high : for example , 90 % of eligible individuals were r and omised , and 93 % of those r and omised were outcome assessed . On average , trials met their sample size targets . However , there were some substantial shortfalls : for example 21 % of trials reporting a sample size calculation failed to achieve adequate numbers at r and omisation , and 48 % at outcome assessment . Reporting of losses to follow up was variable and difficult to interpret . Conclusion The majority of RCTs reported the flow of participants well after r and omisation , although only two-thirds included a complete flow chart and there was great variability over the definition of " lost to follow up " . Reporting of participant eligibility was poor , making assessment s of recruitment practice and external validity difficult . Reporting of participant flow throughout RCTs could be improved by small changes to the CONSORT chart Intragastric balloons are new but commonly used devices for the treatment of obesity ; however , their safety and efficacy have not been established . We report our results of a small , double-blind , r and omized trial in which the effectiveness of intragastric balloons was compared with that of conventional medical therapy for obesity . Twenty-two patients , who were 21 to 77 % over ideal body weight , were studied . Eleven underwent insertion of an intragastric balloon , and 11 underwent sham procedures . One patient with a gastric balloon withdrew from the study after 3 days . Weight loss at 2 to 3 months in the conventional therapy group averaged 2.8 kg ; in the balloon-treated group , the mean weight loss was 5.8 kg ( P greater than 0.15 ) . Of the 10 balloons , 8 spontaneously deflated , and 1 was passed in the stools . We noted gastric erosions in five patients and multiple gastric ulcers in one . We conclude that the intragastric balloon was not clearly effective in inducing weight loss , had a high rate of spontaneous deflation , and was damaging to the gastric mucosa . Controlled trials should be done before similar weight-reduction devices are used in routine clinical practice OBJECTIVE : R and omized , double-blinded , placebo-controlled , clinical trial to determine the effectiveness of palatal implants for treatment of mild/moderate obstructive sleep apnea/hypopnea syndrome ( OSAHS ) . STUDY DESIGN AND SETTING : Sixty-two non-obese adults with history of snoring , daytime sleepiness , and mild/moderate OSAHS , were r and omized to receive palatal implants ( n = 31 ) or placebo procedure ( n = 31 ) . Complete follow-up including quality of life ( QOL , SF-36 ) , snoring visual analog scale ( VAS ) , and Epworth Sleepiness Scale ( ESS ) data were obtained in 62 patients . Seven patients refused follow-up polysomnography for a total of 55 patients ( 29 implant and 26 placebo ) . RESULTS : The treatment group ( change in score of −7.9 ± 7.7 ) was significantly improved compared with the placebo group ( change in score of 0.9 ± 4.3 ) for apnea/hypopnea index ( AHI ) ( P < 0.0001 ) , QOL , SF-36 ( P < 0.0001 ) , snoring VAS ( P < 0.0001 ) , and ESS ( P = 0.0002 ) . CONCLUSIONS : Palatal implants improve AHI , QOL , snoring intensity , and daytime sleepiness for selected patients with mild/moderate OSAHS Surgery and other invasive therapies are complex interventions , the assessment of which is challenged by factors that depend on operator , team , and setting , such as learning curves , quality variations , and perception of equipoise . We propose recommendations for the assessment of surgery based on a five-stage description of the surgical development process . We also encourage the widespread use of prospect i ve data bases and registries . Reports of new techniques should be registered as a professional duty , anonymously if necessary when outcomes are adverse . Case series studies should be replaced by prospect i ve development studies for early technical modifications and by prospect i ve research data bases for later pre-trial evaluation . Protocol s for these studies should be registered publicly . Statistical process control techniques can be useful in both early and late assessment . R and omised trials should be used whenever possible to investigate efficacy , but adequate pre-trial data are essential to allow power calculations , clarify the definition and indications of the intervention , and develop quality measures . Difficulties in doing r and omised clinical trials should be addressed by measures to evaluate learning curves and alleviate equipoise problems . Alternative prospect i ve design s , such as interrupted time series studies , should be used when r and omised trials are not feasible . Established procedures should be monitored with prospect i ve data bases to analyse outcome variations and to identify late and rare events . Achievement of improved design , conduct , and reporting of surgical research will need concerted action by editors , funders of health care and research , regulatory bodies , and professional societies BACKGROUND Vertebroplasty has become a common treatment for painful osteoporotic vertebral fractures , but there is limited evidence to support its use . METHODS We performed a multicenter , r and omized , double-blind , placebo-controlled trial in which participants with one or two painful osteoporotic vertebral fractures that were of less than 12 months ' duration and unhealed , as confirmed by magnetic resonance imaging , were r and omly assigned to undergo vertebroplasty or a sham procedure . Participants were stratified according to treatment center , sex , and duration of symptoms ( < 6 weeks or > or = 6 weeks ) . Outcomes were assessed at 1 week and at 1 , 3 , and 6 months . The primary outcome was overall pain ( on a scale of 0 to 10 , with 10 being the maximum imaginable pain ) at 3 months . RESULTS A total of 78 participants were enrolled , and 71 ( 35 of 38 in the vertebroplasty group and 36 of 40 in the placebo group ) completed the 6-month follow-up ( 91 % ) . Vertebroplasty did not result in a significant advantage in any measured outcome at any time point . There were significant reductions in overall pain in both study groups at each follow-up assessment . At 3 months , the mean ( + /-SD ) reductions in the score for pain in the vertebroplasty and control groups were 2.6+/-2.9 and 1.9+/-3.3 , respectively ( adjusted between-group difference , 0.6 ; 95 % confidence interval , -0.7 to 1.8 ) . Similar improvements were seen in both groups with respect to pain at night and at rest , physical functioning , quality of life , and perceived improvement . Seven incident vertebral fractures ( three in the vertebroplasty group and four in the placebo group ) occurred during the 6-month follow-up period . CONCLUSIONS We found no beneficial effect of vertebroplasty as compared with a sham procedure in patients with painful osteoporotic vertebral fractures , at 1 week or at 1 , 3 , or 6 months after treatment . ( Australian New Zeal and Clinical Trials Registry number , ACTRN012605000079640 . Adequate reporting of r and omized , controlled trials ( RCTs ) is necessary to allow accurate critical appraisal of the validity and applicability of the results . The CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement , a 22-item checklist and flow diagram , is intended to address this problem by improving the reporting of RCTs . However , some specific issues that apply to trials of nonpharmacologic treatments ( for example , surgery , technical interventions , devices , rehabilitation , psychotherapy , and behavioral intervention ) are not specifically addressed in the CONSORT Statement . Furthermore , considerable evidence suggests that the reporting of nonpharmacologic trials still needs improvement . Therefore , the CONSORT group developed an extension of the CONSORT Statement for trials assessing nonpharmacologic treatments . A consensus meeting of 33 experts was organized in Paris , France , in February 2006 , to develop an extension of the CONSORT Statement for trials of nonpharmacologic treatments . The participants extended 11 items from the CONSORT Statement , added 1 item , and developed a modified flow diagram . To allow adequate underst and ing and implementation of the CONSORT extension , the CONSORT group developed this elaboration and explanation document from a review of the literature to provide examples of adequate reporting . This extension , in conjunction with the main CONSORT Statement and other CONSORT extensions , should help to improve the reporting of RCTs performed in this field OBJECTIVES /HYPOTHESIS Radiofrequency ( RF ) surgery of the soft palate ( SP ) is an established treatment option for the treatment of snoring . Due to its minimally invasive character , it has received attention in the management of mild obstructive sleep apnea syndrome ( OSAS ) . STUDY DESIGN The aim of this study was to assess the efficacy and the occurrence of adverse events after single-stage SP RF surgery in patients with mild OSAS in a r and omized single-blinded placebo-controlled trial in an outpatient department at a tertiary care center , academic teaching hospital . METHODS Thirty-two patients with mild OSAS ( apnea-hypopnea index [ AHI ] 5 - 15 , body mass index < 35 ) were r and omized to receive a single session of RF surgery or placebo ( insertion of applicator without energy delivery ) with local anesthesia . The primary outcome measures were ( AHI ) , Epworth Sleepiness Scale , and a 36-item short-form health survey quality -of-life question naire . The secondary measures were the soft tissue airway parameters in cephalometric radiographs , snoring scores , and rates of adverse events . RESULTS Neither objective ly measured significance s ( active AHI 11.0 [ 5.0 - 9.0 ] to 13.0 [ 2.0 - 26.0 ] and placebo AHI 12.0 [ 5.0 - 8.0 ] to 11.0 [ 1.0 - 29.0 ] , P = .628 ) , nor were trends of a diminishing effect on symptoms of mild OSAS found in the treatment arms . No significant changes in the soft tissue airway parameters occurred . One patient ( 5.9 % ) in the active treatment group was cured . CONCLUSIONS RF surgery of SP is not recommended as a single-stage approach in mild OSAS BACKGROUND Vertebroplasty is commonly used to treat painful , osteoporotic vertebral compression fractures . METHODS In this multicenter trial , we r and omly assigned 131 patients who had one to three painful osteoporotic vertebral compression fractures to undergo either vertebroplasty or a simulated procedure without cement ( control group ) . The primary outcomes were scores on the modified Rol and -Morris Disability Question naire ( RDQ ) ( on a scale of 0 to 23 , with higher scores indicating greater disability ) and patients ' ratings of average pain intensity during the preceding 24 hours at 1 month ( on a scale of 0 to 10 , with higher scores indicating more severe pain ) . Patients were allowed to cross over to the other study group after 1 month . RESULTS All patients underwent the assigned intervention ( 68 vertebroplasties and 63 simulated procedures ) . The baseline characteristics were similar in the two groups . At 1 month , there was no significant difference between the vertebroplasty group and the control group in either the RDQ score ( difference , 0.7 ; 95 % confidence interval [ CI ] , -1.3 to 2.8 ; P=0.49 ) or the pain rating ( difference , 0.7 ; 95 % CI , -0.3 to 1.7 ; P=0.19 ) . Both groups had immediate improvement in disability and pain scores after the intervention . Although the two groups did not differ significantly on any secondary outcome measure at 1 month , there was a trend toward a higher rate of clinical ly meaningful improvement in pain ( a 30 % decrease from baseline ) in the vertebroplasty group ( 64 % vs. 48 % , P=0.06 ) . At 3 months , there was a higher crossover rate in the control group than in the vertebroplasty group ( 51 % vs. 13 % , P<0.001 ) [ corrected ] . There was one serious adverse event in each group . CONCLUSIONS Improvements in pain and pain-related disability associated with osteoporotic compression fractures in patients treated with vertebroplasty were similar to the improvements in a control group . ( Clinical Trials.gov number , NCT00068822 . Background R and omized placebo-controlled trials represent the gold st and ard in evaluating healthcare interventions but are rarely performed within orthopedics . Ethical concerns or well-known challenges in recruiting patients for surgical trials in general have been expressed and adding a placebo component only adds to this complexity . The purpose of this study was to report the challenges of recruiting patients into an orthopedic placebo-controlled surgical trial , to determine the number of patients needed to be screened and allocated in order to include one participant into the trial , and to identify reasons associated with participation in a placebo-controlled r and omized surgical trial . Methods Data were extracted from an ongoing placebo-controlled r and omized controlled trial ( RCT ) on meniscectomy versus placebo surgery . We calculated the number of patients needed to be screened in order to include the required number of participants into the RCT . Participating patients were asked about their rationale for joining the study and which type of information was most useful for deciding upon participation . Results A total of 476 patients entered the screening group , of which 190 patients fulfilled the inclusion and exclusion criteria . 102 patients declined to participate in the study due to various reasons and 46 were later excluded ( no meniscus lesion on the magnetic resonance imaging scan or withdrawn consent ) . A total of 40 patients were finally included in the RCT . To include one patient into the RCT , 11.9 individuals needed to be screened . A total of 69 % of participating patients considered the oral information to be the most important and the most common reason for participating was the contribution to research ( 90 % ) . Conclusions Patients are willing to participate in an orthopedic placebo-controlled surgical trial . Oral information given by the surgeon to the patient and the contribution to research are important aspects to enhance patient recruitment . Trial registration Clinical Trials.gov NCT01264991 , registered 21 December 2010 BACKGROUND Arthroscopic partial meniscectomy is one of the most common orthopedic procedures , yet rigorous evidence of its efficacy is lacking . METHODS We conducted a multicenter , r and omized , double-blind , sham-controlled trial in 146 patients 35 to 65 years of age who had knee symptoms consistent with a degenerative medial meniscus tear and no knee osteoarthritis . Patients were r and omly assigned to arthroscopic partial meniscectomy or sham surgery . The primary outcomes were changes in the Lysholm and Western Ontario Meniscal Evaluation Tool ( WOMET ) scores ( each ranging from 0 to 100 , with lower scores indicating more severe symptoms ) and in knee pain after exercise ( rated on a scale from 0 to 10 , with 0 denoting no pain ) at 12 months after the procedure . RESULTS In the intention-to-treat analysis , there were no significant between-group differences in the change from baseline to 12 months in any primary outcome . The mean changes ( improvements ) in the primary outcome measures were as follows : Lysholm score , 21.7 points in the partial-meniscectomy group as compared with 23.3 points in the sham-surgery group ( between-group difference , -1.6 points ; 95 % confidence interval [ CI ] , -7.2 to 4.0 ) ; WOMET score , 24.6 and 27.1 points , respectively ( between-group difference , -2.5 points ; 95 % CI , -9.2 to 4.1 ) ; and score for knee pain after exercise , 3.1 and 3.3 points , respectively ( between-group difference , -0.1 ; 95 % CI , -0.9 to 0.7 ) . There were no significant differences between groups in the number of patients who required subsequent knee surgery ( two in the partial-meniscectomy group and five in the sham-surgery group ) or serious adverse events ( one and zero , respectively ) . CONCLUSIONS In this trial involving patients without knee osteoarthritis but with symptoms of a degenerative medial meniscus tear , the outcomes after arthroscopic partial meniscectomy were no better than those after a sham surgical procedure . ( Funded by the Sigrid Juselius Foundation and others ; Clinical Trials.gov number , NCT00549172 . ) R and omised evaluations of surgical interventions are rare ; some interventions have been widely adopted without rigorous evaluation . Unlike other medical areas , the r and omised controlled trial ( RCT ) design has not become the default study design for the evaluation of surgical interventions . Surgical trials are difficult to successfully undertake and pose particular practical and method ological challenges . However , RCTs have played a role in the assessment of surgical innovations and there is scope and need for greater use . This article will consider the design , conduct and analysis of an RCT of a surgical intervention . The issues will be review ed under three headings : the timing of the evaluation , defining the research question and trial design issues . Recommendations on the conduct of future surgical RCTs are made . Collaboration between research and surgical communities is needed to address the distinct issues raised by the assessment of surgical interventions and enable the conduct of appropriate and well- design ed trials STUDY OBJECTIVES Recent publications have demonstrated a reduction in snoring with radiofrequency ( RF ) surgery of the soft palate . Yet so far , all published data has been based on non-controlled trials . DESIGN Aim of this study was to assess the efficacy of RF surgery of the soft palate in a r and omized , placebo-controlled trial . SETTING Out patients department at university hospital , department of otorhinolaryngology . PATIENTS 26 patients with primary snoring ( AHI < 15 , BMI < 35 ) . INTERVENTIONS Patients were treated with temperature-controlled RF surgery of the soft palate under local anesthesia . In accord with a r and omization protocol they received 2 sessions of RF surgery ( total amount of energy : 3.300 Joule ) or placebo ( insertion of device needle without energy delivery ) . MEASUREMENTS AND RESULTS Snoring was evaluated by the bed partner with 10 cm visual analogue scales . 23 patients completed the study ; 12 received RF-surgery and 11 received placebo . Snoring scores did not change in the placebo group ( 8.4 + /- 1.6 to 8.0 + /- 2.3 ) while improving in the RF-group ( 8.1 + /- 1.3 to 5.2 + /- 2.4 ) . The difference between the groups was statistically significant ( p < 0.05 ) . CONCLUSION RF-surgery was significantly better than placebo , although the reduction in snoring was only moderate in our group of patients . This study underlines the necessity for well-controlled clinical trials in the treatment of snoring Background This study aim ed to assess whether endoscopic implantation of an injectable esophageal prosthesis , the Gatekeeper Reflux Repair System ( GK ) , is a safe and effective therapy for controlling gastroesophageal reflux disease ( GERD ) . Methods A prospect i ve , r and omized , sham-controlled , single-blinded , international multicenter study planned final enrollment of 204 patients in three groups : up to 60 lead-in , 96 GK , and 48 sham patients . The sham patients were allowed to cross over to the GK treatment arm or exit the study at 6 months . The primary end points were ( 1 ) reduction in serious device- and procedure-related adverse device effects compared with a surgical composite complication rate and ( 2 ) reduction in heartburn symptoms 6 months after the GK procedure compared with the sham procedure . The secondary end point was improved esophageal pH ( total time pH was < 4 ) 6 months after the GK procedure compared with baseline . Results A planned interim analysis was performed after 143 patients were enrolled ( 25 lead-in , 75 GK , and 43 sham patients ) , and the GK study was terminated early due to lack of compelling efficacy data . Four reported serious adverse events had occurred ( 2 perforations , 1 pulmonary infiltrate related to a perforation , and 1 severe chest pain ) at termination of the study with no mortality or long-term sequelae . Heartburn symptoms had improved significantly at 6 months compared with baseline in the GK group ( p < 0.0001 ) and the sham group ( p < 0.0001 ) , but no significant between-group difference in improvement was observed ( p = 0.146 ) . Esophageal acid exposure had improved significantly at 6 months compared with baseline in the GK group ( p = 0.021 ) and the sham group ( p = 0.003 ) , but no significant between-group difference in improvement was observed ( p = 0.27 ) . Conclusions The GK procedure was associated with some serious but infrequent complications . No statistically significant difference in outcomes was observed between the treatment and control groups at 6 months compared with baseline IMPORTANCE Revisional laparoscopic surgery after Roux-en-Y gastric bypass ( RYGB ) has been linked to substantial complications and morbidity . OBJECTIVE To investigate the safety and effectiveness of endoscopic gastric plication with the StomaphyX device vs a sham procedure for revisional surgery in RYGB patients to reduce regained weight . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve , single-center , r and omized , single-blinded study from July 2009 through February 2011 , evaluating revisional surgery using StomaphyX was conducted in patients with initial weight loss after RYGB performed at least 2 years earlier . We planned for 120 patients to be r and omized 2:1 to multiple full-thickness plications within the gastric pouch and stoma using the StomaphyX device with SerosFuse fasteners or a sham endoscopic procedure and followed up for 1 year . The primary efficacy end point was reduction in pre-RYGB excess weight by 15 % or more excess body mass index ( BMI ) ( calculated as weight in kilograms divided by height in meters squared ) loss and BMI less than 35 at 12 months after the procedure . Adverse events were recorded . RESULTS Enrollment was closed prematurely because preliminary results indicated failure to achieve the primary efficacy end point in at least 50 % of StomaphyX-treated patients . One-year follow-up was completed by 45 patients treated with StomaphyX and 29 patients in the sham treatment group . Primary efficacy outcome was achieved by 22.2 % ( 10 ) with StomaphyX vs 3.4 % ( 1 ) with the sham procedure ( P < .01 ) . Patients undergoing StomaphyX treatment experienced significantly greater reduction in weight and BMI at 3 , 6 , and 12 months ( P ≤ .05 ) . There was one causally related adverse event with StomaphyX , that required laparoscopic exploration and repair . CONCLUSIONS AND RELEVANCE StomaphyX treatment failed to achieve the primary efficacy target and result ed in early termination of the study . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00939055 OBJECTIVE To assess the efficacy of laser laparoscopic surgery in the treatment of pain associated with minimal , mild , and moderate endometriosis . DESIGN A prospect i ve , r and omized , double-blind , and controlled clinical study . SETTING Royal Surrey County Hospital , Guildford , United Kingdom , a referral center for the laser laparoscopic treatment of endometriosis . PATIENTS Sixty-three patients with pain ( dysmenorrhoea , pelvic pain , or dyspareunia ) and minimal to moderate endometriosis . INTERVENTIONS The patients were r and omized at the time of laparoscopy to laser ablation of endometriotic deposits and laparoscopic uterine nerve ablation or expectant management . Pain symptoms were recorded subjectively and by visual analogue scale . The women were unaware of the treatment allocated as was the nurse who assessed them at 3 and 6 months after surgery . MAIN OUTCOME MEASURE Improvement or resolution of pain symptoms assessed subjectively and by visual analogue score . RESULTS Laser laparoscopy results in statistically significant pain relief compared with expectant management at 6 months after surgery . Sixty-two and a half percent of the lasered patients reported improvement or resolution of symptoms compared with 22.6 % in the expectant group . Results were poorest for minimal disease and , if patients with mild and moderate disease only are included , 73.7 % of patients achieved pain relief . There were no operative or laser complications . CONCLUSIONS Laser laparoscopy is a safe , simple , and effective treatment in alleviating pain symptoms in women with stages I , II , and III endometriosis PURPOSE We evaluated the effectiveness of periurethral autologous fat injection as treatment for female stress urinary incontinence . MATERIAL S AND METHODS Women with stress incontinence were r and omized in a double-blind fashion to receive periurethral injections of autologous fat ( treatment group ) or saline ( placebo group ) . After injection patients were evaluated monthly for 3 months by a vali date d st and ardized incontinence question naire , 1-hour pad test and cough test . Patients who remained incontinent were offered repeat injection using the same initial agent to a maximum of 3 injections . Every 3 months after injection patients were assessed by a st and ardized question naire , pad test , cough test and urodynamics . Those who did not qualify for repeat injection at 3 months were then followed 6 , 9 , 12 , 18 and 24 months or until failure . RESULTS Of the 68 women enrolled 35 received fat and 33 received saline injections . The groups were comparable in terms of baseline parameters . A total of 56 patients completed the study , including 27 in the fat and 29 in the placebo group , for a total of 189 injections ( 91 fat and 98 saline ) . At 3 months 6 of 27 ( 22.2 % ) and 6 of 29 ( 20.7 % ) women were cured or improved in the fat and saline groups , respectively . Complications included cystitis in 9 of 189 injections , urinary retention in 6 in the fat injection group , urge incontinence in 9 of 68 patients and pulmonary fat embolism result ing in death in 1 of 189 procedures . CONCLUSIONS In this study periurethral fat injection did not appear to be more efficacious than placebo for treating stress incontinence OBJECTIVES : It is not known whether patients with symptoms of dysphagia but normal upper endoscopy benefit from empiric esophageal dilation . The aim of this prospect i ve study was to determine whether patients with solid food dysphagia and normal upper endoscopy have symptomatic benefit from empiric dilation using a through-the-scope balloon . METHODS : Patients who were seen for complaints of solid food dysphagia and who had normal endoscopic examinations at our institution from 1998 through 1999 were identified . Those patients who had agreed before sedation to participate in the study , if eligible , were r and omized to either sham or balloon dilation using an 18-mm through-the-scope balloon at the time of esophagogastroduodenoscopy . All potentially eligible patients who had given provisional consent completed a dysphagia question naire and a 10-cm visual analog dysphagia scale before endoscopy . Follow-up question naires were completed on day 1 and at 3 months and 6 months after the procedure . The primary endpoint of the study was the patient 's self- assessment of difficulty swallowing , based on the question naires . RESULTS : A total of 83 patients met the study criteria and were r and omized to balloon dilation ( n = 43 ) or sham ( n = 40 ) . The two groups were comparable in age , sex , severity of baseline dysphagia , and use of antireflux medication . Improvement in dysphagia comparing sham to balloon on day 1 was 66 % versus 67 % ( p = 0.99 ) ; at 3 months it was 82 % versus 76 % ( p = 0.56 ) ; and at 6 months it was 84 % versus 73 % ( p = 0.38 ) . There were no reported complications in either group . CONCLUSION : The data from this prospect i ve r and omized , controlled study do not support the practice of empiric dilation in patients with symptoms of dysphagia without an endoscopically evident cause of dysphagia BACKGROUND Barrett 's esophagus , a condition of intestinal metaplasia of the esophagus , is associated with an increased risk of esophageal adenocarcinoma . We assessed whether endoscopic radiofrequency ablation could eradicate dysplastic Barrett 's esophagus and decrease the rate of neoplastic progression . METHODS In a multicenter , sham-controlled trial , we r and omly assigned 127 patients with dysplastic Barrett 's esophagus in a 2:1 ratio to receive either radiofrequency ablation ( ablation group ) or a sham procedure ( control group ) . R and omization was stratified according to the grade of dysplasia and the length of Barrett 's esophagus . Primary outcomes at 12 months included the complete eradication of dysplasia and intestinal metaplasia . RESULTS In the intention-to-treat analyses , among patients with low- grade dysplasia , complete eradication of dysplasia occurred in 90.5 % of those in the ablation group , as compared with 22.7 % of those in the control group ( P<0.001 ) . Among patients with high- grade dysplasia , complete eradication occurred in 81.0 % of those in the ablation group , as compared with 19.0 % of those in the control group ( P<0.001 ) . Overall , 77.4 % of patients in the ablation group had complete eradication of intestinal metaplasia , as compared with 2.3 % of those in the control group ( P<0.001 ) . Patients in the ablation group had less disease progression ( 3.6 % vs. 16.3 % , P=0.03 ) and fewer cancers ( 1.2 % vs. 9.3 % , P=0.045 ) . Patients reported having more chest pain after the ablation procedure than after the sham procedure . In the ablation group , one patient had upper gastrointestinal hemorrhage , and five patients ( 6.0 % ) had esophageal stricture . CONCLUSIONS In patients with dysplastic Barrett 's esophagus , radiofrequency ablation was associated with a high rate of complete eradication of both dysplasia and intestinal metaplasia and a reduced risk of disease progression . ( Clinical Trials.gov number , NCT00282672 . OBJECTIVE To evaluate the effectiveness of tidal irrigation ( TI ) in comparison with a well-matched sham irrigation ( SI ) procedure as a treatment for knee osteoarthritis ( OA ) . METHODS One hundred eighty subjects with knee OA were r and omized to receive TI or SI , with clinical followup over the ensuing 12 months . The primary outcomes of interest were change in pain and function , as measured by the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) . Subjects and the nurse assessor were blinded , and success of blinding was assessed . RESULTS Although the study groups were otherwise comparable , the baseline WOMAC pain and physical functioning scores were higher ( worse ) in the SI group . After adjustment for baseline , there were no differences between the effects A prolonged r and omized , prospect i ve , double-blind , crossover study , including a sham-sham-treated group , was undertaken to evaluate the efficacy and safety of a 500-mL gastric bubble ( Ballobes ; DOT ApS , Rödovre , Denmark ) as an adjunct to diet , physical training , and behavioral modification . Only supermorbidly obese patients who fulfilled the usual criteria for surgery were admitted . A weight loss of 38 kg in the first 17 weeks and another 12 kg in the second 18 weeks could be achieved . The body mass index , the percentage of overweight and the loss in percentage of initial weight , paralleled this impressive weight loss . In the second period , a plateau effect occurred after the massive changes in the first period , and only one third of the changes in all parameters was seen . Stratification into a sham-sham , sham-balloon , balloon-sham , and balloon-balloon group did not show any statistical difference for all parameters between the four groups . The double-blind nature of the study was affirmed by the patient 's correct judgment of the presence or absence of a balloon in only 21 % of the balloon and 44 % of the sham procedures . Gastrointestinal complications were infrequent and consisted of erosions ( three patients ) , asymptomatic reflux oesophagitis ( one patient ) , and asymptomatic gastric ulcer ( one patient ) . Only the latter patient had elevated gastrin levels . One patient could not tolerate the balloon . All balloons remained airtight during both parts of the study for a mean of 123 days . This study confirmed the safety of the balloon , but no additional benefit could be ascribed to the balloon compared with a very low-calorie diet and medical and dietary support Since its approval by the Food and Drug Administration in September 1985 , the Garren-Edwards gastric bubble has been extensively used as an adjunct to diet and behavioral modification in the treatment of exogenous obesity . In an attempt to evaluate the efficacy of the Garren-Edwards gastric bubble , a double-blind crossover study was undertaken . Ninety patients were r and omized into three groups : bubble-sham , sham-bubble , and bubble-bubble in two successive 12-wk periods . Sixty-one patients completed the entire 24-wk study . All groups participated in ongoing diet and behavioral modification therapy in a free-st and ing obesity program , the members of which were blinded to r and omization arms . All patient groups lost weight during this study . The mean cumulative weight loss in pounds at 12 wk was as follows : bubble-sham = 19 , sham-bubble = 12 , and bubble-bubble = 8 ; and at 24 wk : bubble-sham = 23 , sham-bubble = 16 , and bubble-bubble = 18 . The mean cumulative change in body mass index ( kg/m2 ) at 12 wk was as follows : bubble-sham = -3.1 , sham-bubble = -2.3 , and bubble-bubble = -2.9 ; and at 24 wk : bubble-sham = -3.1 , sham-bubble = -3.0 , and bubble-bubble = -3.3 . Although weight loss occurred more consistently in patients with a Garren-Edwards gastric bubble , there were no significant differences between any of the three groups at 12 or 24 wk with respect to weight loss or change in body mass index . The major part of the weight loss noted during this study occurred during the first 12-wk period , irrespective of therapy ( bubble or sham ) . Side effects observed during this study included gastric erosions ( 26 % ) , gastric ulcers ( 14 % ) , small bowel obstruction ( 2 % ) , Mallory-Weiss tears ( 11 % ) , and esophageal laceration ( 1 % ) . We conclude that , in this study , the use of a Garren-Edwards gastric bubble did not result in significantly more weight loss than diet and behavioral modification alone in the management of exogenous obesity , and it may result in significant morbidity Objective . The Bard EndoCinch plication technique has been reported to improve symptoms and reduce oesophageal acid exposure in patients with gastro-oesophageal reflux disease ( GORD ) . However , no placebo-controlled studies have been published as yet . The purpose of this study was to evaluate the effects of the EndoCinch plication technique in a r and omized , placebo-controlled setting . Material and methods . Forty-six otherwise healthy subjects with objective ly verified GORD requiring regular use of proton-pump inhibitors ( PPIs ) were enrolled in the study . Patients were r and omized to the EndoCinch plication technique or a sham procedure . Pre- and post-procedure assessment s included gastro-oesophageal endoscopy , oesophageal manometry and 24-h pH recording , quality of life ( QoL ) assessment and use of PPIs . Results . Reflux-specific symptoms and use of PPIs ( total intake as well as number of patients not taking PPIs ) improved in both groups at 6 weeks and at 3 and 12 months post-procedure ( p<0.05 ) with an increased improvement in the treatment group at 3 months compared to controls ( p<0.05 versus sham ) . There were no inter- or intra-group differences in endoscopic findings , oesophageal manometry or acid exposure before or at 3 or 12 months post-procedure . Gastro-oesophageal endoscopy showed that 71 % and 67 % of sutures remained at 3 and 12 months , respectively . Conclusions . Although some short-term effects were achieved , it was found that there were no differences between the treatment and control groups after 12 months and the lack of reduction of oesophageal acid exposure suggests that , in its present form , the EndoCinch plication technique is not to be recommended for use in clinical practice . It is suggested that the lack of long-term effects is primarily due to detachment of the sutures Palatal implants have been used to treat snoring and mild to moderate obstructive sleep apnea ( OSA ) . Two previous controlled trials have published conflicting results regarding the effects of palatal implants on objective outcome measures , although they both could demonstrate superiority over placebo . The aim of the present study was to assess the effects of palatal implants in patients with mild to moderate sleep apnea in a r and omised , placebo-controlled trial . Twenty-two patients with mild to moderate OSA ( AHI 18 ± 5 , BMI 28 ± 3 , age 51 ± 13 years ) due to palatal obstruction were enrolled in this r and omised , double-blind , placebo-controlled trial . Respiratory parameters and sleep efficiency ( evaluated by polysomnography ) , snoring ( evaluated by the bed partner ) , and daytime sleepiness ( evaluated by ESS ) were assessed before and 90 days after surgery . One patient in each group did not show up for follow-up . The AHI , HI and LSAT showed statistically significant improvement in the treatment group ( p < 0.05 ) . Snoring as rated by bed partners also showed statistically significant improvement within the treatment group ( p = 0.025 ) . There was no statistical difference when comparing the means of the treatment group with the placebo group . There were no peri- or post-operative complications and no extrusions during the follow-up period . The study supports the idea that palatal implants lead to a reduction in respiratory events in patients with mild to moderate OSA , although a statistically significant superiority of palatal implants over placebo could not be demonstrated in this trial A prospect i ve r and omized controlled trial of endoscopic heater probe therapy in bleeding peptic ulcers was performed to determine whether probe therapy can reduce rebleeding rates . Of 630 patients endoscoped for suspected upper gastrointestinal haemorrhage over a 16‐month period , 166 ( 26 per cent ) were found to have a peptic ulcer . Either minor or no stigmata of recent haemorrhage were found in 115 patients at the time of endoscopy . A single peptic ulcer with either active haemorrhage or a visible vessel was found in 51 patients , 43 of whom were entered into the trial . There were eight exclusions : four were inaccessible , one was a torrential haemorrhage and three were excluded for non‐technical reasons . Patients were r and omized to receive either heater probe ( n = 20 ) or sham ( n = 23 ) therapy . In actively bleeding ulcers , immediate haemostasis was achieved following probe therapy in 14 of 18 patients ( 78 per cent ) compared with none of 21 having sham treatment ( P < 0·002 ) . No rebleeding occurred in the probe therapy group ( n = 20 ) compared with rebleeding in five of 23 sham treated patients ( P = 0·05 ) . Urgent surgery for haemostasis was required in three of the five sham treated patients who rebled . It is concluded that heater probe therapy may be effective in reducing rebleeding rates in peptic ulcers accessible to the endoscope BACKGROUND Intradiscal electrothermal therapy ( IDET ) is a treatment for discogenic low back pain the efficacy of which has not been rigorously tested . PURPOSE To compare the efficacy of IDET with that of a placebo treatment . STUDY DESIGN / SETTING R and omized , placebo-controlled , prospect i ve trial . PATIENT SAMPLE Patients were recruited by referral and the media . No inducements were provided to any patient in order to have them participate . Of 1,360 individuals who were prepared to su bmi t to r and omization , 260 were found potentially eligible after clinical examination and 64 became eligible after discography . All had discogenic low back pain lasting longer than 6 months , with no comorbidity . Thirty-seven were allocated to IDET and 27 to sham treatment . Both groups were satisfactorily matched for demographic and clinical features . METHODS IDET was performed using a st and ard protocol , in which the posterior annulus of the painful disc was heated to 90 C. Sham therapy consisted of introducing a needle onto the disc and exposing the patient to the same visual and auditory environment as for a real procedure . Thirty-two ( 85 % ) of the patients r and omized to the IDET group and 24 ( 89 % ) of those assigned to the sham group complied fully with the protocol of the study , and complete follow-up data are available for all of these patients . OUTCOME MEASURES The principal outcome measures were pain and disability , assessed using a visual analog scale for pain , the Short Form (SF)-36 , and the Oswestry disability scale . RESULTS Patients in both groups exhibited improvements , but mean improvements in pain , disability and depression were significantly greater in the group treated with IDET . More patients deteriorated when subjected to sham treatment , whereas a greater proportion showed improvements in pain when treated with IDET . The number needed to treat , to achieve 75 % relief of pain , was five . Whereas approximately 40 % of the patients achieved greater than 50 % relief of their pain , approximately 50 % of the patients experienced no appreciable benefit . CONCLUSIONS Nonspecific factors associated with the procedure account for a proportion of the apparent efficacy of IDET , but its efficacy can not be attributed wholly to a placebo effect . The results of this trial can not be generalized to patients who do not fit the strict inclusion criteria of this study , but IDET appears to provide worthwhile relief in a small proportion of strictly defined patients undergoing this treatment for intractable low back pain BACKGROUND Human retinal pigment epithelial ( RPE ) cells produce levodopa and their transplantation into the striatum might improve continuity of administration compared with that achieved with oral levodopa . We aim ed to assess the safety , tolerability , and efficacy of transplantation of microcarrier-bound human RPE cells versus a sham surgery control in patients with advanced Parkinson 's disease . METHODS In this r and omised , double-blind study eligible patients were aged 36 - 70 years , had been symptomatic for at least 5 years , were in Hoehn and Yahr stage 3 - 4 and had unified Parkinson 's disease rating scale ( UPDRS ) motor scores of 38 - 70 when off medication ( off state ) , and had symptoms that responded to oral levodopa but were insufficiently controlled by optimised pharmacotherapy . R and omisation was done in a 1:1 ratio . Only the neurosurgical team was aware of treatment assignments . During stereotactic transplantation around 325,000 cells per side were injected into the postcommissural putamen ; sham surgery patients received partial burr holes . The primary efficacy endpoint was change in UPDRS off-state motor score at 12 months . This study is registered with Clinical Trials.gov , number NCT00206687 . FINDINGS Of 71 enrolled patients , 35 underwent cell transplantation and 36 sham surgery . Change in mean motor scores did not differ significantly between groups ( -10.5 [ SD 10.26 ] for transplantation vs -10.1 [ SD 12.26 ] for sham surgery , p=0.9 ) . The overall rate of adverse events was similar in the two study groups , although the number attributable to surgery or RPE cells ( mostly neurological or psychiatric ) was higher in transplant recipients . Two and seven patients died in the sham surgery and transplantation group , respectively ; one death in the latter group was possibly related to surgery or RPE cells . INTERPRETATION Transplantation of human RPE cells provided no antiparkinsonian benefits compared with sham surgery . FUNDING Bayer HealthCare AG Blinding in medical research possesses a rich history spanning a couple of centuries ( 1 ) . Most research ers and readers grasp its meaning . Unfortunately , beyond that general underst and ing lies confusion . In addition to terms such as single blind and double blind meaning different things to different people , some steadfastly refuse to use the term blinding and insist instead on the term masking . Others confuse blinding with other method ologic pre caution s , such as concealment of allocation during the process of creating comparison groups . Still others consider that r and omization is of little use unless accompanied by double-blinding , thus revealing that they have not understood that these separate aspects of methodology address separate sources of bias . A recent survey addressed whether the process historically termed blinding should be termed masking ( 2 ) . The survey revealed a lack of accord on that question and inconsistencies concerning other blinding terminology . Although many re sources address the lexicon of blinding , including clinical trial textbooks ( 3 - 5 ) , clinical trial dictionaries ( 6 , 7 ) , and a recently released epidemiology dictionary ( 8) , these sources do not entirely clear the lexicographic fog . Indeed , a recent study found that investigators , textbooks , and published articles all varied greatly in their interpretations of single- , double- , and triple-blinding ( 9 ) . In other words , terminologic tangles abound with blinding . We delve into the l and scape and lexicon of blinding in r and omized trials in the hope of untangling some of that terminology . Synopsis of the History of Blinding Scientists sometimes portray blinding as a recent method ologic achievement , but research ers have used blinding for more than 200 years . Lavoisier and Franklin introduced blinding in the late 18th century to test therapeutic cl aims made for Mesmerisma therapy founded on the notion that magnetism had healing properties ( 1 , 10 ) . Toward the middle of the 19th century , many homeopaths used blinding in their provings and in comparisons of homeopathy with mainstream medicine ( 11 ) . By the late 19th century , psychological research ers began to use blinding for traditional questions , more to minimize bias than to expose fraud ( 1 ) . The beginning of the 20th century found some physiologists and pharmacologists , particularly in Germany , using blind assessment . That use became more frequent in Germany by the 1930s . Research ers in Britain and the United States developed interest in blind assessment , but a different rationale motivated their interest . The rationale in Germany for blinding centered on the elimination of bias . In contrast , the interest in Britain and the United States initially centered on preventing attrition problems ( 1 ) . Without blinding and a placebo intervention , recruiting and retaining participants for a no-intervention control group became daunting . For Anglo-American clinical research ers , the initial adoption of a placebo sham in an experiment was an architectural device to create a viable and camouflaged concurrent no-treatment arm in a clinical trial ( 1 ) . Toward the end of the 1930s , British and U.S. research ers also began to acknowledge the benefits of blinding in avoiding bias . The evolution of the r and omized , controlled trial during the first half of the 20th century promoted greater use of blinding . Properly concealed r and om allocation to comparison groups abolished selection bias at entry to a trial , and clinical investigators began to appreciate fully the biases that could affect studies after participants had entered a trial . That realization transferred greater credibility to blinding arguments ( 1 ) . We recommend Kaptchuk ( 1 ) for a historical account . Background Blinding is intended to reduce bias in medical research . Although blinding is often associated in people 's minds with r and omized , controlled trials , it can be used in a variety of study design s to reduce observer biases ( 12 ) . For example , investigators can assess outcome measures blinded to exposure status in nonr and omized cohort studies or exposure status blinded to case or control status in casecontrol studies . Indeed , when investigators first used blinding in the 18th century , they assessed the effects of Mesmerism in nonr and omized experiments ( 1 , 10 ) . Having noted this , however , we focus on blinding in the context of r and omized comparisons of interventions . Blinding is widely recognized as reducing differential assessment of outcomes of interest ( known as ascertainment bias , information bias , or observer bias ) , prompted by knowledge of the group assignment of individuals being observed ( 3 - 5 ) . Blinding is less frequently recognized as also operationally improving compliance and retention of trial participants and reducing biased supplemental care or treatment ( sometimes called co-intervention ) ( 3 , 5 ) . We provide glimpses of the potential disadvantages of participants ' , investigators ' , and outcome assessors ' knowing the intervention group to which the participants have been assigned . In many cases , the biases that result might well be subconscious , but they are biases nonetheless . Possible Consequences of Participants ' Knowing Psychological effects could arise from participants ' knowing that they have received a promising new treatment , a thoroughly tested st and ard treatment , an untested new treatment , or a disappointing st and ard treatment . In other words , how the treatment options are perceived may influence the way in which they are evaluated . Despite evidence suggesting that new treatments are as likely to be inferior as they are to be superior to st and ard treatments ( 13 ) , we have the impression that participants generally assume that new treatments will be better than st and ard treatments . In any case , knowledge of the intervention received can affect the psychological or physical responses of the participants ( 3 - 5 ) . Furthermore , knowledge of the intervention could influence participants ' cooperation . For example , if participants believe that they were assigned to what they perceive as an inferior intervention , they may not comply well with the regimen . Moreover , they may not adhere to follow-up procedures , leading to a potentially biased loss to follow-up . Possible Consequences of Investigators ' Knowing We define investigators in an aggregate sense to include a broad trial teamfor example , trial design ers , participant enrollers , r and omization executors , health care providers , intervention counselors , and routine- data collectors . Investigators particularly pertinent to blinding include health care providers ( such as an attending physician or nurse ) and intervention counselors ( for example , someone delivering a behavioral prevention message ) who interact with the participants throughout the trial . The inclinations of investigators for or against the interventions can be directly transferred to participants by their attitudes ( 14 ) . Their inclinations may also be manifested in , for example , differential use of ancillary interventions of supplemental care or treatment ( co- interventions ) . Of note , the implementer could also encourage or discourage continuation in the trial on the basis of knowledge of the intervention group assignment . Possible Consequences of Outcome Assessors ' Knowing When they know the intervention group assignment of the participants whom they are assessing , outcome assessors with inclinations for or against any of the interventions being compared may make biased assessment s. For example , if they believe the new intervention is superior , then they could register more generous responses to that intervention . Obviously , more subjective outcomes present greater opportunities for bias . Pain scores assessed by participants are a good example of a subjective outcome . Even some outcomes considered objective can be fraught with subjectivityfor example , pelvic inflammatory disease and myocardial infa rct ion . In general , blinding becomes less important to reduce observer bias as the outcomes become less subjective . Hard outcomes leave little room for bias . For example , knowledge of the intervention would have little effect on measuring a hard outcome , such as death ( but still could influence the attributed cause of death ) . Of importance , even when participants and investigators have not been blinded , blinding of outcome assessors is often possible and advisable ( 12 ) . Placebos and Blinding Blinding frequently leads to the use of placebos . Placebos may or may not have effects mediated through psychological mechanisms , but they are administered to participants in a trial because they are otherwise inactive . An active placebo is a placebo with properties that mimic the symptoms or side effects ( for example , dry mouth , sweating ) that might otherwise reveal the identity of the ( pharmacologically ) active test treatment . The effect , in practice , of using placebos is contentious ( 15 ) , but the widespread view remains that placebos should be administered , whenever possible , to participants in control groups when assessing the effects of proposed new treatments for a condition for which no effective treatment already exists ( 3 , 4 ) . Placebos are generally used in trials of drugs , vaccines , and other medicinal interventions but can sometimes also be used in trials of procedures , such as ultrasonography , acupuncture , and , occasionally , surgery . For example , perhaps when placebo treatments are inappropriate , some closely analogous approach , such as placebo wound dressings , may suffice in a trial of laparoscopic versus open appendicectomy ( 16 ) . When an effective st and ard treatment exists , it is frequently used in the control group for comparison against a new treatment . Thus , investigators might compare two active treatment groups without a placebo group . Even then , however , investigators frequently attempt to achieve blinding by using the double-dummy method in essence , two placebos ( 12 , 17 ) . For example , in comparing two agents , one in a blue capsule Objective . Determine if the Pillar palatal implant system reduces continuous positive airway pressure ( CPAP ) pressure and improves patient compliance with CPAP therapy . Study Design . R and omized , double-blind , placebo-controlled study . Setting . Four geographically dispersed tertiary sleep disorder referral centers . Methods . Subjects with mild to moderate sleep apnea dissatisfied with CPAP because of pressure-related complaints were r and omized to receive Pillar implants or a sham procedure performed in double-blind fashion . Active and sham groups were compared for changes in therapeutic CPAP pressures ( primary outcome ) with a 90-day follow-up sleep study and CPAP compliance ( secondary outcome ) with a 90-day smart card report . Results . Twenty-six subjects were r and omized to Pillar implants and 25 to a sham implant procedure . There were no differences between groups with regard to demographics and baseline parameters . Both sham and active groups had reduced mean CPAP pressure ( −1.1 vs −0.5 cm H2O ) with no difference between groups ( P = .32 ) at 90-day follow-up . In addition , there was no difference in average daily CPAP use between groups ( P = .80 ) . Both groups experienced improvements in Epworth sleepiness scores and Functional Outcome of Sleep Question naire scores at 90 days with no differences between groups . The active group reported significantly higher CPAP satisfaction scores than the sham group ( P = .04 ) . Conclusion . Pillar implants do not significantly reduce CPAP pressure or increase CPAP compliance compared to sham controls but may subjectively improve CPAP satisfaction . These findings do not presently support the use of Pillar implants as an adjunctive treatment to improve CPAP compliance We investigated the effect of an endoscopically placed gastric balloon , the Garren-Edwards gastric bubble ( GEGB ) , on weight loss in obese patients . Fifty-nine obese patients were entered into a prospect i ve double-blind study and r and omized into two groups . In one group ( 34 patients ) the GEGB was inserted , and in the other group ( 25 patients ) a sham insertion was done . All patients participated in a st and ard weight loss program consisting of dietary therapy , behavior modification , and physical exercise . The bubble was removed endoscopically after 3 months from both groups . Patients were followed for an additional 9 months after bubble removal and weight loss was monitored . Weight loss was the same in both groups at 3 months ( 18.7 lb vs. 17.2 lb ) . This was true whether determined by change in pounds , percentage of body weight , or body mass index . We concluded that the GEGB was of no added benefit as compared with sham insertion , when combined with a st and ard weight loss program . Because of the lack of proven efficacy and the relatively high cost , we recommend that such devices be restricted to controlled studies until significant benefits are proven OBJECTIVE To compare the effectiveness of sharp excision of endometriosis with sham surgical excision in alleviating endometriosis-associated pain for up to 1 year following surgery . METHODS Patients requiring a laparoscopy for severe pelvic pain were eligible . If endometriosis was visually identified at laparoscopy , a biopsy of a representative lesion was taken . The women were then r and omized either to have all remaining endometriosis excised with laparoscopic scissors ( the excision group ) or to have no further surgical treatment ( the control group ) . Patients were asked to complete daily pain scales for 1 month preoperatively and quarterly for 1 year postoperatively . Subjects were blinded to their treatment allocation for 1 year . RESULTS Twenty-nine women underwent laparoscopy and biopsy and were r and omized to have excision or no treatment of endometriosis . The excision and control groups were similar in age , parity , and revised American Society for Reproductive Medicine stage of disease . Sixteen women completed the full year of follow-up : 9 in the excision group , and 7 in the control group . Overall , recorded pain was significantly reduced at 1 year ( P < 0.05 ) , with no significant difference between the excision and control groups . CONCLUSION Laparoscopy with diagnostic biopsy alone is associated with a significant reduction in pain for up to 1 year postoperatively . Although the study lacked sufficient statistical power to exclude an effect of excision , pain relief in each group was similar . These results indicate a potential benefit of sham surgical procedures in assessing novel surgical interventions BACKGROUND & AIMS Gastroesophageal reflux disease is a prevalent disorder that often requires long-term medical therapy or surgery . The United States Food and Drug Administration recently cleared new endoluminal gastroesophageal reflux disease treatments ; however , no controlled trials exist . METHODS We r and omly assigned 64 gastroesophageal reflux disease patients to radiofrequency energy delivery to the gastroesophageal junction ( 35 patients ) or to a sham procedure ( 29 patients ) . Principal outcomes were reflux symptoms and quality of life . Secondary outcomes were medication use and esophageal acid exposure . After 6 months , interested sham patients crossed over to active treatment . RESULTS At 6 months , active treatment significantly and substantially improved patients ' heartburn symptoms and quality of life . More active vs. sham patients were without daily heartburn symptoms ( n = 19 [ 61 % ] vs. n = 7 [ 33 % ] ; P = 0.05 ) , and more had a > 50 % improvement in their gastroesophageal reflux disease quality of life score ( n = 19 [ 61 % ] vs. n = 6 [ 30 % ] ; P = 0.03 ) . Symptom improvements persisted at 12 months after treatment . At 6 months , there were no differences in daily medication use after a medication withdrawal protocol ( n = 17 [ 55 % ] vs. n = 14 [ 61 % ] ; P = 0.67 ) or in esophageal acid exposure times . There were no perforations or deaths . CONCLUSIONS Radiofrequency energy delivery significantly improved gastroesophageal reflux disease symptoms and quality of life compared with a sham procedure , but it did not decrease esophageal acid exposure or medication use at 6 months . This procedure represents a new option for selected symptomatic gastroesophageal reflux disease patients who are intolerant of , or desire an alternative to , traditional medical therapies IN 1996 , THE LANCET PUBLISHED A COMMENTARY “ Surgical Research or Comic Opera : Questions , but Few Answers.”1 The author review ed the first issue of 9 general surgery journals in 1996 and found that only 7 % of papers reported data derived from a r and omized trial , whereas 46 % were based on case series . A decade later ( 2006 ) , we conducted a similar survey and found that the relative percentage of case series , operationally defined as a single institution ’s experience with a single procedure , had decreased to 34 % . At the same time , we found that the relative number of cohort studies ( 51 % ) and the relative percentage of articles reporting data derived from a r and omized trial ( 10 % ) remained relatively similar . Such a review raises several interesting questions about contemporary surgical research . The main issue that st and s out is this one : Why the number of r and omized trials , which had been identified as being low compared with other fields of medicine in the mid-1990s , has not increased over time in an environment where the dem and s for rigorous evidence have grown ? In addressing this question , it is clear that different research design s --- ranging from case series to r and omized trials to meta-analyses --- are needed for the evaluation of surgical procedures . The appropriate choice of research design depends on the effect size of the intervention , the specific clinical circumstances , the relevant clinical question , and the stage of the life cycle in which a surgical procedure is evaluated . Case series , for example , are valuable in rare diseases , whereas prospect i ve single-arm studies can provide important insights if the natural history of a disease is known and the outcome is unequivocal . Moreover , the first stage of clinical evaluation for a novel procedure is usually a single-arm prospect i ve study in a diseased population to assess the feasibility of its use in humans . These studies , which are generally small in size , provide preliminary evidence about short-term safety and efficacy . The major value of these studies is that they offer easily obtainable prima facie evidence for design ing large-scale , pivotal trials that are r and omized or otherwise controlled . However , our review suggests that such large-scale confirmatory trials are not always carried out , especially r and omized studies . The advantage of r and omized trials is well known ; they offer a powerful means to evaluate the efficacy of procedures in that comparison groups are equally constituted with respect to known and unknown predictors of outcome . As such , these trials offer an unbiased assessment of the impact of a procedure . So why are such trials not more prevalent in surgery ? We believe that such trials can be more difficult to design and conduct for surgical procedures than for new pharmaceutical agents . Moreover , because surgical innovation is characterized by a high degree of incremental change and heavy dependence on technical skill and experience , statistical inference from trial data is often more challenging . In this analysis , we first explore the method ological , ethical , and logistic challenges posed by conducting r and omized trials of novel surgical procedures . We review several options for addressing these challenges in terms of trial design and analytic techniques . We then discuss issues involved in the interpretation of clinical trials and the value of so-called pragmatic r and omized trials . We conclude by evaluating some of the larger infrastructure issues that need to be addressed before a robust , surgical clinical trial enterprise can be created BACKGROUND & AIMS The aim of this study was to determine the effectiveness of endoscopic full-thickness plication for the treatment of gastroesophageal reflux disease ( GERD ) in comparison with a sham procedure . METHODS Patients with symptomatic GERD requiring maintenance proton pump inhibitor ( PPI ) therapy were entered into a r and omized , single-blind , prospect i ve , multicenter trial . Seventy-eight patients were r and omly assigned to undergo endoscopic full-thickness restructuring of the gastric cardia with transmural suture . Eighty-one patients underwent a sham procedure . Group assignments were revealed following the 3-month evaluation . The primary end point was > or = 50 % improvement in GERD health-related quality of life ( HRQL ) score . Secondary end points included medication use and esophageal acid exposure . RESULTS By intention-to-treat analysis , at 3 months , the proportion of patients achieving > or = 50 % improvement in GERD-HRQL score was significantly greater in the active group ( 56 % ) compared with the sham group ( 18.5 % ; P < .001 ) . Complete cessation of PPI therapy was higher among patients in the active group than in the sham group by intention-to-treat analysis ( 50 % vs 24 % ; P = .002 ) . The percent reduction in median percent time pH < 4 was significantly improved within the active group versus baseline ( 7 vs 10 , 18 % , P < .001 ) but not in the sham group ( 10 vs 9 , -3 % , P = .686 ) . Between-group analysis revealed the active therapy to be superior to the sham in improving median percent time pH < 4 ( P = .010 ) . There were no perforations or deaths . CONCLUSIONS Endoscopic full-thickness plication more effectively reduces GERD symptoms , PPI use , and esophageal acid exposure than a sham procedure IMPORTANCE Abdominal pain after cholecystectomy is common and may be attributed to sphincter of Oddi dysfunction . Management often involves endoscopic retro grade cholangiopancreatography ( ERCP ) with manometry and sphincterotomy . OBJECTIVE To determine whether endoscopic sphincterotomy reduces pain and whether sphincter manometric pressure is predictive of pain relief . DESIGN , SETTING , AND PATIENTS Multicenter , sham-controlled , r and omized trial involving 214 patients with pain after cholecystectomy without significant abnormalities on imaging or laboratory studies , and no prior sphincter treatment or pancreatitis r and omly assigned ( August 6 , 2008-March 23 , 2012 ) to undergo sphincterotomy or sham therapy at 7 referral medical centers . One-year follow-up was blinded . The final follow-up visit was March 21 , 2013 . INTERVENTIONS After ERCP , patients were r and omized 2:1 to sphincterotomy ( n = 141 ) or sham ( n = 73 ) irrespective of manometry findings . Those r and omized to sphincterotomy with elevated pancreatic sphincter pressures were r and omized again ( 1:1 ) to biliary or to both biliary and pancreatic sphincterotomies . Seventy-two were entered into an observational study with conventional ERCP managemeny . MAIN OUTCOMES AND MEASURES Success of treatment was defined as less than 6 days of disability due to pain in the prior 90 days both at months 9 and 12 after r and omization , with no narcotic use and no further sphincter intervention . RESULTS Twenty-seven patients ( 37 % ; 95 % CI , 25.9%-48.1 % ) in the sham treatment group vs 32 ( 23 % ; 95 % CI , 15.8%-29.6 % ) in the sphincterotomy group experienced successful treatment ( adjusted risk difference , -15.6 % ; 95 % CI , -28.0 % to -3.3 % ; P = .01 ) . Of the patients with pancreatic sphincter hypertension , 14 ( 30 % ; 95 % CI , 16.7%-42.9 % ) who underwent dual sphincterotomy and 10 ( 20 % ; 95 % CI , 8.7%-30.5 % ) who underwent biliary sphincterotomy alone experienced successful treatment . Thirty-seven treated patients ( 26 % ; 95 % CI,19%-34 % ) and 25 patients ( 34 % ; 95 % CI , 23%-45 % ) in the sham group underwent repeat ERCP interventions ( P = .22 ) . Manometry results were not associated with the outcome . No clinical subgroups appeared to benefit from sphincterotomy more than others . Pancreatitis occurred in 15 patients ( 11 % ) after primary sphincterotomies and in 11 patients ( 15 % ) in the sham group . Of the nonr and omized patients in the observational study group , 5 ( 24 % ; 95 % CI , 6%-42 % ) who underwent biliary sphincterotomy , 12 ( 31 % ; 95 % CI , 16%-45 % ) who underwent dual sphincterotomy , and 2 ( 17 % ; 95 % CI , 0%-38 % ) who did not undergo sphincterotomy had successful treatment . CONCLUSIONS AND RELEVANCE In patients with abdominal pain after cholecystectomy undergoing ERCP with manometry , sphincterotomy vs sham did not reduce disability due to pain . These findings do not support ERCP and sphincterotomy for these patients . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00688662 Research on surgical interventions is associated with several method ological and practical challenges of which few , if any , apply only to surgery . However , surgical evaluation is especially dem and ing because many of these challenges coincide . In this report , the second of three on surgical innovation and evaluation , we discuss obstacles related to the study design of r and omised controlled trials and non-r and omised studies assessing surgical interventions . We also describe the issues related to the nature of surgical procedures -for example , their complexity , surgeon-related factors , and the range of outcomes . Although difficult , surgical evaluation is achievable and necessary . Solutions tailored to surgical research and a framework for generating evidence on which to base surgical practice are essential BACKGROUND & AIMS Weight regain or insufficient loss after Roux-en-Y gastric bypass ( RYGB ) is common . This is partially attributable to dilatation of the gastrojejunostomy ( GJ ) , which diminishes the restrictive capacity of RYGB . Endoluminal interventions for GJ reduction are being explored as alternatives to revision surgery . We performed a r and omized , blinded , sham-controlled trial to evaluate weight loss after sutured transoral outlet reduction ( TORe ) . METHODS Patients with weight regain or inadequate loss after RYGB and GJ diameter greater than 2 cm were assigned r and omly to groups that underwent TORe ( n = 50 ) or a sham procedure ( controls , n = 27 ) . Intraoperative performance , safety , weight loss , and clinical outcomes were assessed . RESULTS Subjects who received TORe had a significantly greater mean percentage weight loss from baseline ( 3.5 % ; 95 % confidence interval , 1.8%-5.3 % ) than controls ( 0.4 % ; 95 % confidence interval , 2.3 % weight gain to 3.0 % weight loss ) ( P = .021 ) , using a last observation carried forward intent-to-treat analysis . As-treated analysis also showed greater mean percentage weight loss in the TORe group than controls ( 3.9 % and 0.2 % , respectively ; P = .014 ) . Weight loss or stabilization was achieved in 96 % subjects receiving TORe and 78 % of controls ( P = .019 ) . The TORe group had reduced systolic and diastolic blood pressure ( P < .001 ) and a trend toward improved metabolic indices . In addition , 85 % of the TORe group reported compliance with the healthy lifestyle eating program , compared with 53.8 % of controls ; 83 % of TORe subjects said they would undergo the procedure again , and 78 % said they would recommend the procedure to a friend . The groups had similar frequencies of adverse events . CONCLUSIONS A multicenter r and omized trial provides Level I evidence that TORe reduces weight regain after RYGB . These results were achieved using a superficial suction-based device ; greater levels of weight loss could be achieved with newer , full-thickness suturing devices . TORe is one approach to avoid weight regain ; a longitudinal multidisciplinary approach with dietary counseling and behavioral changes are required for long-term results . Clinical Trials.gov identifier : NCT00394212 BACKGROUND Endoscopic sphincterotomy for biliary-type pain after cholecystectomy remains controversial despite evidence of efficacy in some patients with a high sphincter of Oddi ( SO ) basal pressure ( SO stenosis ) . AIM To evaluate the effects of sphincterotomy in patients r and omised on the basis of results from endoscopic biliary manometry . METHODS Endoscopic biliary manometry was performed in 81 patients with biliary-type pain after cholecystectomy who had a dilated bile duct on retro grade cholangiography , transient increases in liver enzymes after episodes of pain , or positive responses to challenge with morphine/neostigmine . The manometric record was categorised as SO stenosis , SO dyskinesia , or normal , after which the patient was r and omised in each category to sphincterotomy or to a sham procedure in a prospect i ve double blind study . Symptoms were assessed at intervals of three months for 24 months by an independent observer , and the effects of sphincterotomy on sphincter function were monitored by repeat manometry after three and 24 months . RESULTS In the SO stenosis group , symptoms improved in 11 of 13 patients treated by sphincterotomy and in five of 13 subjected to a sham procedure ( p = 0.041 ) . When manometric records were categorised as dyskinesia or normal , results from sphincterotomy and sham procedures did not differ . Complications were rare , but included mild pancreatitis in seven patients ( 14 episodes ) and a collection in the right upper quadrant , presumably related to a minor perforation . At three months , the endoscopic incision was extended in 19 patients because of manometric evidence of incomplete division of the sphincter . CONCLUSION In patients with presumed SO dysfunction , endoscopic sphincterotomy is helpful in those with manometric features of SO stenosis R and omized clinical trials are the most rigorous clinical research design . However , trials are expensive , time-consuming , and challenging to design and complete . In May 2009 , the Clinical Trials in Orthopaedics Research Symposium , sponsored by the American Academy of Orthopaedic Surgeons ( AAOS ) , the Orthopaedic Research and Education Foundation ( OREF ) , and the National Institute of Arthritis and Musculoskeletal and Skin Diseases ( NIAMS ) , brought together multiple disciplines to define a r and omized clinical trials research agenda by focusing on important clinical questions in each subspecialty and to debate the major important method ological , cultural , and practical barriers to performing more r and omized clinical trials in orthopaedics . We defined barriers as any challenge that makes a r and omized clinical trial difficult to design or perform . We plan to report the deliberations of the Clinical Trials in Orthopaedics Research Symposium in three publications . The purpose of this first article is to present the cultural and practical barriers and to highlight the key infrastructure needed to support performing r and omized trials in orthopaedics . We largely focused on r and omized clinical trials but realized that method ologically sound prospect i ve cohort studies also provide important information1 . Our deliberations were clearly not exhaustive , and readers can refer to texts for basic information about r and omized clinical trials not addressed during the symposium2 . We have included the names of symposium speakers in parentheses after the title for each section . R and omized clinical trials have been infrequently performed in surgery3 . We use the term culture in this article to reflect how orthopaedic surgeons resolve clinical questions , respond to clinical controversies , express their participation enthusiasm , and respond to the results of r and omized clinical trials . Culture is one potential explanation for the paucity of trials in orthopaedics and may be a barrier to more trials . Each surgical procedure provides challenges that require ingenuity and often require deviations |
12,763 | 27,814,758 | Conclusion Overall , the risk of developing MPCs appears to have increased since the 1980s when considering studies of all primary cancer sites combined from the USA and Australia but not from Europe . | Background Cancer survivors are at risk of developing second and subsequent primary cancers , referred to as multiple primary cancers ( MPCs ) .
It is not clear whether the risk of MPCs has increased over recent decades , but increasing use of radiological imaging and potentially harmful effects of certain cancer treatments raise this possibility .
A systematic review was undertaken to assess whether there has been a temporal change in the risk of developing MPCs . | The introduction of new treatments for esophageal cancer including surgery , chemotherapy , radiotherapy , or a combination of these modalities has not only improved patient survival , but may also increase the risk of the second primary cancers . The available evidence is conflicting with most risk estimates based on sparse numbers . Here we estimated st and ardized incidence ratios ( SIRs ) of second cancer among 24,557 esophageal cancer survivors ( at least 2 months ) in the Surveillance , Epidemiology , and End Results ( SEER ) Program between 1973 and 2007 , who had been followed up for median 6.5 years ( range 2 months-29.3 years ) . Second cancer risk was statistically significantly elevated ( SIR = 1.34 , 95 % confidence interval [CI]= 1.25 - 1.42 ) among the survivors compared with the general population ; the SIRs for cancers of oral and pharynx , stomach , small intestine , larynx , lung and bronchus , thyroid and prostate cancer were 8.64 ( 95 % CI = 7.36 - 10.07 ) , 2.87 ( 95 % CI = 2.10 - 3.82 ) , 3.80 ( 95 % CI = 1.82 - 7.00 ) , 3.19 ( 95 % CI = 2.12 - 4.61 ) , 1.68 ( 95 % CI = 1.46 - 1.93 ) , 2.50 ( 95 % CI = 1.25 - 4.47 ) , and 0.77 ( 95 % CI = 0.65 - 0.90 ) , respectively . Radiotherapy raised cancer risk of larynx ( SIR = 3.98 , 95 % CI = 2.43 - 6.14 ) and thyroid ( SIR = 3.57 , 95 % CI = 1.54 - 7.03 ) among all esophageal cancer survivors . For patients who had 5 - 9 years of follow up after radiotherapy , the SIR for lung cancer was 3.46 ( 95 % CI = 2.41 - 4.82 ) . Patients with esophageal cancer are at increased risks of second cancers of oral and pharynx , larynx , lung , and thyroid , while at a decreased risk for prostate cancer . These findings indicate that radiotherapy for esophageal cancer patients may increase risk of developing second cancers of larynx , lung , and thyroid . Thus , r and omized clinical trials to address the association of radiotherapy and the risk of secondary cancer are warranted We studied the risk of the development of acute myeloid leukemia ( AML ) during initial remission in 733 consecutive children with acute lymphoid leukemia ( ALL ) who were treated with intensive chemotherapy . This complication was identified according to st and ard morphologic and cytochemical criteria in 13 patients 1.2 to 6 years ( median , 3.0 ) after the diagnosis of ALL . At three years of follow-up , the cumulative risk of secondary AML during the first bone marrow remission was 1.6 percent ( 95 percent confidence limits , 0.7 and 3.5 percent ) ; at six years , it was 4.7 percent ( 2 and 10 percent ) . The development of secondary AML was much more likely among patients with a T-cell than a non-T-cell immunophenotype ( cumulative risk , 19.1 percent [ 6 and 47 percent ] at six years ) . Sequential cytogenetic studies in 10 patients revealed entirely different karyotypes in 9 , suggesting the induction of a second neoplasm . In eight of these patients , the blast cells had abnormalities of the 11q23 chromosomal region , which has been associated with malignant transformation of a pluripotential stem cell . There was no evidence of loss of DNA from chromosome 5 or 7 , a karyotypic change commonly observed in cases of AML secondary to treatment with alkylating agents , irradiation , or both . We conclude that there is a substantial risk of AML in patients who receive intensive treatment for ALL , especially in those with a T-cell immunophenotype , and that 11q23 chromosomal abnormalities may be important in the pathogenesis of this complication IMPORTANCE Screening for lung cancer has the potential to reduce mortality , but in addition to detecting aggressive tumors , screening will also detect indolent tumors that otherwise may not cause clinical symptoms . These overdiagnosis cases represent an important potential harm of screening because they incur additional cost , anxiety , and morbidity associated with cancer treatment . OBJECTIVE To estimate overdiagnosis in the National Lung Screening Trial ( NLST ) . DESIGN , SETTING , AND PARTICIPANTS We used data from the NLST , a r and omized trial comparing screening using low-dose computed tomography ( LDCT ) vs chest radiography ( CXR ) among 53 452 persons at high risk for lung cancer observed for 6.4 years , to estimate the excess number of lung cancers in the LDCT arm of the NLST compared with the CXR arm . MAIN OUTCOMES AND MEASURES We calculated 2 measures of overdiagnosis : the probability that a lung cancer detected by screening with LDCT is an overdiagnosis ( PS ) , defined as the excess lung cancers detected by LDCT divided by all lung cancers detected by screening in the LDCT arm ; and the number of cases that were considered overdiagnosis relative to the number of persons needed to screen to prevent 1 death from lung cancer . RESULTS During follow-up , 1089 lung cancers were reported in the LDCT arm and 969 in the CXR arm of the NLST . The probability is 18.5 % ( 95 % CI , 5.4%-30.6 % ) that any lung cancer detected by screening with LDCT was an overdiagnosis , 22.5 % ( 95 % CI , 9.7%-34.3 % ) that a non-small cell lung cancer detected by LDCT was an overdiagnosis , and 78.9 % ( 95 % CI , 62.2%-93.5 % ) that a bronchioalveolar lung cancer detected by LDCT was an overdiagnosis . The number of cases of overdiagnosis found among the 320 participants who would need to be screened in the NLST to prevent 1 death from lung cancer was 1.38 . CONCLUSIONS AND RELEVANCE More than 18 % of all lung cancers detected by LDCT in the NLST seem to be indolent , and overdiagnosis should be considered when describing the risks of LDCT screening for lung cancer |
12,764 | 23,056,824 | Meta-regression analysis showed that the diagnostic accuracy of IL-6 was not affected by confounding variables .
IL-6 seems to be a valid marker for predicting NS . | OBJECTIVE Neonatal sepsis ( NS ) is a common and life-threatening disorder in infants .
Previous studies showed that interleukin-6 ( IL-6 ) may be a valid non-invasive and rapid method for diagnosis of NS .
We conducted this review to assess the validity of IL-6 for predicting NS . | ABSTRACT No data on lipopolysaccharide-binding protein ( LBP ) in newborns with sepsis have been available up to now . We therefore determined levels of LBP and soluble CD14 ( sCD14 ) in plasma of healthy and septic neonates in order to evaluate their potential diagnostic role . The study included prospect ively collected patient sample s of two recently published studies on cytokine expression in neonatal sepsis . Twenty-nine septic patients were enrolled in the present analysis . Sample s — either cord blood or peripheral blood — from patients admitted within the first 24 h of life for suspicion of sepsis and cord blood sample s of a control group of 40 healthy mature infants delivered spontaneously were analyzed . For seven patients of the septic group , a second sample collected between 24 and 48 h of life was available . Levels of sCD14 and LBP in plasma were determined by an enzyme immunoassay using recombinant CD14 and LBP as st and ards . LBP and sCD14 were correlated to cytokine plasma levels . In septic neonates , LBP ( median , 36.6 versus 7.8 μg/ml ; P < 0.001 ) and sCD14 ( median , 0.42 versus 0.28 μg/ml ; P < 0.001 ) levels were highly elevated when compared to those of healthy neonates and strongly correlated to granulocyte colony-stimulating factor ( G-CSF ) , interleukin-1β ( IL-1β ) , IL-6 , and IL-8 levels . LBP levels in septic neonates analyzed between 24 and 48 h of life even increased when compared to sample s obtained at or shortly after delivery ( median , 36.6 versus 60 μg/ml ; P = 0.038 ) . In summary , levels of LBP in plasma of neonates with early-onset sepsis are significantly elevated ; the elevated plasma levels seem to persist for more than 24 h , which could provide the clinician with a prolonged time period to identify the newborn with bacterial sepsis In a prospect i ve study , levels of interleukin-1 beta ( IL-1 beta ) , interleukin-6 ) ( IL-6 ) , and tumor necrosis factor ( TNF ) were measured in a blind fashion in cord blood plasma from 92 neonates by specific immunoassays , and were correlated with the clinical courses of the infants , including type of delivery and perinatal complications . Plasma IL-1 beta concentration was undetectable in infants born by normal vaginal delivery or elective cesarean section but was significantly increased in infants born after induced vaginal deliveries ( 142 + /- 68 pg/ml ) or urgent cesarean section ( 290 + /- 21 pg/ml ; both p less than 0.05 compared with normal deliveries ) . The IL-1 beta levels were elevated in infants with severe perinatal complications ( 282 + /- 116 pg/ml ; p less than 0.001 ) , whereas TNF and IL-6 levels were not related to these complications . Infants with isolated perinatal infectious complications had elevated levels of plasma IL-6 compared with those of sick neonates without infection ( p less than 0.001 ) . In contrast , TNF plasma levels and IL-1 beta production by cord blood leukocytes were decreased in infants with infectious complications alone ( both p less than 0.05 ) . These studies suggest that the levels of IL-1 beta , IL-6 , and TNF in the cord plasma relate differentially to clinical complications in the perinatal period The first objective of this article was to determine the diagnostic accuracy of tumor necrosis factor-alpha , interleukin-6 ( IL-6 ) , and interleukin-8 ( IL-8 ) in differentiating infected from noninfected neonates during the first 24 hours of suspected sepsis and to compare them to the currently used laboratory parameters : C-reactive protein ( CRP ) , immature-to-total neutrophil ratio , and leukocyte and platelet count . The secondary objective was to compare the cytokine levels in sub population s of neonates . Seventy-five premature and 30 term infants were enrolled . Blood sample s for the " currently used laboratory tests " and the cytokine levels were obtained at the first suspicion of sepsis ( " 0-hour " ) and 18 to 30 hours later ( " 24-hours " ) . Patients were classified as septic ( 48 ) or nonseptic ( 57 ) . Thirty-two septic patients had positive blood cultures and 16 showed clinical signs of sepsis . Twenty septic patients had early-onset and 28 had late-onset sepsis . Sensitivity , specificity , and positive and negative predictive values ( PPV and NPV ) were calculated for each test . Receiver-operating characteristic curves were analyzed to determine the optimal thresholds . A combination of CRP > 10 pg/mL plus IL-6 > 18 pg/mL ( sensitivity = 89 % , specificity = 73 % , PPV = 70 % , NPV = 90 % ) was the best " 0-hour " test , and CRP ( sensitivity = 78 % , specificity = 94 % ) was the best " 24-hours " test . Lower IL-6 at 0-hour ( p = 0.018 ) and IL-8 at 24 hours ( p = 0.023 ) were detected among the patients infected with coagulase-negative staphylococci then with other bacteria . In conclusion , a combination of CRP + IL-6 provided additional diagnostic accuracy for differentiation between septic and nonseptic patients during the first 24 hours of suspected sepsis BACKGROUND Neonatal sepsis is a common and life-threatening disorder , particularly among preterm infants . Early initiation of antibiotic therapy is frequently delayed because the first clinical signs of sepsis are non-specific and there are no reliable early laboratory indicators . We investigated the time course of expression and the prognostic power of the early inflammatory mediators interleukin-1 receptor antagonist ( IL-1ra ) , interleukin-6 ( IL-6 ) , and circulating intercellular adhesion molecule-1 ( cICAM-1 ) before clinical diagnosis of sepsis . METHODS In a prospect i ve multicentre study , we monitored 182 very-low-birthweight infants in six intensive-care units for occurrence of sepsis . During routine or clinical ly indicated blood sampling , an additional sample was collected for measurement of IL-1ra , IL-6 , cICAM-1 , and C-reactive protein ( CRP ) . Infants were grouped into those with proven sepsis , no infection , or unclassified . The mean study duration was 34 days . Whenever sepsis occurred , a study period of 10 days was defined : day 0 was the day of clinical diagnosis of sepsis ; days -4 to -1 were the 4 days before diagnosis ; days + 1 to + 5 were the 5 days after . We compared the concentrations of the immune mediators during the 10-day study period with group-specific baseline values from before day -4 . FINDINGS 101 infants were included in the analysis : 21 with proven sepsis , 20 with no infection , and 60 unclassified . We excluded 57 because of incomplete data sets and 24 who had early-onset sepsis . IL-1ra and IL-6 increased significantly 2 days before diagnosis of sepsis ; maximum median increases within the study period were 15-fold for IL-1ra and 12-fold for IL-6 . The diagnostic sensitivities of IL-1ra , IL-6 , and CRP concentrations on day 0 of diagnosis were 93 % , 86 % , and 43 % , respectively ; corresponding values on day -1 were 64 % , 57 % , and 18 % . The specificities of IL-1ra , IL-6 , and CRP concentrations were 92 % , 83 % , and 93 % . cICAM-1 had a specificity of only 64 % . INTERPRETATION IL-1ra and IL-6 are superior to cICAM-1 and CRP as predictors of sepsis 1 or more days before clinical diagnosis . Ad-hoc measurement of these cytokines could allow earlier initiation of antibiotic therapy with corresponding improvement in outcome in very-low-birthweight infants with sepsis OBJECTIVE To evaluate plasma levels of interleukin-6 ( IL-6 ) and soluble tumor necrosis factor receptors ( sTNF-R ) 55 and 75 in neonates as a contribution to the early diagnosis of infection . STUDY DESIGN We prospect ively measured IL-6 and sTNF-R 55 and sTNF-R 75 plasma levels in 157 newborn infants admitted to our regional neonatal center in a 3-month period and in cord blood of 131 newborn infants delivered in our obstetrics unit . C-reactive protein was sequentially determined after admission . Newborn infants were classified into four groups : group 0 , not infected ; group 1 , possibly infected ; group 2a , infected ( culture positive ) , and group 2b , probably infected ( culture negative ) . We looked for the optimal cutoff point of these parameters , using the receiver operating characteristics ( ROC ) curve . RESULTS IL-6 levels were significantly higher in group 2 ( n = 11 ; median level , 250 pg/ml ; range , 0 to 81,000 ) , group 2b ( n = 25 ; median level , 750 pg/ml ; range , 0 to 180,000 ) , and group 1 ( n = 35 ; median level , 160 pg/ml ; range 0 to 10,000 ) , in comparison with group 0 ( n = 217 ; median level , 0 pg/ml ; range , 0 to 3400 ) . A cutoff value of 100 pg/ml or greater obtained by the ROC method gives a sensitivity of 83.3 % and a specificity of 90.3 % . For inborn infants ( n = 220 ) sample d at birth , sensitivity is 100 % and specificity 92.3 % . This high sensitivity persists until the twelfth hour of life . The sTNF-R 55 levels are significantly higher in group 2a ( median , 12.0 ng/ml ; range , 3.2 to 24.4 ) . In group 2b ( median , 7.0 ng/ml ; range , 3.0 to 25.2 ) , and in group 1 ( median , 7.0 ng/ml ; range , 2.5 to 18.9 ) than in group 0 ( median , 3.9 ng/ml ; range , 1.5 to 15.0 ) , and with a cutoff value of 6 ng/ml , sensitivity is 75 % and specificity 69 % . The sTNF-R 75 levels are significantly higher in group 2a ( median , 17.0 ng/ml ; range , 7.2 to 48.8 ) . In group 2b ( median , 11.2 ng/ ml ; range , ( 2.0 to 31.3 ) , and in group 1 ( median , 10.6 ng/ml ; range , 2.0 to 33.0 ) ; than in group 0 ( median , 7.0 ng/ml ; range , 1 to 23.0 ) . With a cutoff value of 9 ng/ ml , sensitivity is 80 % and specificity 67 % . Sensitivity of C-reactive protein is low initially but improves with time . Combining IL-6 with C-reactive protein provides the possibility of identifying the majority of infected infants in the postnatal period . CONCLUSION A plasma IL-6 level of 100 pg/ml or greater , obtained before the twelfth hour of life , appears to be an ideal marker for detecting early-onset neonatal infection with a high degree of sensitivity and specificity . After the twelfth hour , the combined determination of IL-6 and C-reactive protein may be equally useful . The sTNF-R levels appear to be less useful in the early diagnosis of infection because of their smaller magnitude of variation Objective Late-onset sepsis is responsible for high morbidity and mortality in newborn infants in the world and in particular in developing countries . In this study , we evaluated whether clinical characteristics , laboratory parameters and measurements of serum interleukin-8 ( IL-8 ) are able to discriminate between late neonatal sepsis and normal baby . Methods This was a prospect i ve ( case-control ) study conducted between March 2007 and April 2008 , at the neonatal intensive care unit , Ghaem Hospital , Mashhad , Iran . The study comprised 93 neonates ≥72 hours of life . The infants were categorized in two groups based on the clinical presentation , and biochemical markers including complete blood count , C-reactive protein ( CRP ) and blood culture : 1 ) Control group including 42 infants with routine screening and 2 ) Case group consisting of 38 infants with definitive infection ( positive blood and /or cerebrospinal fluid culture ) or clinical sepsis ( clinical and laboratory signs of infection without positive blood or CSF culture ) . Receiver-operating characteristic curves were used for the determination of thresholds for the infection group versus healthy neonate group . Findings Eighty infants were enrolled in this study . IL-8 and CRP decreased in order of definitive infection , clinical sepsis and healthy subjects respectively ( P<0.001 ) . Sensitivity , specificity , positive predictive value , negative predictive value for serum levels were 0.95 , 0.1 , 0.97 , 0.1 for IL-8 and 0.83 , 0.86 , 0.83 , 0.69 for CRP respectively ( cut-off point for IL-8 > 60pg/ml and for CRP>6mg/dl ) . Conclusion IL-8 may be a valid and early predictive marker of neonatal infection . Also , IL-8 is associated with severity of infection AIMS To evaluate the commonly used markers — namely IL-6 , TNFα , IL-1β , C-reactive protein and E-selectin for identification of late onset neonatal sepsis ; to define the optimal cutoff value for each marker in preterm neonates ; to assess whether these markers could assist in early discontinuation of antibiotics in non-infected cases ; and to delineate the profile of these markers during systemic infection and in relation to successful treatment . METHODS Very low birthweight infants in whom clinical sepsis was suspected when they were > 72 hours of age were eligible for study . A full sepsis screen was performed in each episode . Cytokines , C-reactive protein , and E-selectin were serially measured on days 0 ( at the time of sepsis evaluation ) , 1 , 2 , 4 and 7 . The optimal cutoff value for each marker was calculated after minimising the number of misclassified episodes over all possible cutoff values for days 0 and 1 . The sensitivity , specificity , positive and negative predictive values for each test and combination of tests for predicting systemic infection were also determined . RESULTS One hundred and one episodes of suspected clinical sepsis were investigated in 68 infants . Forty five episodes were proved to be infections . The optimal cutoff values were IL-6 31 pg/ml , TNFα 17 pg/ml , IL-1β 1 pg/ml , C reactive protein 12 mg/l and E-selectin 174 ng/ml . IL-6 had the highest sensitivity ( 89 % ) and negative predictive value ( 91 % ) for detecting late onset infection on day 0 . However , between 24 and 48 hours of onset , C-reactive protein was the best single marker , with an overall sensitivity and specificity of 84 % and 96 % , respectively . The use of serial and multiple markers in the first 48 hours further enhanced the sensitivity and specificity of these tests . Performing IL-6 and C-reactive protein on day 0 , together with either TNFα on day 1 or C-reactive protein on day 2 , showed the best overall sensitivity ( 98 % ) and specificity ( 91 % ) for the diagnosis of late onset infection . CONCLUSIONS Optimal cutoff values for these markers in detecting late onset systemic infection in very low birthweight infants have been defined . Withholding antibiotic treatment at the onset of infection could be fatal and is not recommended , but the concomitant use of IL-6 and C-reactive protein or TNFα should allow antimicrobial treatment to be discontinued at 48 hours without waiting for microbiological results , provided that the infants are in good clinical condition Aim : To investigate whether cord blood levels of C‐reactive protein , interleukin‐1β , interleukin‐6 , interleukin‐8 , tumour necrosis factor‐α and the soluble receptor of interleukin‐2 , are useful markers in the diagnosis of early neonatal sepsis . Design : Umbilical cord blood sample s were obtained at birth from 261 neonates , but 5 of these newborns were excluded from the study . Group I included 10 newborns that developed early neonatal sepsis with a positive blood culture ; Group II included 11 newborns with non‐infectious perinatal diseases ; Group III , which served as the control group , included 10 r and omly selected patients , matched for gestational age , among the 235 healthy newborn babies . Results : There were no differences among the three study groups in levels of C‐reactive protein , interleukin‐1 β , tumour necrosis factor‐α and the soluble receptor of interleukin‐2 . Interleukin‐6 was significantly elevated in Group I ( 360.4 ± 157.8 pg/ml ) and Group II ( 158.8 ± 122.3 pg/ml ) , when compared with Group III ( 8.6 ± 3.12 pg/ml ) ( p < 0.01 ) , whereas interleukin‐8 was significantly elevated in Group I ( 389.3 ± 115.9 pg/ml ) compared with Groups II ( 30.2 ± 5.1 pg/ml ) ( p < 0.05 ) and III ( 33.9 ± 8.6 pg/ml ) ( p < 0.05 ) . A cut‐off of 100.8 pg/ml for interleukin‐6 obtained by the ROC ( receiver operating characteristic ) method gave a sensitivity of 50 % and a specificity of 87 % , and a cut‐off of 111.7 pg/ml for interleukin‐8 showed a sensitivity of 78 % and a specificity of 91 % Background : Cytokine plasma levels are suggested to be sensitive indicators of neonatal sepsis , but conventional assays are time consuming . This study aim ed at evaluating the significance of cord blood levels of interleukin (IL)-6 and IL-8 determined by a fully automated r and om access assay within 90 min of admission to predict systemic bacterial infection . Patients and Methods : Cord blood levels of IL-6 and IL-8 were determined in 71 mature and 100 premature infants by a chemiluminescence assay ( Immulite ® ) . Patients were divided into four groups according to a clinical and laboratory scoring system . Group A : documented early-onset infection ; group B : infection possible ; group C : infection unlikely , and group D : healthy newborns . Results : Median IL-6 levels in the subgroup of premature newborns were as follows : group A , 1,920 pg/ml ( 5–95 % confidence interval 308–4,660 pg/ml ) ; group B , 50 ( 15–102 ) pg/ml ; group C , 21 ( 12–71 ) pg/ml , and group D , 8 ( 6–11 ) pg/ml . For IL-8 , median levels for groups A – D were 289 ( 226–514 ) pg/ml , 87 ( 40–107 ) pg/ml , 44 ( 33–98 ) pg/ml and 21 ( 16–25 ) pg/ml , respectively . The difference between group A and the other groups was highly significant ( IL-6 p < 0.0001 , IL-8 p < 0.001 ) . At a cut-off of 80 pg/ml , the sensitivity of IL-6 for the diagnosis of sepsis was 96 % ( specificity 95 % ) . For IL-8 ( cut-off 90 pg/ml ) , the sensitivity was 87 % ( specificity 94 % ) . Conclusion : In premature infants , the diagnosis of an early-onset infection can be established or ruled out with a high level of confidence by measuring IL-6 or IL-8 levels from cord blood using a r and om access chemiluminescence assay Abstract Background : Late-onset sepsis in the NICU is a major problem associated with high morbidity and mortality . Objective : To determine if clinical characteristics , hematological parameters and serial measurements of serum IL-6 and IL-8 can detect late-onset sepsis in premature neonates prior to positive blood cultures . Design : The study was done in 2 phases . The first phase ( S1 ) was a retrospective evaluation of clinical signs and timing of blood culture positivity in all neonates with late-onset culture proven sepsis from 1991–1998 . The second phase ( S2 ) was a prospect i ve study that enrolled infants ≥72 hours old , suspected of sepsis based on the presence of criteria identified in S1 . At that time ( day 0 ) , blood was drawn for a CBC with differential , blood culture , IL-6 and IL-8 levels ; cytokine levels were repeated on day 1 . Infants with positive cultures were diagnosed as confirmed sepsis ; those with negative cultures , as no sepsis . Results : S1 : Of the 48 episodes of culture proven , late-onset sepsis , 54 % of the blood cultures were positive by 24 hours and 90 % by 48 hours . The most common presenting signs were desaturations ( 50 % ) and increased gastric residuals ( 33 % ) ; I/T ratio > 0.16 differentiated between gram-positive , negative and fungal infections ( p = 0.007 ) . S2 : 27 infants were enrolled . Eight ( mean [ SEM ] gestational age of 28.2 [ 0.94 ] weeks ; birth weight of 1.15 [ 0.11 ] kg ) had positive blood cultures ; 19 ( gestational age of 27.7 [ 0.9 ] weeks ; birth weight of 1.06 [ 0.13 ] kg ) had no sepsis . Infants with sepsis were more likely to have apnea/bradycardia ( p = 0.002 ) ; no differences in hematological profile , as compared to those with no sepsis . Seven ( 88 % ) infants had positive blood cultures by 48 hours . Median values of IL-6 ( pg/ml ) were higher in infants with sepsis vs. those with no sepsis on days 0 [ 40 vs.13 ] ( p = 0.03 ) and 1 [ 24 vs. 9 ] ( p < 0.001 ) . IL-8 levels were not significantly different . Conclusions . In both S1 and S2 , a majority of the blood cultures were positive by 48 hours . IL-6 levels on days 0 and 1 were significantly higher in infants with confirmed sepsis , prior to the blood culture being positive . IL-6 levels may be useful in the initiation as well as early termination of antibiotic therapy in late-onset neonatal sepsis The aim of this study was to examine if TNFα and IL‐6 plasma levels could be of value in diagnosing neonatal sepsis . Tumor necrosis factor α ( TNFα ) and interleukin‐6 ( IL‐6 ) plasma levels were determined in 15 newborn infants with confirmed sepsis ( group I ) , 18 with suspected sepsis ( group II ) and 22 control infants ( group III ) . In 33 newborns , initially suspected of having sepsis ( groups I and 11 ) , a positive test result for plasma concentration of TNFα ( > 70 pg/ml ) had a sensitivity of 73 % and a specificity of 94 % . A positive test result for IL‐6 ( > 500 pg/ml ) had a sensitivity of 80 % and a specificity of 78 % . When plasma levels of TNFα and IL‐6 were combined for the diagnosis of neonatal sepsis , a positive test result for both tests had a sensitivity of 60 % and a specificity of 100 % . When both tests are positive the diagnosis of neonatal sepsis is almost certain ( likelihood ratio = α . The combination of TNFα and IL‐6 determinations appears to be a good predictor of neonatal sepsis OBJECTIVE Early recognition is important for the successful treatment and outcome of neonatal infections . As interleukin-6 ( Il-6 ) plays a critical role in the induction of C-reactive protein ( CRP ) synthesis in the liver , it was hypothesized that this cytokine could be detected earlier in blood than the CRP during the course of bacterial infection . DESIGN In a prospect i ve study of 298 newborns who were admitted to the nursery unit , CRP levels , blood cell count with differential , and Il-6 levels were determined at the time of admission and 24 hours after admission . Seventy-six newborns were excluded from the study because of incomplete or incorrect blood sampling . RESULTS The remaining 222 newborns were assigned to one of five groups : 11 newborns with blood culture-positive sepsis ( sensitivity of Il-6 on admission 73 % ) , 15 newborns with clinical sepsis ( sensitivity of Il-6 on admission 87 % ) , 41 newborns with infection ( sensitivity of Il-6 on admission 68 % ) , and 54 newborns without clinical and laboratory evidence of infection ( specificity 78 % ) . The remaining 101 newborns were defined as a mixed group because the diagnosis of neonatal infection could not clearly be made . Seventy-five percent of infected newborns had negative Il-6 levels 24 hours after admission . Of the 18 infected newborns with negative Il-6 levels on admission , 10 newborns had elevated CRP levels , suggesting that Il-6 was already negative because of the short half-life of Il-6 . Sensitivity of Il-6 in CRP-negative newborns on admission was 100 % in newborns with blood culture-positive and clinical sepsis . Il-6 was more sensitive than CRP in infected newborns on admission ( 73 % vs 58 % ) . CONCLUSION Il-6 is a sensitive parameter for diagnosing neonatal bacterial infection . The combination of CRP and Il-6 seems to be the ideal tool for the early diagnosis of neonatal infection |
12,765 | 23,106,962 | Re source availability positively correlated with mean hospital CBCA scores and maternal and perinatal mortality were inversely correlated with hospital CBCA scores .
Conclusion Our CBCA has substantial inter-rater reliability and there is compelling evidence of its validity as the tool performs according to theory . | Background In Mali and Senegal , over 1 % of women die giving birth in hospital .
At some hospitals , over a third of infants are stillborn .
Many deaths are due to subst and ard medical practice s. Criterion-based clinical audits ( CBCA ) are increasingly used to measure and improve obstetrical care in re source -limited setting s , but their measurement properties have not been formally evaluated .
In 2011 , we published a systematic review of obstetrical CBCA highlighting insufficient considerations of validity and reliability .
The objective of this study is to develop an obstetrical CBCA adapted to the West African context and assess its reliability and validity .
This work was conducted as a sub- study within a cluster r and omized trial known as QUARITE . | Background Maternal and perinatal mortality are major problems for which progress in sub-Saharan Africa has been inadequate , even though childbirth services are available , even in the poorest countries . Reducing them is the aim of two of the main Millennium Development Goals . Many initiatives have been undertaken to remedy this situation , such as the Advances in Labour and Risk Management ( ALARM ) International Program , whose purpose is to improve the quality of obstetric services in low-income countries . However , few interventions have been evaluated , in this context , using rigorous methods for analyzing effectiveness in terms of health outcomes . The objective of this trial is to evaluate the effectiveness of the ALARM International Program ( AIP ) in reducing maternal mortality in referral hospitals in Senegal and Mali . Secondary goals include evaluation of the relationships between effectiveness and re source availability , service organization , medical practice s , and satisfaction among health personnel . Methods / Design This is an international , multi-centre , controlled cluster-r and omized trial of a complex intervention . The intervention is based on the concept of evidence -based practice and on a combination of two approaches aim ed at improving the performance of health personnel : 1 ) Educational outreach visits ; and 2 ) the implementation of facility-based maternal death review s . The unit of intervention is the public health facility equipped with a functional operating room . On the basis of consent provided by hospital authorities , 46 centres out of 49 eligible were selected in Mali and Senegal . Using r and omization stratified by country and by level of care , 23 centres will be allocated to the intervention group and 23 to the control group . The intervention will last two years . It will be preceded by a pre-intervention one-year period for baseline data collection . A continuous clinical data collection system has been set up in all participating centres . This , along with the inventory of re sources and the satisfaction surveys administered to the health personnel , will allow us to measure results before , during , and after the intervention . The overall rate of maternal mortality measured in hospitals during the post-intervention period ( Year 4 ) is the primary outcome . The evaluation will also include cost-effectiveness . Trial Registration The QUARITE trial is registered on the Current Controlled Trials website under the number IS RCT N46950658 Accurate , affordable , and valid measurements of clinical practice are the basis for quality -of-care assessment s ( 1 ) . However , to date , most measurement tools have relied on incomplete data sources , such as medical records or administrative data ; require highly trained and expensive personnel to implement ; and are difficult to vali date ( 2 - 5 ) . Comparisons of clinical practice across different sites and health care systems are also difficult because they require relatively complex instrument design s or statistical techniques to adjust for variations in case mix among the underlying patient population s ( 6 , 7 ) . We have developed a measurement tool , computerized clinical vignettes , that overcomes these limitations and measures physicians ' clinical practice against a predefined set of explicit quality criteria . These vignettes simulate patient visits and can be given to physicians to measure their ability to evaluate , diagnose , and treat specific medical conditions . Each vignette-simulated case contains realistic clinical detail , allowing an identical clinical scenario to be presented to many physicians . Each physician can be asked to complete several vignettes to simulate diverse clinical conditions . This instrument design obviates the need to adjust quality scores for the variation in disease severity and comorbid conditions found in actual patient population s. Our vignettes are also distinct from other quality measurements of clinical practice because they do not focus on a single task , or even a limited set of tasks , but instead comprehensively evaluate the range of skills needed to care for a patient . Vignettes are particularly well-suited for quality assessment s of clinical practice that are used for large-scale ( 8 , 9 ) , cross-system comparisons ( 10 , 11 ) or for cases in which ethical issues preclude involving patients or their records ( 7 , 12 , 13 ) . They are also ideal for evaluations that require holding patient variation constant ( 14 , 15 ) or manipulating patient-level variables ( 15 - 17 ) . The appeal of vignettes has result ed in their extensive use in medical school education ( 18 , 19 ) , as well as various studies that explicitly evaluate the quality of clinical practice in real-life setting s and comparative analysis among national health care systems ( 10 , 20 - 23 ) . Before vignette-measured quality can be used confidently in these setting s , however , 2 important questions must be answered : How valid are vignettes as a measure of actual clinical practice ? Can vignettes discriminate among variations in the quality of clinical practice ? This has led to a search to define a gold st and ard for validation ( 24 - 26 ) . We and others have used st and ardized patients as this st and ard . St and ardized patients are trained actors who present unannounced to outpatient clinics as patients with a given clinical condition . Immediately after meeting with a physician , the st and ardized patient records on a checklist what the physician did during the visit ( 26 - 28 ) . Rigorous methods , which we have described in detail elsewhere ( 29 ) , ensure that st and ardized patients can be considered a gold st and ard . In addition , we have demonstrated the validity of st and ardized patients as a gold st and ard by concealing audio recorders on st and ardized patients during visits . The overall rate of agreement between the st and ardized patients ' checklists and the independent assessment of the audio transcripts was 91 % ( 26 ) . We previously used paper- and -pen vignettes in a study limited to only 1 health care system , the Veterans Administration , and found that they seemed to be a valid measure of the quality of clinical practice according to their rate of agreement with st and ardized patient checklists ( 26 ) . For this study , we wanted to confirm the validity of vignettes by using a more complex study design that introduced many more r and omly assigned physicians , a broader range of clinical cases , and several sites representing different health care systems . We also wanted to test a refined , computerized version of vignettes , which we believe are more realistic and streamline data collection and scoring . We were particularly interested in determining whether the vignettes accurately capture variation in the quality of clinical practice , which has become increasingly prominent in the national debate on quality of care ( 30 , 31 ) . We hoped that vignettes could contribute to this debate by providing a low-cost measure of variation across different health care systems . Methods Sites The study was conducted in 4 general internal medicine clinics : 2 Veterans Affairs ( VA ) medical centers and 2 large , private medical centers . One private site is a closed group model , and the other , primarily staffed by employed physicians , contracts with managed care plans . All sites are located in California , and each has an internal medicine residency training program . One VA medical center and 1 private site are located in 1 of 2 cities . The 2 VA medical centers are large , academically affiliated hospitals with large primary care general internal medicine practice s. We chose the 2 private sites that were generally similar to the VA medical centers and to each other ; each had large primary care practice s and capitated reimbursement systems that provide primary care general internists with a broad scope of clinical decision-making authority . Study Design At each site , all attending physicians and second- and third-year residents who were actively engaged in the care of general internal medicine out patients were eligible to participate in the study . We excluded only interns . Of 163 eligible physicians , 144 agreed to participate . We informed consenting physicians that 6 to 10 st and ardized patients might be introduced unannounced into their clinics over the course of a year and that they might be asked to complete an equal number of vignettes . Sixty physicians were r and omly selected to see st and ardized patients : 5 physicians from each of the 3 training levels at each of the 4 sites ( Figure 1 ) . We assigned st and ardized patients to each selected physician for 8 clinical casessimple and complex cases of chronic obstructive pulmonary disease , diabetes , vascular disease , and depression . We abstract ed the medical records from the 480 st and ardized patient visits . Each selected physician also completed a computerized clinical vignette for each of the 8 cases . For st and ardized patient visits that a selected physician did not complete , a replacement physician , who was r and omly selected from the same training level at the same site , completed the visit . Eleven physicians required replacements . The 11 replacement physicians completed 24 st and ardized patient visits . Each replacement physician completed vignettes for all 8 cases . Finally , we r and omly selected 45 additional physicians to serve as controls and complete vignettes ( only ) for all 8 cases . A total of 116 physicians participated in the study by seeing st and ardized patients , completing vignettes , or both . St and ardized patients presented to the clinics between March and July 2000 , and physicians completed vignettes between May and August 2000 . Figure 1 . Planned study design showing sites and physician sample by level of training and clinical case for the 3 quality measurement methods . Vignette Data Collection We developed the vignettes by using a st and ardized protocol . We first selected relatively common medical conditions frequently seen by internists . All selected conditions had explicit , evidence -based quality criteria and accepted st and ards of practice that could be used to score the vignettes , as well as be measured by st and ardized patients and chart abstract ion . We developed written scenarios that described a typical patient with 1 of the same 4 diseases ( chronic obstructive pulmonary disease , diabetes , vascular disease , or depression ) . For each disease , we developed a simple ( uncomplicated ) case and a more complex case with a comorbid condition of either hypertension or hypercholesterolemia . This yielded a total of 8 clinical cases . ( A sample vignette and scoring sheet are available online . ) Supplement . Appendix Figure : Vignette scoring sheet . Published online with permission from John W. Peabody , MD , PhD The physician completing the vignette sees the patient on a computer . Each vignette is organized into 5 sections , or domains , which , when completed in sequential order , recreate the normal sequence of events in an actual patient visit : taking the patient 's history , performing the physical examination , ordering radiologic or laboratory tests , making a diagnosis , and administering a treatment plan . For example , the computerized vignette first states the presenting problem to the physician and prompts the physician to take the patient 's history ( that is , ask questions that would determine the history of the present illness ; past medical history , including prevention ; and social history ) . Physicians can record components of the history in any order without penalty . The entire format is open-ended : The physician enters the history questions directly into the computer and , in the most recent computerized versions , receives realtime responses . When the history is completed , the computer confirms that the physician has finished and then provides key responses typical of a patient with the specific case . The same process is repeated for the 4 remaining domains . In addition to the open-ended format , we have taken 3 steps to avoid potential inflation of vignette scores . First , physicians are not allowed to return to a previous domain and change their queries after they have seen the computerized response . Second , the number of queries is limited in the history and physical examination domains . For example , in the physical examination domain , physicians are asked to list only the 6 to 10 essential elements of the examination that they would perform . Third , they are given limited time to complete the vignette ( just as time is limited during an actual patient visit OBJECTIVE To determine whether clinical vignettes can measure variations in the quality of clinical care in two economically divergent countries . DATA SOURCE / STUDY SETTING Primary data collected between February 1997 and February 1998 at two Veterans Affairs facilities in the United States and four government-run outpatient facilities in Macedonia . STUDY DESIGN R and omly selected , eligible Macedonian and U.S. physicians ( > 97 percent participation rate ) completed vignettes for four common outpatient conditions . Responses were judged against a master list of explicit quality criteria and scored as percent correct . DATA COLLECTION / EXTRACTION : An ANOVA model and two-tailed t-tests were used to compare overall scores by case , study site , and country . Principal Findings . The mean score for U.S. physicians was 67 percent ( + /-11 percent ) compared to 48 percent ( + /-11 percent ) for Macedonian physicians . The quality of clinical practice , which emphasizes basic skills , varied greatly in both sites , but more so in Macedonia . However , the top Macedonian physicians in all sites approached or-in one case-exceeded the median score in the U.S. sites . CONCLUSIONS Vignettes are a useful method for making cross-national comparisons of the quality of care provided in very different setting s. The vignette measurements revealed that some physicians in Macedonia performed at a st and ard comparable to that of their counterparts in the United States , despite the disparity of the two health systems . We infer that in poorer countries , policy that promotes improvements in the quality of clinical practice -not just structural inputs-could lead to rapid improvements in health |
12,766 | 28,513,621 | In conclusion , lung cancer patients with a higher BMI have a longer survival than those with a lower BMI . | Studies examining the relation of body mass index ( BMI ) and mortality in patients with lung cancer have shown diverse results .
We conducted a meta- analysis to investigate the association using all available studies from January 1982 to October 2016 . | BACKGROUND / AIM We report on survival data of 595 patients with stage I-III lung cancer with respect to TNM classification . MATERIAL S AND METHODS We constructed a basic model consisting of stage and grade , and assessed the improvement of survival prediction after adding comorbidity data , spirometric data , clinical and laboratory parameters . RESULTS Body mass index ( BMI ) and presence of a cardiac disease reached statistical significance for prediction of overall survival in a Cox regression model . In addition to BMI ( < 25 kg/m(2 ) ) and the presence of cardiovascular disease , the spirometric variable ( FEV1 ) predicted early death ( less than five months postoperatively ) . When the survival r and om forest method was employed to predict disease outcome , creatinine levels and VO2 max became additional variables of interest for predicting survival . CONCLUSION We propose that our lung cancer data base may help to identify variables ( aside from histomorphological variables ) that are suitable for identifying patients at risk of death after surgical treatment of lung cancer Physical activity has been associated with lower lung cancer incidence and mortality in several population s. We investigated these relationships in the Women 's Health Initiative Observational Study ( WHI-OS ) and Clinical Trial ( WHI-CT ) prospect i ve cohort of postmenopausal women . The WHI study enrolled 161,808 women aged 50 - 79 years between 1993 and 1998 at 40 U.S. clinical centers ; 129,401 were eligible for these analyses . Cox proportional hazards models were used to assess the association of baseline physical activity levels [ metabolic equivalent (MET)-min/week : none < 100 ( reference ) , low 100 to < 500 , medium 500 to < 1,200 , high 1,200 + ] and sedentary behavior with total lung cancer incidence and mortality . Over 11.8 mean follow-up years , 2,148 incident lung cancer cases and 1,365 lung cancer deaths were identified . Compared with no activity , higher physical activity levels at study entry were associated with lower lung cancer incidence [ p = 0.009 ; hazard ratios ( 95 % confidence intervals ) for each physical activity category : low , HR : 0.86 ( 0.76 - 0.96 ) ; medium , HR : 0.82 ( 0.73 - 0.93 ) ; and high , HR : 0.90 ( 0.79 - 1.03 ) ] , and mortality [ p < 0.0001 ; low , HR : 0.80 ( 0.69 - 0.92 ) ; medium , HR : 0.68 ( 0.59 - 0.80 ) ; and high , HR : 0.78 ( 0.66 - 0.93 ) ] . Body mass index ( BMI ) modified the association with lung cancer incidence ( p = 0.01 ) , with a stronger association in women with BMI < 30 kg/m(2 ) . Significant associations with sedentary behavior were not observed . In analyses by lung cancer subtype , higher total physical activity levels were associated with lower lung cancer mortality for both overall NSCLC and adenocarcinoma . In conclusion , physical activity may be protective for lung cancer incidence and mortality in postmenopausal women , particularly in non-obese women Lung cancer is the most common cause of cancer death with unchanged mortality for 50 years . Only localized nonsmall-cell lung cancer ( NSCLC ) is curable . In these patients it is essential to accurately predict survival to help identify those that will benefit from treatment and those at risk of relapse . Despite needing this clinical information , prospect i ve data are lacking . We therefore prospect ively identified prognostic factors in patients with potentially curable lung cancer . Over 2 years , 110 consecutive patients with confirmed localized NSCLC ( stages 1–3A ) were recruited from a single tertiary center . Prognostic factors investigated included age , gender , body mass index ( BMI ) , performance status , comorbidity , disease stage , quality of life , and respiratory physiology . Patients were followed up for 3 - 5 years and mortality recorded . The data were analyzed using survival analysis methods . Twenty-eight patients died within 1 year , 15 patients died within 2 years , and 11 patients died within 3 years postsurgery . Kaplan-Meier survival estimates show a survival rate of 51 % at 3 years . Factors significantly ( p < 0.05 ) associated with poor overall survival were age at assessment , diabetes , serum albumin , peak VO2 max , shuttle walk distance , and predicted postoperative transfer factor . In multiple-variable survival models , the strongest predictors of survival overall were diabetes and shuttle walk distance . The results show that potentially curable lung cancer patients should not be discriminated against with respect to weight and smoking history . Careful attention is required when managing patients with diabetes . Respiratory physiologic measurements were of limited value in predicting long-term survival after lung cancer surgery Background Whether waist circumference provides clinical ly meaningful information not delivered by body-mass index regarding prediction of cause-specific death is uncertain . Methods We prospect ively examined waist circumference ( WC ) and body-mass index ( BMI ) in relation to cause-specific death in 225,712 U.S. women and men . Cox regression was used to estimate relative risks and 95 % confidence intervals ( CI ) . Statistical analyses were conducted using SAS version 9.1 . Results During follow-up from 1996 through 2005 , we documented 20,977 deaths . Increased WC consistently predicted risk of death due to any cause as well as major causes of death , including deaths from cancer , cardiovascular disease , and non-cancer/non-cardiovascular diseases , independent of BMI , age , sex , race/ethnicity , smoking status , and alcohol intake . When WC and BMI were mutually adjusted in a model , WC was related to 1.37 fold increased risk of death from any cancer and 1.82 fold increase risk of death from cardiovascular disease , comparing the highest versus lowest WC categories . Importantly , WC , but not BMI showed statistically significant positive associations with deaths from lung cancer and chronic respiratory disease . Participants in the highest versus lowest WC category had a relative risk of death from lung cancer of 1.77 ( 95 % CI , 1.41 to 2.23 ) and of death from chronic respiratory disease of 2.77 ( 95 % CI , 1.95 to 3.95 ) . In contrast , subjects in the highest versus lowest BMI category had a relative risk of death from lung cancer of 0.94 ( 95 % CI , 0.75 to 1.17 ) and of death from chronic respiratory disease of 1.18 ( 95 % CI , 0.89 to 1.56 ) . Conclusions Increased abdominal fat measured by WC was related to a higher risk of deaths from major specific causes , including deaths from lung cancer and chronic respiratory disease , independent of BMI BACKGROUND In China , there have been few large prospect i ve studies of the associations of body mass index ( BMI ) with overall and cause-specific mortality that have simultaneously controlled for biases that can be caused by pre-existing disease and smoking . METHODS Prospect i ve cohort study of 224 064 men , of whom 40 700 died during follow-up between 1990 - 91 and 2006 . Analyses restricted to 142 214 men aged 40 - 79 years at baseline with no disease history and , to further reduce bias from pre-existing disease , at least 5 years of subsequent follow-up , leaving 17 800 deaths [ including 4165 stroke , 1297 coronary heart disease ( CHD ) , 3121 chronic obstructive pulmonary disease ( COPD ) ] . Adjusted hazard ratios ( HRs ) and 95 % confidence intervals ( 95 % CIs ) per 5 kg/m(2 ) calculated within either a lower ( 15 to < 23.5 kg/m(2 ) ) or higher ( 23.5 to < 35 kg/m(2 ) ) range . RESULTS The association between BMI and all-cause mortality was U-shaped with the lowest mortality at ∼22.5 - 25 kg/m(2 ) . In the lower range , 5 kg/m(2 ) higher BMI was associated with 14 % lower mortality ( HR 0.86 , 95 % CI 0.82 - 0.91 ) ; in the upper range , it was associated with 27 % higher mortality ( HR 1.27 , 95 % CI 1.15 - 1.40 ) . The absolute excess mortality in the lower range was largely accounted for by excess mortality from specific smoking-related diseases : 54 % by that for COPD , 12 % other respiratory disease , 13 % lung cancer , 11 % stomach cancer . The excess mortality in the upper BMI range was largely accounted for by excess mortality from specific vascular diseases : 55 % by that for stroke , 16 % CHD . In this range , 5 kg/m(2 ) higher BMI was associated with ∼50 % higher mortality from stroke ( HR 1.61 , 95 % CI 1.36 - 1.92 ) and CHD ( HR 1.48 , 95 % CI 1.12 - 1.95 ) . CONCLUSIONS For China , previous evidence may have overestimated the excess mortality at low BMI but underestimated that at high BMI . The main way obesity kills in China appears to be stroke Introduction : Traditional tumor-based staging systems provide limited information on the best treatment option for individual patients with advanced inoperable non-small cell lung cancer ( NSCLC ) . The Glasgow prognostic score ( GPS ) reflects the host systemic inflammatory response and is a vali date d independent prognostic factor in these patients . The aim of this study was to examine the clinical application of the pretreatment GPS in a mature cohort of patients with inoperable NSCLC . Methods : The data of 261 patients with inoperable NSCLC were collected prospect ively and before treatment . Information on patient demographics , body mass index , performance status ( PS ) , the modified Glasgow prognostic score ( mGPS ) , the prognostic index , and treatment received were included . Results : The majority of patients were aged 65 years or older ( 68 % ) , were men ( 59 % ) , had a body mass index more than 20 ( 89 % ) , and an Eastern Cooperative Oncology Group performance status ( ECOG-PS ) 0 or 1 ( 54 % ) . Most patients had a pretreatment mGPS = 1 ( 62 % ) and pretreatment prognostic index = 1 ( 56 % ) . During the follow-up period , 248 ( 95 % ) patients died , 246 from their disease . The median survival was 8 months . On multivariate analysis , age ( p = 0.001 ) , ECOG-PS ( p < 0.05 ) , mGPS ( p < 0.0001 ) , and tumor stage ( p < 0.0001 ) were independently associated with cancer-specific survival . Using 5-year cancer-specific mortality as an end point , the area under the receiver operator curve was 0.735 ( 95 % confidence interval [ CI ] , 0.566–0.903 ; p = 0.024 ) for the mGPS , 0.669 ( 95 % CI , 0.489–0.848 ; p = 0.106 ) for ECOG-PS , and 0.622 ( 95 % CI , 0.437–0.807 ; p = 0.240 ) for tumor , node , metastasis stage . Patients with an increased mGPS were more likely to have a poorer ECOG-PS ( p < 0.05 ) , an increased white cell count ( p < 0.05 ) , and received palliative treatment ( p < 0.05 ) . Conclusion : The pretreatment mGPS is a useful and important predictor of cancer-specific survival in patients with inoperable NSCLC . Basing clinical assessment on the mGPS has implication s for the routine monitoring and treatment of the patients OBJECTIVE Previous studies have suggested that marital status is associated with survival from lung cancer ; however , its association is not conclusive . The association between marital status and survival in Japanese patients with non-small cell lung cancer ( NSCLC ) was prospect ively investigated . METHODS Between July 1999 and July 2004 , a total of 1230 NSCLC patients were enrolled . The baseline survey consisted of the collection of clinical information and various demographic data , including marital status . A Cox regression model was used to estimate the hazards ratio ( HR ) of all-cause mortality adjustments for age , BMI , education level , performance status , histology type , clinical stage , smoking status , choice of definitive treatment , and depression . RESULTS The multivariable adjusted HR of male widowed patients versus male married patients was 1.7 ( 95 % confidence interval=1.2 - 2.5 , p=0.005 ) . However , no significant increased risk of death in female widowed patients compared with female married patients was observed ( HR=0.7 , 95 % confidence interval=0.5 - 1.1 , p=0.15 ) . With regard to separated/divorced and single patients no significant increased risk of death in male and /or female compared with married patients was observed . CONCLUSIONS The present data suggest that male widowed patients with NSCLC have a higher mortality rate than male married patients with NSCLC , after controlling for various factors Summary Background The main associations of body-mass index ( BMI ) with overall and cause-specific mortality can best be assessed by long-term prospect i ve follow-up of large numbers of people . The Prospect i ve Studies Collaboration aim ed to investigate these associations by sharing data from many studies . Methods Collaborative analyses were undertaken of baseline BMI versus mortality in 57 prospect i ve studies with 894 576 participants , mostly in western Europe and North America ( 61 % [ n=541 452 ] male , mean recruitment age 46 [ SD 11 ] years , median recruitment year 1979 [ IQR 1975–85 ] , mean BMI 25 [ SD 4 ] kg/m2 ) . The analyses were adjusted for age , sex , smoking status , and study . To limit reverse causality , the first 5 years of follow-up were excluded , leaving 66 552 deaths of known cause during a mean of 8 ( SD 6 ) further years of follow-up ( mean age at death 67 [ SD 10 ] years ) : 30 416 vascular ; 2070 diabetic , renal or hepatic ; 22 592 neoplastic ; 3770 respiratory ; 7704 other . Findings In both sexes , mortality was lowest at about 22·5–25 kg/m2 . Above this range , positive associations were recorded for several specific causes and inverse associations for none , the absolute excess risks for higher BMI and smoking were roughly additive , and each 5 kg/m2 higher BMI was on average associated with about 30 % higher overall mortality ( hazard ratio per 5 kg/m2 [ HR ] 1·29 [ 95 % CI 1·27–1·32 ] ) : 40 % for vascular mortality ( HR 1·41 [ 1·37–1·45 ] ) ; 60–120 % for diabetic , renal , and hepatic mortality ( HRs 2·16 [ 1·89–2·46 ] , 1·59 [ 1·27–1·99 ] , and 1·82 [ 1·59–2·09 ] , respectively ) ; 10 % for neoplastic mortality ( HR 1·10 [ 1·06–1·15 ] ) ; and 20 % for respiratory and for all other mortality ( HRs 1·20 [ 1·07–1·34 ] and 1·20 [ 1·16–1·25 ] , respectively ) . Below the range 22·5–25 kg/m2 , BMI was associated inversely with overall mortality , mainly because of strong inverse associations with respiratory disease and lung cancer . These inverse associations were much stronger for smokers than for non-smokers , despite cigarette consumption per smoker varying little with BMI . Interpretation Although other anthropometric measures ( eg , waist circumference , waist-to-hip ratio ) could well add extra information to BMI , and BMI to them , BMI is in itself a strong predictor of overall mortality both above and below the apparent optimum of about 22·5–25 kg/m2 . The progressive excess mortality above this range is due mainly to vascular disease and is probably largely causal . At 30–35 kg/m2 , median survival is reduced by 2–4 years ; at 40–45 kg/m2 , it is reduced by 8–10 years ( which is comparable with the effects of smoking ) . The definite excess mortality below 22·5 kg/m2 is due mainly to smoking-related diseases , and is not fully explained . Funding UK Medical Research Council , British Heart Foundation , Cancer Research UK , EU BIOMED programme , US National Institute on Aging , and Clinical Trial Service Unit ( Oxford , UK ) Purpose Although a number of studies have found an inverse association between body mass index ( BMI ) and risk of lung cancer , there is little information on this relation in African Americans , who experience a higher incidence of lung cancer . Methods We assessed the relation of BMI to incidence of lung cancer in the Black Women ’s Health Study , an ongoing prospect i ve follow-up of 59,000 women in the USA . Cox proportional hazard models were used to estimate hazard ratios for various levels of BMI relative to BMI 18.5–24.9 kg/m2 ( “ normal weight ” ) with adjustment for age , education , pack-years of smoking , and other covariates . Two other anthropometric measures , waist circumference ( WC ) and waist/hip ratio ( WHR ) , were also assessed . A total of 323 primary lung cancer cases were identified from 1995 to 2011 . Results The hazard ratio ( HR ) for BMI ≥30 relative to BMI 18.5–24.9 was 0.69 ( 95 % CI 0.51–0.92 ) . As expected , cigarette smoking was strongly associated with increased risk of lung cancer . In analyses stratified by smoking status , the HR for BMI ≥30 relative to BMI 18.5–24.9 was 0.62 ( 0.38–1.00 ) among current smokers , 0.90 ( 0.56–1.42 ) among former smokers , and 0.83 ( 0.41–1.70 ) among never smokers ( p for interaction = 0.28 ) . Control for pack-years of smoking or age started smoking had little effect on the hazard ratios . WC and WHR were not material ly associated with lung cancer risk . Conclusion Our results indicate that high BMI is associated with a lower risk of lung cancer in African American women , particularly among current smokers BACKGROUND Malignancy is the leading cause of death in Hong Kong , and lung cancer tops the list of all cancer deaths . METHODS A cohort of clients aged ≥65 years , enrolled at 18 elderly health centres in Hong Kong from 2000 to 2003 , was followed up prospect ively through linkage with the territory-wide death registry for causes of death until 31 December 2008 , using the identity card number as unique identifier . All subjects with suspected cancer , significant weight loss of > 5 % within past 6 months or obstructive lung disease at the baseline were excluded . RESULTS After a total of 423 061 person-years of follow-up , 932 , 690 and 1433 deaths were caused by lung cancer , other tobacco-related malignancies and non-tobacco-related malignancies , respectively . Body mass index ( BMI ) was independently ( and negatively ) associated with death from lung cancer after adjustment for other baseline variables , whereas there was only a minor or no effect for other smoking-related malignancies and non-tobacco-related malignancies . Obesity with BMI ≥30 [ adjusted hazard ratio ( HR ) , 0.55 , 95 % confidence interval ( CI ) 0.38 - 0.80 ] was associated with reduced lung cancer mortality , which was more prominent than the opposing effect of underweight ( adjusted HR , 1.38 , 95 % CI 1.05 - 1.79 ) . Consistent effects of BMI were observed after stratification into never-smokers and ever-smokers and in sensitivity analysis after excluding deaths within the first 3 years . CONCLUSION Obesity was associated with lower lung cancer mortality in this prospect i ve cohort analysis . As the effect was rather specific for lung cancer , further studies are indicated to explore the underlying mechanism The tumour-node metastasis ( TNM ) classification system is anatomically based . We investigated whether the addition of simple physiological variables , age and body mass index ( BMI ) , would affect survival curves , i.e. a composite anatomical and physiological staging system . We retrospectively analysed a prospect ively vali date d thoracic surgery data base ( n = 1981 ) . Cox multivariate analysis was performed to determine possible significant factors . Kaplan-Meier survival curves were constructed with combined anatomical and physiological factors . Cox multivariate analysis revealed age ( P < 0.001 ) and BMI ( P = 0.01 ) as significant factors affecting survival . Receiver operating curve analysis determined cut-off levels for age of 67 and BMI of 27.6 . A composite anatomical and physiological survival curve based on TNM for BMI > 27.6 and age < 67 was produced . Age and BMI criteria result ed in significantly different survival curves , for stage I ( P < 0.0001 ) and stage II ( P = 0.0032 ) , but not for stage III ( P = 0.06 ) . Neural network analysis confirmed the importance of BMI and age above cancer stage with regard to long-term survival . Combining age < 67 , BMI > 27.6 and TNM anatomical classification results in very different estimated survival curves from the usual TNM system . Patients from stages I , II and III may have survival equivalent to a stage higher or lower depending on their age and BMI BACKGROUND The relative contributions of a low and high body mass index ( BMI [ weight in kilograms divided by height in meters squared ] ) to all-cause and cause-specific mortality are still controversial . OBJECTIVE To examine mortality rates in relation to BMI in a prospect i ve cohort study of 48,287 Dutch men and women aged 30 to 54 years at baseline from 1974 to 1980 . METHODS During an average 12-year follow-up , 1319 deaths occurred . Relative risks ( RRs ) were calculated from the Cox proportional hazard model by using a BMI between 18.5 and 24.9 kg/m2 as the reference category . RESULTS All-cause mortality was significantly increased in obese men ( BMI , > or = 30 kg/m2 ; RR , 1.5 ; 95 % confidence interval [ CI ] , 1.1 - 2.0 ) and in underweight men ( BMI , < 18.5 kg/m2 ; RR , 2.6 ; 95 % CI , 1.8 - 3.9 ) but not in women . The increased risk in underweight men could be attributed to deaths within the first 5 years of follow-up and to lung cancer mortality among smokers . Coronary heart disease ( CHD ) mortality was about 3-fold higher among obese men and women . About 21 % and 28 % of CHD mortality in men and women , respectively , could be attributed to being overweight ( BMI , > or = 25 kg/m2 ) . The RR ( but not the absolute risk ) for CHD among obese men was still significant after adjustment for the presence of smoking , hypertension , hypercholesterolemia , and diabetes mellitus at baseline , and it was more pronounced for CHD among nonsmokers than among smokers ( RR , 7.1 ; 95 % CI , 2.3 - 21.7 ; and RR , 2.7 ; 95 % CI , 1.5 - 4.7 , respectively ) . CONCLUSIONS Total mortality was increased in obese and underweight men but not in women . The increased mortality in overweight men was mainly attributable to CHD and , in underweight men , to early mortality and especially lung cancer mortality among smokers BACKGROUND Unintentional weight loss occurs among advanced non-small-cell lung cancer ( NSCLC ) patients and is associated with worse survival . Small studies have suggested that weight gain during treatment is associated with superior survival . PATIENTS AND METHODS A retrospective analysis analyzed data from three international phase III studies comprising 2301 advanced , non-squamous NSCLC patients who received a platinum-based , first-line doublet , with or without bevacizumab and maintenance therapy . Body weight was recorded before and after treatment by each study 's schedule . The relationship between weight gain and overall survival ( OS ) and progression-free survival ( PFS ) was assessed using log-rank test and adjusted Cox modeling . Logistic regression assessed the association between baseline covariates and post-baseline weight gain . RESULTS Four hundred and twenty-one ( 18.3 % ) patients had > 5 % weight gain after baseline . More than half of the weight gain cohort exhibited initial weight gain by 3 weeks . The median OS was 16.7 months versus 10.7 months for the > 5 % versus ≤5 % weight gain subgroup ( n = 1880 ) ( P < 0.001 ) . PFS was 6.9 versus 4.8 months , respectively ( P < 0.001 ) . Differences in overall tumor response rate ( 50.8 % versus 25.4 % , respectively ) and disease control rate ( tumor response or stable disease ) ( 91.5 % versus 63.6 % , respectively ) were also significant ( P < 0.001 ) . The Cox modeling revealed the > 5 % subgroup had longer survival [ hazard ratio ( HR ) = 0.54 , 95 % confidence interval ( CI ) 0.47 - 0.62 ; P < 0.001 ] than the ≤5 % subgroup after adjusting for baseline factors . Similar significant results were found for PFS ( HR = 0.59 , 95 % CI 0.52 - 0.67 ; P < 0.001 ) . Unadjusted logistic regression indicated a significant association between weight gain ( > 5 % versus ≤5 % ) and age , and BMI . CONCLUSIONS Weight gain during treatment may be an early indicator of clinical benefit . If confirmed in prospect i ve studies , monitoring weight change may provide important information regarding survival outcomes in NSCLC and may provide ideas for new therapeutic strategies Low body mass index ( BMI ) has been associated with increased risk of lung cancer . However , the nature of the association , especially in population s with relatively low BMI , is less well characterized , as is the relevance to it of smoking . A nationally representative prospect i ve cohort study included 217,180 Chinese men aged 40 - 79 years in 1990 - 91 who had no prior history of cancer and were followed up for 15 years . St and ardized hazard ratios ( HRs ) were calculated for lung cancer mortality by baseline BMI . The mean baseline BMI was 21.7 kg/m(2 ) , and 2,145 lung cancer deaths were recorded during 15 years of follow-up . The prevalence of smoking was strongly inversely associated with BMI , but no apparent relationship was seen between amount smoked ( or other measures of smoking intensity ) and BMI among smokers . Overall there was a strong inverse association between BMI and lung cancer mortality ( p < 0.0001 for trend ) after excluding the first 3 years of follow-up . This association appeared to be confined mainly to current smokers , with no apparent relationship in nonsmokers ( p < 0.001 for difference between slopes ) . Among current smokers , the inverse association appeared to be log-linear , with each 5 kg/m(2 ) lower BMI associated with a 35 % ( 95 % confidence interval : 24 - 46 % ; p < 0.0001 ) higher lung cancer mortality , and it persisted after excluding those who had reported poor health status or history of any disease or respiratory symptoms at baseline . In this relatively lean Chinese male population , low BMI was strongly associated with increased risk of lung cancer only among current smokers PURPOSE To retrospectively investigate treatment outcomes of stereotactic ablative body radiation therapy ( SABR ) for octogenarians with non-small cell lung cancer ( NSCLC ) . METHODS AND MATERIAL S Between 2005 and 2012 , 109 patients aged ≥80 years with T1 - 2N0M0 NSCLC were treated with SABR : 47 patients had histology-unproven lung cancer ; 62 patients had pathologically proven NSCLC . The prescribed doses were either 50 Gy/5 fractions for peripheral tumors or 40 Gy/5 fractions for central ly located tumors . The treatment outcomes , toxicities , and the correlating factors for overall survival ( OS ) were evaluated . RESULTS The median follow-up duration after SABR was 24.2 ( range , 3.0 - 64.6 ) months . Only limited toxicities were observed , except for 1 grade 5 radiation pneumonitis . The 3-year local , regional , and distant metastasis-free survival rates were 82.3 % , 90.1 % , and 76.8 % , respectively . The OS and lung cancer-specific survival rates were 53.7 % and 70.8 % , respectively . Multivariate analysis revealed that medically inoperable , low body mass index , high T stage , and high C-reactive protein were the predictors for short OS . The OS for the operable octogenarians was significantly better than that for inoperable ( P<.01 ) . CONCLUSIONS Stereotactic ablative body radiation therapy for octogenarians was feasible , with excellent OS . Multivariate analysis revealed that operability was one of the predictors for OS . For medically operable octogenarians with early-stage NSCLC , SABR should be prospect ively compared with resection Introduction : Few lung cancer studies have focused on lung cancer survival in underserved population s. We conducted a prospect i ve cohort study among 81,697 racially diverse and medically underserved adults enrolled in the Southern Community Cohort Study throughout an 11-state area of the Southeast from March 2002 to September 2009 . Methods : Using linkages with state cancer registries , we identified 501 incident non – small-cell lung cancer cases . We applied Cox proportional hazards models to estimate hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) for subsequent mortality among black and white participants . Results : The mean observed follow-up time ( the time from diagnosis to death or end of follow-up ) was 1.25 years ( range , 0–8.3 years ) and 75 % ( n = 376 ) of cases died during follow-up . More blacks were diagnosed at distant stage than whites ( 57 versus 45 % ; p = 0.03 ) . In multivariable analyses adjusted for pack-years of smoking , age , body mass index , health insurance , socioeconomic status and disease stage , the lung cancer mortality HR was higher for men versus women ( HR = 1.41 ; 95 % CI , 1.09–1.81 ) but similar for blacks versus whites ( HR = 0.99 ; 95 % CI , 0.74–1.32 ) . Conclusion : These findings suggest that although proportionally more blacks present with distant-stage disease there is no difference in stage-adjusted lung cancer mortality between blacks and whites of similar low socioeconomic status Background : Although obesity is an established risk factor for coronary heart disease and stroke mortality , its role as a risk factor for other causes of death has not been extensively investigated , particularly in an industrial population . Methods : This prospect i ve mortality study included 20 years of follow up of middle-aged industrial workers ( n = 7139 ) at Shell Oil Company 's manufacturing and research facilities . Baseline health risk factor data as of December 31 , 1983 , and mortality data as of December 31 , 2003 , were extracted from the company 's Health Surveillance System . Relative risks ( RRs ) for selected causes of death by body mass index ( BMI ) category were calculated using the Cox proportional hazards model adjusted for age , sex , and smoking status as well as other potential risk factors , ie , cholesterol , hypertension , and fasting blood glucose . Results : Compared with employees with BMI between 18.5 and 24.9 kg/m2 , those with BMI of 30 kg/m2 or greater had a statistically increased RR ( adjusted for age , sex , and smoking status ) for all causes ( RR , 1.25 ; 95 % confidence interval [ CI ] = 1.03–1.51 ) , coronary heart diseases ( RR , 2.29 ; 95 % CI = 1.50–3.50 ) , cardiovascular diseases ( RR , 2.22 ; 95 % CI = 1.51–3.27 ) , diabetes ( RR , 16.97 ; 95 % CI = 2.11–136.44 ) , and accidental deaths ( RR , 2.64 ; 95 % CI = 1.23–5.66 ) . After adjusting for additional covariates , coronary heart diseases and cardiovascular diseases remained statistically significant . Conclusions : Obesity was associated with increased death rates for all causes , cardiovascular diseases , diabetes , and all accidents . Overweight individuals had a statistically lower cancer rate . Death rates for lung cancer and respiratory disease were lower among overweight/obese employees but did not reach statistical significance . Reductions of employee obesity can be an effective means of reducing these causes of death PURPOSE Compared to European Americans ( EAs ) , African Americans ( AAs ) suffer a disproportionate share of the lung cancer mortality burden . To investigate whether this disparity in lung cancer mortality is due to differential racial risks related to socioeconomic status ( education , occupation ) , body mass index ( BMI ) , hypertension , or cigarette smoking , we compared associations between these factors and lung cancer mortality by race in a biracial prospect i ve cohort study . METHODS The Charleston ( South Carolina ) Heart Study ( N = 2,054 ) was established in 1960 ; 40 % of the study participants are AAs . The participants have been followed up for mortality for 40 years . Using Cox proportional hazards models , we investigated whether there were racial differences in the associations between the study factors and lung cancer mortality . RESULTS Cigarette smoking was the strongest lung cancer risk factor in both races . The association between cigarette smoking and lung cancer mortality was stronger in EAs than AAs ( hazards ratio [ HR ] 26.1 vs. 7.6 ) . In both races , men were at significantly greater risk than women and BMI was significantly inversely associated with lung cancer mortality . CONCLUSIONS The evidence from the present study does not yield strong clues for the excess lung cancer mortality in AAs . Our results do not support the hypothesis that differential susceptibility to cigarette smoking is a major contributor to the racial disparity in lung cancer . This suggests we must exp and our scope of inquiry beyond the factors included in the present study to fully underst and why lung cancer mortality rates are greater in AAs than EAs Background . More than a dozen studies have examined the association between leanness and increased lung cancer risk . None of the prospect i ve studies has been large enough to allow exclusion of smokers or persons with preexisting disease , two factors that cause both leanness and poor survival and thus may cause a spurious association between low body mass index and fatal lung cancer . Methods . Using Cox proportional hazards models , we examined this issue in a cohort of 941,105 U.S. adults enrolled in an American Cancer Society prospect i ve study in 1982 . During 14 years of follow-up , 14,066 people died of lung cancer . Results . In analyses restricted to lifelong nonsmokers who did not report preexisting disease , leanness was not substantially associated with lung cancer mortality in men ( rate ratio = 0.9 ; 95 % confidence interval = 0.3–3.1 ) or in women ( rate ratio = 1.2 ; 95 % confidence interval = 0.7–2.1 ) . However , leanness was associated with increased lung cancer risk in analyses that attempted to control for , rather than exclude , smokers and persons with preexisting disease . Conclusions . These data suggest that the association between leanness and lung cancer mortality is not causal but rather is an artifact of the effects of smoking and preexisting disease OBJECTIVE To explore the association between body mass index ( BMI ) and mortality in the middle-aged and elderly population of Beijing . METHODS A prospect i ve cohort study was carried out in a natural population ( aged 40 and over ) in September 1991 , totaling 6 209 subjects . After a baseline survey for risk factors , all the subjects were followed-up throughout December 1999 . All deaths occurred during the follow-up period were registered and encoded according to ICD-9 . Proportional hazard regression was used to examine the relationship between BMI ( body weight in kilograms/height in square meters ) and overall and cause-specific mortality . RESULTS During the past ten years , five leading causes of death in the middle-aged and elderly population of Beijing were cardiovascular disease ( CVD ) , cor pulmonale , digestive malignant tumor , sudden death without definite cause and lung cancer , which accounting for 33.3 % , 13.8 % , 11.2 % , 7.4 % and 5.6 % of the total deaths , respectively . The minimum overall mortality in all population and in non-smokers were seen in those with BMI of 23.6 - 26.2 . Compared with those with BMI of 23.6 - 26.2 , the relative risks ( RR ) for all-cause mortality in all population and non-smokers with BMI less than 21.2 and equal to or greater than 26.2 were 1.7 , 1.3 , 1.9 and 1.5 , respectively after adjusted for age , gender , smoking and alcohol drinking . BMI correlated positively with death risk due to CVD in non-smokers , with an RR of 1.2 for those with BMI > 26.2 to non-smokers with BMI < 21.2 after adjusted for age , gender and alcohol drinking . A U-shaped correlationship between BMI and deaths due to other specific causes , including cor pulmonale , digestive malignant tumor , lung cancer , pneumonia and sudden death without definite causes . With the minimum cause-specific death rates all at BMI of 23.6 - 26.2 . In comparison with those with BMI of 23.6 - 26.2 , RRs for these five cause-specific mortality were 14.8 , 1.1 , 5.6 , 2.4 and 2.6 , respectively for non-smokers with BMI < 21.2 and 3.0 , 1.9 , 3.7 , 2.2 and 1.5 , respectively for non-smokers with BMI > /= 26.2 after adjusted for age , gender , and alcohol drinking . The proportion of deaths due to CVD was the highest in each BMI group , with a range of 28.0 % - 54.8 % . CONCLUSIONS There exists a U-shaped correlationship between BMI and overall mortality in the middle-aged and elderly population in Beijing . CVD remains the top leading cause of death in natural population , and its death risk increased with BMI OBJECTIVES Lung cancer and tuberculosis ( TB ) share common risk factors and are associated with high morbidity and mortality . Coexistence of lung cancer and TB were reported in previous studies , with uncertain pathogenesis . The association between lung cancer and latent TB infection ( LTBI ) remains to be explored . METHODS Newly diagnosed , treatment-naïve lung cancer patients were prospect ively enrolled from four referral medical centers in Taiwan . The presence of LTBI was determined by QuantiFERON-TB Gold In-Tube ( QFT-GIT ) . Demographic characteristics and cancer-related factors associated with LTBI were investigated . The survival status was also analyzed according to the status of LTBI . RESULTS A total of 340 lung cancer patients were enrolled , including 96 ( 28.2 % ) LTBI , 214 ( 62.9 % ) non-LTBI , and 30 ( 8.8 % ) QFT-GIT results -indeterminate cases . Non-adenocarcinoma cases had higher proportion of LTBI than those of adenocarcinoma , especially in patients with younger age . In multivariate analysis , COPD ( OR 2.41 , 95 % CI 1.25 - 4.64 ) , fibrocalcified lesions on chest radiogram ( OR 2.73 , 95 % CI 1.45 - 5.11 ) , and main tumor located in typical TB areas ( OR 2.02 , 95 % CI 1.15 - 3.55 ) were independent clinical predictors for LTBI . Kaplan-Meier survival analysis demonstrated patients with indeterminate QFT-GIT results had significantly higher 1-year all-cause mortality than those with LTBI ( p<0.001 ) and non-LTBI ( p=0.003 ) . In multivariate analysis , independent predictors for 1-year all-cause mortality included BMI < 18.5 ( HR 2.09 , 95 % CI 1.06 - 4.14 , p=0.033 ) , advanced stage of lung cancer ( RR 7.76 , 95 % CI 1.90 - 31.78 , p=0.004 ) , and indeterminate QFT-GIT results ( RR 2.40 , 95 % CI 1.27 - 4.54 , p=0.007 ) . CONCLUSIONS More than one-quarter of newly diagnosed lung cancer patients in Taiwan have LTBI . The independent predictors for LTBI include COPD , fibrocalcified lesions on chest radiogram , and main tumor located in typical TB areas . The survival rate is comparable between LTBI and non-LTBI cases . However , indeterminate QFT-GIT result was an independent predictor for all-cause mortality in lung cancer patients OBJECTIVE This phase II study aim ed to assess the effectiveness of the docetaxel plus carboplatin combination in chemotherapy-naive Thai patients with advanced non-small-cell lung cancer ( NSCLC ) . MATERIAL AND METHOD Forty patients with Eastern Cooperative Oncology Group ( ECOG ) performance status ( PS ) 0 - 1 , stage IIIB/IV NSCLC were enrolled in a phase H study between August 2001 and April 2003 . Docetaxel 75 mg/m2 and Carboplatin AUC = 6 were given every 3 weeks . Response to treatment and toxicity were grade d using st and ard WHO criteria . The Thai Functional Living Index Cancer ( T-FLIC ) scale was used to assess the Quality of Life ( QoL ) of all treated patients . RESULTS Forty patients ( median age : 55 years , range , 39 - 68 years ; PS:0 - 1 ) were enrolled : one had stage IIIB disease with effusion , while thirty-nine had stage IV disease . Five patients were non-evaluable due to death within the first cycle ; two dying of febrile neutropenia and sepsis , two of pulmonary infection , and one of unknown etiology . Partial response ( PR ) was seen in 28.6 % patients , stable disease ( SD ) in 25.7 % , and progressive disease ( PD ) in 45.7 % . The median survival time was 32 weeks and the 1-year survival rate was 30.7 % . Body mass index ( BMI ) was the only factor associated with survival time ( univariate analysis : p = 0.006 ; multivariate analysis : p = 0.004 ) . Other factors ( gender , age , histology , ECOG PS , and glomerular filtration rate ) were not predict for survival . The major treatment-related toxicities were neutropenia ( from 152 treatment cycles there were grade 4 : 19.7 % ; grade 3 : 23.7 % ) , febrile neutropenia ( from 152 treatment cycles there was 3.95 % ) , and diarrhea ( grade s 3/4 : 0.66 % ) . The QoL scores improved significantly throughout the treatment period . CONCLUSION The regimen of docetaxel and carboplatin is active in advanced NSCLC and may be considered for first-line therapy Background Lobectomy remains the gold st and ard with regard to potentially curative resection of non-small-cell lung carcinoma . We aim ed to investigate whether there is a survival difference in stage 1 non-small-cell lung cancer patients who undergo lobectomy compared to a wedge resection . Methods We retrospectively analyzed a prospect i ve data base of 1283 patients who had potentially curative resection for stage 1 non-small-cell lung cancer . Only patients with adenocarcinoma , squamous or adenosquamous carcinoma were included . We benchmarked our 5-year survival against the 6th International Association for the Study of Lung Cancer results . Three techniques were used to assess the effect of a lobectomy compared to a wedge resection with regard to long-term survival : Cox multivariate regression analysis , neuronal network analysis , and propensity matching . Results Benchmarking failed to reveal any significant difference compared to the 6th International Association for the Study of Lung Cancer results . Crude analysis demonstrated superiority of lobectomy compared to wedge resection , p = 0.02 . Cox regression analysis confirmed that age , body mass index , female sex , being a current smoker , tumor diameter , and preoperative forced expiratory volume in 1 s were all significant factors determining long-term survival . Wedge resection was not a significant factor . Neuronal network analysis concurred with the Cox regression analysis . Propensity matching with 1:1 matching demonstrated that wedge resections was not inferior to a lobectomy , p = 0.10 . Conclusions Cox regression analysis , neuronal network analysis , and propensity matching in stage 1 non-small-cell lung cancer demonstrate no difference in long-term survival after wedge resection compared to lobectomy Background : Muscle wasting is a component of the diagnosis of cancer cachexia and has been associated with poor prognosis . However , recommended tools to measure sarcopenia are limited by poor sensitivity or the need to perform additional scans . We hypothesized that pectoralis muscle area ( PMA ) measured objective ly on chest CT scan may be associated with overall survival ( OS ) in non – small cell lung cancer ( NSCLC ) . Methods : We evaluated 252 cases from a prospect ively enrolling lung cancer cohort . Eligible cases had CT scans performed prior to the initiation of surgery , radiation , or chemotherapy . PMA was measured in a semi-automated fashion while blinded to characteristics of the tumor , lung , and patient outcomes . Results : Men had a significantly greater PMA than women ( 37.59 vs. 26.19 cm2 , P < 0.0001 ) . In univariate analysis , PMA was associated with age and body mass index ( BMI ) . A Cox proportional hazards model was constructed to account for confounders associated with survival . Lower pectoralis area ( per cm2 ) at diagnosis was associated with an increased hazard of death of 2 % ( HRadj , 0.98 ; confidence interval , 0.96–0.99 ; P = 0.044 ) while adjusting for age , sex , smoking , chronic bronchitis , emphysema , histology , stage , chemotherapy , radiation , surgery , BMI , and ECOG performance status . Conclusions : Lower PMA measured from chest CT scans obtained at the time of diagnosis of NSCLC is associated with a worse OS . Impact : PMA may be a valuable CT biomarker for sarcopenia-associated lung cancer survival . Cancer Epidemiol Biomarkers Prev ; 26(1 ) ; 38–43 . © 2016 AACR . See all the articles in this CEBP Focus section , “ The Obesity Paradox in Cancer : Evidence and New Directions . OBJECTIVES The study aim ed to determine the importance of smoking status at operation and histology type with regard to long-term survival after potential curative surgery for lung cancer . METHODS We analysed a prospect ively vali date d thoracic surgery data base ( n = 2485 ) . We benchmarked our 5-year survival against the International Association for the Study of Lung Cancer ( IALSC ) results . Univariate and Cox multivariate analyses were performed for the study group and for isolated adenocarcinoma and squamous carcinoma histological subtypes . RESULTS Benchmarking failed to reveal any differences in survival of our study cohort compared with the IALSC results , P = 0.16 . Univariate analysis revealed that non-smokers have a statistically better long-term outcome , P < 0.0001 , than ever smokers . Patients with adenocarcinoma , n = 1216 , had a worse outcome in ever smokers , P = 0.006 . In patients with squamous carcinoma , n = 1065 , smoking status made no difference , P = 0.4 . Long-term survival was not significantly different for adenocarcinoma or squamous carcinoma , P = 0.87 . Cox multivariate analysis revealed that patients with adenocarcinoma who were current smokers had a significantly worse long-term survival compared with ex-smokers and non-smokers ( hazard ratio : 1.26 , 95 confidence interval : 1.01 - 1.56 ) , P = 0.04 . Age , body mass index , sex , T stage , N stage , predicted postoperative forced expiratory volume in one second ( FEV1 ) , residual disease , alcohol consumption and oral diabetes were additional significant factors affecting long-term survival . Pneumonectomy , pack years , bronchial resection margin , New York Heart Association class , hypertension , previous cerebrovascular event , diet or insulin-controlled diabetes and previous myocardial infa rct ion were excluded by the analysis as significant risk factors . Smoking status did not affect long-term survival in patients with squamous cell carcinoma . CONCLUSIONS Smoking status at time of surgery does not effect long-term survival in patients with squamous cell carcinoma . Smoking status makes a significant difference to the long-term outcomes of patients with adenocarcinoma even after adjustment for their risk factors . This implies that a histological classification of adenocarcinoma may incorporate genetically diverse adenocarcinomas with regard to prognosis PURPOSE The aim of this study is to present an analysis investigating the association of patient characteristics with overall survival ( OS ) in individuals with stage III non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Ten prognostic factors were analyzed in 203 patients with NSCLC who were enrolled in a phase III trial conducted by the Hoosier Oncology Group and US Oncology between 2002 and 2006 . Eligible patients had untreated stage III NSCLC , forced expiratory volume in one second ( FEV(1 ) ) > or = 1 liter , baseline performance status of 0/1 , and weight loss < 5 % in 3 months preceding the trial . Univariate analysis , Cox proportional hazards regression , and parametric accelerated failure time models were performed to identify the factors that affected survival duration . Variables analyzed included age ( < 70 years vs. > or = 70 years ) , sex , ethnicity , body mass index , performance status ( 0 vs. 1 ) , FEV(1 ) ( > 2 L vs. 1 - 2 L ) , smoking status ( current vs. never/former ) , hemoglobin ( Hb ) level , use of positron emission tomography scan in staging , and stage ( IIIA vs. IIIB ) . RESULTS Median follow-up was 25.6 months and the median OS was 21.2 months . The univariate analysis showed that Hb levels > or = 12 were associated with an improved survival ( P = .033 ) . The multivariable parametric accelerated failure time model demonstrated the association of FEV(1 ) > 2 L ( P = .014 ) , and higher pretreatment Hb values ( P = .007 ) as independent prognostic factors for OS . Similarly in the Cox regression , survival was influenced by Hb and FEV(1 ) > 2 L. CONCLUSION This analysis suggests that FEV(1 ) > 2 L and higher pretreatment Hb values are associated with improved OS in patients with stage III NSCLC . These factors can be useful in predicting for more favorable outcomes in patients with stage III NSCLC and provide additional information when design ing future studies RATIONALE There is compelling evidence that acute and chronic exposure to ambient fine particulate matter ( PM(2.5 ) ) air pollution increases cardiopulmonary mortality . However , the role of PM(2.5 ) in the etiology of lung cancer is less clear , particularly at concentrations that prevail in developed countries and in never-smokers . OBJECTIVES This study examined the association between mean long-term ambient PM(2.5 ) concentrations and lung cancer mortality among 188,699 lifelong never-smokers drawn from the nearly 1.2 million Cancer Prevention Study -II participants enrolled by the American Cancer Society in 1982 and followed prospect ively through 2008 . METHODS Mean metropolitan statistical area PM(2.5 ) concentrations were determined for each participant based on central monitoring data . Cox proportional hazards regression models were used to estimate multivariate adjusted hazard ratios and 95 % confidence intervals for lung cancer mortality in relation to PM(2.5 ) . MEASUREMENTS AND MAIN RESULTS A total of 1,100 lung cancer deaths were observed during the 26-year follow-up period . Each 10 μg/m(3 ) increase in PM(2.5 ) concentrations was associated with a 15 - 27 % increase in lung cancer mortality . The association between PM(2.5 ) and lung cancer mortality was similar in men and women and across categories of attained age and educational attainment , but was stronger in those with a normal body mass index and a history of chronic lung disease at enrollment ( P < 0.05 ) . CONCLUSIONS The present findings strengthen the evidence that ambient concentrations of PM(2.5 ) measured in recent decades are associated with small but measurable increases in lung cancer mortality BACKGROUND This study aim ed to evaluate the characteristics of active anti-cancer treatment ( AAT ) compared with best supportive care ( BSC ) in elderly patients with advanced non-small cell lung cancer ( NSCLC ) . METHODS A retrospective analysis of 144 patients , aged 70 or older , with stage IIIb/IV NSCLC from 672 patients with confirmed lung cancer , was conducted . RESULTS Median age at diagnosis was 77 years and median survival time was five months . On multivariate analysis , AAT independently contributed to a decreased hazard ratio of death ( P = 0.04 ) , whereas male gender ( P = 0.004 ) , a body mass index of less than 18.5 ( P = 0.004 ) , and a poor performance score were associated with an increased risk of death ( P < 0.001 ) . The 52 subjects receiving AAT experienced longer survival than the 92 subjects receiving BSC ( median seven months [ AAT ] versus three months [ BSC ] ; P < 0.001 ) . When sub-classified into five-year age intervals , AAT was a significant advantage in overall survival ( OS ) to patients aged 70 - 74 , but not to those ≥75 years old . CONCLUSIONS AAT for patients ≥70 years old with advanced NSCLC extended OS . However , care should be taken in decisions on active anti-cancer treatments for patients over 75 years old . A prospect i ve multicenter trial is required in the near future PURPOSE This study aim ed to evaluate racial/ethnic differences in lung cancer incidence and mortality in the Women 's Health Initiative Study , a longitudinal prospect i ve cohort evaluation of postmenopausal women recruited from 40 clinical centers . METHODS Lung cancer diagnoses were central ly adjudicated by pathology review . Baseline survey question naires collected sociodemographic and health information . Logistic regression models estimated incidence and mortality odds by race/ethnicity adjusted for age , education , calcium/vitamin D , body mass index , smoking ( status , age at start , duration , and pack-years ) , alcohol , family history , oral contraceptive , hormones , physical activity , and diet . RESULTS The cohort included 129,951 women--108,487 ( 83 % ) non-Hispanic white ( NHW ) ; 10,892 ( 8 % ) non-Hispanic black ( NHB ) ; 4,882 ( 4 % ) Hispanic ; 3,696 ( 3 % ) Asian/Pacific Isl and er ( API ) ; 534 ( < 1 % ) American Indian/Alaskan Native ; and 1,994 ( 1 % ) other . In unadjusted models , Hispanics had 66 % lower odds of lung cancer compared with NHW ( odds ratio [ OR ] , 0.34 ; 95 % CI , 0.2 to 0.5 ) , followed by API ( OR , 0.45 ; 95 % CI , 0.27 to 0.75 ) and NHB ( OR , 0.75 ; 95 % CI , 0.59 to 0.95 ) . In fully adjusted multivariable models , the decreased lung cancer risk for Hispanic compared with NHW women attenuated to the null ( OR , 0.59 ; 95 % CI , 0.35 to 0.99 ) . In unadjusted models Hispanic and API women had decreased risk of death compared with NHW women ( OR , 0.30 [ 95 % CI , 0.15 to 0.62 ] and 0.34 [ 95 % CI , 0.16 to 0.75 , respectively ) ; however , no racial/ethnic differences were found in risk of lung cancer death in fully adjusted models . CONCLUSION Differences in lung cancer incidence and mortality are associated with sociodemographic , clinical , and behavioral factors . These findings suggest modifiable exposures and behaviors may contribute to differences in incidence of and mortality by race/ethnicity for postmenopausal women . Interventions focused on these factors may reduce racial/ethnic differences in lung cancer incidence and mortality |
12,767 | 25,589,172 | A similar effect was found for aspirin , acetaminophen , COX-2 inhibitors and , to a lesser extent , ibuprofen .
The effect of aspirin was similar in preventing hormone-receptor-positive breast cancer .
This meta- analysis suggests a slightly protective effect of NSAIDs-especially aspirin and COX-2 inhibitors- against breast cancer , which seems to be restricted to ER/PR+tumors | Evidence on non-steroidal anti-inflammatory drugs ( NSAID ) use and breast cancer risk shows a slightly protective effect of these drugs , but previous studies lack r and omized clinical trial results and present high heterogeneity in exposure measurement .
This systematic review and meta- analysis widens the knowledge about NSAID use and breast cancer risk , updating the information from the last meta- analysis , focusing on evidence on specific effects of COX-2 inhibitors and differential expression patterns of hormonal receptors . | Chronic inflammation has been consistently associated with cancers of several sites , including the breast , and inhibition of inflammation through the use of non-steroidal anti-inflammatory drugs ( NSAIDs ) has been inversely associated with risk . As NSAIDs bind with cyclooxygenase-2 ( COX-2 ) , genetic variation in COX-2 may influence breast cancer risk by affecting inflammatory response and response to NSAID use . We identified eight single nucleotide polymorphisms ( SNPs ) for COX-2 and examined their association with risk of breast cancer in a population -based case – control study in Western New York . Cases had incident , first primary , histologically confirmed breast cancer ( n = 1077 ) . Controls ( n = 1910 ) were r and omly selected from NY Department of Motor Vehicles records ( < 65 ) or Medicare rolls ( ≥65 ) . Participants were queried on adult lifetime use of aspirin and recent use of ibuprofen . Unconditional logistic regression was used to estimate odds ratios ( OR ) and 95 % confidence intervals ( 95 % CI ) . One SNP , rs2745559 , was associated with an increased risk of breast cancer ( OR 1.23 , 95 % CI 1.03–1.46 ) . Associations with other variants were not evident . Significant interaction ( P interaction = 0.04 ) between recent aspirin use and rs4648261 was also observed . Variation in COX-2 was modestly associated with breast cancer risk , indicating that COX-2 may play a role in breast carcinogenesis . Better underst and ing of the role of COX-2 genetic variation and interaction with NSAID use in breast carcinogenesis has potential to inform prevention strategies OBJECTIVE Previous epidemiological studies have suggested that use of aspirin or other nonsteroidal anti-inflammatory drugs ( NSAIDs ) may be associated with reduced risk of breast cancer , but some studies have been limited in their ability to separate the effects of aspirin from other NSAIDs or to account for breast cancer risk factors . METHODS We examined the incidence of breast cancer in association with self-reported aspirin , as well as other nonaspirin NSAID use in a large prospect i ve cohort of postmenopausal women ( n = 27,616 ) . Over 6 years of follow-up , 938 incident breast cancers were identified . RESULTS After adjustment for other breast cancer risk factors , any current use of aspirin or other NSAIDs compared with no use was associated with a reduction in risk of breast cancer [ relative risk ( RR ) = 0.80 , 95 % confidence interval ( CI ) 0.67 - 0.95 ] . There was a trend of decreasing risk of incident breast cancer with increasing frequency of aspirin use ( P(trend ) = 0.0011 ) . The multivariate-adjusted RR of breast cancer was 0.71 ( 95 % CI 0.58 - 0.87 ) for women who reported using aspirin six or more times per week compared with women who reported no use . These results did not depend on whether women had early or late stage breast cancer . No association was found between nonaspirin NSAID use and incident breast cancer . The adjusted RR of using other NSAIDs six or more times per week compared with no use was 1.01 ( 95 % CI 0.83 - 1.25 ) . CONCLUSION This prospect i ve study corroborates other reports that use of aspirin might reduce risk of breast cancer BACKGROUND The use of aspirin and other nonsteroidal anti-inflammatory drugs ( NSAIDs ) is widespread for treatment of common symptoms such as headaches , muscular pain , and inflammation . In addition , the chemopreventive use of NSAIDs is increasingly common for heart disease and colon cancer . Evidence of a protective association with breast cancer risk has been inconsistent , and few data exist for premenopausal women . METHODS We assessed the associations for use of aspirin , other NSAIDs , and acetaminophen with breast cancer risk among premenopausal women in the prospect i ve Nurses ' Health Study II . In total , 112,292 women , aged 25 to 42 years and free of cancer in 1989 , were followed up until June 2003 . Multivariate relative risks and 95 % confidence intervals were calculated by Cox proportional hazards models , adjusting for age and other important breast cancer risk factors . RESULTS Overall , 1345 cases of invasive premenopausal breast cancer were documented . Regular use of aspirin ( > or = 2 times per week ) was not significantly associated with breast cancer risk ( relative risk , 1.07 ; 95 % confidence interval , 0.89 - 1.29 ) . Regular use of either nonaspirin NSAIDs or acetaminophen also was not consistently associated with breast cancer risk . Results did not vary by frequency ( days per week ) , dose ( tablets per week ) , or duration of use . Furthermore , associations with each drug category did not vary substantially by estrogen and progesterone receptor status of the tumor . CONCLUSION These data suggest that the use of aspirin , other NSAIDs , and acetaminophen is not associated with a reduced risk of breast cancer among premenopausal women UNLABELLED There is evidence that use of aspirin offers several potential health benefits including cancer prevention and cardiovascular disease prevention . The purpose of this study was to assess the association between aspirin use and death from cancer and cardiovascular diseases with a special emphasis on cancer mortality . MATERIAL S AND METHODS The baseline data for this prospect i ve cohort study were collected in 1971 - -1975 for the first National Health and Nutrition Examination Study ( NHANES I ) and 1976 - -1980 as part of the second NHANES ( NHANES II ) with mortality follow-up using the National Death Index ( NDI ) through December 31 , 1992 . The main analyses were the relative risks of total mortality and cause-specific mortality for persons who used aspirin compared to persons who did not use aspirin adjusted for confounding using Cox proportional hazards . RESULTS The proportion of aspirin users was lower among cancer cases than non-cases ( 58 % versus 66 % ) and use of aspirin decreased with age . Consequently , age was a negative confounder attenuating the protective association between aspirin use and cancer and cardiovascular mortality . After adjusting for age , BMI , sex , race , poverty index , education and smoking , we observed a significant association of reduced all cause mortality among all aspirin users ( relative risk [ RR ] = 0.88 ; 95 % confidence interval [ CI ] 0.85 - 0.99 ) and lung cancer mortality among male aspirin users ( RR = 0.69 ; CI 0.49 - 0.96 ) . However , for women we observed adverse associations between aspirin use and bladder ( RR=12.31 ; CI 2.98 - 50.80 ) and brain cancer mortality ( RR=3.13 ; CI 1.09 - 9.00 ) , although case numbers were small . CONCLUSION Aspirin use appears to offer protection from all causes of mortality and lung cancer among men . In women aspirin use is associated with increased risk of bladder and brain cancer . Because of the small number of female bladder ( n=15 ) and brain ( n=20 ) cancer cases in this cohort the findings require confirmation BACKGROUND The cancer chemopreventive benefits of aspirin and nonaspirin nonsteroidal anti-inflammatory drugs ( NSAIDs ) are incompletely defined and may vary by smoking history . We evaluated associations between aspirin and nonaspirin NSAID use with cancer incidence and mortality stratified by smoking history in the Iowa Women 's Health Study , a prospect i ve cohort of postmenopausal women . METHODS Aspirin and nonaspirin NSAID use was self-reported by question naire in 1992 . Cancer incidence and mortality were ascertained by annual linkage to the Iowa Surveillance , Epidemiology , and End Results Cancer Registry and death certificates . Cox proportional hazards models were used to estimate multivariable relative risks ( RRs ) and 95 % confidence intervals ( CIs ) . All statistical tests were two-sided . RESULTS During an average of 10 years of follow-up , 3487 incident cancer cases and 3581 deaths were observed in the cohort of 22,507 women . Compared with nonuse , aspirin use was inversely associated with total cancer incidence ( multivariable-adjusted RR = 0.84 , 95 % CI = 0.77 to 0.90 ) , with age-adjusted incidence rates of 147 and 170 per 10,000 person-years for ever and never users , respectively , and was inversely associated with cancer mortality ( multivariable-adjusted RR = 0.87 , 95 % CI = 0.76 to 0.99 ) , with age-adjusted rates of 47 and 52 per 10,000 person-years . The inverse relationship was stronger among former and never smokers than current smokers , although not statistically significantly ( P = .28 ) . Aspirin use was also inversely associated with coronary heart disease mortality ( multivariable-adjusted RR = 0.75 , 95 % CI = 0.64 to 0.89 ) , with age-adjusted rates of 23 and 30 per 10,000 person-years for ever and never users , respectively , and with all-cause mortality ( multivariable-adjusted RR = 0.82 , 95 % CI = 0.76 to 0.89 ) , with age-adjusted rates of 126 and 155 per 10,000 person-years . Nonaspirin NSAID use was not associated with cancer incidence or mortality , coronary heart disease mortality , or all-cause mortality . CONCLUSIONS Aspirin use , but not nonaspirin NSAID use , was associated with lower risks of cancer incidence and mortality , which was more pronounced among former and never smokers than current smokers Nonsteroidal antiinflammatory drugs ( NSAIDs ) may play a role in breast cancer prevention ; however , breast cancer subtypes and lifestyle/host factors may influence their impact . During 1996 - 1998 in Canada , the authors examined the association between regular NSAID use ( defined as daily use for at least 2 months ) and breast cancer risk by estrogen receptor ( ER ) and progesterone receptor ( PR ) status , cigarette smoking exposure , and history of arthritis . Breast cancer cases ( n = 3,125 , including 1,600 ER+PR+ and 591 ER-PR- ) and an age-matched , r and om sample of controls ( n = 3,062 ) completed a general risk factor question naire , including detailed questions on prescription and nonprescription NSAID use . NSAID use was associated with reduced risk of breast cancer ( odds ratio = 0.76 , 95 % confidence interval : 0.66 , 0.88 ) . The association was not significantly different for ER+PR+ ( odds ratio = 0.71 , 95 % confidence interval : 0.60 , 0.84 ) and ER-PR- cancers ( odds ratio = 0.80 , 95 % confidence interval : 0.62 , 1.03 ) ( p(heterogeneity ) = 0.66 ) . The magnitude of the NSAID inverse association was similar for women with and without arthritis and across smoking strata ( risk estimates ranged from 0.74 to 0.84 ) . Breast cancer risk tended to decrease with increasing duration of NSAID use and was generally lowest for > or=7 years of use , and both acetylsalicylic acid and non-acetylsalicylic acid use were associated with reduced risks We carried out a nested case – control study to measure the rate ratio ( RR ) for invasive female breast cancer in relation to non-steroidal anti-inflammatory drug ( NSAID ) use . The source population consisted of the female beneficiaries of the Saskatchewan Prescription Drug Plan from 1981 to 1995 with no history of cancer since 1970 . Four controls/case , matched on age and sampling time , were r and omly selected . Dispensing rates during successive time periods characterized NSAID exposure . RRs associated with exposure during each period were adjusted for exposure during the others . Confounding by other determinants was studied in analyses adjusted with data obtained by interviewing sample s of subjects accrued from mid-1991 to mid-1995 . We accrued 5882 cases and 23 517 controls . Increasing NSAID exposure 2–5 years preceding diagnosis was associated with a trend towards a decreasing RR ( P -trend = 0.003 ) ; for the highest exposure level RR = 0.76 , 95 % confidence interval 0.63–0.92 . This protective effect could not be attributed to confounding by other determinants . In analyses involving only the cases , NSAID exposure 2–5 and 6–10 years preceding diagnosis was associated with significantly reduced risks of presenting with a large tumour ( > 5 cm diameter ) or distant metastasis , but not regional lymph node metastasis . The use of NSAIDs may retard the growth of breast cancers and prevent distant metastasis . © 2000 Cancer Research Use of non-steroidal anti-inflammatory drugs ( NSAIDs ) has been associated with reduced risk of breast cancer , though findings have been inconsistent . This inconsistency may result from differences in etiology for breast tumors of different subtypes . We examined the association between NSAID use and breast cancer characterized by molecular subtypes in a population -based case – control study in Western New York . Cases ( n = 1,170 ) were women with incident , primary , histologically confirmed breast cancer . Controls ( n = 2,115 ) were r and omly selected from NY Department of Motor Vehicles records ( < 65 years ) or Medicare rolls ( ≥65 years ) . Participants answered questions regarding their use of aspirin and ibuprofen in the year prior to interview and their use of aspirin throughout their adult life . Logistic regression models estimated odds ratios ( OR ) and 95 % confidence intervals ( 95 % CI ) . Recent and lifetime aspirin use was associated with reduced risk , with no differences by subtype . Recent use of ibuprofen was significantly associated with increased risk of ER+/PR+(OR 1.33 , 95 % CI : 1.09–1.62 ) , HER2− ( OR 1.27 , 95 % CI : 1.05–1.53 ) , and p53− breast cancers ( OR 1.28 , 95 % CI : 1.04–1.57 ) , as well as luminal A or B breast cancers . These findings support the hypothesis of heterogeneous etiologies of breast cancer subtypes and that aspirin and ibuprofen vary in their effects BACKGROUND The influence of long-term use of aspirin on total mortality in women remains uncertain . METHODS We conducted a prospect i ve , nested , case-control study of 79 439 women enrolled in the Nurses ' Health Study who had no history of cardiovascular disease or cancer . Women provided data on medication use biennially since 1980 . We assessed relative risk ( RR ) of death according to aspirin use before diagnosis of incident cardiovascular disease or cancer and during the corresponding period for each control subject . RESULTS During 24 years , we documented 9477 deaths from all causes . In women who reported current aspirin use , the multivariate RR of death from all causes was 0.75 ( 95 % confidence interval , 0.71 - 0.81 ) compared with women who never used aspirin regularly . The risk reduction was more apparent for death from cardiovascular disease ( RR , 0.62 ; 95 % confidence interval , 0.55 - 0.71 ) than for death from cancer ( RR , 0.88 ; 95 % confidence interval , 0.81 - 0.96 ) . Use of aspirin for 1 to 5 years was associated with significant reductions in cardiovascular mortality ( RR , 0.75 ; 95 % confidence interval , 0.61 - 0.92 ) . In contrast , a significant reduction in risk of cancer deaths was not observed until after 10 years of aspirin use ( P(linear trend ) = .005 ) . The benefit associated with aspirin was confined to low and moderate doses and was significantly greater in older participants ( P(interaction ) < .001 ) and those with more cardiac risk factors ( P(interaction ) = .02 ) . CONCLUSIONS In women , low to moderate doses of aspirin are associated with significantly lower risk of all-cause mortality , particularly in older women and those with cardiac risk factors . A significant benefit is evident within 5 years for cardiovascular disease , whereas a modest benefit for cancer is not apparent until after 10 years of use BACKGROUND Evidence suggests that aspirin and other nonsteroidal anti-inflammatory drugs ( NSAIDs ) can inhibit tumor development in the large bowel . An inverse association between the use of NSAIDs and the incidence of breast cancer has been observed , but this association has not been statistically significant in all studies . PURPOSE We analyzed data from the prospect i ve Nurses ' Health Study to evaluate the influence of aspirin use on breast cancer risk . METHODS We studied a population of 89,528 female registered nurses who reported no history of breast or other cancers ( excluding nonmelanoma skin cancer ) and who returned a mailed question naire in 1980 that elicited information concerning breast cancer risk factors and current and past aspirin use . Follow-up question naires were mailed to the participants every 2 years ; the women were followed through 1992 . Information concerning current aspirin use was obtained from each biennial question naire , except in 1986 . Cases of breast cancer were identified through question naire responses , and permission was sought for a review of medical records to confirm the diagnoses . Our analysis was based on 2414 cases of invasive breast cancer , which included 2303 cases confirmed with medical records and 111 cases for which no records were obtained . Relative risks ( RRs ) with 95 % confidence intervals ( CIs ) , adjusted for age or age plus other known or potential breast cancer risk factors ( i.e. , multivariate ) , were calculated . RESULTS Regular aspirin use ( two or more tablets per week ) in 1980 was unrelated to breast cancer incidence during the succeeding 12-year period ( with no regular aspirin use as the referent , multivariate RR = 1.03 ; 95 % CI = 0.95 - 1.12 ) . The corresponding risk estimate for consistent regular aspirin use during the period from 1980 through 1988 was 1.01 ( 95 % CI = 0.80 - 1.27 ) . The risks were similar for heavy aspirin use ( for more than two tablets per day [ i.e. , > 14 per week ] in 1980 and in 1980 through 1988 , the multivariate RRs [ 95 % CIs ] were 1.05 [ 0.89 - 1.23 ] and 1.09 [ 0.75 - 1.60 ] , respectively ) and for extended duration s of regular use ( e.g. , for 20 years or more of regular use , multivariate RR = 1.00 ; 95 % CI = 0.71 - 1.41 ) . CONCLUSION Our results indicate that regular aspirin use does not reduce the risk of breast cancer Objective Chronic inflammation is suspected to have a role in breast carcinogenesis . Results of studies of non-steroidal anti-inflammatory drugs ( NSAIDs ) and breast cancer have been inconsistent . Timing of exposure and analysis of individual NSAIDs should be considered . Methods We conducted a population -based case – control study in western New York State between 1996 and 2001 . Cases , 35–79 years , had incident , primary , histologically confirmed breast cancer ( n = 1,170 ) . Controls ( n = 2,115 ) were r and omly selected from NY Department of Motor Vehicles records ( < 65 years ) or Medicare rolls ( ≥65 years ) . Participants were queried on use of aspirin , ibuprofen , and acetaminophen in the year prior and on aspirin during adulthood . Unconditional logistic regression was used to estimate adjusted odds ratios ( OR ) and 95 % confidence intervals ( 95 % CI ) . Results Recent aspirin use was inversely associated with breast cancer risk ( adjusted OR 0.80 , 95 % CI : 0.68–0.94 ) ; the strongest reduction in risk was observed among those who took ≥2 pills/day on days that aspirin was taken ( OR 0.74 , 95 % CI : 0.61–0 . 90 ) . Adult lifetime use was also associated with breast cancer risk ( > 10 days/month , adjusted OR 0.68 , 95 % CI : 0.46–1.00 ) . Use of ibuprofen or acetaminophen was not associated with breast cancer . Conclusions This is the first study to investigate the association of adult lifetime aspirin intake with breast cancer risk . Our findings provide evidence that aspirin use throughout a woman ’s life may confer some benefit Use of non-steroid anti-inflammatory drugs ( NSAIDs ) has been associated with decreased risk of breast cancer in epidemiological studies . Thus , a high-inflammatory response may be associated with increased breast cancer risk . It is thus possible that genetic variations leading to a modified inflammatory response will influence breast cancer risk . The purpose of this study was to determine if polymorphisms associated with an altered inflammatory response are associated with breast cancer risk , and to investigate the possible interaction with lifestyle factors such as alcohol use , smoking and NSAID use . We matched 361 female breast cancer cases with 361 controls , nested within the prospect i ve ' Diet , Cancer and Health ' study . Carriers of the variant Ala-allele of PPARgamma2 Pro12Ala were at lower risk of breast cancer ( IRR=0.67 , 95 % CI=0.46 - 0.97 ) . This was primarily due to an interaction with alcohol consumption . Alcohol consumption was associated with a 1.21-fold increased risk of breast cancer per 10 g alcohol/day ( 95 % CI=1.06 - 1.35 ) among homozygous wild-type carriers , whereas alcohol was not associated with breast cancer risk among variant allele carriers ( P for interaction=0.005 ) . Non-users of NSAID , who were carriers of the variant allele of PPARgamma2 Pro12Ala , were at lower risk of breast cancer ( IRR=0.44 ; 95 % CI=0.26 - 0.73 ) compared with non-users carrying wild-type alleles ( P for interaction=0.03 ) . No effects were found for IL6 G-174C , IL8 T-251A and COX2 T8473C . Our results suggest that PPARgamma2 Pro12Ala is an important determinant in alcohol mediated breast carcinogenesis . We also observe interaction between NSAID , alcohol consumption and PPARgamma2 Pro12Ala genotype in relation to breast cancer risk BACKGROUND Recent epidemiologic and laboratory studies have suggested that non-steroidal anti-inflammatory drugs ( NSAIDs ) may reduce the risk of breast cancer through inhibition of cyclooxygenase-2 ( COX-2 ) . METHODS We conducted a case-control study to measure the association between selective cox-2 inhibitors , particularly celecoxib , rofecoxib , valdecoxib and non-specific NSAID subgroups , and breast cancer risk . Between 2003 and 2006 , a total of 18,368 incident breast cancer cases were identified in the Ingenix/Lab Rx insurance data base , which contains clinical encounter and drug prescription data . Four controls per case were r and omly selected , matched on age and time in data base . Odds ratios ( OR ) and 95 % confidence intervals ( CI ) were estimated using conditional logistic regression . RESULTS Breast cancer risk was inversely associated with both non-specific NSAID and selective COX-2 inhibitor use . Greater than 12 months ' duration of use of Celecoxib at a st and ard dose ( 200mg/day ) was associated with a 16 % decrease in breast cancer risk ( OR=0.84 , 95 % CI=0.73 , 0.97 ) . We observed the greatest risk reduction in association with > 2 years of rofecoxib exposure ( OR=0.54 , 95 % CI=0.37 , 0.80 ) . Acetaminophen , a compound with less biological plausibility for chemoprevention , showed no significant association with the risk of developing breast cancer . CONCLUSION Consistent with animal models and laboratory investigations , higher doses of selective COX-2 inhibitors were more protective against breast cancer than non-specific NSAIDs . With exposure to rofecoxib , a selective COX-2 inhibitor , breast cancer risk reduction was appreciable ( 46 % ) , suggesting a possible role for selective COX-2 inhibitors in breast cancer prophylaxis BACKGROUND Epidemiologic evidence indicates that aspirin use is associated with reduced risks of colon cancer and possibly several other cancers , including prostate and breast cancers . Recent results from the Women 's Health Study r and omized trial indicate that long-term use of low-dose aspirin ( 100 mg every other day ) does not substantially reduce cancer risk . However , the potential effect of long-term daily use of higher doses of aspirin on cancer incidence remains uncertain . METHODS We examined associations between long-term daily use of adult-strength aspirin ( > or = 325 mg/day ) and both overall cancer incidence and incidence of 10 types of cancer among 69,810 men and 76,303 women participating in the Cancer Prevention Study II Nutrition Cohort , a relatively elderly population . Aspirin use was reported at enrollment in 1992 - 1993 and up date d in 1997 , 1999 , and 2001 . Multivariable Cox proportional hazards regression was used to calculate rate ratios ( RRs ) . RESULTS During follow-up through June 2003 , 10,931 men and 7196 women were diagnosed with cancer . Long-term ( > or = 5 years ) daily use of adult-strength aspirin , compared with no use , was associated with lower overall cancer incidence in men ( multivariable-adjusted RR = 0.84 , 95 % confidence interval [ CI ] = 0.76 to 0.93 ) and non-statistically significantly lower overall cancer incidence in women ( multivariable-adjusted RR = 0.86 , 95 % CI = 0.73 to 1.03 ) . Overall cancer incidence per 100,000 person-years ( st and ardized to the age distributions of men and women in the study ) with long-term daily aspirin use and no aspirin use was 1858 and 2163 , respectively , among men and 1083 and 1169 , respectively , among women . Long-term daily aspirin use was associated with lower incidence of colorectal cancer ( RR = 0.68 , 95 % CI = 0.52 to 0.90 among men and women combined ) and prostate cancer ( RR = 0.81 , 95 % CI = 0.70 to 0.94 ) and a non-statistically significant lower risk of female breast cancer ( RR = 0.83 , 95 % CI = 0.63 to 1.10 ) . CONCLUSIONS Long-term daily use of adult-strength aspirin may be associated with modestly reduced overall cancer incidence in population s among whom colorectal , prostate , and breast cancers are common Use of nonsteroidal anti-inflammatory drugs ( NSAIDs ) , particularly aspirin , has consistently been associated with reduced risk of breast cancer in case-control studies . However , results from prospect i ve studies have been less consistent . We examined the association between NSAID use and breast cancer incidence , adjusting for multiple breast cancer risk factors among 77,413 women in the Cancer Prevention Study II Nutrition Cohort . During follow-up from 1992 to 2001 , we observed 3,008 cases of incident breast cancer . Information on NSAID use was obtained from a question naire completed at enrollment in 1992 or 1993 and was up date d using follow-up question naires in 1997 and 1999 . NSAID use was modeled using time-dependent variables to up date exposure status . Neither current total NSAID use ( aspirin and other NSAIDs combined ) nor current aspirin use were associated with breast cancer incidence even at relatively high levels of use [ rate ratio ( RR ) , 1.07 ; 95 % confidence interval ( 95 % CI ) , 0.96 - 1.21 for > or = 60 NSAID pills per month compared with no reported use of NSAIDs ; RR , 1.01 ; 95 % CI , 0.84 - 1.20 for > or = 60 aspirin per month compared with no reported use of aspirin ] . Even long- duration regular use ( > or = 30 pills per month for > or = 5 years ) was not associated with breast cancer incidence ( RR , 1.05 ; 95 % CI , 0.88 - 1.26 for total NSAIDs ; RR , 0.88 ; 95 % CI , 0.69 - 1.12 for aspirin ) . Although we can not exclude a small reduction in breast cancer risk associated with NSAID use , the results of this study provide evidence against a large reduction in risk Aspirin and other nonsteroidal antiinflammatory drugs inhibit prostagl and in synthesis and tumor growth in many experimental systems , but it is unclear which of these tumor models are relevant to humans . We have reported reduced risk of fatal colon cancer among persons who used aspirin in a large prospect i ve study . This analysis examines other fatal cancers in relation to aspirin among 635,031 adults in that study who provided information in 1982 on the frequency and duration of their aspirin use and did not report cancer . Death rates were measured through 1988 . Death rates decreased with more frequent aspirin use for cancers of the esophagus , stomach , colon , and rectum but not generally for other cancers . For each digestive tract cancer , death rates were approximately 40 % lower among persons who used aspirin 16 times/month or more for at least 1 year compared to those who used no aspirin . The trend of decreasing risk with more frequent aspirin use was strongest among persons who had used aspirin for 10 years or more ; it remained statistically significant , except for esophageal cancer , in multivariate analyses that adjusted for other known risk factors . Biases such as early detection or aspirin avoidance among cases do not appear to explain the results . Our data suggest that regular , prolonged use of aspirin may reduce the risk of fatal cancer of the esophagus , stomach , colon , and rectum . Future epidemiological and basic research should examine all digestive tract cancers in considering the chemopreventive or therapeutic potential of nonsteroidal antiinflammatory drugs Objective We prospect ively evaluated the association between average 10-year use of NSAIDs and invasive breast cancer . Methods Between 2000–2002 , 35,323 postmenopausal women participating in the Vitamins And Lifestyle ( VITAL ) study provided detailed information regarding NSAID use , lifestyle and breast cancer risk factors . Using a Cox proportional hazards model , we analyzed associations between NSAID use and incident breast cancer ( N = 482 ) ascertained through linkage to the SEER cancer registry . Results Use of low-dose aspirin at 4 + days/week over ten years was associated with a decreased risk of breast cancer ( HR 0.65 , confidence interval [ CI ] 0.43–0.97 ) versus no use , as was moderate use of other types of NSAIDs ( HR 0.78 , CI 0.61–0.98 ) for 10-yr average use up to 3 days/week . However , more frequent use of NSAIDs other than low – dose aspirin was associated with an increased risk ( HR 1.26 , CI 0.96–1.65 ) , particularly frequent use of regular or extra strength aspirin ( HR 1.43 , CI 1.02–2.00 ) . Conclusions We did not find evidence of a global protective effect of NSAID use for the development of breast cancer . However , long-term moderate use ( frequent use of low doses or moderate frequency of high doses ) was associated with reduced risk , while frequent use of higher dose products was associated with increased risk The objective of this study was to examine the association between nonsteroidal anti-inflammatory drug ( NSAID ) use and the development of breast cancer , and to assess whether this association differed by estrogen receptor ( ER ) subtype . Data were analyzed from 15,651 women participating in CLUE II , a cohort study initiated in 1989 in Washington County , MD . Medication data were collected at baseline in 1989 and in 1996 . Incident cases of invasive breast cancer occurring from baseline to March 27 , 2006 were identified through linkage of cohort participants with the Washington County Cancer Registry and the Maryl and State Cancer Registry . Cox proportional hazards modeling was used to calculate the risk ratios ( RR ) and 95 % confidence intervals ( 95 % CI ) for breast cancer associated with medication use . Among women in the CLUE II cohort , 418 invasive breast cancer cases were identified during the follow-up period . The results showed that self-reported use of NSAIDs in both 1989 and in 1996 was associated with a 50 % reduction in the risk of developing invasive breast cancer compared with no NSAID use in either 1989 or 1996 ( RR = 0.50 ; 95 % CI 0.28 , 0.91 ) . The protective association between NSAID use and the risk of developing breast cancer was consistent among ER-positive and ER-negative breast cancers , although only the RR for ER-positive breast cancer was statistically significant . Overall , findings from this study indicate that NSAID use is associated with a decrease in breast cancer risk and that the reduction in risk is similar for ER-positive and ER-negative tumors Findings from previous epidemiological studies are inconclusive , though they suggest nonsteroidal anti-inflammatory drug ( NSAID ) use is associated with a reduction in breast cancer risk . In addition , animal studies report that NSAIDs inhibit mammary tumor development . The association between NSAID use and breast cancer risk was evaluated using a case-control study design . Cases were a r and om sample of women diagnosed with a first primary cancer of the breast , aged 25 - 74 years , identified through the Ontario Cancer Registry , and diagnosed between July 1996 and September 1998 . Controls were an age-matched r and om sample of the female population of Ontario . Cases ( n = 3133 ) and controls ( n = 3062 ) completed a mailed question naire with information on their past use of NSAID and other medications , as well as many risk factors thought to be associated with breast cancer . Multivariate logistic regression analysis was used to obtain adjusted odds ratio ( OR ) estimates . Use of any NSAID medication ( daily use for > or = 2 months ) was found to be associated with a significant 24 % reduction in breast cancer risk ( OR = 0.76 ; 95 % confidence interval : 0.66 , 0.88 ) . The reduced risk was strongest for use lasting > 8 years , compared with nonusers ( OR = 0.68 ; 95 % confidence interval : 0.54 , 0.86 ) . No marked trends were observed for time since first use or last use or age at first use . Our results suggest a reduction in breast cancer risk associated with any regular NSAID use . NSAID use is a modifiable factor , and any protective effect attributed to its use could be of great public health importance We conducted a prospect i ve cohort study of Nonsteroidal anti-inflammatory drugs ( NSAIDs ) and breast cancer among 32,505 women in central Ohio , USA . After 5 years of follow-up , a total of 393 cases have been detected . The annual incidence of breast cancer per 100,00 women varied inversely with increasing intake of NSAIDs , declining from 323 among non-users to 183 among heavy users ( p<0.01 ) . Breast cancer rates decreased by about 50 % with regular ibuprofen intake ( p<0.01 ) , and by about 40 % with regular aspirin intake ( p<0.05 ) . The results suggest that specific NSAIDs may be effective chemopreventive agents against breast cancer We analyzed data from the prospect i ve Women 's Health Initiative ( WHI ) Observational Study to examine the effects of regular use of aspirin , ibuprofen , and other nonsteroidal anti-inflammatory drugs ( NSAIDs ) on breast cancer risk . We studied a population of 80,741 postmenopausal women between 50 and 79 years of age who reported no history of breast cancer or other cancers ( excluding nonmelanoma skin cancer ) , and we completed a personal baseline interview that elicited comprehensive health information including data on breast cancer risk factors and NSAID use . All of the cases were adjudicated by WHI physicians using pathology reports . Our analysis was based on 1392 confirmed cases of breast cancer . Relative risks ( RRs ) with 95 % confidence intervals ( CIs ) were estimated with adjustment for age and other breast cancer risk factors . Regular NSAID use ( two or more tablets/week ) for 5 - 9 years produced a 21 % reduction in the incidence of breast cancer ( RR , 0.79 ; 95 % CI , 0.60 - 1.04 ) ; regular NSAID use for 10 or more years produced a 28 % reduction ( RR , 0.72 ; CI , 0.56 - 0.91 ) , and there was a statistically significant inverse linear trend of breast cancer incidence with the duration of NSAID use ( P < 0.01 ) . The estimated risk reduction for long-term use of ibuprofen ( RR , 0.51 ; CI , 0.28 - 0.96 ) was greater than for aspirin ( RR , 0.79 ; CI , 0.60 - 1.03 ) . Subgroup analysis by breast cancer risk factors did not result in effect modification . Regular use of acetaminophen ( an analgesic agent with little or no anti-inflammatory activity ) or low-dose aspirin ( < 100 mg ) was unrelated to the incidence of breast cancer . Our results indicate that the regular use of aspirin , ibuprofen , or other NSAIDs may have a significant chemopreventive effect against the development of breast cancer and underscore the need for clinical trials to confirm this effect PURPOSE The associations between use of aspirin , other nonsteroidal anti-inflammatory drugs ( NSAIDs ) , and acetaminophen and breast cancer incidence in postmenopausal women are uncertain . We examined these associations with breast cancer , both overall and by molecular subtype . PATIENTS AND METHODS We observed 84,602 postmenopausal women , free of cancer in 1980 , until June 2008 and prospect ively collected data on analgesic use , reproductive history , and other lifestyle factors using biennial question naires . Proportional hazards models were used to estimate multivariable relative risks ( RRs ) and 95 % CIs . RESULTS We documented 4,734 cases of incident invasive breast cancer . Compared with nonuse of aspirin , multivariable RRs of regular aspirin use ( ≥ two tablets per week ) for more than 20 years were 0.91 for overall breast cancer ( 95 % CI , 0.81 to 1.01 ; P(trend ) = 0.16 ) , 0.90 for estrogen receptor ( ER ) -positive progesterone receptor ( PR ) -positive breast cancer ( 95 % CI , 0.77 to 1.06 ; P(trend ) = 0.17 ) , and 0.91 for ER-negative PR-negative breast cancer ( 95 % CI , 0.68 to 1.22 ; P(trend ) = 0.97 ) . Results did not vary appreciably by past or current use , days per week of use , or dosage of use . Use of other NSAIDs and acetaminophen was largely not significantly associated with breast cancer risk . Additionally , use of higher doses of each analgesic ( ≥ six tablets per week ) for more than 10 years was generally not significantly associated with risk of breast cancer , either overall or by subtype . Furthermore , largely no substantial associations were noted for breast cancer molecular subtypes , including luminal A , luminal B , triple negative , basal-like , human epidermal growth factor receptor 2 positive , cyclooxygenase-2 ( COX-2 ) negative , and COX-2 positive . CONCLUSION Our study suggests that use of aspirin , other NSAIDs , and acetaminophen is not importantly associated with risk of postmenopausal breast cancer , either overall or by specific subtype |
12,768 | 30,290,130 | Study -level data indicated that 5 % NaF varnish was the most effective for arresting or reversing noncavitated facial/lingual carious lesions ( low certainty ) and that 38 % silver diamine fluoride solution applied biannually was the most effective for arresting advanced cavitated carious lesions on any coronal surface ( moderate to high certainty ) . | The goal of nonrestorative or non- and microinvasive caries treatment ( fluoride- and nonfluoride-based interventions ) is to manage the caries disease process at a lesion level and minimize the loss of sound tooth structure .
The purpose of this systematic review and network meta- analysis was to summarize the available evidence on nonrestorative treatments for the outcomes of 1 ) arrest or reversal of noncavitated and cavitated carious lesions on primary and permanent teeth and 2 ) adverse events . | PURPOSE This study 's purpose was to test silver diammine fluoride ( SDF ) in arresting incipient occlusal caries in erupting permanent first molars and to compare it with other approaches . METHODS Sixty-six first erupting permanent molars were r and omly divided into 3 groups : cross tooth-brushing technique ( CTT ) , application of SDF , and glass ionomer fissure sealant ( GIC ) . The clinical procedures were conducted by the same dentist . Teeth were assessed clinical ly by 1 blinded examiner using visual inspection at baseline and after 3 , 6 , 12 , 18 , and 30 months and radiographically at 6- , 12- , and 30-month follow-up evaluations . The Kruskall-Wallis test was used to compare noninvasive treatments , and the Friedman test was performed to evaluate differences for each group during different follow-up periods . RESULTS A reduced number of active caries lesions was noted in all groups . After 3 and 6 months , SDF showed a significantly greater capacity for arresting caries lesions than CTT and GIC . At 18- and 30-month evaluations , no differences were observed among the 3 groups . All groups showed differences between baseline and all follow-up re-examinations . CONCLUSIONS All the tested techniques are equally efficient in controlling initial occlusal caries in erupting permanent first molars after 30-months of follow-up Objective : Considering the minimally invasive approach to dentistry , the scientific community has focused on non-invasive treatments for caries lesions . The aim of this study was to evaluate the efficacy of a nonsurgical approach to arrest occlusal non-cavitated dentin lesions through glass ionomer sealing . Methods : In this controlled clinical trial , 51 teeth with clinical ly non-cavitated occlusal caries radiographically located beneath the enamel-dentine junction ( radiolucent area ) were selected among patients presenting a moderate to high risk of caries . The teeth were r and omly divided into two groups : an experimental group receiving an application of Vidrion-R ( SS White ) glass ionomer and a control group not su bmi tted to any clinical intervention . Caries progression was monitored by clinical and radiographic examination at 4-monthly intervals over a period of one year . In addition , marginal integrity of the sealant was evaluated in the experimental group . Results : Clinical examination showed no statistical difference between the groups ( P=.13 ) . On the other h and , sealed teeth presented lower caries progression when analyzed by radiographic examination ( P=.004 ) . Conclusion : A glass ionomer sealant over non-cavitated occlusal caries lesions in dentin may not be sufficiently effective in arresting their progression The aim of this double-blind r and omized clinical trial was to evaluate the efficacy of 1.23 % APF gel application on the arrest of active incipient carious lesions in children . Sixty 7- to 12-year-old children , with active incipient lesions were included in the study . Children were divided r and omly into 2 groups : 1.23 % APF gel and placebo gel applications . Each group received 8 weekly applications of treatment . The lesions were re-evaluated at the 4th and 8th appointments . Poisson regression analysis was used to estimate relative risks of the presence of active white spot lesions . Groups showed similar results ( PR = 1.67 ; CI 95 % 0.69 - 3.98 ) . The persistence of at least 1 active lesion was associated with a higher number of lesions in the baseline ( PR = 2.67 ; CI 95 % 1.19 - 6.03 ) , but not with sugar intake ( PR = 1.06 ; CI 95 % 0.56 - 2.86 ) and previous exposure to fluoride dentifrice ( PR = 1.26 ; CI 95 % 0.49 - 2.29 ) . The trial demonstrates the equivalence of the treatments . The use of the APF gel showed no additional benefits in this sample of children exposed to fluori date d water and dentifrice . The professional dental plaque removal in both groups may also account for the result ing equivalence of the treatments This 12-week clinical study evaluated the impact of 10 % CPP-ACP and 5 % sodium fluoride varnish regimes on the regression of nonorthodontic white spot lesions ( WSLs ) . The study included 21 children with 101 WSLs who were r and omised into four treatment regimes : weekly clinical applications of fluoride varnish for the first month ( FV ) ; twice daily self-applications of CPP-ACP paste ( CPP-ACP ) ; weekly applications of fluoride varnish for the first month and twice daily self-applications of CPP-ACP paste ( CPP-ACP-FV ) ; and no intervention ( control ) . All groups undertook a st and ard oral hygiene protocol and weekly consultation . Visual appraisal s and laser fluorescence ( LF ) measurements were made in weeks one and twelve . The majority of WSLs in the control and FV groups exhibited no shift in appearance , whereas , in the CPP-ACP and CPP-ACP-FV groups , the lesions predominantly regressed . The visual and LF assessment s indicated that the extent of remineralisation afforded by the treatments was of the following order : control ~ FV < CPP-ACP ~ CPP-ACP-FV . Self-applications of CPP-ACP paste as an adjunct to st and ard oral hygiene significantly improved the appearance and remineralisation of WSLs . No advantage was observed for the use of fluoride varnish as a supplement to either the st and ard or CPP-ACP-enhanced oral hygiene regimes OBJECTIVE To compare the effectiveness of annual topical application of silver diamine fluoride ( SDF ) solution , semi-annual topical application of SDF solution , and annual application of a flowable high fluoride-releasing glass ionomer in arresting active dentine caries in primary teeth . METHODS A total of 212 children , aged 3 - 4 years , were r and omly allocated to one of three groups for treatment of carious dentine cavities in their primary teeth : Gp1-annual application of SDF , Gp2-semi-annual application of SDF , and Gp3-annual application of glass ionomer . Follow-up examinations were carried out every six months to assess whether the treated caries lesions had become arrested . RESULTS After 24 months , 181 ( 85 % ) children remained in the study . The caries arrest rates were 79 % , 91 % and 82 % for Gp1 , Gp2 and Gp3 , respectively ( p=0.007 ) . In the logistic regression model using GEE to adjust for clustering effect , higher caries arrest rates were found in lesions treated in Gp2 ( OR=2.98 , p=0.007 ) , those in anterior teeth ( OR=5.55 , p<0.001 ) , and those in buccal/lingual smooth surfaces ( OR=15.6 , p=0.004 ) . CONCLUSION Annual application of either SDF solution or high fluoride-releasing glass ionomer can arrest active dentine caries . Increasing the frequency of application to every 6 months can increase the caries arrest rate of SDF application . CLINICAL SIGNIFICANCE Arrest of active dentine caries in primary teeth by topical application of SDF solution can be enhanced by increasing the frequency of application from annually to every 6 months , whereas annual paint-on of a flowable glass ionomer can also arrest active dentine caries and may provide a more aesthetic outcome The possibility of achieving a caries-reducing effect by a combination of fortnightly mouthrinsings with 0.2 % NaF-solutions and topical painting with solutions containing Al- , Fe- , and Mn-ions was examined in a 4-year clinical study . In addition to the fluoride rinses one of two r and omized groups was given three paintings per year with a 0.2 % NaF-solution . The other group was painted three times per year with a potassium fluoride solution containing Al- , Fe- , and Mn-ions . This group developed significantly less caries during the study than the NaF-group . The results indicate that certain metal ions can enhance the caries-prophylactic action of the fluoride ions Objectives The hypothesis was that the daily use of a high dose of a xylitol chewing gum for 6 months would reduce the increment of decayed permanent first molar surfaces ( ΔD6S ) in high-risk schoolchildren after 2 years . Methods In this r and omised , clinical trial , 204 schoolchildren with a high caries risk were assigned to two experimental groups , xylitol and non-xylitol . Caries status , salivary mutans streptococci , and lactobacilli were re-evaluated 2 years later in 74 xylitol-treated and 83 non-xylitol-treated schoolchildren . Differences in mean ∆D6S between groups registered at baseline and at follow-up were evaluated using the nonparametric Mann – Whitney U test . Results Outcome was the development of detectable carious lesions initial ( D1–D2 ) and manifest ( D3 ) in the permanent first molars . In the xylitol group , the difference in proportion of children with decayed first permanent molars at baseline and follow-up was 1.43 % for manifest lesion and 2.86 % for initial lesions ; while in the non-xylitol group was 10.26 % ( p < 0.01 ) and 16.66 % ( p < 0.01 ) , respectively . A statistically significant difference regarding means was also observed in the non-xylitol group : the ∆D6S for manifest lesion was 0.18 ( p = 0.03 ) and 0.67 ( p = 0.02 ) for initial lesion . Conclusion The use of a chewing gum containing a high dose of xylitol for a period of 6 months has been shown to produce a long-term effect on caries development in high caries-risk children . Clinical relevance A school-based preventive programme based on 6 months ’ administration of a high dose of xylitol via chewing gum proved to be efficacious in controlling caries increment in high-risk children OBJECTIVES Little is known about the effect of Cervitec , a chlorhexidine-thymol varnish , on root caries . Our objective was to determine whether a 3-monthly application of Cervitec over 1 year would limit the progress of existing root caries lesions and reduce the incidence of dental root caries in a group of dentate institutionalized elderly , as a complement to their usual oral hygiene practice s. METHODS A double-blind r and omized clinical trial was conducted in 68 subjects ( 34 per group ) in two residences in Almería ( Spain ) . Twenty-one subjects with 60 root caries lesions and 25 with 65 lesions , in the Cervitec and placebo groups , respectively , completed the study . Varnishes were applied twice in the first week , 1 month later , and every 3 months until the end of the study . Clinical parameters associated with established lesions were determined at baseline and after 6 and 12 months , as was the incidence of root caries lesions . RESULTS The clinical evolution of lesions was significantly better in the Cervitec group as opposed to the placebo group in terms of width , height , color , and texture . The increase in root caries was significantly lower ( p=0.039 ) in the Cervitec group . CONCLUSION According to these results , Cervitec may help to control established root lesions and reduce the incidence of root caries lesion among institutionalized elderly Sound evidence on the effectiveness of fluoride varnishes ( FV ) to reduce caries incidence in preschool children is lacking . Objective : To assess whether the application of FV in preschool children at 6-month intervals decreases the incidence of caries and produces any adverse effects . Methods : A r and omized , examiner- and patient-blind , placebo-controlled , parallel-group design , clinical trial , comprising 1- to 4-year-old children , 100 in each group ( FV or placebo varnish , PV ) , was conducted in Rio de Janeiro , Brazil . Two trained pediatric dentists performed the clinical examinations ( kappa = 0.85 ) . Dental caries was recorded at the d2 ( cavitated enamel ) and d3 ( dentine ) levels using the International Caries Diagnosis and Assessment System . Results : At baseline , the mean age of the participants was 2.4 years ( SD 0.9 ) and the mean d3mfs was 0.8 ( SD 1.9 ) . Most of the children brushed their teeth with fluoride toothpaste and consumed fluori date d tap water . After 24 months , 89 and 92 children of the test and the control groups were analyzed , respectively . A total of 32 ( 35.9 % ) children in the FV group and 43 ( 46.7 % ) in the PV group presented new dentine caries lesions ( χ2 test ; p = 0.14 ) , showing relative and absolute risk reductions of 23 % ( 95 % CI : -9.5 to 45.9 ) and 11 % ( 95 % CI : -3.5 to 25.0 ) . The mean caries increment differences between the test and control groups were -0.8 ( 95 % CI : -2.0 to 0.4 ) at the d2 level and -0.7 ( 95 % CI : -1.9 to 0.4 ) at the d3 level . Only 2 minor complaints regarding the intervention were reported . Conclusion : Although safe and well accepted , twice-yearly professional FV application , during 2 years , did not result in a significant decrease in caries incidence A clinical trial was conducted to compare the effect of different caries – preventive strategies on caries progression in lower – income , ethnically diverse persons 60 years of age and older . Two hundred and ninety – seven subjects were r and omized into one of five experimental groups . Group 1 received usual care from a public health department or a private practitioner . Group 2 received an educational program of 2 h duration implemented twice a year . Group 3 received the educational program plus a 0.12 % chlorhexidine rinse weekly . Group 4 received the education and chlorhexidine interventions and a fluoride varnish application twice a year . Group 5 received all the above interventions as well as scaling and root planing every 6 months throughout the 3–year study . A carious event was defined as the onset of a carious lesion , a filling , or an extraction on a surface which was sound at baseline . Two hundred and one subjects remained in the study for the 3–year period . Groups that received usual intraoral procedures ( groups 3 , 4 , and 5 ) had a 27 % reduction for coronal caries events ( p = 0.09 ) and 23 % for root caries events ( p = 0.15 ) , when compared to the groups that received no intraoral procedures ( groups 1 and 2 ) . Routine preventive treatments may have had only a small – to – moderate effect upon caries development Background To evaluate the effect of probiotic chewing tablets on early childhood caries development in preschool children living in a low socioeconomic multicultural area . Methods The investigation employed a r and omized double-blind placebo-controlled design . The study group consisted of 138 healthy 2 - 3-year-old children that were consecutively recruited after informed parental consent . After enrollment , they were r and omized to a test or a placebo group . The parents of the test group were instructed to give their child one chewing tablet per day containing three strains of live probiotic bacteria ( ProBiora3 ® ) and the placebo group got identical tablets without bacteria . The duration was one year and the prevalence and increment of initial and manifest caries lesions was examined at baseline and follow-up . All parents were thoroughly instructed to brush the teeth of their off-springs twice daily with fluoride toothpaste . Results The groups were balanced at baseline and the attrition rate was 20 % . Around 2/3 of the children in both groups reported an acceptable compliance . The caries increment ( Δds ) was significantly lower in the test group when compared with the placebo group , 0.2 vs. 0.8 ( p < 0.05 ) . The risk reduction was 0.47 ( 95 % CI 0.24–0.98 ) and the number needed to treat close to five . No differences were displayed between the groups concerning presence of visible plaque or bleeding-on-brushing . No side effects were reported . Conclusions The results suggested that early childhood caries development could be reduced through administration of these probiotic chewing tablets as adjunct to daily use of fluoride toothpaste in preschool children . Further studies on a possible dose – response relationship seem justifiedTrial registration Clinical Trials.gov Identifier : NCT01720771 . First received : October 31 , 2012 Aim : The aim of this study is to reduce the caries risk in cleft lip and palate ( CLP ) patients with multibracket appliances via a compliance-independent method . Patients , Material s and Methods : Sixty-eight CLP patients with multibracket appliances were su bmi tted to professional tooth cleaning at 4-week intervals . After r and omization , patients in group A wore a splint filled with chlorhexidine ( CHX ) gel ( Chlorhexamed ® ) for 15 minutes ( 3 × 5 min ) every 12 weeks . Patients in group B were treated with CHX varnish ( EC40 ® ) every 12 weeks . Fluoride varnish ( Fluoridin ® ) was applied to all teeth 4 and 8 weeks after the respective CHX treatments . Regular salivary bacteria counts ( CRT ® ) were carried out to determine therapeutic effectiveness . Initial DMFS values were compared to the final ones . Results : Initial findings of the salivary test and DMFS index confirmed the high caries risk . The DMFS value increased dramatically in both groups despite this systematic prophylaxis program . The bactericidal effect of both CHX preparations turned out to be markedly weaker than that described in the literature . Conclusions : Though the CHX and fluoride application had a limited effect ( at least in this test population ) , one should keep in mind that it is precisely this population that requires very intensive prophylaxis , and that no antibacterial adjuvant is more effective than CHX . However , the application interval should be individually adapted to the bacteria count . ZusammenfassungZiel : Ziel der vorliegenden Studie ist es , das Kariesrisiko bei LKG-Spalt-Patienten mit Multibracketapparatur durch eine complianceunabhängige Method e zu senken . Patienten , Material ien und Method en : Bei 68 LKG-Spalt-Patienten mit Multibracketapparaturen wurde in 4-wöchigem Abst and eine professionelle Zahnreinigung durchgeführt . Nach einer r and omisierten Aufteilung erhielten die Patienten der Gruppe A alle 12 Wochen eine mit Chlorhexidin-(CHX-)Gel ( Chlorhexamed ® ) gefüllte Trägerschiene , die für 15 Minuten ( 3 × 5 min ) eingesetzt wurde . Patienten der Gruppe B wurden alle 12 Wochen mit CHX-Lack ( EC40 ® ) beh and elt . Auf alle Zähne wurde 4 und 8 Wochen nach den jeweiligen CHX-Beh and lungen Fluoridlack ( Fluoridin ® ) aufgetragen . Regelmäßige Speichelkeimzahlbestimmungen ( CRT ® ) sollten Aufschluss über die therapeutische Wirksamkeit geben . Die anfangs erhobenen DMFS-Werte wurden mit den Endbefunden verglichen . Ergebnisse : Die Ausgangsbefunde der Speicheltests und des DMFS-Index bestätigten das hohe Kariesrisiko . Trotz dieses konsequenten Prophylaxeprogramms nahm der DMFS-Wert in beiden Gruppen dramatisch zu . Der bakterizide Effekt beider CHX-Präparate fiel deutlich geringer aus , als dies in der Literatur beschrieben ist . Schlussfolgerungen : Trotz dieser , zumindest bei dieser Untersuchungsklientel , geringen Wirkung ist an der CHX- und Fluorid-Anwendung festzuhalten , zum einen da es genau diese Klientel ist , die besonders intensiver Prophylaxe bedarf . Zum and eren gibt es keine wirksameren antibakteriell wirkenden Adjuvanzien als CHX . Allerdings sollte das Applikationsintervall individuell an die Bakterienzahl angepasst werden The aim was to evaluate a 3-year r and omised controlled trial of school-based fluoride mouth rinsing ( FMR ) on approximal caries development in 13- to 16-year-olds with low to moderate caries risk . The adolescents used F toothpaste at home and underwent prophylactic treatment at yearly check-ups at public dental clinics . Out of 788 r and omly selected 13-year-olds , 622 completed the trial , carried out in 1999–2003 . Supervised by a dental nurse , the subjects rinsed with a 0.2 % NaF solution at different intervals . Group 1 rinsed their teeth on the first three schooldays every semester ; group 2 on the first three and the last three schooldays every semester ; group 3 on three consecutive days once a month during semesters ; group 4 once every fortnight during semesters , and group 5 ( control ) did not rinse . Radiographic recording of approximal caries was performed . FMR on the three first and the three last schooldays every semester ( group 2 ) had a prevented fraction of 59 % , with approximal enamel lesions as a diagnostic threshold . Corresponding figures for groups 1 , 3 and 4 were 30 , 47 and 41 % , respectively . The control group differed statistically from groups 2–4 for new enamel and dentin lesions and fillings ( p < 0.01 ) . Enamel lesions constituted more than 90 % of the new caries lesions . Caries progression was low for all groups and no significant differences were found between groups . The main conclusion from this r and omised controlled trial is that school-based FMR , as a supplement to the daily use of F toothpaste , reduces caries incidence on approximal surfaces in adolescents with low to moderate caries risk Objectives : The objectives of this study were to measure the caries preventive effect of sealants applied to occlusal surfaces of primary molars compared to fluoride varnish applications , and to assess the retention rate of sealants after 1 year . Methods : 147 first- grade pupils from two kindergarten schools in Kuwait , whose parents gave their written consent , were included . The children were examined by one dentist using the International Caries Detection and Assessment System . After the examination , sealants and fluoride varnish were applied on the selected occlusal surfaces of primary molars by another dentist . The jaw quadrant for intervention was selected r and omly ; molars on the contralateral side of the mouth received the contralateral intervention . Examinations and intervention were provided on the school premises in the mobile dental unit with a portable spotlight . Moisture was controlled by cotton rolls , suction and air drying . The follow-up examinations were conducted after 1 year . All children received fluoride varnish before and 6 months after the intervention . Results : From 267 matched pairs of occlusal surfaces of primary molars , varnished surfaces were significantly more likely to develop new caries lesions than the sealed ones ( odds ratio = 2.92 ; 95 % confidence interval = 1.82 - 4.71 ) during the 1-year follow-up . The majority ( 73.0 % ) of the sealants were completely retained and 15.1 % partially . Conclusions : Sealing fissures seems to be better in preventing occlusal caries lesions in primary molars than applying only fluoride varnish . After 1 year , the majority of sealants were retained sound OBJECTIVES The purpose of this study was to investigate the caries-reducing effect of an amine fluoride toothpaste when used under real-life conditions in a community preventive program . METHODS Approximately 12,500 children 3 - 12 years of age were provided with toothpaste ( four tubes or 360 grams annually during three years ) to be used in kindergartens or schools and once a day at home . The teachers supervised daily toothbrushing sessions . R and om sample s of children in each of the ages 3 , 6 , 9 , and 12 years were selected from the intervention and the reference communities at both the start of the study and after three years , and examined for dental caries experience . RESULTS Amine fluoride dentifrice seemed to provide a reduction in dental caries prevalence compatible to the most commonly used fluoride dentifrice compounds . CONCLUSIONS The implemented fluoride toothpaste program is a feasible and practical method of improving the oral health status of children PURPOSE To evaluate the effects of chlorhexidine-containing varnishes and dentin sealants on the progress of demineralization , cariogenic bacteria and clinical appearance of root caries lesions . METHODS 68 lesions in 22 adult patients , with a mean age of 51.3 + /- 13.8 years were enrolled in this study . After the removal of soft , infected dentin , all lesions were r and omly sealed with ( 1 . ) Cervitec , used as control ( CE ) , ( 2 . ) EC 40 ( EC ) , ( 3 . ) Prime and Bond NT ( PB ) or ( 4 . ) Seal & Protect ( SP ) . Clinical appearance , laser fluorescence diagnosis ( DIAGNOdent ) and bacteriological status were recorded at intervals of 1 and 3 months . RESULTS Regarding alteration of surface texture and color of the lesions , differences between the groups were not detected . Application of EC result ed in suppressed MS counts after 3 months ( P < 0.05 ) . Initial lower MS counts were observed in the CE group ( P = 0.053 ) . Laser fluorescence values increased in the chlorhexidine groups ( CE = 27.9 + /- 17.5 , EC = 28.3 + /- 26.0 ) but remained stable in the sealant groups ( PB = 15.1 + /- 22.0 , SP = 10.2 + /- 7.3 ) , ( P < 0.05 ) Two clinical trials were carried out in order to evaluate differences in caries increment as influenced by various sugars . The first study involved almost complete substitution of sucrose ( S ) by fructose ( F ) or xylitol ( X ) during a period of 2 years . The second study comprised partial substitution , the effects of a S- or X-containing chewing gum being compared during 1 year . In the first trial there were no significant differences initially between the sugar groups ; 35 subjects in the S-group , 38 in the F-group , and 52 in the X-group . During the entire study 10 subjects discontinued , in one case due to osmotic diarrhoea in the X-group , the other cases being due to difficulties in adhering to the strict diet , other personal reasons and in 3 cases due to excessive caries incidence . After 2 years the mean increment of decayed , missed and filled tooth surfaces was 7.2 in the S-group , 3.8 in the F-group and 0.0 in the X-group . The caries incidence was additionally expressed in combined quantitative and qualitative terms by considering also the changes in lesion size . Irrespective of the way of using these indices , a massive reduction of the caries increment was noted in the X-group as compared to the S-group . The second trial comprised initially 102 subjects divided r and omly into S- and X-groups . The subjects consumed 4.5 chewing gums per day in the X-group and 4.0 in the S-group . The frequency of the sucrose intake was 4.94 per day in the X-group , and 4.24 in the S-group . The caries incidence equalled the one-year observations in the first study . The results show a massive reduction of the caries increment not only in relation to total , but also in connection with partial substitution of sucrose and low xylitol consumption . The findings indicate a therapeutic , caries-inhibitory effect of xylitol A 3-year , double-blind caries trial was conducted to evaluate the caries-reducing effect of a modified technique to use toothpaste . At the outset , 369 children , 4 years of age , were r and omly assigned to four groups . At the end of the study , when the children were 7 years old , 281 ( 76 % ) had completed the trial . Two of the groups ( test groups , n = 131 ) were given the following instructions regarding ' toothpaste technique ' : ( 1 ) to spread the paste evenly on the teeth prior to brushing , ( 2 ) not to expectorate more than necessary during brushing , ( 3 ) to filter the remaining dentifrice foam in the dentition , together with a sip of water , by active cheek movements for 1 min before expectorating , and ( 4 ) not to carry out any further water rinsings afterwards , and not to eat or drink for 2 h after brushing . The children in the other two groups ( control groups , n = 150 ) were not given any instruction how to use the dentifrice and how to rinse after the brushing , but were , as the children in the test groups , encouraged to use the test dentifrice and to brush their teeth twice daily . Two commercial fluoride dentifrices ( A and B ) were compared : one of the test groups and one of the control groups used each product . Approximal carious lesions were scored on bite-wing radiographs at baseline and at the end of the study on the distal surface of the first and on the mesial surface of the second primary molars . No difference in caries increment was found between toothpastes A and B. The children in the two test groups developed a mean of 1.14 new dfs during the 3 years compared to 1.55 in the two control groups ( p < 0.05 ) . Thus , the results indicate that the modified toothpaste technique reduced approximal caries in preschool children by an average of 26 % Background / Aims : Root caries among elderly communities is of growing public health concern globally . This controlled clinical trial investigated the effectiveness of silver diamine fluoride and oral health education in preventing and arresting root caries . Methods : Two hundred sixty-six elderly subjects who had at least 5 teeth with exposed root surfaces and did not have serious life-threatening medical diseases were allocated to 3 groups according to a computer-generated r and om list : group 1 ( the control group ) received oral hygiene instructions ( OHI ) annually ; group 2 received OHI and silver diamine fluoride ( SDF ) application annually , and group 3 was given OHI and SDF application annually , plus an oral health education ( OHE ) programme every 6 months . Results : Two hundred twenty-seven elderly subjects were followed for 24 months . The mean numbers of new root caries surfaces in groups 1 , 2 and 3 were 1.33 , 1.00 and 0.70 , respectively ( ANOVA , p < 0.05 ) . Group 3 had fewer root surfaces with new caries than group 1 ( Scheffé multiple-comparison test , p < 0.05 ) . The mean numbers of arrested root caries surfaces in groups 1 , 2 and 3 were 0.04 , 0.28 and 0.33 , respectively ( ANOVA , p < 0.01 ) . Group 3 and group 2 had a greater number of active root caries surfaces which became arrested than group 1 ( Scheffé multiple-comparison test , p < 0.05 ) . Conclusion : Annual application of SDF together with biannual OHE was effective in preventing new root caries and arresting root caries among community-dwelling elderly subjects OBJECTIVE To compare the effectiveness of three applications of silver diammine fluoride ( SDF ) solution at yearly interval and three applications of SDF solution or sodium fluoride ( NaF ) varnish at weekly interval at baseline in arresting active caries in the primary teeth of preschool children . METHODS Children aged 3 - 4 years ( n = 371 ) who had at least one active caries lesion ( ICDAS codes 3 - 6 ) in their primary teeth were r and omly allocated into three groups : Group 1 - annual application of 30 % SDF solution ; Group 2 - three applications of 30 % SDF at weekly intervals ; and Group 3 - three applications of 5 % NaF varnish at weekly intervals . Follow-up examinations were performed every 6 mo nths by the same masked examiner . RESULTS After 30 months , 309 ( 83 % ) children with 1877 caries lesions remained in the study . For cavitated lesions ( ICDAS code 5 or 6 ) , the caries arrest rate of Group 1 ( 48 % ) was significantly higher than those of Group 2 ( 33 % ) and Group 3 ( 34 % ) , ( p < 0.001 ) . Results of multi-level survival analysis showed that the arrest times of cavitated lesions in both SDF groups ( Groups 1 and 2 ) were significantly shorter than that of the NaF varnish group . For moderate caries lesions without visible dentine ( ICDAS code 3 or 4 ) , the caries arrest rates were 45 % , 44 % and 51 % in Groups 1 , 2 and 3 , respectively ( p > 0.05 ) . Presence of plaque on caries lesion , tooth type and tooth surface type had an influence on caries arrest . CONCLUSION Over a 30-month period , annual applications of SDF solution is more effective than three weekly applications of NaF varnish or SDF solution at baseline in arresting active cavitated dentine caries lesions in primary teeth . CLINICAL SIGNIFICANCE As annual application of SDF solution was found to be more effective than 3 weekly applications of NaF varnish or SDF solution at baseline in arresting active cavitated dentine caries lesions , the former application protocol is preferred for young children who are available for regular caries arrest treatment This r and omized clinical trial aim ed to compare the adverse effects and parental satisfaction following the different regimes of silver diamine fluoride ( SDF ) treatment among preschool children . A total of 888 preschool children who had active dentin caries received different SDF application regimes : group 1 , 12 % SDF applied annually ; group 2 , 12 % SDF applied semiannually ; group 3 , 38 % SDF applied annually ; and group 4 , 38 % SDF applied semiannually . Information on adverse effects — including tooth or gum pain , gum swelling , gum bleaching , and systemic toxicity — was collected through a parent-reported question naire within 1 wk after every SDF or placebo application . Information of parental satisfaction on children ’s dental appearance was collected at baseline and 30-mo examination . At the 30 mo , 799 children ( 90 % ) remained in the study . No acute systemic illness or major adverse effect was reported . No differences of all minor adverse effects among the 4 groups were found ( P > 0.05 ) . Overall , prevalence of tooth and gum pain as perceived by patients and reported by parents was 6.6 % , while gum swelling and gum bleaching were 2.8 % and 4.7 % , respectively . Blackening of carious lesions was common among all groups , with 36.7 % , 49.5 % , 65.6 % and 76.3 % in groups 1 to 4 , respectively ( χ2 test , P < 0.001 ) . The proportion of parents who were satisfied with their children ’s dental appearance in groups 1 to 4 was as follows : 67.6 % , 61.5 % , 70.8 % , and 62.3 % , respectively ( χ2 test , P > 0.05 ) . Based on parental reporting , SDF does not cause acute systemic illness . Tooth or gum pain , gum swelling , and gum bleaching were uncommon and not significantly different among the study groups . Parental satisfaction with children ’s dental appearance was similar among all groups . The use of SDF following the study protocol for caries arrest is safe for preschool children . Collecting information on parental satisfaction and adverse effects is beneficial for dental professionals when deciding to adopt SDF treatment for preschool children ( Clinical Trials.gov NCT02385474 ) BACKGROUND The objective of this research was to assess the efficacy and cost-effectiveness of a non-invasive approach to dental caries management in private dental practice . METHODS Private dental practice s from a variety of locations in New South Wales were r and omly allocated to either non-invasive management of caries , or continue with usual care . Patients were followed for three years and caries incidence assessed . A patient-level decision analytic model was constructed to assess the cost-effectiveness of the intervention at two years , three years , and hypothetical lifetime . RESULTS Twenty-two dental practice s and 920 patients were recruited . Within the clinical trial there was a significant difference in caries increment favouring non-invasive therapy at both two and three years . Efficacy was independent of age , gender , medical concerns , fluoride history , or previous history of dental caries , in a population of patients attending for treatment in private dental practice s , in a variety of locations both urban and rural . Cost per DMFT avoided estimate was A$ 1287.07 ( two years ) , A$ 1148.91 ( three years ) decreasing to A$ 702.52 in ( medium ) and A$ 545.93 ( high ) risk patients ( three years ) . CONCLUSIONS A joint preventive and non-invasive therapeutic approach appears to be cost-effective in patients at medium and high risk of developing dental caries when compared to the st and ard care provided by private dental practice Objective : The aim of this study was to test the efficacy of long-term , daily intake of erythritol and xylitol c and y , compared with sorbitol c and y , on the development of enamel and dentin caries lesions . Methods : The study was a double-blind r and omized controlled prospect i ve clinical trial . Altogether 485 primary school children , first- and second- grade rs at baseline , from southeastern Estonia participated in this 3-year intervention . Each child consumed four erythritol , xylitol or sorbitol ( control ) c and ies three times per school day . The daily intake of polyol was about 7.5 g. The International Caries Detection and Assessment System ( ICDAS ) was used in the clinical examinations by four calibrated examiners at baseline and at 12 , 24 and 36 months . Results : The annual examination analyses and the follow-up analyses confirmed that the number of dentin caries teeth and surfaces at 24 months follow-up and surfaces at 36 months follow-up was significantly lower in the mixed dentition in the erythritol group than in the xylitol or control group . Time of enamel/dentin caries lesions to develop and of dentin caries lesions to progress was significantly longer in the erythritol group compared to the sorbitol and xylitol groups . Also the increase in caries score was lower in the erythritol group than in the other groups . Conclusions : In the follow-up examinations , a lower number of dentin caries teeth and surfaces was found in the erythritol group than in the xylitol or control groups . Time to the development of caries lesions was longest in the erythritol group . Trial registration : Clinical Trials.gov Identifier NCT01062633 The purpose of this study was to determine the effect of a 48-month preventive dental program on the incidence of root caries in an urban , geriatric , noninstitutionalized population residing in an optimally fluori date d area . The 466 participants were r and omly assigned to one of three groups at baseline . Group A ( control ) : 171 subjects using a placebo mouthrinse daily ; group B : 147 subjects receiving semiannual applications of a topical APF gel ( 1.2 % F- ) with the daily use of a placebo mouthrinse ; group C : 148 subjects using a fluori date d mouthrinse daily , ACT ( 0.05 % F- ) . At baseline , the numbers of surfaces at risk , and decayed and filled surfaces were recorded . After 48 months , in addition , the number of reversed and new lesions were determined , and the incremental DMFS calculated . The data were analyzed by ANCOVA . The incremental DMFS were : A = 0.91 , B = 0.27 , C = 0.26 . The incremental DMFS in groups B and C were significantly lower than in group A ( P < .05 ) . The number of reversed lesions in group C ( 1.53 + /- 2.03 ) was significantly greater than in group A ( 1.11 + /- 1.74 ) and group B ( 1.01 + /- 1.86 ) ( P < .05 ) . The number of new lesions in group B ( 1.36 + /- 2.00 ) was significantly less than in group A ( 1.99 + /- 2.65 ) ( P < .05 ) . The daily use of the fluoride mouthrinse significantly increased the number of reversed lesions Abstract Background Dental caries is a persistent public health problem with little change in the prevalence in young children over the last 20 years . Once a child contracts the disease it has a significant impact on their quality of life . There is good evidence from Cochrane review s including trials that fluoride varnish and regular use of fluoride toothpaste can prevent caries . The Northern Irel and Caries Prevention in Practice Trial ( NIC-PIP ) trial will compare the costs and effects of a caries preventive package ( fluoride varnish , toothpaste , toothbrush and st and ardised dental health education ) with dental health education alone in young children . Methods / Design A r and omised controlled trial on children initially aged 2 and 3 years old who are regular attenders at the primary dental care services in Northern Irel and . Children will be recruited and r and omised in dental practice s. Children will be r and omised to the prevention package of both fluoride varnish ( twice per year for three years ) , fluoride toothpaste ( 1,450 ppm F ) ( supplied twice per year ) , a toothbrush ( supplied twice a year ) or not ; both test and control groups receive st and ardised dental health education delivered by the dentist twice per year . R and omisation will be conducted by the Belfast Trust Clinical Research Support Centre ( [ CRSC ] a Clinical Trials Unit).1200 participants will be recruited from approximately 40 dental practice s. Children will be examined for caries by independent dental examiners at baseline and will be excluded if they have caries . The independent dental examiners will examine the children again at 3 years blinded to study group . The primary end-point is whether the child develops caries ( cavitation into dentine ) or not over the three years . One secondary outcome is the number of carious surfaces in the primary dentition in children who experience caries . Other secondary outcomes are episodes of pain , extraction of primary teeth , other adverse events and costs which will be obtained from parental question naires . Discussion This is a pragmatic trial conducted in general dental practice . It tests a composite caries prevention intervention , which represents an evidence based approach advocated by current guidance from the English Department of Health which is feasible to deliver to all low risk ( caries free ) children in general dental practice . The trial will provide valuable information to policy makers and clinicians on the costs and effects of caries prevention delivered to young children in general dental practice .Trial registration EudraCT No : 2009 - 010725 - 39IS RCT N : IS RCT N36180119 Ethics Reference No : 09/H1008/93 Evidence regarding the caries-inhibiting effect of chlorhexidine varnish is inconclusive . This study investigated the caries-inhibiting effect of the varnish EC40 on pits and fissures of first permanent molars . A two-year r and omized controlled trial was carried out among 461 six- to seven-year-old children . In a split-mouth design , one group of molars received EC40 at baseline , 6 , 12 , and 18 months , and another group at baseline , 3 , 12 , and 15 months . Control molars did not receive EC40 . Adherence to the treatment protocol was good . The dropout rate was 17 % . Blinded examiners performed dental examinations . The caries-inhibiting effects of the two EC40 application schemes were comparable . The prevented fraction of caries was 25 % ( 95%CI , 1 % , 49 % , p = 0.04 ) after 2 years and 9 % ( 95%CI , −11 % , 29 % , p = 0.20 ) one year after termination of the trial , suggesting a short-term benefit from the use of EC40 . The efficiency of EC40 is question able in low-caries-incidence child population Objective The aim of this study was to determine the effect of casein phosphopeptide-amorphous calcium phosphate ( CPP-ACP ) on caries progression in irradiated nasopharyngeal carcinoma ( NPC ) patients . Methods Twenty-one males and three females ( median age , 50 years ) were r and omized into two groups before radiotherapy . Subjects had at least eight teeth after oral health clearance . The test group used 0.4 % stannous fluoride gel and a crème containing 10 % CPP-ACP daily ; the control group used a similar crème without CPP-ACP and otherwise identical care . Subjects applied the crème three times daily and fluoride gel once daily . Caries status , saliva and plaque parameters were measured pre-radiotherapy , at 2 weeks and 3 months post-radiotherapy . Results Baseline International Caries Detection and Assessment System ( ICDAS ) scores were 0–1126 surfaces ( 93.9 % ) , 1–28 surfaces ( 2.3 % ) , 2–40 surfaces ( 3.3 % ) and 3–6 surfaces ( 0.5 % ) for the control and 0–1186 surfaces ( 95.6 % ) , 1–31 surfaces ( 2.5 % ) , 2–15 surfaces ( 1.2 % ) and 3–8 surfaces ( 0.7 % ) for the test group . Twenty-two subjects returned at 3 months post-radiotherapy with reduced plaque pH , salivary flow , pH and buffering capacity . Nine test and 8 control subjects developed 32 and 59 new caries lesions , respectively . Test subjects showed lower caries progression than the controls : all surfaces ( OR 0.51 , 95 % CI 0.17∼1.59 ) , occlusal ( OR 0.20 , 95 % CI 0.03∼1.29 ) and smooth surfaces ( OR 0.61 , 95 % CI 0.16∼2.38 ) . The difference was not statistically significant . Conclusion Application of CPP-ACP did not significantly reduce caries progression in NPC patients in the first 3 months after radiotherapy as compared to controls . Clinical relevance Adjunct use of CPP-ACP with stannous fluoride gel in irradiated NPC patients gave comparable results compared to stannous fluoride gel alone in reducing caries progression OBJECTIVE This prospect i ve r and omized clinical trial investigated the impact of different tooth brushing strategies and sealant application on patients with fixed appliances : plaque , gingival , caries index scores , periodontal parameters , microbial , and molecular biological parameters were assessed . MATERIAL S AND METHODS Fifty-five male and 63 female patients aged 11 - 15 years were enrolled in this 12-week , four-arm parallel-group trial . Patients of group 1 used a Sonicare FlexCare electric brush , patients of group 2 used a manual ( elmex interX short head ) plus interdental ( Curaprox CPS 15 ) brush , and patients of group 3 and 4 used a manual brush only . The teeth of patients in groups 1 , 2 , and 3 were sealed with a filled resin ( ProSeal ) . Patients were advised to brush twice daily and measured time spent brushing mornings and evenings [ tooth brushing duration ( TBD ) ] . Plaque ( PIB , TQHI , MAPI ) and gingival index ( PBI ) as well as caries index ( DMFT/DMFS ) scores were assessed at baseline and after 4 , 8 , and 12 weeks . RESULTS AND CONCLUSIONS TBD did not differ significantly between patients using the electric or manual brush only ( between 197 and 209 seconds ) but was longer when using the combination of two manual brushes . TBD was slightly longer in the evenings . There was no gender difference . Although TBD was longer for the combination group , we failed to demonstrate any beneficial effect on outcome parameters for this group . No differences between sealed or unsealed tooth surfaces or for use of a manual or electric brush were observed In a municipality near Copenhagen , Denmark , where fortnightly fluoride rinses with 0.2 % neutral sodium fluoride had been performed for more than a decade , 1306 children from kindergarten through 6th grade were stratified by school and grade and r and omly distributed into two groups . One group continued the fluoride rinses , the other group had the fluoride solution replaced with distilled water . Both solutions were slightly flavored . 1083 children completed the 3-yr trial . Caries was recorded clinical ly by the dentists in the municipal dental service using the diagnostic criteria for the Child Dental Health Services , and on bitewing radiographs by one of the authors applying the criteria developed by GRONDAHL et al. Permanent molars and premolars were included in the study . Clinical ly , caries increment in the two groups was the same with pits and fissures containing 94 % of the DMFS . According to the radiographs , caries progression in the water group was higher than in the fluoride group . This difference was statistically significant for the surfaces erupting during the study ( P less than 0.05 ) OBJECTIVES To determine the efficacy of 5 % sodium fluoride ( NaF ) varnish application in reducing caries increments in the permanent dentition of rural Brazilian school children over the course of 12 months . METHODS A double-blind , r and omized , placebo-controlled trial was conducted with 379 children aged 7 - 14 years who attended three schools in Brazil between January 2006 and December 2007 . During this period , each school was visited four times at 6-month interval for recruitment , dental examinations , and fluoride varnish applications . Recruited children were r and omly assigned to either a treatment ( 5 % NaF varnish , n = 198 ) or a control group ( placebo , n = 181 ) . Trained interviewers collected data on oral health habits and sociodemographic characteristics from the children . Information on the child 's diet was collected through a 7-day food frequency diary . Caries examinations were conducted using the International Caries Detection and Assessment System ( ICDAS ) . The efficacy of fluoride varnish application on caries prevention was reported as a preventive fraction ( PF ) . Crude caries increments of decayed and filled surfaces ( DFS ) were compared between fluoride varnish and placebo groups . A generalized linear model ( GLM ) was constructed to test the differences in DFS increments between the groups after accounting for confounding factors . RESULTS Of the total sample ( N = 379 ) , 210 ( 55.4 % ) children had completed 12 months of follow-up including one or two applications of fluoride varnish or placebo . At the baseline examination , the children in the treatment and control groups presented on average 6.2 and 5.6 DFS , respectively ( P < 0.001 ) . After 12 months of follow-up , the children in the varnish group showed significantly lower DFS increments than did children in the control group ( 10.8 versus 13.3 ; P < 0.007 ) , with PF of 40 % ( 95 % CI : 34.3 - 45.7 % ; P < 0.0001 ) . CONCLUSIONS The results of this study suggest that applications of 5 % NaF varnish can be recommended as a public health measure for reducing caries incidence in this high-caries-risk population Aim : To evaluate in vivo the remineralizing efficacy of silver diamine fluoride ( SDF ) , glass ionomer Type VII ( GC VII ) and calcium hydroxide ( Dycal ) . Material s and Methods : 60 subjects in the age group of 18 - 35 years , matching the inclusion criteria and having deep carious lesions in the permanent first and second molars were selected . The teeth were aseptically opened under rubber dam and after gross caries removal , approximately 0.4 mg of soft discolored dentin was removed with a sharp spoon excavator from the mesial or distal aspect of the cavity . The test material was r and omly selected and applied in a thickness of 1.5 - 2 mm and the cavity sealed with cavit . The patients were followed up at regular intervals with radiographic evaluation at 12 weeks . At 3 months the temporary restoration was removed and dentin sample s were collected from the other half of the cavity which was left in the first appointment . Atomic absorption spectrophotometry , Colorimetric test using UV-vis spectrometer and potentiometric titration were used for determining calcium , phosphorous and fluoride respectively . Results : Almost equivalent rise in the percentage of calcium level was seen in GC VII and Ca(OH)2 groups , followed by SDF group . Highest percentage rise in phosphate ions was seen in GC VII group followed by SDF group and Ca(OH)2 group . Highest percentage of fluoride rise was seen in GC VII group followed by SDF group and Ca(OH)2 group . Conclusions : The results indicated that both GC VII and SDF can be potential indirect pulp capping material A community intervention trial was conducted to assess the feasibility of APF gel as a caries-preventive agent in a high-risk group of school children in Bangalore City . The study was conducted in two schools , r and omly selected from a list of schools catering to underprivileged children . These schools were r and omly allocated into experimental and control groups . Children aged 9 - 16 years having three or more incipient or cavitated primary or secondary carious lesions were enrolled in the study . In the experimental group , APF gel was applied and oral health education was provided to both groups at baseline and 6 months . Follow-up examination was performed at 6 and 12 months and the caries status was recorded by an investigator who was blinded to the allocation of intervention . There was no statistically significant difference in DMFT and DMFS values , but a significant difference was seen in incipient carious lesions between the experimental and control groups at 6 and 12 months . These results suggest that biannual APF gel application is an effective preventive measure in reversing incipient carious lesions Even though there is no “ gold st and ard ” for determining caries lesion activity , it is nonetheless possible to evaluate the validity of such diagnostic measures . The aim of this study was to estimate the construct and predictive validity of caries lesion activity assessment s by means of their ability to reflect known effects of fluoride on caries . A three-year trial of the effect of daily supervised brushing with fluoride toothpaste was carried out among 273 12-year-old children . All children were examined clinical ly according to diagnostic criteria for activity assessment . The relative risk ( fluoride vs. control ) for caries lesion transitions among diagnostic categories was calculated . Fluoride inhibited progression of caries at all stages of lesion formation while at the same time enhancing lesion regression . The effects were most pronounced for active non-cavitated lesions . It is concluded that the clinical diagnostic criteria have construct and predictive validity for the assessment of caries lesion activity OBJECTIVE The purpose of this study was to determine whether Cervitec -- a chlorhexidine -- containing varnish could reduce the development of pit and fissure caries in children . METHODS One hundred children each in age groups 7 - 8 and 12 - 14 years were selected from schools in Riyadh , Saudi Arabia . To be included in the study , each child had to have at least two sound contra-lateral first or second permanent molars with deep fissures . A split mouth method was used with one test tooth and one control within the same jaw . The left or the right side was selected r and omly for test or control . The plaque sample s from the occlusal surfaces of the test and control and the saliva sample s were collected at baseline examination and after 9 months to estimate the number of Streptococcus mutans by the strip mutans method of Jensen and Bratthall ( Jensen B , Bratthall D. A new method for the estimation of mutans streptococci in human saliva . Journal of Dental Research 1989;68:468 - 471 ) . Cervitec varnish containing 1 % chlorhexidine ( CHx ) and thymol was applied at baseline , at 3 - 4 months and at 6 months to the test tooth after isolation while the control had prophylaxis using cotton pellet in water each time the varnish was applied to the test tooth . Caries examination of the test and control followed after 9 months , according to the criteria and methods of WHO ( World Health Organization . Oral Health Surveys . Basic Methods 4th ed . , Geneva , WHO 1997 ) . The blind technique was used in the diagnosis of caries and in the examination of the S. mutans count at the end of the study . RESULTS Ninety four of the 7 - 8 year old and 86 of the 12 - 14 year old children completed the study . The results showed that the caries increment in both control groups of teeth after 9 months is significantly higher than in the test teeth ( McNemar test : chi2 = 11.60 , P < 0.001 ) . The rate of caries development in a fissure was significantly correlated to the plaque mutans score of that fissure and there was considerable reduction in the S. mutans count of the plaque in the test teeth compared with the control ( Spearman Rank Correlation : P < 0.001 ) . CONCLUSION It is concluded that the CHx varnish reduced the development of fissure caries significantly PURPOSE The effect of a chlorhexidine varnish delivery system on the levels of selected oral microorganisms was evaluated in caries active pediatric patients , ages 4 to 12 years old . METHODS Forty-six patients were enrolled into the study when they had multiple carious surfaces and salivary mutans streptococci ( MS ) levels higher than 10(4 ) colony forming units ( CFUs ) per milliliter . This study incorporated a double-blind design and patients were r and omly assigned to either the chlorhexidine treatment group or the placebo group . Complete-arch , vacuum-adapted mouthguards ( 0.02 in . polypropylene coping material ) were custom fabricated and coated internally with either a 3.0 % chlorhexidine varnish or a placebo varnish . Two pretreatment paraffin-stimulated saliva sample s were obtained for culturing prior to varnish treatment . Saliva sample s were also obtained immediately after treatment and once a month for up to three months after wearing the mouthguard appliances . Dental restorations were placed at most of these saliva collection visits . Mouthguards were reportedly worn for an average of 9.7 hours per night for approximately seven nights by 40 subjects ( 87 % ) . RESULTS After two months , and after three months , there was a significant reduction in MS levels immediately after the chlorhexidine varnish treatment . Total anaerobic and total facultative bacteria levels were not significantly affected . CONCLUSION One week of nightly use of the chlorhexidine varnish mouthguard system is effective at reducing the number of MS in caries-active pediatric patients in the mixed and primary dentition for at least three months The aim of our study was to compare the changes in children 's oral health-related behavior , knowledge , and attitudes obtained using an oral health-promotion approach , a risk- strategy and promotion approach , and reference area , and to report changes in the behavior of children between the experimental and the control groups of a r and omized clinical trial ( RCT ) . The study population consisted of all fifth and sixth grade rs who started the 2001 - 2002 school year in Pori , Finl and ( n = 1,691 ) , where the RCT and program of oral health promotion were implemented for 3.4 yr . Children with at least one active caries lesion were r and omly assigned to experimental ( n = 250 ) and control ( n = 247 ) groups . Children in Rauma ( n = 807 ) acted as the reference . Changes in children 's self-reported behavior , knowledge , and attitudes were compared between groups . The subjects in the oral health-promotion group and in the risk- strategy and promotion group in Pori tended to show greater improvement in most of their oral health-related behaviors than those in the reference group , and children in the RCT experimental group showed greater improvement in most of their oral health-related behaviors than those in the RCT control group . Children can be helped to improve their oral health-related behavior by intervention , including oral hygiene and dietary counseling , or by implementing a multilevel-approach oral health-promotion program A r and omized double-blind clinical trial was undertaken in a non-fluori date d community to assess the effectiveness of a minimal preventive intervention based on biannual applications of an amine fluoride ( AmF ) solution containing 1 % fluoride . A total of 284 schoolchildren aged 6 years were recruited from a primary school in Milan , Italy , and r and omly assigned to an experimental or a control group . The subjects of the experimental group received two applications each year of AmF to the permanent first molars and the control group subjects received similar applications of a placebo solution . Both in the experimental and control groups caries experience ( DMFT ) of the first molars was recorded every 6 months for 5 years . The mean DMFT scores in the experimental and control group were , respectively , 0.56 and 0.22 at the beginning and 1.14 and 1.75 at the end of the study . The preventive effect of the treatment became statistically significant only after 3 years . Survival analysis performed on the first molars that were sound at baseline showed that the topical AmF treatment caused , after 5 years , a significant reduction of caries incidence . This result confirms observations found in the international literature on the anticaries action of AmF. The administration rate used in this study seems to be useful for community preventive applications as it reduces the total amount of fluoride administered and the potential risks , and involves few personnel The aim of this prospect i ve study was to determine the effectiveness of caries preventive measures started during pregnancy on the caries experience of first-time mothers and their infants . Eighty-one pregnant women with low social background were selected on the basis of the presence of active carious lesions and were r and omly divided into control ( 38 ) and experimental ( 43 ) groups . The initial dental status ( DMFS and white spot lesions ) was established through clinical examination . The prophylactic measures were repeated during pregnancy and 6 and 12 months after delivery . Both groups received primary care intervention . They were instructed in relation to the etiologic factors of dental caries and received oral hygiene kits . Oral hygiene instructions were reinforced through interactive brushing . The experimental group also received antimicrobial treatment ( topical application of NaF and iodine solution immediately after prophylaxis and 3 and 5 days later ) and restorative care using glass ionomer cement . By the time the children were 2 years of age , 33.3 % of the infants in the control group and 14.7 % in the experimental group had caries activity . A significant difference in caries prevalence was observed between children with and without visible dental plaque . The mean number of tooth surfaces with carious lesions ( including areas of demineralization ) was higher among the children in the control group compared to the experimental group ( 6.3 x 3.2 ) , however , with no statistical significance . Maternal caries increase was a significant factor influencing the caries experience of the children . These data support the evidence of an association between caries prevalence in young children and clinical ( dental plaque ) and maternal factors INTRODUCTION Oral care in cancer patients is an important aspect in the quality of life of patients undergoing cancer therapy . Mucositis , trismus , salivary gl and dysfunction are the main complications of the cancer therapy , which lead to long-term complications such as radiation caries , poor oral hygiene and osteoradionecrosis . A timely oral evaluation and intervention in these patients can reduce the severity of the potential complications . Triclosan is an antibacterial agent widely used in periodontal therapy , the effectiveness of triclosan in the management of radiation induced oral mucositis is evaluated here . AIMS 1 ) To determine the effectiveness of triclosan in the management of radiation-induced oral mucositis . 2 ) To compare the effectiveness of triclosan mouth rinse with conventional sodium bicarbonate mouth rinse . MATERIAL S AND METHODS Twenty-four patients who underwent radiation therapy for oral cancer and subsequently developed oral mucositis were included in the study . They were r and omly allocated into two groups on noticing grade I mucositis ( erythema ) . The study group was advised to use triclosan mouthwash containing triclosan 0.03 % W/V and sodium bicarbonate 2 mg mouth wash for the control group . A weekly follow-up evaluation of body weight , food intake , pain and grading of mucositis were made during the radiation treatment period and post radiation treatment period . RESULTS Both the groups were statistically identical . All the 24 patients in both the groups passed through grade 3 mucositis on the last day of radiotherapy . However , 10 patients in the control group and only one patient in the study group entered to grade 4 mucositis . A definite change was noticed in the severity of the mucositis , food intake and weight loss . The control group took more than 45 days to resolve while the study group took only less than 28 days . DISCUSSION The results of the study were evaluated and tried to formulate a hypothesis so as to explain the less severity and early resolution of mucositis in the study group . CONCLUSION Triclosan mouthwash was found to be effective in reducing the severity of radiation- induced oral mucositis and helped in early reversal of symptoms during post treatment period . However , further studies are necessary to confirm this observation Design A double-blind , cluster-r and omised , double-blinded clinical trial was conducted . InterventionAll children within a fluori date d area with low caries received oral health programmes based on their estimated risk of caries . The children were divided into five groups . Four groups received three times daily xylitol/maltitol ( 4.7g/4.6 g ) lozenges or erythritol/maltitol ( 4.5g/4.2 g ) lozenges for either one or two school years . One group did not receive lozenges . Clinical examination was undertaken at baseline and after 48 months primarily by one dentist who was blinded to the assignment of each child . Radiographical examination was undertaken at 48 months , with two calibrated dentists undertaking the analysis . Outcome measureChange in caries : decayed missing or filled surfaces at dentinal level ( ΔD3MFS ) . Results Forty-eight months after commencement of the research there were no statistically significant differences between the proportion of ΔD3MFS=0 ( clinical ly or radiographically ) within the groups ( xylitol/maltitol or erythritol/maltitol lozenges ) . Seventy-five of the children were lost to follow up , seven discontinued through other reasons . Conclusions The use of xylitol-maltitol or erythritol-maltitol lozenges within a cohort of low caries children either over nine months or 21 months were not effective in reducing dental caries in primary school children Arresting Caries Treatment ( ACT ) has been proposed to manage untreated dental caries in children . This prospect i ve r and omized clinical trial investigated the caries-arresting effectiveness of a single spot application of : ( 1 ) 38 % silver diamine fluoride ( SDF ) with tannic acid as a reducing agent ; ( 2 ) 38 % SDF alone ; ( 3 ) 12 % SDF alone ; and ( 4 ) no SDF application in primary teeth of 976 Nepalese schoolchildren . The a priori null hypothesis was that the different treatments have no effect in arresting active cavitated caries . Only the single application of 38 % SDF with or without tannic acid was effective in arresting caries after 6 months ( 4.5 and 4.2 mean number of arrested surfaces ; p < 0.001 ) , after 1 year ( 4.1 and 3.4 ; p < 0.001 ) , and after 2 years ( 2.2 and 2.1 ; p < 0.01 ) . Tannic acid conferred no additional benefit . ACT with 38 % SDF provides an alternative when restorative treatment for primary teeth is not an option The aim of the present trial was to ( 1 ) compare the caries-preventive effect of glass ionomer sealants , placed according to the atraumatic restorative treatment ( ART ) procedure , with composite resin sealants over time and ( 2 ) investigate the caries-preventive effect after complete disappearance of sealant material . Forty-six boys and 57 girls , mean age 7.8 years , were r and omly divided into two treatment groups in a parallel-group study design . A light-polymerized composite resin sealant material and a high-viscosity glass ionomer were each placed in 180 fully erupted first molars in their respective treatment groups . Evaluation took place annually for 5 years by calibrated examiners . After 5 years , 86 % composite resin and 88 % glass ionomer sealants did not survive . Three categories of re-exposure periods for caries development in pits and fissures after complete loss of sealants were distinguished : 0–1 , 1–2 and 2–3 years . In the 2- to 3-year group , 13 and 3 % of pits and fissures previously sealed with composite resin and glass ionomer , respectively , were diagnosed as having developed a dentine lesion . The relative risks ( 95 % CI ) of dentine lesion development in surfaces sealed with glass ionomer compared to those sealed with composite resin after 3 , 4 and 5 years were 0.22 ( 0.06–0.82 ) , 0.32 ( 0.14–0.73 ) and 0.28 ( 0.13–0.61 ) , respectively . The relative risks of dentine lesion development in pits and fissures previously sealed with glass ionomer compared with composite resin over re-exposure periods of 1–2 and 2–3 years were 0.26 ( 0.14–0.48 ) and 0.25 ( 0.09–0.68 ) , respectively . We conclude that the caries-preventive effect of high-viscosity glass ionomer sealants , placed using the ART procedure , was between 3.1 and 4.5 times higher than that of composite resin sealants after 3–5 years . Furthermore , high-viscosity ( ART ) glass ionomer sealants appear to have a four times higher chance of preventing caries development in re-exposed pits and fissures of occlusal surfaces in first molars than light-cured composite resin sealant material over a 1- to 3-year period . A well- design ed clinical trial using different types of oral health personnel should be implemented to confirm these initial results The purpose of this study was to compare the effectiveness of toothbrushing followed by fluoride rinsing , fluoride gel brushing , or fluoride gel dentifrice brushing alone in controlling the demineralization that often follows orthodontic treatment . Seventy-eight consecutive adolescent patients undergoing orthodontic care were divided into 3 groups : group 1 ( control ) used a low-potency , high-frequency fluoride rinse ; group 2 used a high-potency , high-frequency fluoride brush-on gel ; and group 3 used a high-potency , high-frequency fluoride gel dentifrice . When pretreatment levels of demineralization were subtracted from posttreatment values , both gel groups displayed a significant difference ( P < .05 ) in smooth surface demineralization sites when compared to controls . Reversal of white-spot lesions occurred in 15 % of sites that exhibited pathology as a result of the fluoride and preventive regimen . These results indicate that a daily use of a 5000-ppm fluoride gel along with toothbrushing with a fluoride paste or brushing twice daily with a 5000-ppm fluoride dentifrice alone provides greater protection beyond that of tooth-brushing with a fluoride paste ( 1000 ppm ) and rinsing with a 0.05 % sodium fluoride rinse A prospect i ve examination of 10 consecutively treated orthodontic patients was undertaken to examine the effectiveness of fluoride varnish in reducing enamel demineralization . Pairs of dental quadrants for each patient 's mouth ( ie , maxillary right and m and ibular left ; maxillary left and m and ibular right ) were r and omly assigned to an experimental or control group . After placement of resin-bonded orthodontic brackets , fluoride varnish was applied to the 2 experimental dental quadrants for each patient . Subsequent applications were done every 3 months during 12 months of orthodontic treatment . A double-blinded examination of intraoral photographs of the 100 experimental and 100 control teeth was done . The presence of white spot lesions was registered using the enamel decalcification index and the 2 groups were compared using paired Student t tests with a significance level of 5 % ( P < .05 ) . There was no statistically significant difference between the mean enamel decalcification index for the control and experimental groups before or after treatment , since demineralization increased for both groups . Most importantly , the change in mean enamel decalcification index was significantly smaller for the experimental group ( 0.34 ) , compared to the control group ( 0.51 ) . In other words , there was 44.3 % ( P < .05 ) less demineralization noted for teeth that had been treated with fluoride varnish during orthodontic treatment OBJECTIVES To determine whether the cessation for 3 years of a 24-month program of chlorhexidine-thymol varnish applications would affect caries incidence in the first permanent molars of a population of schoolchildren of middle and lower-middle socioeconomic level . METHODS Two groups of 6 - 7-year-old schoolchildren , r and omized by school-class , were followed up in a clinical trial . One group received applications of chlorhexidine-thymol varnish every 3 months and the other group acted as controls . The program ended after 24 months and its effects were evaluated . Three years later , 55.5 % of the schoolchildren were re-examined and the caries increments were documented . RESULTS At the end of the 24-month program , the treated children had significantly fewer decayed and filled surfaces in permanent molars ( lower DFS index ) versus the controls . At 3 years after the discontinuation of the program , this difference had disappeared ; there were no differences in the incidence of decayed , missing and filled surfaces ( DMFS ) index in permanent molars between the treated children and the controls . CONCLUSION The cessation for 3 years of a 3-month program of chlorhexidine-thymol varnish applications result ed in a nonsignificant increase in the prevalence of dental caries in the permanent first molar The purpose of the paper is to describe the essential findings in two clinical trials , carried out in order to evaluate differences in the caries increment rate as influenced by various sugars . The first study involved almost complete substitution of sucrose ( S ) by fructose ( F ) or xylitol ( X ) during a period of 2 years . The second study comprised partial substitution , the effects of a S- or X-containing chewing gum being compared during 1 year . In the first study there were no significant differences initially between the sugar groups ; 35 subjects in the S-group , 38 in the F-group , and 52 in the X-group . During the entire study 10 subjects discontinued or were excluded . After 2 years the mean increment of decayed , missed and filled tooth surfaces was 7 - 2 in the S-group , 3 - 8 in the F-group , and 0 - 0 in the X-group . The second study comprised initially 102 subjects , predominantly dental and medical sutdents , divided r and omly into S- and X-groups . During the study 2 subjects were excluded . The subjects consumed 4 - 0 chewing gums per day in the S-group and correspondingly 4 - 8 in the X-group . The frequency of sucrose intake was 4 - 24 times per day in the S-group , and 4 - 94 in the X-group . The caries incidence assess independently by clinical and radiographical means , equalled the 1-year observations in the first study . The results show a massive reduction of the caries increment not only in relation to total , but also in connection with partial substitution of dietary sucrose and low xylitol consumption . The first study indicates fructose to be somewhat less cariogenic than sucrose . In view of the findings in the chewing gum study it is suggested that the non- and anticariogenic properties of xylitol principally depend on its lack of suitability for microbial metabolism and the physico-chemical effects in plaque and saliva brought about through low and repeated dosage Introduction : To promote the remineralization by ionic exchange mechanism instead of invasive techniques many remineralizing agents can be used . Objective : To evaluate the remineralization effects of casein phosphopeptide-amorphous calcium phosphate ( CPP-ACP ) on white spot lesions ( WSLs ) and its inhibitory effect on Streptococcus mutans colonization . Material s and Methods : The study group consisted of 60 subjects exhibiting at least 1-WSL . Subjects were r and omly divided into 2 groups : A test group using CPP-ACP cream ( GC-Tooth Mousse , Leuven , Belgium ) and a control group using only fluoride containing toothpaste for a period of 3-month . Baseline WSLs were scored using DIAGNOdent device ( KaVo Germany ) and the saliva sample s were collected to measure S. mutans counts . After the 3-month period the WSLs were again recorded and the saliva collection was repeated . Result : DIAGNOdent measurements were increased by time ( P = 0.002 ) in the control group and no statistically significant difference ( P = 0.217 ) was found in the test group by the 3-month period . In both groups , the mutans counts were decreased in the 3-month experimental period . Conclusion : These clinical and laboratory results suggested that CPP-ACP containing cream had a slight remineralization effect on the WSL in the 3-month evaluation period however , longer observation is recommended to confirm whether the greater change in WSLs is maintained The purpose of this study was to demonstrate the effectiveness of two fluoride varnishes ( Duraphat and Fluor Protector ) in the prevention of dental caries in children residing in a non-fluori date d community . At baseline , 787 grade one children ( 6 - 7-yr old ) were examined and r and omly allocated into a control and two treatment groups . At 20 months , 703 children remained in the study . The mean baseline caries experience and the mean number of permanent teeth present at 20 months were not significantly different among the treatment and control groups . The mean DMFS increments after 20 months were 1.70 , 1.73 and 2.02 for Fluor-Protector , Duraphat and control groups respectively ( % reductions of 15.8 and 14.4 for Fluor-Protector and Duraphat groups ) . The mean dfs increments for primary molars after 20 months were 1.56 , 1.62 and 1.74 for Fluor-Protector , Duraphat and control groups respectively ( % reductions of 10 for Fluor-Protector and 7 for Duraphat ) AIM The purpose of the present study was to evaluate in a group of periodontal maintenance patients , the effect of using a dentifrice and mouthrinse containing amine fluoride ( AmF ) and stannous fluoride ( SnF2 ) as compared with a dentifrice and mouthrinse both containing sodium fluoride ( NaF ) with regard to their root caries experience . MATERIAL In total , 80 patients who had been treated for moderate-to-severe periodontitis agreed to participate in this study . Subjects received supportive periodontal therapy at regular intervals of 3 - 4 months for at least a period of 1 year . The patients were r and omly divided into two groups : ( 1 ) the test group used an AmF/SnF2 dentifrice and mouthrinse and ( 2 ) the control group used an NaF-containing dentifrice and mouthrinse . Root caries was recorded at four sites per tooth at baseline and 24 months . RESULTS An increase in number of the exposed root surfaces was noted for both groups during the experimental period ( p<0.05 ) . The mean number of active caries lesions at baseline was 2.1 and 1.8 for the test group and control group , respectively . At 24 months , the corresponding values were 1.8 for the test and 2.2 for the control group . An increase of the mean number of restored surfaces was noted for the AmF/SnF2 group ( from 7.3 to 13.4 ) and the control group ( from 7.9 to 14.7 ) during the course of the study . This increase was found to be statistically significant for both groups in comparison with the baseline values ( p < or = 0.01 ) . No statistically significant differences were noted between groups . Further analysis of the restored surfaces revealed that the major increase in number of the restorations was associated with restorations involving three to four root surfaces in the same tooth . Molars and premolars were the teeth receiving most new restorations . CONCLUSION The present study did not detect a difference in terms of root caries development between the two groups . Root caries development is a common finding associated with surfaces developing recession in patients once treated for periodontal problems Background The Scottish Government set out its policy on addressing the poor oral health of Scottish children in 2005 . This led to the establishment of Childsmile , a national programme design ed to improve the oral health of children in Scotl and . One element of the programme promotes daily tooth brushing in all nurseries in Scotl and ( Childsmile Core ) . A second targeted component ( Childsmile Nursery ) offers twice-yearly application of fluoride varnish to children attending nurseries in deprived areas . Studies suggest that fluoride varnish application can reduce caries in both adult and child population s. This trial aims to explore the effectiveness and cost-effectiveness of additional preventive value fluoride varnish application compared to Childsmile Core . Methods / Design The Protecting Teeth@3 Study is an ongoing 2 year parallel group r and omised treatment as usual controlled trial . Three-year-old children attending the ante pre-school year are r and omised ( 1:1 ) to the intervention arm ( fluoride varnish & treatment as usual ) or the control arm ( treatment as usual ) . Children in the intervention arm will have Duraphat ® fluoride varnish painted on the primary tooth surfaces and will continue to receive treatment as usual : the core Childsmile Nursery intervention . Children in the treatment as usual arm will receive the same series of contacts , without the application of varnish and will also continue with the Childsmile Core intervention . Interventions are undertaken by Childsmile trained extended duty dental nurses at six-monthly intervals . Participants receive a baseline dental inspection in nursery and an endpoint inspection in Primary 1 at the age of 5 years old . We will use primary and secondary outcome measures to compare the effectiveness of Duraphat ® fluoride varnish plus treatment as usual with treatment as usual only in preventing any further dental decay . We will also undertake a full economic evaluation of the trial . Trial registration This study is registered at Clinical Trials.gov . Number : NCT01674933 ( 24 August 2012 ) PURPOSE This r and omized clinical trial compared the ability of two dentifrices , one containing 5000 ppm fluoride ( Duraphat ) and the other 1450 ppm fluoride ( Caries Protection , control ) to reverse non-cavitated fissure carious lesions . METHODS 30 adults having occlusal lesions with DIAGNOdent values between 10 and 20 were r and omly assigned to two groups of 15 participants each . DIAGNOdent measurements were performed after cleaning the teeth with cleaning brushes and after additional cleaning using an airflow device . The participants were instructed to brush their teeth three times a day for 3 minutes after the meals with a 2 cm line of their assigned dentifrice . After a period of 2 weeks , the teeth were cleaned again with the airflow device and laser fluorescence measurement was performed . RESULTS The group using the dentifrice containing 5000 ppm showed a significantly higher decrease in laser fluorescence ( 21 % ) over the test period than the control group ( 4 % ; P < 0.001 ; repeated measures ANOVA ) . The decrease in laser fluorescence in the test group was significant ( P < 0.001 ; Wilcoxon signed-rank test ) . The difference between cleaning the teeth with cleaning brushes and additional cleaning with airflow before DIAGNOdent measurement was not statistically different ( P > 0.05 ; Wilcoxon signed-rank test ) Background One of the most undesirable side effects of comprehensive orthodontic treatment is white spot lesions ( WSLs ) . Despite many attempts at prevention of WSLs , its prevalence remains very high on debonding . There are many agents like fluoride toothpastes , fluoride varnishes , and fluoride mouth rinses , and casein phosphopeptide-amorphous calcium phosphate ( CPP-ACP ) is frequently used for the remineralization of WSLs . However , there is no consensus in the literature with respect to the success rates of these agents . Thus , the present study was design ed to evaluate the efficacy of fluoride toothpaste alone and in combination with fluoride varnish and CPP-ACP plus crème in the remineralization of post-orthodontic WSLs . Methods Forty-five subjects in the age range of 16–25 years having at least one post-orthodontic WSL were included in the study . All the subjects were r and omly divided into three groups ( toothpaste group , varnish group , and CPP-ACP group ) . The efficacy of various remineralizing agents on the remineralization of WSLs was evaluated clinical ly and by DIAGNOdent immediately after debonding and subsequently after 1 , 3 , and 6 months of their use . Results Twice daily use of fluoride toothpaste alone had no significant effect on remineralization of WSLs at various intervals of observations ( P = 0.078 ) . Application of fluoride varnish along with twice daily use of fluoride toothpaste for 6 months significantly decreased the severity of WSLs ( P < 0.01 ) . Twice daily use of CPP-ACP plus crème along with fluoride toothpaste had significant effect on remineralization of WSLs at the end of 6 months of observation ( P < 0.05 ) . Between the group comparison showed that the mean visual and DIAGNOdent scores at various time intervals of observations were decreased more when fluoride varnish and CPP-ACP crème were used in addition to daily use of fluoride toothpaste , but the differences were not statistically significant ( P > 0.05 ) . Conclusions The use of fluoride varnish and CPP-ACP plus crème in addition to twice daily use of fluoride toothpaste had no additional benefit in the remineralization of post-orthodontic WSLs The purpose of this study was to evaluate the efficacy of non-invasive methods of treatment for active incipent occlusal caries . Anamnesis , professional prophylaxis , and visual inspection were used to classify 250 Brazilian pre-school-children . First permanent decayed molars ( n=98 ) from thirty-one subjects ( 6 years+ 6 months ) were selected and divided into three groups . Group 1 : fissure sealants with resin-modified glass ionomer - Vitremer ( n=29 ) ; Group 2 : fluoride varnish -Duraphat ( n=36 ) and control group : tooth brushing and 0.2 percent NaF weekly mouthwashes ( n=33 ) . Four clinical evaluations were carried out over three , six , nine , and twelve months . Caries activity and progression were observed through clinical and radiographic evaluation . The results were analyzed by Fisher = s Exact test . After twelve months , the results showed 100 percent of arrestment of caries activity for Group 1 , 83.3 percent for group 2 , and 72.7 percent for control group . At the same time , the results showed 0 percent of caries progression for group 1 , 5.5 percent for Group 2 , and 6.1 percent for control group . Group 1 showed a better inactivation property than the other groups ( p<0.05 ) . There were no statistically significant differences in caries progression among these groups ( p>0.05 ) . It was concluded that this non-invasive methods were able to arrest the progression of occlusal caries , but fissure sealant showed better results in controlling caries activity PURPOSE To evaluate the effect of casein phosphopeptides ( CPP ) and amorphous calcium phosphate ( ACP ) , as an adjunct to average oral hygiene , on the fluorescence of initial carious fissures and pits in vivo . METHODS For this investigator-blind in vivo study 32 volunteers were recruited . Subjects with premolars and molars showing DIAGNOdent-values between 15 and 20 were r and omly assigned to two treatment groups . During a wash-out period of 2 weeks and during the 3-week treatment period all subjects were instructed to use only st and ard fluoride toothpaste ( 1450 ppm F- as NaF ) and to abstain from any oral hygiene products other than dental tape . During the treatment period , one group additionally applied a CPP-ACP containing cream on the respective fissures for 3 minutes , once per day . At Days 1 , 8 , 15 , and 22 , DIAGNOdent measurements and a visual assessment of the fissures were performed by two calibrated independent examiners . RESULTS No significant changes of DIAGNOdent values were found in the control group during the study period . Fissures additionally treated with the CPP-ACP containing cream showed significantly lower laser fluorescence values after Day 15 ( P = 0.001 ) and Day 22 ( P < 0.001 ) compared to the control group . No significant difference in the visual classification between the two groups could be found The aim was to evaluate , in a 3-year RCT study , school-based fluoride varnish programme on approximal caries incidence and approximal caries progression in 13- to 16-year-olds in high , medium and low caries risk areas on the Swedish west coast . Seven hundred and fifty-eight ( 89 % ) fulfilled the trial . Using a simple mobile unit , 2 dental nurses treated the adolescents with F varnish : ( 1 ) twice a year at 6-month intervals , ( 2 ) 3 times a year within 1 week , ( 3 ) 8 times per year during the semesters with 1-month intervals , and ( 4 ) no treatment ( control ) . Radiographic caries recording was performed blindly by one of the authors . Concerning total approximal caries incidence , control groups in all areas developed more caries than F varnish groups , with the largest difference in the high risk area : 3.05 ± 3.37 new approximal caries lesions ( mean ± SD ) compared to 0.54 ± 1.26 for group 3 , 0.95 ± 1.67 for group 1 and 1.40 ± 1.89 for group 2 ( p < 0.001 ) . More than 90 % of the new approximal lesions in all the groups and in all areas consisted of new enamel lesions . Regarding progression of enamel lesions , there were only significant differences between groups 1–3 and group 4 in the high caries risk area . Prevented fraction for fluoride varnish treatment twice a year at 6-month intervals was 69 % in high , 66 % in medium and 20 % in low risk areas . To conclude , school-based F varnish treatment every 6 months in 13- to 16-year-olds is excellent to prevent approximal caries in medium and high caries risk areas PURPOSE To evaluate the efficacy of a sodium fluoride (NaF)/silica/xylitol dentifrice compared with that of a positive control NaF/silica dentifrice on caries increments in school children over a 3-year period in an area without an optimal level of fluoride in the drinking water ( mean level < 0.1 ppm ) . MATERIAL S AND METHODS A 3-year , double-blind clinical caries study was conducted in 2,630 children initially aged 8 - 10 years at 17 schools in the San Jose , Costa Rica metropolitan area . Clinical dental examinations were performed at participating schools utilizing portable dental equipment . Caries evaluations employed conventional tactile/visual methodology consisting of artificial light , dental mirrors and single-edge # 23 explorers . Children accepted into the study were stratified by age and sex into two balanced groups within each school , and r and omly assigned to use either a positive control dentifrice containing 0.243 % NaF/silica or a test dentifrice containing 0.234 % NaF/silica/10 % xylitol . Children were instructed to brush with the assigned dentifrice twice daily . Caries evaluations were conducted at baseline , 2 years , and 3 years . RESULTS After 3 years , subjects using the 0.234 % NaF/silica/10 % xylitol dentifrice had statistically significantly reduced decayed/filled surfaces ( DFS ; -12.3 % reduction ; P < or = 0.001 ) and decayed/filled buccal and lingual surfaces ( DFS-BL ; -10.5 % reduction ; P < or = 0/01 ) The recording of multiple interval-censored failure times is common in dental research . Modeling multilevel data has been a difficult task . This paper aims to use the Bayesian approach to analyze a set of multilevel clustered interval-censored data from a clinical study to investigate the effectiveness of silver diamine fluoride and sodium fluoride varnish in arresting active dentin caries in Chinese pre-school children . The time to arrest dentin caries on a surface was measured . A three-level r and om-effects Weibull regression model was used . Analysis was performed with WinBUGS . Results revealed a strong positive correlation ( 0.596 ) among the caries lesions ’ arrest times on different surfaces from the same child . The software WinBUGS made the above complicated estimation simple . In conclusion , the annual application of silver diamine fluoride on caries lesions , and caries removal before the application , were found to shorten the arrest time The Caries Management By Risk Assessment ( CAMBRA ) r and omized controlled trial showed that an intervention featuring combined antibacterial and fluoride therapy significantly reduced bacterial load and suggested reduced caries increment in adults with 1 to 7 baseline cavitated teeth . While trial results speak to the overall effectiveness of an intervention , insight can be gained from underst and ing the mechanism by which an intervention acts on putative intermediate variables ( mediators ) to affect outcomes . This study conducted mediation analyses on 109 participants who completed the trial to underst and whether the intervention reduced caries increment through its action on potential mediators ( oral bacterial load , fluoride levels , and overall caries risk based on the composite of bacterial challenge and salivary fluoride ) between the intervention and dental outcomes . The primary outcome was the increment from baseline in decayed , missing , and filled permanent surfaces ( ΔDMFS ) 24 mo after completing restorations for baseline cavitated lesions . Analyses adjusted for baseline overall risk , bacterial challenge , and fluoride values under a potential outcome framework using generalized linear models . Overall , the CAMBRA intervention was suggestive in reducing the 24-mo DMFS increment ( reduction in ΔDMFS : −0.96 ; 95 % confidence interval [ CI ] : –2.01 to 0.08 ; P = 0.07 ) ; the intervention significantly reduced the 12-mo overall risk ( reduction in overall risk : –19 % ; 95 % CI , −7 to −41 % ; ] , P = 0.005 ) . Individual mediators , salivary log10 mutans streptococci , log10 lactobacilli , and fluoride level , did not represent statistically significant pathways alone through which the intervention effect was transmitted . However , 36 % of the intervention effect on 24-mo DMFS increment was through a mediation effect on 12-mo overall risk ( P = 0.03 ) . These findings suggest a greater intervention effect carried through the combined action on multiple aspects of the caries process rather than through any single factor . In addition , a substantial portion of the total effect of the CAMBRA intervention may have operated through unanticipated or unmeasured pathways not included among the potential mediators studied Background Dental caries is one of the primary causes of tooth loss among adults . It is estimated to affect a majority of Americans aged 55 and older , with a disproportionately higher burden in disadvantaged population s. Although a number of treatments are currently in use for caries prevention in adults , evidence for their efficacy and effectiveness is limited . Methods / Design The Prevention of Adult Caries Study ( PACS ) is a multicenter , placebo-controlled , double-blind , r and omized clinical trial of the efficacy of a chlorhexidine ( 10 % w/v ) dental coating in preventing adult caries . Participants ( n = 983 ) were recruited from four different dental delivery systems serving four diverse communities , including one American Indian population , and were r and omized to receive either chlorhexidine or a placebo treatment . The primary outcome is the net caries increment ( including non-cavitated lesions ) from baseline to 13 months of follow-up . A cost-effectiveness analysis also will be considered . Discussion This new dental treatment , if efficacious and approved for use by the Food and Drug Administration ( FDA ) , would become a new in-office , anti-microbial agent for the prevention of adult caries in the United States . Trial Registration A parallel-r and omized controlled trial on caries-preventive strategies was conducted in a general dental practice with a mixed socioeconomic background patient population . The aim of this study was to test the hypothesis that , compared to regular care consisting of check-ups twice a year with professional fluoride applications and pit and fissure sealants in all permanent molars , a larger caries-preventive effect can be achieved by following a non-operative caries treatment and prevention ( NOCTP ) strategy or by following , in addition to regular care , an increased number of professional topical fluoride applications ( IPFA ) . A total of 230 children ( 6.0 years ± 3 months of age ) were r and omly assigned to the two experimental groups or the control group . After 3 years , 179 participants remained in the study ( 54 NOCTP , 62 IPFA and 63 control ) . The children were examined at baseline and at 3 years by the same experienced examiner , who was blinded for the allocation of the children . Caries was scored clinical ly at the D3 level . Per protocol analysis revealed a mean DMFS increment after 3 years of 0.15 ( 95 % CI -0.05 to 0.35 ) for NOCTP , 0.34 ( 95 % CI 0.11 to 0.54 ) for IPFA and 0.47 ( 95 % CI 0.26 to 0.68 ) for the control group . To account for missing data , multiple imputation was used , after which the mean DMFS increment was 0.11 ( 95 % CI -0.05 to 0.27 ) for NOCTP , 0.29 ( 95 % CI 0.11 to 0.46 ) for IPFA and 0.40 ( 95 % CI 0.21 to 0.55 ) for the control group . Testing the differences with independent sample s t test revealed a lower caries increment in the NOCTP group compared to the control group . ANCOVA was used to correct for differences in baseline dmfs , socioeconomic status and perceived dental hygiene burden . The ΔDMFS effect size between the NOCTP and the control group dropped , losing statistical significance ( p = 0.06 ) . Although the results in this study are promising , it has yet to be established in a larger study whether NOCTP has the ability to be effective in regular dental practice with a mixed socioeconomic status population OBJECTIVE To compare the retention and the caries preventive effect of a glass-ionomer developed for fissure sealing ( Fuji III ) and a chemically polymerized resin-based fissure sealant ( Delton ) . DESIGN A split mouth r and omized design using contralateral teeth . SETTING WHO Regional Demonstration , Training and Research Center for Oral Health , Damascus , Syrian Arab Republic . SAMPLE AND METHODS 179 children , 7 years old at the start of the study , were recruited from schools close to the Center . Only children with at least one pair of permanent first molars that were caries free or only had incipient lesions were included in the study . Follow-up examinations for sealant retention were done after 6 months , 1 year , 2 years and 3 years . The number of children available for reexamination was 129 ( after 6 months ) ; 121 ( after 1 year ) ; 115 ( after 2 years ) and 116 ( after 3 years ) . Four dental hygienists were trained in the sealant procedures and did approximately one fourth of the sealants each . RESULTS After 3 years the glass-ionomer sealant was completely lost in almost 90 % of the teeth compared to less than 10 % of the resin sealed teeth . After 3 years the relative risk of a tooth sealed with glass-ionomer over that of a tooth sealed with resin was 3.38 ( 95 % CL : 1.98 ; 5.79 ) . This finding was consistent over type of tooth . CONCLUSIONS The glass-ionomer sealant tested in the present study had poorer retention and less caries protective effect than the resin-based sealant used AIM The aim of this study is to assess the effects of fluoride varnishes on enamel caries lesions on permanent dentition . MATERIAL S AND METHODS 92 children from primary school ( Vasil Shanto , Tirana , Albania ) aged 11 - 12 years were divided into varnish ( experimental ) and control group . The experiment group received the first fluoride varnish application ( Fluoridin , Voco ) at baseline , the second application after 3 months and the third application at 6 months from baseline , while the children in the control group received no professional fluoride application . Examinations were performed at baseline and after 7 months . RESULTS We observed a slight increase in caries prevalence in the control group compared with the varnish group at the 7 month interval ( P < 0.1 for DMFT and P < 0.5 for DMFS and DS ) . When enamel lesions were included the mean of DeMFT , DeMFS , DeS the caries prevalence was significantly lower in the varnish group after 7 months ( P < 0.001 for DeMFT , DeMFS ) . CONCLUSION Fluoride varnish is an effective mean for arresting early enamel lesions . It is a safe , convenient and well accepted method by patients For children in the primary dentition with high caries prevalence the st and ard semiannual application of fluoride varnish may not be successful in preventing tooth decay . Oftentimes this population is mobile and does not receive consistent preventive care . This trial tested whether an intensive fluoride 5 % sodium varnish regimen ( three applications/2 weeks ) applied annually has an equivalent effect on caries progression in the primary dentition compared to single applications applied semiannually . This study was a r and omized clinical trial with two treatment groups . All participants ( n = 600 ; mean age ± SD = 55.3 ± 4.6 months ) received three varnish applications ( active varnish or placebo ) at semiannual visits over 3 years . Once per year the intensive-treatment group received one set of three active treatments and three placebo treatments 6 months later , each time within 2 weeks . The st and ard group received one active and two placebo treatments every 6 months . Children were assessed clinical ly at baseline and 12 , 24 and 36 months after the initiation of the study . The mean ( SD ) numbers of newly decayed primary tooth surfaces observed over 3 years were 9.8 ( 8.6 ) and 7.4 ( 7.7 ) in the intensive and st and ard groups , respectively . The adjusted rate ratio was 1.13 ( 95 % CI = 0.94–1.37 , p = 0.20 ) . In conclusion , the trial failed to demonstrate clear evidence of a difference in efficacy . However , differences of up to 36 % greater rates of caries in the intensive group could not be ruled out , thus equivalence of the treatments can not be concluded Background There is a lack of evidence for effective management of dental caries ( decay ) in children ’s primary ( baby ) teeth and an apparent failure of conventional dental restorations ( fillings ) to prevent dental pain and infection for UK children in Primary Care . UK dental schools ’ teaching has been based on British Society of Paediatric Dentistry guidance which recommends that caries in primary teeth should be removed and a restoration placed . However , the evidence base for this is limited in volume and quality , and comes from studies conducted in either secondary care or specialist practice s. Restorations provided in specialist environments can be effective but the generalisability of this evidence to Primary Care has been question ed . The FiCTION trial addresses the Health Technology Assessment ( HTA ) Programme ’s commissioning brief and research question “ What is the clinical and cost effectiveness of restoration caries in primary teeth , compared to no treatment ? ” It compares conventional restorations with an intermediate treatment strategy based on the biological ( sealing-in ) management of caries and with no restorations . Methods / Design This is a Primary Care-based multi-centre , three-arm , parallel group , patient-r and omised controlled trial . Practitioners are recruiting 1461 children , ( 3–7 years ) with at least one primary molar tooth where caries extends into dentine . Children are r and omized and treated according to one of three treatment approaches ; conventional caries management with best practice prevention , biological management of caries with best practice prevention or best practice prevention alone . Baseline measures and outcome data ( at review /treatment during three year follow-up ) are assessed through direct reporting , clinical examination including blinded radiograph assessment , and child/parent question naires . The primary outcome measure is the incidence of either pain or infection related to dental caries . Secondary outcomes are ; incidence of caries in primary and permanent teeth , patient quality of life , cost-effectiveness , acceptability of treatment strategies to patients and parents and their experiences , and dentists ’ preferences . Discussion FiCTION will provide evidence for the most clinical ly-effective and cost-effective approach to managing caries in children ’s primary teeth in Primary Care . This will support general dental practitioners in treatment decision making for child patients to minimize pain and infection in primary teeth . The trial is currently recruiting patients .Trial registration Protocol ID : NCTU : IS RCT Background and aims Dental caries still remains a major problem in the field of oral and dental health and its prevention is more important than its treatment . Fluoride plays a significant role in prevention of caries , and improving oral and dental health . One of the common ways of fluoride use is the use of a fluoride-containing mouthwash , the most important of which in use is 0.2 % sodium fluoride mouthwash . School-based fluoride mouthwash programs have been used for delivering oral and dental health to children in recent years . The aim of the present study was to assess the efficiency of 0.2 % sodium fluoride mouthwash in prevention of dental caries according to DMFT index . Material s and methods The study included a case and a control group . For each group , 100 students were selected r and omly from elementary schools of Tabriz , Iran . Case group had been participating in school-based fluoride mouthwash program for three years , while control group did not benefit from the program . The two groups were assessed by means of intra-oral examination . Data was recorded using DMFT index . Results Following the use of 0.2 % sodium fluoride mouthwash , mean DMFT index in case group decreased as much as 51.5 % compared to that of control group . The mean values of decrease for the decayed , missing and filled indices were 45 % , 44 % and 59 % , respectively . The decrease in DMFT value of the case group compared to that of control group was statistically significant ( p<0.001 ) . A statistically significant decrease was seen in the decayed and filled indices of case group ( p=0.042 and p=0.016 , respectively ) , however the missing index did not show any statistically significant difference between the two groups ( p=0.361 ) . Conclusion According to this study results , the weekly use of 0.2 % sodium fluoride mouthwash program has been successful in elementary schools of Tabriz . Such program can play an important role in the improvement of oral and dental health among children of school age Demineralizations around orthodontic brackets are a main disadvantage of orthodontic treatment . Several methods have been advocated to prevent their development , such as fluoride rinses or varnishes . In this r and omized clinical trial , a fluoride rinse ( a combination of sodium fluoride and amine fluoride ) was compared with a placebo rinse , to be used every evening after toothbrushing . A total of 81 participants ( mean age : 13.3 yr ) completed the study ( mean treatment period : 24.5 months ) . Demineralizations , measured using quantitative light‐induced fluorescence and the decayed , missing , and filled surfaces ( DMFS ) index , were assessed before treatment ( baseline ) and around 6 wk after debonding ( post treatment ) . Bleeding scores were measured at baseline , and during and post treatment . The incidence rate ratio for demineralizations was 2.6 ( 95 % CI : 1.1–6.3 ) in the placebo group vs. the fluoride group . In the fluoride group , 31 % of participants developed at least one demineralization , compared with 47 % in the placebo group . Relative to baseline , gingival bleeding increased significantly in the placebo group 1 yr after the start of treatment and onwards . For the fluoride group , bleeding scores during treatment were not different from those at baseline . In conclusion , using a fluoride rinse helps to maintain better oral health during fixed appliance treatment , result ing in fewer demineralizations Background Approximal surfaces are a challenge to caries lesions control . Silver diamine fluoride ( SDF ) is a simple , low-cost and promisor intervention for arresting caries lesions , but it has never been tested on approximal surfaces . Our aim is to evaluate the efficacy and cost-efficacy of SDF in arresting initial lesions compared to resin infiltration and exclusively flossing ( control group ) . Our second aim is to assess discomfort and satisfaction regarding interventions . Methods / design This is a r and omized clinical trial , double-blinded , placebo-controlled study . Children/adolescents presenting at least one approximal initial caries lesion in primary molars/permanent premolars and molars will be included . Surfaces with advanced dentine lesions identified by radiography and participants who refuse to participate or present negative behaviors will be excluded . A minimum sample size of 504 surfaces will be required for each subgroup . Individuals will be r and omly allocated in three groups of interventions : SDF , resin infiltration , and control group . Depending on the allocation , the patients will receive the active treatment and respective placebo therapies . All patients will be oriented to daily flossing the included surfaces . Our primary outcome will be caries progression by clinical and radiographic examinations . Appointments will be timed and costs of material s will be considered to calculate cost-efficacy . Patient discomfort will be assessed after interventions . Parent and patient satisfaction with the treatment will be collected after treatment and in the last follow-up visit . Individuals will be assessed at 1 and 3 months after treatment to evaluate dental biofilm and at 6 , 12 , and 24 months to assess caries progression by visual examination and /or radiography . Multilevel analyses will be used to verify if the type of treatment influenced on the tested outcomes . Costs will be compared and analyses of cost-efficacy will be performed . Poisson analysis will test the association between intervention and reported discomfort and satisfaction . Discussion Our hypothesis is that SDF is the most cost-efficacious option from all tested interventions . If our hypothesis is confirmed , the use of SDF in private and public context s could represent an easier and effective option in the treatment of enamel approximal caries in children/adolescents . Trial registration Clinical Trials.gov ( NCT01477385 ) , Initial release : 11/16/2011 : last up date : 06/02/2014 This study compared the ability of two sodium fluoride dentifrices , one containing 5,000 ppm fluoride ( Prevident 5000 Plus ) and the other 1,100 ppm fluoride ( Winterfresh Gel ) , to reverse primary root caries lesions ( PRCLs ) . A total of 201 subjects with at least one PRCL each entered the study and were r and omly allocated to use one of the dentifrices . After 6 months , 186 subjects were included in statistical analyses . At baseline and after 3 and 6 months , the lesions were clinical ly assessed and their electrical resistance measured using an electrical caries monitor . After 3 months , 39 ( 38.2 % ) of the 102 subjects in the 5,000 ppm F– group and 9 ( 10.7 % ) of 84 subjects using the 1,100 ppm F– dentifrice , had one or more PRCLs which had hardened ( p = 0.005 ) . Between baseline and 3 months , the log10 mean ± SD resistance values of lesions for subjects in the 1,100 ppm F– group had decreased by 0.06±0.55 , whereas those in the 5,000 ppm F– group had increased by 0.40±0.64 ( p<0.001 ) . After 6 months , 58 ( 56.9 % ) of the subjects in the 5,000 ppm F– group and 24 ( 28.6 % ) in the 1,100 ppm F– group had one or more PRCLs that had become hard ( p = 0.002 ) . Between baseline and 6 months , the log10 mean ± SD resistance values of lesions for subjects in the 1,100 ppm F– group decreased by 0.004±0.70 , whereas in the 5,000 ppm F– group , they increased by 0.56±0.76 ( p<0.001 ) . After 3 and 6 months , the distance from the apical border of the root caries lesions to the gingival margin increased significantly in the 5,000 ppm F– group when compared with the 1,100 ppm F– group . The plaque index in the 5,000 ppm F– group was also significantly reduced when compared with the 1,100 ppm F– group . The colour of the lesions remained unchanged . It was concluded that the dentifrice containing 5,000 ppm F– was significantly better at remineralising PRCLs than the one containing 1,100 ppm A double-blind r and omized clinical trial was performed in 6- to 7-yr-old schoolchildren to evaluate , in a 30-mo period , whether the caries increment on the distal surface of the second primary molars adjacent to permanent first molars sealed with fluoride release compounds would be lower with respect to those adjacent to permanent first molars sealed with a nonfluori date d sealant . In sum , 2,776 subjects were enrolled and r and omly divided into 3 groups receiving sealants on sound first molars : high-viscosity glass ionomer cement ( GIC group ) ; resin-based sealant with fluoride ( fluoride-RB group ) ; and a resin-based sealant without fluoride ( RB group ) . Caries ( D1 – D3 level ) was recorded on the distal surface of the second primary molar , considered the unit of analysis including only sound surfaces at the baseline . At baseline , no differences in caries prevalence were recorded in the 3 groups regarding the considered surfaces . At follow-up , the prevalence of an affected unit of analysis was statistically lower ( p = .03 ) in the GIC and fluoride-RB groups ( p = .04 ) . In the GIC group , fewer new caries were observed in the unit of analysis respect to the other 2 groups . Incidence rate ratios ( IRRs ) were 0.70 ( 95 % confidence interval : 0.50 , 0.68 ; p < .01 ) for GIC vs. RB and 0.79 ( 95 % confidence interval : 0.53 , 1.04 ; p = .005 ) for fluoride-RB vs. RB . Caries incidence was significantly associated with low socioeconomic status ( IRR = 1.18 ; 95 % confidence interval : 1.10 , 1.42 ; p = .05 ) . Dental sealant high-viscosity GIC and fluoride-RB demonstrated protection against dental caries , and there was evidence that these material s afforded additional protection for the tooth nearest to the sealed tooth ( clinical trial registration NCT01588210 ) The effects of some oral hygiene measures on Streptococcus mutans and approximal dental caries were evaluated . One hundred and eighty-seven 13-year-old individuals with high levels of salivary S. mutans ( > 106/mL ) were selected . They were r and omly distributed into three groups . Group I initially received professional mechanical toothcleaning , tongue-scraping , chlorhexidine treatment , and oral hygiene instructions concentrated on the approximal surfaces most colonized by S. mutans . The treatment was given four times with intervals of two days , followed by one single treatment every six months throughout the experimental period . The initial treatment period for group II , also consisting of four visits , included the same oral hygiene instructions as for group 1 . The instructions were repeated every six months . Group III was maintained in the preventive program provided by the local Dental Health Office , based on mechanical plaque control and topical use of fluorides and chlorhexidine at individualized intervals . Group I showed a significant immediate reduction of S. mutans in saliva as well as on approximal tooth surfaces . After six months , there were no differences among the three groups regarding these variables . Compared with baseline , there was a significant reduction of S. mutans in all groups . There was no significant difference in caries progression among the three groups . However , the selected " high-risk " individuals in group I developed 0.25 new manifest caries lesions approximallylyear , compared with 0.27 for all children of the same age group in the area . Seventeen individuals had approximal surfaces with consistently high or consistently low S. mutans levels . Forty-six percent of the surfaces with high values developed new or progressive caries , compared with 2 % of the surfaces with low values One hundred and sixty 11-year-olds were r and omly allocated to two experimental groups , one test ( group 1 ) and one control group ( group 2 ) , for a 3-year clinical test comparing different modes of fluoride varnish treatment . In the test group , children received Duraphat varnish treatments 3 times a week , once a year . The children in group 2 were treated with Duraphat every 6 months . During the experimental period , children in group 1 received 9 fluoride varnish applications , and in group 2 , 6 applications . Four bitewing radiographs were taken in each child each year for the measurements of the incidence and progression of proximal caries . Repeated fluoride varnish treatment with Duraphat , 3 times a week once a year , appears to inhibit proximal caries progression and development since the children in this group showed even a lower caries status , 1.3 + /- 0.3 DS , at the end of the study compared to 1.6 + /- 0.2 DS at the outset . In group 2 , the children increased their caries status from 1.7 + /- 0.2 to 2.4 + /- 0.4 DS during the experimental period . The caries difference was statistically significant ( p less than 0.05 ) between the two groups . A health economic comparison of the two modes of application showed 30 % lower costs for the children in the test group based on time used for preventive measures and assumed filling therapy Abstract The aim of this 2-year prospect i ve r and omized clinical study was to evaluate the efficacy of a prevention program for schoolchildren with high caries risk . A sample of 419 subjects was divided into a test ( T , n=259 ) and control group ( C , n=160 ) . Four times a year , the test group received professional tooth-cleaning and application of a 0.1 % fluoride varnish as well as motivation and instruction in oral hygiene . The control group received only oral hygiene instruction and took part in supervised tooth-brushing once a year . At baseline and after 2 years , the D3,4MFS and the incipient lesions ( D1,2 ) were recorded . After 2 years , 318 subjects ( T=187 , C=131 ) were included in the data analysis . The baseline D1,2 was 6.18 ( T ) and 5.50 ( C ) , the D3,4MFS 2.13 ( T ) and 2.08 ( C ) , respectively . No statistically significant difference was found for the baseline values . At the final examination , the D1,2 increment was 3.96 in the test and 6.53 in the control group , showing a statistically significant difference ( P<0.001 ) . No such difference was found for the D3,4MFS increment ( T : 2.22 ; C : 2.61 ) . The results indicate that it might not be possible to prevent cavities in high caries risk children by means of the described program PURPOSE The aim of this work is to study and compare the retention rate , caries-preventing and antibacterial effects of resin-modified glass ionomer and flowable composite in comparison to conventional fissure sealant . METHODS Forty-five children aged 7 - 10 years with newly erupted lower first permanent molars were r and omly divided into three equal treatment groups . Group I : sealed by a conventional resin sealant ; Group II : sealed by resin modified glass ionomer ( RMGI ) ; and Group III : sealed by flowable composite . Retention and caries status of the sealed teeth were recorded after 1 month , 6 months , year and 2 years . In addition , Streptococcus mutans counts were assessed at baseline , 1 day , 1 month , 6 months , 1 year and 2 years after sealant application . Data were analyzed by Fisher exact , chi-square and ANOVA tests . RESULTS Group III and Group I showed significantly higher retention rates than Group II fissure sealant ( p<0.05 ) . There were no differences of the caries-preventive effects between the tested sealant material s throughout the duration of the study . Streptococcus mutans counts were significantly lower in group II compared to group I or group III up to 6 months of the study ( p<0.05 ) . After 1 year of the study the differences of Streptococcus mutans counts were not significant ( p>0.05 ) . CONCLUSION This study indicated a lower retention of RMGI compared to flowable composite and resin sealant without significant difference in caries prevention or long-term bacterial inhibition OBJECTIVES This study compared a 10 % chlorhexidine varnish treatment with placebo and sham treatments for preventing dental caries in adult patients with xerostomia ( dry mouth ) . DESIGN The study was a multicentred , r and omized , parallel group , double blind , placebo-controlled clinical trial . SETTING All examinations and procedures were performed at Tuft 's University , Boston , MA , the University of British Columbia , Vancouver , BC or the University of Western Ontario , London , ON . SUBJECTS Subjects were adults with recent or current dental caries experience , high salivary levels of cariogenic microorganisms and low salivary flow rates . RESULTS 236 subjects completed at least one post-treatment examination . There were 697 new carious lesions diagnosed , 446 ( 64 % ) located on coronal surfaces and 251 ( 36 % ) located on root surfaces . The mean attack rate was 0.23 surfaces/100 surfaces at risk . A treatment difference observed between the Active and Placebo groups was statistically significant for root caries increment ( p = .02 ) and total caries increment ( p = .03 ) . A treatment difference observed between the Active and Sham groups was not statistically significant for coronal , root or total caries increment . Analysis of variance of treatment group differences was performed using mutans streptococci counts , salivary flow rates , age , sex , caries prevalence , medications , time to first event and early withdrawal as co-variables . These factors did not meaningfully alter the findings . CONCLUSIONS The difference between the 10 % chlorhexidine varnish and placebo treatments is considered to be highly clinical ly significant for root caries increment ( 41 % reduction ) and for total caries increment ( 25 % reduction ) but only for coronal caries increment ( 14 % ) OBJECTIVE To investigate the bacteriostatic and cariostatic effect of a novel povidone-iodine/fluoride foam in children at high risk for caries . METHOD AND MATERIAL S Sixty-one 6- to 9-year-old children with at least 1 active dental caries lesion were r and omly assigned to 2 groups and treated weekly with either povidone-iodine/fluoride foam ( n = 30 , experimental group ) or placebo fluoride foam ( n = 31 , control group ) for 4 weeks . Stimulated saliva sample s were collected for bacteriostatic assessment before each treatment and at 2 and 6 months during the experiment . In addition , laser fluorescence readings of the permanent first molars were taken for the evaluation of cariostatic effect before the treatment and at 2 , 6 , and 12 months during the experiment . RESULTS Both groups showed a constant decrease of salivary mutans streptococci over 6 months . Significantly lower laser fluorescence readings were observed for both groups at the 6th month , although with a slight reverse at the 12th month . However , no statistically significant difference was achieved between the 2 groups either for salivary bacteria levels over 6 months or laser fluorescence readings within 1 year . CONCLUSION As far as bacteriostatic and cariostatic effects are concerned , clinical application of povidone-iodine/fluoride foam shows no superiority over the regular fluoride foam during a 1-year period . Evidence is still lacking for the combination use of povidone-iodine and fluoride to achieve a better caries-prevention effect in a high-caries-risk population The objective of this study was to measure the effectiveness of fluoride varnish as a public health intervention to prevent caries on partially erupted first and second permanent molars among 6 - 11 year old children at high risk for caries . In a six-month clinical trial , 105 children were r and omly divided into a fluoride varnish ( Duraphat ) group ( 117 molars ) or a control group ( 117 molars ) . The chi-square test used to compare caries occurrence in each group with a 95 % level of confidence ( p<0.05 ) at the intervals of 3 months . Compared to control , fluoride varnish result ed in 79 % and 77.5 % caries reduction in partially erupted permanent molars at 3 and 6 months , respectively . There were statistically significant differences in caries progression between the groups at 3 and 6 months . Fluoride varnish significantly reduced carious lesions in partially erupted molars at six months among high caries risk children The effects of fluoride and chlorhexidine varnishes on the microflora of dental root surfaces and on the progression of root-surface caries were studied . Forty-four patients , surgically treated for advanced periodontal disease , were distributed at r and om among three groups . All patients received a st and ardized preventive treatment . Furthermore , the dentition of the patients in the two experimental groups was treated , at three-month intervals , with chlorhexidine and fluoride varnish , respectively . Patients in the control group received no additional treatment . In the experimental groups , plaque sample s were collected from selected sound and carious root surfaces at baseline and at three , six , and nine months after the onset of the study . The presence of root-surface caries was scored at baseline and after one year . In addition , the texture , depth , and color of the root-surface lesions were monitored . Mutans streptococci on root surfaces were suppressed significantly ( p<0.05 ) during the whole experimental period in the chlorhexidine varnish group , but not in the fluoride varnish group . A non-significant increase in the number of Actinomyces viscosus/naeslundii was noted after treatment with chlorhexidine and fluoride varnish . The increase in the number of decayed and filled root surfaces after one year was significantly lower in the experimental groups than in the control group . After treatment with chlorhexidine varnish , significantly more initial root-surface lesions had hardened than in the other groups The objectives were to demonstrate that a combination of preventive regimens could significantly reduce dental disease in a school population , to demonstrate the feasibility of a school-based program in relation to sustained benefits . There were 1286 students in 1st and 6th grade s enrolled in the study . Subjects were stratified by grade , sex , and race and r and omly placed in a treatment or education group . Procedures included ingestion of fluori date d water , oral hygiene education program , dental examinations , prophylaxis , acidulated phosphate fluoride gel ( 1.23 % ) applied in trays , pit and fissure sealants ( bis-GMA ) on occlusal surfaces of all eligible posterior teeth , and provision of all restorative care . Fluoride and sealant procedures were repeated at 6-month intervals . After 3 years the treatment group was r and omly divided to provide a group that would not continue with treatment and serve as a comparison . The study population was enrolled in 18 schools and clinical procedures were provided on-site , using mobile dental vans . Five-year results indicate high degree of success with fall-off of benefits to those for whom treatment was terminated . This pilot program gives strong evidence for the possibility of implementing school-based dental programs . The study also indicates that prevention programs must be comprehensive and continuous for maximum benefit to occur Abstract Objective . The purpose of the study was to determine the efficacy of a 10 % chlorhexidine tooth coating in reducing the incidence of cavitated carious lesions in adults . Material s and methods . The trial was a r and omized , double-blind , multi-center , placebo controlled study with 983 participants , receiving the application of either the active or the placebo coatings to the entire dentition . Four applications were made in the first month and one at the 7th month . The final examination was performed at 13 months . Results . Coronal caries showed a statistical reduction ( p = 0.02 ) . Examination of the results by site showed that the highest risk participants experienced the most significant preventive effect ( p = 0.003 ) . When two sites ( uninsured and public health ) are pooled the treatment p-value is 0.0009 , interaction term has a p-value of 0.0001 . Conclusion . 10 % Chlorhexidine was highly effective in high risk participants with more than two cavities at the initial examination . This trial in conjunction with other published trials of this topical medication indicates that chlorhexidine exerts its action by preventing the transition of D1 lesions to cavitated lesions , not on sound to D1 lesions The objective of this study was to assess the effect of six-monthly professional applications of chlorhexidine varnish on the prevention of dental caries in primary molars in Chinese preschool children . In a double-blinded , r and omized , placebo-controlled clinical trial , 334 children aged 4–5 years were r and omly divided into two groups . Children in the test group received six-monthly applications of a 40 % chlorhexidine varnish , and the control children received a placebo varnish . Caries status of the children was assessed by two calibrated examiners at baseline and after 24 months , according to criteria recommended by the World Health Organization . The two-year mean caries increments in the test and the control group children were 1.0 and 1.6 decayed , missing , or filled molar surfaces ( dmfs-molar ) , respectively , a 37.3 % reduction ( t test , p = 0.036 ) . No side-effects were found . It was concluded that six-monthly applications of chlorhexidine varnish were effective in reducing the incidence of dental caries in primary molars Home-care use of fluoride ( F ) requires a motivated individual and several F products rely on a person ’s ability to follow instructions and to cooperate with the treatment . The aim of this crossover study was to investigate concentrations , distribution in the oral cavity and duration of the elevated F concentrations after using four F products : ( 1 ) a mucosa adhesive paste with 0.1 % F , ( 2 ) a mouth rinsing solution with 0.2 % NaF , ( 3 ) toothpaste containing 0.5 % F and ( 4 ) a tablet with 0.75 mg F. Fourteen subjects used the four products in r and omized order either during the daytime or just before going to bed . The F concentration was measured both in saliva and at interproximal sites . After 6 h of sleep , the F concentration after using the mucosa adhesive paste and the mouth rinse solution was high in saliva . In the interproximal area , the adhesive paste showed the highest values . During daytime use , all the products increased the F concentration , but only the mucosa adhesive paste and the rinsing solution elevated F in saliva for up to 2 h. In the interproximal area , the paste increased the F concentration most . In conclusion , this study showed that the mucosa adhesive paste and the mouth rinse solution led to higher F concentrations and for a longer time than tablets and toothpaste . For patients who are unable to comply with traditional F treatment , an F-containing adhesive paste therefore has the potential to be a useful vehicle . For individuals who are able to cooperate , a mouth rinse with an F solution is a simple , efficient and well-known method for preventing dental caries Casein phosphopeptide-amorphous calcium phosphate nanocomplexes ( CPP-ACP ) exhibit anticariogenic potential in laboratory , animal , and human in situ experiments . The aim of this study was to determine the ability of CPP-ACP in sugar-free chewing gum to remineralize enamel subsurface lesions in a human in situ model . Thirty subjects in r and omized , cross-over , double-blind studies wore removable palatal appliances with six human-enamel half-slabs inset containing subsurface demineralized lesions . The appliances were inserted immediately before gum-chewing for 20 min and then retained for another 20 min . This was performed four times per day for 14 days . At the completion of each treatment , the enamel half-slabs were paired with their respective demineralized control half-slabs , embedded , sectioned , and subjected to microradiography and densitometric image analysis , for measurement of the level of remineralization . The addition of CPP-ACP to either sorbitol- or xylitol-based gum result ed in a dose-related increase in enamel remineralization , with 0.19 , 10.0 , 18.8 , and 56.4 mg of CPP-ACP producing an increase in enamel remineralization of 9 , 63 , 102 , and 152 % , respectively , relative to the control gum , independent of gum weight or type PURPOSE To compare the effectiveness of fluoride vanish , fluoride foam , pit and fissure sealant with fluoride in prevention of dental caries , and investigate appropriate approach to prevent dental caries at schools . METHODS A r and omized controlled clinical trial with 4 parallel groups was conducted . Totally 1016 children from 4 schools and 33 classes with a mean age of 7 to 8 years were included . They were r and omly allocated into 4 groups : ( 1 ) fluoride vanish , semi-annual application ; ( 2 ) fluoride foam , semi-annual application ; ( 3 ) resin sealant , single placement ; and ( 4 ) placebo control with oral hygiene instruction . Follow-up examinations were conducted after 2 years to monitor dental caries increment of first molars among these children . Data analysis was performed using SPSS 18.0 software package . RESULTS Two years later , 977 children ( 96.2 % ) were examined . The results of multiple factor ANCOVA showed that fluoride vanish and resin sealant had significantly lower mean dental caries increment on tooth surface compared with control group ( P<0.05 ) . No significant difference of mean dental caries increment on tooth surface was found between fluoride foam and control group ( P>0.05 ) . CONCLUSIONS The placement of resin sealant with fluoride and annual application of fluoride protector are effective in prevention of dental caries in permanent teeth of children BACKGROUND Chlorhexidine ( CHX ) varnishes have been mainly used for the prevention of caries in high-risk population s. Reports regarding their anti-plaque effect on a clinical level are limited to non-existing as opposed to their microbiological impact on plaque formation . AIM The aim of this preliminary investigation was to evaluate the anti-plaque effect of two CHX varnishes applied on sound enamel in relation to a positive control , a negative control and to one another . METHODS Sixteen healthy subjects volunteered for this r and omized-controlled , single-blind , four-treatment-four-period crossover- design ed clinical trial . A 3-day plaque re-growth model was used to determine de novo plaque accumulation following CHX rinsing , Cervitec application , EC40 application and no therapy . The amount of plaque was measured using the Quigley and Hein plaque index and " automatic image analysis " ( AIA ) . RESULTS AND CONCLUSIONS Varnish treatment result ed in significantly higher plaque levels than CHX rinsing irrespective of the varnish that was used ( p < or = 0.002 ) , implying that the latter is likely to remain the gold st and ard as an anti-plaque agent . However , highly significant differences were also found in favour of both varnish systems when compared with no therapy ( p<0.001 ) , which indicates that varnish treatment is an effective means of inhibiting plaque formation in a short time span . Cervitec exhibited slightly , yet significantly , higher plaque levels in comparison with EC40 as determined by AIA ( p=0.006 ) . Large-scale trials with a longer observation period are necessary to substantiate these results Correlated or multilevel grouped survival data are common in medical and dental research . Two common approaches to analyze such data are the marginal and the r and om-effects approaches . Models and methods in the literature generally assume that the treatment effect is constant over time . A research er may be interested in study ing whether the treatment effects in a clinical trial vary over time , say fade out gradually . This is of particular clinical value when study ing the long-term effect of a treatment . This paper proposed to extend the r and om effects grouped proportional hazards models by incorporating the possibly time-varying covariate effects into the model in terms of a state-space formulation . The proposed model is very flexible and the estimation can be performed using the MCMC approach with non-informative priors in the Bayesian framework . The method is applied to a data set from a prospect i ve clinical trial investigating the effectiveness of silver diamine fluoride ( SDF ) and sodium fluoride ( NaF ) varnish in arresting active dentin caries in the Chinese preschool children . It is shown that the treatment groups with caries removal prior to the topical fluoride applications are most effective in shortening the arrest times in the first 6-month interval , but their effects fade out rapidly since then . The effects of treatment groups without caries removal prior to topical fluoride application drop at a very slow rate and can be considered as more or less constant over time . The applications of SDF solution is found to be more effective than the applications of NaF vanish The aim of this study was to determine whether cessation of weekly fluoride rinsing leads to an increase in caries incidence in a group of adolescents with low caries prevalence . Sixty r and omly selected 12- to 14- year-olds were asked to stop rinsing at school ( test group ) . After 3 years caries increment and caries progression were compared with an age- and sex-matched control group ( n = 60 ) , who continued to rinse weekly with a 0.2 % sodium fluoride solution . All children in both groups had followed a school-based fluoride rinsing program from the age of 6 years . The mean ( st and ard deviation ) caries increment , including only open lesions , during the 3 years was 1.58 ( 1.73 ) in the test group and 1.48 ( 1.80 ) in the control group . The corresponding figures for incipient lesions were 3.13 ( 3.63 ) and 4.03 ( 4.23 ) , respectively . The mean caries progression was 0.92 ( 1.34 ) in the test group and 0.72 ( 1.03 ) in the control group . None of these differences were statistically significant . Thus , this study showed that a cessation of weekly fluoride rinsing did not lead to an increase of caries incidence in a group of adolescents with low caries prevalence A clinical field trial was conducted , over a 2-yr period , to evaluate the efficacy of bi-annual APF gel topical applications without previous prophylaxis in reducing dental caries among high-risk children living in non-fluori date d communities . 488 children 6 yr old , presenting at least three cavities on proximal surfaces of their primary teeth , were r and omly assigned to two groups . The experimental group received bi-annual topical APF gel applications and the control group received a placebo . All treatments were given at school without any prior toothcleaning . The APF gel provided a 34.3 % reduction in caries incidence ( P-value = 0.03 ) among the children with 3 - 14 cavities on their primary teeth at the beginning of the study . However , the treatment did not show any efficacy in reducing caries incidence among the higher-risk children having initially more than 14 cavities . These findings suggest that the efficacy of APF gel applications without previous prophylaxis varies according to the individual risk of the subjects and that more comprehensive programs should be targeted to very high-risk children A longitudinal study was carried out in order to evaluate the caries incidence as affected by partial substitution of dietary sucrose ( S ) with xylitol ( X ) , the effects of S- or X-containing chewing gums being compared during one year . The material comprised initially 102 young adults , predominantly dental and medical students , divided r and omly into S- and X-groups . During the study 2 subjects were excluded , one due to lack of cooperation , the other not being allowed to enter the assigned S-group due to excessive caries prevalence . The subjects consumed 4.0 chewing gums per day in the S-group and 4.5 in the X-group . The frequency of sucrose intake was 4.2 times per day in the S-group , and 4.9 in the X-group . The caries incidence , assessed independently by clinical and radiographical means , expressed as the mean increment of decayed , missed and filled tooth surfaces , was 2.92 in the S-group , and --1.04 in the X-group . The corresponding values , when considering additionally the secondary caries reverals , were 3.76 in the S-group , and 0.33 in the X-group . The caries incidence was also expressed in combined quantitative and qualitative terms by considering in addition to the above parameters , also the changes in lesion size . The caries activity index thus calculated was 4.96 in the S-group , and 0.88 in the X-group . The results show a profound difference in the caries increment rate between the two experimental groups . The findings clearly indicate a therapeutic , caries inhibitory effect of xylitol Casein phosphopeptide-amorphous calcium phosphate ( CPP-ACP ) slows the progression of caries and remineralizes enamel subsurface lesions . The aim of this study was to determine the ability of CPP-ACP to increase the incorporation of fluoride into plaque and to promote enamel remineralization in situ . R and omized , double-blind , cross-over studies involved mouthrinses and dentifrices containing CPP-ACP and fluoride . The mouthrinses were used for 60 sec , three times/day for 5 days , and supragingival plaque was collected and analyzed for F. The dentifrices were rinsed as a water slurry for 60 sec four times/day for 14 days in an in situ model . The addition of 2 % CPP-ACP to the 450-ppm-F mouthrinse significantly increased the incorporation of fluoride into plaque . The dentifrice containing 2 % CPP-ACP produced a level of remineralization similar to that achieved with a dentifrice containing 2800 ppm F. The dentifrice containing 2 % CPP-ACP plus 1100 ppm F was superior to all other formulations AIM The aim of this paper was to investigate the effects of fluorotherapy on the oral health of subjects who had been following a vegan diet ( lacking in meat and animal derivatives ) for a long period of time ( at least 1 year and 6 months ) . METHODS A preliminary study ( t0 ) evaluated 50 subjects , all from northern Italy and aged 24 - 60 years ( 28 male and 22 female ) who had been following a vegan diet for a minimum of 18 months to a maximum of 20 years , and compared them with a control group of 50 individuals following a Mediterranean diet . All vegan subjects showed oral changes such as white spots , lesions invisible to the naked eye and decreased salivary pH values ( ~5 - 6 ) . In a second study ( t1 ) , the 50 vegan subjects were r and omly divided into two subgroups of 25 . Subgroup SG1 underwent fluorotherapy with sodium fluoride ( Elmex fluoride gel ® 1.25 % ) administered once daily for 1 year . Subgroup SG2 served as controls and did not receive fluorotherapy . The following parameters were recorded before the start of fluorotherapy and again after 1 year : salivary pH ; Decayed , Missing , Filled teeth Index ; presence and location of white spots and lesions not visible to the naked eye ; Plaque Index , and Gingival Index . RESULTS In SG1 , larger lesions became smaller in diameter and small lesions disappeared , a statistically significant improvement compared with SG2 , despite the persistence of restricted eating habits and the oral hygiene conditions being similar to those at t0 . Salivary pH showed no significant change in either subgroup . CONCLUSION Daily application of a topical 1.25 % fluoride gel is effective in reducing the incidence of white spot lesions caused by a vegan diet The purpose of this study was to determine the efficacy of fluoride varnish ( 5 % sodium fluoride , Duraphat ® , Colgate ) in reverting white spot lesions ( WSLs ) after fixed orthodontic treatment . This study was a r and omized , parallel group , controlled clinical trial . Using saline solution as control , 110 participants ( mean age ± st and ard deviation : 16.6 ± 3.2 years ) ranging from 12 to 22 years old were r and omly assigned to either the test group ( group 1 ) or the control group ( group 2 ) . Application of fluoride varnish or saline was applied onto tooth surfaces with WSLs every month during the first 6 months after debonding . The labial ( buccal ) surfaces of the teeth were assessed by the use of a DIAGNOdent pen ( DD ) at the baseline , 3- and 6-month follow-up visits . After 6 months , 96 subjects with a total of 209 study teeth ( 47 subjects , 104 teeth in group 1 ; 49 subjects , 105 teeth in group 2 ) remained . The WSLs had a mean DD reading at baseline of 17.66 ± 5.36 in group 1 and 16.19 ± 5.70 in group 2 , which decreased by 5.78 and 2.44 , respectively , at the 3-month follow-up visit and decreased by 7.56 and 3.09 , respectively , at the 6-month follow-up visit . The mean baseline DD readings in the two groups were similar ( t test , P > 0.05 ) . There was statistically significant differences between the mean DD readings of the two groups at the 3-month ( P < 0.05 ) and at the 6-month follow-up visits ( P < 0.01 ) . Topical fluoride varnish application is effective in reversing WSLs after debonding and should be advocated as a routine caries prevention measure after orthodontic treatment OBJECTIVE To compare the effects of sodium fluoride mouth rinse , casein phosphopeptide-amorphous calcium phosphate ( CPP-ACP ) , and the microabrasion technique in treating white spot lesions . MATERIAL S AND METHODS The study population consisted of 80 patients ( 46 females , 34 males ; 966 affected teeth ) who had developed multiple decalcified enamel lesions after fixed orthodontic therapy . The study population was divided into four groups of 20 patients each . The control group ( group I ) participants were to just brush their teeth , the fluoride group ( group II ) participants were instructed to use 20 ml of neutral 0.025 % sodium fluoride rinse , the participants in the CPP-ACP group ( group III ) were instructed to use tooth mousse twice a day in addition to fluoride toothpaste for 6 months , and the participants in the microabrasion group ( group IV ) were to undergo treatment by the microabrasion technique , which is a commonly used mixture of 18 % hydrochloric acid . Data were analyzed with the generalized linear mixed model and Tukey HSD at the P < .05 level . RESULTS The area of the white spot lesions decreased significantly in all groups . Inter group differences in the treatment success rates were significant . The highest success rate was observed for group IV ( 97 % ) . The success rate of group III ( 58 % ) was significantly higher than that of groups II ( 48 % ) and I ( 45 % ) . CONCLUSIONS The use of CPP-ACP can be more beneficial than fluoride rinse for postorthodontic remineralization . Microabrasion is an effective treatment for cosmetic improvement of long-st and ing white spot lesions OBJECTIVES ( i ) Initially , to devise and examine the validity of a system for determining lesion activity on root surfaces , and ( ii ) compare the effectiveness of two preventive programmes in controlling root caries in elderly people using the devised system . MATERIAL S AND METHODS ( i ) Four clinical variables : texture , contour , location and colour of root caries lesions were selected to evaluate lesion activity . The intraexaminer reproducibility of the scoring system was assessed on 28 elderly patients . The accuracy was assessed on 10 of these persons using an impression material ( Clinpro , 3 M ESPE ) . ( ii ) Of total , 215 homebound 75 + year olds were r and omly assigned to one of three groups : group 1 , once a month a dental hygienist brushed the teeth of the participants and applied Duraphat vanish to active root caries lesions . The participants in groups 2 and 3 received 5000 and 1450 ppm F-toothpaste , respectively , to use twice a day . This study included an interview , a baseline examination and a final follow-up examination after 8 months . RESULTS ( i ) Intraexaminer reproducibility of the root caries scoring system was 0.86 ( Kappa ) . The sensitivity and specificity was 0.86 and 0.81 . ( ii ) Data from those 189 ( 88 % ) who completed the study disclosed that there were no inter-group differences at the baseline examination concerning relevant conditions . At the end of the study , the root caries status of participants in groups 1 and 2 had improved significantly when compared with group 3 ( p < 0.02 ) . No significant difference was observed between groups 1 and 2 ( p = 0.14 ) . CONCLUSION The data suggest that the root caries scoring system is reliable . Both the intervention programmes controlled root caries development ; the hygienist in eight of 10 persons , the 5000 ppm F-toothpaste in seven of 10 . In contrast , five of 10 participants who only brushed with 1450 ppm F-toothpaste had root caries progression Untreated dental caries in Chinese pre-school children is common . This prospect i ve controlled clinical trial investigated the effectiveness of topical fluoride applications in arresting dentin caries . Three hundred seventy-five children , aged 3 - 5 years , with carious upper anterior teeth were divided into five groups . Children in the first and second groups received annual applications of silver diamine fluoride solution ( 44,800 ppm F ) . Sodium fluoride varnish ( 22,600 ppm F ) was applied every three months to the lesions of children in the third and fourth groups . For children in the first and third groups , soft carious tissues were removed prior to fluoride application . The fifth group was the control . Three hundred eight children were followed for 30 months . The respective mean numbers of arrested carious tooth surfaces in the five groups were 2.5 , 2.8 , 1.5 , 1.5 , and 1.3 ( p < 0.001 ) . Silver diamine fluoride was found to be effective in arresting dentin caries in primary anterior teeth in pre-school children PURPOSE To clinical ly evaluate the effectiveness of resin infiltration in conjunction with fluoride varnish treatment vs fluoride varnish treatment alone on facial smooth-surface caries lesions in deciduous teeth . MATERIAL S AND METHODS This r and omised clinical trial was conducted in 419 children aged 18 - 71 months with at least two active smooth-surface caries lesions in deciduous teeth ( ICDAS II score 2 ) . Eighty-one participants met the inclusion criteria and were allocated to one of the two treatment groups : resin infiltration and fluoride varnish ( RI+FV ) ( n = 41 ) and fluoride varnish only ( FV ) ( n = 40 ) . The prevalence of treated white spot lesions ( WSL ) was scored . Fluoride varnish was applied in both groups every 3 months for a year . RESULTS The mean baseline age of children was 3.8 ± 1.3 years . The effectiveness of resin infiltration measured as the percentage of children who did not present any progression of the treated lesions amounted to 43.1 % . After one year , 92.1 % of the infiltrated lesions ( RI+FV ) and 70.6 % of the FV lesions had not progressed ( p < 0.001 ) . CONCLUSION Resin infiltration in conjunction with fluoride varnish treatment of early facial smooth-surface caries lesions in deciduous teeth is superior to fluoride varnish treatment alone for reducing lesion progression OBJECTIVE The aim of this study was to compare the effectiveness and caries-preventive effects of a fluoride varnish ( Fluor Protector ; 0.1 % fluoride ) and a chlorhexidine varnish ( Cervitec ; 1 % chlorhexidine and 1 % thymol ) on initial caries of occlusal fissures and to monitor the durability of the varnishes by the use of a fluorescence system , DIAGNOdent ( Dd ) . METHOD AND MATERIAL S Nineteen subjects underwent professional tooth cleaning at the beginning of the study . Afterward , fluorescence measurements ( baseline ) were obtained from 56 test sites and 28 control sites on the central fossae of molars . Each subject had Fluor Protector and Cervitec application on r and omly assigned experimental teeth , and applications were followed by Dd measurements . Measurements were repeated after 1 and 6 months . RESULTS There was an increase in fluorescence values immediately after application of varnish in the two test groups . One month after varnish application , Dd scores for group Fluor Protector were not significantly different from Dd scores obtained immediately after application ( P = .108 ) , whereas Dd scores for group Cervitec decreased significantly ( P = .007 ) . For both test groups , there was a significant decrease between the values obtained immediately after application and those acquired after 6 months . There was also a significant decrease between 1 month and 6 months for test groups and a slight but significant increase for the control group ( P = .011 ) . No significant difference was found between the Fluor Protector and Cervitec groups after 6 months . CONCLUSION It was concluded that the Dd system may be used to monitor the existence of these two varnishes BACKGROUND The authors conducted a r and omized , single-masked clinical trial involving patients who had completed orthodontic treatment to assess changes in the appearance of white-spot lesions ( WSLs ) that were treated with resin infiltration . METHODS The authors divided affected teeth into control and treatment groups . In the treatment group , they restored teeth with WSLs by using resin infiltration . They evaluated changes in WSLs photographically by using a visual analog scale ( VAS ) ( 0 = no change , 100 = complete disappearance ) and area measurements ( in square millimeters ) . The authors analyzed the data by using two-way analysis of variance . RESULTS The mean VAS ratings for treated teeth demonstrated marked improvement relative to that for control teeth immediately after treatment ( 67.7 versus 5.2 , P < .001 ) and eight weeks later ( 65.9 versus 9.2 , P < .001 ) . The results for treated teeth showed a mean reduction in WSL area of 61.8 percent immediately after treatment and 60.9 percent eight weeks later , compared with a -3.3 percent change for control teeth immediately after treatment and a 1.0 percent reduction eight weeks later . CONCLUSIONS Resin infiltration significantly improved the clinical appearance of WSLs , with stable results seen eight weeks after treatment . PRACTICAL IMPLICATION S Resin infiltration , a minimally invasive restorative treatment , was shown to be effective for WSLs that formed during orthodontic treatment OBJECTIVES Secondary analyses were performed to study the cariostatic efficacy of semi-annual professional fluoride gel application on incipient carious lesions in low-caries children initially aged 9.5 - 11.5 years . METHODS Double-blind r and omized controlled clinical trial . RESULTS The mean treatment effect of fluoride gel for enamel and dentinal caries lesions after 4 years ' follow-up was 0.92 D(2,3)FS and 0.20 D(3)FS , respectively . When enamel lesions were included in the DFS count ( i.e. D(2,3)FS ) , the preventive fraction ( PF ) showed borderline significance ( 23 % ; P = 0.05 ) . No significant treatment effect of professionally applied fluoride gel was found for D(2,3)FS and D(3)FS scores of the second molars . The PF for D(2,3)FS of occlusal , approximal , buccal and lingual surfaces and for buccal and palatal pits and fissures differed not significantly . CONCLUSION Professionally applied fluoride gel showed no statistically significant caries-inhibiting effect on both enamel and dentine lesions in the permanent dentition of low-caries children The aim of this study was to assess the remineralizing effect of an amine fluoride (AmF)- and stannous fluoride (SnF2)-containing toothpaste and mouthrinse on exposed root surfaces . A total of 44 adults participated in the 20-week , double-blind study and were grouped as follows : ( 1 ) 20 participants ( mean age 45.7 years ) used an AmF/SnF2 experimental toothpaste plus AmF/SnF2 ( Meridol ) mouthwash , and ( 2 ) 24 participants ( mean age 48.8 years ) used an NaF-containing toothpaste and mouthrinse . Root caries index ( RCI ) and root surface scores were determined by a modified method of Katz ( J Dent Res , 1984 ) . RCI mean values showed decreases of approximately 47 % in the AmF/SnF2 group , and 10 % in the NaF group . With respect to root caries scores , the number of persons with decreased softened ( non-carious ) surfaces between the baseline and control examinations was statistically significant ( p less than 0.05 ) in the AmF/SnF2 group but not significant in the NaF group . A statistically significant difference ( p less than 0.05 ) in the results of the groups favored the AmF/SnF2 subgroup . Thus , the data point to a possible remineralizing effect of topically applied AmF/SnF2 on softened root caries surfaces BACKGROUND The aim of this study was to evaluate the effect of fluoride varnish on enamel caries progression in the primary dentition . METHODS One hundred forty-two children in Head Start schools ( 3 to 5 years old ) were r and omized into the varnish and control groups . Children in the varnish group received fluoride varnish ( Duraphat , Colgate-Palmolive Co. ) at baseline and after four months , and children in the control group received no professional fluoride applications . Two calibrated examiners performed the examinations at baseline and at nine months . RESULTS At nine months , the authors found that in the control group , 37.8 percent of active enamel lesions on occlusal , buccal and lingual surfaces became inactive , 3.6 percent progressed and 36.9 percent did not change . In the varnish group , 81.2 percent became inactive , 2.4 percent progressed and 8.2 percent did not change . The difference between the groups was statistically significant ( P < .0001 ) . The mean decayed surfaces , or ds , value in the varnish group was significantly lower after nine months than it was at baseline ( P < .0001 ) . When enamel lesions were included in the data analysis ( along with dentinal lesions ) , the decayed with initial enamel lesions , missing and filled surfaces , or dEmfs , values ; decayed with initial enamel lesions , missing and filled teeth , or dEmft , values ; and decayed surfaces with initial enamel lesions , or dEs , values were significantly lower in the varnish group after nine months than they were at baseline ( P < .0001 ) . CONCLUSIONS These results suggest that fluoride varnish applications may be an effective measure in reversing active pit- and -fissure enamel lesions in the primary dentition . CLINICAL IMPLICATION S Fluoride varnishes are safe , easy to apply and well-accepted by patients . This study shows that fluoride varnish may offer an efficient , nonsurgical alternative for the treatment of decay in children This study assessed the efficacy of sealing proximal lesions on adult patients using a split-mouth design . Eighty-two 15- to 39-year-olds from the Dental Faculties in Copenhagen and Bogotá participated , each having 2 or more proximal lesions in the following radiographic stages : ( 1 ) lesion restricted to the outer half of enamel ; ( 2 ) lesion from the inner half of enamel including the enamel dentine junction , and ( 3 ) lesion restricted to the outer third of dentine . St and ardized geometrically aligned baseline and follow-up radiographs were obtained . One r and omly selected lesion ( test ) in each patient was sealed with 1 of 2 resins . The patients were instructed to floss all the proximal lesions 3 times per week . The baseline to 18 months difference in caries lesion progression status was assessed using 3 methods : ( 1 ) radiographs were independently assessed visually ; ( 2 ) radiographs were read in pairs , and ( 3 ) using subtraction radiography of digitized images . A total of 72 subjects finished the study ( 12.2 % dropout ) . The compliance concerning flossing was poor ( 15 % ) . For the repeated examinations kappa was 0.84 for the visual examination , 0.44 for the paired readings and 0.84 for the subtraction examination . Two test lesions and 1 control lesion were restored . For the independent radiograph assessment method 10 and 26 % progressed in the test and control group , respectively ( p > 0.05 ) ; with the paired radiograph method the corresponding data were 22 % in the test and 47 % in the control groups ( p < 0.01 ) . By subtraction radiography 44 % of the test group and 84 % of the control were judged to have progressed ( p < 0.001 ) . The sealing technique was superior to instructing patients to floss , and subtraction radiography appeared to be the most sensitive method for assessing lesion progression OBJECTIVES To investigate the effectiveness of silver diammine fluoride ( SDF ) solution application in arresting dental root caries and to assess the color of arrested caries lesions . METHODS This study was conducted in elderly centers in Hong Kong . A total of 83 elders with 157 root surfaces with active caries lesion were r and omly allocated into 3 groups : Gp1 ( placebo control)-annual application of soda water ; Gp2-annual application of SDF solution ; Gp3-annual application of SDF solution immediately followed by potassium iodide ( KI ) solution . Color of the arrested root caries lesion was assessed with reference to PANTONE color plates and classified into one of the followings : yellow ( 7401U ) ; light brown ( 1245U ) ; dark brown ( 4635U ) ; and black ( Black U ) . Status of root surfaces was assessed every 6 months by the same independent examiner . RESULTS After 30 months , 100 ( 64 % ) of the included root caries lesions were review ed . The arrest rates of root caries were 45 % , 90 % , and 93 % in Gp1 ( control ) , Gp2 ( SDF ) and Gp3 ( SDF/KI ) , respectively ( χ(2 ) test , p<0.001 ) . Pairwise comparisons showed elders in the control group had a lower proportion of the active root caries changed to arrested ( p<0.001 ) and the proportions of root caries being arrested in the SDF and SDF/KI groups were not significantly different ( p>0.05 ) . The distributions of arrested caries lesions by color were not significantly different between the SDF and SDF/KI groups ( χ(2 ) test , p>0.05 ) . CONCLUSIONS Application of SDF solution , with or without application of KI afterwards , is effective in arresting root caries among elders in a water fluori date d area . In the long term , blackening of arrested root caries is not reduced by immediate application of KI after the application of SDF . CLINICAL SIGNIFICANCE In a water fluori date d area , annual application of SDF solution or SDF/KI solution can arrest dental root caries in elders . In the long term , application of KI does not reduce the blackening of arrested caries lesions caused by SDF The present study was design ed to investigate the pattern of the caries inhibiting effect of school fluoride mouthrinse programs in children of different baseline caries experience . In Phase I , 170 children 10 and 11 years of age were r and omly assigned to a test group who rinsed with a 0.5 % NaF solution once every 2 weeks for 3 years or to a control group who rinsed with distilled water . In Phase II , the dental records of 345 children were used . Here , the test group had rinsed weekly with a 0.2 % NaF solution , while the control group consisted of children 3 years older who were not included in the program during the ages under study ( 10 - 11 to 13 - 14 ) . The statistical analysis of the data was performed as linear regression of caries increments on baseline scores . The analyses included all tooth surfaces , as well as separate studies of proximal and free smooth surfaces , respectively . It was shown that caries increments increased as the baseline scores increased . The slope of the regression lines indicated that the fluoride mouthrinses were more effective in high caries groups than in low caries groups . The results are in agreement with earlier findings concerning the interaction between factors in the caries process We hypothesized that the six-monthly application of silver diamine fluoride ( SDF ) can arrest the development of caries in the deciduous dentition of six-year-old schoolchildren and prevent caries in their first permanent molars . A prospect i ve controlled clinical trial was conducted on the efficacy of a 38 % SDF solution for caries reduction . Four hundred and twenty-five six-year-old children were divided into two groups : One group received SDF solution in primary canines and molars and first permanent molars every 6 mos for 36 mos . The second group served as controls . The 36-month follow-up was completed by 373 children . The mean number of new decayed surfaces appearing in primary teeth during the study was 0.29 in the SDF group vs. 1.43 in controls . The mean of new decayed surfaces in first permanent molars was 0.37 in the SDF group vs. 1.06 in controls . The SDF solution was found to be effective for caries reduction in primary teeth and first permanent molars in schoolchildren A professionally applied two – stage chlorhexidine varnish , Chlorzoin ® , was developed to achieve sustained release and minimise the problems of staining and bad taste associated with chlorhexidine mouthrinses . The primary aim of this r and omised controlled clinical trial was to assess the efficacy of Chlorzoin in reducing the caries increment in high – caries – risk adolescents . Secondary aims included investigating the effect of compliance upon caries increment , the effect of Chlorzoin upon salivary mutans streptococci levels and assessing the benefit of individual dental health advice by dental auxiliaries in a community setting . 1,240 children , initially aged 11–13 years , assessed to be at high caries risk were recruited into the trial . The trial design involved four arms : an observational group , a control group , an active ( Chlorzoin ) varnish group and a placebo varnish group . All subjects were examined annually by a calibrated examiner who was blind to the group allocation . Three – year caries increments were calculated using clinical , clinical and fibre – optic transillumination , and clinical and bitewing data sets . The results indicated that the use of Chlorzoin had an initial effect on mutans streptococci levels but that no long – term reduction in caries increment or mutans streptococci infection could be detected . One reason for this lack of efficacy may have been the regimen of reduced frequency of varnish applications after the initial period . Children who followed the protocol and , therefore , were seen regularly by dental auxiliaries had a lower caries increment than those who did not . This finding was independent of varnish allocation . In summary , under this regimen , Chlorzoin has been found to be effective in decreasing salivary mutans streptococci but ineffective as a caries – preventive agent in high – risk Scottish children when applied pragmatically in a community setting OBJECTIVES The aim of this clinical study was to evaluate the retention rate and caries-prevention effect of a flowable composite compared to a conventional resin-based sealant in a young population over a 24-month period . METHODS Thirty-four patients , ranging in age from 16 to 22 years , diagnosed with at least 2 non-cavitated pit- and -fissure caries in the first and second molars were selected for this r and omized split-mouth design trial . A total of 220 sealants , were placed in 117 upper molars and 103 lower molars . The teeth were sealed with a flowable resin composite ( Tetric Evo Flow ) or a sealant material ( Helioseal F ) . Each restoration was independently evaluated in terms of retention and the presence of caries at baseline and at 1 , 6 , 12 , and 24 months . Data were analyzed using non-parametric Mann-Whitney U and Friedman 1-way ANOVA tests at p<0.05 . RESULTS Tetric Evo Flow showed complete retention with 100 % , 95.5 % , 93.8 % , and 88.5 % at 1 , 6 , 12 , and 24-month evaluations , respectively , while Helioseal F retention rates were 98.1 % , 95.5 % , 94.8 % , and 85.4 % , respectively , for the same evaluation periods . At the 24-month recall , 4 ( 4.2 % ) total losses were observed in subjects treated with Tetric Evo Flow and 2 total losses ( 2.1 % ) for Helioseal F , respectively . No significant differences were observed between the material s in retention rates or caries incidence for each evaluation period ( p>0.05 ) . CONCLUSION Placement of flowable composite as fissure sealants in the younger population seems to be as effective as conventional fluoride containing fissure sealants for the prevention of fissure caries . CLINICAL RELEVANCE The use of a flowable composite as a fissure sealant material , in conjunction with a total-etch , single bottle adhesive , yielded better retention than did the conventional fluoride containing resin-based fissure sealant over a 24-month period in young patients fixed orthodontic appliances can result in rapid demineralization,1 - 7 sometimes within only a few weeks after bracket placement.1 - 3 Vigilant home hygiene , including the use of a fluoride mouthwash , is effective in preventing white spots,6 - 9 but requires unusual patient compliance . Periodic application of fluoride varnish is much more efficient , reducing demineralization around brackets by as much as 50%.9 - 15 In this study , we evaluated the in vivo effectiveness of a fluoride varnish in preventing demineralization of the enamel surrounding orthodontic brackets , as measured with a laser fluorescence monitoring device OBJECTIVES The effectiveness of either a 0.2 % neutral sodium fluoride ( NaF ) solution or a 0.12 % chlorhexidine ( CHX ) solution as a daily mouthrinse for controlling caries was tested against a placebo rinse in this 2-year r and omized clinical trial among elders in long-term care ( LTC ) facilities . METHODS At baseline , 369 recruits were examined clinical ly for caries and allocated r and omly to one of the mouthrinse groups . RESULTS After 2 years , 116 participants remained in the trial . The prevalence of caries and the dental status of the groups were similar at baseline and after 2 years . On average , each group lost less than one tooth per person , but the fluoride group compared with the others had significantly less caries and significantly more reversals from carious to sound dental surfaces at the end of the trial . CONCLUSIONS We conclude that 0.2 % neutral NaF mouthrinse every day does reduce the incidence of caries among elders in LTC facilities This study compared caries inhibition in children by an amine fluoride and an acidulated phosphate fluoride when administered in a topically applied gel . In addition , the effects of applying amine fluoride daily and weekly were compared . Four hundred and sixty-eight children , ages 6 to 13 , were r and omly assigned to one of five treatment groups and received a total of five , 5-minute treatments . The treatment and interval between each of the five treatments were as follows:(A)acidulated phosphate fluoride daily , ( B ) amine fluoride daily , ( C ) amine fluoride weekly , ( D ) placebo daily , and ( E ) placebo weekly . When the children were examined for total Decayed , Missing , and Filled Surfaces ( DMFS ) increments 2 years later , no significant differences were observed . However , when the data were examined for effects of DMFS for specific tooth surface , significant restriction ( 61 % ) of occlusal increment was shown in the group which was treated with amine fluoride daily for 5 consecutive days as compared with the control group The aim of this study was to determine the effects of 3 wk of daily rinsing with amine fluoride/stannous fluoride ( AmF/SnF(2 ) ) mouthrinse on plaque formation at buccal and interproximal sites , and on the acid production in plaque , in a r and omized clinical trial with 30 participants . The amount of plaque was scored according to Turesky 's modification of the Quigley and Hein index . Plaque sample s were collected , before and after sucrose rinsing , from the buccal and interproximal surfaces of upper (pre)molars at two baseline visits and on days 2 and 7 after the discontinuation of 3 wk of daily rinsing . Metabolic acid ions were determined by capillary electrophoresis . The results at baseline showed higher lactic acid concentrations in resting interproximal plaque than in buccal plaque , and a higher acid production in response to sucrose challenge in buccal plaque than in interproximal plaque . After 3 wk of use of the AmF/SnF(2 ) mouthrinse , no significant differences in plaque scores were observed , and the alleged reduction in acidogenicity of dental plaque was not significant on the second day after the last mouthrinse . We conclude that 3 wk of use of AmF/SnF(2 ) rinse once daily does not result in a reduction of plaque formation or in a reduction of sucrose metabolism in buccal and interproximal plaque after discontinuing the rinse Previous studies have shown that topical application of the fluoride varnish Duraphat reduces caries incidence . The aim of the present study was to compare the caries inhibiting effect of a new fluoride varnish ( Carex ) containing 1.8 % fluoride ( F ) with that of Duraphat ( 2.26 % F ) . Informed consent was obtained from the guardians of 495 children 10 - 12 yr old in Voss Dental Health District ( low F area ) . The children were r and omly allocated to two groups . One group of subjects received 6-monthly application of Duraphat ( n = 185 ) , the other Carex ( n = 165 ) . Ethical considerations precluded the use of a placebo varnish . All participants received dental examinations including one pair of posterior bitewing radiographs and necessary dental care annually . One trained examiner interpreted bitewing radiographs blindly . Total 3-yr net DFS increment for 24 posterior approximal surfaces was 2.63 ( SD = 3.81 ) in the Duraphat group and 2.12 ( SD = 3.50 ) in the Carex group . DMFS increments based on 40 posterior occlusal and approximal surfaces were 5.21 ( SD = 5.79 ) and 4.04 ( SD = 4.92 ) , respectively . Thus the results indicate a comparable efficacy for Carex and Duraphat at the caries activity level exhibited by these study participants 251 9 - 12-yr-old children completed a 3-yr , double-blind , clinical trial of two caries preventive fluoride programs . Caries increments and progression patterns were compared in two groups of children who rinsed every fortnight with a 0.2 % NaF solution or received biannual topical applications with a fluoride varnish ( Fluor-Protector ) . Clinical ly recorded mean DFS increments were 3.3 + /- 0.2 ( SE ) in the rinse group and 3.5 + /- 0.2 in the varnish group . In both groups nearly half of these increments were recorded in the occlusal surfaces of second molars . The mean incremental DFS recorded radiographically on approximal surfaces of posterior teeth were 1.1 + /- 0.2 and 1.5 + /- 0.2 in the rinse and varnish group , respectively . None of the inter-group differences were statistically significant ( P greater than 0.05 ) . Detailed analyses of the radiographic scores revealed a similar and extremely slow caries progression in the two study groups and they strengthened the conclusion of equal clinical efficacy of the two treatments . None of the fluoride programs had been able to change preestablished patterns of caries development among the children PURPOSE To clinical ly evaluate the additional effect of adding 0.12 % chlorhexidine digluconate ( CHX ) to a 0.05 % sodium fluoride ( NaF ) mouth rinse in arresting active enamel caries lesions after 28 days . MATERIAL S AND METHODS A short-term double-blind clinical trial that included a total of 170 children , aged 11 to 15 years , with active smooth surface caries lesions ( average 6.52 ) was conducted . The participants were enrolled and r and omly distributed into two equal groups . Under the supervision of the research team , the children rinsed with a 15 ml solution of either 0.05 % NaF ( G1 ) or 0.05 % NaF + 0.12 % CHX ( G2 ) for 1 min/day for 28 days . A clinical examination was carried out at the beginning and at the end of the study with children who underwent supervised tooth brushing . A calibrated examiner , who was unaware of the treatment given to each subject , examined all smooth surfaces dried with compressed air , isolated and illuminated with a reflector . The surface was considered active ( A ) or arrested ( I ) . The frequency of A or I surfaces was evaluated by calculating the difference between the number found at the beginning and at the end of the trial . RESULTS No significant differences were detected between the two groups with respect to caries lesion surfaces at baseline ( 6.49 + /- 4.45 - G1 , 6.55 + /- 4.23 - G2 , respectively ) , nor were differences found when age and gender wer taken into consideration . Arrestment proportions were 84.4 % ( G1 ) and 85.3 % ( G2 ) ( P = 0.71 ; not significant ) . CONCLUSIONS Although both solutions showed high arrestment proportions , the addition of CHX did not improve the arrestment capacity of the NaF mouth rinse In a double-blind r and omized controlled clinical trial , the caries-reducing effect of semi-annually applied fluoride gel in a low-caries child population initially aged 4.5–6.5 years ( n = 773 ) has been investigated . Secondary analyses of the data were performed to study the caries reduction including non-cavitated lesions . The treatment effect of fluoride gel was calculated as preventive fraction ( PF ) . When enamel lesions were included in DFS count ( D2 grade ) , the PF was 22 % as compared to 26 % counting dentinal lesions . The PFs showed that the mean effect of professionally applied fluoride gel was highest ( 71 % ) for D3S in the permanent dentition and lowest for d3s in the primary dentition ( 5 % ) . The PFs for approximal and buccal and lingual surfaces of the permanent dentition significantly decreased from 80 to 25 % and from 60 to 37 % when enamel lesions ( D2S ) were included . With the exception of the buccal and lingual surfaces , in the primary dentition the PFs varied slightly when enamel lesions were included . Inclusion of non-cavitated lesions in the treatment effect statistics did not change the former conclusion that the treatment effect of fluoride gel application on dental caries reduction in a low-caries child population was considered not clinical ly relevant To determine the effect of chewing sugar-free gum on caries incidence , the authors conducted a r and omized clinical study . A total of 1,402 children in Puerto Rico , in grade s 5 through 7 at baseline , completed the study . They were r and omized by classroom into a control group or chewing gum group ; those in the gum group were instructed to chew sugar-free gum for 20 minutes after each of three meals a day . Clinical and radiographic evaluations were performed at baseline and after two and three years . The results show that all subjects and high-risk subjects , respectively , in the gum group developed 7.9 percent and 11.0 percent fewer decayed , missing or filled surfaces than subjects in the control group . Based on these findings , the authors concluded that chewing sorbitol-based sugar-free gum after eating significantly reduces the incidence of dental caries PURPOSE To evaluate the efficacy of conservative treatment of dentin non-cavitated caries using a resin-based fluoride-containing pit and fissure sealant . METHODS In this controlled clinical trial , 60 teeth with clinical ly non-cavitated occlusal caries radiographically located beneath the enamel-dentin junction ( radiolucent area ) were selected among patients presenting a moderate to high caries risk . The teeth were r and omly divided into two groups of 30 teeth each : an experimental group receiving an application of Fluorshield ( Dentsply ) sealant and a control group not su bmi tted to any clinical intervention . Caries progression was monitored by clinical and radiographic examination at 4-month intervals over a period of 1 year . In addition , marginal integrity of the sealant was evaluated in the experimental group . RESULTS Clinical and radiographic caries progression was significantly more frequent in control teeth when compared to the experimental group ( P < 0.05 ) PURPOSE To compare the effectiveness of Prevident 5000 Plus ( 5,000 ppm F ) and Colgate Winterfresh Gel ( 1100 ppm F ) to arrest root carious lesions . MATERIAL S AND METHODS 201 subjects with at least one root carious lesion were recruited from dental school patients . They were r and omly assigned to use either Prevident 5000 Plus ( 5000 ppm F ) or Colgate Winterfresh Gel ( 1100 ppm F ) as sodium fluoride in the same silica base . Measurements of lesion hardness , area , distance from the gingival margin , cavitation and plaque were recorded at baseline and after 3 months by a single examiner . RESULTS After 3 months 38 % of subjects using Prevident 5000 Plus and 10 % using Winterfresh Gel had one or more lesions that had become hard ( P < 0.001 ) . Non-cavitated lesions at baseline were more likely to become hard than cavitated lesions . Compared to the Winterfresh group there was significant increase in the distance from the base of the lesion to the gingival margin and plaque scores were reduced in those using Prevident 5000 Plus Aim : To evaluate the effect of xylitol-containing tablets on mutans streptococci colonisation and caries development in preschool children . Study design : R and omised single-blind prospect i ve design . Methods : The material consisted of 132 healthy 2-year-old children , 71 boys and 61 girls and they were assigned to a xylitol tablet ( test ) group or a non-intervention control group . The mean age was 2 years + 1 month in both groups . The drop-out rate was 10.6 % during the 2-year trial . The test group was given 1`-2 xylitol tablets ( 0.5`-1 g ) per day during 1.5 years . Mutans streptococci ( MS ) enumeration was performed at baseline and semi-annually in the children and at baseline or shortly after in the mothers with a chair-side technique . Caries prevalence was scored at baseline and the age of 4 years . Results : No statistically significant differences in MS colonisation were disclosed between the test and control groups at baseline or any of the design ated follow-ups . A statistically significant positive relationship was found between the maternal salivary MS levels and the colonisation of the children in the control group at 2.5 years , 3 years and 3.5 years ( r=0.39 , r=0.35 ; r=0.30 ; p<0.01 , p<0.01 and p<0.05 ) but not in the xylitol tablet group ( p>0.05 ) . The mean caries prevalence was lower in the test group compared with the control group at 4 years of age ( dmfs 0.38 ±1.05 vs. 0.80 ±2.60 ) but the difference was not statistically significant . Conclusion : The findings do not support a low-dose xylitol tablet program for caries prevention in preschool children The objective was to test a fluoride-containing slow-release device in preventing dental caries in children . Accordingly a population of 174 children aged 8 years living in a high-caries , low socio-economic area of Leeds ( UK ) was assembled . Two slow-release/dissolving glass ( SFG ) pellets , one with fluoride ( F ) and one without , were r and omly attached to the maxillary molars of the children . Baseline caries as dmft/s , DMFT/S , periodontal disease , plaque and calculus were recorded using st and ard indices . Unstimulated saliva sample s were collected 2 h postpr and ial for F analysis . All parameters were measured at 6-month intervals for 2 years . There were 132 children completing the trial of whom 63 ( test n = 31 , control n = 32 ) still retained the glass devices at the end . Comparison of mean values for gingival health and calculus showed no differences between groups throughout the trial . Mean caries as dmfs at the end of the trial ( 2.26 ) was significantly lower for the test ( SFG , 2.26 ) compared with that for the control children ( 8.41 ; p ≤ 0.001 ) . DMFS was significantly lower at 0.84 and 2.34 , respectively ( p ≤ 0.05 ) . Mean salivary fluoride concentrations were 0.11 and 0.03 mg/l for test and control groups . It was concluded that placement of a glass slow-releasing fluoride device significantly reduced caries incidence in a group of low socio-economic schoolchildren over 2 years PURPOSE Control of Streptococcus mutans can prevent caries in high-risk preschool children . The purpose of this study was to assess the effect of casein phosphopeptide amorphous calcium phosphate ( CPP-ACP ) on Streptococcus mutans in the plaque of high-risk preschool children . METHODS A triple blind , r and omized , controlled clinical trial included 40 healthy three- to five-year-olds with at least one white spot lesion . They were r and omized into test ( daily applications of GC Tooth Mousse : CPP-ACP ) and control groups ( placebo mousse ) . Both groups received health education . Plaque sample s were collected at baseline and after 15 days and cultured on Mitis Salivarius Agar . Percent reduction in S mutans count was calculated and compared between groups using t-test . RESULTS Percent reduction of S mutans in the test group was slightly higher than in the control group ( 59 percent and 52 percent ) but not significantly different after 15 days ( P=0.27 ) , with both groups showing a significant reduction from baseline ( P<0.0001 ) . CONCLUSIONS Casein phosphopeptide amorphous calcium phosphate reduced Streptococcus mutans in the plaque of preschool children with noncavitated lesions after two weeks of daily application compared to baseline . It was not , however , significantly different from the reduction occurring after only a single session of health education Experimental evidence has clearly demonstrated that the early stages of lesion formation ( enamel demineralization ) are reversible following exposure to saliva and /or fluoride . Clinical evidence for remineralization has also been reported extensively in the literature . However , the literature is lacking with respect to data from well-controlled clinical studies regarding the quantitative contribution of remineralization to arrestment and reversal of caries . Retrospective analysis of an existing clinical trial data base provided an opportunity to examine the incidence of clinical lesion reversals in a placebo-controlled , double-blinded caries clinical study . The clinical study examined three treatment groups : 1 ) 0.243 % sodium fluoride/silica dentifrice , 2 ) 0.4 % stannous fluoride/calcium pyrophosphate ( positive control ) dentifrice and 3 ) non-fluori date d placebo/calcium pyrophosphate ( negative control ) dentifrice . Clinical measures in this study included both radiographic and visual-tactile assessment s of caries . Examination of all subjects revealed a statistically greater frequency for caries reversals in the sodium fluoride group as compared to the placebo group at Year 3 , for both total and radiographic caries . In contrast , while caries reversals in the stannous fluoride group occurred with greater frequency than in the placebo group at Year 3 , for both total and radiographic caries , the differences were not statistically significant . When only subjects who were " at risk " for potential reversals ( i.e. , those with a minimum of one carious lesion at baseline ) were examined , a statistically greater frequency in caries reversals was observed in both the sodium fluoride ( total , incipient , and radiographic caries ) and stannous fluoride ( total and radiographic caries ) groups as compared to the placebo group at Year 3 . Collectively , these data confirm the ability of both 0.243 % sodium fluoride/silica and 0.4 % stannous fluoride/calcium pyrophosphate dentifrices to clinical ly reverse caries . The results suggest that sodium fluoride may deliver a greater frequency of caries reversals than stannous fluoride , although these treatments were not found to be significantly different OBJECTIVES To evaluate the efficacy of weekly supervised tooth-brushing with a toothpaste and a 1.23 % acidulated phosphate fluoride gel ( APF ) gel on white lesion reversal to treat incipient enamel lesions . DESIGN A double-blind and r and omized controlled trial . SAMPLE AND METHODS Three-hundred seven to 12-year-old Brazilian schoolchildren who presented with white spots on the buccal surfaces of permanent upper incisors were r and omly allocated to three groups . In group I , children underwent supervised tooth-brushing and APF gel ( 1.23 % ) for one minute once a week . In group II , children were subjected to a weekly supervised tooth-brushing and a topical application of placebo , whereas group III ( control ) received no intervention . An expert dental examiner performed all intra-oral examinations for dental caries ( DMF-s and dmf-s ) and oral hygiene ( Visible Plaque Index , Gingival Blood Index ) . RESULTS After three months , 258 children and 460 lesions were analyzed . The results of the clinical evaluation of arrested white spots did not differ significantly ( p = 0.95 ) between the two experimental groups ( 57.9 % in group I and 56.8 % in group II ) but differed significantly between them and the control group ( p = 0.022 ) . Logistic regression analysis identified gingival blood index ( OR = 1.70 , CI = 1.13 -2.55 ) , DMF-s2 ( OR = 1.61 , CI = 1.07 - 2.43 ) and number of white spot lesions ( OR = 1.76 , CI = 1.04 to 2.98 ) as independent ' risk ' factors for white spot lesion activities . On the other h and , supervised tooth-brushing with APF ( OR = 0.55 , CI = 0.34 - 0.91 ) or without APF ( OR = 0.58 , CI = 0.35 - 0.94 ) was a protective factor . CONCLUSIONS These results suggest that the weekly supervised tooth-brushing was able to arrest enamel white spots and that poor oral hygiene increases the probability of keeping white spots active Different regimens of silver diamine fluoride ( SDF ) have been used to manage early childhood caries . So far , there is limited information regarding the concentrations and frequency of applications for effective caries control in primary teeth . This study aim ed to compare the efficacy of 2 commercially available SDF solutions at preprepared concentrations of 38 % and 12 % when applied annually or biannually over 18 mo in arresting dentine caries in primary teeth . This r and omized double-blinded clinical trial recruited kindergarten children aged 3 to 4 y who had at least 1 tooth with dentine caries . The children were r and omly allocated to receive 4 treatment protocol s : group 1 , annual application of 12 % SDF ; group 2 , biannual application of 12 % SDF ; group 3 , annual application of 38 % SDF ; and group 4 , biannual application of 38 % SDF . Clinical examinations at 6-mo intervals were conducted to assess whether active carious lesions became arrested . Information on the children ’s background and oral hygiene habits was collected through a parental question naire at baseline and follow-up examinations . A total of 888 children with 4,220 dentine carious tooth surfaces received treatment at baseline . After 18 mo , 831 children ( 94 % ) were examined . The caries arrest rates were 50 % , 55 % , 64 % , and 74 % for groups 1 , 2 , 3 , and 4 , respectively ( P < 0.001 ) . Lesions treated with SDF biannual application had a higher chance of becoming arrested compared with those receiving SDF annual application ( odds ratio , 1.33 ; 95 % confidence interval , 1.04–1.71 ; P = 0.025 ) . The interaction between concentration and lesion site was statistically significant ( P < 0.001 ) . Compared with 12 % SDF , the use of 38 % SDF increased a chance of becoming arrested ( P < 0.05 ) , except lesions on occlusal surfaces . Based on the 18-mo results , SDF is more effective in arresting dentin caries in the primary teeth of preschool children at 38 % concentration than 12 % concentration and when applied biannually rather than annually . Knowledge Transfer Statement : The results of this study can be used by clinicians and dental public health professionals when deciding which concentrations and frequency of application of silver diamine fluoride solution should be adopted for arresting dentine caries . With consideration of caries arrest treatment with silver diamine fluoride , which is painless , simple , and low cost , this information could lead to more appropriate therapeutic decisions for caries control in young children or those who lack access to affordable conventional dental care The purpose of the study was to evaluate the caries preventive effect and cost of an intensive application of Duraphat varnish , added to the regular preventive program for 11 - 15-yr-old children in a Swedish Dental Community Clinic . In 1987 , the 134 11-yr-old children in Floda were divided into two groups , every second child to each . Children with fixed orthodontic appliances were excluded . The test group received three applications of Duraphat varnish during 1 week , once a year , by a dental nurse . The control group received one application at the annual check-up . Both groups were included in the regular preventive program at the clinic . The total time cost for the clinic was estimated and used to calculate the cost per hour for dentists and nurses . The caries increment and progression were estimated both by routine diagnosis and by a careful study of radiographs taken at the beginning and end of the study period . There was a small caries increment and progression in the test group as compared to the control group . The difference was statistically significant for all aspects studied . The costs were about the same in both groups but more time was used in the test group . The administrative effort for the staff was considerable for the intensive Duraphat application OBJECTIVES The aim of the present study was to evaluate the effects of fluorescence-controlled Er : YAG laser radiation , an ultrasonic device or h and instruments on periodontally diseased root surfaces in vivo . MATERIAL AND METHODS Seventy-two single-rooted teeth ( n=12 patients ) were r and omly treated in vivo by a single course of subgingival instrumentation using ( 1 - 3 ) an Er : YAG laser ( ERL1 : 100 mJ ; ERL2 : 120 mJ ; ERL3 : 140 mJ ; 10 Hz ) , or ( 4 ) the Vector ultrasonic system ( VUS ) or ( 5 ) h and instruments ( SRP ) . Untreated teeth served as control ( UC ) . Areas of residual subgingival calculus ( RSC ) and depth of root surface alterations were assessed histo-/morphometrically . RESULTS Highest values of RSC areas ( % ) were observed in the SRP group ( 12.5+/-6.9 ) . ERL(1 - 3 ) ( 7.8+/-5.8 , 8.6+/-4.5 , 6.2+/-3.9 , respectively ) revealed significantly lower RSC areas than SRP . VUS ( 2.4+/-1.8 ) exhibited significantly lower RSC areas than SRP and ERL(1 , 2 ) . Specimens treated with SRP revealed conspicuous root surface damage , while specimens treated with ERL(1 - 3 ) and VUS exhibited a homogeneous and smooth appearance . CONCLUSION Within the limits of the present study , it may be concluded that ERL and VUS enabled ( i ) a more effective removal of subgingival calculus and ( ii ) a predictable root surface preservation in comparison with SRP Root caries is prevalent in elderly disabled nursing home residents in Denmark . This study aim ed to compare the effectiveness of tooth brushing with 5,000 versus 1,450 ppm of fluori date d toothpaste ( F-toothpaste ) for controlling root caries in nursing home residents . The duration of the study was 8 months . Elderly disabled residents ( n = 176 ) in 6 nursing homes in the Copenhagen area consented to take part in the study . They were r and omly assigned to use one of the two toothpastes . Both groups had their teeth brushed twice a day by the nursing staff . A total of 125 residents completed the study . Baseline and follow-up clinical examinations were performed by one calibrated examiner . Texture , contour , location and colour of root caries lesions were used to evaluate lesion activity . No differences ( p values > 0.16 ) were noted in the baseline examination with regards to age , mouth dryness , wearing of partial or full dentures in one of the jaws , occurrence of plaque and active ( 2.61 vs. 2.67 ; SD , 1.7 vs.1.8 ) or arrested lesions ( 0.62 vs. 0.63 ; SD , 1.7 vs. 1.7 ) between the 5,000 and the 1,450 ppm fluoride groups , respectively . Mean numbers of active root caries lesions at the follow-up examination were 1.05 ( 2.76 ) versus 2.55 ( 1.91 ) and mean numbers of arrested caries lesions were 2.13 ( 1.68 ) versus 0.61 ( 1.76 ) in the 5,000 and the 1,450 ppm fluoride groups , respectively ( p < 0.001 ) . To conclude , 5,000 ppm F-toothpaste is significantly more effective for controlling root caries lesion progression and promoting remineralization compared to 1,450 ppm F-toothpaste Orthodontic patients have an increased risk of white-spot lesion formation . A clinical trial was conducted to test whether , in a post-orthodontic population using fluoride toothpastes and receiving supervised fluoride mouthrinses , more lesions would regress in participants using a remineralizing cream containing casein phosphopeptide- amorphous calcium phosphate compared with a placebo . Forty-five participants ( aged 12–18 yrs ) with 408 white-spot lesions were recruited , with 23 participants r and omized to the remineralizing cream and 22 to the placebo . Product was applied twice daily after fluoride toothpaste use for 12 weeks . Clinical assessment s were performed according to ICDAS II criteria . Transitions between examinations were coded as progressing , regressing , or stable . Ninety-two percent of lesions were assessed as code 2 or 3 . For these lesions , 31 % more had regressed with the remineralizing cream than with the placebo ( OR = 2.3 , P = 0.04 ) at 12 weeks . Significantly more post-orthodontic white-spot lesions regressed with the remineralizing cream compared with a placebo over 12 weeks Probiotic bifidobacteria are widely used in the prevention of childhood diseases . These bacteria are also associated with caries occurrence . The present secondary analysis in a low-caries population evaluated the effect of early administration of Bifidobacterium animalis subsp . lactis BB-12 ( BB-12 ) on caries occurrence and identified markers of dental decay in early childhood . In the original r and omized , double-blind , placebo-controlled study ( NCT00638677 , http://www . clinical trials.gov ) , infants ( n = 106 ) received BB-12 , xylitol or sorbitol tablets from the age of 1 - 2 months to 2 years with a slow-release pacifier or a spoon ( daily dose of BB-12 1010 colony-forming units , polyol 200 - 600 mg ) . The present data were collected using clinical examinations and question naires at the age of 4 years . The occurrence of dental caries was assessed using the International Caries Detection and Assessment System . Oral hygiene status and mutans streptococci ( MS ) levels were also determined . No differences were detected between the study groups in the occurrence of enamel caries ( p = 0.268 ) or obvious dentinal caries ( p = 0.201 ) . The occurrence of caries was associated with daily consumption of sweet drinks ( p = 0.028 ) , visible plaque observed ( p = 0.002 ) and MS detected in the dental plaque ( p = 0.002 ) . Administration of BB-12 in infancy does not seem to increase or decrease the occurrence of caries by 4 years of age in a low-caries population Probiotic bacteria are thought to reduce the risk of disease . Previous studies have suggested that lactobacilli-derived probiotics in dairy products may affect the oral ecology , but the effect of bifidobacteria has not previously been reported . The aim of the present study was to examine whether or not short-term consumption of yogurt containing bifidobacteria would affect the salivary levels of mutans streptococci and lactobacilli in young adults . A double-blind , r and omized crossover study was performed and 21 healthy subjects were followed over four periods . During periods 2 and 4 ( 2 weeks each ) , they ingested 200 g yogurt containing Bifidobacterium DN-173 010 once daily or a control yogurt without viable bacteria . Periods 1 and 3 were run-in and washout periods , respectively . Salivary mutans streptococci and lactobacilli were enumerated with chair-side kits . A statistically significant reduction ( p<0.05 ) of salivary mutans streptococci was recorded after the probiotic yogurt consumption , which was in contrast to the controls . A similar trend was seen for lactobacilli , but this decrease failed to reach statistical significance . In conclusion , probiotic bifidobacteria in yogurt may reduce the levels of selected caries-associated microorganisms in saliva This split-mouth study aim ed to assess the efficacy of resin-infiltrated lesions covered by fluoride varnish ( FV ) versus FV treatment only of proximal lesions on deciduous molar teeth . The study lasted for 1 year . Children with 2 or more superficial proximal lesions on deciduous molar teeth detected on bitewing radiographs were included . After written parental consent , two lesions in each of 50 children were r and omly allocated to one of two treatments : resin infiltration followed by FV ( 2.26 % F ) application ( test lesion ) versus only FV ( control lesion ) . The ICDAS scores of the selected lesions were recorded by 2 clinicians before the treatments ( weighted kappa for inter- and intra-examiner agreement > 0.79 ) . FV was applied to both test and control lesions 6 and 12 months after the first treatment . After 1 year ICDAS scores were obtained for 42 children and radiographs for 39 . One external examiner not familiar with the study scored the radiographs twice ( weighted kappa 0.88 ) . Baseline mean age of the children was 7.17 ± ( SD ) 0.68 and mean def-s was 8.1 ± ( SD ) 6.9 . After 1 year the ICDAS scores of 31 % of the test lesions and 67 % of the control lesions had progressed ( p < 0.01 ) . Radiographically , 23 % of the test lesions and 62 % of the control lesions had progressed ( p < 0.01 ) . Thus , the clinical and radiographic therapeutic effect of both resin infiltration/FV over FV alone was > 35 % and significant . To conclude , resin infiltration in conjunction with fluoride varnish seems promising for controlling proximal lesion progression on deciduous molar teeth Objectives : Fluoride varnish ( FV ) is efficacious in caries prevention although its effects among different tooth surfaces are poorly understood . This study sought to determine the extent to which caries-preventive effects of a community intervention that included FV application among preschool-aged children varied according to primary tooth anatomy and baseline tooth pathology . Methods : Secondary analysis was undertaken of data from a community-r and omized controlled trial among 543 3- to 5-year-old Aboriginal children in 30 Northern Territory Australian communities . Children in intervention communities received community health promotion and FV application once every 6 months . Net caries ( d3mfs ) risk and 95 % confidence limits ( CL ) were estimated for the control and intervention arms , and stratified according to tooth anatomy/location and baseline pathology ( sound , enamel opacity , hypoplastic defect or precavitated carious lesion ) . The intervention ’s efficacy was quantified using generalized estimating equation modeling accounting for study design and clustering . The assumption of efficacy homogeneity was tested using a Wald χ2 test with a p < 0.2 criterion and post hoc pairwise comparisons . Results : The intervention result ed in a 25 % reduction ( relative risk , RR = 0.75 ; 95 % CL = 0.71 , 0.80 ) in the 2-year surface-level caries risk . There was substantial heterogeneity in FV efficacy by baseline surface pathology : RRs were 0.73 for sound , 0.77 for opaque , 0.90 for precavitated , and 0.92 for hypoplastic surfaces . Among sound surfaces , maxillary anterior facials received significantly more benefit ( RR = 0.62 ) compared to pits and fissures ( RR = 0.78 ) . Conclusion : The intervention had greatest efficacy on surfaces that were sound at baseline . Among those sound surfaces , maxillary anterior facials received most caries-preventive benefit AIM The aim of the study was to assess the caries inhibition effect of fluoride varnishes among preschool children with high caries risk . At the same time , the suitability of this measure should be examined in the frame of group prevention programmes in kindergartens . METHOD This was an examiner-blind , clinical ly controlled 2-year study with 200 r and omly selected 2- to 4-year-old preschool children with high caries risk . At the baseline , caries-free surfaces , initial caries lesions as well as the caries status ( dmfs ) were recorded . After the baseline , all subjects were divided into 3 groups . Subjects of group A received every 6 months ( altogether four times ) applications with the fluoride varnish Fluoridin N5 ( VOCO GmbH , Cuxhaven , Germany ) , children of the group B received every 6 months ( altogether four times ) applications with Duraphat ( Colgate Palmolive GmbH , Hamburg , Germany ) , while the subjects of group C did not receive any fluoride varnish applications and constituted the control group . A final examination was performed after two years similar to the baseline . Statistical analysis was based on the SPSS programme at a significance level of 95 % . RESULTS AND CONCLUSIONS The results confirmed the caries inhibition efficacy of both fluoride varnishes . This is shown as well in the almost constant number of caries-free surfaces and initial caries lesions in the two F-groups during the observation period . The caries-free surfaces in group C were significantly reduced along with an increase of initial caries lesions . The caries reduction , based on the control group , amounted in group A to 56 % and in group B to 57 % . The results documented the caries inhibition effect of both fluoride varnishes which are suitable for intensive group prevention programmes for pre-school children Background : The prevalence of proximal caries in primary molar teeth is high in many countries . Aims : ( 1 ) To study by means of a split-mouth design the 1- and 2.5-year efficacy of sealing proximal lesions vs. flossing instructions ( control ) on primary molar teeth . ( 2 ) To assess children ’s behaviour and pain perception during the procedure . Methods : Ninety-one 4- to 6-year-old children from Bogotá , Colombia participated . Participants had to have at least two proximal lesions scored according to the following radiographic classification system : radiolucency ( 1 ) in enamel outer half , ( 2 ) restricted to enamel-dentine junction , or ( 3 ) restricted to dentine outer third . Baseline , 1- and 2.5-year follow-up bitewing radiographs were taken . Test and control lesions were r and omly selected . After temporary separation test lesions were sealed ( adhesive ) . Parents/caregivers received a flossing leaflet for their children . Progression of the lesions was assessed by means of independent reading of conventional bitewing radiographs . Results : One-year ( n = 73 ) test vs. control lesion progression was 27.4 vs. 50.7 % , respectively ( p < 0.01 , McNemar ’s test ) , and 2.5-year ( n = 56 ) test vs. control lesion progression was 46.4 vs. 71.4 % , respectively ( p < 0.01 ) . The dropouts did not differ from those who remained in the study regarding relevant caries baseline data . More than 88 % of the participants presented positive to definitively positive behaviour and very low or low pain intensity at both first and second appointments . Conclusion : The sealing technique was superior to flossing instructions both after 1 and 2.5 years of follow-up and the majority of the participants had no anxiety or pain during the treatment OBJECTIVES This study aim ed to compare the effectiveness of three topical fluoride application protocol s in arresting dentine caries in primary teeth of preschool children in a fluori date d area . METHODS Children aged 3 - 4 years who had at least one active dentine caries lesion were r and omly allocated into three intervention groups : Group 1-application of 30 % silver diammine fluoride ( SDF ) solution every 12 months ; Group 2-three applications of 30 % SDF solution at weekly interval at baseline ; and Group 3-three applications of 5 % sodium fluoride ( NaF ) varnish at weekly interval at baseline . A masked examiner carried out follow-up examinations every 6 months to assess whether the treated lesions had become arrested . RESULTS A total of 304 children with 1670 tooth surfaces with dentine caries received treatment at baseline . After 18 months , 275 children ( 91 % ) remained in the study . The caries arrest rates at tooth surface level were 40 % , 35 % and 27 % for Groups 1 , 2 and 3 , respectively ( p<0.001 ) . Result of the multi-level survival analysis showed that the two SDF application protocol s could shorten the time to arrest of dentine caries compared with the NaF application protocol . Presence of plaque on lesion surface , tooth type and tooth surface all had significant effects on caries arrest rates . CONCLUSIONS Annual or three consecutive weekly applications of SDF solution is more effective in arresting dentine caries in primary teeth than three consecutive weekly applications of NaF varnish . CLINICAL SIGNIFICANCE In a water fluori date d area , application of SDF solution , either three weekly applications at baseline or annually , can arrest active dentine caries lesions in primary teeth faster than three weekly applications of NaF varnish at baseline The aim of the study was to investigate the efficacy of the use of xylitol-containing tooth-wipes in preventing dental caries in young children . In a double-blinded r and omized controlled clinical trial , 44 mothers with active caries and their 6- to 35-month-old children were r and omized to xylitol-wipe or placebo-wipe groups . The children ’s caries scores were recorded at baseline and 1 year . Salivary levels of mutans streptococci and lactobacilli were enumerated at baseline , 3 , 6 , and 12 months . Data were analyzed by intent-to-treat modeling with imputation for caries lesions and a linear mixed-effect model for bacterial levels . Significantly fewer children in the xylitol-wipe group had new caries lesions at 1 year compared with those in the placebo-wipe group ( P < 0.05 ) . No significant differences between the two groups were observed in levels of mutans streptococci and lactobacilli at all time-points . Daily xylitol-wipe application significantly reduced the caries incidence in young children as compared with wipes without xylitol , suggesting that the use of xylitol wipes may be a useful adjunct for caries control in infants ( Clinical trials.gov registration number CT01468727 ) Minimal invasive approaches to managing caries , such as partial caries removal techniques , are showing increasing evidence of improved outcomes over the conventional complete caries removal . There is also increasing interest in techniques where no caries is removed . We present the 1-yr results of clinical efficacy for 3 caries management options for occlusoproximal cavitated lesions in primary molars : conventional restorations ( CR ; complete caries removal and compomer restoration ) , Hall technique ( HT ; no caries removal , sealing in with stainless steel crowns ) , and nonrestorative caries treatment ( N RCT ; no caries removal , opening up the cavity , teaching brushing and fluoride application ) . In sum , 169 children ( 3 - 8 yr old ; mean , 5.56 ± 1.45 yr ) were enrolled in this secondary care – based , 3-arm , parallel-group , r and omized clinical trial . Treatments were carried out by specialist pediatric dentists or postgraduate trainees . One lesion per child received CR , HT , or N RCT . Outcome measures were clinical failure rates , grouped as minor failure ( restoration loss/need for replacement , reversible pulpitis , caries progression , etc . ) and major failure ( irreversible pulpitis , abscess , etc . ) . There were 148 children ( 87.6 % ) with a minimum follow-up of 11 mo ( mean , 12.23 ± 0.98 mo ) . Twenty teeth were recorded as having at least 1 minor failure : N RCT , n = 8 ( 5 % ) ; CR , n = 11 ( 7 % ) ; HT , n = 1 ( 1 % ) ( p = .002 , 95 % CI = 0.001 to 0.003 ) . Only the comparison between N RCT and CR showed no significant difference ( p = .79 , 95 % CI = 0.78 to 0.80 ) . Nine ( 6 % ) experienced at least 1 major failure : N RCT , n = 4 ( 2 % ) ; CR , n = 5 ( 3 % ) ; HT , n = 0 ( 0 % ) ( p = .002 , 95 % CI = 0.001 to 0.003 ) . Individual comparison of N RCT and CR showed no statistically significant difference in major failures ( p = .75 , 95 % CI = 0.73 to 0.76 ) . Success and failure rates were not significantly affected by pediatric dentists ’ level of experience ( p = .13 , 95 % CI = 0.12 to 0.14 ) . The HT was significantly more successful clinical ly than N RCT and CR after 1 yr , while pairwise analyses showed comparable results for treatment success between N RCT and CR ( Clinical Trials.gov NCT01797458 ) OBJECTIVE The purpose of this study was to compare the caries preventive efficacy of a mouthrinse solution containing casein derivatives coupled with calcium phosphate ( CD-CP ) with that of a 0.05 % sodium fluoride mouthrinse among individuals with dry mouth . STUDY DESIGN A r and omized control trial design was used . Participants included individuals who had had radiotherapy for head and neck cancer ( n = 82 ) and others with Sjögren 's syndrome ( n = 56 ) . Baseline data collection was followed by reexamination 12 months later . Posterior bite-wing radiographs were taken on both occasions . RESULTS A total of 124 participants , 61 ( 49.2 % ) in the sodium fluoride group and 63 ( 50.8 % ) in the CD-CP group , completed the 12-month examination . The baseline characteristics of the 2 groups did not differ . Coronal caries incidence was higher in the sodium fluoride group than in the CD-CP group ( 34.4 % and 27 % , respectively ) , but the difference was not statistically significant . Similarly , the small difference in coronal caries increment between the 2 groups was not statistically significant ( 0.4 and 0.3 surfaces , respectively ) . There was insufficient root surface caries experience between the 2 groups observed for differences to be examined . Proportionately more of the CD-CP group lost 1 or more teeth , and the mean number of tooth loss was higher . The participants with the highest incidence and increment were those with Sjögren 's syndrome in the CD-CP group . Some of that difference was accounted for by differences in baseline caries status . CONCLUSION It appears that CD-CP preparations hold promise as caries preventive agents for individuals with dry mouth , although confirmation of this study 's findings in other setting s is warranted before a definitive conclusion can be reached In a two-year pragmatic clinical trial , the effect of the mineralizing agent was evaluated on permanent teeth of the first eruption group among Finnish children ( 7-years old at the beginning of the study ) with a low prevalence of DFS . In the test group ( n = 123 , biweekly mouthrinsing with a 2 % solution of mineralizing agent and 0.2 % NaF solution ) the percentage reduction in increment of both EFDS and DFS was high , whereas in the control group ( n = 123 , biweekly mouthrinsing with placebo and 0.2 % NaF solutions ) the incidence for symptoms of caries disease did not differ from that normally found in this age cohort . Positive clinical effect of tested solution was age-related and was associated with remineralization of old and inhibition of occurrence of new EFD lesions To determine the efficacy of fluoride varnish ( 5 % NaF , Duraphat ® , Colgate ) added to caregiver counseling to prevent early childhood caries , we conducted a two-year r and omized , dental-examiner-masked clinical trial . Initially , 376 caries-free children , from low-income Chinese or Hispanic San Francisco families , were enrolled ( mean age ± st and ard deviation , 1.8 ± 0.6 yrs ) . All families received counseling , and children were r and omized to the following groups : no fluoride varnish , fluoride varnish once/year , or fluoride varnish twice/year . An unexpected protocol deviation result ed in some children receiving less active fluoride varnish than assigned . Intent-to-treat analyses showed a fluoride varnish protective effect in caries incidence , p < 0.01 . Analyzing the number of actual , active fluoride varnish applications received result ed in a dose-response effect , p < 0.01 . Caries incidence was higher for ‘ counseling only ’ vs. ‘ counseling + fluoride varnish assigned once/year ’ ( OR = 2.20 , 95 % CI 1.19–4.08 ) and ‘ twice/year ’ ( OR = 3.77 , 95 % CI 1.88–7.58 ) . No related adverse events were reported . Fluoride varnish added to caregiver counseling is efficacious in reducing early childhood caries incidence The aim of this r and omized , double-blind study was to measure the cariostatic effect of Bifluorid 12 ( VOCO GmbH ) , containing 6 % sodium fluoride and 6 % calcium fluoride and Laweflour-Schüttellack ( LAW ) , containing 5 % sodium fluoride in comparing of placebo varnish . The caries study included 400 schoolchildren , aged 12 - 14 years . The tests according to the DMFS were carried out by two independent examiners . The 400 children were divided into 3 test and 1 placebo group , each group consisting of 100 subjects . After two years there was a significant inhibition of caries increment in all test groups compared to placebo group . Percentage caries reduction ranged from 25 to 30 % . The highest effect was stated at proximal surfaces The Prevention of Adult Caries Study , an NIDCR-funded multicenter , double-blind , r and omized clinical trial , enrolled 983 adults ( aged 18 - 80 yrs ) at high risk for developing caries ( 20 or more intact teeth and 2 or more lesions at screening ) to test the efficacy of a chlorhexidine diacetate 10 % weight per volume ( w/v ) dental coating ( CHX ) . We excluded participants for whom the study treatment was contraindicated or whose health might affect outcomes or ability to complete the study . Participants were r and omly assigned to receive either the CHX coating ( n = 490 ) or a placebo control ( n = 493 ) . Coatings were applied weekly for 4 weeks and a fifth time 6 months later . The primary outcome ( total net D1 - 2FS increment ) was the sum of weighted counts of changes in tooth surface status over 13 months . We observed no significant difference between the two treatment arms in either the intention-to-treat or per- protocol analyses . Analysis of 3 protocol -specified secondary outcomes produced similar findings . This trial failed to find that 10 % ( w/v ) chlorhexidine diacetate coating was superior to placebo coating for the prevention of new caries ( Clinical trials.gov registration number NCT00357877 ) AIM The purpose of this study was to evaluate the clinical success of three fissure sealants(FSs ) with different contents on primary teeth . STUDY DESIGN Three FSs were used to seal 150 primary molars in 75 children aged 4 - 7 years . All FSs were placed on occlusal surfaces in a split-mouth and r and omized clinical trial . For patients in Group1,amorphous calcium phosphate(ACP ) containing resin-based sealant(RBS)(Aegis ) was applied to a primary molar tooth on one side , and non-fluoride RBS(Helioseal ) FS was applied to symmetrical molar tooth . For patients in Group2 , fluoride-containing RBS(Helioseal F ) was applied to a primary molar tooth on one side , and Helioseal FS was applied to symmetrical molar tooth . For patients in Group3,Helioseal FS was applied to a primary molar tooth on one side , and Aegis FS was applied to symmetrical molar tooth . Clinical evaluation of FSs was carried out to assess retention , marginal discoloration , marginal adaptation , and the presence of caries in months 1,3,6,12,18 and 24 after FS application . RESULTS There were no significant differences for all criteria in groups 2 and 3(p≯0.05 ) . In group 1,cumulative success rates according to 24 months ' follow-up were statistically insignificant during the comparisons performed in terms of retention , marginal adaptation , and presence of caries(p≯0.05 ) . Marginal discoloration was found to be statistically significant(p<0.05 ) . CONCLUSION RBS containing ACP or fluoride may be more effective than conventional RBS for caries prevention This paper presents final results of an eight-year clinical trial design ed to compare the caries-preventive benefits of two self-administered fluoride procedures when used separately and in combination with one another . Children in kindergarten and first grade residing in Springfield , Ohio , a nonfluori date d community , were assigned r and omly within school to one of three groups that either ( a ) rinsed once a week in school with a 0.2 percent neutral NaF solution ; ( b ) chewed , rinsed with , and then swallowed daily in school a neutral 2.2 mg NaF tablet ; or ( c ) carried out both procedures . At baseline ( 1981 ) , 1,640 participants were examined clinical ly using the DMF surface index . Findings for 640 children remaining after eight years show that subjects in the combination group experienced a mean caries increment of 2.40 DMFS , 15.2 percent lower than the mean score of 2.83 DMFS for children in the tablet group and 32.8 percent lower than the 3.57 DMFS for those in the rinse group . Only the difference in incremental caries scores between the combined fluoride procedure and the fluoride rinse was statistically significant ( P less than .05 ) . The pattern of these findings is similar to that found on the two interim examinations . Even though the combined regimen showed an additional caries-preventive benefit compared with the rinse , considerations of cost effectiveness and feasibility do not support changing an ongoing rinse program to one that employs both procedures . For new programs the best choice appears to be the tablet procedure alone To evaluate the retention and caries experience effects of three different material s used as fissure sealants after 24 months of clinical application : a resin-modified glass ionomer cement ( A ) , a flowable resin composite ( B ) and a compomer ( C ) . One hundred and seventeen ( 117 ) teeth were sealed with material A , 119 teeth with material B and 120 teeth with material C. Children were r and omly assigned . Each one received only one of the material s studied . Plaque index , dmft score and socioeconomic level were scored at baseline . The clinical exams were conducted 6 , 12 and 24 months after application of the sealant . Statistical analysis ( Kruskal-Wallis ) revealed that there were statistically significant differences between the retention rates of groups A and B and between groups B and C after 2 years , with material B showing better results . After 2 years , 3.1 % of the teeth of group A , 4.3 % of group B and 6.7 % of group C were Carious+Filled . There was no evidence of association between caries presence after 2 years and plaque index , dmft score and socioeconomic level . These results suggest that flowable resin composite had a satisfactory retention after this period of evaluation and all three material s were effective on occlusal caries prevention OBJECTIVE To assess the efficacy and effectiveness of a dental-health programme after 7.5-years of follow-up . DESIGN The study follows a prospect i ve cohort design without r and omization . POPULATION AND METHODS The study group cohort consisted of 547 school children , 266 girls and 281 boys , the control group was composed of 237 school children , 121 girls and 116 boys . Dental examinations were carried out using WHO criteria . Preventive measures included health education , a weekly mouth rinse using sodium fluoride ( NaFI ) at 0.2 % concentration , fissure sealants to first permanent molars and topical application of fluoride gel . The outcomes using different indices of tooth decay and socio-demographic variables were compared between study and control groups and statistical significance determined through the Mann-Whitney U-test . Logistic regression was used in the multivariate analysis . RESULTS There were statistically significant differences between cohorts in the indices of decay . The mean DMFT value for study group children was 1.52 and for first permanent molars ( DMFM ) 1.10 per child , mean DMFS was 2.09 . In the control group , values were DMFT-3.07 , DMFM-2.03 per child , DMFS-4.33 . Logistic regression showed the preventive programme to have a significant independent effect . CONCLUSION The preventive programme had been effective and had a clear protective effect PURPOSE The aim of this study was to evaluate the efficacy of three topical fluoride treatments to arrest initial root carious lesions . MATERIAL S AND METHODS Forty patients participated in a r and omised study . Of the 60 root carious lesions that were included , 20 were r and omised for treatment with the Carisolv chemo-mechanical technique and the Duraphat ( 2.23 % F ) fluoride varnish , 20 with Duraphat alone and 20 with stannous fluoride solution ( 8 % ) . The lesions were treated at baseline and after three and six months ; a clinical evaluation was carried out on these occasions and after 1 year . RESULTS All but four lesions were categorised as arrested caries during the 1-year follow-up period : 18 in the Carisolv/Duraphat group and 19 each in the Duraphat and the stannous fluoride groups , respectively . There was a minor reduction in the mean size of the lesions of around 0.1 to 0.2 mm height and width and a moderate change in colour from a lighter to a darker appearance . No obvious differences were found between the groups . The mean percentage of mutans streptococci in plaque from all lesions was 3.5 % at baseline , and it decreased to 1.8 % during the year . The decrease was , however , not statistically significant , and no significant differences were found between the groups . CONCLUSIONS It can be concluded that the frequent topical application of fluoride could be a successful treatment for incipient root carious lesions , irrespective of the type of fluoride treatment used Proximal caries infiltration has been shown to be efficacious in hampering caries lesion progression when performed by dentists working in a university setting . The aim of this r and omized split-mouth , placebo-controlled clinical trial was to assess the efficacy of resin infiltration of proximal caries lesions being performed by several dentists in private practice s , in combination with individualized oral hygiene plus noninvasive measures compared with these alone . In this study , 87 children and young adults ( with 238 pairs of proximal caries lesions radiographically extending into the inner half of the enamel [ E2 ] or the outer third of the dentin [ D1 ] ) were r and omly allocated to either 1 of 2 treatments . Test lesions were infiltrated , and a mock treatment was performed in control lesions by 5 German private practitioners . All patients received instructions for a noncariogenic diet , flossing and fluoridation , and individualized noninvasive interventions . The primary outcome was radiographic lesion progression ( pairwise comparison ) evaluated independently by 2 evaluators who were blinded to treatment allocation . After approximately 10 mo ( mean ± SD 307 ± 43 d ) , 92 of 148 lesion pairs in 24 of 38 treated patients who were at high caries risk could be re-evaluated clinical ly as well as radiographically using individualized bitewing holders , as at baseline ; 186 of 204 lesion pairs in 70 of 77 patients ( 35 of 38 high-risk patients ) could be evaluated after 18 mo ( mean 542 ± 110 d ) . No unwanted effects were observed . After 10 mo , progression was recorded in 2 of 92 test lesions ( 2 % ) and in 22 of 92 control lesions ( 24 % ) ( P = 0.001 , McNemar/Obuchowski test ; relative risk reduction , 91 ; 95 % confidence interval , 62%–98 % ) . After 18 mo , lesion progression was recorded in all included patients in 10 of 186 test lesions ( 5 % ) and in 58 of 186 control lesions ( 31 % ) ( P < 0.001 ; relative risk reduction , 83 ; 95 % confidence interval , 67%–91 % ) . Thus , resin infiltration seems to be more efficacious in reducing lesion progression compared with individualized noninvasive measures alone over a period of 18 mo when performed in a private practice setting by various practitioners ( German Clinical Trials Register / Deutsches Register Klinischer Studien DRKS00009963 ) A three-year , double blind , r and omised clinical trial was conducted in Polk County , Florida from 1983 - 1987 . The objective was to compare the effect of four dose levels of sodium monofluorophosphate ( SMFP ) and a single dose level of sodium fluoride ( NaF ) on DMFS , DMFT , and DFS Interproximal indices . A total of 8,027 children were examined clinical ly and radiographically at baseline , and 5,474 children completed the three-year study , which included daily supervised brushing at school . No differences existed at baseline between the five study cells on age or gender distribution , or on any of the dental indices . Results indicated that the 2000 ppm F NaF group had significantly smaller DMFS increment than the 2000 ppm F SMFP group p < 0.005 . The 2000 ppm F NaF group demonstrated an 18 per cent ( 26 per cent for children > 10 years at baseline ) reduction in DMFS over the 1500 ppm F SMFP group , the 2500 ppm F group a 15 per cent ( 19 per cent ) reduction , and the 2000 ppm F SMFP a 5 per cent ( 9 per cent ) reduction . Results are strongest in children at greatest risk -- older children with previous caries . This study concludes that the anticaries efficacy of SMFP dentifrices rises with increasing fluoride , and that the anticaries efficacy of a 2000 ppm NaF dentifrice is superior to that of a 2000 ppm F SMFP dentifrice , p < 0.005 ) This 30-mo r and omized clinical trial compared the effectiveness of 2 concentrations ( 12 % or 38 % ) of silver diamine fluoride ( SDF ) and 2 periodicity of application ( once or twice a year ) in arresting cavitated dentin caries in primary teeth . Children aged 3 to 4 y who had at least 1 active cavitated caries lesion were enrolled and r and omly allocated into 4 groups for intervention . Group 1 had 12 % SDF applied annually ( every 12 mo ) , group 2 had 12 % SDF applied semiannually ( every 6 mo ) , group 3 had 38 % SDF applied annually , and group 4 had 38 % SDF applied semiannually . Clinical examinations were performed semiannually in kindergarten by a single examiner to investigate whether the SDF-treated caries became arrested . A total of 888 children with 4,220 decayed tooth surfaces received SDF application at baseline , and 799 ( 90.0 % ) children with 3,790 surfaces ( 89.8 % ) were evaluated at the 30-mo examination . The caries arrest rates were 55.2 % , 58.6 % , 66.9 % , and 75.7 % for groups 1 , 2 , 3 , and 4 , respectively ( P < 0.001 ) . Caries treated with 38 % SDF had a higher chance of becoming arrested than those treated with 12 % SDF ( odds ratio [ OR ] , 1.98 ; 95 % confidence interval [ CI ] , 1.51–2.60 , P < 0.001 ) . The interaction between frequency of SDF application and visible plaque index ( VPI ) score was significant ( P = 0.017 ) . Among those children who received annual SDF application , children with a higher VPI score had a lower chance to have their caries become arrested ( OR , 0.59 , 95 % CI , 0.49–0.72 ) . In conclusion , SDF at a concentration of 38 % is more effective than that of 12 % in arresting active caries in primary teeth . For children with poor oral hygiene , caries arrest rate of SDF treatment can be increased by increasing the frequency of application from annually to semiannually ( Clinical Trials.gov NCT02385474 ) The caries-preventive effect of daily applications of a fluoride gel was studied in 55 patients receiving radiotherapy for tumors of the head and neck . The study was design ed as a r and omized , double-blind study with two parallel groups . From the start of radiotherapy one group received a 0.42 % F gel once a day for 1 year . The other group received a daily application of a 1.23 % F gel for 4 weeks followed by the use of the 0.42 % F gel daily for 1 year . The results showed that in patients with an unstimulated saliva flow of > 0.1 ml/min daily fluoride gel treatment with a fluoride concentration of 0.42 % F was sufficient to inhibit caries almost completely . The use of the 1.23 % F gel was not superior to the 0.42 % gel treatment program alone . In an attempt to evaluate the salivary flow rate as a diagnostic criterion for increased caries risk , sensitivity and specificity were evaluated . It was found that with an unstimulated saliva flow rate of < 0.1 ml/min the positive predictive value was 80 % . The corresponding value for stimulated salivary flow rate of < 0.5 ml/min was 85 % . One can therefore predict that 80 % of patients with flow rates < 0.1 ml/min will develop at least one carious lesion per year . The corresponding negative predictive value for unstimulated saliva flow > 0.1 ml/min was 75 % . That means that 75 % of patients using the 0.42 % F gel daily and with at least some saliva secretion will not develop any new carious lesions The aim of this trial was to compare the caries-preventive effect of sodium fluoride varnish and acidulated phosphate fluoride ( APF ) gel . A total of 254 children aged 12 - 13 years with high past caries experience were r and omly divided into two groups . The participants received semi-annual applications of either fluoride varnish or APF gel for 3 years . During the study , the mean ( + /- SD ) total DMFS increments of the varnish and gel groups were 6.8 + /- 5.6 and 7.7 + /- 6.4 , respectively , when initial caries was included , and 3.1 + /- 3.7 and 3.6 + /- 4.6 when initial caries was excluded . The difference was most evident on the approximal surfaces ( varnish : 1.4 + /- 2.4 ; gel : 1.9 + /- 3.1 ) . However , this difference was not statistically significant . Although larger studies are needed for firm conclusions about the comparative effect of the two fluoride measures , the results suggest that fluoride varnish is as effective as fluoride gel at least in preventing approximal caries . Taking into account the shorter treatment time , using fluoride varnish for professional applications seems justified OBJECTIVE A pilot investigation was performed to test the null hypothesis that highly filled ( 58 % ) resin sealants do not prevent white spot lesions in patients undergoing active orthodontic treatment . MATERIAL S AND METHODS A split-mouth design was applied to 60 healthy patients , with the sealant r and omly allocated to either the right or the left side of each jaw . The sealant was applied to the incisors and canines from the gingival surface of the bracket to the free gingival margin . The contralateral teeth had the same type of bracket with no sealant . Sealants were placed on the experimental teeth 2 weeks to 3 months after initial bonding and were removed after 15 to 18 months . Intraoral photographs , visual assessment s , and DIAGNOdent ( KaVo Dental Corporation , Lake Zurich , Ill ) measurements were used to assess white spot lesions after sealant removal . RESULTS Six lesions on the teeth with sealants were identified visually , compared with 22 lesions on the teeth without sealants . The teeth without sealants had 3.8 times the number of white spot lesions than were noted on the sealed teeth . These sealants showed no visible signs of discoloration . The DIAGNOdent measured statistically significant differences between sealed and unsealed teeth in the maxilla ( P < .001 ) and in the m and ible ( P = .010 ) . DIAGNOdent measurements also showed a difference between sealed and unsealed teeth after the 28 teeth with visible lesions were excluded . CONCLUSION The hypothesis was rejected . Ultraseal XT Plus clear sealant ( Ultradent Products , South Jordon , Utah ) produced a significant reduction in enamel demineralization during fixed orthodontic treatment and should be considered for use by clinicians to minimize white spot lesions |
12,769 | 31,616,691 | IMT_Ph had the highest effect sizes for VO2 peak and 6MWT , IMT_Pm highest for QoL , and Qi_Ex highest for heart rate .
Aerobics had the second highest for VO2 peak , Qi_Ex second highest for 6MWT , and IMT_Ph second highest for heart rate and QoL. CONCLUSION This study supports that high- and medium-intensity machine-assisted training improves exercise capacity and QoL in hospital-based heart failure patients .
After hospital discharge , non-machine-assisted training continuously improves cardiac function | BACKGROUND Prior studies indicate that doing breathing exercises improves physical performance and quality of life ( QoL ) in heart failure patients .
However , these effects remain unclear and contradictory .
AIM To determine the effects of machine-assisted and non-machine-assisted respiratory training on physical performance and QoL in heart failure patients . | BACKGROUND Preliminary evidence suggests that meditative exercise may have benefits for patients with chronic systolic heart failure ( HF ) ; this has not been rigorously tested in a large clinical sample . We sought to investigate whether tai chi , as an adjunct to st and ard care , improves functional capacity and quality of life in patients with HF . METHODS A single-blind , multisite , parallel-group , r and omized controlled trial evaluated 100 out patients with systolic HF ( New York Heart Association class I-III , left ventricular ejection fraction ≤40 % ) who were recruited between May 1 , 2005 , and September 30 , 2008 . A group-based 12-week tai chi exercise program ( n = 50 ) or time-matched education ( n = 50 , control group ) was conducted . Outcome measures included exercise capacity ( 6- minute walk test and peak oxygen uptake ) and disease-specific quality of life ( Minnesota Living With Heart Failure Question naire ) . RESULTS Mean ( SD ) age of patients was 67 ( 11 ) years ; baseline values were left ventricular ejection fraction , 29 % ( 8 % ) and peak oxygen uptake , 13.5 mL/kg/min ; the median New York Heart Association class of HF was class II . At completion of the study , there were no significant differences in change in 6-minute walk distance and peak oxygen uptake ( median change [ first quartile , third quartile ] , 35 [ -2 , 51 ] vs 2 [ -7 , 54 ] meters , P = .95 ; and 1.1 [ -1.1 , 1.5 ] vs -0.5 [ -1.2 , 1.8 ] mL/kg/min , P = .81 ) when comparing tai chi and control groups ; however , patients in the tai chi group had greater improvements in quality of life ( Minnesota Living With Heart Failure Question naire , -19 [ -23 , -3 ] vs 1 [ -16 , 3 ] , P = .02 ) . Improvements with tai chi were also seen in exercise self-efficacy ( Cardiac Exercise Self-efficacy Instrument , 0.1 [ 0.1 , 0.6 ] vs -0.3 [ -0.5 , 0.2 ] , P < .001 ) and mood ( Profile of Mood States total mood disturbance , -6 [ -17 , 1 ] vs -1 [ -13 , 10 ] , P = .01 ) . CONCLUSION Tai chi exercise may improve quality of life , mood , and exercise self-efficacy in patients with HF . Trial Registration clinical trials.gov Identifier : NCT00110227 Background : Capacity to exercise may not be fully restored in patients with heart failure even in the long term after ventricular assist device ( VAD ) implantation . The benefits of exercise training in patients with VAD are unknown . Design and methods : Fifteen patients , aged 38.3 ± 15.9 years , bridged to heart transplantation with left ventricular assist device or biventricular assist device were r and omized at a ratio of 2 : 1 to a training group ( TG , n = 10 ) or a control group ( n = 5 ) , 6.3 ± 4 months after implantation . Both the groups were advised to walk 30–45 min/day . TG also underwent moderate-intensity aerobic exercise using a bike or treadmill for 45 min , three to five times a week , combined with high-intensity inspiratory muscle training using a computer- design ed software to respiratory exhaustion , two to three times a week for 10 weeks . The patients were tested using cardiopulmonary exercise testing , 6-min walk test , spirometry and electronic pressure manometer for inspiratory muscle strength ( Pimax ) and endurance ( sustained Pimax ) measurement . Quality of life was assessed with the Minnesota Living with Heart Failure question naire . Results : TG improved peak oxygen consumption ( 19.3 ± 4.5 vs. 16.8 ± 3.7 ml/kg per min , P = 0.008 ) and VO2 at ventilatory threshold ( 15.1 ± 4.2 vs. 12 ± 5.6 ml/kg per min , P = 0.01 ) , whereas the ventilation/carbon dioxide slope decreased ( 35.9 ± 5.6 vs. 40 ± 6.5 , P = 0.009 ) . The 6-min walk test distance increased ( 527 ± 76 vs. 462 ± 88 m , P = 0.005 ) and quality of life was improved ( 38.2 ± 11.6 vs. 48.9 ± 12.8 , P = 0.005 ) , as well as Pimax ( 131.8 ± 33 vs. 95.5 ± 28cmH2O , P = 0.005 ) , sustained Pimax ( 484 ± 195 vs. 340 ± 193cmH2O/s/10 3 , P = 0.005 ) , and inspiratoty lung capacity ( 2.4 ± 0.9 vs. 1.7 ± 0.7 L , P = 0.008 ) were improved . No significant changes were noted in the control group . Conclusion : Our findings indicate that exercise training may improve the functional status of VAD recipients even at a later period after implantation and thus , may have additional importance in cases of destination therapy BACKGROUND We hypothesised that combined aerobic training ( AT ) with resistance training ( RT ) and inspiratory muscle training ( IMT ) could result in additional benefits over AT alone in patients with chronic heart failure ( CHF ) . METHODS Twenty-seven patients , age 58 ± 9 years , NYHA II/III and LVEF 29 ± 7 % were r and omly assigned to a 12-week AT ( n=14 ) or a combined AT/RT/IMT ( ARIS ) ( n=13 ) exercise program . AT consisted of bike exercise at 70 - 80 % of max heart rate . ARIS training consisted of AT with RT of the quadriceps at 50 % of 1 repetition maximum ( 1RM ) and upper limb exercises using dumbbells of 1 - 2 kg as well as IMT at 60 % of sustained maximal inspiratory pressure ( SPI(max ) ) . At baseline and after intervention patients underwent cardiopulmonary exercise testing , echocardiography , evaluation of dyspnea , muscle function and quality of life ( QoL ) scores . RESULTS The ARIS program as compared to AT alone , result ed in additional improvement in quadriceps muscle strength ( 1RM , p=0.005 ) and endurance ( 50%1 RM × number of max repetitions , p=0.01 ) , SPI(max ) ( p<0.001 ) , exercise time ( p=0.01 ) , circulatory power ( peak oxygen consumption × peak systolic blood pressure , p=0.05 ) , dyspnea ( p=0.03 ) and QoL ( p=0.03 ) . CONCLUSIONS ARIS training was safe and result ed in incremental benefits in both peripheral and respiratory muscle weakness , cardiopulmonary function and QoL compared to that of AT . The present findings may add a new prospect i ve to cardiac rehabilitation programs of heart failure patients whilst the clinical significance of these outcomes need to be addressed in larger r and omised studies BACKGROUND The effects of mind-body interventions ( MBIs ) ( eg , Tai Chi , yoga , meditation ) for individuals with heart failure ( HF ) have not been systematic ally evaluated . METHODS AND RESULTS We performed a systematic review of r and omized controlled trials ( RCTs ) examining the effects of MBIs in HF . We extracted participant characteristics , MBI procedure , outcomes assessed , and main results of English- language RCTs before October 2016 . We identified 24 RCTs ( n = 1314 participants ) of 9 MBI types : Tai Chi ( n = 7 ) , yoga ( n = 4 ) , relaxation ( n = 4 ) , meditation ( n = 2 ) , acupuncture ( n = 2 ) , biofeedback ( n = 2 ) , stress management ( n = 1 ) , Pilates ( n = 1 ) , and reflexology ( n = 1 ) . Most ( n = 22 , 95.8 % ) reported small-to-moderate improvements in quality of life ( 14/14 studies ) , exercise capacity ( 8/9 studies ) , depression ( 5/5 studies ) , anxiety and fatigue ( 4/4 studies ) , blood pressure ( 3/5 studies ) , heart rate ( 5/6 studies ) , heart rate variability ( 7/9 studies ) , and B-type natriuretic peptide ( 3/4 studies ) . Studies ranged from 4 minutes to 26 weeks and group sizes ranged from 8 to 65 patients per study arm . CONCLUSIONS Although wide variability exists in the types and delivery , RCTs of MBIs have demonstrated small-to-moderate positive effects on HF patients ' objective and subjective outcomes . Future research should examine the mechanisms by which different MBIs exert their effects Aims : The aims of this study were to determine whether yoga and hydrotherapy training had an equal effect on the health-related quality of life in patients with heart failure and to compare the effects on exercise capacity , clinical outcomes , and symptoms of anxiety and depression between and within the two groups . Methods : The design was a r and omized controlled non-inferiority study . A total of 40 patients , 30 % women ( mean±SD age 64.9±8.9 years ) with heart failure were r and omized to an intervention of 12 weeks , either performing yoga or training with hydrotherapy for 45–60 minutes twice a week . Evaluation at baseline and after 12 weeks included self-reported health-related quality of life , a six-minute walk test , a sit-to-st and test , clinical variables , and symptoms of anxiety and depression . Results : Yoga and hydrotherapy had an equal impact on quality of life , exercise capacity , clinical outcomes , and symptoms of anxiety and depression . Within both groups , exercise capacity significantly improved ( hydrotherapy p=0.02 ; yoga p=0.008 ) and symptoms of anxiety decreased ( hydrotherapy p=0.03 ; yoga p=0.01 ) . Patients in the yoga group significantly improved their health as rated by EQ-VAS ( p=0.004 ) and disease-specific quality of life in the domains symptom frequency ( p=0.03 ) , self-efficacy ( p=0.01 ) , clinical summary as a combined measure of symptoms and social factors ( p=0.05 ) , and overall summary score ( p=0.04 ) . Symptoms of depression were decreased in this group ( p=0.005 ) . In the hydrotherapy group , lower limb muscle strength improved significantly ( p=0.01 ) . Conclusions : Yoga may be an alternative or complementary option to established forms of exercise training such as hydrotherapy for improvement in health-related quality of life and may decrease depressive symptoms in patients with heart failure BACKGROUND Despite recent advances in pharmacologic and device therapy , morbidity and mortality from heart failure ( HF ) remain high . Yoga combines physical and breathing exercises that may benefit patients with HF . We hypothesized that an 8-week regimen of yoga in addition to st and ard medical therapy would improve exercise capacity , inflammatory markers , and quality of life ( QoL ) in patients with HF . METHODS AND RESULTS New York Heart Association Class I-III HF patients were r and omized to yoga treatment ( YT ) or st and ard medical therapy ( MT ) . Measurements included a grade d exercise test ( GXT ) to V O(2Peak ) and the following serum biomarkers : interleukin-6 ( IL-6 ) , high-sensitivity C-reactive protein ( hsCRP ) , and extracellular superoxide dismutase ( EC-SOD ) . The Minnesota Living with Heart Failure Question naire ( MLHFQ ) was administered to assess changes in QoL. A total of 19 patients were enrolled after the initial screening . Of the 19 patients , 9 were r and omized to YT and 10 to MT . Patients had a mean EF of 25 % . GXT time and V O(2Peak ) were significantly improved in the YT versus MT groups ( + 18 % in the YT and -7.5 % in MT ; P = .03 vs. control and + 17 in YT and -7.1 in MT ; P = .02 , respectively ) . There were statistically significant reductions in serum levels of IL-6 and hsCRP and an increase in EC-SOD in the YT group ( all P < .005 vs. MT ) . MLHFQ scores improved by 25.7 % in the YT group and by 2.9 % in the MT group . CONCLUSIONS Yoga improved exercise tolerance and positively affected levels of inflammatory markers in patients with HF , and there was also a trend toward improvements in Background Heart failure with preserved ejection fraction ( HFpEF ) is remarkably common in elderly people with highly prevalent comorbid conditions . Despite its increasing in prevalence , there is no evidence -based effective therapy for HFpEF . We sought to evaluate whether inspiratory muscle training ( IMT ) improves exercise capacity , as well as left ventricular diastolic function , biomarker profile and quality of life ( QoL ) in patients with advanced HFpEF and nonreduced maximal inspiratory pressure ( MIP ) . Design and methods A total of 26 patients with HFpEF ( median ( interquartile range ) age , peak exercise oxygen uptake ( peak VO2 ) and left ventricular ejection fraction of 73 years ( 66–76 ) , 10 ml/min/kg ( 7.6–10.5 ) and 72 % ( 65–77 ) , respectively ) were r and omized to receive a 12-week programme of IMT plus st and ard care vs. st and ard care alone . The primary endpoint of the study was evaluated by positive changes in cardiopulmonary exercise parameters and distance walked in 6 minutes ( 6MWT ) . Secondary endpoints were changes in QoL , echocardiogram parameters of diastolic function , and prognostic biomarkers . Results The IMT group improved significantly their MIP ( p < 0.001 ) , peak VO2 ( p < 0.001 ) , exercise oxygen uptake at anaerobic threshold ( p = 0.001 ) , ventilatory efficiency ( p = 0.007 ) , metabolic equivalents ( p < 0,001 ) , 6MWT ( p < 0.001 ) , and QoL ( p = 0.037 ) as compared to the control group . No changes on diastolic function parameters or biomarkers levels were observed between both groups . Conclusions In HFpEF patients with low aerobic capacity and non-reduced MIP , IMT was associated with marked improvement in exercise capacity and BACKGROUND The number of African American ( AA ) patients living with heart failure ( HF ) has been increasing , especially among the economically disadvantaged . Yoga therapy has been found to improve physical and psychological parameters among healthy individuals , but its effect in patients with HF remains unknown . The purpose of this study was to examine the effects of yoga therapy on cardiovascular endurance ( VO2peak ) , flexibility , quality of life ( QoL ) , and inflammatory markers on medically stable HF patients . METHODS Forty patients ( 38 AA , 1 Asian , and 1 Caucasian ) with systolic or diastolic HF were r and omized to the yoga group ( YG , n = 21 ) or the control group ( CG , n = 19 ) . All patients were asked to follow a home walk program . Premeasurement and postmeasurement included a treadmill stress test to peak exertion , flexibility , interleukin-6 ( IL-6 ) , C-reactive protein ( CRP ) , and extracellular superoxide dismutase ( EC-SOD ) . QoL was assessed by the Minnesota Living with Heart Failure Question naire ( MLwHFQ ) . RESULTS The statistical analyses ( assessed by ANOVA and t-tests ) were significant for favorable changes in the YG , compared with those in the CG , for flexibility ( P = 0.012 ) , treadmill time ( P = 0.002 ) , VO2peak ( P = 0.003 ) , and the biomarkers ( IL-6 , P = 0.004 ; CRP , P = 0.016 ; and EC-SOD , P = 0.012 ) . Within the YG , pretest to posttest scores for the total ( P = 0.02 ) and physical subscales ( P < 0.001 ) of the MLwHFQ were improved . CONCLUSIONS Yoga therapy offered additional benefits to the st and ard medical care of predominantly AA HF patients by improving cardiovascular endurance , QoL , inflammatory markers , and flexibility Background —Regular slow breathing is known to improve autonomic cardiac regulation and reduce chemoreflex sensitivity in heart failure . We explored the acceptability and usefulness of a device for paced slow breathing at the home setting . Methods and Results —In this open pilot study , 24 patients with chronic heart failure ( 61 % males , mean age , 64±9 years ; New York Heart Association class , 2.81±0.01 ) were r and omized to a control group receiving conventional treatment ( n=12 ) or to a group receiving conventional treatment and device-guided paced breathing ( n=12 ) . Groups were comparable for age , therapies , and clinical characteristics . They were evaluated at baseline and again after 10 weeks by Doppler echocardiography , pulmonary function , cardiopulmonary stress test , and quality of life ( Minnesota Quality of Life question naire ) . The treatment group was instructed to use the equipment for 18 minutes twice daily . The device is a computerized box connected to a belt-type respiration sensor and to headphones ; it generates musical tones ( based on the user ’s breathing rate and inspiration ratio ) , which guide the user to progressively and effortlessly slow his or her breathing rate < 10 breaths/min . The treatment group showed high compliance to the device ( 90 % of the prescribed sessions were completed ) . Blinded analysis of data demonstrated increased ejection fraction and decreased estimated pulmonary pressure in the echocardiograms of the treated group versus controls and favorable changes in New York Heart Association class , Ve/Vco2 , FEV1 , and a quality of life measure , as well ( all P<0.05 ) . Conclusions —This pilot investigation demonstrates that device-guided paced breathing at home is feasible and results in an improvement in clinical ly relevant parameters for patients with heart failure and systolic dysfunction PURPOSE To examine the effects of a 12-week tai chi program on quality of life and exercise capacity in patients with heart failure . METHODS Thirty patients with chronic stable heart failure and left ventricular ejection fraction < or = 40 % ( mean [ + /- SD ] age , 64 + /- 13 years ; mean baseline ejection fraction , 23 % + /- 7 % ; median New York Heart Association class , 2 [ range , 1 to 4 ] ) were r and omly assigned to receive usual care ( n = 15 ) , which included pharmacologic therapy and dietary and exercise counseling , or 12 weeks of tai chi training ( n = 15 ) in addition to usual care . Tai chi training consisted of a 1-hour class held twice weekly . Primary outcomes included quality of life and exercise capacity . Secondary outcomes included serum B-type natriuretic peptide and plasma catecholamine levels . For 3 control patients with missing data items at 12 weeks , previous values were carried forward . RESULTS At 12 weeks , patients in the tai chi group showed improved quality -of-life scores ( mean between-group difference in change , -25 points , P = 0.001 ) , increased distance walked in 6 minutes ( 135 meters , P = 0.001 ) , and decreased serum B-type natriuretic peptide levels ( -138 pg/mL , P = 0.03 ) compared with patients in the control group . A trend towards improvement was seen in peak oxygen uptake . No differences were detected in catecholamine levels . CONCLUSION Tai chi may be a beneficial adjunctive treatment that enhances quality of life and functional capacity in patients with chronic heart failure who are already receiving st and ard medical therapy Purpose . To assess if Tai Chi added to endurance training ( ET ) is more effective than ET alone in improving exercise tolerance and quality of life ( QOL ) of elderly patients with chronic heart failure ( CHF ) . Design . Sixty CHF patients , age 73.8 ± 6 years , M/F 51/9 , were enlisted . Thirty pts were r and omized to combined training ( CT ) performing Tai Chi + ET and 30 patients to ET ( ET only ) . Methods . At baseline and after 12 weeks all patients underwent 6-minute walking test ( 6MWT ) , assessment of amino terminal probrain natriuretic peptide ( NT-pro BNP ) , quadriceps maximal voluntary contraction ( MVC ) and peak torque ( PT ) , QOL question naire ( MacNewQLMI ) , blood pressure ( BP ) , and heart rate ( HR ) . All patients performed 4 sessions of exercise/week . Results . Distance at 6mwt improved in both groups with significant between-groups differences ( P = .031 ) . Systolic BP and NT-proBNP decreased significant in the CT group compared to ET ( P = .025 ) and P = .015 ) , resp . ) . CT group had a greater significant improvement in physical perception ( P = .026 ) and a significant increase of PT compared to ET group . Conclusions . The association of Tai Chi and ET improves exercise tolerance and QOL of patients with CHF more efficiently than ET Background : Health-related quality of life ( HRQOL ) , functional status , and cardiac event-free survival are outcomes used to assess the effectiveness of interventions in patients with heart failure ( HF ) . However , the nature of the relationships among HRQOL , functional status , and cardiac event-free survival remains unclear . Objective : The purpose of this study is to examine the nature of the relationships among HRQOL , functional status , and cardiac event-free survival in patients with HF . Methods : This was a prospect i ve , observational study of 313 patients with HF that was a secondary analysis from a registry . At baseline , patient demographic and clinical data were collected . Health-related quality of life was assessed using the Minnesota Living With Heart Failure Question naire and functional status was measured using the Duke Activity Status Index . Cardiac event-free survival data were obtained by patient interview , hospital data base , and death certificate review . Multiple linear and Cox regressions were used to explore the relationships among HRQOL , functional status , and cardiac event-free survival while adjusting for demographic and clinical factors . Results : Participants ( n = 313 ) were men ( 69 % ) , white ( 79 % ) , and aged 62 ± 11 years . Mean left ventricular ejection fraction was 35 % ± 14 % . The mean HRQOL score of 32.3 ± 20.6 indicated poor HRQOL . The mean Duke Activity Status Index score of 16.2 ± 12.9 indicated poor functional status . Cardiac event-free survival was significantly worse in patients who had worse HRQOL or poorer functional status . Patients who had better functional status had better HRQOL ( P < .001 ) . Health-related quality of life was not a significant predictor of cardiac event-free survival after entering functional status in the model ( P = .54 ) , demonstrating that it was a mediator of the relationship between HRQOL and outcome . Conclusion : Functional status was a mediator between HRQOL and cardiac event-free survival . These data suggest that intervention studies to improve functional status are needed AIM To investigate the effects of inspiratory muscle training ( IMT ) on functional capacity and balance , respiratory and peripheral muscle strength , pulmonary function , dyspnea , fatigue , depression , and quality of life in heart failure patients . METHODS A prospect i ve , r and omized controlled , double-blinded study . Thirty patients with heart failure ( NYHA II-III , LVEF<40 % ) were included . Sixteen patients received IMT at 40 % of maximal inspiratory pressure ( MIP ) , and 14 patients received sham therapy ( 15 % of MIP ) for 6 weeks . Functional capacity and balance , respiratory muscle strength , quadriceps femoris muscle strength , pulmonary function , dyspnea , fatigue , quality of life , and depression were evaluated . RESULTS Functional capacity and balance , respiratory and peripheral muscle strength , dyspnea , depression were significantly improved in the treatment group compared with controls ; quality of life and fatigue were similarly improved within groups ( p < 0.05 ) . Functional capacity ( 418.59 ± 123.32 to 478.56 ± 131.58 m , p < 0.001 ) , respiratory ( MIP = 62.00 ± 33.57 to 97.13 ± 32.63 cmH(2)O , p < 0.001 ) and quadriceps femoris muscle strength ( 240.91 ± 106.08 to 301.82 ± 111.86 N , p < 0.001 ) , FEV(1)% , FVC% and PEF% , functional balance ( 52.73 ± 3.15 to 54.25 ± 2.34 , p < 0.001 ) , functional dyspnea ( 2.27 ± 0.88 to 1.07 ± 0.79 , p < 0.001 ) , depression ( 11.47 ± 7.50 to 3.20 ± 4.09 , p < 0.001 ) , quality of life , fatigue ( 42.73 ± 11.75 to 29.07 ± 13.96 , p < 0.001 ) were significantly improved in the treatment group . Respiratory muscle strength ( MIP = 78.64 ± 35.95 to 90.86 ± 30.23 cmH(2)O , p = 0.001 ) , FVC% , depression ( 14.36 ± 9.04 to 9.50 ± 10.42 , p = 0.011 ) , quality of life and fatigue ( 42.86 ± 12.67 to 32.93 ± 15.87 , p = 0.008 ) were significantly improved in the control group . CONCLUSION The IMT improves functional capacity and balance , respiratory and peripheral muscle strength ; decreases depression and dyspnea perception in patients with heart failure . IMT should be included effectively in pulmonary rehabilitation programs BACKGROUND This small clinical trial tested the hypothesis that the addition of inspiratory muscle training ( IMT ) to aerobic exercise training ( AE ) results in further improvement in cardiorespiratory responses to exercise than those obtained with AE in patients with chronic heart failure ( CHF ) and inspiratory muscle weakness ( IMW ) . METHODS Twenty-four patients with CHF and IMW ( maximal inspiratory pressure < 70 % of predicted ) were r and omly assigned to a 12-week program of AE plus IMT ( AE + IMT , n = 12 ) or to AE alone ( AE , n = 12 ) . Before and after intervention , the following measures were obtained : maximal inspiratory muscle pressure ( PI(max ) ) , peak oxygen uptake ( Vo(2)peak ) , peak circulatory power , oxygen uptake efficiency slope , ventilatory efficiency , ventilatory oscillation , oxygen uptake kinetics during recovery ( T(1/2)Vo(2 ) ) , 6-minute walk test distance , and quality of life scores . RESULTS Compared to AE , AE + IMT result ed in additional significant improvement in PI(max ) ( 110 % vs 72 % ) , Vo(2)peak ( 40 % vs 21 % ) , circulatory power , oxygen uptake efficiency slope , ventilatory efficiency , ventilatory oscillation , and T(1/2)Vo(2 ) . Six-minute walk distance and quality of life scores improved similarly in the 2 groups . CONCLUSION This r and omized trial demonstrates that the addition of IMT to AE results in improvement in cardiorespiratory responses to exercise in selected patients with CHF and IMW . The clinical significance of these findings should be addressed by larger r and omized trials Background Inspiratory and peripheral muscle training improves muscle strength , exercise tolerance , and quality of life in patients with chronic heart failure ( HF ) . However , studies investigating different workloads for these exercise modalities are still lacking . Objective To examine the effects of low and moderate intensities on muscle strength , functional capacity , and quality of life . Design A r and omized controlled trial . Methods Thirty-five patients with stable HF ( aged > 18 years , NYHA II/III , LVEF < 40 % ) were r and omized to : non-exercise control group ( n = 9 ) , low-intensity training group ( LIPRT , n = 13 , 15 % maximal inspiratory workload , and 0.5 kg of peripheral muscle workload ) or moderate-intensity training group ( MIPRT , n = 13 , 30 % maximal inspiratory workload and 50 % of one maximum repetition of peripheral muscle workload ) . The outcomes were : respiratory and peripheral muscle strength , pulmonary function , exercise tolerance by the 6-minute walk test , symptoms based on the NYHA functional class , and quality of life using the Minnesota Living with Heart Failure Question naire . Results All groups showed similar quality -of-life improvements . Low and moderate intensities training programs improved inspiratory muscle strength , peripheral muscle strength , and walking distance . However , only moderate intensity improved expiratory muscle strength and NYHA functional class in HF patients . Conclusions The low-intensity inspiratory and peripheral resistance muscle training improved inspiratory and peripheral muscle strength and walking distance , demonstrating that LIPRT is an efficient rehabilitation method for debilitated HF patients . In addition , the moderate-intensity resistance training also improved expiratory muscle strength and NYHA functional class in HF patients Although exercise is an important component of heart failure management , optimal regimens , particularly in heart failure with preserved ejection fraction ( HFPEF ) , are uncertain . Tai chi ( TC ) is a mind-body exercise that may have potential benefits but has not been studied in this population . The authors r and omized 16 patients with HFPEF to either 12 weeks TC or aerobic exercise . Assessment s included peak oxygen uptake , 6-minute walk , quality of life , echocardiography , mood , and self-efficacy at baseline and at 12 weeks . Cardiorespiratory measures during exercise were obtained to characterize training intensities . Baseline characteristics were as follows : age 66±12 years , E/A ratio 1.3±0.7 , and E/e ' ratio 15.9±4.8 . Overall , adherence was excellent ( 89 % attendance ) . Change in peak oxygen uptake was similar between groups after 12 weeks , but 6-minute walk distance increased more after TC ( 69±46 m vs 10±31 m , P=.02 ) . While both groups had improved Minnesota Living With Heart Failure scores and self-efficacy , Profile of Mood States (POMS)-Depression scores improved more with TC ( -1.7±2.8 vs 1.6±3 , P=.05 ) . Cardiorespiratory assessment during TC showed lower oxygen uptake ( 4.3 mL/kg/min vs 9.4 mL/kg/min , P<.01 ) , respiratory rate , and heart rate . TC is feasible and safe in HFPEF . Therepeutic endpoints appear similar with TC relative to aerobic exercise despite a lower aerobic training workload OBJECTIVES This study sought to evaluate the effects of inspiratory muscle training in inspiratory muscle strength , as well as in functional capacity , ventilatory responses to exercise , recovery oxygen uptake kinetics , and quality of life in patients with chronic heart failure ( CHF ) and inspiratory muscle weakness . BACKGROUND Patients with CHF may have reduced strength and endurance in inspiratory muscles , which may contribute to exercise intolerance and is associated with a poor prognosis . METHODS Thirty-two patients with CHF and weakness of inspiratory muscles ( maximal inspiratory pressure [ Pi(max ) ] < 70 % of predicted ) were r and omly assigned to a 12-week program of inspiratory muscle training ( IMT , 16 patients ) or to a placebo-inspiratory muscle training ( P-IMT , 16 patients ) . The following measures were obtained before and after the program : Pi(max ) at rest and 10 min after maximal exercise ; peak oxygen uptake , circulatory power , ventilatory oscillations , and oxygen kinetics during early recovery ( VO2/t-slope ) ; 6-min walk test ; and quality of life scores . RESULTS The IMT result ed in a 115 % increment Pi(max ) , 17 % increase in peak oxygen uptake , and 19 % increase in the 6-min walk distance . Likewise , circulatory power increased and ventilatory oscillations were reduced . The VO2/t-slope was improved during the recovery period , and quality of life scores improved . CONCLUSIONS In patients with CHF and inspiratory muscle weakness , IMT results in marked improvement in inspiratory muscle strength , as well as improvement in functional capacity , ventilatory response to exercise , recovery oxygen uptake kinetics , and quality of life Aims : The purpose of this study was to examine the effects of Baduanjin exercise on fatigue and quality of life in patients with heart failure . Methods : The study was a r and omized controlled trial . Participants diagnosed with heart failure were recruited from two large medical centers in northern Taiwan . Participants were r and omly assigned to the intervention ( n=39 ) or control ( n=41 ) groups . Patients in the intervention group underwent a 12-week Baduanjin exercise program , which included Baduanjin exercise three times per week for 12 weeks at home , a 35-minute Baduanjin exercise demonstration video , a picture-based educational brochure , and a performance record form . The control group received usual care and received no intervention . Fatigue and quality of life were assessed using a structural question naire at baseline , four weeks , eight weeks , and 12 weeks after the intervention . Results : Participants in the Baduanjin exercise group showed significant improvement in fatigue ( F=5.08 , p=0.009 ) and quality of life ( F=9.11 , p=0.001 ) over time from baseline to week 12 after the intervention . Those in the control group showed significantly worse fatigue ( F=3.46 , p=0.033 ) over time from baseline to week 12 and no significant changes in quality of life ( F=0.70 , p=0.518 ) . Compared to the control group , the exercise group demonstrated significantly greater improvement in fatigue and quality of life at four weeks , eight weeks , and 12 weeks . Conclusions : This simple traditional exercise is recommended for Taiwanese patients with heart failure in order to improve their fatigue and quality of life OBJECTIVE To evaluate the change in the 6-minute walk test ( 6-MWT ) distance relative to changes in key functional capacity measures after 16 weeks of exercise training in older patients ( ≥65y ) who have heart failure with preserved ejection fraction ( HFpEF ) . DESIGN Prospect i ve , r and omized , single-blinded ( by research ers to patient group ) comparison of 2 groups of HFpEF patients . SETTING Hospital and clinic records ; ambulatory out patients . PARTICIPANTS Participants ( N=47 ) r and omly assigned to an attention control ( AC ) ( n=24 ) or exercise training ( ET ) ( n=23 ) group . INTERVENTION The ET group performed cycling and walking at 50 % to 70 % of peak oxygen uptake ( V˙o2peak ) intensity ( 3d/wk , 60min each session ) . MAIN OUTCOME MEASURES V˙o2peak , ventilatory threshold ( VT ) , and 6-MWT distance were measured at baseline and after the 16-week study period . RESULTS At follow-up , the 6-MWT distance was higher than at the baseline in both the ET ( 11 % , P=.005 ) and AC ( 9 % , P=.004 ) groups . In contrast , V˙o2peak and VT values increased in the ET group ( 19 % and 11 % , respectively ; P=.001 ) , but decreased in the AC group at follow-up ( 2 % and 0 % , respectively ) . The change in V˙o2peak versus 6-MWT distance after training was also not significantly correlated in the AC group ( r=.01 , P=.95 ) or in the ET group ( r=.13 , P=.57 ) . The change in 6-MWT distance and VT ( an objective submaximal exercise measure ) was also not significantly correlated in the AC group ( r=.08 , P=.74 ) or in the ET group ( r=.16 , P=.50 ) . CONCLUSIONS The results of this study challenge the validity of using the 6-MWT as a serial measure of exercise tolerance in elderly HFpEF patients and suggest that submaximal and peak exercise should be determined objective ly by VT and V˙o2peak in this patient population AIMS Vent-HeFT is a multicentre r and omized trial design ed to investigate the potential additive benefits of inspiratory muscle training ( IMT ) on aerobic training ( AT ) in patients with chronic heart failure ( CHF ) . METHODS AND RESULTS Forty-three CHF patients with a mean age of 58 ± 12 years , peak oxygen consumption ( peak VO2 ) 17.9 ± 5 mL/kg/min , and LVEF 29.5 ± 5 % were r and omized to an AT/IMT group ( n = 21 ) or to an AT/SHAM group ( n = 22 ) in a 12-week exercise programme . AT involved 45 min of ergometer training at 70 - 80 % of maximum heart rate , three times a week for both groups . In the AT/IMT group , IMT was performed at 60 % of sustained maximal inspiratory pressure ( SPImax ) while in the AT/SHAM group it was performed at 10 % of SPImax , using a computer biofeedback trainer for 30 min , three times a week . At baseline and at 3 months , patients were evaluated for exercise capacity , lung function , inspiratory muscle strength ( PImax ) and work capacity ( SPImax ) , quality of life ( QoL ) , LVEF and LV diameter , dyspnoea , C-reactive protein ( CRP ) , and NT-proBNP . IMT result ed in a significantly higher benefit in SPImax ( P = 0.02 ) , QoL ( P = 0.002 ) , dyspnoea ( P = 0.004 ) , CRP ( P = 0.03 ) , and NT-proBNP ( P = 0.004 ) . In both AT/IMT and AT/SHAM groups PImax ( P < 0.001 , P = 0.02 ) , peak VO2 ( P = 0.008 , P = 0.04 ) , and LVEF ( P = 0.005 , P = 0.002 ) improved significantly ; however , without an additional benefit for either of the groups . CONCLUSION This r and omized multicentre study demonstrates that IMT combined with aerobic training provides additional benefits in functional and serum biomarkers in patients with moderate CHF . These findings advocate for application of IMT in cardiac rehabilitation programmes Little is known about the burden of illness associated with advanced congestive heart failure ( CHF ) . Underst and ing the needs of this population requires further information about symptoms and other factors related to quality of life . We studied a convenience sample of 103 community-dwelling patients with New York Heart Association Class III/IV CHF . The primary outcome , quality of life , was measured with the Multidimensional Index of Life Quality . Potential correlates of quality of life included overall symptom burden ( Memorial Symptom Assessment Scale , MSAS ) , including global symptom distress ( MSAS Global Distress Index , GDI ) ; psychological state ( Mental Health Inventory-5 ) ; functional status ( Sickness Impact Profile ) ; spirituality ( Functional Assessment of Chronic Illness Therapy-Spirituality Scale ) ; and co-morbid conditions ( Charlson Comorbidity Index ) . Patients had a mean age of 67.1 years ( SD=12.1 ) ; were mostly white ( 72.8 % ) , male ( 71.8 % ) , and married ( 51.5 % ) ; and had a mean ejection fraction of 22.3 % ( SD=6.8 ) . The most prevalent symptoms were lack of energy ( 66 % ) , dry mouth ( 62 % ) , shortness of breath ( 56 % ) , and drowsiness ( 52 % ) . Pain was reported by about one-third of patients . For each of these symptoms , high symptom-related distress was reported by 14.1%-54.1 % . Quality of life was moderately compromised ( Multidimensional Index of Life Quality composite , median=56 , possible range 12 - 84 ) . Impairment in quality of life was strongly associated with global symptom distress ( MSAS GDI ; r=0.74 , P<0.001 ) ; burden of comorbid conditions ( r = -0.32 , P=0.002 ) , female sex ( r=-0.22 , P=0.03 ) , functional impairment , particularly psychological impairment ( r=-0.55 , P<0.001 ) , and poorer psychological well-being ( r=0.68 , P<0.001 ) . In multivariate analyses , impairment in quality of life was significantly related to high symptom distress , poorer psychological well-being , and poor functional mobility ( R2=0.67 ; P=0.002 for all ) . Distressful symptoms related to impaired quality of life included lack of energy ( P=0.04 ) , irritability ( P=0.03 ) , and drowsiness ( P=0.02 ) . Community-dwelling patients with advanced CHF experience numerous symptoms , significant symptom distress , and a compromised quality of life . Overall quality of life was strongly associated with symptom distress , psychological well-being and functional status . A focus on ameliorating prevalent physical symptoms and psychological distress , along with supportive measures that promote functional mobility , may lead to an improvement in the overall quality of life in this patient population |
12,770 | 29,534,130 | These findings demonstrate that plasma concentrations of a prophylactic dose of amoxicillin are higher than the minimum inhibitory concentration needed to prevent the common dental bacteria involved in peri-implantitis and periodontal diseases | PURPOSE The use of antibiotic prophylaxis in dental implant surgery is a routine dental practice to prevent implant failure .
Current systematic review s have yet to confirm the effectiveness of antibiotic treatment at reducing postoperative infection rates in implant procedures .
The aim of this study was to quantify amoxicillin plasma levels at the peripheral venous blood and at the surgical implant site in patients undergoing dental treatment . | Objectives The main purpose of this study is the detection of amoxicillin and clindamycin concentrations in teeth . Material s and methods Eleven patients received 2 g of amoxicillin , and 11 patients received 600 mg of clindamycin in a single dose of oral medication at least 60 min prior to tooth extraction due to systemic diseases . The concentrations were determined in crowns and roots separately using liquid chromatography – t and em mass spectrometry ( LC-MS-MS ) . Results Amoxicillin ( 13 sample s ) and clindamycin ( 12 sample s ) were detected in the sample s of the root and crown preparations of the extracted teeth . The mean concentration of amoxicillin was 0.502 μg/g in the roots and 0.171 μg/g in the crowns . The mean concentration of clindamycin was 0.270 μg/g in the roots and 0.064 μg/g in the crowns . Conclusions A single dose of oral amoxicillin and clindamycin leads to concentrations of both antibiotics in teeth which exceed the minimal inhibition concentration of some oral bacteria . Clinical relevance The proof of antibacterial activity in dental hard tissue after oral single-dose application is new . The antimicrobial effect of amoxicillin and clindamycin concentrations in roots of teeth may be of clinical relevance to bacterial reinfection from dentinal tubules The objective of this prospect i ve study was to estimate the incidence of early loss of dental implants and the potential risk factors . The predictive variables were classified as being patient , implant , anatomical , or operation-specific . The outcome variable was early failure of the implant . The significance of differences was assessed using bivariate analyses , and then a multivariate logistic regression model to identify independent predictors for early loss of implants . A total of 169 patients , 116 women and 53 men , mean age 47 ( range 16 - 80 ) years , had 399 implants inserted . Fifteen implants were lost in 14 patients ( 8 % ) . The early loss of dental implants was significantly associated with width of keratinised gingiva ( p=0.008 ) , the use polyglactin sutures ( p=0.048 ) , and the use of narrow implants ( p=0.035 ) . Multivariate logistic regression analysis established the significance of narrow keratinised gingiva ( OR=4.7 , p=0.005 ) and the use of polyglactin sutures ( OR=3.8 , p=0.042 ) , which we conclude are probably the strongest predictors of early failure of implants The purpose of this study was to compare the efficacy of two antibiotic regimens in reducing early dental implant failure . A preoperative single-dose regimen and a 3-day antibiotic course were compared . Eighty subjects needing dental implant placement were r and omly allocated to one of the two antibiotic prophylaxis regimen groups . In the first group , dental implants were placed after the administration of a single preoperative dose of antibiotic ( 1 g of amoxicillin ) ; no postoperative antibiotics were given . In the second group , dental implants were inserted in patients who received the same preoperative dose of antibiotic as the first group , but the antibiotic was then continued postoperatively for 3 days . Patients returned for postoperative evaluation at 3 days , 7 days , and 12 weeks . The surgical sites were assessed for pain , swelling , wound dehiscence , and pus formation . No statistically significant difference was observed between the two groups , probably because of the limited number of patients . Although minor complications were seen in a few patients , all implants were successfully osseointegrated . Until a study with a larger population rules definitively on the role of antibiotics in implant surgery , a single dose of antibiotic before implant placement may be sufficient PURPOSE The purpose of this prospect i ve study was to compare the efficacy of prophylactic antibiotic regimens commonly used in dental implant surgery . Preoperative single-dose and long-term prophylactic antibiotic regimens were compared . MATERIAL S AND METHODS This was a 2-center prospect i ve study in which 215 patients underwent ambulatory endosseous implant placement . In the first group , 445 dental implants were placed in 125 patients after the administration of a single preoperative dose of prophylactic antibiotic with no postoperative antibiotics . In the second group , 302 dental implants were placed in 90 patients who received a preoperative dose of antibiotics and were instructed to take antibiotics postoperatively for 7 days . In both groups , 0.12 % chlorhexidine pre- and postoperative mouth rinses were used . Patients returned for postoperative evaluation at 1 week , 2 weeks , and just prior to surgical uncovering . The surgical sites were assessed for pain , swelling , erythema , and purulence . RESULTS In the first group , 3 patients developed wound dehiscence at 5 implant sites and 1 developed a minor inflammatory response . None of the patients in this group received further antibiotics . In the second group , 3 patients developed wound dehiscence , 2 developed an inflammatory response , and 1 was diagnosed with infection , for which another course of antibiotics was required . There was no statistical difference between the 2 groups according to the Fisher 2 x 4 exact test ( P = .56 ) . DISCUSSION Indiscriminate use of antibiotics is unacceptable in clinical practice today . Surgeons must adhere to basic principles to gain the most benefit from the use of prophylactic antibiotics . CONCLUSION Long-term prophylactic antibiotic use in implant surgery was of no advantage or benefit over a single-dose preoperative antibiotic regimen in this patient population Peri-implantitis is a biofilm-induced destructive inflammatory process that , over time , results in loss of supporting bone around an osseointegrated dental implant . Biofilms at peri-implantitis sites have been reported to be dominated by Gram-negative anaerobic rods with a proteolytic metabolism such as , Fusobacterium , Porphyromonas , Prevotella and Tannerella , as well as anaerobic Gram-positive cocci . In this study , we hypothesized that protease activity is instrumental in driving bone destruction and we therefore compared the microbial composition and level of protease activity in sample s of peri-implant biofluid ( PIBF ) from 25 healthy subjects ( H group ) and 25 subjects with peri-implantitis ( PI group ) . Microbial composition was investigated using culture techniques and protease activity was determined using a FITC-labelled casein substrate . The microbial composition was highly variable in subjects both in the H and PI groups but one prominent difference was the prevalence of Porphyromonas/Prevotella and anaerobic Gram positive cocci which was significantly higher in the PI than in the H group . A subgroup of subjects with peri-implantitis displayed a high level of protease activity in the PIBF compared to healthy subjects . However , this activity could not be related to the presence of specific bacterial species . We propose that a high level of protease activity may be a predictive factor for disease progression in peri-implantitis . Further longitudinal studies are however required to determine whether assessment of protease activity could serve as a useful method to identify patients at risk for progressive tissue destruction The aim of this study was to attempt to determine the minimum effective regimen of amoxicillin antibiotic prophylaxis for dental implant surgery . One hundred patients were r and omly allocated to 4 different antibiotic prophylactic treatment groups . At second-stage surgery , only 2 implants failed in the nonantibiotic group . No statistically significant differences were found in the 4 groups , probably because of the limited number of the sample s. Until a study with a larger population may definitely rule on the role of antibiotics in oral implant surgery , in may be prudent for the practitioner to adopt the single preoperative antibiotic dose as the minimal effective regimen The aim of the present r and omized controlled clinical trial was to investigate the adjunctive effect of systemic antibiotics and the local use of chlorhexidine for implant surface decontamination in the surgical treatment of peri-implantitis . One hundred patients with severe peri-implantitis were recruited . Surgical therapy was performed with or without adjunctive systemic antibiotics or the local use of chlorhexidine for implant surface decontamination . Treatment outcomes were evaluated at 1 y. A binary logistic regression analysis was used to identify factors influencing the probability of treatment success , that is , probing pocket depth ≤5 mm , absence of bleeding/suppuration on probing , and no additional bone loss . Treatment success was obtained in 45 % of all implants but was higher in implants with a nonmodified surface ( 79 % ) than those with a modified surface ( 34 % ) . The local use of chlorhexidine had no overall effect on treatment outcomes . While adjunctive systemic antibiotics had no impact on treatment success at implants with a nonmodified surface , a positive effect on treatment success was observed at implants with a modified surface . The likelihood for treatment success using adjunctive systemic antibiotics in patients with implants with a modified surface , however , was low . As the effect of adjunctive systemic antibiotics depended on implant surface characteristics , recommendations for their use in the surgical treatment of peri-implantitis should be based on careful assessment s of the targeted implant ( Clinical Trials.gov NCT01857804 ) |
12,771 | 20,449,755 | Conclusions There is an increased risk of clinical ly significant oral fungal infection during cancer therapy .
Systemic antifungals are effective in the prevention of clinical oral fungal infection in patients receiving cancer therapy . | Purpose The aims of this systematic review were to determine , in patients receiving cancer therapy , the prevalence of clinical oral fungal infection and fungal colonization , to determine the impact on quality of life and cost of care , and to review current management strategies for oral fungal infections . | AIMS : To compare the efficacy of and tolerance to oral fluconazole and intraconazole in preventing fungal infection in neutropenic patients with haematological malignancies . PATIENTS : 213 consecutive , afebrile adult patients treated with or without autologous stem cell transplantation for haematological malignancies . METHODS : A r and omised , double blind , single centre study . Patients were r and omly assigned to receive fluconazole 50 mg or itraconazole 100 mg , both twice daily in identical capsules . An intention to treat analysis was performed on 202 patients , 101 in each group . RESULTS : Microbiologically documented systemic fungal infections occurred in four patients in each group . Clinical fungal infection was thought to be present in seven recipients of fluconazole and four of itraconazole . In all 202 patients , 29 proceeded to intravenous amphotericin ( amphotericin B ) , 16 in the fluconazole group and 13 in the itraconazole group . Superficial fungal infection was seen only in three non-compliant patients in the fluconazole group . All these infections were oral . No major differences were noted in the isolates of fungi in mouth washes and fecal sample s. Overall mortality was 8.9 % ( 18 deaths ; seven in the fluconazole group , 11 in the itraconazole group ) . Mortality from microbiologically and clinical ly documented fungal infection was 4.5 % ( nine deaths ; three in the fluconazole group , six in the itraconazole group ) . Median time to suspected or proven fungal infection was 16 days in both groups . None of these comparisons reached statistical significance ( p < 0.05 ) . No major clinical toxicity was noted and compliance was excellent . CONCLUSIONS : In neutropenic patients treated for haematological malignancies with or without autologous stem cell transplantation , fluconazole and itraconazole in low doses result in a similar low frequency of fungal disease . Fluconazole may be the preferable drug because of the smaller number of capsules and lack of need for timing relative to meals Goal of workThe aim of the study is to evaluate the effect of fluconazole antifungal prophylaxis on the severity of mucositis in head and neck cancer patients receiving radiotherapy . Patients and methods Sixty-three patients , with malignant head and neck tumor , eligible to receive radiotherapy , entered the study . Thirty-four patients ( group A ) received 100 mg/day of fluconazole prophylaxis during radiotherapy and were compared with 29 patients , who received radiotherapy alone ( group B ) . The two groups were similar in terms of patients and radiotherapy characteristics . Smear to test for C and ida carriage was taken before and after radiotherapy . Oral c and idiasis was diagnosed using the criteria described before . Oral mucositis was recorded according to EORTC/RTOG criteria .Main results A significant reduction of severe mucositis at the end of radiotherapy ( 14.7 vs 44.8 % , p=0.018 ) and of interruptions ( 0 vs 17.2 % , p=0.017 ) was observed in group A. C and idiasis was prevented ( 0 vs 34.5 % , p=0.001 ) , with a significant reduction of C and ida carriage of 40.7 % ( p=0.001 ) . Conclusion Fluconazole prophylaxis showed a significant beneficial impact on the severity of mucositis and on radiotherapy interruptions in this group of patients . The current study provides data on the build of a r and omized controlled trial on the effect of fluconazole prophylaxis on treatment schedule and quality of life of the patients during head and neck radiotherapy The aim of this study was to investigate oral yeast colonization and oral yeast strain diversity in irradiated ( head and neck ) , dentate , xerostomic individuals . Subjects were recruited from a nasopharyngeal carcinoma clinic and were segregated into group A ( age , < 60 years [ n = 25 ; average age + /- st and ard deviation ( SD ) , 48 + /- 6 years ; average postirradiation time + /- SD , 5 + /- 5 years ] ) and group B ( age , > /=60 years [ n = 8 ; average age + /- SD , 67 + /- 4 years ; average postirradiation time + /- SD , 2 + /- 2 years ] ) and were compared with age- and sex-matched healthy individuals in group C ( age , < 60 years [ n = 20 ; average age + /- SD , 44 + /- 12 years ] and group D ( age , > /=60 years [ n = 10 ; average age , 70 + /- 3 years ] ) . Selective culture of oral rinse sample s was carried out to isolate , quantify , and speciate yeast recovery . All test subjects underwent a 3-month comprehensive oral and preventive care regimen plus topical antifungal therapy , if indicated . A total of 12 subjects from group A and 5 subjects from group B were recalled for re assessment of yeast colonization . Sequential ( pre- and posttherapy ) C and ida isolate pairs from patients were phenotypically ( all isolate pairs ; biotyping and resistotyping profiles ) and genotypically ( C and ida albicans isolate pairs only ; electrophoretic karyotyping by pulsed-field gel electrophoresis , restriction fragment length polymorphism [ RFLP ] , and r and omly amplified polymorphic DNA [ RAPD ] assays ) evaluated . All isolates were C and ida species . Irradiated individuals were found to have a significantly increased yeast carriage compared with the controls . The isolation rate of C and ida posttherapy remained unchanged . A total of 9 of the 12 subjects in group A and 3 of the 5 subjects in group B harbored the same C. albicans or C and ida tropicalis phenotype at recall . Varying degrees of congruence in the molecular profiles were observed when these sequential isolate pairs of C. albicans were analyzed by RFLP and RAPD assays . Variations in the genotype were complementary to those in the phenotypic characteristics for some isolates . In conclusion , irradiation-induced xerostomia seems to favor intraoral colonization of C and ida species , particularly C. albicans , which appeared to undergo temporal modifications in clonal profiles both phenotypically and genotypically following hygienic and preventive oral care which included topical antifungal therapy , if indicated . We postulate that the observed ability of C and ida species to undergo genetic and phenotypic adaptation could strategically enhance its survival in the human oral cavity , particularly when salivary defenses are impaired Guidelines for the management of patients with invasive c and idiasis and mucosal c and idiasis were prepared by an Expert Panel of the Infectious Diseases Society of America . These up date d guidelines replace the previous guidelines published in the 15 January 2004 issue of Clinical Infectious Diseases and are intended for use by health care providers who care for patients who either have or are at risk of these infections . Since 2004 , several new antifungal agents have become available , and several new studies have been published relating to the treatment of c and idemia , other forms of invasive c and idiasis , and mucosal disease , including oropharyngeal and esophageal c and idiasis . There are also recent prospect i ve data on the prevention of invasive c and idiasis in high-risk neonates and adults and on the empiric treatment of suspected invasive c and idiasis in adults . This new information is incorporated into this revised document To evaluate the efficacy of itraconazole capsules in prophylaxis for fungal infections in neutropenic patients , we conducted a prospect i ve , double-blind , placebo-controlled , r and omized trial . Patients with hematologic malignancies or those who received autologous bone marrow transplants were assigned either a regimen of itraconazole ( 100 mg orally twice daily ; n=104 ) or of placebo ( n=106 ) . Overall , fungal infections ( superficial or systemic ) occurred more frequently in the placebo group ( 15 % vs. 6 % ; P=.03 ) . There were no differences in the empirical use of amphotericin B or systemic fungal infections . Among patients with neutropenia that was profound ( < 100 neutrophils/mm3 ) and prolonged ( for at least 7 days ) , those receiving itraconazole used less empirical amphotericin B ( 22 % vs. 61 % ; P=.0001 ) and developed fewer systemic fungal infections ( 6 % vs. 19 % ; P=.04 ) . For patients with profound and prolonged neutropenia , itraconazole capsules at the dosage of 100 mg every 12 h reduce the frequency of systemic fungal infections and the use of empirical amphotericin Fungal infections are a major problem in patients with hematologic malignancy . Attempts to reduce their frequency with antifungal agents have not been successful . A double-blind , controlled , single-center trial was conducted with 96 consecutive patients undergoing 154 episodes of chemotherapy . Patients received 400 mg of fluconazole or placebo until bone marrow recovery or initiation of intravenous amphotericin B infusions . End points were amphotericin B use , fungal infection , stable neutrophil count > 0.5 x 10(9)/L , toxicity precluding further fluconazole use , and death . By Kaplan-Meier estimation , the time to initiation of amphotericin B therapy was shorter in 76 patients treated with placebo than in 75 treated with fluconazole ( P = .003 ) . Also , fluconazole reduced the number of febrile days by 20 % ( P = .002 ) and prevented oropharyngeal c and idiasis ( 1/75 vs. 9/76 , P = .018 ) . The frequency of deep mycoses ( 8/76 vs. 8/75 ) and outcome were unaffected . Fluconazole did not have a favorable effect on infection-related health care costs and was associated with prolonged severe neutropenia ( P = .01 ) In a prospect i ve r and omized study the efficacy of fluconazole ( 50 mg in one single daily dose ) was compared with oral amphotericin B in suspension and tablets ( each 200 mg four times daily ) for prevention of colonization and subsequent infection by yeasts in 50 patients undergoing remission induction treatment for acute leukaemia . All patients received ciprofloxacin for prevention of bacterial infections . Fluconazole was as effective as amphotericin B in preventing severe local and disseminated fungal disease ( one documented and one highly suspected infection in each group of patients ) . Fluconazole effectively prevented yeast colonization of the oropharynx but was less effective than amphotericin B in preventing colonization of the lower alimentary tract . Fifty-two percent of patients receiving fluconazole had persistent positive stool cultures as compared to 4 % in the amphotericin B group ( P less than 0.01 ) . Fluconazole was better tolerated than amphotericin B. One patient developed an extended rash leading to the termination of fluconazole PURPOSE To identify predictors of oral mucositis and gastrointestinal toxicity after high-dose therapy . PATIENTS AND METHODS Mucositis and gastrointestinal toxicity were prospect ively evaluated in 202 recipients of high-dose therapy and autologous or allogeneic stem-cell rescue . Of 10 outcome variables , three were selected as end points : the peak value for the University of Nebraska Oral Assessment Score ( MUCPEAK ) , the duration of parenteral nutritional support , and the peak daily output of diarrhea . Potential covariates included patient age , sex , diagnosis , treatment protocol , transplantation type , stem-cell source , and rate of neutrophil recovery . The three selected end points were also examined for correlation with blood infections and transplant-related mortality . RESULTS A diagnosis of leukemia , use of total body irradiation , allogeneic transplantation , and delayed neutrophil recovery were associated with increased oral mucositis and longer parenteral nutritional support . No factors were associated with diarrhea . Also , moderate to severe oral mucositis ( MUCPEAK > or = 18 on a scale of 8 to 24 ) was correlated with blood infections and transplant-related mortality : 60 % of patients with MUCPEAK > or = 18 had positive blood cultures versus 30 % of patients with MUCPEAK less than 18 ( P = .001 ) ; 24 % of patients with MUCPEAK > or = 8 died during the transplantation procedure versus 4 % of patients with MUCPEAK less than 18 ( P = .001 ) . CONCLUSION Gastrointestinal toxicity is a major cause of transplant-related morbidity and mortality , emphasizing the need for corrective strategies . The peak oral mucositis score and the duration of parenteral nutritional support are useful indices of gastrointestinal toxicity because these end points are correlated with clinical ly significant events , including blood infections and treatment-related mortality The goal of this prospect i ve r and omized single-center study was the comparison of safety and efficacy of high-dose oral/intravenous fluconazole ( 400 mg daily ) ( group A ) with oral nystatin plus miconazole inhalations ( group B ) in the prevention of fungal infections on a hemato-oncological isolation Ward . Of 157 patients admitted to the isolation ward during the study period only 90 ( 57 % ) were eligible for r and omization ; 22 ( 14 % ) had a fungal infection at admission . Of the 90 r and omized patients , 89 were evaluable , 43 in group A and 46 in group B. The age , sex , diagnosis , planned therapy and risk factors for fungal infections at admission as well as the duration of neutropenia were in the same proportions in both groups . Oral thrush and mucocutaneous c and idiasis were prevented in all patients of both groups , and 29 patients ( 32 % : 17 in group A , 12 in group B ) were discharged after successful prophylaxis ( NS ) . Empiric amphotericin B was given according to predetermined criteria to 45 patients ( 51 % : 23 group A , 22 group B ; NS ) . Fluconazole significantly delayed the time before the start of intravenous amphotericin B. It was begun after a median of 10 days ( 0–45 days , range ) of neutropenia below 0.5x109 granulocytes/l in group A and 7.5 days ( 0–26 , range ) in group B ( P<0.05 ) . The duration of successful prophylaxis was significantly longer in group A ( 26 days median ) than in group B ( 21 days , median ) ( P<0.05 ) . Systemic fungal infection was documented in 3 patients ( 1 group A , 2 group B ; NS ) . Colonisation with C and ida persisted for more than 14 days or occurred de novo after admission in 1 patient in group A and in 7 patients in group B ( NS ) . Oral nystatin had to be discontinued because of oral intolerance in 3 patients and fluconazol had to be stopped because of increased liver values in one patient . Compliance was worse ( P<0.01 ) in group B ; 82 % of the planned dose was given in group B compared to 99 % in group A. Both regimens successfully prevented oral fungal complications . Fluconazole was better tolerated and delayed the need for empiric amphotericin B. Neither approach cancelled the need for the empiric use of amphotericin B nor prevented fungal infections or colonization . Systemic fungal infections occur probably independently of oral or mucocutaneous c and idiasis C and ida overgrowth and invasion constitute a serious threat with a high mortality in BMT recipients . Currently available topical antifungal prophylaxis is largely ineffective , and as resistance to existing , absorbable drugs for systemic use is rapidly developing , new forms of therapy are needed . We investigated the effect of oral treatment of BMT recipients with a bovine immunoglobulin product derived from animals immunized against several C and ida species . The natural C and ida colonization was first followed in 19 patients to establish the colonization pattern . Half of the patients were found to be colonized prior to transplantation and altogether 72 % were colonized at some point during follow-up . Those with a high pre-transplant concentration of C and ida in saliva ( > 100 CFU/ml ) remained colonized throughout the BMT treatment period . The therapeutic effect was monitored in two other patient groups . The first group consisted of nine patients , where , due to a low number of primary colonized patients , response in colonized patients was suggestive of a therapeutic effect . In the second group , 10 patients with a high level of colonization ( > 100 CFU/ml ) were given 10 g daily of the product in three divided doses . The results suggest a treatment-related reduction in C and ida colonization in a majority ( 7/10 ) of patients and one patient became completely negative . As no adverse effects were noted , our findings encourage additional studies in immuno- compromised , transplant patients The goal of reducing oral complications during chemotherapy and bone marrow transplantation has received attention at several centers . The current r and omized study of 86 adults with leukemia treated with chemotherapy or bone marrow transplantation assessed the potential role of chlorhexidine , nystatin , and saline solution rinses to reduce the findings of oral mucositis , gingivitis , and oral infection . The results of this study did not show a reduction in mucositis with the use of these rinses . However , potential bacterial and fungal pathogens were identified less frequently in the patients using chlorhexidine rinse The efficacy and safety of oral fluconazole versus a polyene regimen in preventing mycoses in neutropenic patients was compared . Patients with haematological malignancy or bone marrow transplantation received as antifungal prophylaxis either fluconazole 200 mg daily or a regimen consisting of clotrimazole trouches 10 mg twice daily with mycostatin , 500,000 i.u . four times daily , benadryl and cepacol mouthwash . Ninety patients at risk for fungus infection were evaluable . Four of 42 patients ( 9.5 % ; confidence interval 2 % –23 % ) on fluconazole and 17 of 48 patients ( 35.4 % ; confidence interval 22 % –52 % ) ( p<0.01 ) on the clotrimazole regimen developed a clinical ly significant fungal infection , including 3 ( 7.1 % ) and 11 ( 22.9 % ) patients respectively who had severe fungal infection , mainly pulmonary aspergillosis . Death directly due to a fungal infection within 100 days of the start of prophylaxis occurred in 2 of 42 patients ( 4.8 % ) and 9 of 48 patients ( 18.8 % ) respectively ( p<0.06 ) . Kaplan-Meier analysis showed that the chance of survival on fluconazole was statistically greater than for the clotrimazole regimen ( p<0.04 ) . A decrease of c and idal colonisation of the gastrointestinal and genitourinary tracts occurred only in patients receiving fluconazole . No significant toxicity occurred . A 200 mg daily dose of fluconazole given to these patients thus appears to be well tolerated and to provide a protective effect against the development of fungal infection and death from severe fungal disease BACKGROUND Acute myeloid leukemia ( AML ) and myelodysplastic syndrome ( MDS ) patients experience prolonged neutropenia after treatment with intensive chemotherapy , leading to a high risk of invasive fungal infections ( IFI ) . The present study evaluates the cost effectiveness of posaconazole vs. st and ard azoles for the prevention of IFIs in neutropenic patients in the Netherl and s. METHODS A decision-tree model was developed using data from a r and omized trial that compared posaconazole and st and ard azole ( fluconazole or itraconazole ) prophylaxis in neutropenic patients receiving remission-induction chemotherapy for AML/MDS ( Cornely et al. , N Engl J Med 2007;356:348 - 359 ) . Following initiation of prophylaxis , clinical events are modeled with chance nodes reflecting probabilities of IFIs , IFI-related death , and death from other causes . Patients surviving the prophylaxis are assumed to have a life expectancy according to the underlying condition . This allows translation of the trial outcomes to a lifetime horizon . Data on life expectancy , quality of life , medical re source consumption and costs were obtained from the literature . Model outcomes include cost per life year ( LY ) gained and cost per quality adjusted life year ( QALY ) gained . RESULTS The total cost ( treatment of breakthrough IFI + prophylaxis ) for posaconazole amounted to 4412 euros ( 95 % uncertainty interval 3403 euros - 5666 euros ) , which is -183 euros ( -1985 euros to 1564 euros ) less than costs with st and ard azoles . Posaconazole prophylaxis result ed in 0.08 ( 0.02 - 0.15 ) QALYs gained in comparison with prophylaxis with st and ard azoles . Results from a probabilistic sensitivity analysis indicate that there is a 90 % probability that the cost per QALY gained with posaconazole is below 20,000 euros . Additional scenario analyzes with different assumptions confirmed these findings . CONCLUSION Given the underlying data and assumptions , the economic evaluation demonstrated that posaconazole prophylaxis is expected to be cost-effective compared with fluconazole/itraconazole in neutropenic AML/MDS patients after intensive chemotherapy We studied the efficacy and safety of itraconazole for the prevention of fungal infection in neutropenic patients given cytotoxic chemotherapy for hematologic malignancies . Patients were r and omly allocated to receive either itraconazole ( 200 mg bd ) or placebo in addition to oral amphotericin B until the patient either developed fungal infection or had completed antileukemic treatment . Forty six patients ( 83 neutropenic episodes ) treated with itraconazole and 46 placebo treated patients ( 84 neutropenic episodes ) were evaluable . No specific toxicity was noted . Nine fungal infections developed in the itraconazole group , of which four were histologically or microbiologically proven and 15 in the patients given placebo ( eight proven ) ( p < 0.12 ) . All these patients received IV amphotericin B. The incidence of C and ida albicans infections tended to be lower in the itraconazole group , but overall , there was no measurable improvement in the prevention of fungal infections and mortality by itraconazole This controlled study assessed the incidence of oral c and idiasis , a xerostomia-related complication , in head and neck cancer patients receiving radiotherapy , with amifostine cytoprotection . Thirty-eight patients received 500 mg amifostine i.v . , prior to each radiotherapy fraction , while 16 patients received radiotherapy alone . Oral c and idiasis was diagnosed according to the criteria described before . Subjective xerostomia scales were completed by all patients . Mucositis was evaluated using the RTOG criteria . Oral c and idiasis was diagnosed in 11/38 amifostine patients and in 9/16 controls ( P = 0.07 ) . Severe xerostomia was reported by 4/38 amifostine patients and by 7/16 controls . Oral c and idiasis was reduced with amifostine cytoprotection . Oral c and idiasis is suggested as an objective , early , though indirect , endpoint for amifostine 's radioprotective effect on salivary gl and An open , r and omized study was performed at 18 European centres to compare the efficacy , safety and tolerance of oral fluconazole with oral polyenes for the prophylaxis of fungal colonization and infection in adults at high risk of developing neutropenia . Five hundred and thirty-six hospitalized patients with malignant disease , about to receive chemotherapy , radiotherapy , or bone marrow transplantation , and who were already neutropenic or were expected to develop neutropenia were included in the study . Before therapy or transplantation , patients commenced either oral fluconazole therapy ( 50 mg/day as a single dose ) or oral polyenes therapy ( amphotericin B 2 g/day and /or nystatin 4 x 10(6 ) units/day in four or more divided doses ) , for a mean of 29.3 days and 31.3 days , respectively . After baseline clinical and mycological testing , patients were re-evaluated at least weekly during prophylaxis , at the end of prophylaxis and two to six weeks later to identify proven or suspected fungal infection and to determine rates of colonization with fungi . Fungal infection was diagnosed in 41 of 511 evaluable patients , 10 ( 3.9 % ) of 256 in the fluconazole group and 31 ( 12.2 % ) of 255 in the polyene group ( P = 0.001 ) . This total included four patients ( 1.6 % ) in the fluconazole group who developed oropharyngeal c and idiasis compared with 22 ( 8.6 % ) in the polyene group ( P < 0.001 ) . Systemic infections comprised 6 ( 2.3 % ) in the fluconazole group and 9 ( 3.5 % ) in the polyene group ( P = not significant ) , and included three C and ida krusei infections in each group . Parenteral amphotericin B therapy was given empirically for persistent fevers in an additional 62 ( 24.2 % ) patients receiving fluconazole and 59 ( 23.1 % ) receiving polyenes ( P = not significant ) . Colonization with fungi was generally similar in each treatment group , although an increased proportion of patients receiving fluconazole developed colonization of the faeces ( P < 0.01 ) . Adverse reactions , possibly related to treatment , were recorded in 15 ( 5.6 % ) of 269 patients in the fluconazole group and 14 ( 5.2 % ) of 267 in the polyene group ; these necessitated discontinuation of therapy in seven patients in each group . Once-a-day fluconazole was therefore more effective than oral polyenes for the prevention of oropharyngeal fungal infection and as effective for the prevention of infections at other sites in patients with neutropenia To evaluate the efficacy and safety of itraconazole oral solution for preventing fungal infections , a r and omized , placebo-controlled , double-blind , multicenter trial was conducted : 405 neutropenic patients with hematologic malignancies were r and omly assigned to receive either itraconazole , 2.5 mg/kg every 12 hours ( 201 patients ) , or placebo ( 204 patients ) . Proven and suspected deep fungal infection occurred in 24 % of itraconazole recipients and in 33 % of placebo recipients , a difference of 9 percentage points ( 95 % confidence interval [ CI ] , 0.6 % to 22.5 % ; P = .035 ) . Fungemia due to C and ida species was documented in 0.5 % of itraconazole recipients and in 4 % of placebo recipients , a difference of 3.5 percentage points ( 95 % CI , 0.5 % to 6 % ; P = .01 ) . Deaths due to c and idemia occurred in none of the itraconazole recipients compared with 4 placebo recipients , a difference of 2 percentage points ( 95 % CI , 0.05 % to 4 % ; P = .06 ) . Aspergillus infection was documented in four itraconazole recipients ( one death ) and one placebo recipient ( one death ) . Side effects causing drug interruption occurred in 18 % of itraconazole recipients and 13 % of placebo recipients . Itraconazole oral solution was well-tolerated and effectively prevented proven and suspected deep fungal infection as well as systemic infection and death due to C and ida species Superficial and systemic fungal infections are a major problem among neutropenic patients with acute leukemia [ 1 ] or those having bone marrow transplantation [ 2 ] . It remains a leading cause of morbidity and mortality , and many centers administer amphotericin B empirically to patients with neutropenia and fever refractory to antibacterial treatment [ 3 , 4 ] . Antifungal prophylaxis is also used widely , but its efficacy in reducing systemic fungal infection is debated [ 5 ] . However , oral polyene antibiotics , usually poorly tolerated because of their bitter taste , have been shown to reduce oral c and idiasis , and , in a placebo-controlled study , oral amphotericin B was shown to decrease autopsy-proven systemic c and idiasis [ 6 ] . Among the imidazoles , ketoconazole and miconazole have been used with contrasting results in the prevention of systemic fungal infections , but because of their toxicities and the emergence of fungal-resistant strains , they are rarely used . Fluconazole , an oral triazole with systemic activity , tested in placebo-controlled trials in a daily oral dose of 400 mg , was found to be effective in reducing systemic fungal infections in marrow recipients [ 7 ] but did not show the same benefit in patients with acute leukemia receiving therapy to induce remission [ 8 ] . Our aim was to clarify the role of systemic and topical antifungal prophylactic agents in neutropenic patients with acute leukemia by doing a large , r and omized , multicenter trial that compared the efficacy and tolerability of oral fluconazole with high-dose amphotericin B suspension . Methods Eligible patients included consecutive adults who had acute leukemia , were hospitalized at participating centers , and were receiving cytotoxic therapy likely to induce neutropenia ( neutrophil count < 1000/mm3 ) within 7 days . Patients received remission-induction or reinduction therapy according to the GIMEMA protocol s [ 9 , 10 ] . We excluded from the study before r and omization patients younger than 14 years , patients with a history of hypersensitivity to triazoles , patients treated with antifungal therapy in the previous 15 days , patients with evidence of a preexisting systemic fungal infection , and patients who had nasal colonization with Aspergillus spp . Study Protocol After informed consent was obtained , the patients were r and omly assigned to receive either fluconazole , 150 mg as a once-daily capsule , or amphotericin B suspension , 500 mg every 6 hours . Patients were r and omly assigned to treatments using r and om permuted blocks of 10 containing different and balanced sequences of the two regimens . Antifungal prophylaxis was started 1 to 3 days before the administration of cytotoxic chemotherapy and continued until the neutrophil count returned to 1000/L or a systemic fungal infection was proved or suspected . All patients received oral ciprofloxacin , 500 mg twice daily , as antibacterial prophylaxis [ 11 ] ; antiviral prophylaxis and central venous catheters were used according to autonomous decisions made at each participating center . The patients were treated under conventional ward conditions or in single rooms , depending on the center . Prophylactic granulocyte transfusions and colony-stimulating factors were not used . All patients were examined daily for clinical signs of fungal infection . When axillary temperature increased to more than 38 C or infection was suspected , sample s for microbiological cultures , including at least three separate blood specimens , were obtained , prophylactic therapy with ciprofloxacin was discontinued , and treatment with amikacin , ceftazidime , and a glycopeptide antibiotic ( teicoplanin or vancomycin ) was started ; if fever persisted despite 4 to 6 days of systemic antibiotics , empiric intravenous amphotericin B was administered . Documented systemic fungal infections were treated with systemic antifungal agents ( mainly intravenous amphotericin B ) , and superficial fungal infections were treated with topical antifungal agents . To compare the efficacy and tolerability of the two prophylactic regimens , the following variables were measured : documented systemic fungal infection ; suspected systemic fungal infection ; superficial fungal infection ; the interval to the development of documented systemic fungal infection or to the use of empiric antifungal therapy ; compliance ; treatment interruption caused by side effects ; and mortality . Definition of Fungal Infection Superficial fungal infection was defined as clinical ly apparent infection of the oropharynx or skin , along with positive cultures ; a suspected case of systemic fungal infection was defined as any episode of fever that persisted despite 4 to 6 days of empiric antibiotic therapy , for which empiric intravenous amphotericin B therapy was administered ; definite systemic fungal infection was defined as one in which there was both clinical evidence of blood or tissue infection and a culture or biopsy specimen from the involved site showing a pathogenic fungal organism [ 7 ] . Compliance Compliance was monitored by the nurse who counted capsules of fluconazole and measured the volume of amphotericin B oral suspension each day and recorded these data on the clinical report form . Compliance was defined as excellent if the patient took all the drug doses , as good if the patient missed fewer than three consecutive doses or took more than 80 % of the total number of doses , and as poor if the patient missed more than three consecutive doses or took less than 80 % of the total number of doses . Statistical Analysis Statistical analysis was done at the GIMEMA Infection Program Data Center with the SAS package ( SAS Institute , Inc. , Cary , North Carolina ) . Results are reported for all patients enrolled in the study ( intention-to-treat analysis ) . Except for three patients r and omly assigned to fluconazole and two patients assigned to amphotericin B who did not receive the study drugs and six additional patients in the fluconazole group and five in the amphotericin B group who had a duration of neutropenia of less than 7 days , all other patients were evaluable for the clinical efficacy analysis . The chi-square test with a correction for continuity , or the Fisher exact test when appropriate , was used to compare differences in proportions between the two groups . The log-rank test was used to compare the Kaplan-Meier survival curves . The Student unpaired t-test was used to compare the means . Confidence intervals ( CIs ) of 95 % are given where appropriate . Results A total of 820 patients with acute leukemia and neutropenic episodes from 30 centers were studied ; 420 were r and omly assigned to receive fluconazole , and 400 were r and omly assigned to receive oral amphotericin B. The two groups of patients were similar in sex , age , underlying diseases , type of chemotherapy , protective environment , use of central venous catheters , and duration and severity of neutropenia . Patients receiving first-induction chemotherapy were equally distributed in the two treatment groups ( Table 1 ) . Table 1 . Patient Characteristics according to Treatment Group Systemic Fungal Infection Proven systemic fungal infection occurred in 11 ( 2.6 % ) fluconazole recipients and in 10 ( 2.5 % ) amphotericin B recipients ( P > 0.2 ) . The distribution of fungal isolates was similar in both groups ( Table 2 ) : C and ida spp . caused 55 % of systemic infections in fluconazole recipients and 70 % in amphotericin B recipients ; no difference was found in the isolation of different C and ida spp . , including C. krusei , between the two groups . Rates of infections caused by Aspergillus spp . were 45 % in fluconazole recipients and 30 % in amphotericin B recipients , a difference of 15 percentage points ( 95 % CI for difference , 25 % to 56 % , P > 0.2 ) , and the Aspergillus isolates were equally distributed . Fungemia caused by C and ida spp . was documented in five patients receiving fluconazole and in three treated with amphotericin B. The characteristics of the patients with proven cases of systemic fungal infection and their clinical outcomes are summarized in Table 3 . Table 2 . Types of Fungi Isolated in Systemic Infections according to Treatment Group * Table 3 . Characteristics and Outcomes of the Definite Cases of Systemic Fungal Infection according to Treatment Group Overall , the sites of infection between the two treatment groups were similar ( P > 0.2 ) . Simple fungemia caused by C and ida isolates was documented in three patients in each group ( two cases of C. krusei and one of C. parapsilosis in fluconazole recipients ; one case each of C. albicans , C. krusei , and C. parapsilosis in amphotericin B recipients ) , and tissue infection was documented in three fluconazole recipients ( C. tropicalis , C. albicans , and C. parapsilosis ) , and two amphotericin recipients ( C and ida spp . , C. albicans ) . In patients receiving amphotericin B , esophagitis caused by C and ida spp . and urinary tract infection caused by C. tropicalis were also documented . Tissue infection caused by Aspergillus spp . occurred in five fluconazole recipients ( four cases of pneumonia and one disseminated infection ) and in three amphotericin B-treated patients ( two cases of pneumonia and one case of disseminated infection ) . Deaths from fungal infection were similar . C and ida krusei fungemia and C. albicans and C. parapsilosis tissue infections caused death in three fluconazole recipients ; C. albicans fungemia and C and ida spp . tissue infection caused death in two amphotericin B recipients . Aspergillus pneumonia caused two deaths in the fluconazole group and one death in the amphotericin B group . The interval to the documented systemic fungal infection was 21 days in fluconazole recipients and 15 days in amphotericin B recipients , a nonstatistically significant difference ( 95 % CI for difference , 3 to 15 days ; P = 0.15 ) . Superficial Fungal Infection Superficial infections were reported in 7 of the 420 patients receiving fluconazole ( 1.7 % ) and in 11 of 400 of those receiving amphotericin B ( 2.7 % ) , a difference of 1 percentage point ( CI for The aim of the present study was to investigate the incidence of C and ida stomatitis and result ing interruptions in radiation and radiochemotherapy in 50 patients suffering from squamous cell carcinomas of the head and neck region receiving fluconazole ( 100 mg d-1 ) in comparison with a historical control group ( n = 50 ) without specific prophylaxis . Twenty of the control patients ( 40 % ) demonstrated C and ida stomatitis , with seven of them ( 14 % ) requiring interruptions in anticancer therapy . In contrast , none of the patients with fluconazole had evidence of C and ida stomatitis ( P = 0.0000051 ) and subsequent interruption of anti-cancer therapy ( P = 0.0061 ) . Laboratory monitoring for the presence of C and ida species was performed in 30 patients before and after therapy with fluconazole . C and ida albicans was identified less frequently after therapy when compared with the pretreatment status . However , C. glabrata and C. krusei were isolated in some of the patients , probably because of drug resistance of these subspecies . The results demonstrate the clinical usefulness of prophylactic fluconazole applications in patients suffering from head and neck tumours with the aim of reducing C and ida stomatitis and the result ing interruptions in radiation and radiochemotherapy PURPOSE To characterize non-albicans C and ida oral infections in patients with head- and -neck cancer receiving external beam radiotherapy ( EBRT ) with or without concurrent chemotherapy . METHODS AND MATERIAL S Thirty-seven patients with head- and -neck cancer received EBRT in 2.0-Gy daily fractions to a median dose of 60.4 Gy ( range 38 - 82.8 , mean 64.6 ) . They were followed for oropharyngeal c and idiasis ( OPC ) confirmed by positive examination , positive KOH smear , and /or positive swab or swish culture . Sample s were identified and plated on chromogenic media to identify non-albicans yeasts . Colonies were plated on Sabouraud dextrose slants for microdilution antifungal susceptibility testing to fluconazole . DNA typing , including karyotyping , restriction fragment length polymorphism analysis , and Southern blot hybridization with the moderately repetitive Ca3 probe , was performed on selected isolates to confirm individual species . RESULTS Of the 37 patients , 10 ( 27 % ) developed OPC , and 26 ( 70.3 % ) displayed C and ida carriage state . The median EBRT dose at time of positive culture was 22.5 Gy and at time of OPC was 28.6 Gy . Of the 6 patients receiving chemotherapy and EBRT , 4 ( 66 % ) developed OPC at median dose of 27.6 Gy . Three ( 8 % ) of 37 patients were infected with non-albicans C and ida , and 3 ( 30 % ) of all 10 infections were caused by these organisms . CONCLUSION Non-albicans C and ida is emerging as a relatively common cause of OPC in head- and -neck cancer patients . Chromogenic media are helpful to screen these infections . Our data also suggest a greater likelihood of developing OPC in patients receiving concomitant chemotherapy and EBRT In order to determine the incidence rate of oral lesions associated with chemotherapy , as well as well as its association with clinical and laboratory parameters and potential risk factors , 50 in- patients with non-Hodgkin 's lymphoma or leukaemia under chemotherapy were followed from January 1993 to May 1994 . Basal and weekly oral examinations were performed . Clinical and laboratory data were registered . Wilcoxon 's rank sum test , chi square test , univariate and multivariate logistic regression analyses were used , 36 individuals with leukaemia and 14 with non-Hodgkin 's lymphoma were followed for 158 weeks ; mean age was 33 years ( range 15 - 85 ) . Oral lesion incidence rate was 45/100 patients -week . Exfoliative cheilitis and infections ( herpes and c and idosis ) were the most common oral complications , followed by haemorrhagic lesions and mucositis . Haemorrhagic lesions correlated with thrombocytopenia ( RR = 30.5 ) . Etoposide administration ( RR = 8.6 ) , alkylating agents ( RR = 15.6 ) , a prior course of chemotherapy ( RR = 23.2 ) and neutropenia ( RR = 4.16 ) were predictors of mucositis . Oral lesions were a common complication in this study , and a possible association of mucositis with several factors is suggested Infections continue to be common causes of morbidity and mortality in neutropenic patients undergoing chemotherapy for acute leukemia [ 1 , 2 ] . Although bacteria are usually the primary pathogens in neutropenic patients , most bacterial infections can now be treated successfully with currently available antibacterial drugs [ 3 , 4 ] . In contrast , fungal infections , often documented only at autopsy , are increasing in frequency in patients with acute leukemia and are now responsible for most fatal infections [ 5 - 7 ] . C and ida species are the predominant fungal pathogens , followed by Aspergillus species , the zygomycetes , and several newly recognized opportunistic fungi . Survival from invasive fungal infections has generally been poor in neutropenic patients with acute leukemia . In many cases , this poor survival can be linked to delays in diagnosis . Obstacles to the rapid diagnosis of invasive fungal infection include difficulty in isolation of fungi in cultures , inability to perform biopsies or other invasive diagnostic procedures in patients with disorders of coagulation , and the nonavailability of reliable serologic tests [ 8 ] . Because of these difficulties , amphotericin B is frequently administered empirically to patients with neutropenia and persistent fever refractory to antibacterial therapy [ 3 , 9 , 10 ] . This approach , however , is limited by the toxicity of amphotericin B , especially in patients receiving other nephrotoxic drugs . The problems associated with effective therapy of serious fungal infections in neutropenic patients with acute leukemia have been the stimulus for using antifungal drugs for prophylaxis . Unfortunately , prophylaxis with oral agents such as nystatin , clotrimazole , and ketoconazole has produced inconsistent results either due to lack of efficacy or poor patient compliance [ 11 ] . Similarly , prophylaxis with parenteral drugs like intravenous miconazole or amphotericin B has been used only on a limited basis because of concerns about toxicity and overall effectiveness [ 12 , 13 ] . Thus , there is currently no uniformly accepted or proven approach for prevention of fungal infections in neutropenic patients with acute leukemia . Fluconazole is a new triazole antifungal agent with activity against many common fungal pathogens causing infection in patients with acute leukemia [ 14 ] . Fluconazole has a favorable pharmacokinetic profile that includes a long serum half-life , making once-daily administration possible , more consistent absorption from the gastrointestinal tract than that of ketoconazole , excellent penetration into the cerebrospinal fluid , and elimination predominantly by renal mechanisms . Significant side effects related to fluconazole have been uncommon and occur less frequently than those associated with amphotericin B. Fluconazole is currently approved for treatment of C and ida and cryptococcal infections [ 15 , 16 ] . Studies in neutropenic animal models also suggest that fluconazole may be effective for prevention of C and ida infection and for treatment of invasive aspergillosis when given at high doses [ 17 , 18 ] . Similar studies in neutropenic bone marrow transplants found that prophylactic fluconazole prevents both systemic and superficial fungal infections [ 19 ] . For these reasons , we did a double-blind , placebo-controlled trial of prophylactic fluconazole in neutropenic patients undergoing chemotherapy for acute leukemia . Methods Patients Patients were eligible for the study if they satisfied the following criteria : 1 ) undergoing chemotherapy for acute leukemia or the blast crisis of chronic myelogenous leukemia ; 2 ) 13 years of age or older ; 3 ) anticipated neutropenia of less than 500 neutrophils per mm3 for 7 or more days ; 4 ) no clinical evidence of fungal infection at time of study entry ; 5 ) no systemic antifungal therapy within the 2 weeks before r and omization ; and 6 ) no allergy to the imidazoles or azoles . Patients with moderate or severe liver disease ( aspartate aminotransferase [ AST ] , alanine aminotransferase [ ALT ] , or alkaline phosphatase greater than five times the upper limit of normal or a total bilirubin greater than 43 mol/L ) and patients with renal insufficiency ( creatinine clearance of less than 0.83 mL/s ) were excluded from the study . Our trial involved 18 oncology centers . Informed consent approved by the institutional review board at each center was obtained from each patient . Study Drugs Eligible patients were r and omly assigned to receive either prophylactic fluconazole or placebo in a double-blind fashion . The fluconazole or placebo was begun at the time of initiation of chemotherapy and administered in identically appearing capsules . A capsule contained 100 mg of fluconazole , and each patient received four capsules ( 400 mg ) as a single daily dose . For patients unable to tolerate oral capsules , the fluconazole or placebo was administered intravenously . The intravenous dose of fluconazole was 200 mg every 12 hours and was infused over 1 hour . The daily dose of fluconazole was reduced in patients who developed renal failure [ 20 ] . Prophylaxis with the study drug was continued through the course of chemotherapy and neutropenia and until 7 days after the neutrophil count reached 1000 cells per mm3 or greater . The maximum duration of prophylaxis was 10 weeks . Prophylaxis was discontinued if one of the following events occurred : 1 ) development of a documented invasive fungal infection ; 2 ) initiation of empiric systemic antifungal therapy ( amphotericin B ) for clinical ly suspected invasive fungal infection ; 3 ) adverse side effects related to the study drug ; or 4 ) patient 's inability to continue in the study due to noncompliance or death . Patients who developed a documented superficial fungal infection could be treated with topical clotrimazole while continuing to receive the study drug . Laboratory Procedures Complete blood counts , prothrombin times , blood urea nitrogen levels , serum creatinine and electrolyte determinations , urinalyses , and liver function studies ( AST , ALT , alkaline phosphatase , and total bilirubin ) were obtained at the time of study entry , once or twice weekly during the study , and at the end of prophylaxis to assess patients for drug-related side effects . Patients were also examined at least twice weekly for clinical symptoms and signs of adverse effects related to the study drugs . A serum pregnancy test was done on all women of child-bearing potential before the study began . Surveillance cultures of the nasopharynx , oropharynx , axillae , urine , perirectal area , and stool were done at the time of study entry , once weekly during the study , and at the end of prophylaxis to determine the presence of fungal colonization . Cultures of blood and other suspected sites of fungal infection were obtained during the study whenever a patient 's clinical condition suggested the possibility of fungal infection . Amphotericin B therapy was initiated in accordance with previously established guidelines when a reasonable clinical suspicion of systemic fungal infection existed [ 3 , 9 , 10 ] . Definition of Fungal Colonization and Infection Fungal colonization was defined as the presence of a fungus in one or more surveillance cultures in the absence of any clinical symptoms or signs of infection . Superficial fungal infections were diagnosed by the isolation of a fungus from the skin , oropharynx , or gastrointestinal tract in association with signs of inflammation , ulcerations , plaques , or exu date s not explainable by other pathogens . Invasive fungal infections were diagnosed by the presence of fungus in the blood , pulmonary tissue or secretions , sinuses , soft tissues , or other organ structures in association with symptoms and signs of infection not explainable by other pathogens . Data Collection and Statistical Analysis Data required by the study protocol were collected and recorded in case report forms by the investigators at each oncology center . Barton and Polansky Associates independently review ed all case report forms for accuracy and compliance with the protocol by comparing the case report forms with patients ' medical and pharmacy records . The case report forms were then su bmi tted to clinical research personnel at Pfizer Central Research for review and entry of data into computer programs . All review s , classifications of infections , and data entry were done blindly before the statistical analyses were performed . Proven fungal infections were required to meet the definitions of infection established by the protocol and approved by the Federal Drug Administration before the study . There was no interim analysis . All statistical tests were performed as two-tailed tests . The Fisher exact test was used to compare differences in proportions , whereas the e quality of two distributions was compared by the Wilcoxon rank-sum test . Univariate comparisons of times to specific events were performed by using Kaplan-Meier estimates of survival distributions and the Gehan generalized Wilcoxon test [ 21 ] . The SAS procedure LIFETEST was used for these comparisons [ 22 ] . The Cochran-Mantel-Haenszel chi-square test was used to check the e quality of mean scores of ordinal response variables adjusted for center effect . Except for one placebo patient who did not receive the study drug and one fluconazole patient with invasive fungal infection at baseline , all patients were included in the efficacy analysis ( intent-to-treat analysis ) . Center by treatment interactions were tested by using the Breslow-Day test of homogeneity of odds ratio [ 23 ] . Results Patient Characteristics Two hundred fifty-seven patients were enrolled into the study . One patient r and omized to the placebo group did not receive the study drug and was excluded from all analyses . The characteristics of the other 256 patients are summarized in Table 1 . One hundred thirty-two patients received placebo , and 124 patients were given fluconazole . The two groups of patients were similar in terms of age , sex , underlying disease , and baseline fungal BACKGROUND Patients undergoing radiotherapy for head and neck cancer are at increased risk of developing oral c and idiasis . The objective of this study was to investigate the clinical C and ida mucositis and interruptions in radiotherapy in patients suffering from head and neck cancer , receiving fluconazole in comparison with a control group without specific prophylaxis . METHODS Eighty consecutive patients were r and omized in a prospect i ve double-blind trial of prophylactic oral fluconazole or treatment with the same drug when mycotic infections appeared . Adult head and neck cancer patients who were undergoing treatment with radiotherapy and /or chemotherapy , radiotherapeutic coverage of the entire oropharynx and oral cavity at least 3 cm anterior to the retromolar trigone and receiving a total dose of more than 6000 cGy and Karnofsky Performance Status ( KPS ) > 70 were included in the study . Group A received radiation therapy plus fluconazole ( Fluzole 100 mg/day ) starting from the sixth irradiation session throughout the treatment ; 40 patients in group B received the same baseline treatment , but were given fluconazole only when mycotic infections appeared . RESULTS We evaluated 37 patients in group A and the first 37 patients were evaluated in group B. Three of the patients in group A ( 8.1 % ) and 14 of the patients in group B ( 37.8 % ) demonstrated clinical c and idasis . Radiotherapy was interrupted in all of these patients . The differences between the two groups were statistically significant with respect to clinical c and idiasis ( P = 0.005 ) . The median discontinuation time was 5 days ( range , 3 - 7 days ) in group A and 7 days ( range , 4 - 10 days ) in group B. The median dose result ing in clinical c and idiasis was 3200 cGy ( range , 2200 - 5800 cGy ) in all groups . In the fluconazole group it was 4200 cGy and in the control group 2800 cGy . CONCLUSION These results suggest that patients undergoing head and neck radiation therapy are at risk of developing c and idiasis and that fluconazole may be used to reduce the frequency of mycotic infections and to improve the radiotherapy schedule in head and neck cancer patients Fungal colonization profiles from four different anatomical sites were evaluated in 266 neutropenic cancer patients receiving intensive cytotoxic therapy for acute leukaemia or for autologous marrow transplantation . At the beginning of chemotherapy patients were allocated r and omly to receive oral fluconazole 400 mg daily or an identical placebo until prophylaxis failure or marrow recovery . C and ida albicans colonization was reduced from 30 to 10 % in the fluconazole recipients while it increased from 32 to 57 % in the placebo patients ( P<0.001 ) . By the end of prophylaxis , colonization with non-albicans C and ida species increased from 7 to 21 % and 8 to 18 % in the fluconazole and placebo patients , respectively ( P = 0.396 ) . Although C and ida glabrata was isolated more frequently at the end of the prophylactic period in the fluconazole patients than in the placebo patients ( 16 versus 7 % ) , only one definite invasive C. glabrata infection was noted . Overall , definite invasive fungal infections were documented in 26 patients [ four fluconazole versus 22 placebo patients ( P < or = 0.001 ) ] . In 23 ( 92 % ) patients the infections were caused by persistently colonizing or newly acquired organisms . While probable invasive fungal infections were noted in five fluconazole patients , 10 placebo patients were also affected ( P = 0.19 ) . An end-of-prophylaxis colonization index > 0.25 was 76 % sensitive but only 69 % specific for invasive fungal infection . However , a colonization index < or = 0.25 at baseline had a negative predictive value of 88 % for development of invasive fungal infection . Fluconazole prophylaxis decreased colonization by fungi and subsequent invasive fungal infections in neutropenic cancer patients In this multicentre , r and omised , double-blind study , the safety and efficacy of oral fluconazole ( 200 micrograms/day ) and nystatin suspension ( 6,000,000 IU/day ) for the prevention of fungal infections were compared in patients with leukaemia undergoing remission induction chemotherapy . Antifungal prophylaxis was initiated at the time chemotherapy was started and continued throughout the hospital stay or the period of neutropenia to a maximum of 42 days . Prophylaxis was successful ( no evidence of fungal infection or fever of unknown origin unresponsive to antibiotics ) in 38 of 56 ( 68 % ) fluconazole-treated and 25 of 53 ( 47 % ) nystatin-treated patients ( P = 0.03 ) . 2 patients ( 4 % ) in the fluconazole group and 6 ( 11 % ) patients in the nystatin group developed systemic fungal infections ( P = 0.15 ) . The overall frequency of adverse events was similar among fluconazole-treated ( 29 % ) and nystatin-treated ( 32 % ) ; most events in both treatment groups involved the gastrointestinal tract . These results indicated fluconazole was more effective than nystatin in preventing C and ida infections in patients with leukaemia ; fluconazole was well tolerated |
12,772 | 20,506,175 | Comparative analyses revealed that interventions utilizing more self-regulation techniques reduced depressive symptoms and anxiety significantly more than interventions utilizing fewer such techniques .
Additionally , depressive symptoms were reduced significantly more among recently diagnosed RA patients than among those with longst and ing RA .
Psychological interventions are beneficial for many patients with RA , particularly when it comes to increasing physical activity levels .
Intervention techniques derived from self-regulation theory appear to play a role in reducing depressive symptoms and anxiety among patients with RA | OBJECTIVE To examine the efficacy of psychological interventions for rheumatoid arthritis ( RA ) , and to determine whether self-regulation interventions demonstrate efficacy superior to that of other psychological treatments . | OBJECTIVE Joint protection aims to reduce pain and local inflammation , preserve the integrity of joint structures and improve function . There is evidence that it can improve pain and function in the short term , but the long-term effects are uncertain . This study evaluated the effects of joint protection in early rheumatoid arthritis ( RA ) . METHODS A r and omized , controlled , assessor-blinded trial of duration 1 yr was conducted . Two interventions ( both 8 h ) were compared : st and ard arthritis education , including 2.5 h of joint protection education based on typical UK practice ; and a joint protection arthritis education programme , using educational-behavioural teaching methods . Assessment s were made at entry and 6 and 12 months . RESULTS Sixty-five people with RA attended the joint protection programme and 62 the st and ard programme . The groups were matched for age ( 51 and 49 yr ) , disease duration ( 21 and 17.5 months ) and use of non-steroidal anti-inflammatory drugs and disease-modifying anti-rheumatic drugs . In comparison with the st and ard group , the joint protection group significantly improved with respect to adherence to the joint protection programme ( P=0.001 ) , h and pain ( P=0.02 ) , general pain ( P=0.05 ) , early morning stiffness ( P=0.01 ) , self-reported number of disease flare-ups ( P=0.004 ) , visits to the doctor for arthritis ( P<0.01 ) , and the AIMS 2 ( Arthritis Impact Measurement Scales ) activities of daily living scale ( P=0.04 ) . A trend to improved swollen joint counts was identified ( P=0.07 ) . Within-group analyses also showed improvements in arthritis self-efficacy and perceived control . H and deformity scores continued to increase in both groups . CONCLUSION We found significant improvements in adherence , pain , disease status and functional ability amongst those attending the joint protection programme . Benefits became more apparent with time , suggesting that joint protection can help slow the progression of the effects of RA over and above the effects of drug therapy The present study examined the efficacy of a behavioral intervention design ed to increase adherence to fluid-intake restrictions among hemodialysis patients . Twenty intervention-group patients were compared with 20 matched control patients on an indicator of fluid-intake adherence at 3 time points . The Group x Time interaction was significant , indicating that patients in the 2 groups exhibited a differential pattern of change in fluid-intake adherence across the follow-up period . The intervention and control groups did not differ significantly in terms of adherence at the initial postintervention period but did differ at the 8-week follow-up . The observed group differences were , in part , due to a trend toward increasingly better adherence in the intervention group and poorer adherence in the control group across the follow-up period Developing more effective behavioural interventions requires an underst and ing of the mechanisms of behaviour change , and methods to rigorously test their theoretical basis . The delivery and theoretical basis of an intervention protocol were assessed in ProActive , a UK trial of an intervention to increase the physical activity of those at risk of Type 2 diabetes ( N = 365 ) . In 108 intervention sessions , behaviours of facilitators were mapped to four theories that informed intervention development and behaviours of participants were mapped to 17 theoretical components of these four theories . The theory base of the intervention specified by the protocol was different than that delivered by facilitators , and that received by participants . Of the intervention techniques delivered , 25 % were associated with theory of planned behaviour ( TPB ) , 42 % with self-regulation theory ( SRT ) , 24 % with operant learning theory ( OLT ) and 9 % with relapse prevention theory ( RPT ) . The theoretical classification of participant talk showed a different pattern , with twice the proportion associated with OLT ( 48 % ) , 21 % associated with TPB , 31 % with SRT and no talk associated with RPT . This study demonstrates one approach to assessing the extent to which the theories used to guide intervention development account for any changes observed OBJECTIVE In rheumatoid arthritis , education programmes successfully impart knowledge but , notwithst and ing issues of empowerment , this knowledge has to be translated into behavioural change to have a chance of improving disease outcome . Arguably , behavioural change must also occur early if outcomes are to be improved . For these reasons , we planned a study of patient education in early disease , with radiological damage and quality of life as the main outcome variables . METHODS We performed a r and omized controlled trial in people with rheumatoid arthritis of < 5 yr duration . The main intervention was a 4 week education programme , each weekly session lasting 2 h. Assessment s were made at entry , at 4 weeks and at 12 months . The main outcome variables were the modified Larsen radiological score for the h and s and the SF-36 quality of life question naire . Secondary outcome variables were the Health Assessment Question naire ( HAQ ) , Ritchie Articular Index ( RAI ) , Patient Knowledge Question naire ( PKQ ) , Compliance Question naire ( CQ ) , plasma viscosity ( PV ) , pharmaceutical changes and consulting behaviour . RESULTS The patient numbers were 34 ( 10 male , 24 female ) for the control group and 43 ( 16 male , 27 female ) for the education group . The groups were matched for age ( 56.5 yr for control , 55 yr for education ) , disease duration ( 3.5 yr vs 3.0 yr ) and duration of second-line drug therapy ( 14 months vs 12 months ) . We found no significant difference between the groups for Larsen scores at 12 months , although scores for the education group were lower ( 39.5 vs 43.0 , P = 0.13 ) . The ' social functioning ' and ' general health perception ' subscales of the SF-36 showed a significant improvement in the education group , but no significant differences between groups were seen . No significant differences were found for the HAQ , RAI , PV and CQ , but the education group had more disease-specific knowledge than the control group at 12 months ( PKQ scores : 17 vs 21 , P = 0.0002 ) . No differences were found for out-patient visits and in-patient admissions , but the education group had slightly more changes in second-line drugs during the study ( 0.43 changes/person in the control group , 0.51 changes/person in the education group ) . CONCLUSIONS We found no significant difference between the groups in our primary outcome measures , but a trend in favour of the education group was found in radiological progression . Further studies of this kind , using larger patient numbers , are required since the difference may result from improved self-care , better compliance with joint protection strategies and , possibly , improved drug compliance Group counseling and education were studied in patients with rheumatoid arthritis ( RA ) . Patients were matched and r and omly assigned to a control ( CG ) or experimental ( EG ) group . Each group attended an educational session but only the EG participated in 12 weekly group counseling sessions . A test of knowledge about RA and psychological tests were administered before and after these sessions . The EG improved their scores in 2 areas of self-concept and in factual knowledge . There was no increase in depression level . These results provide evidence that formal educational sessions and group counseling may be important in the management of patients with RA The purpose of the study was to investigate the effects of supervised muscle relaxation training in individuals with rheumatoid arthritis ( RA ) . Sixty-eight participants were allocated at r and om either to a muscle relaxation training group or to a control group . Every participant was evaluated for health-related quality of life , muscle function , pain , and disease activity . The training group exercised 30 minutes , twice a week for 10 weeks , while no intervention was made in the control group . The results indicated improvements in the training group regarding self-care according to the Arthritis Impact Measurement Scales 2 , and in recreation and pastimes according to the Sickness Impact Profile-RA ( p < 0.05 ) directly after the intervention . Mobility and arm function ( p < 0.01 ) according to the Arthritis Impact Measurement Scales 2 , and muscle function of the lower limbs ( p < 0.05 ) were improved after six months . No improvements remained after twelve months . It thus seems that 10 weeks ' relaxation training might have some short-term influence in individuals with RA OBJECTIVE To investigate the effects of a 21-week concurrent strength and endurance training protocol on physical fitness profile in women with early or longst and ing rheumatoid arthritis ( RA ) compared with healthy subjects . METHODS Twenty-three female patients with RA volunteered for the study . Twelve had early RA and eleven had longst and ing RA . Twelve healthy women served as controls . Maximal strength of different muscle groups was measured by dynamometers , walking speed with light cells , and vertical squat jump on the force platform to mirror explosive force . Maximal oxygen uptake was measured by gas analyzer . Six training sessions ( 3 strength training and 3 endurance training ) were carried out in a 2-week period for 21 weeks . RESULTS The training led to large gains in maximal strength both in women with RA and in healthy women ( P < 0.043 - 0.001 ) . The strength gains were accompanied by increases in walking speed ( P < 0.034 - 0.001 ) and vertical squat jump ( P < 0.034 - 0.001 ) . Significant improvements also occurred in maximal aerobic capacity in all groups ( P < 0.023 - 0.014 ) . CONCLUSIONS Both early and longst and ing RA patients with stable disease can safely improve all characteristics of their physical fitness profile using a progressive concurrent strength and endurance training protocol & NA ; This study examined the efficacy of a cognitive and behavioural intervention ( CBT ) for patients with recent onset , seropositive rheumatoid arthritis . Fifty‐three participants with a diagnosis of classical or definite rheumatoid arthritis , who were seropositive and had less than 2 years of disease history were recruited into the trial . All participants received routine medical management during the study , although half were r and omly allocated to receive an adjunctive psychological intervention . All pre‐ and post‐treatment assessment s were conducted blind to the allocation . Analyses were conducted of treatment completers and also by intention‐to‐treat . Significant differences were found between the groups at both post‐treatment and 6‐month follow‐up in depressive symptoms . While the CBT group showed a reduction in depressive symptoms , the same symptoms increased in the St and ard group . At outcome but not follow‐up , the CBT group also showed reduction in C‐reactive protein levels . However , the CBT group did show significant improvement in joint involvement at 6‐month follow‐up compared with the St and ard group , indicating physical improvements above those achieved with st and ard care . These results indicate that cognitive‐behavioural intervention offered as an adjunct to st and ard clinical management early in the course of RA is efficacious in producing reductions in both psychological and physical To examine the effectiveness of a cognitive-behavioral pain management program for patients with rheumatoid arthritis , three patient groups were studied : a cognitive-behavioral group ( CB ) , an attention-placebo group , and a control group . The CB group received a comprehensive , 12-month pain management program that taught coping strategies such as problem-solving techniques , relaxation training , strategies for attention diversion , and training in family dynamics and communication . Dependent measures included pain , coping strategies , psychological status , functional status , and disease status . Data analysis at 12 months revealed benefits for the CB group in the area of enhanced coping strategies . Specifically , the CB subjects showed significantly greater use of coping strategies and significantly more confidence in their ability to manage pain . The findings are discussed in terms of the importance of enhanced self-efficacy and personal control for patients with rheumatoid arthritis The objective of this study was to determine whether the Arthritis Self-Management Programme ( ASMP ) improves perceptions of control , health behaviours and health status , and changes use of health care re sources . The design was a pragmatic r and omized controlled study ; participants were allocated to ASMP ( Intervention Group ) or a 4-month waiting-list Control Group . The Intervention Group completed a 12-month follow-up . In total , 544 people with arthritis were recruited from the community--311 in the Intervention Group and 233 in the Control Group . Main outcome measures included : arthritis self-efficacy , health behaviours ( exercise , cognitive symptom management , diet and relaxation ) and health status ( pain , fatigue , anxiety , depression and positive affect ) . At 4 months follow-up , the ASMP had a significant effect on arthritis self-efficacy for other symptoms and pain subscales . Performance of a range of health behaviours ( cognitive symptom management , communication with physicians , dietary habit , exercise and relaxation ) was significantly greater among the Intervention Group . The Intervention Group were significantly less depressed and had greater positive mood . In addition , trends towards decreases on fatigue and anxiety were noted . Physical functioning , pain and GP visits remained stable at 4 months . A similar pattern of findings was found at 12 months follow-up for the Intervention Group . Furthermore , a significant improvement was found on pain and visits to GPs had decreased . Apart from a small improvement on physical functioning among the Intervention Group participants with osteoarthritis 12 months , all effects were independent of the type of arthritis . The findings suggest that the ASMP is effective in promoting improvements in perception of control , health behaviours and health status , when delivered in UK setting OBJECTIVE To examine relationships among changes in self-efficacy and changes in other clinical ly relevant outcome measures . METHOD Subjects ( n = 44 ) were participants in a prospect i ve , r and omized stress-management study followed over 15 months . Outcome measures included self-efficacy , depression , pain , health status , and disease activity . RESULTS Correlational analyses revealed significant associations between changes in self-efficacy ( particularly total self-efficacy ) and changes in selected measures of depression , pain , health status , and disease activity . The observed associations were not due to changes in medication regimen or to nonadherence to the stress-management program . CONCLUSIONS Evidence is provided that induced changes in self-efficacy following a stress-management program were significantly related to other clinical ly important outcome measures Preliminary work regarding the development and pilot study of an individualized instructional program for rheumatoid arthritis clients is presented . The effect of the individualized instructional program was tested with 31 out patients . Using analysis of covariance , the experimental group subjects scored significantly higher on the knowledge post-test when compared to scores of control group subjects ( P = 0.0045 ) . Analysis of variance for repeated measures revealed no significant difference in performance of tasks for the control group and experimental group ( P = 0.08 ) . In a follow-up study , the effect of the self-instructional program , practice time , and contracting were explored for their effect on adherence to self-care activities . Experimental groups ( n = 42 ) scored significantly better than the control group ( n = 11 ) on the knowledge post-test ( P < 0.01 ) , performance of joint protection practice s ( P = 0.01 ) , range of motion exercises ( P = 0.01 ) , and adherence to joint protection practice s at home ( P < 0.01 ) . Groups did not differ on adherence to range of motion exercises at home ( P = 0.83 ) OBJECTIVE To assess the effect of a meditation training program , Mindfulness-Based Stress Reduction ( MBSR ) , on depressive symptoms , psychological status , and disease activity in patients with rheumatoid arthritis ( RA ) through a r and omized , waitlist-controlled pilot study . METHODS Participants were r and omized to either an MBSR group , where they attended an 8-week course and 4-month maintenance program , or to a waitlist control group , where they attended all assessment visits and received MBSR free of charge after study end . Participants received usual care from their rheumatologists throughout the trial . Self-report question naires were used to evaluate depressive symptoms , psychological distress , well-being , and mindfulness . Evaluation of RA disease activity ( by Disease Activity Score in 28 joints ) included examination by a physician masked to treatment status . Adjusted means and mean changes in outcomes were estimated in mixed model repeated measures analyses . RESULTS Sixty-three participants were r and omized : 31 to MBSR and 32 to control . At 2 months , there were no statistically significant differences between groups in any outcomes . At 6 months , there was significant improvement in psychological distress and well-being ( P = 0.04 and P = 0.03 , respectively ) , and marginally significant improvement in depressive symptoms and mindfulness ( P = 0.08 and P = 0.09 , respectively ) . There was a 35 % reduction in psychological distress among those treated . The intervention had no impact on RA disease activity . CONCLUSION An 8-week MBSR class was not associated with change in depressive symptoms or other outcomes at 2-month followup . Significant improvements in psychological distress and well-being were observed following MBSR plus a 4-month program of continued reinforcement . Mindfulness meditation may complement medical disease management by improving psychological distress and strengthening well-being in patients with RA In order to examine the effectiveness of cognitive behavioral therapy for patients with rheumatoid arthritis ( RA ) three patients groups were studied : a cognitive behavioral therapy group ( CBT ) , an occupational therapy group ( OT ) , and a waiting-list control group . The CBT received a comprehensive , 10-session treatment package that taught progressive relaxation , rational thinking and the differential use of pain coping strategies . CBT result ed in minor changes in pain coping behavior at posttreatment , while CBT and OT showed an increase of knowledge of RA . No therapeutic effects with regard to health status were demonstrated at posttreatment and at 6 months follow-up . Clinical and laboratory measures of disease activity revealed progressive deterioration of the patients during the course of the study . It is suggested that the ineffectiveness of CBT might be due to the progressive course of RA in the patients studied , as well as to the rather small changes in coping behavior OBJECTIVE To determine whether a patient education programme ( PE ) would improve rates of adherence to a slow acting antirheumatic drug and to assess any subsequent effect on patient outcome . METHODS A r and omly controlled study comprising 100 patients with rheumatoid arthritis ( 49 control CG ; 51 experimental EG ) requiring D-penicillamine ( DPA ) . The same practitioner saw patients on seven occasions , for the same length of time . The EG received 7 x 30 minute one to one sessions of PE , while the CG received st and ard management . The primary measure of adherence was a pharmacological marker ( phenobarbitone ) encapsulated with the DPA assayed at monthly intervals for six months . Plasma viscosity ( PV ) , C reactive protein , articular index , morning stiffness , and pain score were used to assess outcome . RESULTS 454 blood sample s were collected and assayed and the pharmacological marker showed the EG to be significantly more adherent on more occasions than the CG ( p<0.05 ) . Patterns of adherence over time showed that at 12 weeks 86 % ( 38/44 ) of those in the EG compared with 64 % ( 29/45 ) of the CG remained adherent ( p=0.01 ) . These trends continued and by the end of the study 85 % ( 29/34 ) of the EG compared with 55 % ( 23/42 ) of the CG were taking their DPA as prescribed . Fifteen patients ( 12 from the EG ) experienced side effects requiring study withdrawal and 14 patients requested study withdrawal ( two from the EG ) . On study entry patients in the CG had significantly higher levels of PV than the EG and this remained so throughout the research . However , on completion , the health status of patients in both groups had improved significantly ( p<0.01 ) . CONCLUSIONS PE significantly increased adherence to DPA and its effects persisted over a period of six months . No additional clinical benefit was detected in the EG in comparison with the CG OBJECTIVES To determine the effects of patient education on compliance and on health in patients with active , recent onset rheumatoid arthritis ( RA ) . METHODS A r and omised , controlled , assessor blinded , one year trial . The experimental group followed an education programme . All patients started on sulphasalazine therapy . Compliance with sulphasalazine was measured by pill counting . Compliance rates with regimens of physical exercise , endurance activities , and energy conservation were measured by question naires . Compliance with prescriptions of joint protection was scored using a test for joint protection performance . Health was measured by a Disease Activity Score ( function of erythrocyte sedimentation rate , Ritchie score , and number of swollen joints ) , C reactive protein , Dutch- AIMS scores , and M-HAQ scores , range of motion of shoulder , elbow , and knee joints . Parameters were scored at baseline and after three , six , and 12 months . RESULTS Sixty of 65 patients gave informed consent , five of them withdrew from follow up . Compliance with sulphasalazine exceeded 80 % with no differences between groups . Compliance with physical exercise ( at three months ) , energy conservation ( at three and at 12 months ) , and joint protection ( at three months ) improved significantly more in the experimental group . The improvements of health were not different in the groups . CONCLUSION Compliance with sulphasalazine among patients with active , recent onset RA is high , whether formal patient education is followed or not . Compliance with physical exercise , energy conservation , and joint protection was increased by patient education . Formal patient education did not improve health status OBJECTIVE To examine the effects of stress-management training on clinical outcomes in persons with rheumatoid arthritis ( RA ) . METHODS Patients with RA ( n = 141 ) were r and omly assigned to 1 of 3 groups : a stress management group , an attention control group , or a st and ard care control group . The stress management and the attention control groups received a 10-week intervention followed by an additional 15-month maintenance phase . RESULTS The stress management group showed statistically significant improvements on measures of helplessness , self-efficacy , coping , pain , and health status . Selected beneficial effects were still detectable at the 15-month followup evaluation . CONCLUSION The data indicated that stress management interventions are capable of producing important clinical benefits for persons with RA OBJECTIVE To assess the sustainable benefits of a professional , multidisciplinary training program for patients with rheumatoid arthritis . DESIGN Two studies with different observation periods . Study I was a prospect i ve , r and omized trial for 1 year . Study II was a noncontrolled observation over 5 years . SETTING The 9-day program for eight patient groups encompassed a multidisciplinary cooperation between rheumatologists , orthopedists , physicotherapists , psychologists and social workers . PATIENTS Sixty-eight consecutive patients with rheumatoid arthritis participated in an arthritis training program either immediately after enrollment in the program or after 1 year . INTERVENTIONS The program covered the following fields : pathogenesis of rheumatoid arthritis , drug therapy , physicotherapy , practical exercise in remedial gymnastics , use of joint protection devices , orthopedic perspectives , psychological counseling , dietetics , information about unproven cures and social assistance . MAIN OUTCOME MEASURES Clinical outcome was assessed by self-report question naires : ( 1 ) Stanford Health Assessment Question naire , ( 2 ) Freiburg Question naire of Coping with Illness , ( 3 ) Beck Depression Inventory , and ( 4 ) a 21-point scale to evaluate cognitive-behavioral and environmental impact . RESULTS A significant and persistent improvement of all investigated parameters was demonstrated in the 1-year controlled trial . Between the end-point of the 1-year study and the 5-year evaluation , this improvement increased even more for functional status and coping with illness , whereas depression returned to baseline values . These effects were seen even without reinforcement of the training . CONCLUSION A professional , multidisciplinary approach to educate patients with rheumatoid arthritis leads to a significant and sustained improvement of the clinical outcome and is an approach that should be established as a part of conventional therapy Because there is little information about the efficacy of home occupational therapy , we decided to assess the effects of a home service on patients with rheumatoid arthritis . 105 patients aged 18 - 70 years , on stable medical therapy , were r and omised to receive a 6-week comprehensive programme of occupational therapy ( experimental group , 53 patients ) or to receive no such treatment ( control group , 52 ) . At 6 weeks , control patients received the experimental regimen , and experimental patients were continued on treatment as needed up to 12 weeks . Outcomes were measured at baseline , 6 , and 12 weeks with a global functional capacity score ( functional score ) . At 6 weeks the functional score for the experimental group was significantly higher than that for the control group ( mean difference = 8.1 , 95 % Cl 1.7 to 15.8 , p = 0.012 ) . Control patients at 12 weeks showed a similar improvement to experimental patients at 6 weeks , and between 6 and 12 weeks the experimental patients were stable . Occupational therapy leads to a statistically significant and clinical ly important improvement in function in patients with rheumatoid arthritis BACKGROUND Women with asthma have greater mortality and morbidity than men in the United States . To date , there has been no rigorous evaluation of an intervention focused on the particular problems in asthma management faced by women . This study was a r and omized clinical trial of a self-regulation , telephone counseling intervention emphasizing women 's concerns , and sex and gender role factors in their management of asthma . METHODS A total of 808 women with diagnosed asthma were r and omly assigned to the intervention group or a usual-care control group , including conventional asthma education . Interviews and medical record data were collected to assess psychosocial factors , and the behavioral factors of functioning , quality of life , symptoms , and health-care use at baseline and the subsequent 1 year . Generalized estimating equations , identity link , logit link , and log link were employed to analyze the data . RESULTS Compared to control subjects , the women receiving treatment had greater annual reductions in the average number of nights with asthma symptoms ( p = 0.04 ) , days of missed work/school ( p = 0.03 ) , emergency department visits ( p = 0.04 ) , unscheduled office visits ( p = 0.01 ) , and scheduled office visits ( p = 0.04 ) . They had greater recognition of asthma symptoms during the menstrual cycle ( p = 0.0003 ) , had decreased asthma symptoms with sexual activity ( p = 0.008 ) , and had greater improvement in quality of life ( p = 0.0005 ) , self-regulation ( p = 0.03 ) , and self-confidence to manage asthma ( p = 0.001 ) . CONCLUSION The intervention improved women 's clinical status , functioning , quality of life , and health-care use . A program with a focus on asthma management problems particular to women can significantly assist female asthma patients OBJECTIVES To determine 4-month and 1-year health-related outcomes of a 6-week , lay-led , and community-based arthritis self-management program for Spanish-speaking participants and to determine the role of self-efficacy in predicting health status for this population . METHODS Three hundred and thirty one subjects were r and omized to the program or to a 4-month wait list control group . One hundred ninety eight subjects continued in a 1-year longitudinal study . Data were collected via mailed question naires with telephone follow up . RESULTS At 4 months , treatment subjects , compared with controls , demonstrated positive changes in exercise , disability , pain , and self-efficacy ( P < 0.05 ) . At 1 year , compared with baseline , treatment subjects demonstrated improvements in exercise , general health , disability , pain , self-efficacy , and depression ( P < 0.05 ) . Baseline and 4-month changes in self-efficacy predicted health status at 1 year . CONCLUSIONS Spanish-speaking participants of an arthritis self-management program demonstrate short- and long-term benefits ( improved health behaviors , health status , and self-efficacy ) OBJECTIVE To develop and evaluate the effect of a new arthritis education program based on a previous study . METHODS One hundred individuals with established rheumatoid arthritis r and omized to an intervention group or a control group completed self-report question naires . RESULTS Three months after the education program the patients in the intervention group had increased their knowledge about their disease . They reported increased practice of exercise and joint protection and reduction of disability and pain . After 12 months , increased knowledge and practice of joint protection was maintained . However , there was no longer any difference between the intervention group and the control group regarding reported pain , disability , and practice of exercise . At both intervals the individuals in the intervention group reported an increased ability to h and le their pain and a reduction of problems with their disease . The control group remained stable except for a slight increase in pain . CONCLUSION A structured patient education program had positive impact for 3 months , and some improvements were maintained for 12 months . We suggest that patient education should become an integrated part of the total management of rheumatoid arthritis Stress management and mutual support groups are employed widely in chronic illness , although their efficacy has not been established . To determine the effect of these measures on morbidity and psychologic health in rheumatoid arthritis , 105 patients meeting diagnostic criteria for rheumatoid arthritis were evaluated for depression , life satisfaction , functional disability , and indicators of disease activity . Patients were r and omly assigned to one of three groups : ( 1 ) stress management ; ( 2 ) mutual support ; ( 3 ) no intervention ( control ) . After completion of 10 weekly sessions , identical tests were performed for all patients in the intervention and control groups . Patients in the intervention groups showed greater improvement in joint tenderness than did the control patients but did not differ significantly from the patients in the control group in any of the other outcome measures OBJECTIVE There are insufficient data on the effects of long-term intensive exercise in patients with rheumatoid arthritis ( RA ) . We undertook this r and omized , controlled , multicenter trial to compare the effectiveness and safety of a 2-year intensive exercise program ( Rheumatoid Arthritis Patients In Training [ RAPIT ] ) with those of physical therapy ( termed usual care [ UC ] ) . METHODS Three hundred nine RA patients were assigned to either the RAPIT program or UC . The primary end points were functional ability ( assessed by the McMaster Toronto Arthritis [ MACTAR ] Patient Preference Disability Question naire and the Health Assessment Question naire [ HAQ ] ) and the effects on radiographic progression in large joints . Secondary end points concerned emotional status and disease activity . RESULTS After 2 years , participants in the RAPIT program showed greater improvement in functional ability than participants in UC . The mean difference in change of the MACTAR Question naire score was 2.6 ( 95 % confidence interval [ 95 % CI ] 0.1 , 5.2 ) over the first year and 3.1 ( 95 % CI 0.7 , 5.5 ) over the second year . After 2 years , the mean difference in change of the HAQ score was -0.09 ( 95 % CI -0.18 , -0.01 ) . The median radiographic damage of the large joints did not increase in either group . In both groups , participants with considerable baseline damage showed slightly more progression in damage , and this was more obvious in the RAPIT group . The RAPIT program proved to be effective in improving emotional status . No detrimental effects on disease activity were found . CONCLUSION A long-term high-intensity exercise program is more effective than UC in improving functional ability of RA patients . Intensive exercise does not increase radiographic damage of the large joints , except possibly in patients with considerable baseline damage of the large joints This study investigated factors related to an initial exercise experience to explain exercise maintenance in 120 adults with rheumatoid arthritis or osteoarthritis . Integral secondary analysis was used to incorporate data from a prospect i ve , controlled trial of exercise ( Minor et al. : Arthritis Rheum 32:1396 , 1989 ) with data collected at 18 months follow-up . The dependent variable was self-directed exercise ( min/wk ) reported at 3 , 9 , and 18 or more months after exercise class participation . Predictor variables included physical , psychosocial , disease , and programmatic factors . The all possible regressions search procedure result ed in three explanatory models ( p = .0001 ) . At 3 months the model ( R2 = .45 ) included initial aerobic capacity , depression , and anxiety ; and changes in depression and social activity . The 9-month model ( R 2 = .35 ) consisted of initial anxiety and physical activity , change in depression , support of friends for exercise , and exercise behavior at prior assessment . At 18 or more months ( R2 = .42 ) , model variables were initial aerobic capacity , change in pain , and exercise behavior at the two prior assessment s. Neither disease nor program factors appeared as significant . This limited study indicates that factors associated with exercise behavior in this sample are similar to those in the general population ; explanatory factors change over time , and changes ascribed to a trial behavior may influence subsequent decision making & NA ; Recent developments in chronic pain research suggest that effectiveness of cognitive‐behavioral therapy ( CBT ) may be optimized when applying early , customized treatments to patients at risk . For this purpose , a r and omized , controlled trial with tailor‐made treatment modules was conducted among patients with relatively early rheumatoid arthritis ( RA disease duration of < 8 years ) , who had been screened for psychosocial risk profiles . All participants received st and ard medical care from a rheumatologist and rheumatology nurse consultant . Patients in the CBT condition additionally received an individual CBT treatment with two out of four possible treatment modules . Choice of treatment modules was determined on the basis of patient priorities , which result ed in most frequent application of the fatigue module , followed by the negative mood , social relationships and pain and functional disability modules . Analyses of completers and of intention‐to‐treat revealed beneficial effects of CBT on physical , psychological and social functioning . Specifically , fatigue and depression were significantly reduced at post‐treatment and at the 6‐month follow‐up in the CBT condition in comparison to the control condition , while perceived support increased at follow‐up assessment . In addition , helplessness decreased at post‐treatment and follow‐up assessment , active coping with stress increased at post‐treatment , and compliance with medication increased at follow‐up assessment in the CBT condition in comparison to the control condition . Results indicate the effectiveness of tailor‐made CBT for patients at risk in relatively early RA , and supply preliminary support for the idea that customizing treatments to patient characteristics may be a way to optimize CBT effectiveness in RA patients OBJECTIVE This trial was performed to evaluate the efficacy of an adjunctive cognitive-behavioral treatment compared with rheumatological treatment alone in unselected rheumatoid arthritis out patients . DESIGN A prospect i ve r and omized control design was used . Change in medication during treatment was controlled by matching therapy- and control-group subjects according to this change in medication , sex , age , duration of disease , and functional class . SETTING A rheumatological outpatient clinic , University of Goettingen , Germany . PATIENTS Fifty-five consecutive out patients with a diagnosis of rheumatoid arthritis ( age 52.7 years , 74.5 % female , duration of disease 9.4 years ) finished the study . INTERVENTIONS Subjects received routine care by the rheumatologists and routine medical treatment . Cognitive-behavioral treatment subjects ( n = 19 ) received adjunctive st and ardized cognitive-behavioral group treatment with 12 weekly sessions . OUTCOME MEASURES Outcome measures included disease activity variables , pain variables ( pain intensity , affective pain ) , psychological symptoms , and coping . RESULTS Subjects mostly demonstrated an increasing disease activity during treatment ; change in medication during treatment was necessary in some patients . In the cognitive-behavioral treatment group the course of rheumatoid arthritis seemed less progressive than in the control group . The core effects of cognitive-behavioral treatment pertain more to improved coping , emotional stabilization , and reduced impairment than to reduced pain intensity . Passive , emotion-focused coping , helplessness , depression , anxiety , affective pain , and fluctuation of pain are reduced , " Acceptance of Illness " is improved . CONCLUSIONS Cognitive-behavioral therapy has proven an effective adjunct to st and ard treatment of rheumatoid arthritis out patients . These effects were shown in an unselected sample with increasing disease activity and with comparable changes in medication during treatment . We recommend cognitive-behavioral treatment as an desirable adjunct to st and ard medical treatment of rheumatoid arthritis Patients with rheumatoid arthritis must learn to adjust their exercise , rest and medication to the varying activity of the disease . Patient education can help patients in making the right decisions about adjustments in their treatment regimen and in attaining " self-management " behaviors . We developed a group education program based on social learning theory and the ' Arthritis Self-Management Course ' developed in the USA by Lorig . Goal of the program is the strengthening of self-efficacy , outcome expectations and self-management behaviors of RA patients which may lead to better health status . The program has been evaluated in an experimental design . We established significant positive effects of the group training on functional disability , joint tenderness , practice of relaxation and physical exercises , self-management behavior , outcome expectations , self-efficacy function and knowledge . After 14 months we still found effects on practice of physical exercises , self-efficacy function and knowledge |
12,773 | 18,518,981 | Efficacy was higher for meditation , among volunteers and for longer treatments .
Conclusion The results show consistent and significant efficacy of relaxation training in reducing anxiety .
This meta- analysis extends the existing literature through facilitation of a better underst and ing of the variability and clinical significance of anxiety improvement subsequent to relaxation training | Background Relaxation training is a common treatment for anxiety problems .
Lacking is a recent quantitative meta- analysis that enhances underst and ing of the variability and clinical significance of anxiety reduction outcomes after relaxation treatment . | Objective : The underlying changes in biological processes that are associated with reported changes in mental and physical health in response to meditation have not been systematic ally explored . We performed a r and omized , controlled study on the effects on brain and immune function of a well‐known and widely used 8‐week clinical training program in mindfulness meditation applied in a work environment with healthy employees . Methods : We measured brain electrical activity before and immediately after , and then 4 months after an 8‐week training program in mindfulness meditation . Twenty‐five subjects were tested in the meditation group . A wait‐list control group ( N = 16 ) was tested at the same points in time as the meditators . At the end of the 8‐week period , subjects in both groups were vaccinated with influenza vaccine . Results : We report for the first time significant increases in left‐sided anterior activation , a pattern previously associated with positive affect , in the meditators compared with the nonmeditators . We also found significant increases in antibody titers to influenza vaccine among subjects in the meditation compared with those in the wait‐list control group . Finally , the magnitude of increase in left‐sided activation predicted the magnitude of antibody titer rise to the vaccine . Conclusions : These findings demonstrate that a short program in mindfulness meditation produces demonstrable effects on brain and immune function . These findings suggest that meditation may change brain and immune function in positive ways and underscore the need for additional research Using a quasiexperimental design , in an intensive outpatient chemical dependency treatment program , this research compared a psychoeducational addiction treatment group with an intervention that combined progressive relaxation and visualization in a group setting . The progressive relaxation and visualization treatment consisted of six hour-long sessions that replaced psychoeducation treatment groups over the space of a 3-week period . The visualization group and the psychoeducation treatment groups were compared via pretest and posttest instruments to examine the impact of treatments on levels of emotional arousal , self-efficacy , and coping re sources . The State-Trait Anxiety Inventory ( STAI ) , the Situational Confidence Question naire ( SCQ ) , and the Coping Re sources Inventory ( CRI ) were used as part of the st and ardized measures . A total of 76 participants were involved in this study , which was conducted over an 8-month period . ( As they entered treatment , participants were assigned to groups in a fashion that would maintain equivalency of group size . ) Statistical tests determined that the nonr and omly assigned treatment groups were not significantly different from each other at the outset of the treatment interventions , t-tests and multivariate analysis of variance and covariance ( MANOVA/MANCOVA ) were used to examine the results of the study . The t-tests revealed that there were significant pretest/posttest differences ( p < .05 ) for both groups on almost all the dependent measures . MANCOVA , using pretest levels of the dependent measures as the covariate , did not reveal significant differences between the two groups ( i.e. , both groups showed equal levels of improvement on the posttest measures ) . Also , there were outcome differences for individuals who achieved greater degrees of relaxation and increased involvement in visualization session . In conclusion , both psychoeducation and visualization treatments were equally effective in producing positive effects . Although there is little empirical research that evaluates the effectiveness of psychoeducation treatment provided by chemical dependency treatment programs , these findings support that psychoeducation treatment is producing positive treatment effects . Further research is needed to assess the incremental benefit of using visualization as an adjunct to psychoeducation treatment BACKGROUND : Night eating syndrome ( NES ) is characterized by a lack of appetite in the morning , consumption of 50 % or more of daily food intake after 6:00 p.m. , and difficulty falling and /or staying asleep . It has been associated with stress and with poor results at attempts to lose weight . OBJECTIVE : The purpose of this study was to determine whether a relaxation intervention ( Abbreviated Progressive Muscle Relaxation Therapy , APRT ) that has been shown to significantly reduce stress levels in normal , healthy adults would also benefit an NES sample . RESEARCH METHODS AND PROCEDURES : A total of 20 adults with NES were r and omly assigned to either a relaxation training ( APRT ) or a Control ( quietly sitting for the same amount of time ) group , and all subjects attended two laboratory sessions 1 week apart . Pre- and postsession indices of stress , anxiety , relaxation , and salivary cortisol were obtained , as well as Day 1 and Day 8 indices of mood . Food diaries and hunger ratings were also obtained . RESULTS : The results indicated that 20 min of a muscle relaxation exercise significantly reduced stress , anxiety , and salivary cortisol immediately postsession . After practicing these exercises daily for a week , subjects exhibited lowered stress , anxiety , fatigue , anger , and depression on Day 8 . APRT was also associated with significantly higher a.m. and lower p.m. ratings of hunger , and a trend of both more breakfast and less night-time eating . DISCUSSION : These data support the role of stress and anxiety in NES and suggest that practicing relaxation may be an important component of treatment for this condition BACKGROUND Lost productivity from attending work when unwell , or " presenteeism " , is a largely hidden cost of mental disorders in the workplace . Sensitive measures are needed for clinical and policy applications , however there is no consensus on the optimal self-report measure to use . This paper examines the sensitivity of four alternative measures of presenteeism to depression and anxiety in an Australian employed cohort . METHODS A prospect i ve single-group study in ten call centres examined the association of presenteeism ( presenteeism days , inefficiency days , Work Limitations Question naire , Stanford Presenteeism Scale ) with Patient Health Question naire depression and anxiety syndromes . RESULTS At baseline , all presenteeism measures were sensitive to differences between those with ( N=69 ) and without ( N=363 ) depression/anxiety . Only the Work Limitations Question naire consistently showed worse productivity as depression severity increased , and sensitivity to remission and onset of depression/anxiety over the 6-month follow-up ( N=231 ) . There was some evidence of individual depressive symptoms having a differential association with different types of job dem and s. LIMITATIONS The study findings may not generalise to other occupational setting s with different job dem and s. We were unable to compare responders with non-responders at baseline due to anonymity . CONCLUSIONS In this community sample the Work Limitations Question naire offered additional sensitivity to depression severity , change over time , and individual symptoms . The comprehensive assessment of work performance offers significant advantages in demonstrating both the individual and economic burden of common mental disorders , and the potential gains from early intervention and treatment The purpose of this project was to investigate the psychological and physical effects of training of body awareness and slow stretching on persons with chronic toxic encephalopathy ( CTE ) . In the present study , a method of self-regulation , a body-mind training , is presented . The body-mind training used was a guided relaxation technique combined with meditative stretching . The techniques are introduced and the psychological and physiological effects of the training is presented . Eight subjects with CTE , 48.5 years , were trained for 8 weeks . Outcome measures were percentage alpha brain waves ( alpha% ) , electromyography ( EMG ) on the frontalis muscle , state-trait anxiety ( STAI ) , creativity ( RAT ) , and mood measured as anxiousness , humour and mental fatigue . The mean alpha% increased 52 % during the training period ( P < 0.01 ) , and the EMG decreased 31 % ( P < 0.001 . State anxiety decreased 22 % during the training period ( P < 0.01 ) , but no changes were observed in trait anxiety and in the creativity score . The level of anxiousness and fatigue before a training session decreased during the training period . In conclusion , the body-mind training result ed in an improved ability for physical and mental relaxation as indicated from the lower EMG , the higher alpha% and the decrease in state anxiety OBJECTIVES : Psychological treatments are considered to be useful in the irritable bowel syndrome ( IBS ) , although the evidence is based on small , often flawed trials . Although cognitive behavior therapy ( CBT ) and relaxation therapy have both been promising , we hypothesized that CBT would be superior to relaxation and st and ard care alone in IBS patients . The objective of this study was to test this assumption by comparing the effects of cognitive behavior therapy with relaxation therapy and routine clinical care alone in individuals with IBS . METHODS : Patients ( n = 105 ) with Rome I criteria for IBS were recruited from advertisement ( n = 51 ) and outpatient clinics ( n = 54 ) ; those patients with resistant IBS were not included . A r and omized controlled trial with three arms ( st and ard care for all groups plus either CBT or relaxation ) for 8 wk was conducted , which applied blinded outcome assessment s using vali date d measures with 1 yr of follow-up . The primary outcome for this study was bowel symptom severity . RESULTS : Of 105 patients at the commencement of treatment , the mean bowel symptom frequency score for the whole sample was 21.1 and at the end of treatment had fallen to 18.1 ; this persisted at the 52-wk follow-up , with a significant linear trend for scores to change over time ( F= 39.57 p < 0.001 ) . However , there were no significant differences among the three treatment conditions . Significant changes over time were found for physical functioning ( F= 4.37 , p < 0.001 ) , pain ( F= 3.12 , p < 0.05 ) , general health ( F= 2.71 , p < 0.05 ) , vitality ( F= 2.94 , p < 0.05 ) , and the social functioning scales on the Medical Outcomes Study Short Form 36 ( F= 4.08 , p < 0.05 ) ; however , all three arms showed similar improvement . There were significant reductions in anxiety , depression , and locus of control scales , but no significant differences among the treatment groups were detected . CONCLUSION : Cognitive behavior and relaxation therapy seem not to be superior to st and ard care alone in IBS Poppen ( Behavior Relaxation Training and Assessment , 1988 ) has developed an observational method of assessing the degree to which individuals show a relaxation response . Although promising , this method , the Behavioral Rating Scale ( BRS ) , has yet to be thoroughly investigated . Subjects in this study were r and omly assigned to a progressive relaxation training group or an attention-control group . Following a training period , subjects participated in a laboratory session in which self-report measures of relaxation were obtained , physiological measures were monitored , and behavioral observations were made using the BRS . Results supported the use of the BRS as a valid , observable measure of an individual 's relaxation response . Discriminant validity was demonstrated by between-group differences on the BRS and construct validity was shown by significant correlations between changes on the BRS and changes on self-report and physiological measures . It is argued that , though alternative explanations are feasible , this study 's results support the use of the BRS as an effective assessment tool when measuring an individual 's response to progressive muscle relaxation Cognitive therapy ( CT ) and applied relaxation ( AR ) as treatments of generalized anxiety disorder ( GAD ) were compared in a sample of 45 patients of a community mental health center , r and omly allocated to condition . Patients were assessed before and after a 12-session treatment , and at one and six months follow-ups . There was a 20 % drop out from CT and 15 % from AR ( NS ) , with some drop outs being considerably improved . Both completers and intention-to-treat analyses revealed that both treatments were effective ( ESs of composite and specific measures ranging from 0.53 to 1.14 ) . At one-month follow-up AR tended to do better than CT , with CT catching up with AR at six months . Recovery rates and proportions of patients showing reliable change were comparable to other studies on AR and CT , with 55 % of CT and 53.3 % of AR patients recovered on the STAI-trait at six-month follow-up . These results confirm that both CT and AR are effective treatments for GAD , and also that there is still room for improvement Background The aim of this open trial was to examine the influence of acute bright light exposure on anxiety in older and young adults . Methods This study was ancillary to a complex 5-day laboratory experiment testing phase-responses to light at all times of the day . On 3 consecutive days , participants were exposed to bright light ( 3,000 lux ) for 3 hours . The Spielberger State-Trait Anxiety Inventory ( Form Y1 ) was administered 5 minutes before and 20 minutes after each treatment . Mean state anxiety before and after treatment were analyzed by age , sex , and time ANOVA . To avoid floor effects , only participants with baseline STAI levels of ≥ 25 were included . Results A significant anxiolytic effect of bright light was found for the mean data , as well as for each of the three days . No significant main effect of age , sex , or interaction of these factors with STAI change were found . Conclusion The results show consistent and significant ( albeit modest ) anxiolytic effects following acute bright light exposure in low anxiety adults . Further r and omized , controlled trials in clinical ly anxious individuals are needed The present study examined the effects of progressive relaxation training and EMG biofeedback on acute glucose disposal in diabetic subjects , as measured by glucose tolerance and three other measures of diabetic metabolic control . Twenty subjects with non-insulin-using Type II diabetes took part in progressive relaxation training and EMG biofeedback in a pre-post treatment versus wait-list experimental design . Treatment effects were assessed on glucose tolerance along with three measures of diabetic control : fasting blood glucose , two-hour postpr and ial blood glucose , and fructosamine . Stress reduction and relaxation was assessed with two physiological measures and two subjective question naires . The training program produced significant reductions in stress , as measured by State Anxiety , and significant changes in physiological measures of muscle activity and skin conductance compared to the control condition . However , no changes were found in glucose tolerance ( while practicing relaxation ) nor in any of the three measures of general diabetic metabolic control . The major implication of this study is that relaxation training does not appear to directly improve diabetic control in mildly stressed non-insulin-using Type II diabetic patients Abstract The psychometric properties of the Italian version of the Hospital Anxiety and Depression Scale and its utility as a screening instrument for anxiety and depression in a non-psychiatric setting were evaluated . The question naire was administered twice to 197 breast cancer patients r and omised in a phase III adjuvant clinical trial : before the start of chemotherapy and at the first follow-up visit . The presence of psychiatric disorders was evaluated at the follow-up visit using the Structured Clinical Interview for DSM-III-R in 132 patients . Factor analyses identified two strictly correlated factors . Crohnbach 's alpha for the anxiety and depression scales ranged between 0.80 and 0.85 . At follow-up , 50 patients ( 38 % ) were assigned a current DSM-III-R diagnosis , in most cases adjustment disorders ( 24 % ) or major depressive disorder ( 10 % ) . Receiver operating characteristics ( ROC ) analysis was used to test the discriminant validity for both anxiety and depressive disorders . The comparison of the areas under the curve ( AUC ) between the two scales did not show any difference in identifying either anxiety ( P=0.855 ) or depressive disorders ( P=0.357 ) . The 14-item total scale showed a high internal consistency ( alpha=0.89 and 0.88 ) and a high discriminating power for all the psychiatric disorders ( AUC=0.89 ; 95 % CI=0.83–0.94 ) . The cut-off point that maximised sensitivity ( 84 % ) and specificity ( 79 % ) was 10 . These results suggest that the total score is a valid measure of emotional distress , so that the Italian version of HADS can be used as a screening question naire for psychiatric disorders . The use of the two subscales as a ' case identifier ' or as an outcome measure should be considered with caution Vocal characteristics of therapists , including voice volume , pitch and timbre of speech , and rate of speech have been hypothesized to facilitate the therapeutic process , particularly during procedures like progressive relaxation training ( PRT ) . Very little empirical work , however , has examined the relation between vocal characteristics and treatment process or outcome . The purpose of this study was to examine the role of vocal characteristics during a single session of PRT applying technological innovations devised for speech pathology and audiology setting s for evaluating therapist 's vocal characteristics . Forty-eight high anxious young adult women were r and omly assigned to one of four conditions for training : PRT with the recommended therapist voice ( RV ) that decreased in tone , volume , and rate across the session , PRT with conversational therapist voice during the session ( CV ) , a credible treatment control called systematic self-relaxation ( SR ) , or no treatment control ( NT ) . All subjects participated in a single PRT session during which heart rate , EMG , self-report measures of tension ( SRT ) and anxiety , and treatment credibility ratings were obtained . Results revealed significant reductions in SRT , self-reported anxiety , and heart rate for participants in all groups . Only the RV group displayed significant reductions in EMG when compared with the other three groups . Participants in the RV group also rated the therapist 's voice as “ more facilitating ” of relaxation when compared to the CV group . These results suggest that methods employed for evaluating the quality of vocal characteristics in speech and audiology clinics may be useful for evaluating the quality of therapist 's voice when conducting PRT The purpose of this study was to assess the impact of a multidisciplinary intervention program on the attitudes and symptoms associated with bulimia nervosa ( BN ) . The Bulimia Test ( BULIT ) and subscales from the Eating Disorder Inventory-2 ( EDI-2 ) associated with BN were administered to 373 females to determine eligibility for participation in the study . In order to qualify for the study , participants had to be female , not be anorexic , and meet one of four criteria indicating that they had some of the symptoms of BN . Following the screening , 12 females were r and omly assigned to a control group ( C , n=6 ) or an intervention group ( I , n=6 ) . The I group then participated in an 8-week multidisciplinary intervention program consisting of small group discussion s , movement improvisation , and relaxation techniques . Dependent variables consisted of scores from st and ardized instruments for anxiety , self-esteem , and BN . A multivariate analysis of variance ( MANOVA ) on the difference score from post- to pretest was calculated for state and trait anxiety . That analysis indicated that compared to the C group , which showed no reduction in anxiety , the I group had a significant reduction in anxiety following the intervention program . No significant differences were found between groups for self-esteem or symptoms of BN . Conclusions were that anxiety levels were lowered in the I group ; however , attitudes or behaviors associated with BN were not affected by the intervention BACKGROUND Unrelieved pain after surgery can lead to complications , prolonged hospital stay , and delayed recovery . Because of side effects from opioids and differences in response , it is important to use non-pharmacological methods in addition to analgesics to decrease patient discomfort and anxiety . AIMS We examined the effects of a systematic method of relaxing the body on the sensory and affective components of postoperative pain , anxiety , and opioid intake after initial ambulation . DESIGN A r and omized controlled trial with relaxation and control groups was used . METHOD The convenience sample of 102 adults underwent abdominal surgery at a large hospital in Thail and . Systematic relaxation was used for 15 minutes during recovery from the first ambulation after surgery . Pain was measured with 100 mm Visual Analogue Sensation and Distress of Pain Scales before and after the intervention . State anxiety was measured before surgery and after the intervention ; opioid intake was recorded 6 hours later . RESULTS The relaxation group had less post-test sensation and distress of pain ( 26 and 25 mm less , respectively ) than the control group ( P = 0.001 ) . Relaxation did not result in significantly less anxiety or 6-hour opioid intake . However , group differences in state anxiety were in the expected direction and fewer participants in the relaxation group requested opioids . Nearly all reported that systematic relaxation reduced their pain and increased their sense of control . CONCLUSION Substantial reductions in the sensation and distress of pain were found when postoperative patients used systematic relaxation . Although tested in Thail and , we recommend that nurses in other countries try systematic relaxation with postoperative patients , in addition to analgesic medication , measuring pain scores and asking about cultural acceptance A new cognitive therapy ( CT ) program was compared with an established behavioral treatment . Sixty-two patients meeting Diagnostic and Statistical Manual of Mental Disorders ( 4th ed . ; American Psychiatric Association , 1994 ) criteria for social phobia were r and omly assigned to CT , exposure plus applied relaxation ( EXP = AR ) , or wait-list ( WAIT ) . CT and EXP = AR were superior to WAIT on all measures . On measures of social phobia , CT led to greater improvement than did EXP = AR . Percentages of patients who no longer met diagnostic criteria for social phobia at posttreatment-wait were as follows : 84 % in CT , 42 % in EXP = AR , and 0 % in WAIT . At the 1-year follow-up , differences in outcome persisted . In addition , patients in EXP = AR were more likely to have sought additional treatment . Therapist effects were small and nonsignificant . CT appears to be superior to EXP = AR in the treatment of social phobia A r and omized trial was conducted of two different self-help programs for panic disorder ( PD ) on the Internet . After confirming the PD-diagnosis with an in-person structured clinical interview for DSM-IV ( SCID ) interview 22 participants were r and omized to either applied relaxation ( AR ) or a multimodal treatment package based on cognitive behavioral therapy ( CBT ) . Overall , the results suggest that Internet-administered self-help plus minimal therapist contact via e-mail has a significant medium to large effect ( Cohen 's d=0.71 for AR and d=0.42 for CBT ) . The results from this study generally provide evidence to support the continued use and development of Internet-distributed self-help programs OBJECTIVES Autogenic training ( AT ) is a method of autosuggestion with some potential for reducing anxiety . This study tests whether AT lowers anxiety levels experienced by patients undergoing coronary angioplasty . METHODS Fifty-nine patients were r and omly assigned to receive regular AT or no such therapy as an adjunct to st and ard care for 5 months . The primary outcome measure was State Anxiety at 2 months . Qualitative information was generated by face-to-face interviews . RESULTS State Anxiety showed a significant intergroup difference both at 2 and 5 months . This finding was corroborated by secondary outcome measures , for example , quality of life , and by qualitative information about patients ' experiences . The results do not allow us to determine whether the observed effects are specific to AT or of a nonspecific nature . CONCLUSIONS Our results suggest that AT may have a role in reducing anxiety of patients undergoing coronary angioplasty Eighteen patients who had undergone stoma surgery were assessed with respect to their anxiety level and self-reported quality of life ( QoL ) on three occasions ; namely , immediately after surgery , 5 weeks after surgery , and 10 weeks after surgery . The patients were r and omised into a control group ( n = 10 ) and an experimental group ( n = 8) . A 20-min set of audiotaped instructions on progressive muscle relaxation training ( PMRT ) was given to the patients in the experimental group for home practice . Assessment instructions included the Chinese State-Trait Anxiety Inventory ( C-STAI ) , the Quality of Life Index for Colostomy ( QoL-Colostomy ) and the Hong Kong Chinese version of the World Health Organisation Quality of Life Scale ( WHOQoL ) . Results indicated that there was a significant decrease in both the C-STAI score ( F = 4.66 , P < 0.05 ) and the WHOQoL score ( F = 4.74 , P < 0.05 ) in the experimental group . Among the domains of WHOQoL , a significant difference was shown in physical health/independence and general perception of QoL , with the experimental group demonstrating better functioning . For the QoL-Colostomy , however , there was no significant difference between the control and experimental groups . The results suggest that the use of PMRT could enhance quality of life and decrease state anxiety in patients after stoma surgery OBJECTIVES This study was initially design ed to test the notion that generalized anxiety is a predominant factor in the maintenance of psychologically determined sleep-onset insomnia and that a trait anxiety reducing technique can provide significant therapeutic gains . METHODS Twenty participants ( age 19 - 63 ) with moderate to severe sleep-onset chronic insomnia were first asked to monitor their sleep-onset latency ( SOL ) for a 3-week baseline period at home using a SOL clock device . Then , 10 received anxiety management training ( AMT ) for 9 weeks , while the remaining 10 were trained in the use of progressive relaxation ( PR ) . All participants were measured before and after therapy using sleep laboratory recordings ( three nights each ) , the Spielberger Trait Anxiety Inventory and the Beck Depression Inventory . Daily home sleep-onset measures with the SOL clock device were also taken during therapy . RESULTS There was no change in SOL over the 3-week baseline period . However , both groups experienced a significant improvement in SOL from pretreatment ( end of baseline ) to posttreatment periods . In the laboratory , both groups experienced a reduction in Stage 1 sleep as well as an increase in slow wave sleep ( SWS ) and sleep satisfaction . On the personality measures , both groups experienced a significant reduction in trait anxiety and a decrease in depression . Overall , there was no indication that one of the therapies was significantly better than the other in effecting changes . CONCLUSION These results suggest that both PR and AMT are efficient therapies for sleep onset insomnia and overall sleep quality . Improvements in the application of the AMT technique are proposed to maximize its usefulness Abstract The authors examined the effect of a 6-week mind/body intervention on college students ' psychological distress , anxiety , and perception of stress . One hundred twenty-eight students were r and omly assigned to an experimental group ( n = 63 ) or a waitlist control group ( n = 65 ) . The experimental group received 6 90-minute group-training sessions in the relaxation response and cognitive behavioral skills . The Symptom Checklist-90-Revised , Spielberger State-Trait Anxiety Inventory , and the Perceived Stress Scale were used to assess the students ' psychological state before and after the intervention . Ninety students ( 70 % of the initial sample ) completed the post assessment measure . Significantly greater reductions in psychological distress , state anxiety , and perceived stress were found in the experimental group . This brief mind/body training may be useful as a preventive intervention for college students , according to the authors , who called for further research to determine whether the observed treatment effect can be sustained over a longer period of time This study evaluated the contribution of regular home practice in the treatment of tension headache ( HA ) with progressive muscle relaxation ( PMR ) by giving 14 tension HA sufferers 10 sessions ( over 8 weeks ) of st and ard PMR with home practice and application instructions while 13 additional patients received the same PMR training ( except for the omission of cue-controlled relaxation ) with no home practice or application instruction . A third group of 6 patients merely monitored HA activity . Both treated groups showed significant reduction in HA activity , whereas the symptom monitoring group did not change . The 2 treated groups did not differ . On a measure of clinical ly significant reduction in HA activity ( at least 50 % reduction in HA activity ) , however , the group receiving home practice instruction ( 50 % ) showed a trend ( p = .056 ) to improve more than did those receiving PMR without home practice ( 15 % ) The present study investigated the efficacy of a coping-technique , applied relaxation ( AR ) and cognitive therapy ( CT ) , in the treatment of generalized anxiety disorder . Thirty-six out patients fulfilling the DSM-III-R criteria for generalized anxiety were assessed with independent assessor ratings and self-report scales before and after treatment and at a 1 yr follow-up . The patients were r and omized and treated individually for 12 weekly sessions . The results showed that both treatments yielded large improvements , which were maintained , or furthered at follow-up . There was no difference between AR and CT on any measure . The drop-out rate was 12 % for AR and 5 % for CT . The proportions of clinical ly significantly improved patients were 53 and 62 % at post-treatment and 67 and 56 % at follow-up for AR and CT , respectively . Besides affecting generalized anxiety the treatments also yielded marked and lasting changes on ratings of worry , cognitive and somatic anxiety and depression . The conclusion that can be drawn is that both AR and CT have potential as treatments for generalized anxiety disorder but they have to be developed further in order to increase the efficacy to the level usually seen in panic disorder , 80 - 85 % clinical ly improved This study evaluated a relaxation intervention design ed to prevent anxiety during magnetic resonance imaging ( MRI ) , and assessed the development of fears in patients who felt anxious during the procedure . Patients were assigned to a control condition ( no intervention ; n = 52 ) , relaxation before the scan ( n = 44 ) , or relaxation before and during the scan ( n = 43 ) . Compared to the control group , patients who practised relaxation showed reduced anxiety during the scan . Seven months or more after undergoing MRI , there was a positive correlation between anxiety experienced during the scan and the development of MRI-related fears . The intervention did not prevent the development of MRI-related fears at follow-up The present study examined the effects of repeated exposure of flight phobics to flights in virtual reality ( VR ) . Flight phobics were r and omly assigned either to complete one VR test flight followed by four VR exposure flights ( VR group ; N=15 ) in one lengthy session or to complete one VR test flight followed by a lengthy relaxation training session ( relaxation group ; N=15 ) . All participants completed a second VR test flight at the end of the session . Fear reports and physiological fear reactions ( heart rate , skin conductance level ) during VR exposures were registered , and fear of flying was assessed psychometrically from 3 weeks before to 3 months after exposure . Exposure to VR flights elicited subjective and physiological fear responses in flight phobics , and these responses attenuated within and across VR flights . Fear reduction associated with repeated VR exposure was greater than fear reduction caused by relaxation training . Fear of flying improved in both treatment groups , but several outcome measures indicated greater effects in the VR treated group than in the relaxation group . These findings indicate that exposure in virtual reality may offer a new and promising approach for the treatment of fear of flying Nurse managers are under increased stress because of excessive workloads and hospitals ' restructuring which is affecting their work tasks . High levels of stress could affect their mental health . Yet , few stress management training programmes are provided for this population . The purpose of this study was to apply stretch-release relaxation and cognitive relaxation training to enhance the mental health for nurse managers . A total of 65 nurse managers in Hong Kong were r and omly assigned to stretch-release relaxation ( n = 17 ) , cognitive relaxation ( n = 18 ) , and a test control group ( n = 35 ) . Mental health status was assessed using the Chinese version of State-Trait Anxiety Inventory and the Chinese version of the General Health Question naire . Participants were assessed at the pretreatment session , the fourth posttreatment session , and at the 1-month follow-up session . The results revealed both the stretch-release and cognitive relaxation training enhanced mental health in nurse managers in Hong Kong . The application of relaxation training in enhancing mental health status for nurses and health professionals is discussed Rheumatoid arthritis ( RA ) is a chronic disease and has the highest rate of prevalence among rheumatic inflammatory diseases . The purpose of this study was to determine the effect of Benson Relaxation Technique ( BRT ) combined with medication on disease activity in patients with RA . Following ethical approval , 50 consecutive matched patients were selected and allocated into two groups , either an experimental or a control group . Patients in the experimental group received BRT combined with medication and patients in the control group were given only medication . Clinical symptoms , laboratory findings , anxiety , depression and feeling of well-being were measured before and after intervention to evaluate the effect of BRT . There was a significant difference between the two groups in anxiety , depression and feeling of well-being . Changes in clinical symptoms and laboratory findings were not large enough to be statistically significant between the two groups , but they indicated decline in disease progress . The results demonstrate that BRT can be an effective technique in reducing disease process in patients suffering from RA . However , in order to support the findings of this trial , studies with large sample size and > 8-week intervention are recommended |
12,774 | 28,479,203 | The present analysis confirms the superiority of MUS over Burch colposuspension .
The studies comparing insertion of RT-TVT and TO-TVT showed higher subjective and objective cure rates for the RP-TVT but at the cost of higher risks of some complications and voiding lower urinary tract symptoms .
Efficacy of inside-out and outside-in techniques of TO-TVT insertion was similar , although the risk of vaginal perforation was lower in the inside-to-out TO-TVT .
PATIENT SUMMARY Retropubic and transobturator midurethral slings are a popular treatment for female stress urinary incontinence .
The available literature suggest that those slings are either more effective or safer than other older surgical procedures .
Retropubic tapes are followed with slightly higher continence rates as compared with the transobturator tapes but are associated with higher risk of intra- and postoperative complications | CONTEXT Retropubic ( RP-TVT ) and transobturator miurethral ( TO-TVT ) midurethral sling ( MUS ) are popular surgical treatments for female stress urinary incontinence .
The long-term efficacy and safety of the procedures is still a topic of intense clinical research and several r and omised controlled trials ( RCTs ) have been published in the last years OBJECTIVE : To evaluate the efficacy and safety of MUS compared with other surgical treatments for female stress urinary incontinence . | Abstract Objectives : To present the first experience in Iraq of autologous rectus fascia sling ( RFS ) procedures and transobturator tape ( TOT ) for treating female stress urinary incontinence ( SUI ) , and to review the validity of the RFS in the era of synthetic tapes . Patients and methods : From December 2004 to July 2012 , 80 female patients with SUI were enrolled in the study , and r and omly assigned into two types of surgery , with 40 treated by RFS ( retropubic route ) and 40 by TOT . The surgical results were compared between the groups and with those from previous studies . Results : The mean operative duration was 80 min for RFS vs. 20 min for TOT . The early cure rate was 98 % for RFS ( with one failure due to prolonged urinary retention ) and 95 % for TOT ( with two failures due to persistent incontinence ) . The early complications were mainly abdominal wound problems ( 20 % ) for RFS , and groin and upper thigh pain ( 13 % ) for TOT . The late complications were the development of postvoid residual urine ( 8 % in RFS vs. 5 % in TOT ) and de novo detrusor overactivity ( 5 % in each group ) . There were no vaginal or urethral erosions up to the end of the study . Conclusions : RFS and TOT have comparable efficacy and safety in treating SUI . Nevertheless RFS , with its more invasive nature and long operative duration , should only be used when synthetic tapes are not available or not preferable Introduction and hypothesisSynthetic mid-urethral slings are currently considered the treatment of choice for stress urinary incontinence ( SUI ) . In this study , two types of slings are compared : TVT vs. TOT . Methods In a prospect i ve r and omized study , 40 patients underwent either TVT ( 19 patients ) or TOT ( 21 patients ) . Stress-specific and overall success was evaluated . Perioperative complications were classified according to Clavien ’s classification . Results Mean duration of follow-up was 20 months . At last follow-up , stress-specific success rate was 94.6 % in TVT vs. 81 % in TOT . No significant difference was detected in terms of post-void residual urine , symptom score , and filling and voiding parameters . Thigh pain represented the main complication in the TOT group . Conclusions Both TVT and TOT are effective procedures for treatment of SUI . When compared to each other , TOT seems to be inferior to TVT in terms of efficacy , causing less serious complications BACKGROUND There is a lack of information on the long-term outcomes of transobturator tension-free vaginal tape ( TO-TVT ) in the surgical treatment of female stress urinary incontinence ( SUI ) . OBJECTIVES To assess the 3-yr outcomes following TO-TVT and to compare the effectiveness of inside-out versus outside-in approaches . DESIGN , SETTING , AND PARTICIPANTS A 3-yr follow-up study of the Evaluation of Transobturator Tapes ( E-TOT ) trial , a r and omised controlled trial ( RCT ) conducted with women undergoing TO-TVT as a sole procedure between April 2005 and April 2007 in a tertiary urogynaecology centre in the United Kingdom . INTERVENTION Patients ( n=341 ) were r and omised to undergo either TVT-O ( Ethicon Inc. , Somerville , NJ , USA ) for the inside-out approach or TOT-Aris ( Coloplast Corp. , Minneapolis , MN , USA ) for the outside-in approach . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The primary outcome was patient-reported success rate . Secondary outcomes included further treatment for SUI , improvement in quality of life , late complications , and risk factors for late failures . Categorical variables were compared using the chi-square or Fisher exact test . Within-group comparison was undertaken using Wilcoxon and Mann-Whitney tests . Risk factors for late failures were assessed in a multivariate regression model . All statistical analysis was performed using SPSS v.18.0 ( IBM Corp. , Armonk , NY , USA ) . RESULTS AND LIMITATIONS The 3-yr follow-up was completed by 238 of the 341 women ( 70 % ) . The overall success rate , based on Patient 's Global Impression of Improvement response , was 73.1 % , with no significant difference between the inside-out and the outside-in TO-TVT ( 73.18 % vs 72.3 % ; odds ratio : 0.927 ; 95 % confidence interval , 0.552 - 1.645 ; p=0.796 ) . Compared with the 1-yr follow-up , there was a significant reduction in the patient-reported success rate ( p=0.005 ) ; however , no independent risk factors were identified . A clinical ly significant improvement ( ≥10 points ) was seen in 80 % ( n=191 ) of women , with no significant difference between both groups ( p=0.113 ) . Twenty-two women ( 6 % ) underwent further surgical treatment within 3 yr . The lack of an objective outcome assessment is a potential limitation of this RCT . CONCLUSIONS The E-TOT RCT showed a 73 % patient-reported success rate for TO-TVT at 3-yr follow-up , with no significant differences between inside-out and outside-in approaches . There was a significant drop in patient-reported success rates between 1 and 3 yr Purpose To evaluate in a comprehensive way TVT in comparison with TOT , the results of a single-center RCT are presented . Many studies addressed efficacy and safety of TVT and TOT . Methods Women included were adults having predominant SUI with positive stress test . They were r and omized to get either TVT ( Gynecare ® ) or TOT ( Aris ® ) . All women were seen 1 week , 3 , 6 , 12 , 18 , and 24 months . Results Seventy-one women completed 2-year follow-up . Median age was 47 ( range 33–60 years ) . Mean ± SD BMI in TVT group was 34 ± 5 while in TOT group was 32 ± 5 kg/m2 . POP of any degree was seen in 50 % ( 35 women ) . At 1 year , pad test – negative women were 31 and 29 for TVT and TOT , respectively . At 2 years , figures became 28 in TVT group and 27 in TOT . At 1 year , UDI 6 and IIQ 7 decreased by 78.5 and 81 % for TVT and by 69 % and 75 % for TOT group . At 2 year , comparable percentages were 73 and 79 % for TVT and 69 and 82 % for TOT . Fifteen unique patients had adverse events , 10 of them had TOT . Conclusions Both tapes have similar efficacy , regarding cure of incontinence . TVT is more effective , albeit insignificantly , than TOT at 2 years . However , serious adverse events were more frequent with TVT , yet TOT has more unique adverse events Purpose Transobturator approaches to midurethral sling surgery are one of the most commonly performed operations for female stress urinary incontinence throughout the world . However , very few results of r and omized clinical trials of transobturator midurethral sling surgery ( MONARC vs. TVT-O ) for the treatment of female urinary incontinence have been reported . In this study , we compared the 3-year follow-up cure rates of these two procedures . Material s and Methods From July 2006 to June 2008 , 74 patients who had undergone MONARC ( 35 patients ) or TVT-O ( 39 patients ) were included in the study and were analyzed prospect ively . The mean follow-up duration of both groups was 39.2 months . Preoperative and postoperative evaluations included physical examination , uroflowmetry and postvoid residual measurement , involuntary urine loss with physical activity , and urinary symptoms . Cure of female urinary incontinence was defined as patient report of no loss of urine upon physical activity . The patients ' satisfaction after treatment was rated as very satisfied , satisfied , equivocal , and unsatisfied . Very satisfied and satisfied were considered as the satisfied rate . Results There were no significant differences in preoperative patient characteristics , postoperative complications , or success rate between the two groups . The cure rate of the MONARC and TVT-O groups was 85.7 % and 84.6 % , respectively . The patient satisfaction ( very satisfied , satisfied ) rate of the MONARC and TVT-O groups was 82.8 % and 82.1 % , respectively . Conclusions The MONARC and TVT-O procedures were equally efficient for the treatment of female urinary incontinence , with maintenance of high cure rates for 3 years . Longer follow-up is needed to confirm these results Introduction and hypothesisA prospect i ve study comparing the effect of the tension-free vaginal tape ( TVT ) to the Monarc sling on sexual function in women with urodynamic stress incontinence ( USI ) and intrinsic sphincter deficiency ( ISD ) is presented . Methods Eighty-seven sexually active women with USI and ISD were enrolled . Sexual function was assessed pre-operatively and at 6 and 12 months post-operatively by history , PISQ-12 , UDI-6 and IIQ-7 question naires . Results A significant increase was detected in PISQ-12 score following both TVT and Monarc insertion . This score was greater in the TVT group at 6 months but not at 12 months when compared to the Monarc group . A significant decrease in UDI-6 and IIQ-7 score was detected . Specifically , coital incontinence and fear of leakage were reduced in both groups , and no change in dyspareunia or orgasm intensity was found . Conclusions Sexual function improves 6 months after TVT or Monarc sling , and this benefit is maintained at 12 months BACKGROUND Many studies have assessed the equivalent effectiveness of tension-free vaginal tape ( TVT ) and transobturator suburethral tape ( TVT-O ) at short- to medium-term follow-up , but no long-term r and omised trials appear in the literature . OBJECTIVE We compared the use of TVT to TVT-O , providing a longer follow-up than currently appears in the literature . DESIGN , SETTING , AND PARTICIPANTS Seventy-two consecutive patients affected by stress urinary incontinence ( SUI ) were included in this r and omised , controlled trial . Patients were r and omly allocated to the TVT or TVT-O procedure using a predetermined , computer-generated r and omisation code . INTERVENTION After preoperative assessment , patients were r and omly allocated to the TVT or TVT-O procedure . MEASUREMENTS This 5-yr study represents the extension of our original r and omised trial , which was design ed to assess the incidence of long-term complications ( primary end point ) and successes ( secondary end point ) for both techniques . RESULTS AND LIMITATIONS At 60-mo follow-up , 52 patients ( 72 % ) were objective ly cured of SUI ( 72.9 % after TVT-O and 71.4 % after TVT ) , but only 44 patients ( 61 % ) were satisfied . The late complication rate was 16.6 % ( 10 women ) : five women ( 16.1 % ) in the TVT-O group and five women ( 17.2 % ) in the TVT group ( p=1 ) . In this follow-up , 62 % of the patients from the TVT-O group and 60 % from the TVT group ( p=1 ) expressed that they were satisfied or very satisfied with the results . The mean cause of dissatisfaction was the development of sexual dysfunction result ing from dyspareunia or incontinence during intercourse , which was found in 6 of 16 dissatisfied patients ( 37.5 % ) . The limitations of our study included the adequate but small sample size and the lack of question naires . CONCLUSIONS Both surgical techniques are safe , with similar results ( 72.9 % and 71 % of patients objective ly cured after TVT-O and TVT , respectively ) and low complication rates ( 16.6 % : 16.1 % and 17.2 % , respectively , for TVT-0 and TVT ) , even after 5-yr follow-up Purpose To evaluate long-term ( over 4 years ) functional outcomes and quality of life of transobturator ( TOR ) and retropubic ( RPR ) routes in the cure of stress urinary incontinence ( SUI ) . Methods Prospect i ve , r and omized multicentre study involving 88 women with SUI from March 2004 to May 2005 ( RPR group ( n = 42 ) , TOR group ( n = 46 ) ) . Long-term functional results and quality of life were evaluated using vali date d question naires and compared with those observed at the first year . Results Eight patients ( 19 % ) in the RPR group and 9 patients ( 19.5 % ) in the TOR group were lost to follow-up ( NS ) . The mean follow-up in the RPR and the TOR groups was 52.7 months and 53.1 months , respectively . In intention to treat , the success rate at 4 years was 64.3 % in the RPR group and 69.5 % in the TOR group ( NS ) . At 4 years , no significant differences in the IIQ scores were observed in either group compared to the preoperative scores with no difference between the groups ( RPR group : 32 vs. 14.9 ( NS ) , TOR group : 25.7 vs. 21.4 ( NS ) ) . Compared to 1 year UDIQ and IIQ scores , a decrease in quality of life was observed for both groups at 4 years ( RPR group : 4.7 vs. 34 ( P < 0.0001 ) and 2.6 vs. 14.9 ( P < 0.001 ) , TOR group : 1.2 vs. 38.7 ( P < 0.0001 ) and 0 vs. 21.4 ( P < 0.0001 ) ) without difference between the groups . Conclusions This study shows similar relatively high long-term success rates for both the RPR and TOR procedures . Patients should be informed about a possible time-dependent alteration in functional results Introduction and hypothesisA study was conducted to compare the efficacy and complications of TVT and TVT-O. Methods This study is a prospect i ve r and omized trial involving 300 women with primary SUI ; 149 received TVT , and 151 patients were treated with TVT-O. At the 1 year follow-up , 141 TVT patients and 147 TVT-O patients ( dropout , 5.3 % and 2.6 % ) were evaluated using urodynamic studies , vali date d question naires , and a 1-h pad test . Results The mean operating time was shorter in the TVT-O group ( p < 0.001 ) . Urinary retention was not significantly different ( p > 0.05 ) . Inner thigh discomfort was reported by 5.4 % of TVT-O patients . In the TVT and the TVT-O groups , respectively , 90.1 % and 88.4 % women were objective ly cured . The satisfaction with the surgical outcome reflects the significant decrease in the question naire mean symptom scores in both groups . Postoperative de novo urgency was significantly more common in the TVT-O patients ( p = 0.015 ) . Conclusion The groups showed comparable objective and subjective cure rates Introduction and hypothesisThe tension-free vaginal tape ( TVT ) and inside-out transobturator tape ( TVT-O ) are first-line surgical treatments for stress urinary incontinence ( SUI ) . However , there is a lack of information regarding the long-term comparative safety of these procedures . Methods A total of 140 SUI patients were r and omized to the TVT or TVT-O procedure and were interviewed by an independent investigator at the follow-up . The primary outcomes were the proportions of patients with long-term postoperative complications . The secondary outcomes included the cure rates , quality of life ( QOL ) and sexual function based on vali date d question naires . Results One hundred and twenty ( 85.71 % ) patients completed the long-term follow-up . More TVT patients experienced perioperative complications ( P < 0.05 ) . However , in a mean follow-up of 95 months , no significant between-group difference was found in the proportions of patients with long-term complications or in the variety of reported complications . The long-term complication rates for TVT and TVT-O were 43.1 % and 27.4 % respectively ( P = 0.07 ) . De novo voiding ( 15.8 % ) and storage symptoms ( 10.8 % ) were the primary long-term complications . Tape exposure was possible up to 7 years after TVT-O. The objective cure rates of TVT and TVT-O procedures were 79.30 and 69.35 % respectively , which were not significantly higher than the subjective rates . The Pelvic Floor Impact Question naire ( PFIQ-7 ) scores remained improved ( P < 0.001 ) after both procedures , even at the 95-month follow-up . No difference was observed in the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Question naire Short Form ( PISQ-12 ) scores after either procedure . Conclusions In the long term , the proportion of patients with complications and the cure rates of the two procedures did not differ significantly . The long-term complication rates were high , but morbidity was low , and the QOL remained improved Abstract Purpose To report the extended long-term results of the use of tension-free vaginal tape(TVT ) and trans-obturator tape ( TOT ) for the treatment of female stress urinary incontinence ( SUI ) . Methods A prospect i ve , multicentre r and omized clinical trial comparing the use of TVT and TOT was used to evaluate 87 patients . The inclusion criteria were stress or mixed UI associated with urethral hyper mobility ( the stress component was clinical ly predominant ) , while the exclusion criteria were previous anti-incontinence surgery and /or pelvic organ prolapse . The objective cure criteria were a negative provocative stress test and a negative 1-h pad test , with no further treatment for SUI . The subjective cure criteria were a 3-day voiding diary , quality -of-life question naires ( UDI6–IIQ7 ) , and patient satisfaction on a scale from 0 to 10 . Results Eighty-seven patients were evaluated ( 47 TOT and 40 TVT ) at a median follow-up of 100 months . Subjective and objective cure rates were 59.6 and 70.2 % in the TOT group and 75 and 87.5 % in the TVT group . The mid-to-long-term trend was a decreasing continence rate in patients who underwent TOT , compared with a stable rate for TVT . The Kaplan – Meier survival curve showed that continence rate decreased for up to 25 months after surgery , with stabilization thereafter for the TVT group while continuing to drop in the TOT group , with no inter-group difference . Conclusion The patients in both groups were highly satisfied at long-term follow-up . The overall continence rate worsened for both groups within 25 months . While the results tend to stabilize in the TVT group , a further decline in the TOT was observed This study aim was to compare the efficacy of transobturator tape ( TOT ) as a new sling procedure , and Burch colposuspension as the gold st and ard surgical technique , in the treatment of stress urinary incontinence ( SUI ) . This prospect i ve r and omised clinical trial was conducted on 62 women with SUI diagnosed with urodynamic test in Vali-e-Asr Hospital , Tehran , Iran . Patients were allocated into two surgery groups , r and omly ; TOT and Burch ( 31 patients in each group ) . After treatment , they were followed-up for long-term outcome . The average duration of follow-up was 22 and 28 months in the TOT and Burch group , respectively . Operation duration and hospital stay in the TOT group was significantly less than the Burch group ( p = 0.001 ) . The rate of complete cure , improvement and failure in the TOT group was 90.3 % , 9.7 % and 0 % , respectively , as well as 74.2 % , 19.4 % and 6.5 % in the Burch group . In the TOT group , 90.3 % of patients were very satisfied , 6.5 % moderately satisfied and 3.2 % were less satisfied ; none of them were unsatisfied . It is concluded that the TOT procedure is a safe and effective option with less operation time and shorter in-hospital stay for SUI treatment Introduction and hypothesisBefore the introduction of the tension-free vaginal tape ( TVT ) procedure for the treatment of female stress urinary incontinence , the colposuspension operation was regarded as the “ gold st and ard ” procedure . The laparoscopic variant of the colposuspension was introduced as a less invasive operation . The aim of the present trial was to compare the new minimally invasive TVT procedure with laparoscopic mesh colposuspension ( LCM ) . Methods A multicenter r and omized clinical trial conducted in six public hospitals in Finl and including primary cases of stress incontinence . Objective treatment success criteria were a negative stress test and no retreatment for stress incontinence . Patient satisfaction was assessed by Patients Global Impression of Improvement , a visual analog scale , and the Urinary Incontinence Severity Score . Results Of 128 r and omized patients , 121 underwent the allocated operation . At the 5-year follow-up 77 % in the TVT group and 84 % in the LCM group could be assessed according to the protocol . The objective cure rate was significantly higher in the TVT group ( 94 % ) than in the LCM group ( 78 % ) . Subjective treatment satisfaction ( completely satisfied with the procedure ) was significantly higher in the TVT group ( 64 % ) than in the LCM group ( 51 % ) . Conclusions By per protocol analysis both objective and subjective cure rates were significantly higher in the TVT group than in the LCM group . If cases that were lost to follow-up were regarded as failures , the intension-to-treat analysis found no difference between the groups Objective : The aim of this study was to evaluate the safety and efficacy of retropubic ( RP ) or transobturator ( TO ) midurethral slings ( MUS ) in a prospect i ve r and omized cohort of Turkish women . Patients and Methods : A total of 54 women with urodynamic stress urinary incontinence ( SUI ) were r and omized to undergo either RP or TO MUS between August 2006 and February 2013 in a tertiary referral center by a single surgeon . All patients had history , physical examination , urodynamic evaluation and quality of life assessment s. The vali date d Turkish versions of the SEAPI , ICIQ-SF and OAB-V8 question naires were used . The Advantage ® RP and the Obtryx ® TO MUS Systems were used for all RP and TO procedures . Results : Twenty-seven patients were r and omized to each group . The median follow-up was 48.5 ± 21.8 months . The median hospital stay was 24.0 ± 4.8 h and median operative time was 35.0 ± 19.9 min . The overall objective and subjective cure rates were 92.6 and 79.6 % , respectively . The quality of life of all patients significantly increased after the operation compared to their preoperative status . Patients with a poorer subjective cure rate were those with mixed urinary incontinence , whose preoperative SEAPI and OAB-V8 scores were significantly higher . Conclusion : MUS surgery is highly effective and could safely be performed in a cohort of Turkish women with SUI in subspecialty centers by experienced surgeons . There is no significant difference between RP or TO applications in terms of safety and efficacy . Further studies with long-term follow-up data are required Introduction and hypothesisThe purpose of this study is to compare the retropubic tension-free vaginal tape ( TVT ) procedure with the inside-out transobturator approach ( TVT-O ) . Methods Multicenter r and omized controlled trial . One hundred forty-nine patients were r and omly allocated to either TVT ( n = 75 ) or TVT-O ( n = 74 ) . Interview , medical examination , pain scores , success rates , and quality of life assessment were recorded pre-operatively , and 2 , 6 , 12 , and 24 months post-operatively . Results One hundred forty-nine patients underwent surgery , and 132 completed a 24-month follow-up . Bladder injury rate was 5 % ( 4/75 ) in the TVT group and 2 % ( 2/74 ) in the TVT-O group ( p = 0.68 ) . There was no significant difference between the two groups , concerning overall cure rate and the patients ' satisfaction rate at 24 months follow-up . The range of mean pain scores was significantly higher after the TVT-O procedure post-operatively but not at 24 months follow-up . Conclusion TVT and TVT-O procedures both have an outcome associated with an increase in quality of life with no significant differences in satisfaction rates at 2 years follow-up Please cite this paper as : Abdel‐fattah M , Ramsay I , Pringle S , Hardwick C , Ali H , Young D , Mostafa A. R and omised prospect i ve single‐blinded study comparing ‘ inside‐out ’ versus ‘ outside‐in ’ transobturator tapes in the management of urodynamic stress incontinence : 1‐year outcomes from the E‐TOT study . BJOG 2010;117:870–878 PURPOSE We compared the efficacy and complications of tension-free vaginal tape and tension-free vaginal tape-obturator . MATERIAL S AND METHODS Women with pure urodynamic stress incontinence undergoing only primary continence surgery were r and omized to tension-free vaginal tape or tension-free vaginal tape-obturator at 2 centers between March 2005 and March 2007 . Primary outcome was objective cure rate at 6 months , defined by a 24-hour pad test of less than 5 gm . Secondary outcomes were the subjective cure rate on the Patient Global Impression of Improvement , quality of life on the King 's Healthcare Question naire and symptom severity scores on the International Consultation on Incontinence Question naire . RESULTS A total of 127 women were recruited . The study was stopped early due to excess leg pain in the tension-free vaginal tape-obturator group . Of the women 66 were r and omized to tension-free vaginal tape and 61 were r and omized to tension-free vaginal tape-obturator . Analysis was done by intent to treat . The objective and subjective cure rate at 6 months for tension-free vaginal tape vs tension-free vaginal tape-obturator was 69.7 % vs 72.1 % and 72.7 % vs 67.2 % ( p = 0.76 and 0.49 , respectively ) . Cure rates at 1 year were similar but loss to followup was high . Objective and subjective cure rates at 1 year for tension-free vaginal tape vs tension-free vaginal tape-obturator were 50 % vs 41 % and 53 % vs 42.6 % ( p = 0.31 and 0.24 , respectively ) . More women complained of leg pain after receiving a tension-free vaginal tape-obturator ( 26.4 % vs 1.7 % , p = 0.0001 ) . The incidence of perioperative complications was low and similar between the groups . Time to discharge home and time to normal activity were not significantly different . CONCLUSIONS Short-term cure rates at 6 months were similar . Tension-free vaginal tape-obturator caused more transient leg pain . Each procedure achieved a high cure rate and a low complication rate OBJECTIVE The purpose of this study was to assess prospect ively the effects of midurethral sling surgery on sexual function and activity . STUDY DESIGN Sexual activity and function was assessed in 597 women with stress urinary incontinence who were enrolled in a r and omized equivalence trial of retropubic compared with transobturator midurethral slings . Repeated measures analysis of variance was used to assess changes in Pelvic Organ Prolapse/Urinary Incontinence Sexual Question naire scores over a 2-year period . RESULTS Significant , similar improvements in sexual function were seen in both midurethral sling groups . Mean Pelvic Organ Prolapse/Urinary Incontinence Sexual Question naire scores increased from 32.8 at baseline to 37.6 at 6 months and 37.3 at 24 months ( P < .0001 ) . Dyspareunia , incontinence during sex , and fear of incontinence during sex each significantly improved after surgery . Preoperative urge incontinence was associated with abstinence after surgery ( P = .02 ) ; postoperative urge incontinence negatively impacted sexual function ( P = .047 ) . CONCLUSION Midurethral sling surgery for stress urinary incontinence significantly improves sexual function , although coexistent urge incontinence has a negative impact PURPOSE We prospect ively compared the efficacy and safety of tension-free vaginal tape and transobturator vaginal tape inside-out for female stress urinary incontinence . MATERIAL S AND METHODS A total of 120 women with stress urinary incontinence were alternately assigned to the tension-free vaginal tape group ( 60 ) or the transobturator vaginal tape inside-out group ( 60 ) . Preoperative evaluation included urodynamic study and a Korean version of the incontinence quality of life question naire . One year after operation the surgical result , patient satisfaction , incontinence quality of life question naire , long-term complications and uroflowmetry were evaluated in the 2 groups . RESULTS Patient characteristics were comparable in the 2 groups . Mean + /- SD operative time was significantly shorter in the transobturator vaginal tape inside-out vs the tension-free vaginal tape group ( 11 + /- 1.4 vs 15 + /- 1.8 minutes ) . In the transobturator vaginal tape inside-out and the tension-free vaginal tape groups the rates of cure ( 86.8 % and 86.8 % ) , improvement ( 6.6 % and 8.2 % ) and failure ( 6.6 % and 5.0 % , respectively ) were similar . Incontinence quality of life question naire parameters 1 year after surgery were improved significantly in each group and there was no difference between the 2 groups ( p < 0.001 and > 0.05 , respectively ) . There was no long-term complication in either group . Preoperative urge incontinence resolved in 80 % of the tension-free vaginal tape group and in 100 % of the transobturator vaginal tape inside-out group . De novo urgency developed in 4 patients ( 6.6 % ) in the transobturator vaginal tape inside-out group . CONCLUSIONS The tension-free vaginal tape and transobturator vaginal tape inside-out procedures were minimally invasive and similar in operation related morbidity . Transobturator vaginal tape inside-out appeared to be as effective and safe as tension-free vaginal tape for the surgical treatment of stress urinary incontinence in women at 1-year followup Introduction and hypothesisThe purpose of this study is to compare retropubic tension-free vaginal tape ( TVT ) with transobturator out-in TOT and in-out TVT-O for female stress urinary incontinence . Uroflow rate was primary ; continence rates , quality of life ( QoL ) and complication pattern were secondary endpoints . Methods A prospect i ve r and omised trial with 2:1:1 r and omisation at two Swiss teaching hospitals . Patients were followed up at 12 months . Results Eighty TVT , 40 transobturator tape ( TOT ) and 40 TVT-O were r and omised . At 12 months , there was no difference in Qmax among the groups . Continence was comparable ( ≥89 % ) . QoL was improved significantly in all groups ( P < 0.05 ) . Five vaginal tape exposures occurred ( one TVT , four TOT , zero TVT-O ; P = 0.028 ) . Two percent ( 1/52 ) of sexually active patients after TVT , 17 % ( 5/29 ) after TOT , but 0 % ( 0/25 ) after TVT-O reported de novo female sexual dysfunction ( P = 0.011 ) . We considered this clinical ly important enough to stop enrolment . Conclusions There was no difference for Qmax at 12 months between TVT , TOT and TVT-O. Female sexual dysfunction and tape exposure may be higher with a transobturator tape PURPOSE Longer term comparative efficacy information regarding transobturator and retropubic mid urethral slings is needed . We report 24-month continence rates , complications and symptom outcomes from a r and omized equivalence trial . MATERIAL S AND METHODS Primary outcomes were objective ( negative stress test , negative pad test and no re-treatment for stress urinary incontinence ) and subjective ( no self-report of stress urinary incontinence symptoms , no leakage episodes on 3-day bladder diary and no re-treatment for stress urinary incontinence ) success at 24 months . The predetermined equivalence margin was ± 12 % . RESULTS Of 597 r and omized participants 516 ( 86.4 % ) were assessed . Objective success rates for retropubic and transobturator mid urethral slings were 77.3 % and 72.3 % , respectively ( 95 % CI for difference of 5.1 % was -2.0 , 12.1 ) , and subjective success rates were 55.7 % and 48.3 % , respectively ( CI for difference of 7.4 % was -0.7 , 15.5 ) . Neither objective nor subjective success rates met the prespecified criteria for equivalence . Patient satisfaction ( retropubic 86.3 % vs transobturator 88.1 % , p = 0.58 ) , frequency of de novo urgency incontinence ( retropubic 0 % vs transobturator 0.3 % , p = 0.99 ) and occurrence of mesh exposure ( retropubic 4.4 % vs transobturator 2.7 % , p = 0.26 ) were not significantly different . The retropubic mid urethral sling group had higher rates of voiding dysfunction requiring surgery ( 3.0 % vs 0 % , p = 0.002 ) and urinary tract infections ( 17.1 % vs 10.7 % , p = 0.025 ) , whereas the transobturator group had more neurological symptoms ( 9.7 % vs 5.4 % , p = 0.045 ) . CONCLUSIONS Objective success rates met the criteria for equivalence at 12 months but no longer met these criteria at 24 months . Subjective success rates remained inconclusive for equivalence . Patient satisfaction remained high and symptom severity remained markedly improved . Continued surveillance is important in women undergoing mid urethral sling surgery BACKGROUND Midurethral slings have become the most preferred surgical treatment for female urinary incontinence . OBJECTIVE To compare the efficacy and safety of two midurethral sling procedures with a different technique of sling insertion 5 yr after intervention . DESIGN , SETTING , AND PARTICIPANTS Multicenter r and omized clinical trial conducted in seven public hospitals in Finl and including primary cases of stress urinary incontinence . INTERVENTION Surgical treatment with the retropubic tension-free vaginal tape ( TVT ) procedure or the transobturator tension-free vaginal tape ( TVT-O ) procedure . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Objective treatment success criteria were a negative stress test , a negative 24-h pad test , and no retreatment for stress incontinence . Patient satisfaction was assessed by condition-specific quality -of-life question naires . RESULTS AND LIMITATIONS A total of 95 % of the included women could be assessed according to the protocol 5 yr after surgery . The objective cure rate was 84.7 % in the TVT group and 86.2 % in the TVT-O group , with no statistical difference between the groups . Subjective treatment satisfaction was 94.2 % in the TVT group and 91.7 % in the TVT-O group , with no difference between groups . Complication rates were low , with no difference between groups . CONCLUSIONS Both objective and subjective cure rates were > 80 % in both groups even when women lost to follow-up were included as failures . The complication rates were low , with no difference between the groups . No late-onset adverse effects of the tape material were seen . PATIENT SUMMARY Female urinary stress incontinence can be treated surgically with minimally invasive midurethral sling procedures . Two main approaches of sling placement have been developed : the retropubic and the transobturatory . We compared both approaches and followed the patients for 5 yr . We found no difference in cure rate between the procedures , and patient satisfaction was high . TRIAL REGISTRATION Clinical Trials.gov identifier NCT00379314 PURPOSE Few studies have characterized longer-term outcomes after retropubic and transobturator mid urethral slings . MATERIAL S AND METHODS Women completing 2-year participation in a r and omized equivalence trial who had not undergone surgical re-treatment for stress urinary incontinence were invited to participate in a 5-year observational cohort . The primary outcome , treatment success , was defined as no re-treatment or self-reported stress incontinence symptoms . Secondary outcomes included urinary symptoms and quality of life , satisfaction , sexual function and adverse events . RESULTS Of 597 women 404 ( 68 % ) from the original trial enrolled in the study . Five years after surgical treatment success was 7.9 % greater in women assigned to the retropubic sling compared to the transobturator sling ( 51.3 % vs 43.4 % , 95 % CI -1.4 , 17.2 ) , not meeting prespecified criteria for equivalence . Satisfaction decreased during 5 years but remained high and similar between arms ( retropubic sling 79 % vs transobturator sling 85 % , p=0.15 ) . Urinary symptoms and quality of life worsened with time ( p < 0.001 ) , and women with a retropubic sling reported greater urinary urgency ( p=0.001 ) , more negative impact on quality of life ( p=0.02 ) and worse sexual function ( p=0.001 ) . There was no difference in the proportion of women experiencing at least 1 adverse event ( p=0.17 ) . Seven new mesh erosions were noted ( retropubic sling 3 , transobturator sling 4 ) . CONCLUSIONS Treatment success decreased during 5 years for retropubic and transobturator slings , and did not meet the prespecified criteria for equivalence with retropubic demonstrating a slight benefit . However , satisfaction remained high in both arms . Women undergoing a transobturator sling procedure reported more sustained improvement in urinary symptoms and sexual function . New mesh erosions occurred in both arms over time , although at a similarly low rate Aims A study was conducted to compare the efficacy and complications of tension-free vaginal tape ( TVT ) , transobturator vaginal tape inside-out TVT-0 and transobturator vaginal tape out-inside ( TOT ) procedures for the surgical treatment of female stress urinary incontinence SUI . Methods This study is a prospect i ve r and omized trial involving 187 women with primary SUI ; 77 received TVT , 65 received TVT-O , and 45 patients were treated with TVT-0 between June 2002 and December 2009 . Before the operation , a complete medical history was taken and a gynecologic examination was performed , including subjective symptoms , history and urodynamic studies . Postoperative data included mean operation time , days of hospitalization , postoperative complications and efficacy evaluation . Therapeutic effect was assessed by presence or absence of incontinence when abdominal pressure increased . Results The history , physical examination and urodynamic studies among the three groups have no significant difference ( P>0.05 ) . The total cure rate was 91.4 % . The cure rate in TVT , TVT-O and TOT groups were 90.9 % , 92.3 % and 91.1 % , respectively . There was no significant difference ( P>0.05 ) . Mean operative time showed no significant difference between TVT-O and TOT groups , but both were significantly shorter than TVT group ( 26.90±16.80 , 20.00±13.50 vs 48.20±21.90 ) . The mean postoperative hospital stay showed no significant difference between TVT and TVT-O groups , but both groups were significantly longer than TOT group . Mean postoperative hospital stay of TVT , TVT-O and TOT were 5.00±2.40 days , 4.00±2.20 days and 2.30±0.80 days , respectively . The complication rate in TVT , TVT-O and TOT groups was 15.60 % , 9.20 % and 8.90 % , respectively . In TVT group , 4 patients experienced bladder perforation , postoperative dysuria or retention occurred in 7 cases and was cured by urethral dilation , hematomas of retropubic space in 1 patient . No bladder injury occurred in TVT-O and TOT group , 3 patients had postoperative dysuria or retention and 3 patients had transient dysfunction of both lower limbs postoperatively in TVT-O group , 2 patients had postoperative dysuria or retention and 2 patients had transient dysfunction of both lower limbs postoperatively in TOT group . Summary The three tension-free urethral suspension techniques have similar efficacy , all of them are safe and effective procedures for the treatment of female SUI . Compared with TVT , TVT-O and TOT are simpler , less invasive and have fewer complications Introduction and hypothesisThis is a r and omized multicenter study comparing two mid-urethra tape procedures , the tension-free vaginal tape ( TVT ) with the tension-free vaginal tape-obturator ( TVT-O ) in terms of cure rate and complication rate . Methods Seven Finnish hospitals participated . Power calculations required 130 women in each group to detect a 10 % difference in cure rate . A total of 267 underwent the allocated operation . Follow-up was scheduled at 2 , 12 , 36 and 60 months . A cough stress test was used as an objective outcome measure . Subjective outcome was assessed by five different condition-specific quality of life question naires . Results At 36 months of follow-up , 96 % of the patients were evaluated . Objective cure rate was 94.6 % in the TVT group and 89.5 % in the TVT-O group ( p = 0.131 ) . Subjective cure rates were significant with no difference between the groups . Conclusion The TVT and the TVT-O are equally effective in the treatment of stress urinary incontinence after 36-month follow-up with no difference in complication rates Introduction and hypothesisIn a r and omised trial comparing transobturator tape ( TOT ) to retropubic tension-free vaginal tape ( TVT ) for women with stress urinary incontinence ( SUI ) , vaginal examination at 12 months showed that tapes were palpable for 80.0 % of the TOT group versus 26.7 % of the TVT group . We hypothesized that this difference would lead to more women in the TOT group experiencing vaginal mesh erosion or other serious adverse events compared to women in the TVT group 5 years after surgery . Methods All participants were invited to join the follow-up study after being r and omised to receive TOT or TVT for SUI . Consenting women had a vaginal examination , a pad test for urinary incontinence ( UI ) and completed Health-related Quality of Life Question naires ( HRQOL ) . Women unable to attend the clinic completed question naires only . The primary composite outcome incorporated mesh exposure , urinary retention , repeat incontinence surgery and moderate to severe pelvic pain . Assuming 80 % follow-up , our study would have 67 % power to detect a difference in primary outcome ( two-sided 5 % level of significance ) . Comparisons between groups used chi-square tests and t tests . Results One hundred and seventy-six ( 88.4 % ) women participated in the 5-year follow-up ( 83 TOT , 93 TVT ) . The primary composite outcome occurred in 21.8 % of the TOT and 27.6 % of the TVT groups [ difference = −5.8 % , 95 % confidence interval ( CI ) −18.9 % to 7.3 % , p value 0.39 ) ] Vaginal examination found more women with palpable tapes in the TOT versus the TVT group ( 48.5 % versus 22.4 % , p value 0.001 ) . There were no other significant differences between groups . Conclusions Serious adverse events and tape effectiveness did not differ between groups at 5 years . Palpable tape remains a concern for women who receive TOT for treating SUI OBJECTIVE : To compare the efficacy of tension-free vaginal tape ( TVT ) to transobturator tape in the treatment of women with stress urinary incontinence ( SUI ) and intrinsic sphincter deficiency at 3-year follow-up . METHODS : One hundred sixty-four women were r and omized to either TVT or transobturator tape after diagnosis of urodynamic stress incontinence and intrinsic sphincter deficiency . Concomitant pelvic organ prolapse surgery was not an exclusion criterion . The primary outcome assessed at 3-year follow-up was symptomatic stress incontinence requiring repeat surgery . Secondary outcomes were quality -of-life parameters assessed by vali date d question naires and numerical success score . RESULTS : One hundred sixty-four women were enrolled in the study . At 3 years , 15 of the 75 ( 20 % ) women in the transobturator tape group underwent repeat surgery to correct SUI compared with one of the 72 ( 1.4 % ) in the TVT group . In other words , if TVT had been used exclusively , repeat surgery would have been avoided in one in six patients . The risk ratio of repeat surgery was 15 ( 95 % confidence interval 2–113 ; P<.001 ) times greater in the transobturator tape group . In the transobturator tape group , the median time to repeat surgery was 15.6 months compared with 43.7 months for TVT ( P<.001 ) . The quality -of-life outcomes did show an improvement in both groups before and after surgery but no difference between the two slings in the Urogenital Distress Inventory short form , the Incontinence Impact Question naire short form , and a patient-rated numerical success score . CONCLUSION : The long-term cure rates for retropubic TVT are significantly greater than for transobturator tape in women with urodynamic stress incontinence and intrinsic sphincter deficiency . Urethral functions tests such as urethral closure pressure and Valsalva leak point pressures are of value in determining what surgery to perform . CLINICAL TRIAL REGISTRATION : Australian New Zeal and Clinical Trials Registry , www.anzctr.org.au , ACTRN12608000093381 . LEVEL OF EVIDENCE : |
12,775 | 23,917,769 | CONCLUSION With this systematic review , it is possible to conclude that motor physical therapy is a feasible and safe therapy for critically ill patients and can minimize the deleterious effects of prolonged immobilization .
Approaches involving electrostimulation , cycle ergometry and kinesiotherapy showed positive responses in patients under intensive care . | OBJECTIVE To analyze the outcomes achieved by motor physical therapy in critically ill patients admitted to intensive care units . | Introduction Critically ill patients are characterized by increased loss of muscle mass , partially attributed to sepsis and multiple organ failure , as well as immobilization . Recent studies have shown that electrical muscle stimulation ( EMS ) may be an alternative to active exercise in chronic obstructive pulmonary disease ( COPD ) and chronic heart failure ( CHF ) patients with myopathy . The aim of our study was to investigate the EMS effects on muscle mass preservation of critically ill patients with the use of ultrasonography ( US ) . Methods Forty-nine critically ill patients ( age : 59 ± 21 years ) with an APACHE II admission score ≥13 were r and omly assigned after stratification upon admission to receive daily EMS sessions of both lower extremities ( EMS-group ) or to the control group ( control group ) . Muscle mass was evaluated with US , by measuring the cross sectional diameter ( CSD ) of the vastus intermedius and the rectus femoris of the quadriceps muscle . Results Twenty-six patients were finally evaluated . Right rectus femoris and right vastus intermedius CSD decreased in both groups ( EMS group : from 1.42 ± 0.48 to 1.31 ± 0.45 cm , P = 0.001 control group : from 1.59 ± 0.53 to 1.37 ± 0.5 cm , P = 0.002 ; EMS group : from 0.91 ± 0.39 to 0.81 ± 0.38 cm , P = 0.001 control group : from 1.40 ± 0.64 to 1.11 ± 0.56 cm , P = 0.004 , respectively ) . However , the CSD of the right rectus femoris decreased significantly less in the EMS group ( -0.11 ± 0.06 cm , -8 ± 3.9 % ) as compared to the control group ( -0.21 ± 0.10 cm , -13.9 ± 6.4 % ; P < 0.05 ) and the CSD of the right vastus intermedius decreased significantly less in the EMS group ( -0.10 ± 0.05 cm , -12.5 ± 7.4 % ) as compared to the control group ( -0.29 ± 0.28 cm , -21.5 ± 15.3 % ; P < 0.05 ) . Conclusions EMS is well tolerated and seems to preserve the muscle mass of critically ill patients . The potential use of EMS as a preventive and rehabilitation tool in ICU patients with polyneuromyopathy needs to be further investigated . Trial Registration clinical trials.gov : Objective : To determine whether early activity is feasible and safe in respiratory failure patients . Design : Prospect i ve cohort study . Setting : From June 1 , 2003 , through December 31 , 2003 , we assessed safety and feasibility of early activity in all consecutive respiratory failure patients who required mechanical ventilation for > 4 days admitted to our respiratory intensive care unit ( RICU ) . A majority of patients were treated in another intensive care unit ( ICU ) before RICU admission . We excluded patients who required mechanical ventilation for ≤4 days . Patients : Eight‐bed RICU at LDS Hospital . Interventions : We assessed patients for early activity as part of routine respiratory ICU care . We prospect ively recorded activity events and adverse events . We defined three activity events as sit on bed , sit in chair , and ambulate . We defined six activity‐related adverse events as fall to knees , tube removal , systolic blood pressure > 200 mm Hg , systolic blood pressure < 90 mm Hg , oxygen desaturation < 80 % , and extubation . Measurements and Main Results : During the study period , we conducted a total of 1,449 activity events in 103 patients . The activity events included 233 ( 16 % ) sit on bed , 454 ( 31 % ) sit in chair , and 762 ( 53 % ) ambulate . In patients with an endotracheal tube in place , there were a total of 593 activity events , of which 249 ( 42 % ) were ambulation . There were < 1 % activity‐related adverse events , including fall to the knees without injury , feeding tube removal , systolic blood pressure > 200 mm Hg , systolic blood pressure < 90 mm Hg , and desaturation < 80 % . No patient was extubated during activity . Conclusions : We conclude that early activity is feasible and safe in respiratory failure patients . A majority of survivors ( 69 % ) were able to ambulate > 100 feet at RICU discharge . Early activity is a c and i date therapy to prevent or treat the neuromuscular complications of critical illness Objectives : To investigate whether a daily exercise session , using a bedside cycle ergometer , is a safe and effective intervention in preventing or attenuating the decrease in functional exercise capacity , functional status , and quadriceps force that is associated with prolonged intensive care unit stay . A prolonged stay in the intensive care unit is associated with muscle dysfunction , which may contribute to an impaired functional status up to 1 yr after hospital discharge . No evidence is available concerning the effectiveness of an early exercise training intervention to prevent these detrimental complications . Design : R and omized controlled trial . Setting : Medical and surgical intensive care unit at University Hospital Gasthuisberg . Patients : Ninety critically ill patients were included as soon as their cardiorespiratory condition allowed bedside cycling exercise ( starting from day 5 ) , given they still had an expected prolonged intensive care unit stay of at least 7 more days . Interventions : Both groups received respiratory physiotherapy and a daily st and ardized passive or active motion session of upper and lower limbs . In addition , the treatment group performed a passive or active exercise training session for 20 mins/day , using a bedside ergometer . Measurements and Main Results : All outcome data are reflective for survivors . Quadriceps force and functional status were assessed at intensive care unit discharge and hospital discharge . Six-minute walking distance was measured at hospital discharge . No adverse events were identified during and immediately after the exercise training . At intensive care unit discharge , quadriceps force and functional status were not different between groups . At hospital discharge , 6-min walking distance , isometric quadriceps force , and the subjective feeling of functional well-being ( as measured with “ Physical Functioning ” item of the Short Form 36 Health Survey question naire ) were significantly higher in the treatment group ( p < .05 ) . Conclusions : Early exercise training in critically ill intensive care unit survivors enhanced recovery of functional exercise capacity , self-perceived functional status , and muscle force at hospital discharge STUDY OBJECTIVES To evaluate the effects of early exercise training in patients recovering from acute respiratory failure needing mechanical ventilation ( MV ) . DESIGN Prospect i ve , r and omized , and controlled study . SETTING Three respiratory intermediate ICUs ( RIICUs ) . PATIENTS Of 228 patients admitted to an RIICU , 66 patients weaned from MV from > 48 to < 96 h were considered eligible and enrolled in the study . INTERVENTION Sixty-six patients were r and omized to either supported arm exercise training plus general physiotherapy ( gPT ) [ group 1 , 32 patients ] or to gPT alone ( group 2 , 34 patients ) . MEASUREMENTS AND RESULTS Twenty-five patients in each group completed the protocol . Group 1 showed a greater improvement in exercise capacity , as assessed by an arm incremental test ( IT ) [ p = 0.003 ] and an endurance test ( ET ) [ p = 0.021 ] , compared to group 2 . Posttraining maximal inspiratory pressure ( MIP ) significantly improved in both groups ( p < 0.001 and p = 0.003 in groups 1 and 2 respectively ; not significant ) . IT isoworkload dyspnea improved significantly in both groups ( p = 0.005 and p = 0.009 in groups 1 and 2 , respectively ; not significant between groups ) , whereas IT isoworkload peripheral muscle fatigue ( p < 0.001 ) , ET isotime dyspnea ( p < 0.01 ) , and ET isotime muscular fatigue ( p < 0.005 ) improved significantly in group 1 but not in group 2 . IT improvers ( chi2 = 0.004 ) and ET improvers ( chi2 = 0.047 ) were more frequently observed in group 1 than in group 2 . Baseline MIP could discriminate for IT ( p = 0.013 ; odds ratio [ OR ] , 1.116 ) and ET improvers ( p = 0.022 ; OR , 1.067 ) . CONCLUSION Early upper-limb exercise training is feasible in RIICU patients recently weaned from MV and can enhance the effects of gPT . Baseline inspiratory muscle function is related to exercise capacity improvement OBJECTIVE It is known that patients in the intensive care unit show an enormous loss of muscle mass . Neuromuscular electrical stimulation is effective in enhancing strength and endurance in immobilized patients . The aim of this study was to evaluate the effects of neuromuscular electrical stimulation on muscle layer thickness of knee extensor muscles in intensive care unit patients . DESIGN R and omized , controlled , double-blind , pilot trial . PATIENTS Thirty-three patients , male to female ratio 26:7 , mean age 55 years ( st and ard deviation 15 ) . METHODS After enrolment in the study , intensive care unit patients ( main diagnoses : polytrauma , cardiovascular diseases , transplantation , pneumonia , cancer ) were stratified ( based on the length of their stay in hospital ) into 2 groups : 17 acute patients ( < 7 days ) and 16 long-term patients ( > 14 days ) . Both groups were r and omized to a stimulation group or a sham-stimulation group . Neuromuscular electrical stimulation was applied to knee extensor muscles for a period of 4 weeks ( session time 30 - 60 minutes , 5 days/week ) . Ultrasound measurements were performed before and after the stimulation period to quantify muscle layer thickness of knee extensor muscles . RESULTS Only stimulated long-term patients ( + 4.9 % ) showed a significant ( p = 0.013 ) increase in muscle layer thickness compared with sham-stimulated patients ( -3.2 % ) . CONCLUSION Neuromuscular electrical stimulation appears to be a useful adjunct to revert muscle wasting in intensive care unit long-term patients ; however , larger studies with a larger sample size are needed to confirm these promising , but preliminary , results OBJECTIVE Patients in intensive care exhibit a high degree of loss of muscle mass . Appropriate instruments are needed to document muscle wasting in these patients . The aim of this pilot study was to describe muscle wasting in patients in the intensive care unit . DESIGN Two-fold study setting : prospect i ve longitudinal and cross-sectional single-blind . PATIENTS A total of 118 patients in the intensive care unit ( length of stay 1 - 98 days ; male : female ratio 88:30 ; age 55 + /- 17 years ) were included in a two-fold study setting . METHODS Muscle layer thickness of the M. quadriceps femoris was documented using ultrasound measurement at well-defined points . Seventeen pilot- patients were measured twice ; at baseline and after 28 days . In another group of 101 patients , muscle layer thickness was determined once after a r and om length of stay . The results of both groups were compared and correlated . RESULTS In both groups , M. quadriceps femoris thickness showed a significant negative correlation with length of stay in the intensive care unit ( p < 0.01 ) . Furthermore , muscle wasting in intensive care patients could be described using a logarithmic function . CONCLUSION Loss of muscle mass shows a negative correlation with length of stay , and seems to be higher during the first 2 - 3 weeks of immobilization/intensive care unit stay . Ultrasound is a valid and practical measurement tool for documenting muscle mass ( e.g. muscle layer thickness ) as part of the daily routine at an intensive care unit STUDY OBJECTIVE To compare the effects of active limb mobilization ( ALM ) with or without electrical stimulation ( ES ) on muscle strength , respiratory rate ( RR ) , heart rate , oxygen saturation , and time needed to transfer from bed to chair in two groups of patients with COPD . DESIGN R and omized , controlled study . SETTING Respiratory high-dependency care unit . PATIENTS Twenty-four bed-bound patients with chronic hypercapnic respiratory failure due to COPD who were receiving mechanical ventilation , with marked peripheral muscle hypotonia and atrophy . METHODS Patients were r and omly assigned either to ALM alone or to ALM plus ES ( ALM/ES ) . ES was applied using square-wave alternate , symmetric , and compensated impulses for 30 min bid . The duration of treatment was 28 days for all patients . RESULTS Muscle strength improved significantly in the overall group of patients ( from 1.75 + /- 0.73 to 3.44 + /- 0.65 , p < 0.05 ) . Comparing the change ( end minus beginning ) of the analyzed variables , ALM/ES significantly improved muscle strength ( 2.16 + /- 1.02 vs 1.25 + /- 0.75 , p = 0.02 ) and RR ( - 1.91 + /- 1.72 vs 0.41 + /- 1.88 , p = 0.004 ) , and decreased the number of days needed to transfer from bed to chair ( 10.75 + /- 2.41 days vs 14.33 + /- 2.53 days , p = 0.001 ) . CONCLUSION In bed-bound patients with COPD receiving mechanical ventilation , with marked peripheral muscle hypotonia and atrophy , application of ES in addition to classical ALM significantly improved muscle strength and decreased the number of days needed to transfer from bed to chair Background and Purpose . Patients requiring prolonged mechanical ventilation ( PMV ) are frequently deconditioned because of respiratory failure precipitated by the underlying disease , the adverse effects of medications , and a period of prolonged immobilization . The effects of 6 weeks of physical training on the strength of respiratory and limb muscles , on ventilator-free time , and on functional status in patients requiring PMV were examined . Subjects . Thirty-nine patients with PMV were initially enrolled in the study and were assigned to either a treatment group ( n=20 ) or a control group ( n=19 ) . Three subjects in the treatment group and 4 subjects in the control group died during the 6-week intervention period and thus their data were excluded from the final analysis . Methods . Subjects in the treatment group received physical training 5 days a week for 6 weeks . Strength of respiratory and limb muscles , ventilator-free time , and functional status , which was measured by the Barthel Index of Activities of Daily Living ( BI ) and Functional Independence Measure ( FIM ) , were examined at baseline and at the third and sixth weeks of the study period . Results . Respiratory and limb muscle strength improved significantly at the third and sixth weeks in the treatment group compared with baseline measurements . Total BI and FIM scores increased significantly in the treatment group and remained unchanged in the control group . Effect sizes of the BI and FIM scores were 2.02 and 1.93 , respectively , at the sixth week . Discussion and Conclusion . The results show that a 6-week physical training program may improve limb muscle strength and ventilator-free time and thus improve functional outcomes in patients requiring PMV Objective : Immobilization and subsequent weakness are consequences of critical illness . Despite the theoretical advantages of physical therapy to address this problem , it has not been shown that physical therapy initiated in the intensive care unit offers benefit . Design and Setting : Prospect i ve cohort study in a university medical intensive care unit that assessed whether a mobility protocol increased the proportion of intensive care unit patients receiving physical therapy vs. usual care . Patients : Medical intensive care unit patients with acute respiratory failure requiring mechanical ventilation on admission : Protocol , n = 165 ; Usual Care , n = 165 . Interventions : An intensive care unit Mobility Team ( critical care nurse , nursing assistant , physical therapist ) initiated the protocol within 48 hrs of mechanical ventilation . Measurements and Main Results : The primary outcome was the proportion of patients receiving physical therapy in patients surviving to hospital discharge . Baseline characteristics were similar between groups . Outcome data are reflective of survivors . More Protocol patients received at least one physical therapy session than did Usual Care ( 80 % vs. 47 % , p ≤ .001 ) . Protocol patients were out of bed earlier ( 5 vs. 11 days , p ≤ .001 ) , had therapy initiated more frequently in the intensive care unit ( 91 % vs. 13 % , p ≤ .001 ) , and had similar low complication rates compared with Usual Care . For Protocol patients , intensive care unit length of stay was 5.5 vs. 6.9 days for Usual Care ( p = .025 ) ; hospital length of stay for Protocol patients was 11.2 vs. 14.5 days for Usual Care ( p = .006 ) ( intensive care unit/hospital length of stay adjusted for body mass index , Acute Physiology and Chronic Health Evaluation II , vasopressor ) . There were no untoward events during an intensive care unit Mobility session and no cost difference ( survivors + nonsurvivors ) between the two arms , including Mobility Team costs . Conclusions : A Mobility Team using a mobility protocol initiated earlier physical therapy that was feasible , safe , did not increase costs , and was associated with decreased intensive care unit and hospital length of stay in survivors who received physical therapy during intensive care unit treatment compared with patients who received usual care Objective : Intensive care unit admission is associated with muscle wasting and impaired physical function . We investigated the effect of early transcutaneous electrical muscle stimulation on quadriceps muscle volume in patients with septic shock . Design : R and omized interventional study using a single-legged exercise design with the contralateral leg serving as a paired control . Setting : A mixed 18-bed intensive care unit at a tertiary care university hospital . Patients : Eight adult male intensive care unit patients with septic shock included within 72 hrs of diagnosis . Interventions : After r and omization of the quadriceps muscles , transcutaneous electrical muscle stimulation was applied on the intervention side for 7 consecutive days and for 60 mins per day . All patients underwent computed tomographic scans of both thighs immediately before and after the 7-day treatment period . The quadriceps muscle was manually delineated on the computed tomography slices , and muscle volumes were calculated after three-dimensional reconstruction . Measurements and Main Results : Median age and Acute Physiology and Chronic Health Evaluation II score were 67 years ( interquartile range , 64–72 years ) and 25 ( interquartile range , 20–29 ) , respectively . During the 7-day study period , the volume of the quadriceps muscle on the control thigh decreased by 16 % ( 4–21 % , p = .03 ) corresponding to a rate of 2.3 % per day . The volume of the stimulated muscle decreased by 20 % ( 3–25 % , p = .04 ) corresponding to a rate of 2.9 % per day ( p = .12 for the difference in decrease ) . There was no difference in muscle volume between the stimulated and nonstimulated thigh at baseline ( p = .10 ) or at day 7 ( p = .12 ) . The charge delivered to the muscle tissue per training session ( 0.82 [ 0.66–1.18 ] coulomb ) correlated with the maximum sequential organ failure assessment score . Conclusions : We observed a marked decrease in quadriceps volume within the first week of intensive care for septic shock . This loss of muscle mass was unaffected by transcutaneous electrical muscle stimulation applied for 60 mins per day for 7 days 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 . CONTEXT Although electrophysiologic and histologic neuromuscular abnormalities are common in intensive care unit ( ICU ) patients , the clinical incidence of ICU-acquired neuromuscular disorders in patients recovering from severe illness remains unknown . OBJECTIVES To assess the clinical incidence , risk factors , and outcomes of ICU-acquired paresis ( ICUAP ) during recovery from critical illness in the ICU and to determine the electrophysiologic and histologic patterns in patients with ICUAP . DESIGN Prospect i ve cohort study conducted from March 1999 to June 2000 . SETTING Three medical and 2 surgical ICUs in 4 hospitals in France . PARTICIPANTS All consecutive ICU patients without preexisting neuromuscular disease who underwent mechanical ventilation for 7 or more days were screened daily for awakening . The first day a patient was considered awake was day 1 . Patients with severe muscle weakness on day 7 were considered to have ICUAP . MAIN OUTCOME MEASURES Incidence and duration of ICUAP , risk factors for ICUAP , and comparative duration of mechanical ventilation between ICUAP and control patients . RESULTS Among the 95 patients who achieved satisfactory awakening , the incidence of ICUAP was 25.3 % ( 95 % confidence interval [ CI ] , 16.9%-35.2 % ) . All ICUAP patients had a sensorimotor axonopathy , and all patients who underwent a muscle biopsy had specific muscle involvement not related to nerve involvement . The median duration of ICUAP after day 1 was 21 days . Mean ( SD ) duration of mechanical ventilation after day 1 was significantly longer in patients with ICUAP compared with those without ( 18.2 [ 36.3 ] vs 7.6 [ 19.2 ] days ; P = .03 ) . Independent predictors of ICUAP were female sex ( odds ratio [ OR ] , 4.66 ; 95 % CI , 1.19 - 18.30 ) , the number of days with dysfunction of 2 or more organs ( OR , 1.28 ; 95 % CI , 1.11 - 1.49 ) , duration of mechanical ventilation ( OR , 1.10 ; 95 % CI , 1.00 - 1.22 ) , and administration of corticosteroids ( OR , 14.90 ; 95 % CI , 3.20 - 69.80 ) before day 1 . CONCLUSIONS Identified using simple bedside clinical criteria , ICUAP was frequent during recovery from critical illness and was associated with a prolonged duration of mechanical ventilation . Our findings suggest an important role of corticosteroids in the development of ICUAP Unloaded inactivity induces atrophy and functional deconditioning of skeletal muscle , especially in the lower extremities . Information is scarce , however , regarding the effect of unloaded inactivity on muscle size and function about the hip . Regional bone loss has been demonstrated in hips and knees of elderly orthopaedic patients , as quantified by computerized tomography ( CT ) . This method remains to be vali date d in healthy individuals rendered inactive , including real or simulated weightlessness . In this study , ten healthy males were subjected to 5 weeks of experimental bedrest and five matched individuals served as ambulatory controls . Maximum voluntary isometric hip and knee extension force were measured using the strain gauge technique . Cross-sectional area ( CSA ) of hip , thigh and calf muscles , and radiological density ( RD ) of the proximal tibial bone were measured using CT . Bedrest decreased ( P < 0.05 ) average ( SD ) muscle strength by 20 (8)% in knee extension , and by 22 (12)% in hip extension . Bedrest induced atrophy ( P < 0.05 ) of extensor muscles in the gluteal region , thigh and calf , ranging from 2 to 12 % . Atrophy was more pronounced in the knee extensors [ 9 (4)% ] and ankle plantar flexors [ 12 (3)% ] than in the gluteal extensor muscles [ 2 (2)% ] . Bone density of the proximal tibia decreased ( P < 0.05 ) by 3 (2)% during bedrest . Control subjects did not show any temporal changes in muscle or bone indices ( P > 0.05 ) , when examined at similar time intervals . The present findings of a substantial loss in hip extensor strength and a smaller , yet significant atrophy of these muscles , demonstrate that hip muscle deconditioning accompanies losses in thigh and calf muscle mass after bedrest . This suggests that comprehensive quantitative studies on impaired locomotor function after inactivity should include all joints of the lower extremity . Our results also demonstrate that a decreased RD , indicating bone mineral loss , can be shown already after 5 weeks of unloaded bedrest , using a st and ard CT technique Purpose . To evaluate the functional status of patients within the first week of discharge from an intensive care unit ( ICU ) , and to identify predictors and explanatory factors of functional status . Methods . A prospect i ve , observational , cohort study was conducted with consecutive ICU patients who had stayed in a mixed , closed-format , university-level ICU for longer than 48 h. Results . Between 3 and 7 days of discharge from the ICU , functional status ( as primary outcome ) , walking ability , muscle strength , and sensory and cognitive functioning were assessed in 69 survivors . The overall functional status was poor ( median Barthel Index 6 ) . In their ability to perform basic activities of daily living , 67 % percent were severely dependent , 15 % were moderately dependent , and 9 % were slightly dependent on other people . Independent walking was impossible for 73 % of participants , grip strength was reduced for 50 % , and 30 % had cognitive impairments . Duration of ventilation was associated with functional status after ICU discharge . Reduced grip strength and walking ability were identified as explanatory factors for poorer functional status shortly after discharge from the ICU . Conclusion . In the first week after discharge from the ICU , the majority of the patients had substantial functional disabilities in activities of daily living . These disabilities were more severe in patients who experienced ventilation for a longer period of time . There is a need for prospect i ve studies focusing on functional recovery to support informed decision-making concerning the care of critically ill patients after ICU discharge |
12,776 | 16,080,794 | There were significant pain reductions with OMT regardless of whether trials were performed in the United Kingdom or the United States .
Significant pain reductions were also observed during short- , intermediate- , and long-term follow-up .
Conclusion OMT significantly reduces low back pain .
The level of pain reduction is greater than expected from placebo effects alone and persists for at least three months . | Background Osteopathic manipulative treatment ( OMT ) is a distinctive modality commonly used by osteopathic physicians to complement their conventional treatment of musculoskeletal disorders .
Previous review s and meta-analyses of spinal manipulation for low back pain have not specifically addressed OMT and generally have focused on spinal manipulation as an alternative to conventional treatment .
The purpose of this study was to assess the efficacy of OMT as a complementary treatment for low back pain . | Abstract Objective To estimate the effect of adding exercise classes , spinal manipulation delivered in NHS or private premises , or manipulation followed by exercise to “ best care ” in general practice for patients consulting with back pain . Fig 1 Progress of the UK BEAM trial Design Pragmatic r and omised trial with factorial design . Setting 181 general practice s in Medical Research Council General Practice Research Framework ; 63 community setting s around 14 centres across the United Kingdom . Participants 1334 patients consulting their general practice s about low back pain . Main outcome measures Scores on the Rol and Morris disability question naire at three and 12 months , adjusted for centre and baseline scores . Results All groups improved over time . Exercise improved mean disability question naire scores at three months by 1.4 ( 95 % confidence interval 0.6 to 2.1 ) more than “ best care . ” For manipulation the additional improvement was 1.6 ( 0.8 to 2.3 ) at three months and 1.0 ( 0.2 to 1.8 ) at 12 months . For manipulation followed by exercise the additional improvement was 1.9 ( 1.2 to 2.6 ) at three months and 1.3 ( 0.5 to 2.1 ) at 12 months . No significant differences in outcome occurred between manipulation in NHS premises and in private premises . No serious adverse events occurred . Conclusions Relative to “ best care ” in general practice , manipulation followed by exercise achieved a moderate benefit at three months and a small benefit at 12 months ; spinal manipulation achieved a small to moderate benefit at three months and a small benefit at 12 months ; and exercise achieved a small benefit at three months but not 12 months BACKGROUND Spinal pain is common and frequently disabling . Management guidelines have encouraged referral from primary care for spinal manipulation . However , the evidence base for these recommendations is weak . More pragmatic trials and economic evaluations have been recommended . OBJECTIVES Our aim was to assess the effectiveness and health care costs of a practice -based osteopathy clinic for subacute spinal pain . METHODS A pragmatic r and omized controlled trial was carried out in a primary care osteopathy clinic accepting referrals from 14 neighbouring practice s in North West Wales . A total of 201 patients with neck or back pain of 2 - 12 weeks duration were allocated at r and om between usual GP care and an additional three sessions of osteopathic spinal manipulation . The primary outcome measure was the Extended Aberdeen Spine Pain Scale ( EASPS ) . Secondary measures included SF-12 , EuroQol and Short-form McGill Pain Question naire . Health care costs were estimated from the records of referring GPs . RESULTS Outcomes improved more in the osteopathy group than the usual care group . At 2 months , this improvement was significantly greater in EASPS [ 95 % confidence interval ( CI ) 0.7 - 9.8 ] and SF-12 mental score ( 95 % CI 2.7 - 10.7 ) . At 6 months , this difference was no longer significant for EASPS ( 95 % CI -1.5 to 10.4 ) , but remained significant for SF-12 mental score ( 95 % CI 1.0 - 9.9 ) . Mean health care costs attributed to spinal pain were significantly greater by 65 UK pounds in the osteopathy group ( 95 % CI 32 - 155 UK pounds ) . Though osteopathy also cost 22 UK pounds more in mean total health care cost , this was not significant ( 95 % CI - 159 to 142 UK pounds ) . CONCLUSION A primary care osteopathy clinic improved short-term physical and longer term psychological outcomes , at little extra cost . Rigorous multicentre studies are now needed to assess the generalizability of this approach A national telephone survey was conducted in 1998 using r and om-digit dialing and the first Osteopathic Survey of Healthcare in America ( OSTEOSURV-I ) instrument to determine patients ' satisfaction with their healthcare , as well as their perceptions of osteopathic medicine . Of the 1106 respondents , 243 ( 22.0 % ) had received medical care from an osteopathic physician , and another 307 ( 27.8 % ) cl aim ed to be aware of osteopathic physicians . Patients of osteopathic physicians reported the highest levels of satisfaction in 8 of the 11 elements studied when compared with patients of allopathic physicians , chiropractors , and nonphysician clinicians other than chiropractors . Respondents perceived osteopathic manipulative treatment ( OMT ) to be beneficial for musculoskeletal disorders ( P < .001 ) . In addition , respondents perceived that healthcare services provided by osteopathic physicians were similar to those provided by allopathic physicians ( P < .001 ) , but not to those provided by chiropractors ( P = .01 ) . A total of 97.9 % of current patients of osteopathic physicians agreed with the statement that osteopathic physicians practice d in their local community , compared with 80.6 % of former patients of osteopathic physicians and 67.8 % of patients who had never visited osteopathic physicians ( P < .001 ) . In general , the most favorable perceptions of osteopathic medicine were reported by current patients of osteopathic physicians , followed by former patients of such physicians . The least favorable perceptions came from patients who had never been patients of osteopathic physicians . The perception that OMT should be covered by health insurance was significantly associated with the use of osteopathic physicians ( odds ratio , 3.2 ; 95 % confidence interval , 1.5 to 6.7 , among patients who had ever been to an osteopathic physician ) . The results of our survey suggest that greater access to osteopathic services , including OMT , is desirable and that promotional efforts aim ed at encouraging the use of osteopathic medical services among the general population are warranted 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 Abstract Objective To assess the cost effectiveness of adding spinal manipulation , exercise classes , or manipulation followed by exercise ( “ combined treatment ” ) to “ best care ” in general practice for patients consulting with low back pain . Design Stochastic cost utility analysis alongside pragmatic r and omised trial with factorial design . Setting 181 general practice s and 63 community setting s for physical treatments around 14 centres across the United Kingdom . Participants 1287 ( 96 % ) of 1334 trial participants . Main outcome measures Healthcare costs , quality adjusted life years ( QALYs ) , and cost per QALY over 12 months . Results Over one year , mean treatment costs relative to “ best care ” were £ 195 ( $ 360 ; € 279 ; 95 % credibility interval £ 85 to £ 308 ) for manipulation , £ 140 ( £ 3 to £ 278 ) for exercise , and £ 125 ( £ 21 to £ 228 ) for combined treatment . All three active treatments increased participants ' average QALYs compared with best care alone . Each extra QALY that combined treatment yielded relative to best care cost £ 3800 ; in economic terms it had an “ incremental cost effectiveness ratio ” of £ 3800 . Manipulation alone had a ratio of £ 8700 relative to combined treatment . If the NHS was prepared to pay at least £ 10 000 for each extra QALY ( lower than previous recommendations in the United Kingdom ) , manipulation alone would probably be the best strategy . If manipulation was not available , exercise would have an incremental cost effectiveness ratio of £ 8300 relative to best care . Conclusions Spinal manipulation is a cost effective addition to “ best care ” for back pain in general practice . Manipulation alone probably gives better value for money than manipulation followed by exercise Back pain is a common illness and chiropractors provide a large proportion of back pain care in the United States . This is the first study to systematic ally compare chiropractic patients with those who saw other providers for back pain . The authors analyzed data from the R AND Health Insurance Experiment , a community-based study of the use of health services . Insurance cl aims forms were examined for all visits specified by the patient as occurring for back pain . Visits were grouped into episodes using decision rules and clinical judgment . The primary provider of back pain care was defined as the provider who delivered most of the services . Sociodemographic and health status and attitudes variables of patients were examined for association with the choice of chiropractor . Multivariate logistic regression models were constructed to calculate adjusted odds ratios for independent predictors . There were 1020 episodes of back pain care made by 686 different persons and encompassing 8825 visits . Results indicated that chiropractors were the primary provider for 40 % of episodes , and retained as primary provider a greater percentage of their patients ( 92 % ) who had a second episode of back pain care than did medical doctors . Health insurance experiment site , white race , male sex , and high school education were independent predictors of choosing a chiropractor . Conclusions suggested that chiropractors were the choice of one third of all patients who sought back pain care , and provided care for 40 % of all episodes of care . Geographic site , education , gender , and income were independent patient factors predicting chiropractic use Fifty-four subjects volunteered to participate in a controlled study contrasting spinal manipulation with spinal mobilization without the rotational forces and leverage required to move facet joints . All suffered from regional low-back pain for less than 1 month , were ages 18–40 , had never previously undergone any form of spinal manipulation , and denied a prior episode of backache within the previous 6 months . R and omization was stratified at outset into those who suffered for less than 2 weeks and those whose discomfort had persisted for 2–4 weeks . Outcome was monitored by a question naire assessing functional impairment . A treatment effect of manipulation was demonstrated only in the strata with more prolonged illness at entry . In the first week following manipulation , these patients improved to a greater degree ( P=.009 , t test ) and more rapidly ( P < .025 , Wilcoxon rank-sum test ) The effectiveness of spinal manipulation carried out by a non-medical qualified osteopath was compared with that of short-wave diathermy ( SWD ) and a placebo ( detuned SWD ) in 109 patients with low back pain . More than half the subjects in each of the 3 treatment groups benefited immediately from therapy . Significant improvements were observed in the 3 groups at the end of 2 weeks ' treatment , and these were still apparent at 12 weeks . The outcome of treatment was unrelated to the initial severity or duration of pain or to the trend of pain towards deterioration or improvement . It is , therefore , unlikely that the results simply reflect the natural history of low back pain . Benefits obtained with osteopathy and SWD in this study may have been achieved through a placebo effect Previous studies have shown that dysmenorrhea produces low-back pain and an electromyographic ( EMG ) pattern typical of trauma-induced low-back pain . To determine the effects of high-velocity low-amplitude osteopathic manipulative treatment ( OMT ) on this type of low-back pain , 12 dysmenorrheic subjects were assigned to a group receiving OMT or to a group not receiving OMT ( or both ) . Eight subjects participated in both groups , the other four being equally distributed between groups . Osteopathic manipulative treatment significantly decreased EMG activity during extension of the lumbar spinae erector muscles and abolished the spontaneous EMG activity . These EMG changes coincided with the patient 's report of alleviated low-back pain and menstrual cramping . Osteopathic manipulative treatment did not change the creatinine kinase , lactate dehydrogenase or lactate-dehydrogenase isoenzyme activity , or myoglobin concentration A r and omized clinical trial of rotational manipulation was conducted on 95 patients with low back pain selected for ( 1 ) the absence of any contraindications for vertebral manipulation , ( 2 ) the absence of any psychosocial problems that might affect the outcome of treatment , ( 3 ) the absence of any previous experience with manipulative therapy , and ( 4 ) the presence of palpatory cues indicating that manipulation might be successful . Patients were r and omly assigned to one of two groups : an experimental group receiving manipulation therapy and a control group receiving soft-tissue massage . Comparison of the two groups indicated that ( 1 ) patients who received manipulative treatment were much more likely to report immediate relief after the first treatment , and ( 2 ) at discharge , there was no significant difference between the two groups because both showed substantial improvement In a multicentre trial 456 selected patients with low back pain were r and omly allocated to one of four treatments-manipulation , definitive physiotherapy , corset , or analgesic tablets . Patients were reassessed clinical ly after three weeks ' treatment and again after a further three weeks . Question naires were used to find out the patients ' condition three months and one year after admission to the trial . There were never any important differences among the four groups of patients . A few patients responded well and quickly to manipulation , but there was no way of identifying such patients in advance . The response to a corset was slow , but the long-tern effects were at least as good as those of the other treatments . Patients treated only with analgesics fared marginally worse than those on the other three treatments . There is no strong reason , however , for recommending manipulation over physiotherapy or corset Study Design . A r and omized controlled trial was conducted . Objective . To determine the efficacy of osteopathic manipulative treatment as a complementary treatment for chronic nonspecific low back pain . Summary of Background Data . Osteopathic manipulative treatment may be useful for acute or subacute low back pain . However , its role in chronic low back pain is unclear . Methods . This trial was conducted in a university-based clinic from 2000 through 2001 . Of the 199 subjects who responded to recruitment procedures , 91 met the eligibility criteria . They were r and omized , with 82 patients completing the 1-month follow-up evaluation , 71 completing the 3-month evaluation , and 66 completing the 6-month evaluation . The subjects were r and omized to osteopathic manipulative treatment , sham manipulation , or a no-intervention control group , and they were allowed to continue their usual care for low back pain . The main outcomes included the SF-36 Health Survey , a 10-cm visual analog scale for overall back pain , the Rol and –Morris Disability Question naire , lost work or school days because of back pain , and satisfaction with back care . Results . As compared with the no-intervention control subjects , the patients who received osteopathic manipulative treatment reported greater improvements in back pain , greater satisfaction with back care throughout the trial , better physical functioning and mental health at 1 month , and fewer cotreatments at 6 months . The subjects who received sham manipulation also reported greater improvements in back pain and physical functioning and greater satisfaction than the no-intervention control subjects . There were no significant benefits with osteopathic manipulative treatment , as compared with sham manipulation . Conclusions . Osteopathic manipulative treatment and sham manipulation both appear to provide some benefits when used in addition to usual care for the treatment of chronic nonspecific low back pain . It remains unclear whether the benefits of osteopathic manipulative treatment can be attributed to the manipulative techniques themselves or whether they are related to other aspects of osteopathic manipulative treatment , such as range of motion activities or time spent interacting with patients , which may represent placebo effects An open controlled pilot trial on nonspecific low-back pain sufferers demonstrated responsiveness to osteopathic manipulation of some patients presenting with pain duration s of 14 to 28 days . No response was demonstrated in those with shorter episodes at presentation . The advantage to manipulated patients was maximal between 1 and 2 weeks after commencing treatment , but was not discernable after 4 weeks . The demonstration of a similar responsive stratum by other investigators , with both teams totally unaware of each other 's work during data collection , suggests a high degree of reliability for this finding The Second Osteopathic Survey of Health Care in America ( OSTEOSURV-II ) , a national telephone survey conducted during 2000 using r and om-digit dialing , was used to address questions about public awareness of the osteopathic medical profession and use of osteopathic physicians . A total of 499 adult , noninstitutionalized , household respondents were surveyed . The main outcomes included prevalence of and multivariate factors associated with awareness and use of osteopathic physicians . The overall response rate was 64 % . The prevalence of awareness , lifetime use , and current use of osteopathic physicians among unscreened respondents was 46 % , 16 % , and 7 % , respectively . Among lifetime users , 84 % received primary care ; 52 % , osteopathic manipulative treatment ; and 25 % , specialty care . The multivariate factors most strongly associated with awareness of osteopathic physicians were college education ( rate ratio [ RR ] , 1.86 ; 95 % confidence interval [ CI ] , 1.43 - 2.40 ) , 60 or more years of age ( RR , 1.52 ; 95 % CI , 1.15 - 2.01 ) , and Midwest residence ( RR , 1.39 ; 95 % CI , 1.05 - 1.84 ) . Nonwhites , including Hispanics , were less likely to be aware of osteopathic physicians ( RR , 0.54 ; 95 % CI , 0.38 - 0.76 ) . Respondents with college education ( RR , 2.34 ; 95 % CI , 1.44 - 3.79 ) , respondents of intermediate age ( RR , 1.71 ; 95 % CI , 1.12 - 2.61 ) , and women ( RR , 1.68 ; 95 % CI , 1.12 - 2.52 ) were more likely to report lifetime use of osteopathic physicians . Nonwhites were less likely to report lifetime use ( RR , 0.25 ; 95 % CI , 0.11 - 0.57 ) . Greater promotional efforts are needed to increase awareness of osteopathic medicine and to remove barriers to using osteopathic physicians , particularly among nonwhites |
12,777 | 27,527,152 | We conclude that the DII score seems to be a useful tool to appraise the inflammatory capacity of the diet and to better underst and the relationships between diet , inflammation , and cardio-metabolic diseases | Inflammation is an underlying pathophysiological process in chronic diseases , such as obesity , type 2 diabetes mellitus and cardiovascular disease .
In fact , a number of systematic review s have shown the association between inflammatory biomarkers , such as CRP , IL-1β , IL-6 , TNF-α , IL-4 , or IL-10 , and cardio-metabolic diseases .
Diet is one of the main lifestyle-related factors which modulates the inflammatory process .
Different individual foods and dietary patterns can have a beneficial health effect associated with their anti-inflammatory properties .
The dietary inflammatory index ( DII ) was recently developed to estimate the inflammatory potential of overall diet .
The aim of this review is to examine the findings of recent papers that have investigated the association between the DII , cardio-metabolic risk factors and cardiovascular disease . | Objective —The goal of this study was to examine the association of the antiinflammatory interleukin-10 ( IL-10 ) with risk of cardiovascular disease ( CVD ) . Methods and Results —In the PROSPER ( PROspect i ve Study of Pravastatin in the Elderly at Risk ) cohort , we related baseline concentrations of circulating IL-10 to risk of CVD events in a nested case (n=819)-control ( n=1618 ) study of 3.2 years of follow-up . Circulating IL-10 showed few strong associations with classical risk factors but was positively correlated with IL-6 and C-reactive protein . IL-10 was positively associated with risk of CVD events ( odds ratio [ OR ] 1.17 , 95 % CI 1.05 to 1.31 per unit increase in log IL-10 ) after adjusting for classical risk factors and C-reactive protein . Furthermore , IL-10 was associated more strongly with CVD risk among those with no previous history of CVD ( OR 1.42 , 95 % CI 1.18 to 1.70 ) , compared with those with previous CVD ( OR 1.04 , 95 % CI 0.90 to 1.19 ; P=0.018 ) . Overall , IL-10 showed a modest ability to add discrimination to classical risk factors ( C-statistic + 0.005 , P=0.002 ) . Conclusion —Baseline circulating levels of the antiinflammatory IL-10 are positively associated with risk of CVD among the elderly without prior CVD events , although the association is less evident in those with a history of CVD . Additional epidemiological and mechanistic studies investigating the role of IL-10 in CVD are warranted The Healthy Eating Index-2005 ( HEI-2005 ) measures adherence to the 2005 Dietary Guidelines for Americans , but the association between the HEI-2005 and risk of chronic disease is not known . The Alternative Healthy Eating Index ( AHEI ) , which is based on foods and nutrients predictive of chronic disease risk , was associated inversely with chronic disease risk previously . We up date d the AHEI , including additional dietary factors involved in the development of chronic disease , and assessed the associations between the AHEI-2010 and the HEI-2005 and risk of major chronic disease prospect ively among 71,495 women from the Nurses ' Health Study and 41,029 men from the Health Professionals Follow-Up Study who were free of chronic disease at baseline . During ≥24 y of follow-up , we documented 26,759 and 15,558 incident chronic diseases ( cardiovascular disease , diabetes , cancer , or nontrauma death ) among women and men , respectively . The RR ( 95 % CI ) of chronic disease comparing the highest with the lowest quintile was 0.84 ( 0.81 , 0.87 ) for the HEI-2005 and 0.81 ( 0.77 , 0.85 ) for the AHEI-2010 . The AHEI-2010 and HEI-2005 were most strongly associated with coronary heart disease ( CHD ) and diabetes , and for both outcomes the AHEI-2010 was more strongly associated with risk than the HEI-2005 ( P-difference = 0.002 and < 0.001 , respectively ) . The 2 indices were similarly associated with risk of stroke and cancer . These findings suggest that closer adherence to the 2005 Dietary Guidelines may lower risk of major chronic disease . However , the AHEI-2010 , which included additional dietary information , was more strongly associated with chronic disease risk , particularly CHD and diabetes BACKGROUND Adherence to a Mediterranean diet may improve longevity , but relevant data are limited . METHODS We conducted a population -based , prospect i ve investigation involving 22,043 adults in Greece who completed an extensive , vali date d , food-frequency question naire at base line . Adherence to the traditional Mediterranean diet was assessed by a 10-point Mediterranean-diet scale that incorporated the salient characteristics of this diet ( range of scores , 0 to 9 , with higher scores indicating greater adherence ) . We used proportional-hazards regression to assess the relation between adherence to the Mediterranean diet and total mortality , as well as mortality due to coronary heart disease and mortality due to cancer , with adjustment for age , sex , body-mass index , physical-activity level , and other potential confounders . RESULTS During a median of 44 months of follow-up , there were 275 deaths . A higher degree of adherence to the Mediterranean diet was associated with a reduction in total mortality ( adjusted hazard ratio for death associated with a two-point increment in the Mediterranean-diet score , 0.75 [ 95 percent confidence interval , 0.64 to 0.87 ] ) . An inverse association with greater adherence to this diet was evident for both death due to coronary heart disease ( adjusted hazard ratio , 0.67 [ 95 percent confidence interval , 0.47 to 0.94 ] ) and death due to cancer ( adjusted hazard ratio , 0.76 [ 95 percent confidence interval , 0.59 to 0.98 ] ) . Associations between individual food groups contributing to the Mediterranean-diet score and total mortality were generally not significant . CONCLUSIONS Greater adherence to the traditional Mediterranean diet is associated with a significant reduction in total mortality BACKGROUND Dietary factors can affect telomere length ( TL ) , a biomarker of aging , through oxidation and inflammation-related mechanisms . A Dietary Inflammatory Index ( DII ) could help to underst and the effect of the inflammatory potential of the diet on telomere shortening . OBJECTIVE This study aim ed to determine the association of the DII with TL and to examine whether diet-associated inflammation could modify the telomere attrition rate after a 5-y follow-up of a Mediterranean dietary intervention . DESIGN This was a prospect i ve study of 520 participants at high cardiovascular disease risk ( mean ± SD age : 67.0 ± 6.0 y , 45 % males ) from the PREDIMED-NAVARRA ( PREvención con DIeta MEDiterránea-NAVARRA ) trial . Leukocyte TL was measured by quantitative real-time polymerase chain reaction at baseline and after 5 y of follow-up . The DII was calculated from self-reported data by using a vali date d 137-item food-frequency question naire . RESULTS Longer telomeres at baseline were found in participants who had a more anti-inflammatory diet ( lowest DII score ) ( P-trend = 0.012 ) . Longitudinal analyses further showed that a greater anti-inflammatory potential of the diet ( i.e. , a decrease in the DII ) could significantly slow down the rate of telomere shortening . Moreover , the multivariable-adjusted OR for short telomeres ( z score ≤20th percentile ) was 1.80 ( 95 % CI : 1.03 , 3.17 ) in a comparison between the highest ( proinflammatory ) and the lowest ( anti-inflammatory ) DII tertiles . Similarly , a greater DII ( greatest proinflammatory values ) after a 5-y follow-up was associated with almost a 2-fold higher risk of accelerated telomere attrition compared with the highest decrease in DII ( greatest anti-inflammatory values ) during this period ( P-trend = 0.025 ) . CONCLUSIONS This study showed both cross-sectional and longitudinal associations between the inflammatory potential of the diet and telomere shortening in subjects with a high cardiovascular disease risk . Our findings are consistent with , but do not show , a beneficial effect of adherence to an anti-inflammatory diet on aging and health by slowing down telomere shortening . These results suggest that diet might play a key role as a determinant of TL through proinflammatory or anti-inflammatory mechanisms . This trial was registered at controlled-trials.com as IS RCT N35739639 Background Diet is known to play a key role in atherogenesis and in the development of cardiovascular events . Dietary factors may mediate these processes acting as potential modulators of inflammation . Potential Links between inflammatory properties of diet and the occurrence of cardiovascular events have not been tested previously . Objective We aim ed to assess the association between the dietary inflammatory index ( DII ) , a method to assess the inflammatory potential of the diet , and incident cardiovascular disease . Methods In the prospect i ve , dynamic SUN cohort , 18,794 middle-aged , Spanish university graduates were followed up for 8.9 years ( median ) . A vali date d 136-item food-frequency question naire was used to calculate the DII . The DII is based on scientific evidence about the relationship between diet and inflammatory biomarkers ( C-reactive protein , IL-1β , IL-4 , IL-6 , IL-10 and TNF-α ) . Cox proportional hazard models were used to estimate hazard ratios ( HR ) and 95 % confidence intervals ( CI ) for the association between the DII and incident cardiovascular disease ( myocardial infa rct ion , stroke or cardiovascular death ) . Results The risk for cardiovascular events progressively increased with each increasing quartile of DII ( ptrend = 0.017 ) . The multivariable-adjusted HR for participants in the highest ( most pro-inflammatory ) vs. the lowest quartile of the DII was 2.03 ( 95 % CI 1.06–3.88 ) . Conclusions A pro-inflammatory diet was associated with a significantly higher risk for developing cardiovascular events CONTEXT Associations between adiposity and circulating inflammation markers are assumed to be causal , although the direction of the relationship has not been proven . OBJECTIVE The aim of the study was to explore the causal direction of the relationship between adiposity and inflammation using a bidirectional Mendelian r and omization approach . METHODS In the PROSPER study of 5804 elderly patients , we related C-reactive protein ( CRP ) single nucleotide polymorphisms ( SNPs ) ( rs1800947 and rs1205 ) and adiposity SNPs ( FTO and MC4R ) to body mass index ( BMI ) as well as circulating levels of CRP and leptin . We gave each individual two allele scores ranging from zero to 4 , counting each pair of alleles related to CRP levels or BMI . RESULTS With increasing CRP allele score , there was a stepwise decrease in CRP levels ( P for trend < 0.0001 ) and a 1.98 mg/liter difference between extremes of the allele score distribution , but there was no associated change in BMI or leptin levels ( P > or= 0.89 ) . By contrast , adiposity allele score was associated with 1 ) an increase in BMI ( 1.2 kg/m(2 ) difference between extremes ; P for trend 0.002 ) ; 2 ) an increase in circulating leptin ( 5.77 ng/ml difference between extremes ; P for trend 0.0027 ) ; and 3 ) increased CRP levels ( 1.24 mg/liter difference between extremes ; P for trend 0.002 ) . CONCLUSIONS Greater adiposity conferred by FTO and MC4R SNPs led to higher CRP levels , with no evidence for any reverse pathway . Future studies should extend our findings to other circulating inflammatory parameters . This study illustrates the potential power of Mendelian r and omization to dissect directions of causality between intercorrelated metabolic factors BACKGROUND Because of the high density of fat , high-fat diets are perceived as likely to lead to increased bodyweight , hence health-care providers are reluctant to recommend them to overweight or obese individuals . We assessed the long-term effects of ad libitum , high-fat , high-vegetable-fat Mediterranean diets on bodyweight and waist circumference in older people at risk of cardiovascular disease , most of whom were overweight or obese . METHODS PREDIMED was a 5 year parallel-group , multicentre , r and omised , controlled clinical trial done in primary care centres affiliated to 11 hospitals in Spain . 7447 asymptomatic men ( aged 55 - 80 years ) and women ( aged 60 - 80 years ) who had type 2 diabetes or three or more cardiovascular risk factors were r and omly assigned ( 1:1:1 ) with a computer-generated number sequence to one of three interventions : Mediterranean diet supplemented with extra-virgin olive oil ( n=2543 ) ; Mediterranean diet supplemented with nuts ( n=2454 ) ; or a control diet ( advice to reduce dietary fat ; n=2450 ) . Energy restriction was not advised , nor was physical activity promoted . In this analysis of the trial , we measured bodyweight and waist circumference at baseline and yearly for 5 years in the intention-to-treat population . The PREDIMED trial is registered with IS RCT N.com , number IS RCT N35739639 . FINDINGS After a median 4·8 years ( IQR 2·8 - 5·8 ) of follow-up , participants in all three groups had marginally reduced bodyweight and increased waist circumference . The adjusted difference in 5 year changes in bodyweight in the Mediterranean diet with olive oil group was -0·43 kg ( 95 % CI -0·86 to -0·01 ; p=0·044 ) and in the nut group was -0·08 kg ( -0·50 to 0·35 ; p=0·730 ) , compared with the control group . The adjusted difference in 5 year changes in waist circumference was -0·55 cm ( -1·16 to -0·06 ; p=0·048 ) in the Mediterranean diet with olive oil group and -0·94 cm ( -1·60 to -0·27 ; p=0·006 ) in the nut group , compared with the control group . INTERPRETATION A long-term intervention with an unrestricted-calorie , high-vegetable-fat Mediterranean diet was associated with decreases in bodyweight and less gain in central adiposity compared with a control diet . These results lend support to advice not restricting intake of healthy fats for bodyweight maintenance . FUNDING Spanish Government , CIBERobn , Instituto de Salud Carlos III , Hojiblanca , Patrimonio Comunal Olivarero , California Walnut Commission , Borges SA , and Morella Nuts Background Cardiovascular diseases ( CVD ) are the leading cause of death in the world , and diet plays a major role in CVD incidence , especially through lipid oxidation mechanisms . This , in turn , leads to tissue inflammation and formation of atheromatous plaques . Methods and Results Our objective was to evaluate the association between the inflammatory potential of the diet and the incidence of overall CVD or its subclasses . We included 7743 participants from the Supplémentation en Vitamines et Minéraux AntioXydants ( SU.VI.MAX ) cohort . All cardiovascular events were recorded using self‐reported information or clinical visits , and were vali date d. The dietary inflammatory index ( DII ) was computed using repeated 24‐hour dietary records ( mean=9.5±3.4 records/subject ) . Hazard ratio and 95 % CI for outcomes ( CVD and subclasses ) were estimated across sex‐specific quartiles of the DII using Cox proportional hazard models . A total of 292 cardiovascular events were recorded and vali date d during an average of 11.4 years of follow‐up : 93 myocardial infa rct ions , 58 strokes , 128 angina pectoris and revascularization interventions , and 13 sudden deaths . When considering CVD subclasses , a diet with pro‐inflammatory properties , as expressed by higher DII scores , was significantly associated with a higher risk of myocardial infa rct ion ( hazard ratioQuartile 4 versus Quartile 1=2.24 , 95 % CI : 1.08–4.67 ) . No significant association was observed between the DII score and stroke or both angina pectoris and revascularization intervention . Conclusions A pro‐inflammatory diet , as measured by a higher DII score , was prospect ively associated with a higher risk of myocardial infa rct ion . Promotion of a diet exhibiting anti‐inflammatory properties may help prevent myocardial infa rct ions Previous studies have reported an association between a more pro-inflammatory diet profile and various chronic metabolic diseases . The Dietary Inflammatory Index ( DII ) was used to assess the inflammatory potential of nutrients and foods in the context of a dietary pattern . We prospect ively examined the association between the DII and the incidence of cardiovascular disease ( CVD : myocardial infa rct ion , stroke or cardiovascular death ) in the PREDIMED ( Prevención con Dieta Mediterránea ) study including 7216 high-risk participants . The DII was computed based on a vali date d 137-item food frequency question naire . Multivariate-adjusted hazard ratios ( HR ) and 95 % confidence intervals of CVD risk were computed across quartiles of the DII where the lowest ( most anti-inflammatory ) quartile is the referent . Risk increased across the quartiles ( i.e. , with increasing inflammatory potential ) : HRquartile2 = 1.42 ( 95%CI = 0.97–2.09 ) ; HRquartile3 = 1.85 ( 1.27–2.71 ) ; and HRquartile4 = 1.73 ( 1.15–2.60 ) . When fit as continuous the multiple-adjusted hazard ratio for each additional st and ard deviation of the DII was 1.22 ( 1.06–1.40 ) . Our results provide direct prospect i ve evidence that a pro-inflammatory diet is associated with a higher risk of cardiovascular clinical events Background Adherence to the Mediterranean diet ( MD ) is associated with reduced morbidity and mortality due to cardiovascular disease . However , how the MD exerts its effects is not fully known . Aim To assess the 12-month effects of two enhanced MDs compared to a low-fat diet on inflammatory biomarkers related to atherosclerosis and plaque vulnerability in a subcohort of the PREDIMED ( Prevención con Dieta Mediterránea ) study . Methods A total of 164 participants at high risk for cardiovascular disease were r and omized into three diet groups : MD supplemented with 50mL/d of extra virgin olive oil ( MD+EVOO ) or 30 g/d of nuts ( MD+Nuts ) and a low-fat diet . Changes in classical cardiovascular risk factors , inflammatory biomarkers of atherosclerosis and plaque vulnerability were measured after 12 months of intervention . Results Compared to participants in the low-fat diet group , those receiving MD+EVOO and MD+Nuts showed a higher decrease in systolic ( 6mmHg ) and diastolic ( 3mmHg ) blood pressure ( P = 0.02 ; both ) , as well as a reduction of 10 % and 8 % in LDL-cholesterol ( P = 0.04 ) , respectively . Patients in the MD+Nuts group showed a significant reduction of 34 % in CD40 expression on monocyte surface compared to low-fat diet patients ( P = 0.03 ) . In addition , inflammatory biomarkers related to plaque instability such as C-reactive protein and interleukin-6 were reduced by 45 % and 35 % and 95 % and 90 % in the MD+EVOO and MD+Nuts groups , respectively ( P<0.05 ; all ) compared to the low-fat diet group . Likewise , sICAM and P-selectin were also reduced by 50 % and 27 % , respectively in the MD+EVOO group ( P = 0.04 ) and P-selectin by 19 % in MD+Nuts group ( P = 0.04 ) compared to the low-fat diet group . Conclusions Adherence to the MD is associated with an increase in serum markers of atheroma plaque stability which may explain , at least in part , the protective role of MD against ischemic heart disease . Trial Registration www.controlled-trials.com IS RCT Mendelian r and omization studies using genetic instrumental variables ( IVs ) are now being commonly used to estimate the causal association of a phenotype on an outcome . Even when the necessary underlying assumptions are valid , estimates from analyses using IVs are biased in finite sample s. The source and nature of this bias appear poorly understood in the epidemiological field . We explain why the bias is in the direction of the confounded observational association , with magnitude relating to the statistical strength of association between the instrument and phenotype . We comment on the size of the bias , from simulated data , showing that when multiple instruments are used , although the variance of the IV estimator decreases , the bias increases . We discuss ways to analyse Mendelian r and omization studies to alleviate the problem of weak instrument bias Context : The assignment of direction and causality within networks of observational associations is problematic outside r and omized control trials , and the presence of a causal relationship between body mass index ( BMI ) and C-reactive protein ( CRP ) is disputed . Objective : Using reciprocal Mendelian r and omization , we aim to assess the direction of causality in relationships between BMI and CRP and to demonstrate this as a promising analytical technique . Participants and methods : The study was based on a large , cross-sectional European study from Copenhagen , Denmark . Genetic associates of BMI ( FTO(rs9939609 ) ) and circulating CRP ( CRP(rs3091244 ) ) have been used to reexamine observational associations between them . Results : Observational analyses showed a strong , positive association between circulating CRP and BMI ( change in BMI for a doubling in logCRP of 1.03 kg m−2 ( 95 % confidence interval ( 95 % CI ) : 1.00 , 1.07 ) , P<0.0001 ) . Analysis using CRP(rs3091244 ) to re-estimate the causal effect of circulating CRP on BMI yielded null effects ( change in BMI for a doubling in logCRP of −0.24 kg m−2 ( 95 % CI : −0.58 , 0.11 ) , P=0.2 ) . In contrast , analysis using FTO(rs9939609 ) to assess the causal effect of BMI on circulating CRP confirmed observational associations ( ratio of geometric means of CRP per s.d . increase in BMI 1.41 ( 95 % CI : 1.10 , 1.80 ) , P=0.006 ) . Conclusions : Taken together , these data suggest that the observed association between circulating CRP and measured BMI is likely to be driven by BMI , with CRP being a marker of elevated adiposity . More generally , the method of reciprocal r and omization has general applicability in determining the direction of causation within inter-correlated networks of metabolic components Purpose To investigate prospect ively the associations of Dietary Inflammatory Index ( DII ) and Mediterranean Diet Score ( MDS ) with lung cancer . Methods We used data from men and women aged 40–69 years at recruitment in 1990–1994 , who were participants in the Melbourne Collaborative Cohort Study ( n = 35,303 ) . A total of 403 incident lung cancer cases were identified over an average 18-year follow-up . Hazard ratios ( HR ) were estimated using Cox regression , adjusting for smoking status and other risk factors , with age as the time metric . Results An inverse correlation was observed between the DII and MDS ( ρ = −0.45 ) , consistent with a higher DII being pro-inflammatory and less ‘ healthy , ’ while a high MDS reflects a ‘ healthier ’ diet . The DII was positively associated with risk of lung cancer in current smokers [ HRQ4 vs Q1 = 1.70 ( 1.02 , 2.82 ) ; Ptrend = 0.008 ] ( p interaction between DII quartiles and smoking status = 0.03 ) . The MDS was inversely associated with lung cancer risk overall [ HR7–9 vs 0–3 = 0.64 ( 0.45 , 0.90 ) ; Ptrend = 0.005 ] and for current smokers ( HR7–9 vs 0–3 = 0.38 ( 0.19 , 0.75 ) ; Ptrend = 0.005 ) ( p interaction between MDS categories and smoking status = 0.31 ) . Conclusions The MDS showed an inverse association with lung cancer risk , especially for current smokers . A high DII , indicating a more pro-inflammatory diet , was associated with risk of lung cancer only for current smokers . A healthy diet may reduce the risk of lung cancer , especially in smokers Abstract Introduction Chronic inflammation is associated with increased risk of cancer , cardiovascular disease ( CVD ) , and diabetes . The role of pro-inflammatory diet in the risk of cancer mortality and CVD mortality in prediabetics is unclear . We examined the relationship between diet-associated inflammation , as measured by dietary inflammatory index ( DII ) score , and mortality , with special focus on prediabetics . Methods This prospect i ve cohort study used data from the Third National Health and Nutrition Examination Survey ( NHANES III ) . We categorized 13,280 eligible participants , ages 20–90 years , according to glycosylated hemoglobin ( HgbA1c ) level and identified 2681 with prediabetes , defined as a glycosylated hemoglobin percentage of 5.7–6.4 . Computation of DII scores and all statistical analyses were conducted in 2015 . The DII was computed based on baseline dietary intake assessed using 24-h dietary recalls ( 1988–1994 ) . Mortality was determined from the National Death Index records through 2006 . Over follow-up ranging between 135 and 168 person-months , a total of 3016 deaths were identified , including 676 cancer , 192 lung cancer , 176 digestive-tract cancer , and 1328 CVD deaths . Cox proportional hazard regression was used to estimate hazard ratios . Results The prevalence of prediabetes was 20.19 % . After controlling for age , sex , race , HgbA1c , current smoking , physical activity , BMI , and systolic blood pressure , DII scores in tertile III ( vs tertile I ) was significantly associated with mortality from all causes ( HR 1.39 , 95 % CI 1.13 , 1.72 ) , CVD ( HR 1.44 , 95 % CI 1.02 , 2.04 ) , all cancers ( HR 2.02 , 95 % CI 1.27 , 3.21 ) , and digestive-tract cancer ( HR 2.89 , 95 % CI 1.08 , 7.71 ) . Findings for lung cancer ( HR 2.01 , 95 % CI 0.93 , 4.34 ) suggested a likely effect . These results were moderately enhanced after additional adjustment for serum low-density lipoprotein and triglyceride and following eliminating deaths during the first year . Conclusions A pro-inflammatory diet , as indicated by higher DII scores , is associated with an increased risk of all-cause , CVD , all-cancer , and digestive-tract cancer mortality among prediabetic subjects BACKGROUND Chronic inflammation is a central mechanism involved in cardiovascular diseases , cancer , diabetes , and chronic respiratory diseases , 4 leading causes of mortality . Diet is a major source of pro- and anti-inflammatory bioactive compounds . The Dietary Inflammatory Index ( DII ) was design ed to estimate the overall inflammatory potential of the diet . OBJECTIVE Our aim was to study the prospect i ve association between the DII and mortality , as well as assess whether antioxidant supplementation could modulate this association . DESIGN The Supplémentation en Vitamines et Minéraux Antioxydants study was a r and omized , double-blind , placebo-controlled trial in which participants received low-dose antioxidants or a placebo from 1994 to 2002 . In this observational prospect i ve analysis , 8089 participants ( mean ± SD age at baseline : 49.0 ± 6.3 y ) were followed between 1994 and 2007 ( median : 12.4 y ) . The DII was calculated from repeated 24-h dietary records ; higher scores correspond to more proinflammatory diets . A total of 207 deaths occurred during follow-up , including 123 due to cancer and 41 due to cardiovascular events . Multivariate Cox proportional hazards models were computed . RESULTS Sex-specific tertiles of the DII were positively associated with cardiovascular + cancer mortality ( HR for tertile 3 compared with tertile 1 = 1.53 ; 95 % CI : 1.01 , 2.32 ; P-trend = 0.05 ) and specific cancer mortality ( HR for tertile 3 compared with tertile 1 = 1.83 ; 95 % CI : 1.12 , 2.99 ; P-trend = 0.02 ) . The corresponding P value was 0.07 for all-cause mortality . The DII was statistically significantly associated with increased all-cause mortality in the placebo group ( HR for tertile 3 compared with tertile 1 = 2.10 ; 95 % CI : 1.15 , 3.84 ; P-trend = 0.02 ) but not in the antioxidant-supplemented group ( P-trend = 0.8 ; P-interaction = 0.098 ) . CONCLUSION These results suggest that a proinflammatory diet is associated with increased all-cause and cancer mortality and antioxidants may counteract some of the proinflammatory effects of the diet . This trial was registered at clinical trials.gov as NCT00272428 OBJECTIVE This study prospect ively assessed the association of the inflammatory potential of a diet using the dietary inflammatory index ( DII ) with average yearly weight changes and incident overweight/obesity . METHODS Seven thous and and twenty-seven university graduates with body mass index < 25 from the Seguimiento Universidad de Navarra ( SUN ) cohort were followed up during a median of 8.1 years . The DII , a vali date d tool based on scientific evidence to appraise the relationship between dietary parameters and inflammatory biomarkers , was used . A vali date d food-frequency question naire was used to assess intake of total energy , food , and nutrients , from which DII scores were calculated at baseline and after 10 years of follow-up . RESULTS After a median follow-up of 8.1 years , 1,433 incident cases of overweight or obesity were observed . Hazard ratios for overweight/obesity were calculated , including multivariable time-dependent Cox regression models with repeated measures of diet . The hazard ratio for subjects in the highest quartile ( most pro-inflammatory diet ) was 1.32 ( 95 % confidence interval 1.08 - 1.60 ) compared with participants in the lowest quartile ( most anti-inflammatory diet ) , with a significant linear dose-response relationship ( P = 0.004 ) . Consistently , increases in average yearly weight gains were significantly associated with proinflammatory diets . CONCLUSIONS A proinflammatory diet was significantly associated with a higher annual weight gain and higher risk of developing new-onset overweight or obesity Adherence to a Mediterranean diet ( MD ) is associated with a reduced risk of coronary heart disease . However , the molecular mechanisms involved are not fully understood . The aim of this study was to compare the effects of 2 MD with those of a low-fat-diet ( LFD ) on circulating inflammatory biomarkers related to atherogenesis . A total of 516 participants included in the Prevention with Mediterranean Diet Study were r and omized into 3 intervention groups [ MD supplemented with virgin olive oil ( MD-VOO ) ; MD supplemented with mixed nuts ( MD-Nuts ) ; and LFD ] . At baseline and after 1 y , participants completed FFQ and adherence to MD question naires , and plasma concentrations of inflammatory markers including intercellular adhesion molecule-1(ICAM-1 ) , IL-6 , and 2 TNF receptors ( TNFR60 and TNFR80 ) were measured by ELISA . At 1 y , the MD groups had lower plasma concentrations of IL-6 , TNFR60 , and TNFR80 ( P < 0.05 ) , whereas ICAM-1 , TNFR60 , and TNFR80 concentrations increased in the LFD group ( P < 0.002 ) . Due to between-group differences , participants in the 2 MD groups had lower plasma concentrations of ICAM-1 , IL-6 , TNFR60 , and TNFR80 compared to those in the LFD group ( P ≤ 0.028 ) . When participants were categorized in tertiles of 1-y changes in the consumption of selected foods , those in the highest tertile of virgin olive oil ( VOO ) and vegetable consumption had a lower plasma TNFR60 concentration compared with those in tertile 1 ( P < 0.02 ) . Moreover , the only changes in consumption that were associated with 1-y changes in the geometric mean TNFR60 concentrations were those of VOO and vegetables ( P = 0.01 ) . This study suggests that a MD reduces TNFR concentrations in patients at high cardiovascular risk |
12,778 | 19,890,618 | Results In the manufacturing and warehousing sector strong evidence was found in support of the financial merits of ergonomic interventions from a firm perspective .
In the administrative support and health care sectors moderate evidence was found , in the transportation sector limited evidence , and in remaining sectors insufficient evidence .
Conclusions Most intervention studies focus on effectiveness .
Few consider their financial merits .
Often only a small part of the overall evaluation of many studies focused on evaluating their cost-effectiveness | Introduction This article reports on a systematic review of workplace ergonomic interventions with economic evaluations .
The review sought to answer the question : “ what is the credible evidence that incremental investment in ergonomic interventions is worth undertaking ? ”
Past efforts to synthesize evidence from this literature have focused on effectiveness , whereas this study synthesizes evidence on the cost-effectiveness/financial merits of such interventions . | BACKGROUND Occupational low back pain ( OLBP ) is widespread in industrialized societies . We present a model to estimate the net economic costs of investments in ergonomic interventions at the company level to reduce work-related low back pain . METHODS Costs of interventions are defined by incorporating not only the costs of investment of equipment and labor , but also by taking into account the avoided costs of lost work time , medical care costs , and productivity improvements . In the net-cost model , all costs are annualized and are calculated at the level of an individual organization . Three case studies have been performed based on data from three companies in the manufacturing sector of the United States using the above approach . RESULTS The net-cost estimates for the three case studies consistently show that ergonomic interventions applied appropriately can result in substantial cost savings for the companies . CONCLUSIONS Although generalizing on the basis of three case studies is not ideal , our analyses show that it might be in the economic interest of management to play a more active role to prevent back pain . Gathering useful retrospective cost data , even on interventions deemed effective by corporate innovators , proved to be extremely difficult . We conclude that it is essential to incorporate a protocol for collecting cost and effectiveness data in the st and ard operating procedures of ergonomists and companies introducing such innovation . We intend to vali date the net-cost model for the monitoring and reporting of such data through prospect i ve studies in a variety of industrial setting s and in countries at various stages of economic development BACKGROUND High rates of work-related injuries are seen among health care workers involved in lifting and transferring patients . We studied the effects of a participatory worker-management ergonomics team among hospital orderlies . METHODS This prospect i ve intervention trial examined work injuries and other outcomes before and after the intervention , with other hospital employees used as a concurrent control . All orderlies in a 1,200-bed urban hospital were studied using passively collected data ( mean employment during study period 100 - 110 orderlies ) ; 67 orderlies ( preintervention ) and 88 orderlies ( postintervention ) also completed a question naire . The intervention was the formation of a participatory ergonomics team with three orderlies , one supervisor , and technical advisors . This team design ed and implemented changes in training and work practice s. RESULTS The 2-year postintervention period was marked by decreased risks of work injury ( RR = 0.50 , 95 % CI 0.35 - 0.72 ) , lost time injury ( RR = 0.26 , 95 % CI 0.14 - 0.48 ) , and injury with three or more days of time loss ( RR = 0.19 , 95 % CI 0.07 - 0.53 ) . Total lost days declined from 136.2 to 23.0 annually per 100 full-time worker equivalents ( FTE ) . Annual workers ' compensation costs declined from $ 237/FTE to $ 139/FTE . The proportion of workers with musculoskeletal symptoms declined and there were statistically significant improvements in job satisfaction , perceived psychosocial stressors , and social support among the orderlies . CONCLUSION Substantial improvements in health and safety were seen following implementation of a participatory ergonomics program Background : Call centre work with computers is associated with increased rates of upper body pain and musculoskeletal disorders . Methods : This one year , r and omised controlled intervention trial evaluated the effects of a wide forearm support surface and a trackball on upper body pain severity and incident musculoskeletal disorders among 182 call centre operators at a large healthcare company . Participants were r and omised to receive ( 1 ) ergonomics training only , ( 2 ) training plus a trackball , ( 3 ) training plus a forearm support , or ( 4 ) training plus a trackball and forearm support . Outcome measures were weekly pain severity scores and diagnosis of incident musculoskeletal disorder in the upper extremities or the neck/shoulder region based on physical examination performed by a physician blinded to intervention . Analyses using Cox proportional hazard models and linear regression models adjusted for demographic factors , baseline pain levels , and psychosocial job factors . Results : Post-intervention , 63 participants were diagnosed with one or more incident musculoskeletal disorders . Hazard rate ratios showed a protective effect of the armboard for neck/shoulder disorders ( HR = 0.49 , 95 % CI 0.24 to 0.97 ) after adjusting for baseline pain levels and demographic and psychosocial factors . The armboard also significantly reduced neck/shoulder pain ( p = 0.01 ) and right upper extremity pain ( p = 0.002 ) in comparison to the control group . A return-on-investment model predicted a full return of armboard and installation costs within 10.6 months . Conclusion : Providing a large forearm support combined with ergonomic training is an effective intervention to prevent upper body musculoskeletal disorders and reduce upper body pain associated with computer work among call centre employees BACKGROUND Low back injuries are common and costly , accounting for 15 to 25 percent of injuries covered by workers ' compensation and 30 to 40 percent of the payments made under that program . The high costs of injury , the lack of effective treatment . and the evidence that there are behavioral risk factors have led to widespread use of employee education programs that teach safe lifting and h and ling . The effectiveness of those programs , however , has received little rigorous evaluation . METHODS We evaluated an educational program design ed to prevent low back injury in a r and omized , controlled trial involving about 4000 postal workers . The program , similar to that in wide use in so-called back schools , was taught by experienced physical therapists . Work units of workers and supervisors were trained in a two-session back school ( three hours of training ) , followed by three to four reinforcement sessions over the succeeding few years . Injured subjects ( from both the intervention and the control groups ) were r and omized a second time to receive either training or no training after their return to work . RESULTS Physical therapists trained 2534 postal workers and 134 supervisors . Over 5.5 years of follow-up , 360 workers reported low back injuries , for a rate of 21.2 injuries per 1000 worker-years of risk . The median time off from work per injury was 14 days ( range , 0 to 1717 ) ; the median cost was $ 204 ( range , zero to $ 190,380 ) . After their return to work , 75 workers were injured again . Our comparison of the intervention and control groups found that the education program did not reduce the rate of low back injury , the median cost per injury , the time off from work per injury , the rate of related musculoskeletal injuries , or the rate of repeated injury after return to work ; only the subjects ' knowledge of safe behavior was increased by the training . CONCLUSIONS A large-scale , r and omized , controlled trial of an educational program to prevent work-associated low back injury found no long-term benefits associated with training To define the cost-effectiveness of a back school program in industry , a controlled longitudinal field study was carried out in a Dutch bus company . The experimental group received a program consisting of information on back care , physical fitness , nutrition , stress , and relaxation . Objective data on absenteeism were collected and compared during a 6-year period for the control and experimental groups . Results showed that a tailor-made back school program reduced absenteeism by at least 5 days per year per employee , therefore being cost-effective to industry . A reduction was not observed in incidence , but in mean length of absenteeism . This effect turned out to be persistent during a 2-year period following the program |
12,779 | 20,483,498 | Chronic hepatitis B patients receiving medium-term nucleos(t)ide analogue therapy had a significantly lower incidence of HCC compared to untreated patients but treatment does not completely eliminate the risk of HCC .
Among the treated patients , cirrhosis , HBeAg negative at baseline and failure to remain in virological remission were associated with an increased risk of HCC | BACKGROUND & AIMS Chronic hepatitis B patients are at increased risk for hepatocellular carcinoma ( HCC ) .
The effect of medium-term nucleos(t)ide analogue therapy on HCC incidence is unclear ; therefore , we systematic ally review ed all the data on HCC incidence from studies in chronic hepatitis B patients treated with nucleos(t)ide analogues . | BACKGROUND Long-term effects of lamivudine treatment on chronic hepatitis B patients without advanced disease remain unknown . Our aim was to investigate the effects of long-term lamivudine treatment and lamivudine-resistant virus ( YMDD ) on the development of cirrhosis and hepatocellular carcinoma ( HCC ) in asymptomatic patients without advanced disease . METHODS One hundred and forty-two hepatitis B e antigen (HBeAg)-positive patients ( median age : 33.9 years ) on long-term lamivudine ( median treatment duration : 89.9 months ) and 124 HBeAg-positive controls ( median age : 33.4 years ) were prospect ively followed up . Patients were monitored for the development of cirrhosis and HCC , liver biochemistry , hepatitis B virus ( HBV ) DNA levels , HBeAg seroconversion and hepatitis flares . YMDD mutations ( YMDD-MT ) were determined annually . RESULTS Lamivudine-treated patients had a significantly lower cumulative rate of development of cirrhosis and /or HCC compared with controls ( P = 0.005 ) . YMDD-MT occurred in 76.3 % of patients after 8 years of lamivudine treatment . When compared with controls and patients with YMDD-MT , patients without YMDD-MT had the greatest reduction of HBV DNA and bilirubin levels , slowest decline of albumin level , highest rate of HBeAg seroconversion and lowest risk of hepatitis flare . Patients with YMDD-MT still had a lower risk for developing cirrhosis and /or HCC ( P = 0.024 ) and a greater HBV DNA reduction ( P = 0.001 ) in comparison with controls . Patients with YMDD-MT and controls had a similar chance of hepatitis flares and hepatic decompensation . CONCLUSIONS Long-term lamivudine treatment was associated with a reduced chance of developing cirrhosis and HCC in patients without advanced disease . Although YMDD-MT reduced the benefits from lamivudine therapy , the outcome of these patients was still better than untreated patients BACKGROUND The effectiveness of antiviral therapy in preventing disease progression in patients with chronic hepatitis B and advanced fibrosis or cirrhosis is unknown . METHODS Patients with chronic hepatitis B who had histologically confirmed cirrhosis or advanced fibrosis were r and omly assigned in a 2:1 ratio to receive lamivudine ( 100 mg per day ) or placebo for a maximum of five years . Of 651 patients , 436 were assigned to receive lamivudine and 215 to receive placebo . The primary end point was time to disease progression , defined by hepatic decompensation , hepatocellular carcinoma , spontaneous bacterial peritonitis , bleeding gastroesophageal varices , or death related to liver disease . An independent data and safety monitoring board monitored the progress of the study and performed interim analyses of the data . RESULTS We r and omly assigned 651 patients ( 98 percent Asian and 85 percent male ) to receive lamivudine or placebo . The study was terminated after a median duration of treatment of 32.4 months ( range , 0 to 42 ) owing to a significant difference between treatment groups in the number of end points reached . End points were reached by 7.8 percent of the patients receiving lamivudine and 17.7 percent of those receiving placebo ( hazard ratio for disease progression , 0.45 ; P=0.001 ) . The Child-Pugh score increased in 3.4 percent of the patients receiving lamivudine and 8.8 percent of those receiving placebo ( hazard ratio , 0.45 ; P=0.02 ) , whereas hepatocellular carcinoma occurred in 3.9 percent of those in the lamivudine group and 7.4 percent of those in the placebo group ( hazard ratio , 0.49 ; P=0.047 ) . Genotypic resistance YMDD mutations developed in 49 percent of the patients treated with lamivudine , and the Child-Pugh score was more likely to increase in patients with these mutations than in the other patients treated with lamivudine ( 7 percent vs. < 1 percent ) . Overall , 12 percent of the patients in the lamivudine group and 18 percent of the patients in the placebo group reported serious adverse events . CONCLUSIONS Continuous treatment with lamivudine delays clinical progression in patients with chronic hepatitis B and advanced fibrosis or cirrhosis by significantly reducing the incidence of hepatic decompensation and the risk of hepatocellular carcinoma BACKGROUND The long-term efficacy of lamivudine treatment for patients suffering from severe acute exacerbation of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B is unknown . METHODS Consecutive patients with severe acute exacerbation of HBeAg-positive chronic hepatitis B were prospect ively recruited from 1999 to 2004 and treated with lamivudine . All patients had alanine aminotransferase ( ALT ) and serum bilirubin levels 10x and 3x above the upper limit of normal , respectively . HBeAg-positive patients without severe acute exacerbation served as controls . RESULTS Forty-five patients with severe acute exacerbation and 31 controls were treated with lamivudine for a median of 2.8 ( range 1.0 - 7.1 ) years and 3.8 ( range 3.5 - 8.4 ) years , respectively . Compared with controls , patients with severe acute exacerbation had higher HBeAg seroconversion rates ( 78 % versus 52 % ; P=0.02 ) and lower risk of virological breakthrough . However , 33 % of patients with severe acute exacerbation still developed lamivudine resistance and virological breakthrough by year 5 . HBV DNA levels at week 4 and prolonged baseline prothrombin time were independent factors associated with virological breakthrough . All patients with week 4 HBV DNA <3 log10 copies/ml had maintained virological response . Among 15 patients who stopped lamivudine after sustained HBeAg seroconversion for > or = 6 months , 11 ( 73 % ) had virological relapse at a median of 1.4 ( 0.2 - 3.9 ) years . ALT increased beyond 10x the upper limit of normal in six ( 38 % ) patients who stopped lamivudine and two ( 7 % ) patients on maintained lamivudine treatment ( P=0.02 ) . CONCLUSION Among patients with severe acute exacerbation of HBeAg-positive chronic hepatitis B treated with lamivudine , virological breakthrough and post-treatment relapse are common despite a high rate of HBeAg seroconversion . Severe hepatitis flare is also common particularly among patients developing virological relapse after discontinuation of lamivudine CONTEXT Serum hepatitis B virus ( HBV ) DNA level is a marker of viral replication and efficacy of antiviral treatment in individuals with chronic hepatitis B. OBJECTIVE To evaluate the relationship between serum HBV DNA level and risk of hepatocellular carcinoma . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study of 3653 participants ( aged 30 - 65 years ) , who were seropositive for the hepatitis B surface antigen and seronegative for antibodies against the hepatitis C virus , recruited to a community-based cancer screening program in Taiwan between 1991 and 1992 . MAIN OUTCOME MEASURE Incidence of hepatocellular carcinoma during follow-up examination and by data linkage with the national cancer registry and the death certification systems . RESULTS There were 164 incident cases of hepatocellular carcinoma and 346 deaths during a mean follow-up of 11.4 years and 41,779 person-years of follow-up . The incidence of hepatocellular carcinoma increased with serum HBV DNA level at study entry in a dose-response relationship ranging from 108 per 100,000 person-years for an HBV DNA level of less than 300 copies/mL to 1152 per 100,000 person-years for an HBV DNA level of 1 million copies/mL or greater . The corresponding cumulative incidence rates of hepatocellular carcinoma were 1.3 % and 14.9 % , respectively . The biological gradient of hepatocellular carcinoma by serum HBV DNA levels remained significant ( P<.001 ) after adjustment for sex , age , cigarette smoking , alcohol consumption , serostatus for the hepatitis B e antigen ( HBeAg ) , serum alanine aminotransferase level , and liver cirrhosis at study entry . The dose-response relationship was most prominent for participants who were seronegative for HBeAg with normal serum alanine aminotransferase levels and no liver cirrhosis at study entry . Participants with persistent elevation of serum HBV DNA level during follow-up had the highest hepatocellular carcinoma risk . CONCLUSION Elevated serum HBV DNA level ( > or = 10,000 copies/mL ) is a strong risk predictor of hepatocellular carcinoma independent of HBeAg , serum alanine aminotransferase level , and liver cirrhosis BACKGROUND & AIMS Data on the long-term safety of lamivudine are limited . The aim of this analysis was to determine the incidence of hepatitis flares , hepatic decompensation , and liver-disease-related ( LDR ) serious adverse events ( SAE ) during long-term lamivudine treatment . METHODS We review ed data on 998 patients with HBeAg-positive compensated chronic hepatitis B who received lamivudine for up to 6 years ( median , 4 years ) and 200 patients who received placebo for 1 year . RESULTS Hepatitis flares occurred in 10 % of the lamivudine-treated patients in year 1 and in 18%-21 % in years 2 - 5 . A temporal association between hepatitis flares and lamivudine-resistant mutations increased from 43 % in year 1 to > 80 % in year 3 . Ten hepatic decompensation events occurred in 8 ( < 1 % ) lamivudine-treated patients . Fifty-three ( 5 % ) lamivudine-treated patients experienced a total of 60 LDR SAEs . Four patients died , 2 from liver-related causes . The proportion of patients with a documented lamivudine-resistant mutation increased from 23 % in year 1 to 65 % in year 5 . During each year of the study , patients with lamivudine-resistant mutations experienced significantly more hepatitis flares than patients without lamivudine-resistant mutations ( P < 0.005 ) . The occurrence of hepatic decompensation ( 0%-2 % ) and LDR SAEs ( 1%-10 % ) among patients with lamivudine resistance remained stable during the first 4 years with mutations and increased afterward to 6 % ( P = 0.03 ) and 20 % ( P = 0.009 ) , respectively . CONCLUSIONS This study demonstrated that lamivudine treatment for up to 6 years has an excellent safety profile in patients with HBeAg-positive compensated liver disease , but patients with long-st and ing lamivudine-resistant mutations may experience worsening liver disease BACKGROUND / AIMS This study aim ed to evaluate the effect of interferon-alpha therapy on the long-term outcome of HBeAg-negative chronic hepatitis B. METHODS A cohort of 209 interferon-alpha treated and 195 untreated patients with histologically documented HBeAg-negative chronic hepatitis B were closely followed for a mean of 6 ( 1 - 13.5 ) years . Patients with decompensated liver disease and /or hepatocellular carcinoma at presentation were excluded . RESULTS Survival and complication ( liver decompensation and /or hepatocellular carcinoma ) -free survival were significantly worse in patients with compared to those without baseline cirrhosis and in patients older compared to those younger than 45 years ( P < 10(-4 ) ) . Sustained biochemical remission was achieved in 57 treated patients . Sustained responders had significantly better survival and complication-free survival than non-sustained responders ( P = 0.027 and P = 0.019 , respectively ) or than untreated patients ( P = 0.048 and P = 0.012 , respectively ) . Multivariate analysis showed that absence of baseline cirrhosis , younger age , and sustained biochemical remission were independently associated with an improved outcome . CONCLUSION In patients with HBeAg-negative chronic hepatitis B , sustained biochemical remission induced by interferon-alpha is associated with improved long-term outcome , even in the presence of cirrhosis and old age , both known factors associated with worse survival . Therefore , long-term biochemical remission appears to represent a satisfactory therapeutic target in this setting To assess whether extended treatment with interferon improves the outcome of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B , 101 consecutive patients were treated with 6 MU of interferon alfa 2b 3 times weekly for 24 months . During the 68-month study , 30 patients ( 30 % ) had a sustained response ( i.e. , normal serum transaminase levels and undetectable hepatitis B virus DNA by non-polymerase chain reaction [ PCR ] assays ) , and 15 cleared serum surface antigen . Twenty-five nonresponders , 16 relapsers , and 30 who discontinued treatment were considered treatment failures . Multivariate analysis predicted a sustained response for young age ( odds ratio , 0.94 ; 95 % confidence interval , 0.89 - 0.99 ; P = .041 ) and high pretreatment serum levels of immunoglobulin M ( IgM ) anti-hepatitis B core antigen ( HBc ) ( odds ratio , 4.52 ; 95 % confidence interval , 1.63 - 12.5 ; P = .004 ) . Liver disease progressed in none of the sustained responders but in 16 with treatment failure ( 0 % vs. 22 % , P = .002 ) ; hepatocellular carcinoma ( HCC ) developed with similar frequency in both groups ( 7 % ) . Overall , estimated 8-year complication-free survival was longer for the 30 sustained responders than the 71 patients with treatment failure ( 90 % vs. 60 % , P < .001 ) , but 8-year patient survival was similar in the 2 groups ( 100 % and 90 % ) . Short complication-free survival was predicted by failure to respond to interferon ( hazard ratio , 7.8 ; 95 % confidence interval , 1.8 - 34.0 ; P = .006 ) and high scores for liver fibrosis ( hazard ratio , 1.71 ; 95 % confidence interval , 1.17 - 2.50 ; P = .005 ) . In conclusion , 24 months of treatment with interferon alfa 2b led to sustained disease suppression in a significant proportion of patients with HBeAg-negative chronic hepatitis The long-term efficacy of lamivudine therapy in patients with hepatitis B virus ( HBV ) infection is still not clear . In this study , 20 non-cirrhotic Japanese patients infected with HBV received lamivudine therapy for more than 1 year and were followed for a median period of 8.5 years ( range , 6.7 - 8.7 years ) . The rates of HBe antigen ( HbeAg ) negative , HBV-DNA undetectable , and alanine aminotransferase ( ALT ) normal level at the start of lamivudine were 55 % , 25 % , and 20 % and 85 % , 80 % , and were 80 % , respectively , at the last visit , including patients who received additional treatment . The values at the last visit tended to and were significantly higher than those at the start . The values improved at the last visit regardless of the emergence of YMDD motif mutant and continuation of lamivudine . YMDD mutant and biochemical relapse with mutant virus ( breakthrough hepatitis ) appeared in 65 % and 45 % during follow-up , respectively , but severe breakthrough hepatitis occurred in only 5 % . Furthermore , 80 % of patients who received additional treatment for breakthrough hepatitis , regardless of continuation of lamivudine , were ALT normal level at the last visit , in contrast to 25 % untreated . HBsAg clearance occurred in two patients of the discontinuous lamivudine group with non-vertical transmission , who were relatively young . One was infected with HBV genotype C with breakthrough hepatitis and the other had no YMDD mutant and was infected with genotype D , a rare type in Japan . None developed cirrhosis or hepatocellular carcinoma ( HCC ) during follow-up . Our results suggest that long-term lamivudine therapy improves long-term prognosis , especially when additional treatment for breakthrough hepatitis is used BACKGROUND & AIMS Adefovir monotherapy is an established treatment modality for lamivudine-experienced patients with chronic hepatitis B , but it carries a significant risk of resistance in the long term . We assessed whether this risk could be overcome by adefovir-lamivudine combination therapy . METHODS A total of 145 lamivudine-resistant patients with chronic hepatitis B ( 73 % cirrhotics , 86 % hepatitis B e antigen negative , 92 % genotype D ) were treated with adefovir 10 mg in addition to lamivudine 100 mg . Liver function tests and hepatitis B virus ( HBV ) DNA ( Versant 3.0 ) were assessed bimonthly , whereas adefovir-related mutations were search ed by INNO-LiPA assay at baseline and at yearly intervals . RESULTS During 42 months ( range , 12 - 74 ) , 116 patients ( 80 % ) cleared serum HBV DNA , 67 ( 84 % ) had normalized alanine aminotransferase levels , and 145 ( 100 % ) remained free of virologic and clinical breakthroughs , independently of the degree of HBV suppression . The rtA181V/T was the only adefovir-related mutation detected , which occurred in 6 patients at baseline ( 4 % ; 1 rtA181V and 5 rtA181 T ) and in an additional 3 patients ( 2 % ; all rtA181 T ) during treatment . In all these 9 patients , HBV DNA levels progressively declined during therapy to become undetectable in 7 ( 78 % ) . The 1- , 2- , 3- , and 4-year cumulative rates of de novo rtA181 T were 1 % , 2 % , 4 % , and 4 % , respectively . None of the cirrhotic patients clinical ly decompensated , but 11 ( 12 % ) developed hepatocellular carcinoma . CONCLUSIONS Under prolonged adefovir-lamivudine therapy , patients with lamivudine-resistant hepatitis B were unlikely to develop genotypic resistance to adefovir and had durable prevention of virologic and clinical breakthrough Introduction In hepatitis B virus (HBV)-related liver cirrhosis , patients with HBV replication show a higher mortality rate than those without . We aim ed to investigate the long-term effects of lamivudine on HBV DNA suppression , Child-Pugh score , and survival in patients with hepatitis Be antigen (HBeAg)-negative liver cirrhosis . Methods Sixty-eight patients ( 51 male , 17 female ) diagnosed with HBV-positive liver cirrhosis , who were monitored by the hepatology and liver transplantation outpatient clinics of our hospital between June 1999 and May 2007 , were included in the study . Lamivudine ( 100 mg/day ) was administered orally . Follow-up visits were scheduled monthly during the first 3 months , and every 3 months thereafter . Complete blood count , haemostasis , biochemistry ( aspartate aminotransferase [ AST ] , alanine aminotransferase [ ALT ] , amylase , urea , creatinine , total bilirubin , direct bilirubin , total protein , albumin ) , and alpha-foetoprotein were recorded every 3 months . HBV DNA levels , abdominal ultrasound and the Child-Pugh score were evaluated every 6 months . Results Sixty-eight patients ( mean age , 52.05±12.6 years ) were monitored for 49.51±18.51 months . Basal ALT , HBV DNA levels and Child-Pugh scores were 103.9±73.9 IU/ml , 4133±121,94 IU/ml , and 7.6±2.4 , respectively . The ALT normalisation was 59.7 % during the first year , 68.2 % during the second year and 44.4 % during the fifth year . There was a significant decrease in Child-Pugh scores in the first 3 follow-up years when compared with the baseline score ( P<0.05 ) . During the treatment , HBV DNA positivity and YMDD mutations were determined in 20 of 68 ( 29.4 % ) patients at 46±17.9 months . Nine patients ( 13.2 % ) developed hepatocellular carcinoma at 44.8±21.5 months . Thirteen patients ( 19.1 % ) died during the treatment due to liver failure or variceal bleeding . Conclusion Lamivudine is beneficial in patients with HBeAg-negative liver cirrhosis in terms of improvement in liver function and enhancement of survival and quality of life . An HBV DNA suppressive effect and improvement in Child-Pugh score were seen especially in the first years . It is important to be aware of YMDD mutation early , as addition of new antivirals is necessary to overcome unwanted results of the mutation The emergence of drug-resistant virus in hepatitis B virus patients treated with lamivudine is well documented . However , its clinical impact in the long-term treatment of anti-HBe positive compensated cirrhotic patients is not well known . In this study , we treated 22 consecutive patients with anti-HBe compensated cirrhosis with lamivudine for a median period of 42 months . All patients responded to lamivudine , but viral breakthrough occurred in 13 patients ( 59 % ) between 9 and 42 months of therapy due to the emergence of a mutant strain . During the follow-up , 11 developed hepatocellular carcinoma . Of these , 10 occurred soon after the emergence of viral resistance , generally showing aggressive behaviour , and one in the nine long-term responder patients ( P = 0.013 ) . Lamivudine resistance was the only independent predictor of hepatocellular carcinoma development ( risk ratio : 10.4 ; 95 % CI : 1.3 - 84.9 ) . Our study suggests that the occurrence of lamivudine resistance increases the risk of hepatocellular carcinoma in anti-HBe positive cirrhosis and warrants further research BACKGROUND / AIMS The aim of this study was to evaluate long term safety and antiviral activity of different doses of emtricitabine given once daily to patients chronically infected with hepatitis B. METHODS Eligible patients were r and omized in a double-blind , parallel study to evaluate 25 , 100 or 200 mg once daily doses of emtricitabine for 48 weeks . Patients were then followed for an additional 48 weeks on open-label 200 mg emtricitabine . Serum HBV DNA , ALT , and hepatitis B serology were measured at regular intervals over the 2 years . Resistance surveillance was performed after 1 and 2 years on viremic sample s , i.e. > 4700 copies/mL. RESULTS Emtricitabine was well tolerated and produced a dose proportional antiviral response . After 2 years , 53 % of the patients had serum HBV DNA < or = 4700 copies/mL , 33 % seroconverted to anti-HBe and 85 % had normal ALT . Eighteen percent of the patients who had received 200 mg emtricitabine for 2 years developed resistance mutations . CONCLUSIONS Emtricitabine was well tolerated and demonstrated a potent antiviral response for up to 2 years in patients with chronic hepatitis B infection . Based on these data , 200 mg emtricitabine once daily was chosen as the optimal dose for future hepatitis B studies |
12,780 | 30,159,775 | This meta- analysis suggests that PPI user have a 26 % increased risk of hip fracture as compared to non-PPI user . | In the last decade , epidemiological studies presented inconsistent findings concerning the proton pump inhibitors ( PPI ) use and the risk of hip fracture .
So , this systematic review and meta- analysis were performed with the aim to quantify the risk of hip fracture associated with PPI use .
Primary outcome of this study was to assess the risk of hip fracture among PPI user . | This study was performed to investigate the effects of the co-administration of proton pump inhibitor ( PPI ) on the efficacy of bisphosphonate ( BP ) treatment for osteoporosis . A total of 180 women with low bone mineral density were r and omly divided into four groups , one in which sodium risedronate was administered with sodium rabeprazole and one in which only risedronate was administered ( BP + PPI and BP groups , respectively ) . The biomarkers were measured at the baseline and every 3 months , inlcuding : N-terminal telopeptide of type I collagen corrected for creatinine , bone-specific alkaline phosphatase ( BAP ) , parathyroid hormone , bone mineral density ( BMD ) of the lumbar spine and physical parameters evaluated according to the SF-36v2 ™ Health Survey . Statistical comparisons of these parameters were performed after 9 months . Data were available for a total of 137 patients ( 62 in the BP group and 75 in the BP + PPI group ) . The Δ % value of increase in BMD and improvement of physical functioning in the BP + PPI group were significantly larger , and its decrease in BAP in the BP + PPI group was significantly smaller than that in the BP group . It is expected that risedronate administration in combination with a PPI may be more effective not only for treating osteoporosis but also improving physical fitness than treatment with risedronate alone We studied the effect of proton pump inhibitors , histamine H2 receptor antagonists , and other types of antacid drugs on fracture risk . All cases were subjects with any fracture sustained during the year 2000 ( n = 124,655 ) . For each case , three controls ( n = 373,962 ) matched on age and gender were r and omly drawn from the background population . The primary exposure variables were use of proton pump inhibitors , histamine H2 antagonists , and other antacid drugs . Adjustments were made for several confounders , including diagnosis of an ulcer , nonsteroidal anti-inflammatory drug use , use of histamine H1 antagonists , stomach resection , previous fracture , and use of corticosteroids . The effect of dose was examined by stratifying for cumulated dose ( defined daily dose ) . Use of proton pump inhibitors was associated with an increase in fracture risk for use within the last year [ odds ratio ( OR ) = 1.18 , 95 % confidence interval ( CI ) 1.12–1.43 for overall fracture risk ; OR = 1.45 , 95 % CI 1.28–1.65 for hip fractures ; and OR = 1.60 , 95 % CI 1.25–2.04 for spine fractures ) . Histamine H2 antagonists were associated with a decreased fracture risk if they had been used within the last year ( OR = 0.88 , 95 % CI 0.82–0.95 for any fracture , OR = 0.69 , 95 % CI 0.57–0.84 for hip fractures ) . Other antacids were not associated with overall fracture risk but were associated with hip and spine fractures . Proton pump inhibitors appeared to be associated with a limited increase in fracture risk , in contrast to histamine H2 antagonists , which seemed to be associated with a small decrease in fracture risk . In all cases , the changes in risk estimates were small and the clinical significance was limited BACKGROUND No studies have estimated disability-adjusted life-years ( DALYs ) lost due to hip fractures using real-life follow-up cohort data . We aim ed to quantify the burden of disease due to incident hip fracture using DALYs in prospect i ve cohorts in the CHANCES consortium , and to calculate population attributable fractions based on DALYs for specific risk factors . METHODS We used data from six cohorts of participants aged 50 years or older at recruitment to calculate DALYs . We applied disability weights proposed by the National Osteoporosis Foundation and did a series of sensitivity analyses to examine the robustness of DALY estimates . We calculated population attributable fractions for smoking , body-mass index ( BMI ) , physical activity , alcohol intake , type 2 diabetes and parity , use of hormone replacement therapy , and oral contraceptives in women . We calculated summary risk estimates across cohorts with pooled analysis and r and om-effects meta- analysis methods . FINDINGS 223 880 men and women were followed up for a mean of 13 years ( SD 6 ) . 7724 ( 3·5 % ) participants developed an incident hip fracture , of whom 413 ( 5·3 % ) died as a result . 5964 DALYs ( 27 per 1000 individuals ) were lost due to hip fractures , 1230 ( 20·6 % ) of which were in the group aged 75 - 79 years . 4150 ( 69·6 % ) DALYs were attributed to disability . Current smoking was the risk factor responsible for the greatest hip fracture burden ( 7·5 % , 95 % CI 5·2 - 9·7 ) followed by physical inactivity ( 5·5 % , 2·1 - 8·5 ) , history of diabetes ( 2·8 % , 2·1 - 4·0 ) , and low to average BMI ( 2·0 % , 1·4 - 2·7 ) , whereas low alcohol consumption ( 0·01 - 2·5 g per day ) and high BMI had a protective effect . INTERPRETATION Hip fracture can lead to a substantial loss of healthy life-years in elderly people . National public health policies should be strengthened to reduce hip fracture incidence and mortality . Primary prevention measures should be strengthened to prevent falls , and reduce smoking and a sedentary lifestyle . FUNDING European Community 's Seventh Framework Programme Proton pump inhibitors are taken by millions of patients for prevention and treatment of gastroesophageal diseases . Case-control studies have suggested that use of omeprazole is associated with an increased risk of hip fractures . The aim of this prospect i ve study was to assess the risk of vertebral fractures in postmenopausal women using omeprazole . We studied 1,211 postmenopausal women enrolled in the Osteoporosis and Ultrasound Study from the general population . Information on omeprazole and other risk factors for fractures including prevalent fractures and bone mineral density was obtained at baseline . Vertebral fractures were assessed on X-rays obtained at baseline and at the end of the 6-year follow-up and analyzed central ly . At baseline , 5 % of this population was using omeprazole . Age-adjusted rates for vertebral fractures were 1.89 and 0.60 for 100 person-years for omeprazole users and nonusers , respectively ( P = 0.009 ) . In the multivariate analysis , omeprazole use was a significant and independent predictor of vertebral fractures ( RR = 3.50 , 95 % CI 1.14–8.44 ) . The other predictors were age higher than 65 years ( RR = 2.34 , 95 % CI 1.02–5.34 ) , prevalent vertebral fractures ( RR = 3.62 , 95 % CI 1.63–8.08 ) , and lumbar spine T score ≤ −2.5 ( RR = 2.38 , 95 % CI 1.03–5.49 ) . Omeprazole use is associated with an increased risk of vertebral fractures in postmenopausal women . Further studies are required to determine the mechanism of the association between the underlying gastric disease , omeprazole use , and risk of osteoporotic fractures Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objective To examine the association between chronic use of proton pump inhibitors ( PPIs ) and risk of hip fracture . Design Prospect i ve cohort study . Setting Nurses ’ Health Study , which originally recruited from the 11 most populous states in the US . Participants 79 899 postmenopausal women enrolled in the Nurses ’ Health Study who provided data on the use of PPIs and other risk factors biennially since 2000 and were followed up to 1 June 2008 . Main outcome measure Incident hip fracture Results During 565 786 person years of follow-up , we documented 893 incident hip fractures . The absolute risk of hip fracture among regular users of PPIs was 2.02 events per 1000 person years , compared with 1.51 events per 1000 person years among non-users . Compared with non-users , the risk of hip fracture among women who regularly used PPIs for at least two years was 35 % higher ( age adjusted hazard ratio 1.35 ( 95 % confidence interval 1.13 to 1.62 ) ) , with longer use associated with increasing risk ( Ptrend<0.01 ) . Adjustment for risk factors , including body mass index , physical activity , and intake of calcium did not material ly alter this association ( hazard ratio 1.36 ( 1.13 to 1.63 ) ) . These associations were also not changed after accounting for reasons for PPI use . The relation between PPI use and fracture differed by smoking history ( Pinteraction=0.03 ) . Among current and former smokers , PPI use was associated with greater than 50 % increase in risk of fracture , with a multivariate hazard ratio for fracture of 1.51 ( 1.20 to 1.91 ) . In contrast , among women who never smoked there was no association ( multivariate hazard ratio 1.06 ( 0.77 to 1.46 ) ) . In a meta- analysis of these results with 10 prior studies , the pooled odds ratio of hip fracture associated with PPI use was 1.30 ( 1.25 to 1.36 ) . Conclusion Chronic use of PPIs is associated with increased risk of hip fracture , particularly among women with a history of smoking Summary A large Canadian cohort was studied over 10 years to see if proton pump inhibitor ( PPI ) use increased the risk of sustaining a fragility fracture . We found an increased risk of fracture in individuals who used PPIs . The risk remained after controlling for other known fracture risk factors . Introduction Multiple retrospective studies have linked proton pump inhibitor use with increased risk of fragility fracture . We prospect ively studied the association between PPI use and fracture in a large cohort over a 10-year period while controlling for known fracture risk factors . Methods We studied 9,423 participants in the Canadian Multicenter Osteoporosis Study . The cohort was formed in 1995–1997 and followed for 10 years with monitoring for incident nontraumatic fracture and PPI use . Cox regression analyses were used to assess the association between PPI use and incident fracture risk . Results PPI use , coded as a time-dependent variable , was associated with a shorter time to first nontraumatic fracture , hazard ratio ( HR ) = 1.75 ( 95 % confidence interval ( CI ) 1.41–2.17 , p < 0.001 ) . After controlling for multiple risk factors , including femoral neck bone density , the association remained significant , HR = 1.40 ( 95 % CI 1.11–1.77 , p = 0.004 ) . Similar results were obtained after controlling for bisphosphonate use , using PPI “ ever ” use , or when the outcome was restricted to hip fracture . Conclusions In this large prospect i ve population -based cohort study , we found an association between PPI use and increased risk of fragility fracture . Although the increased risk found was modest , this finding is important , given the high prevalence of PPI use and the excess morbidity and mortality associated with osteoporosis-related fractures BACKGROUND Proton pump inhibitor ( PPI ) medications have been inconsistently shown to be associated with osteoporotic fractures . We examined the association of PPI use with bone outcomes ( fracture , bone mineral density [ BMD ] ) . METHODS This prospect i ve analysis included 161 806 postmenopausal women 50 to 79 years old , without history of hip fracture , enrolled in the Women 's Health Initiative ( WHI ) Observational Study and Clinical Trials with a mean ( SD ) follow-up of 7.8 ( 1.6 ) years . Analyses were conducted for 130 487 women with complete information . Medication information was taken directly from drug containers during in-person interviews ( baseline , year 3 ) . The main outcome measures were self-reported fractures ( hip [ adjudicated ] , clinical spine , forearm or wrist , and total fractures ) and for a sub sample ( 3 densitometry sites ) , 3-year change in BMD . RESULTS During 1 005 126 person-years of follow-up , 1500 hip fractures , 4881 forearm or wrist fractures , 2315 clinical spine fractures , and 21 247 total fractures occurred . The multivariate-adjusted hazard ratios for current PPI use were 1.00 ( 95 % confidence interval [ CI ] , 0.71 - 1.40 ) for hip fracture , 1.47 ( 95 % CI , 1.18 - 1.82 ) for clinical spine fracture , 1.26 ( 95 % CI , 1.05 - 1.51 ) for forearm or wrist fracture , and 1.25 ( 95 % CI , 1.15 - 1.36 ) for total fractures . The BMD measurements did not vary between PPI users and nonusers at baseline . Use of PPIs was associated with only a marginal effect on 3-year BMD change at the hip ( P = .05 ) but not at other sites . CONCLUSION Use of PPIs was not associated with hip fractures but was modestly associated with clinical spine , forearm or wrist , and total fractures Proton pump inhibitors ( PPIs ) are widely used in the elderly . Recent studies have suggested that long-term PPI therapy is associated with fractures in the elderly , however the mechanism remains unknown . We investigated the association between long-term PPI therapy ≥1 year and fracture risk factors including bone structure , falls , and balance-related function in a post hoc analysis of a longitudinal population -based prospect i ve cohort of elderly postmenopausal women and replicated the findings in a second prospect i ve study of falling in elderly postmenopausal women . Long-term PPI therapy was associated with increased risk of falls and fracture-related hospitalizations ; adjusted odds ratio ( AOR ) 2.17 ; 95 % CI , 1.25 - 3.77 ; p = 0.006 and 1.95 ; 95 % CI , 1.20 - 3.16 ; p = 0.007 , respectively . In the replication study , long-term PPI use was associated with an increased risk of self-reported falling ; AOR , 1.51 ; 95 % CI , 1.00 - 2.27 ; p = 0.049 . No association of long-term PPI therapy with bone structure was observed ; however , question naire-assessed falls-associated metrics such as limiting outdoor activity ( p = 0.002 ) and indoor activity ( p = 0.001 ) due to fear of falling , dizziness ( p < 0.001 ) and numbness of feet ( p = 0.017 ) and objective clinical measurement such as Timed Up and Go ( p = 0.002 ) and Romberg eyes closed ( p = 0.025 ) tests were all significantly impaired in long-term PPI users . Long-term PPI users were also more likely to have low vitamin B12 levels than non-users ( 50 % versus 21 % , p = 0.003 ) . In conclusion , similar to previous studies , we identified an increased fracture risk in subjects on long-term PPI therapy . This increase in fracture risk in elderly women , already at high risk of fracture , appears to be mediated via increased falls risk and falling rather than impaired bone structure and should be carefully considered when prescribing long-term PPI therapy |
12,781 | 31,456,961 | The challenge related to design was poor planning .
Conclusion : Based on the results of this systematic review , the most important challenges were barriers related to h and ling ethical and regulatory systems , patient recruitment , and lack of budget and skilled staff for conducting clinical trials . | Background : R and omized clinical trials have been considered as the gold st and ard for evaluating the effectiveness and safety of medical interventions ; however , there are major barriers to their design , conduct , analysis , and reporting .
They are multidisciplinary and involve different steps and face a variety of challenges that may vary from one country to another .
The aim of this study was to provide a comprehensive presentation of the challenges of clinical trial studies in different steps including design , conducting , analysis , and reporting . | Solutions are employed to support clinical research trial tasks in community-based practice setting s. Using the IT Implementation Framework ( ITIF ) , an integrative framework intended to guide the synthesis of theoretical perspectives for planning multi-level interventions to enhance IT use , we sought to underst and the barriers and facilitators to clinical research in community-based practice setting s preliminary to implementing new informatics solutions for improving clinical research infrastructure . The studies were conducted in practice s within the Columbia University Clinical Trials Network . A mixed- method approach , including surveys , interviews , time-motion studies , and observations was used . The data collected , which incorporates predisposing , enabling , and reinforcing factors in IT use , were analyzed according to each phase of ITIF . Themes identified in the first phase of ITIF were 1 ) processes and tools to support clinical trial research and 2 ) clinical research peripheral to patient care processes . Not all of the problems under these themes were found to be amenable to IT solutions . Using the multi-level orientation of the ITIF , we set forth strategies beyond IT solutions that can have an impact on reengineering clinical research tasks in practice -based setting s. Developing strategies to target enabling and reinforcing factors , which focus on organizational factors , and the motivation of the practice at large to use IT solutions to integrate clinical research tasks with patient care processes , is most challenging . The ITIF should be used to consider both IT and non-IT solutions concurrently for reengineering of clinical research in community-based practice setting Background The feasibility of r and omized trials often depends on successful patient recruitment . Although numerous recruitment barriers have been identified it is unclear which of them complicate recruitment most . Also , most surveys have focused on the patients ' perspective of recruitment barriers whereas the perspective of recruiting physicians has received less attention . Therefore , our aim was to conduct a postal survey among recruiting physicians of a multi-center trial to weigh barriers according to their impact on recruitment . Methods We identified any potential recruitment barriers from the literature and from our own experience with a multi-center trial of respiratory rehabilitation in patients with chronic obstructive pulmonary disease . We developed and pilot-tested a self-administered question naire where recruiting physicians were asked to express their agreement with statements about recruitment barriers on a Likert-type scale from 1 ( full agreement with statement = very substantial recruitment barrier ) to 7 ( no agreement with statement = no recruitment barrier ) . Results 38 of 55 recruiting physicians returned question naires ( 69 % response rate ) , of which 35 could be analyzed ( 64 % useable response rate ) . Recruiting physicians reported that " time constraints " ( median agreement of 3 , interquartile range 2–5 ) had the most negative impact on recruitment followed by " difficulties including identified eligible patients " ( median agreement of 5 , IQR 3–6 ) . Other barriers such as " trial design barriers " , " lack of access to treatment " , " individual barriers of recruiting physicians " or " insufficient training of recruiting physicians " were perceived to have little or no impact on patient recruitment . Conclusion Physicians perceived time constraints as the most relevant recruitment barrier in a r and omized trial . To overcome recruitment barriers interventions , that are affordable for both industry- and investigator-driven trials , need to be developed and tested in r and omized trials . Trial registration IS RCT 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 Background Recent cohort studies of r and omised controlled trials have provided evidence of within- study selective reporting bias ; where statistically significant outcomes are more likely to be more completely reported compared to non-significant outcomes . Bias result ing from selective reporting can impact on meta-analyses , influencing the conclusions of systematic review s , and in turn , evidence based clinical practice guidelines .In 2006 we received funding to investigate if there was evidence of within- study selective reporting in a cohort of RCTs su bmi tted to New Zeal and Regional Ethics Committees in 1998/99 . This research involved accessing ethics applications , their amendments and annual reports , and comparing these with corresponding publications . We did not plan to obtain informed consent from trialists to view their ethics applications for practical and scientific reasons .In November 2006 we sought ethical approval to undertake the research from our institutional ethics committee . The Committee declined our application on the grounds that we were not obtaining informed consent from the trialists to view their ethics application . This initiated a seventeen month process to obtain ethical approval . This publication outlines what we planned to do , the issues we encountered , discusses the legal and ethical issues , and presents some potential solutions . Discussion and conclusion Method ological research such as this has the potential for public benefit and there is little or no harm for the participants ( trialists ) in undertaking it . Further , in New Zeal and , there is freedom of information legislation , which in this circumstance , unambiguously provided rights of access and use of the information in the ethics applications . The decision of our institutional ethics committee defeated this right and did not recognise the nature of this observational research . Method ological research , such as this , can be used to develop processes to improve quality in research reporting . Recognition of the potential benefit of this research in the broader research community , and those who sit on ethics committees , is perhaps needed . In addition , changes to the ethical review process which involve separation between those who review proposals to undertake method ological research using ethics applications , and those with responsibility for review ing ethics applications for trials , should be considered . Finally , we contend that the research community could benefit from quality improvement approaches used in allied sectors Public health interventions usually operate at the level of groups rather than individuals , and cluster r and omized controlled trials ( RCTs ) are one means of evaluating their effectiveness . Using examples from six such trials in Bangladesh , India , Malawi and Nepal , we discuss our experience of the ethical issues that arise in their conduct . We set cluster RCTs in the broader context of public health research , highlighting debates about the need to reconcile individual autonomy with the common good and about the ethics of public health research in low-income setting s in general . After a brief introduction to cluster RCTs , we discuss particular challenges we have faced . These include the nature of - and responsibility for - group consent , and the need for consent by individuals within groups to intervention and data collection . We discuss the timing of consent in relation to the implementation of public health strategies , and the problem of securing ethical review and approval in a complex domain . Finally , we consider the debate about benefits to control groups and the st and ard of care that they should receive , and the issue of post-trial adoption of the intervention under test Background Excessive protocol violations ( PV ) , which can be defined as preventable mistakes in study conduct , may result in patient harm and introduce errors into a clinical trial 's results leading to flawed trial conclusions .The purpose of this project was to gain a better underst and ing of reported PVs , to describe current practice with regards to the use of methods for the reduction of PVs and to investigate relationships between clinical trial characteristics and PVs . Methods We review ed 80 clinical trials conducted across a broad range of medical specialties published in four major general medical journals ( The Lancet , NEJM , JAMA , BMJ ) . Eligible papers were identified using a PubMed search . For each included trial , two authors independently abstract ed information on trial characteristics , PV reporting and PV rates and interventions used to reduce PVs . PVs were categorised into one of five distinct types : enrolment , r and omisation , study intervention , patient compliance and data collection errors . Associations between PVs and study characteristics were investigated using logistic regression . Results Eighty clinical trials ( 20 from each journal ) were identified from 101 consecutive PubMed abstract s. The median number of participants was 701 ( range : 20 to 162 , 367 ) and the median number of participating sites was 15 ( range : 1 to 701 ) . Nineteen percent ( 15/80 ) of included trials were single centre trials . The median study duration was 24 months ( range : 5.81 - 127 months ) and 74 % ( 59/80 ) of included trials were primarily academic funded . Thirty two percent ( 26/80 ) of included trials failed to provide explicit reporting of any type of PV and none ( 0/80 ) of the trials provided explicit reporting of all five types of PVs . Larger clinical trials ( more patients , more sites , longer duration , more complex management structure ) were more likely to have more complete reporting of PV's . Only 9 % ( 7/80 ) of trials reported the use of a specific study method to prevent PVs . Use of a run-in phase was the only method reported . Conclusions PVs are under-reported . Although the CONSORT statement provides guidance on the reporting of PVs , reporting requirements are not explicit for all types of PVs . As a first step towards improved reporting by authors , we recommend the CONSORT statement highlight the importance of PVs by making reporting requirements more explicit 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 OBJECTIVE Latinas are underrepresented in clinical trials despite the rise in Hispanic population . This study examines the factors associated with Latinas ' willingness to participate in preventive breast cancer r and omized clinical trials ( RCTs ) . METHODS Women self-identifying as Latina , over age 40 , with no prior history of breast cancer were eligible . Using the Behavior Model for Vulnerable Population s , we administered a survey ( n=168 ) to assess predisposing ( e.g. , knowledge ) , enabling ( e.g. , trust ) and need factors ( e.g. , risk perception ) . Intention to participate was defined using a lenient ( maybe , probably or definitely ) and a stringent criterion ( probably and definitely ) . Chi-square tests and logistic regression models examined the associations of predisposing , enabling , and need factors with women 's intentions to participate in RCTs . RESULTS Most participants ( 74.9 % ) were monolingual Spanish-speaking immigrants . Most ( 83.9 % ) reported willing to participate in clinical trials using the lenient definition ( vs. 43.1 % under the stringent definition ) . Using the lenient definition , the odds of willing to participate in RCTs were significantly lower for unmarried women ( OR=.25 , 95 % CI=.08-.79 ) and those with lower cancer risk perceptions ( OR=.20 , 95 % CI=.06-.63 ) , while being significantly higher for women with lower language acculturation ( OR=6.2 , 95 % CI=1.8 - 20.9 ) . Using the stringent definition , women who did not endorse a motivation to enroll to help family members ( if they had cancer ) had significantly lower odds to report intent ( OR=.33 , 95 % CI=.13-.86 ) . CONCLUSION Many RCTs may have limited generalizability due to the low representation of minorities . Culturally targeted interventions that address the importance of family for Latinos may ultimately increase their participation in RCTs Background Online technology is a promising re source for conducting clinical research . While the internet may improve a study 's reach , as well as the efficiency of data collection , it may also introduce a number of challenges for participants and investigators . The objective of this research was to determine the challenges that potential participants faced during the enrollment phase of a r and omized controlled intervention trial of Stepping Up to Health , an internet-mediated walking program that utilized a multi-step online enrollment process . Methods We conducted a quantitative content analysis of 623 help tickets logged in a participant management data base during the enrollment phase of a clinical trial investigating the effect of an automated internet-mediated walking intervention . Qualitative coding was performed by two trained coders , and 10 % of the sample was coded by both coders to determine inter-coder reliability . Quantitative analyses included st and ard descriptive statistics on ticket characteristics and theme frequency , and a Poisson regression analysis identified characteristics of potential participants who reported more frequent problems during enrollment . Results In total , 880 potential participants visited the study website and 80 % completed the enrollment screening . Of the potential participants who visited the study website , 38 % had help tickets logged in the participant management data base . The total number of help tickets associated with individual potential participants ranged from 0 to 7 ( M = .71 ) . Overall , 46 % of help tickets were initiated by email and 54 % were initiated by phone . The most common help ticket theme was issues related to the study process ( 48 % ) . The next most prominent theme was discussion related to obtaining medical clearance ( 34 % ) , followed by issues related to pedometers and uploading ( 31 % ) . Older individuals , women , and those with lower self-rated internet ability were more likely to report problems during the enrollment process . Conclusion Prospect i ve participants in an online clinical trial encountered a number of barriers to enrollment that led them to request help from study staff . Questions about the complex enrollment process itself were common . In a complex multi-step enrollment process , providing personalized feedback to potential participants indicating their status within the enrollment process may be beneficial . Trial Registration Clinical Trials.gov Background Recruitment of sufficient participants in an efficient manner is still widely acknowledged to be a major challenge to the mounting and completion of r and omised controlled trials ( RCTs ) . Few recruitment interventions have involved staff undertaking recruitment . This study aim ed i ) to underst and the recruitment process from the perspective of recruiters actively recruiting RCT participants in six pragmatic RCTs , and ii ) to identify opportunities for interventions to improve recruitment . Methods Interviews were undertaken with 72 individuals ( 32 doctors or RCT Chief investigators ( CIs ) ; 40 nurses/other health professionals ) who were actively recruiting participants in six RCTs to explore their experiences of recruitment . The RCTs varied in scale , duration , and clinical context s. Interviews were fully transcribed and analysed using qualitative content and thematic analytic methods derived from grounded theory . For this analysis , data were systematic ally extracted from each RCT and synthesis ed across all six RCTs to produce a detailed and nuanced underst and ing of the recruitment process from the perspectives of the recruiters . Results Recruiters readily identified organisational difficulties , fewer than expected eligible patients , and patients ’ treatment preferences as the key barriers to recruitment . As they described their experiences of recruitment , several previously hidden issues related to their roles as research ers and clinicians emerged , imbued with discomfort and emotion . The synthesis across the RCTs showed that doctors were uncomfortable about aspects of patient eligibility and the effectiveness of interventions , whereas nurses were anxious about approaching potential RCT participants and conflicts between the research and their clinical responsibilities . Recruiters seemed unaware that their views contributed to recruitment difficulties . Their views were not known to RCT CIs . Training and support needs were identified for both groups of staff . Conclusions The synthesis showed that recruitment to these RCTs was a complex and fragile process . Clear obstacles were identified but hidden challenges related to recruiters ’ roles undermined recruitment , unbeknown to RCT CIs . Qualitative research can elicit and identify the hidden challenges . Training and support are then needed for recruiters to become more comfortable with the design and principles of RCTs , so that they can engage more openly with potentially eligible participants and create a more resilient recruitment process Clinical equipoise is widely accepted as the basis of ethics in clinical research and requires investigators to be uncertain of the relative therapeutic merits of trial comparators . When clinical equipoise is in question , innovative trial design s are needed to reduce ethical tension while satisfying regulators ’ requirements . We report a novel response-conditional crossover study design used in a Phase 3 , r and omized , double-blind , placebo-controlled clinical trial of intravenous 10 % caprylate-chromatography purified immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy . During the initial 24-week period , patients crossed over to the alternative treatment at the first sign of deterioration or if they failed to improve or were unable to maintain improvement at any time after 6 weeks . This trial design addressed concerns about lack of equipoise raised by physicians interested in trial participation and proved acceptable to regulatory authorities . The trial design may be applicable to other studies where clinical equipoise is in question The results of good r and omized controlled trials ( RCTs ) published in leading peer- review ed journals have been deemed the best possible basis for good medical practice . However , several limitations may decrease their value . These include flaws and weaknesses in the design and the timeliness of RCTs . Progress in a treatment method or control arm may invali date a trial . So too can defects in patient selection , physician competence , r and omization , applicability , end points , and the population being studied . Idiosyncratic flaws can also invali date an RCT . Examples of these flaws and weaknesses are presented . Another problem with articles describing RCTs is the potential for the conclusions of the trial report to be misleading because of error or bias . This plus subsequent misinterpretation of the trial results or conclusions by others can make the effect of the trial misleading with an unintended detrimental result on medical practice . Guidelines based on such errors or bias-based conclusions and misinterpretations can further compound the problem . This article provides examples of misleading conclusions and /or misinterpretations ( spinning ) of trial results in articles describing RCTs in leading journals . All physicians should recognize these value-limiting processes so that RCTs can be evaluated adequately and fairly . In that way , they can be used along with good physician judgment to optimize the care delivered to individual patients and to society at large BACKGROUND No national South African institution provides a coherent suite of support , available skills and training for clinicians wishing to conduct r and omised controlled trials ( RCTs ) in the public sector . We report on a study to assess the need for establishing a national South African Clinical Trials Support Unit . OBJECTIVES To determine the need for additional training and support for conduct of RCTs within South African institutions ; identify challenges facing institutions conducting RCTs ; and provide recommendations for enhancing trial conduct within South African public institutions . DESIGN Key informant interviews of senior decision-makers at institutions with a stake in the South African public sector clinical trials research environment . RESULTS Trial conduct in South Africa faces many challenges , including lack of dedicated funding , the burden on clinical load , and lengthy approval processes . Strengths include the high burden of disease and the prevalence of treatment-naïve patients . Participants expressed a significant need for a national initiative to support and enhance the conduct of public sector RCTs . Research methods training and statistical support were viewed as key . There was a broad range of views regarding the structure and focus of such an initiative , but there was agreement that the national government should provide specific funding for this purpose . CONCLUSIONS Stakeholders generally support the establishment of a national clinical trials support initiative . Consideration must be given to the sustainability of such an initiative , in terms of funding , staffing , expected research outputs and permanence of location Summary Objectives To determine the consistency between information contained in the registration and publication of r and omised controlled trials ( RCTs ) . Design An observational study of RCTs published between May 2011 and May 2012 in the British Medical Journal ( BMJ ) and the Journal of the American Medical Association ( JAMA ) comparing registry data with publication data . Participants and Setting s Data extracted from published RCTs in BMJ and JAMA . Main outcome measures Timing of trial registration in relation to completion of trial data collection and publication . Registered versus published primary and secondary outcomes , sample size . Results We identified 40 RCTs in BMJ and 36 in JAMA . All 36 JAMA trials and 39 ( 98 % ) BMJ trials were registered . All registered trials were registered prior to publication . Thirty-two ( 82 % ) BMJ trials recorded the date of data completion ; of these , in two trials the date of trial registration post date d the registered date of data completion . There were discrepancies between primary outcomes declared in the trial registry information and in the published paper in 18 ( 47 % ) BMJ papers and seven ( 19 % ) JAMA papers . The original sample size stated in the trial registration was achieved in 24 ( 60 % ) BMJ papers and 21 ( 58 % ) JAMA papers . Conclusions Compulsory registration of RCTs is meaningless if the content of registry information is not complete or if discrepancies between registration and publication are not reported . This study demonstrates that discrepancies in primary and secondary outcomes and sample size between trial registration and publication remain commonplace , giving further strength to the World Health Organisation ’s argument for m and atory completion of a minimum number of compulsory fields |
12,782 | 18,176,936 | No significant difference was noted between the two techniques in terms of the total incidence of complications .
Stapled haemorrhoidopexy offers some short-term benefits over conventional operation but the total complication rates are similar for both techniques .
Stapled haemorrhoidopexy is associated with a higher rate of recurrent disease | BACKGROUND This paper compares stapled haemorrhoidopexy with conventional haemorrhoidectomy for the treatment of haemorrhoids . | HYPOTHESIS Stapled hemorrhoidectomy offers several advantages over excision hemorrhoidectomy , including reduced postoperative pain , a reduced hospital stay , and an earlier recovery time . Furthermore , stapled hemorrhoidectomy is associated with lower hemorrhoidal recurrence on long-term follow-up . DESIGN A r and omized prospect i ve trial . Patients were blinded to the operation technique used . Follow-up occurred at 1 and 3 weeks and 12 months postoperatively . SETTING A university hospital providing primary , secondary , and tertiary care . PATIENTS Forty patients with second- and third-degree hemorrhoid disease were r and omized to undergo either stapled or excision hemorrhoidectomy . Two patients were excluded . All patients were subject to a follow-up examination . INTERVENTIONS Stapled hemorrhoidectomy ( Longo technique ) vs excision hemorrhoidectomy ( Ferguson technique ) . MAIN OUTCOME MEASURES Operating time , postoperative pain ( measured by the visual analog scale ) , hospital stay , histologic features , morbidity , defecation habit , continence , recovery time ( return to work ) , and hemorrhoid recurrence at 1 year . RESULTS Stapled vs excision hemorrhoidectomy was associated with a significantly reduced operating time ( 30 vs 43.25 minutes ; P<.001 ) , reduced postoperative pain scores ( visual analog score ) on the first 4 postoperative days ( day 1 : 2.7 vs 6.3 ; day 2 : 1.7 vs 6.3 ; day 3 : 0.8 vs 5.4 ; and day 4 : 0.5 vs 4.8 , where 0 indicates no pain , and 10 , maximum pain ; P < or = .001 ) , and an earlier return to work ( 6.7 vs 20.7 days;P = .001 ) . There were no differences for stapled vs excision hemorrhoidectomy in length of hospital stay ( 2.4 vs 2.1 days ) , complications ( 3 [ 15 % ] of 20 patients vs 5 [ 25 % ] of 20 patients ) , and recurrence rate ( 1 [ 5 % ] of 20 patients vs 1 [ 5 % ] of 20 patients ) . CONCLUSIONS Stapled hemorrhoidectomy is associated with reduced postoperative pain , earlier recovery time and return to work , and a similar recurrence rate compared with the excision technique . Provided further clinical trials confirm these findings , stapled hemorrhoidectomy may become a future gold st and ard Abstract Purpose : To compare the postoperative evolution and the long-term efficacy after stapled haemorrhoidopexy ( PPH ) and Milligan-Morgan haemorrhoidectomy ( MM ) . Methods : In a prospect i ve r and omized study , 40 patients requiring surgical treatment for prolapsing haemorrhoids grade II or III were assigned to either MM or PPH ( 20 each ) . Postoperative pain , wound healing were evaluated , as well as anal pressures and sphincter anatomy . Mean follow-up is 46 months . Results : Postoperative pain at rest and during defecation was less important after PPH if no resection of external piles or skin tags was associated ( P < 0.0001 ) . Healing time was shorter after PPH ( P < 0.0001 ) . Endoanal ultrasound remained unchanged postoperatively . Resting and squeeze pressures decreased after MM , but not after PPH ( P < 0.01 ) . After a mean follow-up of 46 months ( 12 - 56 ) , persistent or recurrent symptoms , mostly mild and temporary , were observed after both MM and PPH , in 7 and 11 patients respectively ( NS ) . After PPH , five patients ( 25 % ) complained of recurrent external swelling and /or prolapse ( P = 0.047 vs. MM ) requiring redo surgery in four of them , after 10 , 13 , 14 and 21 months . No redo-surgery was required after MM . Long term patient satisfaction after PPH was not better than after MM . Conclusions : Postoperative pain is less important after PPH . This advantage disappears if any resection is associated with the stapling . At medium to long-term follow-up , PPH seems to carry a higher risk of symptomatic external haem-orrhoidal disease , needing further surgery PURPOSE It has been shown that for hemorrhoidal surgery both LigaSure ™ and stapler cause less pain than diathermy or scissor dissection . This study has attempted to establish which of the less painful alternatives proves best in an unselected series of patients with hemorrhoidal disease . METHODS Fifty patients were r and omized to undergo stapling hemorrhoidopexy or LigaSure ™ hemorrhoidectomy . Parameters investigated were pain ( primary parameter ) , patient satisfaction with treatment , and recovery of personal activity . Other factors investigated were operative result , ease of h and ling , analgesic requirements , and postoperative course . RESULTS Both methods were found to be equivalent in all major aspects analyzed . Postoperative pain scores ( P = 0.99 ) , patient satisfaction ( P = 1 ) , and self- assessment of activity ( P = 0.99 ) were almost identical in both groups of patients . Significant differences were found in none of the numerous factors investigated . CONCLUSION Both methods can be used safely and without major disadvantage for the patient regardless of stage and extent of hemorrhoidal disease Background and aims Stapled hemorrhoidectomy is a relatively new procedure , and studies on long-term outcomes are few . We present the results of a 5-year follow-up on patients recruited to a r and omized controlled trial comparing stapled and Milligan – Morgan hemorrhoidectomy . Patients and methods We performed telephone interviews and office visits between May and July 2005 on patients who had taken part in a r and omized controlled trial from May 1999 to December 2000 . Results Occasional pain and bleeding were referred by the patients with no difference between the two groups . The patients were also equally satisfied with both procedures . No recurrent hemorrhoidal prolapse or stenosis was detected at anorectal exploration and rigid sigmoidoscopy . Conclusion Both stapled and Milligan – Morgan techniques guarantee satisfactory long-term results . Larger studies are needed to assess the durability of stapled hemorrhoidectomy Advantages of the stapling procedure for haemorrhoids include reduced postoperative pain and shortened convalescence ; however , there are few data with respect to functional and symptomatic outcome . At a dedicated clinic , we review ed patients between Dec , 2001 , and March , 2002 , who had taken part in a r and omised controlled trial undertaken at the unit in 1999 , which compared outcomes after open or stapled haemorrhoidectomy . We noted the presence or absence of haemorrhoid specific symptoms , and assessed overall satisfaction , continence , and quality of life . Rigid sigmoidoscopy and an anorectal examination were also used to examine symptomatic recurrence and disease activity . At minimum follow-up of 33 months since surgery , both techniques seem to be equally effective PURPOSE A r and omized trial was undertaken to evaluate and compare stapled hemorrhoidopexy with excisional hemorrhoidectomy in which the Harmonic Scalpel ™ was used . METHODS Patients with Grade III hemorrhoids who were employed during the trial period were recruited and r and omized into two groups : ( 1 ) Harmonic Scalpel ™ hemorrhoidectomy , and ( 2 ) stapled hemorrhoidopexy . All operations were performed by a single surgeon . In the stapled group , the doughnut obtained was sent for histopathologic examination to determine whether smooth muscles were included in the specimen . Operative data and complications were recorded , and patients were followed up through a structured pro forma protocol . An independent assessor was assigned to obtain postoperative pain scores and satisfaction scores at six-month follow-up . Patients were also administered a simple question naire at follow-up to assess continence functions . RESULTS Over a 20-month period , 88 patients were recruited . The two groups were matched for age and gender distribution . No significant difference was identified between the two groups in terms of operation time , blood loss , day of first bowel movement after surgery , and complication rates . Despite a similar parenteral and oral analgesic requirement , the stapled group had a significantly better pain score ( P = 0.002 ) ; these patients also had a significantly shorter length of stay ( P = 0.02 ) , and on average resumed work nine days earlier than the group treated with the Harmonic Scalpel ™ ( 6.7 vs. 15.6 , P = 0.002 ) . Although 88 percent of doughnuts obtained in the stapled group contained some smooth muscle fibers , no association was found between smooth muscle incorporation and postoperative continence function , and as a whole the continence outcomes of the stapled group were similar to those after Harmonic Scalpel ™ hemorrhoidectomy . Finally , at six-month follow-up , patients who underwent the stapled procedure had significantly better satisfaction scores ( P = 0.001 ) . CONCLUSIONS tapled hemorrhoidopexy is a safe and effective procedure for Grade III hemorrhoidal disease . Patients derive greater short-term benefits of reduced pain , shorter length of stay , and earlier resumption to work . Long-term follow-up is necessary to determine whether these initial results are lasting The aim of this study was to assess the short- and long-term results of treatment for haemorrhoids by prospect ively comparing two techniques , namely , stapled rectal prolapse mucosectomy according to Longo and open hemorrhoidectomy . One hundred consecutive patients were r and omised to stapled ( 50 patients ) or manual hemorrhoidectomy ( 50 patients ) . We analysed postoperative pain , preoperative and postoperative anorectal function , intraoperative and postoperative complications , time needed to return to work and to normal social activities , and costs . Long-term follow data were obtained by means of an outpatient visit . The operative time of the stapled technique was less than that of open haemorrhoidectomy ( 22 vs 35 minutes ) . Two cases of early postoperative bleeding occurred after the stapled technique . The mean pain score on a visual scale was significantly less in patients undergoing the stapled technique . In addition , the time needed to return to work and to normal social activities was significantly less after the stapled technique , which , however , proved to be a more expensive procedure . Stapled mucosectomy of the prolapsed rectal mucosa is a safe , rapid , and relatively painless technique , which has a low incidence of complications . It can be performed in a day surgery unit . Patient satisfaction , early return to normal activities and good long-term results counterbalance the high cost of the procedure PURPOSE Stapled hemorrhoidectomy may be associated with less pain and faster recovery than conventional hemorrhoidectomy for prolapsing hemorrhoids . Therefore , the outcome of stapled hemorrhoidectomy was compared with that of diathermy hemorrhoidectomy in a r and omized , controlled trial . METHODS Sixty patients with third-degree hemorrhoids were r and omly assigned to stapled hemorrhoidectomy ( n = 30 ) or to diathermy hemorrhoidectomy in a day-case setting . Visual analog scale was used for postoperative pain scoring . Surgical and functional outcome was assessed at six weeks and one year after surgery . RESULTS Operation time was a median of 21 ( range , 11–59 ) minutes in the stapled group vs. 22 ( range , 14–40 ) minutes in the diathermy group . Day-case surgery was successful in 24 patients ( 80 percent ) in the stapled group vs. 29 patients ( 97 percent ) in the diathermy group . Average pain in the stapled group was significantly lower than in the diathermy group ( median , 1.8 ( 0.1–4.8 ) vs. 4.3 ( 1.4–6.2 ) , 95 percent confidence interval difference medians , 1.15–3.85 , P = 0.0002 , Mann-Whitney U test ) as was the average pain expected by the patients ( median −2.7 ( −0.15–0.8 ) vs. 0.006 ( −4.05–0.5 ) respectively , 95 percent confidence interval difference medians , 0.5–3.55 , P = 0.0018 , Mann-Whitney U test ) . Postoperative morbidity and time off work were not significantly different between the diathermy and stapled groups . Seven treatment failures in the stapled group and one in the diathermy group necessitated other treatments at a later date . Patient satisfaction scores in the stapled and diathermy group were similar . Symptoms attributed to difficult rectal evacuation decreased significantly after surgery . CONCLUSIONS Stapled hemorrhoidectomy is a significantly less painful operation than diathermy hemorrhoidectomy , but does not seem to offer significant advantages in terms of hospital stay or symptom control in the long term . Hemorrhoidectomy may improve symptoms of difficult rectal evacuation PURPOSE : Stapled hemorrhoidectomy is performed without leaving painful perianal wounds . The aim of this study was to assess any benefits , compared with a conventional open diathermy technique . METHODS : A total of 119 consecutive patients with prolapsed irreducible hemorrhoids were r and omly assigned ( conventional open diathermy technique=62 ; stapled hemorrhoidectomy=57 ) . Preoperative fecal incontinence scoring , anorectal manometry , and endoanal ultrasound were performed . Postoperatively , these were repeated at up to three months with pain scores , analgesic requirements , quality of life assessment , and total related medical costs . RESULTS : Conventional open diathermy technique was quicker to perform ( mean , 11.4 ( st and ard error of the mean , 0.9)vs . 17.6 ( 3.1 ) minutes ) . Hospitalization was similar , but conventional open diathermy technique patients felt more pain during defecation ( 5.1 (0.4)vs . 2.6 (0.4);P<0.005 ) at two weeks , and analgesic requirements were more for up to six weeks ( P<0.05 ) . Up to the latter , 85.5 percent conventional open diathermy technique wounds remained unhealed , with more bleeding ( 33 ( 53.2 percent)vs . 19 ( 33.3 percent);P<0.05 ) and pruritus ( 27 ( 43.5 percent)vs . 9 ( 15.8 percent);P<0.05 ) . Total complication rates were similar ( conventional open diathermy technique 16 ( 25.8 percent)vs . stapled hemorrhoidectomy 10 ( 17.5 percent ) ) , including mild strictures and bleeding in both groups . Minor incontinence occurred postoperatively in two conventional open diathermy technique and two stapled hemorrhoidectomy patients at six weeks . Endoanal ultrasound internal anal sphincter defects were found in the incontinent conventional open diathermy technique patients , but were asymptomatic in another one conventional open diathermy technique and one stapled hemorrhoidectomy . Only one patient ( conventional open diathermy technique with internal sphincter defect ) remained incontinent at three months . Changes between preoperative and postoperative anorectal manometry were similar in the two groups . Patients ' satisfaction scores and quality of life assessment s were also similar . Conventional open diathermy technique patients resumed work later ( mean 22.9 (1.8)vs . 17.1 ( 1.9 ) days;P<0.05 ) , but the total costs incurred were less ( $ 921.17 (16.85)vs . $ 1,283.09 (31.59);P<0.005 ) . CONCLUSIONS : Stapled hemorrhoidectomy is a safe and effective option in treating irreducible prolapsed piles . It is more expensive but less painful , with less time needed off work . Nonetheless , long-term results are still awaited Abstract . Background and aims : Postoperative pain is the most distressing sequela of conventional hemorrhoidectomy . A modern alternative of circumferential mucosectomy has been proposed to reduce the pain in this procedure . Patients and methods : This controlled trial included 80 patients with second to fourth degree hemorrhoidal disease operated on over a 2-year period . The patients were r and omly allocated to undergo either the stapled Longo procedure ( group 1 ) or Milligan-Morgan hemorrhoidectomy ( group 2 ) under epidural anesthesia . The operating time , postoperative pain scores at 3 , 6 , 12 , and 24 h , analgesic consumption , hospital stay , and complication rate were recorded . At follow-up the outcome and patient satisfaction were evaluated . Results : The mean operating time in group 1 was shorter than in group 2 , postoperative pain scores at all time points and the mean epidural morphine requirement was lower , and mean hospital stay was shorter . The complication rate did not differ ( three cases of postoperative bleeding in group 1 and two cases in group . At follow-up no recurrence or complains were recorded except three cases of mild incontinence ( one in group 1 and two in group 2 ) . The patients in group 1 ( 95 % ) were more satisfied than in group 2 ( 89 % ) . Conclusion : The Longo procedure is thus a simple , safe , and effective method that entails less postoperative pain , more satisfaction , and shorter hospital stay than the st and ard Milligan-Morgan hemorrhoidectomy Abstract PURPOSE : Hemorrhoidectomy is the most effective long-term treatment for hemorrhoids . Although it is possible to perform hemorrhoidectomy as a day case with a high degree of patient satisfaction , patients take an average of 14 days off work after surgery . Stapled hemorrhoidectomy is believed to be less painful than conventional hemorrhoidectomy and should allow an earlier return to work . The aim of this study was to compare both the immediate and the long-term results of stapled hemorrhoidectomy with diathermy hemorrhoidectomy in patients with prolapsing internal hemorrhoids in an intended day-care setting . METHODS : Thirty-one patients were r and omly assigned to undergo diathermy hemorrhoidectomy ( n = 16 ) or stapled hemorrhoidectomy performed with a purpose - design ed endoluminal stapling device , PPH01 T ™ ( n = 15 ) . All operations were planned as day or short-stay cases . All patients received lactulose , commenced preoperatively , together with postoperative topical glyceryl trinitrate and oral metronidazole . Patients were assessed by structured interview to assess their symptoms before and after surgery , with an intended follow-up of six months . All patients completed a 10-cm visual analog pain scale daily for the first ten days after surgery . RESULTS : The total pain score ( sum of all pain scores ) was significantly higher in the diathermy group ( 50 ( range , 9.8–79.9 ) vs. 19.6 ( range , 1.3–89.5 ) , P = 0.03 ) . Patients took a median of 14 ( range , 3–21 ) days off work after diathermy hemorrhoidectomy compared with 10 ( range , 3–38 ) days for the patients undergoing stapled hemorrhoidectomy ( P = 0.15 ) . At long-term follow-up , three patients ( all in the stapled group ) developed new symptoms of fecal urgency and anal pain , and three patients required further surgery to remove symptomatic external hemorrhoids after stapled hemorrhoidectomy . CONCLUSIONS : Although stapled hemorrhoidectomy is less painful in the short term , this does not lead to a significantly earlier return to work , and some patients develop new symptoms at long-term follow-up Abstract PURPOSE : This trial compares stapled anopexy with open hemorrhoidectomy in patients with prolapsing ( Grade 3 ) hemorrhoids . Particular attention was paid to changes in anorectal physiology , nature of tissue resected , quality -of-life assessment s , and cost implication s of the treatments studied . METHODS : An initial pilot study was followed by a r and omized , controlled trial in a District General Hospital in the United Kingdom . All patients had Grade 3 hemorrhoids . Nineteen patients were studied in the pilot study , with 99 patients in the r and omized , controlled trial . All patients in the pilot study and 59 in the r and omized , controlled trial underwent stapled anopexy . Thirty patients in the r and omized , controlled trial underwent open hemorrhoidectomy . Of the 59 patients in the stapled group , 32 were treated with the Ethicon PPH ™ stapling device , and 27 received stapling with a reusable Autosuture ™ stapling device . The following variables were measured : demographic details , quality of life ( Medical Outcomes Study Short Form 36 and directed questions ) , anorectal manometry , and histology . RESULTS : There was no difference in the case mix within or between the groups . The stapled anopexy groups showed a significant reduction in operative time ( P < 0.001 ) and blood loss ( P < 0.001 ) compared with open hemorrhoidectomy . Open hemorrhoidectomy result ed in significantly greater usage of protective pads postoperatively ( P < 0.001 ) and longer rehabilitation ( P < 0.006 ) . CONCLUSIONS : Stapled anopexy is an effective alternative treatment for prolapsing hemorrhoids that allows reduced operative time and shorter rehabilitation . It does not appear to affect continence or overall quality of life Background and aims The notable success of stapled prolapsectomy in recent years led us to compare this technique with Milligan-Morgan hemorrhoidectomy in terms of the results obtained both in the immediate postoperative period and in the long term . Patients and methods We performed conventional hemorrhoidectomy on 50 r and omly selected patients and operated on a further 50 using the stapler technique . The patients were monitored over the immediate postoperative period ( e.g. , type of anesthesia , mean duration of operation , mean hospitalization time , analgesic administration , time before returning to work ) and over a long-term follow-up period of 48 months ( later complications such as prolapse relapse , bleeding , stenosis , incontinence ) . Results The stapled group experienced significantly less pain ( mean number of analgesic tablets 2.60 vs. 15.9 ) and returned to normal activity sooner ( 8.04 vs. 16.9 days ) , as reported by other authors . In the long-term follow-up at 48 months , stapled hemorrhoidectomy was found to control prolapse , discharge , and bleeding , with no stenosis or significant incontinence , in 94 % of cases . Conclusion Our conclusions confirm the excellent advantages of stapled hemorrhoidectomy which allows the rapid recovery of patients and also promises the complete resolution of hemorrhoidal prolapse in the long term Objective This article presents the results of a three and a half year follow up of patients recruited to a r and omised controlled clinical trial comparing circumferential mucosectomy ( stapled haemorrhoidectomy ) vs conventional haemorrhoidectomy BACKGROUND The new technique of circular stapler for the treatment of hemorrhoids has shown early promise in terms of minimal or no postoperative pain , early discharge from hospital , and quick return to work . This study was design ed to compare stapled technique with the well-accepted conventional Milligan Morgan hemorrhoidectomy . METHODS After fulfilling the selection criteria , 84 patients were r and omly allocated to the stapled ( n = 42 ) or open group ( n = 42 ) . All patients were operated on under spinal anesthesia . The 2 techniques were evaluated with respect to the operative time , pain scores , complications , day of discharge , return to work , and level of satisfaction . RESULTS The mean age of patients was 46.02 years ( SD , 12.33 ) in the stapled group and 48.64 years ( 14.57 ) in the open group . Grade III or IV hemorrhoids were more common in men ( ie , 80.9 % and 85.7 % in the stapled and open group , respectively ) . The mean operative time was shorter in the stapled group 24.28 minutes ( 4.25 ) versus 45.21 minutes ( 5.36 ) in the Milligan-Morgan group ( P < .001 ) . The blood loss , pain scores and requirement of analgesics was significantly less in the stapled group . Mean hospital stay was 1.24 days ( 0.62 ) and 2.76 days ( 1.01 ) ( P < .001 ) in the stapled and open group , respectively . The patients in the stapled group returned to work or routine activities earlier ( ie , within 8.12 days [ 2.48 ] ) as compared with 17.62 ( 5.59 ) in the open group . Only 88.1 % of patients were satisfied by the open method compared with 97.6 % after the stapled technique . The median follow-up period was 11 months with a maximum follow-up of 19 months ( range 2 - 19 months ) . CONCLUSIONS Stapled hemorrhoidectomy is a safe and effective day-care procedure for the treatment of grade III and grade IV hemorrhoids . It ensures lesser postoperative pain , early discharge , less time off work , complications similar to the open technique , and in the end a more satisfied patient with no perianal wound . However , more such r and omized trials are essential to deny any long-term complication Stapled mucosectomy has been developed as an alternative to conventional haemorrhoidectomy for the elective treatment of haemorrhoids , but has not been assessed in the emergency setting . The aim of this study was to compare this technique with a conventional procedure for acute thrombosed circumferential prolapsed haemorrhoids Forty patients admitted at the Saudi German Hospital were r and omly assigned to Milligan-Morgan haemorrhoidectomy ( n = 20 ) or the circular stapled procedure . Under general anesthesia patients underwent st and ardized haemorrhoidectomy or had a circumferential doughnut of rectal mucosa and submucosa above the dentate line excised and closed with a st and ard circular end to end stapling device . All patients received the same preoperative and postoperative analgesic and laxative regimens . Patients completed linear analogue pain charts each day and were interviewed at 1 , 3 , and 12 weeks postoperatively . Summary measures of average pain experience were calculated from 10 cm linear analogue pain scores and were used as the primary outcome measure . The stapled group was found to have shorter anesthesia time ( 9 - 25 minutes , median 18 ) versus ( 15 - 35 minutes , median 22 ) . Average pain in the stapled group was significantly lower than it was in the Milligan-Morgan group ( 0.2 - 7.6 , median 2.1 ) versus ( 3.1 - 8.5 , median 6.5 ) . Hospital stay and time to first bowel motion were not significantly different between both groups . Return to normal activity was significantly shorter in the stapled group ( 3 - 60 days , median 17 ) versus ( 14 - 90 days , median 34 ) . Early and late complications , patient assessed symptom control , and functional outcome appear to be similar after short term follow up BACKGROUND Surgical haemorrhoidectomy has a reputation for being a painful procedure for a fairly benign disorder . The circular transanal stapled technique for the treatment of haemorrhoids has the potential to offer a less painful rectal procedure in place of ablative perianal surgery . We compared the short-term outcome of the circular stapled procedure for haemorrhoids with current st and ard surgery in a r and omised controlled trial . METHODS 40 patients admitted for surgical treatment of prolapsing haemorrhoids were r and omly assigned to Milligan-Morgan haemorrhoidectomy ( n=20 ) or the circular stapled procedure . Under general anaesthesia patients underwent st and ardised diathermy excision haemorrhoidectomy or had a circumferential doughnut of rectal mucosa and submucosa above the dentate line excised and closed with a st and ard circular end-to-end stapling device . All patients received st and ardised preoperative and postoperative analgesic and laxative regimens . Patients completed linear analogue pain charts each day and were interviewed at 1 , 3 , and 6 - 10 weeks postoperatively . Summary measures of average pain experience were calculated from 10 cm linear analogue pain scores and were used as the primary outcome measure . FINDINGS The stapled group had shorter anaesthesia time ( median 18 [ range 9 - 25 ] vs 22 [ 15 - 35 ] mins ) . Average pain in the stapled group was significantly lower than it was in the Milligan-Morgan group ( 2.1 [ 0.2 - 7.6 ] vs 6.5 [ 3.1 - 8.5 ] , 95.1 % CI difference medians 1.9 - 4.7 , p<0.0001 . Mann-Whitney U test ) . Average pain relative to what the patient expected was also significantly less in the stapled group ( -2.8 [ -4.4 to 1.3 ] vs 0.7 [ -1.8 to 3.4 ] . Hospital stay and time to first bowel motion were not significantly different between groups . Return to normal activity was significantly shorter in the stapled group ( 17 [ 3 - 60 ] vs 34 [ 14 - 90 ] . Early and late complications , patient-assessed symptom control , and functional outcome appear similar after short-term follow-up . INTERPRETATION The circular stapled technique offers a significantly less painful alternative to Milligan-Morgan haemorrhoidectomy and is associated with an earlier return to normal activity . Early symptom control and functional outcome appear similar . However , long-term symptomatic and functional outcome need further study Abstract INTRODUCTION : We compared the safety and clinical outcome between stapled rectal mucosectomy and closed hemorrhoidectomy for the surgical treatment of noncomplicated hemorrhoidal disease . METHODS : Eighty-four patients with Grade III and IV hemorrhoidal disease were r and omly assigned to two groups : 1 ) stapled rectal mucosectomy group ( n = 42 ) and 2 ) closed hemorrhoidectomy group ( n = 42 ) . Postoperative pain , analgesic use , symptoms , disability , early and late complications , and patient satisfaction were evaluated , among others . Follow-up was six months . RESULTS : Eighty-four patients , averaging 45 ± 9 years of age , underwent surgery . Two were lost to follow-up . Length of surgery and disability , postoperative pain , and use of analgesics were significantly less for patients in the stapled rectal mucosectomy group . In the closed hemorrhoidectomy group early complications were more frequent but not statistically significant , and there were no statistically significant differences regarding the frequency of late complications . No serious complications were reported in either group . Closed hemorrhoidectomy proved to be superior for bleeding control ( 95.1 percent closed hemorrhoidectomy vs. 80.5 percent stapled rectal mucosectomy ; P = 0.04 ) . Patient satisfaction was similar in the two groups , but stapled rectal mucosectomy patients were more willing to undergo the same procedure ( P = 0.02 ) . CONCLUSION : Both stapled rectal mucosectomy and closed hemorrhoidectomy are safe procedures . Closed hemorrhoidectomy was superior for bleeding control in Grade III and IV hemorrhoidal disease , but more painful and disabling than stapled rectal mucosectomy The aim of this study was to compare the results of stapled haemorrhoidopexy ( commonly called stapled haemorrhoidectomy ) with those of conventional diathermy haemorrhoidectomy PURPOSE There is a growing body of evidence supporting the lesser degrees of pain with stapled hemorrhoidopexy , also called the procedure for prolapse and hemorrhoids . However , there have been few r and omized comparisons assessing both perioperative and long-term outcomes of the procedure for prolapse and hemorrhoids and Ferguson hemorrhoidectomy . Results are presented here from the first prospect i ve , r and omized , multicenter trial comparing these hemorrhoid procedures in the United States . METHODS Patients with prolapsing hemorrhoids ( Grade III ) were r and omized to undergo the procedure for prolapse and hemorrhoids or Ferguson hemorrhoidectomy by colorectal surgeons who had training in using the stapling technique . Primary end points were acute postoperative pain , and hemorrhoid symptom recurrence requiring additional treatment at one-year follow-up from surgery . RESULTS A total of 156 patients ( procedure for prolapse and hemorrhoids , 77 ; Ferguson , 79 ) completed r and omization and the surgical procedure , 18 ( procedure for prolapse and hemorrhoids , 12 ; Ferguson , 6 ) had significant protocol violations . One hundred seventeen patients ( procedure for prolapse and hemorrhoids , 59 ; Ferguson , 58 ) returned for one-year follow-up . Demographic parameters , hemorrhoid symptoms , preoperative pain scores , and bowel habits were similar between groups . There were a similar number of patients with adverse events in each group ( procedure for prolapse and hemorrhoids , 28 ( 36.4 percent ) vs. Ferguson , 38 ( 48.1 percent ) ; P = 0.138 ) . Reoperation for an adverse effect was required in six ( 7.6 percent ) Ferguson patients and in 0 patients having the procedure for prolapse and hemorrhoids ( P = 0.028 ) . Postoperative pain during the first 14 days , pain at first bowel movement , and need for postoperative analgesics were significantly less in the procedure for prolapse and hemorrhoids group . Control of hemorrhoid symptoms was similar between groups ; however , significantly fewer patients having the procedure for prolapse and hemorrhoids required additional anorectal procedures during one-year follow-up ( procedure for prolapse and hemorrhoids , 2 ( 2.6 percent ) , vs. Ferguson , 11 ( 13.9 percent ) ; P = 0.01 ) . Only four of the Ferguson patients ( 5 interventions ) required additional procedures more than 30 days after surgery . CONCLUSIONS These data demonstrate that stapled hemorrhoidopexy offers the benefits of less postoperative pain , less requirement for analgesics , and less pain at first bowel movement , while providing similar control of symptoms and need for additional hemorrhoid treatment at one-year follow-up from surgery OBJECTIVE To compare stapled haemorrhoidectomy with open diathermy haemorrhoidectomy in Chinese patients with respect to the postoperative pain , symptom control , and manometric alterations . DESIGN Prospect i ve r and omised controlled trial . SETTING A regional general surgical unit , Hong Kong . PATIENTS Twenty-four patients with second- or third-degree haemorrhoids or who have had failed medical treatment . INTERVENTION Open diathermy haemorrhoidectomy or stapled haemorrhoidectomy . MAIN OUTCOME MEASURES Structured question naire for symptoms , anorectal manometry , transrectal ultrasound , and postoperative pain . RESULTS Stapled haemorrhoidectomy compared with open diathermy haemorrhoidectomy result ed in similar postoperative pain and drug requirements . Postoperative control of prolapse symptoms was significantly better with open diathermy haemorrhoidectomy than with stapled . The control of other symptoms was similar with regard to bleeding , pain , pruritus , and incontinence scores . Anorectal manometry showed a decrease in the maximum resting pressure and maximum squeeze pressure in both groups , but the decrease was only significant in the stapled haemorrhoidectomy group . CONCLUSIONS Stapled haemorrhoidectomy is as effective as conventional haemorrhoidectomy for the treatment of haemorrhoids , but with the exception of skin tag prolapse . There is a need for long-term follow-up for the changes in manometric parameters after haemorrhoidectomy Abstract PURPOSE : The introduction of stapled hemorrhoidectomy may replace local techniques such as rubber b and ligation as a first-line treatment for Grade III and small Grade IV piles . We conducted a r and omized trial to determine the role of rubber b and ligation in the era of stapled hemorrhoidectomy . METHODS : Fifty-five patients with Grade III or small Grade IV hemorrhoids were r and omly allocated to either rubber b and ligation or stapled hemorrhoidectomy . Patient demographics and procedure-related details were recorded . Follow-up was at two weeks and two and six months to assess complications , symptom relief , incontinence scores , quality of life , and patient satisfaction . RESULTS : Twenty-five patients were r and omly assigned to rubber b and ligation and 30 to stapled hemorrhoidectomy . The groups were equally matched for age , gender , grade of piles , continence scores , and quality of life . Stapled hemorrhoidectomy was associated with increased pain and analgesia usage at both 2-week and 2-month follow-up ( P < 0.001 ) . Rubber b and ligation and stapled hemorrhoidectomy were equally effective in controlling symptomatic prolapse , but rubber b and ligation was associated with an increased incidence of recurrent bleeding ( P = 0.002 ) . There were 6 procedure-related complications in the stapled hemorrhoidectomy group compared with none in the rubber b and ligation group ( P = 0.027 ) . There was no difference between the two groups in terms of continence scores , patient satisfaction , or quality of life . CONCLUSION : Stapled hemorrhoidectomy is associated with more pain and minor morbidity than rubber b and ligation in the treatment of Grade III and small Grade IV piles . However , for those patients who do not want the risk of further intervention procedures , stapled hemorrhoidectomy offers the better chance of a symptomatic cure BACKGROUND Haemorrhoidectomy is commonly an inpatient procedure because it is frequently associated with postoperative pain . Day case haemorrhoidectomy is a similar operation to that used on in patients but with different strategies for managing postoperative pain . Circumferential mucosectomy ( stapled haemorrhoidectomy ) may be associated with less postoperative pain than conventional haemorrhoidectomy . We compared stapled haemorrhoidectomy with conventional haemorrhoidectomy in patients with third degree haemorrhoids . METHODS We r and omly assigned 22 patients to conventional haemorrhoidectomy by the diathermy dissection or to stapled haemorrhoidectomy with the use of an intraluminal stapling device . Patients were discharged when free of pain , took co-codamol as required , completed visual analogue charts each day , and were assessed at 1 and 6 weeks postoperatively for symptom control . FINDINGS All patients received the assigned treatment . Mean inpatient stay was lower in the group assigned to stapled as opposed to conventional haemorrhoidectomy ( 1.09 [ 0.3 ] vs 2.82 [ 0.09 ] nights , p<0.001 ) , experienced less pain overall ( p=0.003 ) , and returned to normal activities sooner ( 8.1 [ 1.53 ] vs 16.9 [ 2.33 ] days , p<0.005 ) . Stapled haemorrhoidectomy controlled symptoms of prolapse , discharge and bleeding in all patients . INTERPRETATION Stapled haemorrhoidectomy is an effective treatment for third degree haemorrhoids with significant advantages for patients compared with conventional haemorrhoidectomy Objectives To compare by prospect i ve r and omised trial the postoperative tissue reaction of stapled vs. conventional haemorrhoidectomy Background The aim of the study was to compare the results in 95 patients r and omly allocated to undergo either stapled or open hemorrhoidectomy using Ligasure . Methods Ninety-five patients with grade III and IV hemorrhoids were r and omly allocated to undergo either stapled ( 50 patients ) or open using Ligasure ( 45 patients ) . Stapled hemorrhoidectomy was performed with the use of a circular stapling device . Open hemorrhoidectomy was accomplished according to the Milligan-Morgan technique by using Ligasure . Postoperative pain was assessed by means of a visual analog scale ( VAS ) . Recovery evaluation included return to pain-free defecation and normal activities . A 6-month clinical follow-up and an 18 ( 12 - 24 ) month median telephone follow-up were obtained in all patients . Results Operation time for open hemorrhoidectomy using Ligasure was shorter [ median 13 ( range 9.2 - 16.1 ) min vs 15 ( range 8 - 17 ) minutes , p < 0.05 ] . Median range of VAS score in the stapled group were significantly lower [ VAS score after 8 h : 3 ( 2 - 6 ) vs 5 ( 3 - 8 ) , p < 0.01 ; VAS score after first defecation : 5 ( 3 - 8 ) vs 7 ( 3 - 9 ) , p < 0.001 . The stapled hemorrhoidectomy was associated with an increased incidence of intraoperative bleeding in 18 cases ( 36 % ) vs four cases ( 8.8 % ) of the Ligasure group . There were three cases ( 6 % ) from the stapled group with recurrence of the hemorrhoids and none from the open technique . Conclusions Hemorrhoidectomy with a circular stapler device is easy to perform , but one more line of clips must be added to the device to avoid intraoperative bleeding from the cut line . Hemorrhoidectomy performed using Ligasure is more painful postoperatively but is a more radical operation The aim of the study was to compare the early results in 52 patients r and omly allocated to undergo either stapled or open hemorrhoidectomy . Seventy-four patients with grade III and IV hemorrhoids were r and omly allocated to undergo either stapled ( 37 patients ) or open ( 37 patients ) hemorrhoidectomy . Stapled hemorrhoidectomy was performed with the use of a circular stapling device . Open hemorrhoidectomy was accomplished according to the Milligan-Morgan technique . Postoperative pain was assessed by means of a visual analogue scale ( V.A.S. ) . Recovery evaluation included return to pain-free defecation and normal activities . A 6-month clinical follow-up and a 17.5 ( 10 to 27)-month median telephone follow-up was obtained in all patients . Operation time for stapled hemorrhoidectomy was shorter ( median 25 [ range 15 to 49 ] minutes versus 30 [ range 20 to 44 ] minutes , p = 0.041 ) . Median ( range ) V.A.S. scores in the stapled group were significantly lower ( V.A.S. score after 4 hours : 4 [ 2 to 6 ] versus 5 [ 2 to 8 ] , p = 0.001 ; V.A.S. score after 24 hours : 3 [ 1 to 6 ] versus 5 [ 3 to 7 ] , p = 0.000 ; V.A.S. score after first defecation : 5 [ 3 to 8 ] versus 7 [ 3 to 9 ] , p = 0.000 ) . Resumption of pain-free defecation was significantly faster in the stapled group ( 10 [ 6 to 14 ] days vs 12 [ 9 to 19 ] days , p = 0.001 ) . At follow-up 4 weeks and 6 months postoperatively the median ( range ) symptom severity score was similar in both groups ( 1 [ 0 to 2 ] versus 0 [ 0 to 3 ] , p = 0.150 and 0 [ 0 to 2 ] versus 0 [ 0 to 2 ] , p = 0.731 ) . At long-term follow-up occasional pain was present in 6/37 ( 16.2 ) patients in the stapled group and 7/37 ( 18.9 % ) in the Milligan-Morgan group ( p = 1.000 ) ; episodes of bleeding were reported by 8/37 ( 21.6 % ) patients in the stapled group and 5/37 ( 13.5 % ) patients in the Milligan-Morgan group ( p = 0.542 ) . No problems related to continence and defecation were reported in either group . Patients were satisfied with the operation in 33/37 ( 89.2 % ) cases in the stapled group and 31/37 ( 83.8 % ) cases in the Milligan-Morgan group ( p = 0.735 ) . Hemorrhoidectomy with a circular staple device is easy to perform and achieves better results than the Milligan-Morgan technique in terms of postoperative pain and recovery . Comparable results are obtained at long-term follow-up Stapled haemorrhoidectomy does not involve dissection , with its attendant potential morbidity , required to perform closed haemorrhoidectomy . This study compared haemorrhoidectomy with ( sutured ) and without ( stapled ) preliminary dissection BACKGROUND This r and omized prospect i ve study compared the outcome of circular hemorrhoidectomy according to the Hospital Leopold Bellan ( HLB ) technique ( Paris ) with Longo stapled circumferential mucosectomy ( LSCM ) in two homogeneous groups of patients affected by circular fourth-degree hemorrhoids with external mucosal prolapse . METHODS From December 1996 to December 1999 , 80 consecutive patients with fourth-degree hemorrhoids and external mucosal prolapse were r and omly assigned to two groups . Forty patients ( group A : 18 men , 22 women , mean age 50.5 years , range 21 to 82 ) underwent HLB hemorrhoidectomy , and 40 patients ( group B : 15 men , 25 women , mean age 51.0 years , range 29 to 92 ) underwent LSCM . Before surgery , all patients were selected with a st and ard question naire for symptom evaluation , full proctological examination , flexible rectosigmoidoscopy , dynamic defecography , and anorectal manometry . No significant differences among the two groups were found . All patients were controlled with follow-up question naire and with clinical examination at 1 , 2 , 4 , 12 , and 54 weeks after the operation . A postoperative manometry was performed 3 months after surgery . RESULTS The length of the operation was significantly lower in group B ( 25 + /- 3.1 SD versus 50 + /- 5.3 minutes , P < 0.001 ) . Mean hospital stay was 3 + /- 0.4 days in group A and 2 + /- 0.5 days in group B ( P < 0.01 ) . Mean duration of inability to work was 8 + /- 0.9 days in group B and 15 + /- 1.4 days in group A ( P < 0.001 ) . Postoperative pain was significantly lower in group B ( P < 0.001 ) . Mean length of follow-up was 20 + /- 8.0 months in group A and 20 + /- 7.8 months in group B. Late complications were similar in the two groups , with 0 % , at present , recurrence rate . CONCLUSIONS Our results confirm that both operations are safe , easy to perform , and effective in the treatment of advanced hemorrhoids with external mucosal prolapse . However , the LSCM seems to be preferable owing to the fewer postoperative complications , easier postoperative management , and shorter time to return to work . A longer follow-up is required to confirm the true efficacy of this surgical method Purpose : The purpose of this study was to compare the outcome of stapled hemorrhoidopexy ( SH group ) performed using a circular stapler with that of the Milligan-Morgan technique ( MM group ) . The goals of the study were to evaluate the efficacy and reproducibility of stapled hemorrhoidopexy and define its place among conventional techniques . Methods : A series of 134 patients were included at 7 hospital centers . They were r and omized according to a single-masked design and stratified by center ( with balancing every 4 patients ) . Patients were clinical ly evaluated preoperatively and at 6 weeks , 1 year , and a minimum of 2 years after treatment . Patients completed a question naire before and 1 year after surgery to evaluate symptoms , function , and overall satisfaction . Results : The mean follow-up period was 2.21 years ± 0.26 ( 1.89–3.07 ) . Nine patients ( 7 % ) could not be monitored at 1 or 2 years , but 4 of these 9 nevertheless filled in the 1-year question naire . The patients in the SH group experienced less postoperative pain/discomfort as scored by pain during bowel movement ( P < 0.001 ) , total analgesic requirement over the first 3 days ( according to the World Health Organization [ WHO ] class II analgesics [ P = 0.002 ] ; class III [ P = 0.066 ] ) , and per-patient consumption frequency of class III analgesics ( P = 0.089 ) . A clear difference in morphine requirement became evident after 24 hours ( P = 0.010 ) . Hospital stay was significantly shorter in the SH group ( SH 2.2 ± 1.2 [ 0 ; 5.0 ] versus MM 3.1 ± 1.7 [ 1 ; 8.0 ] P < 0.001 ) . At 1 year , no differences in the resolution of symptoms were observed between the 2 groups , and over 2 years , the overall incidence of complications was the same , specifically fecaloma ( P = 0.003 ) in the MM group and external hemorrhoidal thrombosis ( P = 0.006 ) in the SH group . Impaired sphincter function was observed at 1 year with no significant difference between the groups for urgency ( 12 % ) , continence problems ( 10 % ) , or tenesmus ( 3 % ) . No patient needed a second procedure for recurrence within 2 years , although partial residual prolapse was detected in 4 SH patients ( 7.5 % ) versus 1 MM patient ( 1.8 % ) ( P = 0.194 ) . Conclusion : Stapled hemorrhoidopexy causes significantly less postoperative pain . The technique is reproducible and can achieve comparable outcomes as those of the MM technique as long as the well-described steps of the technique are followed . Like with conventional surgery , anorectal dysfunction can occur after stapled hemorrhoidopexy in some patients . Its effectiveness in relieving symptoms is equivalent to conventional surgery , and the number of hemorrhoidal prolapse recurrences at 2 years is not significantly different . Hemorroidopexy is applicable for treating reducible hemorrhoidal prolapse The introduction of a stapling technique for the treatment of haemorrhoids has the potential for less postoperative pain , a short operating time and an early return to full activity . The outcome of stapled haemorrhoidectomy was compared with that of current st and ard surgery in a r and omized controlled study |
12,783 | 23,499,340 | This systematic review and meta- analysis demonstrate that neurological testing procedures have limited overall diagnostic accuracy in detecting disc herniation with suspected radiculopathy .
Pooled diagnostic accuracy values of the tests were poor , whereby all tests demonstrated low sensitivity , moderate specificity , and limited diagnostic accuracy independent of the disc herniation reference st and ard or the specific level of herniation . | BACKGROUND CONTEXT Disc herniation is a common low back pain ( LBP ) disorder , and several clinical test procedures are routinely employed in its diagnosis .
The neurological examination that assesses sensory neuron and motor responses has historically played a role in the differential diagnosis of disc herniation , particularly when radiculopathy is suspected ; however , the diagnostic ability of this examination has not been explicitly investigated .
PURPOSE To review the scientific literature to evaluate the diagnostic accuracy of the neurological examination to detect lumbar disc herniation with suspected radiculopathy . | Study Design . Cross sectional Objective . To investigate the ability of the neurological examination to identify the specific level of a disc herniation in patients with sciatica and confirmed disc herniation . Summary of Background Data . Tests included in a neurological examination theoretically provide accurate diagnostic information about the level of the herniated disc . However , there is currently very little evidence about the diagnostic accuracy of individual tests or combinations of tests . Methods . The study included 283 patients with sciatica and confirmed disc herniation from a previous r and omized controlled trial . The reference test for the current study was the MRI scan , reported for level of disc herniation . Index tests investigated were a neurologist 's overall impression of the level of disc herniation , individual neurological tests ( e.g. , sensation testing ) and multiple test findings ( i.e. , the number of positive tests ) . The index tests were performed blinded to the MRI results . The diagnostic accuracy of the index tests in predicting herniations at the lower three lumbar discs was investigated using area under the curve ( AUC ) , sensitivity and specificity . Results . None of the individual neurological tests from the clinical examination were highly accurate for identifying the level of disc herniation ( AUC < 0.75 ) . The outcome of multiple test findings was slightly more accurate but did not produce high sensitivity and specificity . The dermatomal pain location was generally the most informative individual neurological test . The overall suspected level of disc herniation rated by the neurologist after a full examination of the patient was more accurate than individual tests . At L4/5 and L5/S1 herniations the AUC for neurologist ratings was 0.79 and 0.80 respectively . Conclusion . The current study did not find evidence to support the accuracy of individual tests from the neurological examination in identifying the level of disc herniation demonstrated on MRI . A neurologist 's overall impression was moderately accurate in identifying the level of disc herniation Summary The diagnostic power or clinical parameters in the diagnosis of lumbar disc herniation in patients with monoradicular pain was evaluated in a prospect i ve study with a 100 % verification of the diagnosis . Eighty patients with monoradicular pain corresponding to the fifth lumbar or the first sacral nerve root were included . Pre-operatively a number of clinical parameters were recorded and compared to the intra-operative finding of a disc herniation . The parameters were analysed by receiver operating characteristic ( ROC ) curves . Results from the available literature were analysed by ROC curves for comparison . In 76 % of the cases a disc herniation was discovered . The level of the disc herniation was correctly predicted in 93 % of these cases by the location of the pain alone or supplemented by neurological signs . Apart from radicularly distributed pain , all parameters in the present study and in the literature had no or low diagnostic accuracy . Thus , in patients with monoradicular sciatica further clinical parameters do not add to the diagnosis of lumbar disc herniation OBJECTIVE To establish the level of cardiorespiratory fitness and the rate of decrease in maximal aerobic capacity according to age in patients with chronic low back pain and compare these with normative data . DESIGN Prospect i ve case series with historical controls . SUBJECTS/ PATIENTS Seventy patients with chronic low back pain . METHODS A maximal cycle ergometer protocol was used to measure VO2max , heart rate , respiratory exchange ratio and blood lactate levels . RESULTS Seventy patients achieved absolute and normalized for weight VO2max values of 2.17 ( st and ard deviation ( SD ) 0.65 ) l/min and 30.79 ( SD 7.77 ) ml/kg/min , respectively . Absolute VO2max was poorly related to age in both men and women with chronic low back pain ( r = -0.22 and r = -0.28 , respectively ) . VO2max normalized for weight was also inversely related to age in both men and women ( r = -0.36 and r = -0.42 , respectively ) . The rate of VO2max decline between 20 and 59 years was -3.3 ml/kg/min/decade for the entire population and -1.2 and -5.4 ml/kg/min/decade in men and women , respectively . CONCLUSION The level of physical fitness of patients with chronic low back pain is comparable to the physical fitness of healthy , but poorly conditioned subjects . Patients with chronic low back pain show a VO2max decline with ageing that is slower than of active subjects This prospect i ve and consecutive study was design ed to evaluate the validity of different clinical tests , e.g. lumbar extension in lying and slump test for patients with suspected herniated nucleus pulposus , in comparison with findings on computed tomography ( CT ) and /or magnetic resonance imaging ( MRI ) scan . There were 105 patients who were seen and examined by the senior author ( for the sake of the study ) at the Orthopaedic Physiotherapy Department , on an average of 5.5 days ( range 0 - 21 days ) before CT and /or MRI examination were carried out . There were 36 women and 69 men with an average age of 42.7 + /- 9.8 ( range 19 - 64 ) years . According to the radiological findings on CT and /or MRI , the patients were divided into three groups : 52 patients with disc hernia , 41 patients with bulging discs and 12 patients without positive findings . The mean values with st and ard deviations of 25 variables of three diagnostic groups were studied . Multiple comparison adjustment according to Bonferroni showed significant differences for three variables that were of diagnostic value ( lumbar range of motion for forward flexion , left side-bending in st and ing , and pain distribution during extension in st and ing ) . The agreement between clinical and radiological findings for type and level of diagnosis of disc herniation was accurate in 72 patients ( 69 % ) . The diagnostic sensitivity for disc herniation was 82.6 % and the specificity 54.7 % Summary In a prospect i ve , consecutive study of patients with lumbar back pain and sciatica , various clinical features and surgical findings were evaluated in order to analyse the predictive value regarding ( 1 ) level of diseased interspace ( 2 ) presence and type of lesion responsible for root compression ( 3 ) outcome after surgery . One hundred patients underwent surgery solely on clinical grounds . Fifty-eight had disc herniation . The level of disc herniation was correctly predicted in three quarters of patients with aprolapsed disc . The outcome after surgery was good in 77 patients .Only few clinical features , namely male sex and scoliosis were predictors of a good outcome . Lasegue 's sign was indicative of root compression in 90 % , but only two-thirds had disc herniation . Conversely one-third had disc herniation in spite of a “ negative ” test . Lasegue 's sign was not superior to other clinical tests in predicting outcome .The most important indicator of a good outcome was the presence of disc herniation at surgery . Patients with disc pathology other than true disc herniation fared equally with patients , who had normal discs disclosed at surgery . Myelography was undertaken in all patients prior to surgery , the results of which are analysed in the following paper . ( Espersenet al. : Predictive value of radiculography in patients with lumbago-sciatica . A prospect i ve Currently , there are over 300,000 lumbar discectomies performed in the US annually without an objective st and ard for patient selection . A prospect i ve clinical outcome study of 200 cases with 5-year follow-up was used to develop and vali date an MRI-based classification scheme to eliminate as much ambiguity as possible . 100 consecutive lumbar microdiscectomies were performed between 1992 and 1995 based on the criteria for “ substantial ” herniation on MRI . This series was used to develop the MSU Classification as an objective measure of lumbar disc herniation on MRI to define “ substantial ” . It simply classifies herniation size as 1 - 2 - 3 and location as A-B-C , with inter-examiner reliability of 98 % . A second prospect i ve series of 100 discectomies was performed between 2000 and 2002 , based on the new criteria , to vali date this classification scheme . All patients with size-1 lesions were electively excluded from surgical consideration in our study . The Oswestry Disability Index from both series was better than most published outcome norms for lumbar microdiscectomy . The two series reported 96 and 90 % good to excellent outcomes , respectively , at 1 year , and 84 and 80 % at 5 years . The most frequent types of herniation selected for surgery in each series were types 2-B and 2-AB , suggesting the combined importance of both size and location . The MSU Classification is a simple and reliable method to objective ly measure herniated lumbar disc . When used in correlation with appropriate clinical findings , the MSU Classification can provide objective criteria for surgery that may lead to a higher percentage of good to excellent outcomes Study Design . A cross-sectional study of interobserver variability in primary care patients . Objective . To investigate the consistency of signs and symptoms of nerve root compression in primary care patients with pain irradiating pain into the leg ( sciatica ) . Summary of Background Data . The literature does not report on all the clinical tests for nerve root compression . In previous studies , most patients had low back pain with no irradiation . Often , little information on examination technique , proportion of positive test results , or clinical patient characteristics was provided . Methods . A r and om selection of 91 patients was investigated by a neurologist-resident couple . Agreement percentages , proportions of positive test results , and kappas were calculated . Results . The kappa of the overall conclusion after the history taking was 0.40 , increasing to 0.66 after physical examination . Kappas were good for decreased muscle strength and sensory loss ( 0.57–0.82 ) , intermediate for reflex changes ( 0.42–0.53 ) , and poor for the examination of the lumbar spine ( 0.16–0.33 ) . The straight leg raising , crossed straight leg raising , Bragard ’s sign , and Naffziger ’s sign were the most consistent nerve root tension signs ( > 0.66 ) . Conclusions . Two clinicians disagreed on the presence of nerve root involvement in one of four patients after history taking , and in one of five patients after physical examination . For a more consistent overall diagnosis , the physician probably should put more emphasis on the history of pain on coughing – straining – sneezing , a feeling of coldness in the legs , and urinary incontinence . The investigation of paresis , sensory loss , reflex changes , straight leg raising , and Bragard ’s sign provide the most consistent results OBJECTIVE To determine the extent to which the history and physical examination predict the outcome of the electrodiagnostic ( EDX ) evaluation in patients with suspected lumbosacral radiculopathy . DESIGN Data for 170 subjects referred for low-back and lower limb symptoms were prospect ively collected at five EDX laboratories . The sensitivity , specificity , positive and negative predictive values , and odds ratios were determined for symptoms and neurologic signs . RESULTS Symptoms were not significantly associated with an EDX study or a lumbosacral radiculopathy . The physical examination was better at predicting that an EDX study would be abnormal in general than it was at predicting a lumbosacral radiculopathy in particular . Of those subjects with normal physical examinations , 15%-18 % still had abnormal EDX findings . CONCLUSIONS In a population of patients referred for an EDX study , the history and physical examination alone can not reliably predict electrodiagnostic outcome & NA ; Chronic low back pain ( CLBP ) is a major clinical problem with a substantial socio‐economical impact . Today , diagnosis and therapy are insufficient , and knowledge concerning interaction between musculoskeletal pain and motor performance is lacking . Most studies in this field have been performed under static conditions which may not represent CLBP patients ' daily‐life routines . A st and ardized way to study the sensory‐motor interaction under controlled motor performance is to induce experimental muscle pain by i.m . injection of hypertonic saline . The aim of the present controlled study was to analyze and compare electromyographic ( EMG ) activity of and coordination between lumbar muscles ( 8 paraspinal recordings ) during gait in 10 patients with CLBP and in 10 volunteers exposed to experimental back muscle pain induced by bolus injection of 5 % hypertonic saline . When the results are compared to sex‐ and age‐matched controls , the CLBP patients showed significantly increased EMG activity in the swing phase ; a phase where the lumbar muscles are normally silent . These changes correlated significantly to the intensity of the back pain . Similar EMG patterns were found in the experimental study together with a reduced peak EMG activity in the period during double stance where the back muscles are normally active . Generally , these changes were localized ipsilaterally to the site of pain induction . The clinical and experimental findings indicate that musculoskeletal pain modulates motor performance during gait probably via reflex pathways . Initially , these EMG changes may be interpreted as a functional adaptation to muscle pain , but the consequences of chronic altered muscle performance are not known . New possibilities to monitor and investigate altered motor performance may help to develop more rational therapies for CLBP patients In a prospect i ve study of 163 consecutive patients operated on because they were thought to have lumbar disc hernia , the authors investigated whether physical signs could predict the degree of hernia ( complete hernia , incomplete hernia , protruded disc , and normal disc ) found at surgery . Stepwise discriminant analysis showed that there were only 2 physical signs of diagnostic value : lumbar range of motion and crossed Lasegue sign . By these signs , 74 % of the uncontained hernias and 68 % of the contained hernias could be correctly classified . Discrimination also was made between intact annuli ( negative exploration and protruded disc ) versus ruptured annuli ( incomplete hernias and complete hernias ) . Again , lumbar range of motion and crossed Lasegue sign were the only significant parameters , predicting 71 % of the ruptured annuli and 80 % of the intact annuli . These 2 physical signs are important because the degree of the hernia is the most important prognostic factor for the outcome of lumbar disc surgery . The degree of the hernia also has an impact on the choice of invasive therapy : open surgery , percutaneous surgery , or enzymatic nucleolysis . Neurologic signs often were absent , showed low correlation to the degree of the hernia , and had a limited value for predicting the level of the hernia . However , they are important for the differential diagnosis in distinguishing between radicular and referred pain Study Design . Cross-sectional study with prospect i ve recruitment . Objective . To determine the accuracy of the physical examination for the diagnosis of midlumbar nerve root impingement ( L2 , L3 , or L4 ) , low lumbar nerve root impingement ( L5 or S1 ) and level-specific lumbar nerve root impingement on magnetic resonance imaging , using individual tests and combinations of tests . Summary of Background Data . The sensitivity and specificity of the physical examination for the localization of nerve root impingement has not been previously studied . Methods . Sensitivities , specificities , and likelihood ratios ( LRs ) were calculated for the ability of individual tests and test combinations to predict the presence or absence of nerve root impingement at midlumbar , low lumbar , and specific nerve root levels . Results . LRs ≥5.0 indicate moderate to large changes from pre-test probability of nerve root impingement to post-test probability . For the diagnosis of midlumbar impingement , the femoral stretch test ( FST ) , crossed FST , medial ankle pinprick sensation , and patellar reflex testing demonstrated LRs ≥5.0 ( LR ∞ ) . LRs ≥5.0 were observed with the combinations of FST and either patellar reflex testing ( LR 7.0 ; 95 % confidence interval [ CI ] 2.3–21 ) or the sit-to-st and test ( LR ∞ ) . For the diagnosis of low lumbar impingement , the Achilles reflex test demonstrated an LR ≥5.0 ( LR 7.1 ; 95 % CI 0.96–53 ) ; test combinations did not increase LRs . For the diagnosis of level-specific impingement , LRs ≥5.0 were observed for anterior thigh sensation at L2 ( LR 13 ; 95 % CI 1.8–87 ) ; FST at L3 ( LR 5.7 ; 95 % CI 2.3–4.4 ) ; patellar reflex testing ( LR 7.7 ; 95 % CI 1.7–35 ) , medial ankle sensation ( LR ∞ ) , or crossed FST ( LR 13 ; 95 % CI 1.8–87 ) at L4 ; and hip abductor strength at L5 ( LR 11 ; 95 % CI 1.3–84 ) . Test combinations increased LRs for level-specific root impingement at the L4 level only . Conclusion . Individual physical examination tests may provide clinical information that substantially alters the likelihood that midlumbar impingement , low lumbar impingement , or level-specific impingement is present . Test combinations improve diagnostic accuracy for midlum-bar impingement |
12,784 | 25,228,742 | Meta-regression demonstrated some modulation influence by female gender , age and diabetes on the flow capacity of grafts .
In summary , in terms of flow capacity , a skeletonized ITA appears to be superior in comparison with a pedicled ITA during CABG | Many surgeons are concerned about the flow capacity of a skeletonized internal thoracic artery ( ITA ) in comparison with a pedicled ITA used during coronary artery bypass graft ( CABG ) .
This work aims to summarize the evidence comparing the flow capacity of a skeletonized versus pedicled ITA during CABG . | Background — Observational studies suggest that skeletonization of the internal thoracic artery ( ITA ) can improve conduit flow and length and reduce deep sternal infections and postoperative pain . We performed a r and omized , double-blind , within-patient comparison of skeletonized and nonskeletonized ITAs in patients undergoing coronary surgery . Methods and Results — Patients ( n=48 ) undergoing bilateral ITA harvest were r and omized to receive 1 skeletonized and 1 nonskeletonized ITA . Intraoperatively , ITA flow was assessed directly and with a Doppler flow probe before and after topical application of papaverine . ITA harvest time and conduit length were recorded . A blinded assessment of pain ( visual analog scale ) and dysesthesia ( physical examination ) was performed at discharge , at 2 weeks , and at a 3-month follow-up . Sternal perfusion was assessed with nuclear imaging ( n=7 ) . Skeletonization required longer ITA harvest times ( 27±1 versus 24±1 minutes ; P=0.04 ) . There was a trend toward increased ITA length in the skeletonized group ( 18.2±0.3 versus 17.7±0.3 cm ; P=0.09 ) . In situ ITA flow was lower in skeletonized arteries ( 7.4±0.9 versus 10.1±1.0 mL/min ; P=0.01 ) and increased significantly after ITA division and papaverine application . Postanastomotic flows were similar between groups . Skeletonization was associated with decreased pain at the 3-month follow-up and a reduction in major sensory deficits at the 4-week and 3-month ( 17 % versus 50 % ; P=0.002 ) follow-ups . Baseline adjusted sternal perfusion was significantly greater by 17±6 % ( P=0.03 ) on the skeletonized side . Conclusions — Skeletonization results in reduced postoperative pain and dysesthesia and increased sternal perfusion at follow-up but does not produce increased conduit flow . ITA skeletonization may be a strategy for reducing morbidity after CABG BACKGROUND This study was conceived to evaluate the effect of internal thoracic artery ( ITA ) skeletonization on vessel wall integrity . METHODS Forty consecutive patients undergoing coronary artery bypass were r and omized to receive a skeletonized ( n = 22 ) or a pedicled ( n = 18 ) ITA graft . ITA harvesting was performed by 2 experienced surgeons using the same instrumentation and technique . Specimens were examined by light and electron microscope in order to assess vascular wall integrity . A specific immunohistochemical staining and a computerized method were used to quantify the degree of endothelial integrity after surgical preparation . RESULTS Morphologic analysis revealed 2 cases of limited subadventitial hemorrhage ( one for each group ) and no case of major arterial damage . Immunohistochemical staining demonstrated an extremely high degree of maintenance of the endothelial integrity in both groups ( 97.2 % + /- 1.9 % in the skeletonized and 96.8 % + /- 2.1 % in the pedicled one ; p = 0.53 ) . CONCLUSIONS Skeletonization does not affect ITA wall integrity in humans su bmi tted to coronary artery bypass procedures BACKGROUND The skeletonization of internal thoracic artery is postulated to improve graft length , early blood flow , sternal blood supply , and postoperative respiratory function . Concern exists that skeletonization may injure internal thoracic artery , precluding good results of surgery . Reports on endothelial function of skeletonized internal thoracic artery are lacking . METHODS A prospect i ve assessment of early clinical outcomes of 357 consecutive patients undergoing coronary artery bypass grafting was performed : 287 patients with nonskeletonized and 70 with skeletonized left internal thoracic artery ( LITA ) . The lengths of LITA and of its discarded distal segment , as well as free LITA blood flow , were measured . The dose-effect relationship for relaxation to acetylcholine was studied in the organ bath . RESULTS Apart from a higher incidence of breaching the pleura with nonskeletonized LITA the clinical outcomes were comparable . The length of skeletonized LITA was 17.8+/-1.14 cm versus 20.3+/-0.52 cm skeletonized ( p = 0.11 ) . The length of discarded LITA was shorter in nonskeletonized artery ( 0.8+/-0.28 cm versus 2.6+/-0.49 cm ; p = 0.022 ) . The free LITA blood flow was 66.3+/-7.42 mL/min in nonskeletonized vessel versus 100.3+/-14.84 mL/min in skeletonized ( p = 0.048 ) . The acetylcholine-induced relaxation was similar in both groups ( maximal relaxation , 80.7%+/-5.95 % in nonskeletonized versus 72.9%+/-9.11 % in skeletonized ; not significant ; negative logarithm of half-maximal effect , 7.43+/-0.18 versus 7.1+/-0.10 , respectively ; p = 0.063 ) . CONCLUSIONS Skeletonization does not damage the endothelial function of the LITA . Higher free blood flow and available LITA length should encourage the use of skeletonized LITA in clinical practice BACKGROUND Skeletonization of the internal thoracic artery ( ITA ) has advantages , but the variation of ITA preparation may be traumatic for the arterial wall . We sought to compare intraoperative results and endothelial nitric oxide synthase ( e-NOS ) expression on the vessel wall after left ITA harvesting with skeletonization and the conventional technique . METHODS A prospect i ve evaluation of 84 consecutive patients undergoing coronary artery bypass grafting was performed : 40 patients with skeletonized and 44 patients with pedicled left ITA . The lengths of ITA and free ITA blood flow were measured . Distal ITA segments were analyzed histopathologically and stained by antibodies against e-NOS . RESULTS In the skeletonized group , the length of the ITA were significantly longer than in the pedicled group ( 15.7 + /- 0.4 cm versus 19.0 + /- 0.6 cm ; P = .001 ) . Also , the free-flow capacity of the ITA was significantly higher than in the pedicled group ( 62.4 + /- 4.8 mL/min versus 88.6 + /- 6.9 mL/min ; P = .001 ) . e-NOS expressions on endothelial cells were similar between the groups . Dense e-NOS immunostaining was observed in vaso vasorum of the adventitia in the pedicled group . However , there was not any e-NOS immunostaining in vaso vasorum of the adventitia in the skeletonized group . CONCLUSIONS Although skeletonization of the ITA is a more technically dem and ing procedure , it provides some advantages such as increased available graft length and reduced sternal devascularization . This technique did not have any detrimental effects on the endothelial cell lining and e-NOS expressions on the endothelial layer . To reach a definitive judgment for using skeletonized ITA , we need information about the long-term angiographic patency rates OBJECTIVE To compare the free blood flow , caliber , and length of the left internal thoracic artery ( LITA ) , dissected in the pedicled ( P ) and skeletonized ( S ) manners , during surgery before and after topical vasodilator ( TV ) application . METHODS A r and omized , blind , clinical trial was carried out with 50 patients undergoing elective myocardial revascularization to assess the use of the LITA in situ in its pedicled or skeletonized form . The 25 patients in the pedicled group ( GP ) had NYHA class II or III angina , ejection fraction ( EF ) of 50.8+/-9.2 % , and 16 were of the male sex . The patients in the skeletonized group ( SG ) had NYHA class II angina , EF of 46.8+/-9.3 % , and 19 were of the male sex . The measurements were performed before extracorporeal circulation and divided into 2 phases : phase 1 ( before topical papaverine application ) and phase 2 ( 15 min after topical application of papaverine , 2.5 mg/mL , at 37 degrees C ) . During the measurements , mean blood pressure , central venous pressure , and heart rate were monitored . RESULTS The phase 1 and 2 results are as follows : 1 ) PG : blood flow , 46+/-16 and 77+/-28 mL/min ; caliber , 1.4+/-0.1 and 1.7+/-0.1 mm , respectively ; 2 ) SG : blood flow , 57+/-27 and 97+/-35 mL/min ; and caliber , 1.4+/-0.1 and 1.8+/-0.2 mm , respectively . No significant differences were observed in length . CONCLUSION The LITA in SG had a significant increase in blood flow and caliber after the use of TV compared with blood flow and caliber in PG ( P=0.03 and P=0.01 , respectively ) BACKGROUND We examined the hypothesis that complete skeletonization of an internal thoracic artery ( ITA ) results in increased diameter of the graft for anastomosis and therefore improves graft flow in coronary artery bypass grafting . METHODS We studied 65 consecutive patients who underwent coronary artery bypass grafting , in which the left ITA was anastomosed to the left anterior descending artery . The first 20 consecutive ITA were harvested as a pedicle ( group P ) and later 45 consecutive ITAs were harvested as an ultrasonically skeletonized graft ( group S ) . Intraoperative ITA graft mean flows were obtained with a transit-time flowmeter . Three diameters of the ITA graft were measured quantitatively in postoperative angiograms performed 14 + /- 5 days after the coronary artery bypass grafting ; D1 , at the origin from the subclavian artery ; D2 , at the level of the second intercostal space ; and D3 , just proximal to the anastomosis . RESULTS Intraoperative mean flow was significantly greater in group S than in group P ( S : 42.6 + /- 29.1 mL/min versus P : 26.4 + /- 16.1 mL/min , p = 0.03 ) . Although the diameters D1 and D2 were not significantly different between groups , D3 was significantly larger in group S than in group p ( S : 1.77 + /- 0.28 mm versus P : 1.57 + /- 0.17 mm , p = 0.02 ) . CONCLUSIONS Compared with pedicle harvesting , complete skeletonization of ITA may make it possible to anastomose an ITA with a larger diameter in coronary artery bypass grafting , which leads to increased graft flow by decreasing vascular resistance BACKGROUND The preferential harvesting technique of the internal mammary artery has been periodically debated . This r and omized study evaluated the flow outcome of the skeletonized versus pedicled left internal mammary artery . METHODS Two hundred patients undergoing surgery for left anterior descending coronary artery revascularization were enrolled and r and omized to pedicled ( n=100 ) or skeletonized ( n=100 ) harvesting . Intraoperative baseline flow and post adenosine infusion into the left ventricle , hospital outcome , echocardiographic results , and troponin I leakage were analyzed . Noninvasive periodic evaluation of flow was carried out at rest and during intravenous adenosine infusion by transthoracic Doppler ultrasound , and was stratified according to the harvesting technique . Final angiographic evaluation was performed by 64-slice multidetector computed tomography . RESULTS Skeletonized left internal mammary arteries demonstrated better flow capacity at rest and during adenosine recruitment perioperatively and at all time points of follow-up . Troponin I leakage was significantly higher in the pedicled group ( 59 vs 42 , p=0.02 ) . Pedicled harvesting ( hazard ratio [ HR ] 3.6 , 95 % confidence interval [ CI ] 2.5 to 6.9 , p<0.001 ) ; indexed left ventricular mass greater than 150 g/m2 ( HR 4.6 , 95 % CI 3.1 to 7.5 , p<0.001 ) ; and baseline corrected thrombolysis in myocardial infa rct ion frame count greater than 30 ( HR 4.4 , 95 % CI , 3.8 to 7.2 , p<0.001 ) were the most powerful multivariable predictors of graft flow reserve less than 2.0 . Postoperative echocardiographic results and clinical and angiographic outcomes were comparable between the two groups . CONCLUSIONS Skeletonization of the left internal mammary artery , beyond traditional proven advantages , provided significantly higher flow capacity and better graft flow reserve |
12,785 | 29,693,331 | The heath belief model is the most popular used framework for cervical cancer screening interventions .
The results of our study showed that different health education methods ( such as calls , mailed postcards , mother/daughter education .
consultation sessions , picture books , videos , PowerPoint slides , small group discussion s , educational brochures , radio broadcast education , lecture presentations , tailored counseling and a fact sheet , Self-learning package , face-to- face interviews and etc ) are effective in modifying cervical cancer screening behavior of women .
Conclusions : Our results showed that the different interventions and health behavior change frameworks provide an effective base for cervical cancer prevention . | Background : Cervical cancer is the second most common cancer in women worldwide ; early detection can play a key role in reducing the associated morbidity .
The objective of this study was to systematic ally assess the effects of educational interventions on cervical cancer screening ( CCS ) behavior of women . | BACKGROUND Few Iranian women take the Papanicolaou test despite its important role in preventing cervical cancer . This study aim ed to determine the effectiveness of an educational intervention based on the protection motivation theory ( PMT ) variables and implementation intentions in the first and second Pap test practice among Iranian women . MATERIAL S AND METHODS In this quasi-r and omized controlled trial , 200 women who were referred to 30 primary health care clinics in Tehran were r and omly selected . PMT variables and Pap test practice were measured at baseline and again after 3 and 15 months . The 4-week educational intervention program was conducted for the intervention group . RESULTS Following the intervention , the mean scores of self-efficacy , perceived vulnerability , and behavior intention variables were significantly higher in the intervention group when compared to the control group ( p<0.05 ) . No significant differences were found in the perceived severity , response efficacy , response cost , and fear between the two groups following the intervention . Higher percent of women in the intervention group had obtained first and second Pap test compared to the controls . CONCLUSIONS The PMT and implementation intentions provide a suitable theory-based framework for developing educational interventions regarding Pap test practice in Iran BACKGROUND Low-income African American women are more likely to die of breast cancer than their Caucasian counterparts , and at least part of the difference in mortality results from differential screening adherence . The purpose of this study was to identify more efficacious methods of promoting routine mammography screening in underserved population s. METHODS A prospect i ve r and omized intervention study of 344 low income African American women compared the impact of three interventions on mammography adherence and stage of readiness : ( 1 ) pamphlet only ; ( 2 ) culturally appropriate video ; and ( 3 ) interactive computer-assisted instruction program . RESULTS The interactive computer intervention program produced the greatest level of adherence to mammography ( 40.0 % ) compared to the video group ( 24.6 % ) and the pamphlet group ( 32.1 % ) . When subjects in the pamphlet and video groups were combined to form a non-interactive group , this group had a significantly lower adherence than the group who received the interactive computer intervention ( 27.0 % versus 40.0 % ) . There was also significantly more forward movement in mammography stage of readiness among participants in the computer group ( 52.0 % ) compared to those in the pamphlet group ( 46.4 % ) or the video group ( 31.3 % ) . When combining the non-interactive technology ( pamphlet and video ) there was also more forward movement in mammography stage of readiness for those in the interactive intervention group ( 52.0 % moved 1 or 2 stages ) compared to those in the non-interactive group ( 36.2 % ) . CONCLUSIONS These data indicate that tailored approaches are more effective than targeted messages either in print or video format . Another finding of this study is that interactive interventions are more effective than non-interactive interventions in increasing adherence and moving African American women forward in their mammogram stage of readiness The Pap smear test is recommended for early diagnosis of cervical cancer . The aim of this study was to assess knowledge and behavior regarding the Pap smear test based on the Health Belief Model ( HBM ) in women referred to premarital counseling classes , Hamadan , Iran . This quasi-experimental study was conducted on 330 women , who were allocated r and omly to two case and control groups ( n=165 ) . Two educational session classes were performed in the case group . Two stages in before and after intervention groups were evaluated . Analysis of data was performed by SPSS/16.0 , using t-test , x2 , and McNemar 's test . P-values < 0.05 were regarded as significant . There was no significant difference between the mean scores of the various structures of this model in two groups before the intervention . However , after the intervention there were significant increase in mean score of knowledge and all variables of HBM in the intervention group(<0.001 ) . The findings of this study highlight the important role of education about cervical cancer on changing women 's beliefs about cervical screening Under-screening may increase the risk of cervical cancer in middle-aged women . This study aim ed to investigate cervical cancer screening behaviour and its predictors among women aged 50 years or above . A population -based sample of 959 women was recruited by telephone from domestic households in Hong Kong , using r and om methods , and a structured question naire developed to survey participants . Multivariable logistic regressions were performed to examine the factors independently associated with cervical screening behaviour . Nearly half the sample ( 48 % ) had never had a cervical smear test . Multivariable analyses showed that age , educational level , marital status , family history of cancer , smoking status , use of complementary therapy , recommendation from health professionals , and believing that regular visits to a doctor or a Chinese herbalist were good for their health were predictors of cervical screening behaviour . Misconceptions concerned with menopause may reduce women ’s perceived susceptibility to cervical cancer , especially if they are 50 or above , and exert a negative effect on their screening behaviour . Healthcare professionals should actively approach these high-risk groups – older unmarried women , smokers , those less educated and who are generally not much concerned with their health Background Cervical cancer is the second most common form of cancer observed among women in Turkey . The participation of women in cervical cancer screening programs is strongly affected by Turkish attitudes , beliefs , and sociocultural structure . Aim This study was conducted to assess the effectiveness of health education that aim ed to raise awareness about Papanicolaou testing and to emphasize the importance of the early diagnosis of cervical cancer . Material s and Methods The study was conducted as a prospect i ve , r and omized , controlled trial and was carried out in 148 women . Seventy-five women in the control group were asked to fill out question naire forms . A 45-minute conference-style training was given to 73 women in the study group , and all of the subjects were asked to fill out the forms after the training . The sociodemographic characteristics of the 2 groups and the mean “ Health Belief Model Scale for Cervical Cancer and Pap Smear Test ” scores of the 2 groups were statistically analyzed by Statistical Package of Social Sciences ( SPSS ) , version 15 . Results There was no statistically significant difference noticed between the sociodemographic characteristics of the 2 groups ( P > 0.05 ) . The difference in test scores , which represented knowledge about cervical cancer and Papanicolaou testing , was statistically significant between the control group and the study group ( t = 10.122 , P < 0.05 ) . In the Health Belief Model Scale for Cervical Cancer and Pap Smear Test , there were statistically significant differences in the following measures : lower levels of susceptibility to cervical cancer score ( t = −2.035 , P < 0.05 ) , lower levels of perceived benefit from a Papanicolaou test score ( t = 3.278 , P < 0.05 ) and lower levels of perceived barriers to Papanicolaou test score ( t = −3.182 , P < 0.05 ) . Conclusion Nurses should be involved in educating women about cervical cancer and Papanicolaou testing . By doing so , they can change the attitudes , knowledge , and beliefs of the women Background Cervical cancer is a disease of public health importance affecting many women and contributing to avoidably high levels of cancer deaths in Nigeria . In spite of the relative ease of prevention , the incidence is on the increase . This study aim ed to determine the effect of health education on the awareness , knowledge and perception of cervical cancer and screening among women in rural Nigerian communities . Methods The study design was quasi-experimental . The study was carried out among adult women in Odogbolu ( intervention ) and Ikenne ( control ) local government areas ( LGA ) of Ogun state . Three hundred and fifty ( 350 ) women were selected per group by multistage r and om sampling technique . Data was collected by semi structured interviews with the aid of question naire . The intervention consisted of structured health education based on a movie . Result The intervention raised the level of awareness of cervical cancer and screening to 100 % ( p < 0.0001 ) . The proportion of women with very good knowledge of cervical cancer and screening rose from 2 % to 70.5 % ( χ2 = 503.7 , p < 0.0001 ) while the proportion of those with good perception rose from 5.1 % to 95.1 % ( p < 0.0001 ) . The mean knowledge and mean perception scores were also increased ( p < 0.0001 ) . There was increase in the proportion of women who had undertaken cervical screening from 4.3 % to 8.3 % ( p = 0.038 ) . The major reason stated by the women for not having had cervical screening done was lack of awareness about cervical cancer and screening . There was statistically significant difference between the intervention and control groups concerning their knowledge attitude and practice towards cervical and screening ( p < 0.05 ) after the intervention . Conclusion Multiple media health education based on a movie is effective in creating awareness for and improving the knowledge and perception of adult women about cervical cancer and screening . It also improves the uptake of cervical cancer screening . The creation of awareness is very crucial to the success of a cervical cancer prevention programme BACKGROUND Cervical cancer is one of the most common forms of carcinoma among women worldwide , accounting for about 12 % of all cancers . Tragically , studies have shown generally low awareness levels on its symptoms , risk factors and prevention . This study evaluated the effect of a health education program on knowledge of cervical cancer amongst women at risk in Africa . METHOD This study was conducted in the city of Lagos , Nigeria , using a multistage sampling technique . Two model markets were chosen by simple r and om sampling method from a total of 10 local governments with model markets . One was design ated the intervention/experimental group while the other was the control . Systematic sampling method was used in selecting 350 women comprising of 175 participants from each model market . A baseline survey on cervical cancer awareness and screening practice s was carried out in both sample groups with the aid of interviewer-administered , structured and pre-tested question naires . Thereafter , respondents in the intervention group received sessions of community-based educational messages on cervical cancer and its prevention . Subsequently , participants in both groups were reassessed to evaluate the effect of the educational program . Data analysis was conducted with Epi-info statistical software . RESULTS Knowledge level was low on cervical cancer at baseline ; only about 15 % and 6.9 % of participants in the intervention and control groups respectively had heard of cervical cancer . The most common sources of information were friends and media prior to the intervention . Significant increase in proportions were found in the intervention/experimental group on awareness of cervical cancer ( 61.7 % ) , associated symptoms and risk factors such as early sexual debut , promiscuity and smoking . CONCLUSION It is apparent that efforts must be put in place by all stakeholders in reaching women at risk of cervical cancer through well organized educational campaigns using culturally sensitive information , education and communication BACKGROUND North American Chinese women have lower levels of Papanicolaou ( Pap ) testing than other population subgroups . We conducted a r and omized controlled trial to evaluate the effectiveness of two alternative cervical cancer screening interventions for Chinese women living in North America . METHODS Four hundred and eighty-two Pap testing underutilizers were identified from community-based surveys of Chinese women conducted in Seattle , Washington , and Vancouver , British Columbia . These women were r and omly assigned to one of two experimental arms or control status . Several Chinese- language material s were used in both experimental arms : an education-entertainment video , a motivational pamphlet , an educational brochure , and a fact sheet . Women in the first experimental group ( outreach worker intervention ) received the material s , as well as tailored counseling and logistic assistance , during home visits by trilingual , bicultural outreach workers . Those in the second experimental group ( direct mail intervention ) received the material s by mail . The control group received usual care . Follow-up surveys were completed 6 months after r and omization to ascertain participants ' Pap testing behavior . All statistical tests were two-sided . RESULTS A total of 402 women responded to the follow-up survey ( 83 % response rate ) . Of these women , 50 ( 39 % ) of the 129 women in the outreach group , 35 ( 25 % ) of the 139 women in the direct mail group , and 20 ( 15 % ) of the 134 women in the control group reported Pap testing in the interval between r and omization and follow-up data collection ( P<.001 for outreach worker versus control , P = .03 for direct mail versus control , and P = .02 for outreach worker versus direct mail ) . Intervention effects were greater in Vancouver than in Seattle . CONCLUSION Culturally and linguistically appropriate interventions may improve Pap testing levels among Chinese women in North America Despite declines in cervical cancer mortality in developed countries , cervical cancer incidence and mortality rates remain high in Jamaica due to low levels of screening . Effective interventions are needed to decrease barriers to preventive behaviors and increase adoption of behaviors and services to improve prospect s of survival . We enrolled 225 women attending health facilities in an intervention consisting of a pre-test , educational presentation and post-test . The question naires assessed attitudes , knowledge , risk factors , and symptoms of cervical cancer among women . Changes in knowledge and intention to screen were assessed using paired t-tests and tests for correlated proportions . Participants were followed approximately six months post-intervention to determine cervical cancer screening rates . We found statistically significant increases from pre-test to post-test in the percentage of questions correctly answered and in participants ’ intention to screen for cervical cancer . The greatest improvements were observed in responses to questions on knowledge , symptoms and prevention , with some items increasing up to 62 % from pre-test to post-test . Of the 123 women reached for follow-up , 50 ( 40.7 % ) screened for cervical cancer . This theory-based education intervention significantly increased knowledge of and intention to screen for cervical cancer , and may be replicated in similar setting s to promote awareness and increase screening rates Background Breast cancer is the most common neoplasm among Hispanic women . Cervical cancer has a higher incidence and mortality among Hispanic women compared with non-Hispanic White women . Objective To assess the effectiveness of a promotora-administered educational intervention to promote breast and cervical cancer screening among post-reproductive age , medically underserved Hispanic women residing along the U.S .– Mexico border . Methods Women age 50 or older were eligible to participate in this intervention study . A total of 381 subjects agreed to participate . Women were r and omly assigned into one of two groups , educational intervention or usual care . The primary outcomes were self-reported mammogram and Pap smear screening . Logistic regression analysis was used to compute odds ratios for comparisons between intervention and control groups . Results Women in the intervention group were 2.0 times more likely to report having had a mammogram within the last year when compared with the usual care group ( 95 % CI = 1.3–3.1 ) . Likewise , women in the intervention group were 1.5 times more likely to report having a Pap smear within the last year when compared with the usual care group , although this was not statistically significant ( 95 % CI = 0.9–2.6 ) . In a secondary analysis , the intervention suggests a stronger effect on those that had not had a mammogram or Pap smear within the past year at baseline . Conclusions A promotora-based educational intervention can be used to increase breast and cervical cancer screening utilization among Hispanic women OBJECTIVE Cervical cancer screening uptake may be influenced by inadequate knowledge in re source -limited setting s. This r and omized trial evaluated a health talk 's impact on cervical cancer knowledge , attitudes , and screening rates in rural Kenya . METHODS 419 women attending government clinics were r and omized to an intervention ( N=207 ) or control ( N=212 ) group . The intervention was a brief health talk on cervical cancer . Participants completed surveys at enrollment ( all ) , immediately after the talk ( intervention arm ) , and at three-months follow-up ( all ) . The primary outcomes were the change in knowledge scores and the final screening rates at three-months follow-up . Secondary outcomes were changes in awareness about cervical cancer screening , perception of personal cervical cancer risk , cervical cancer and HIV stigma , and screening acceptability . RESULTS Mean Knowledge Scores increased by 26.4 % ( 8.7 points increased to 11.0 points ) in the intervention arm compared to only 17.6 % ( 8.5 points increased to 10.0 points ) in the control arm ( p<0.01 ) . Screening uptake was moderate in both the intervention ( 58.9 % ; N=122 ) and control ( 60.9 % ; N=129 ) arms , with no difference between the groups ( p=0.60 ) . CONCLUSION A brief health talk increased cervical cancer knowledge , although it did not increase screening over simply informing women about free screening . PRACTICAL IMPLICATION S Screening programs can increase patient underst and ing with just a brief educational intervention Purpose . To assess the efficacy of an intervention to promote mammography and Papanicolaou ( Pap ) testing among women with mobility impairments overdue for screenings Design . R and omized controlled trial . Setting . Urban and suburban Oregon . Participants . Women aged 35 to 64 with mobility impairments who reported not receiving a Pap test in the past 3 years and /or mammogram ( if age > 40 years ) in the last 2 years were eligible . A total of 211 women were r and omized , and 156 completed the study ( 26 % attrition ) . The majority were not employed and reported annual income < $ 10,000 . Intervention . The Promoting Access to Health Services ( PATHS ) program is a 90-minute , small-group , participatory workshop with 6 months of structured telephone support , based on the health belief model and social cognitive theory . Measures . Perceived susceptibility to breast and cervical cancer , perceived benefits of and self-efficacy for screening intention to be screened , and self-reported receipt of mammography and Pap testing . Analysis . Chi-square tests to examine the proportion of women obtaining screening ; analysis of covariance to examine change in theoretical mediators . Results . The intervention group received more Pap tests than the control group at posttest ( intervention 61 % , control 27 % , n = 71 , p < .01 ) . No significant group effect was observed for mammography ( intervention 49 % , control 42 % , n = 125 , p = .45 ) . Conclusion . Findings indicate that the PATHS intervention promotes Pap testing but not mammography among women with mobility impairments Introduction : Cervical cancer is the most common gynecological cancer in Iran . The single most effective tool in reducing death due to cervical cancer is the use of pap smear as a screening tool . Therefore , the aim of this study was to determine the effectiveness of education based on Health Belief Model about giving pap smear in women . Methods : This quasi-experimental study was performed on 70 women who referred to two health center in Kouhdasht ( Lorestan- Iran ) . The sample s were r and omly divided in two groups ( 35 in intervention group and 35 in control group ) . The data were collected by a vali date d and reliable question naire . Interventions were run based on Health Belief Model during three sessions only for intervention group . Each educational session was for 45–60 min . The independent t-test and paired t-test were used to analyze data . A two-tailed P value lower than 0.05 was considered statistically significant . Result : According to results , the mean scores of knowledge were significantly different between two groups after intervention ( P < 0.001 ) . The mean scores of the model variables ( perceived susceptibility and severity , perceived benefits , and barriers ) had no significant difference in the two groups before intervention , but after intervention had significant difference between the two groups ( P < 0.001 ) . Conclusion : Design ing and executing health education programs based on health belief model can promote the practice of women regarding to pap smear tests BACKGROUND The purpose s of the study were to ( 1 ) assess the impact of direct-mail communications with and without phone intervention , and ( 2 ) examine the characteristics of women who were more likely to respond . METHODS Women were recruited from female family members of in patients admitted to one of the major teaching hospitals in Taiwan ( n = 424 ) , and were r and omly assigned into an intervention group , who received direct-mails and a phone follow-up , or a control group , who received placebo messages . RESULTS Logistic regression analysis showed that women in the intervention group ( ORadj . = 2.31 ) and contemplation stage ( ORadj . = 4.18 ) were more likely to receive a screening at the end of the program . Among women in the intervention group , contemplators were 5.58 times more likely to receive a screening before the phone intervention ( early adopters ) ; and 40 % of the screening adopters responded after the phone intervention ( late adopters ) . Late and early adopters were similar in their stage , age , and education . CONCLUSIONS Stage and intervention are both significant predictors of screening adoption . The study provides justification for programs to target women in contemplation stage . It also suggests that the boost of a later phone intervention may be consequential for encouraging more women with similar demographics to take action INTRODUCTION U.S. Hispanic women suffer a disproportionate burden of cervical cancer , with incidence and mortality rates almost twice that of whites . Community health workers , or promotoras , are considered a potential strategy for eliminating such racial and ethnic health disparities . The current study is a r and omized trial of a promotora-led educational intervention focused on cervical cancer in a local Hispanic community . METHODS Four promotoras led a series of two workshops with community members covering content related to cervical cancer . Sociodemographic characteristics , cervical cancer risk , previous screening history , cervical cancer knowledge , and self-efficacy were measured by a pre-intervention question naire . The post-intervention question naire measured the following outcomes : cervical cancer knowledge ( on a 0–6 scale ) , self-efficacy ( on a 0–5 scale ) , and receipt of Pap smear screening during the previous 6 months ( dichotomous ) . Univariate analyses were performed using chi square , t-test , and the Mann – Whitney test . Multivariate logistic regression was used to model the association between explanatory variables and receipt of Pap smear screening . RESULTS There were no statistically significant differences between the two experimental groups at baseline . Follow-up data revealed significant improvements in all outcome measures : Pap smear screening ( 65 % vs. 36 % , p-value 0.02 ) , cervical cancer knowledge ( 5.4 vs. 3.5 , p-value < 0.001 ) , and self-efficacy ( 4.7 vs. 4.0 , p-value 0.002 ) . In multivariate analysis , cervical cancer knowledge ( OR 1.68 , 95 % CI 1.10 - 2.81 ) and intervention group assignment ( OR 6.74 , 95 % CI 1.77 - 25.66 ) were associated with receiving a Pap smear during the follow-up period . DISCUSSION Our r and omized trial of a promotora-led educational intervention demonstrated improved Pap screening rates , in addition to increased knowledge about cervical cancer and self-efficacy . The observed association between cervical cancer knowledge and Pap smear receipt underscores the importance of educating vulnerable population s about the diseases that disproportionately affect them . Future research should evaluate such programs on a larger scale , and identify novel targets for intervention OBJECTIVE The objective of this study was to evaluate the effect of a call-recall approach in enhancing Pap smear practice by changes of motivation stage among non-compliant women . METHODS A cluster r and omized controlled trial with parallel and un-blinded design was conducted between January and November 2010 in 40 public secondary schools in Malaysia among 403 female teachers who never or infrequently attended for a Pap test . A cluster r and omization was applied in assigning schools to both groups . An intervention group received an invitation and reminder ( call-recall program ) for a Pap test ( 20 schools with 201 participants ) , while the control group received usual care from the existing cervical screening program ( 20 schools with 202 participants ) . Multivariate logistic regression was performed to determine the effect of the intervention program on the action stage ( Pap smear uptake ) at 24 weeks . RESULTS In both groups , pre-contemplation stage was found as the highest proportion of changes in stages . At 24 weeks , an intervention group showed two times more in the action stage than control group ( adjusted odds ratio 2.44 , 95 % CI 1.29 - 4.62 ) . CONCLUSION The positive effect of a call-recall approach in motivating women to change the behavior of screening practice should be appreciated by policy makers and health care providers in developing countries as an intervention to enhance Pap smear uptake BACKGROUND The Cochrane Collaboration is strongly encouraging the use of a newly developed tool , the Cochrane Collaboration Risk of Bias Tool ( CCRBT ) , for all review groups . However , the psychometric properties of this tool to date have yet to be described . Thus , the objective of this study was to add information about psychometric properties of the CCRBT including inter-rater reliability and concurrent validity , in comparison with the Effective Public Health Practice Project Quality Assessment Tool ( EPHPP ) . METHODS Both tools were used to assess the method ological quality of 20 r and omized controlled trials included in our systematic review of the effectiveness of knowledge translation interventions to improve the management of cancer pain . Each study assessment was completed independently by two review ers using each tool . We analysed the inter-rater reliability of each tool 's individual domains , as well as final grade assigned to each study . RESULTS The EPHPP had fair inter-rater agreement for individual domains and excellent agreement for the final grade . In contrast , the CCRBT had slight inter-rater agreement for individual domains and fair inter-rater agreement for final grade . Of interest , no agreement between the two tools was evident in their final grade assigned to each study . Although both tools were developed to assess ' quality of the evidence ' , they appear to measure different constructs . CONCLUSIONS Both tools performed quite differently when evaluating the risk of bias or method ological quality of studies in knowledge translation interventions for cancer pain . The newly introduced CCRBT assigned these studies a higher risk of bias . Its psychometric properties need to be more thoroughly vali date d , in a range of research fields , to underst and fully how to interpret results from its application BACKGROUND : Breast cancer has been considered as a major health problem in females , because of its high incidence in recent years . Due to the role of breast self-examination ( BSE ) in early diagnosis and prevention of morbidity and mortality rate of breast cancer , promoting student knowledge , capabilities and attitude are required in this regard . This study was conducted to evaluation BSE education in female University students using Health Belief Model . METHODS : In this semi-experimental study , 243 female students were selected using multi-stage r and omized sampling in 2008 . The data were collected by vali date d and reliable question naire ( 43 questions ) before intervention and one week after intervention . The intervention program was consisted of one educational session lasting 120 minutes by lecturing and showing a film based on HBM constructs . The obtained data were analyzed by SPSS ( version11.5 ) using statistical paired t-test and ANOVA at the significant level of α = 0.05 . RESULTS : 243 female students aged 20.6 ± 2.8 years old were studied . Implementing the educational program result ed in increased knowledge and HBM ( perceived susceptibility , severity , benefit and barrier ) scores in the students ( p ≤ 0.01 ) . Significant increases were also observed in knowledge and perceived benefit after the educational program ( p ≤ 0.05 ) . ANOVA statistical test showed significant difference in perceived benefit score in students of different universities ( p = 0.05 ) . CONCLUSIONS : Due to the positive effects of education on increasing knowledge and attitude of university students about BSE , the efficacy of the HBM in BSE education for female students was confirmed ABSTRACT Cervical cancer incidence and mortality rates are disproportionally high among women living in Appalachia Ohio . This study used the Transtheoretical Model to examine screening barriers before and after a lay health advisor ( LHA ) intervention ( 2005–2009 ) to increase cervical cancer screening rates . Ohio Appalachian women ( n = 90 ) who were in need of a Pap test , based on risk-appropriate guidelines , were r and omized to a 10-month LHA intervention and received two in-person visits , two phone calls , and four mailed postcards targeted to the participant ’s stage of change . Findings revealed that 63 % had forward stage movement 10 months after the intervention . The most frequently reported screening barriers were time constraints , forgetting to make an appointment , and cost . Women who reported the following barriers — doctor not recommending the test ; being unable to afford the test ; and being embarrassed , nervous , or afraid of getting a Pap test — were less likely to be in the action stage . Underst and ing the stages of change related to Pap testing and reported barriers among this underserved population may help inform research ers and clinicians of this population ’s readiness for change and how to set realistic intervention goals The purpose of this study was to determine the effect of a three-stage nursing intervention to increase Turkish women 's participation in Pap smear testing . Knowledge and beliefs about cervical cancer screening and barriers to Pap smears also were explored . In a quasi-experimental study in a target population of 2,500 women , 237 completed pre-test measures to inform the intervention , and an educational brochure was distributed to all 2,500 . As a result , 510 women ( 20.4 % ) accepted free Pap smears . Of the remaining 1,990 women , 417 were r and omly selected for telephone interviews , 302 participated , and 158 of these ( 52.3 % ) participated in free Pap smear testing . Of the 144 who did not have Pap smears after participating in telephone interviews , 54 were then interviewed face-to-face , and 20 ( 37.0 % ) decided to accept free Pap smears . A total of 668 women had accepted free Pap smears by the end of the intervention period Barriers to screening and early detection often result in cancers in low-income and minority women diagnosed at stages too advanced for optimal treatment . This r and omized controlled trial examined whether a personalized form ( PF ) letter containing generic cancer information and a personalized tailored ( PT ) letter containing minimally tailored individualized risk factor information based on medical records data affected breast and cervical cancer screening among 1574 urban low-income and minority women . The personalized form-letter group was significantly more likely to schedule a screening appointment and to have undergone a Pap test and mammography within 1 year after the intervention than were the tailored letter and control groups ( P<0.001 for all comparisons ) . Personalized tailored letters that contain individualized cancer risk factor information may decrease the likelihood of receiving cancer screening among medically underserved low-income and minority women , but personalized form letters that contain generic cancer information may improve these rates in this disadvantaged population OBJECTIVES To assess cervical cancer screening behaviors among underserved women participating in an intervention design ed to increase mammography use . METHODS This was a r and omized trial of 897 women from three racial groups ( white , African American , Native American ) living in a rural county in North Carolina . Baseline and followup surveys were completed by 815 women ; 775 women provided data to be included in these analyses . The intervention group received an educational program focused on mammography delivered by a lay health advisor , and the control group received a physician letter/brochure focusing on Pap tests . RESULTS Women in both the intervention ( OR 1.70 ; 1.31 , 2.21 , p < 0.001 ) and control groups ( OR 1.38 ; 1.04 , 1.82 , p = 0.025 ) significantly increased cervical cancer screening rates within risk appropriate guidelines . No differences by racial group were documented . Women categorized in the high-risk group for developing cervical cancer ( > 2 sexual partners , age < 18 years at first sexual intercourse , smoker ; treated for sexually transmitted disease [ STD ] or partner with treated STD ) significantly ( OR 1.88 ; 1.54 , 2.28 , p < 0.001 ) increased Pap test completion . However , a nonsignificant increase ( OR 1.25 ; 0.87 , 1.79 , p = 0.221 ) in Pap test completion was demonstrated in women categorized as low risk for cervical cancer . CONCLUSIONS This study suggests that women in an intensive behavioral intervention design ed to increase mammography use may also increase Pap test completion , similar to a minimal intervention focused only on increasing Pap test completion . These results have implication s for the design and evaluation of behavioral intervention studies OBJECTIVE Despite high incidence rates of cervical cancer in Korea , Papanicolaou ( Pap ) tests are not utilized as a preventive behavior . This study examined the effects of an emotion-cognition focused program on the decision of taking Pap tests in Korean women . DESIGN A non-equivalent control group post-test only design was utilized . SAMPLE A convenience sample was r and omly assigned to either experimental ( N=48 ) or control group ( N=48 ) after matching for education and age . MEASUREMENTS Knowledge of Cervical Cancer and Pap Smear Test , Champion 's Health Belief Model , and Self-Efficacy Scale were used . Intention and stage of adoption to take a Pap test were measured with single items . RESULTS Women in the experimental group had significantly higher scores on knowledge of cervical cancer ( t=6.99 , p<.001 ) and perceived benefits of Pap tests ( t=2.91 , p<.05 ) , lower scores on procedural ( t=-2.45 , p<.05 ) and cognitive ( t=-2.66 , p<.01 ) barriers to testing . Improvement in self-efficacy ( t=3.38 , p<.01 ) , strong intention to have the test ( t=2.99 , p<.01 ) , and advanced stages of behavior adoption ( chi2=12.93 , p<.01 ) were also found . CONCLUSIONS Women 's perspectives , attitudes of health care practitioners , and clinical environment need to be considered if change is to happen in women 's preventive behavior related to Pap test screening BACKGROUND This paper reports the first evaluation of an intervention to increase breast and cervical cancer screening among Filipino American women . METHODS Filipino women over 40 years of age were recruited through nine community-based organizations and six churches in Los Angeles County . After completion of a short baseline interview , all women were invited to attend a group session with some of their peers and a female Filipino health educator . Women within each organization were r and omized to receive a cancer screening module ( intervention ) or a physical activity module ( control ) . Telephone follow-up interviews 12 months after the group session assessed the impact of the intervention . RESULTS Of the 530 women invited , 444 ( 84 % ) attended a session . At baseline and follow-up , screening rates for breast and cervical cancer did not differ between study groups . Moderate increases in screening rates ( 9 to 12 percentage points ) were observed in both arms of the study . Among relatively recent immigrants who had spent less than 10 years in the United States , mammography screening increased substantially more in the intervention arm than under the control condition ( a 27 vs 6 percentage point increase , P<0.05 ) . CONCLUSION Our intervention was only effective in increasing cancer screening among relatively recent immigrants who had very low baseline screening rates AIM This study is a report of the development and psychometric testing of the Health Belief Model Scale for Cervical Cancer and the Pap Smear Test . BACKGROUND While the Champion Health Belief Model scales have been tested extensively for breast cancer and screening for this , evaluation of these scales in explaining the beliefs of women with regard to cervical cancer and the Pap Smear Test has only received limited attention . METHODS This method ological research was carried out in Turkey in 2007 . The data were collected with 237 r and omly selected women who met the criteria for inclusion and agreed to participate in this study . The Champion Health Belief Model scales were translated into Turkish , adapted for cervical cancer , vali date d by professional experts , translated back into English and pilot-tested . FINDINGS Factor analysis yielded five factors : Pap smear benefits and health motivation , Pap smear barriers , seriousness , susceptibility and health motivation . Cronbach 's alpha reliability coefficients for the five subscales ranged from 0·62 to 0·86 , and test-retest reliability coefficients ranged from 0·79 to 0·87 for the subscales . CONCLUSION The Health Belief Model Scale for Cervical Cancer and the Pap Smear Test was found to be a valid and reliable tool in assessing the women 's health beliefs . Underst and ing the beliefs of women in respect of cervical cancer and the Pap Smear Test will help healthcare professionals to develop more effective cervical cancer screening programmes |
12,786 | 27,878,805 | There is limited evidence of benefit from enteric-coated microspheres when compared to non-enteric coated pancreatic enzyme preparations up to one month .
In the only comparison where we could combine any data , the fact that these were cross-over studies is likely to underestimate the level of inconsistency between the results of the studies due to over-inflation of confidence intervals from the individual studies .There is no evidence on the long-term effectiveness and risks associated with pancreatic enzyme replacement therapy .
There is also no evidence on the relative dosages of enzymes needed for people with different levels of severity of pancreatic insufficiency , optimum time to start treatment and variations based on differences in meals and meal sizes . | BACKGROUND Most people with cystic fibrosis ( 80 % to 90 % ) need pancreatic enzyme replacement therapy to prevent malnutrition .
Enzyme preparations need to be taken whenever food is taken , and the dose needs to be adjusted according to the food consumed .
A systematic review on the efficacy and safety of pancreatic enzyme replacement therapy is needed to guide clinical practice , as there is variability between centres with respect to assessment of pancreatic function , time of commencing treatment , dose and choice of supplements .
This is an up date d version of a published review .
OBJECTIVES To evaluate the efficacy and safety of pancreatic enzyme replacement therapy in children and adults with cystic fibrosis and to compare the efficacy and safety of different formulations of this therapy and their appropriateness in different age groups .
Also , to compare the effects of pancreatic enzyme replacement therapy in cystic fibrosis according to different diagnostic subgroups ( e.g. different ages at introduction of therapy and different categories of pancreatic function ) . | BACKGROUND Pancreatic enzyme replacement therapy ( PERT ) is essential for maintaining adequate nutrition in children with exocrine pancreatic insufficiency ( EPI ) due to cystic fibrosis ( CF ) . The US Food and Drug Administration regulations now require all PERT products to undergo clinical efficacy and safety studies before they can be considered for marketing approval . OBJECTIVE This study was conducted to compare the efficacy of a new formulation of pancrelipase ( pancreatin ) delayed-release 12,000-lipase unit capsules with placebo in children with EPI due to CF . METHODS This was a multicenter , r and omized , double-blind , placebo-controlled , 2-period crossover , superiority study of the new formulation of pancrelipase delayed-release 12,000-lipase unit capsules in children aged 7 to 11 years with CF and EPI . In each period , pancrelipase or identical placebo capsules were taken for 5 days . The primary outcome measure was the coefficient of fat absorption ( CFA ) ; secondary outcome measures were the coefficient of nitrogen absorption ( CNA ) and clinical symptoms . The latter were assessed based on patient-reported daily stool frequency , stool consistency ( hard , formed/normal , soft , or watery ) , flatulence ( none , mild , moderate , or severe ) , and abdominal pain ( none , mild , moderate , or severe ) . Safety measures included vital signs , physical examinations , st and ard laboratory safety tests ( hematology and biochemistry ) , and adverse events . RESULTS Seventeen patients were r and omized to treatment and 16 completed the study ; 1 patient withdrew consent during the first treatment period and was not included in the efficacy analysis . Patients ' median age was 8.0 years ( range , 7 - 11 years ) ; 12 patients ( 70.6 % ) were male . CFA values were significantly greater for pancrelipase compared with placebo , with least squares mean ( SE ) values of 82.8 % ( 2.7 % ) and 47.4 % ( 2.7 % ) , respectively ( P < 0.001 ) . The results were similar for CNA , with mean values of 80.3 % ( 3.2 % ) and 45.0 % ( 3.2 % ) ( P < 0.001 ) . Pancrelipase treatment had significantly greater effects on CFA and CNA in patients with a placebo CFA < 50 % than in those with a placebo CFA > 50 % ( both parameters , P < 0.001 and P = 0.008 , respectively ) . Significant improvements in stool fat , weight , and nitrogen and a significant reduction in daily stool frequency were observed with pancrelipase compared with placebo ( all , P < 0.001 ) . Symptoms of EPI were less severe and remained relatively stable during pancrelipase treatment , but worsened slightly during receipt of placebo . Treatment-emergent adverse events were reported in 5 patients ( 29.4 % ) during receipt of pancrelipase and in 9 patients ( 56.3 % ) during receipt of placebo ; these were predominantly gastrointestinal events . There were no discontinuations due to treatment-emergent adverse events and no serious adverse events . CONCLUSIONS In this study in children with EPI due to CF , the new formulation of pancrelipase delayedrelease capsules was associated with improvements in CFA , CNA , stool properties , and EPI symptoms compared with placebo . Pancrelipase delayed-release capsules appeared to be well tolerated . Clinical Trials.gov identifier : NCT00690820 . ( Clin Ther ABSTRACT . In order to compare the efficacy of pancreatic enzyme supplementation as pH‐sensitive enteric‐coated microspheres Pancrease ® to that of conventional supplementation with enteric‐coated Pancreatin ® in cystic fibrosis , a double blind cross‐over study was conducted . Eleven patients under 12 years of age received each of the enzyme preparations for four weeks . Treatment efficacy was evaluated by means of a symptom score card recording stool frequency , consistency , colour , odour , abdominal cramps and appetite as well as a 3 days fat absorption test . Weight increments were recorded 3 months before the study when patients were on Pancreatin , and 3 months after the study when patients were on Pancrease . In eight of the patients fat absorption was improved on Pancrease , but the difference did not reach statistical significance . However , the patients experienced significantly less dyspeptic symptoms , decreased stool frequency , better appetite and increments in weight were significantly higher on Pancrease compared to Pancreatin OBJECTIVES to compare the efficacy and tolerance of Creon and Pancrease in children and young adults with cystic fibrosis . METHODS a double blind , crossover study of two pH sensitive microsphere preparations of pancreatin ( Creon , Pancrease ) , given in equivalent lipase dosage to 27 children with cystic fibrosis , was conducted . RESULTS at similar lipase activity no significant difference was found in the following : coefficient of fat absorption ( CFA ) , coefficient of nitrogen absorption ( CNA ) , weight gain , mean adequate daily intake for energy , and subjective symptoms . Three children who had a CFA less than 70 % while receiving Pancrease all improved on Creon . No children had a CFA less than 70 % while receiving Creon . A significant reduction in the number of capsules required daily to achieve similar control was possible when changing from Pancrease ( mean 25/day ) to Creon ( mean 15/day ) . Seventy percent of patients preferred Creon and this was likely to be related to a perceived reduction in abdominal pain and stool frequency , and need for less capsules per day . CONCLUSION Creon and Pancrease are equally effective at doses providing equal lipase activity , however , the reduced number of capsules , fewer symptoms , and possible improvement of more severe steatorrhoea result in an increased patient preference for Creon Abstract The failure of conventional pancreatic enzyme supplements to correct completely the malabsorption that is caused by pancreatic insufficiency in cystic fibrosis ( CF ) is partly due to acid-peptic inactivation of ingested enzymes . To compare various methods of preventing acid-peptic inactivation we studied 10 CF patients during four r and omised crossover 14-day treatment periods : ( i ) conventional supplements of pancrelipase ( 68±5 capsules daily ) ; ( ii ) pH-sensitive enteric-coated microspheres of pancrelipase ( ECMP ; 31±3 capsules/day ) ; ( iii ) ECMP plus cimetidine ( 20 mg/kg/day ) ; and ( iv ) ECMP plus antacid suspension . Faecal fat excretion , measured as mmol/24 h and as a percentage of recorded ad-libitum intake , faecal nitrogen excretion , measured as g/24h and as a percentage of intake , and faecal weight/24 h were measured during each treatment period . During the ECMP treatment period there were significant decreases in faecal fat excretion ( A comparative study of the efficacy of pH sensitive enteric coated microspheres ( ECM ) with an enteric coated tablet ( ECT ) pancreatic enzyme preparation was carried out in 20 children with cystic fibrosis in a double-blind doubleplacebo crossover manner . Steatorrhoea was assessed by 3 day faecal fat analysis and dosage of medication , stool frequency and consistency ; abdominal pain and appetite were documented by a patient-kept diary card . ECM controlled steatorrhoea ( 11.8±9.2 g vs 23.2±18.9 g , P<0.02 ) , stool frequency ( 1.7±0.6 vs 2.1±0.9,P<0.01 ) and abdominal pain ( 8.8±13.8 vs 23.4±24.1,P<0.05 ) significantly better than ECT . Out of 20 patients 17 preferred ECM to ECT ( P<0.00036 ) . ECM preparations should allow more satisfactory dietary management of patients with cystic fibrosis with longterm beneficial effect This study compared the relative effectiveness of a st and ard pancreatic enzyme supplement ( ‘ Creon ’ , Duphar ) and a new preparation ( ‘ Pancrease HL ’ , Cilag ) containing about 3 times the lipase and more than 5 times the protease activity . Capsule dosage was adjusted to a ratio of approximately 3:1 . Fat balances showed that absorption of fat did not change significantly on conversion to the new high‐lipase product , and the coefficient of absorption of total energy was similarly maintained . The coefficient of protein absorption was significantly enhanced with the high enzyme preparation ( P < 0.01 ) , which may explain the reported subjective improvement in stool odour . No adverse effects were recorded . Patient acceptability of the new compound was high ; the great reduction in the number of capsules required at each meal was cited by all patients as the reason for their preference BACKGROUND Zenpep ( APT-1008 ) is a pancreatic enzyme product for the treatment of exocrine pancreatic insufficiency ( EPI ) associated with cystic fibrosis ( CF ) . METHODS Zenpep and Kreon , both containing 25,000 lipase units , were compared in a r and omised , double-blind , crossover , non-inferiority study for CF-associated EPI in patients aged ≥12years . Patients on a st and ardised diet and stabilised treatment were r and omised to two treatment sequences : Zenpep/Kreon or Kreon/Zenpep . The primary efficacy endpoint was the coefficient of fat absorption over 72h ( CFA-72h ) . RESULTS 96 patients ( mean age 19.2years , 60.4 % males ) were r and omised with 83 completers of both sequences comprising the efficacy population . Zenpep demonstrated non-inferiority and equivalence to Kreon in fat absorption ( LS mean CFA-72h : Zenpep , 84.1 % [ SE 1.1 ] vs. Kreon , 85.3 % [ SE 1.1 ] ; p=0.297 ) . Safety and tolerability were similar . CONCLUSIONS Zenpep is comparable with Kreon in efficacy and safety for the treatment of adolescents and adults with CF-associated EPI . NCT01641393 Fifteen patients with cystic fibrosis and pancreatic insufficiency were studied during four r and omised seven day treatment periods in which they received only pancreatic supplement ( Pancrelipase , 27 capsules per day ) or supplement plus cimetidine ( 20 mg/kg body weight/24 h ) or sodium bicarbonate ( 15 g/m2/24 h ) alone or in combination . Dietary intake was not fixed but was restricted to foods of known fat and nitrogen content from which daily intakes could be computed . Faecal fat and nitrogen were calculated as g/24 h and percentage of intake . Addition of either cimetidine or bicarbonate result ed in significant improvement in fat and nitrogen excretion , which was not greater with the combination of both drugs . Cimetidine and sodium bicarbonate in these doses are therefore sufficient to produce maximal improvement in digestive activity of pancreatic supplements . Fat excretion per gram of intake fell with cimetidine and bicarbonate from 12 times the normal level , to normal , in patients consuming less than 120 g fat daily . Above this intake the dose of pancreatic supplement appeared to be inadequate . Faecal nitrogen excretion increased with nitrogen intake in all four periods , but , in contrast with fat excretion , the response to cimetidine and bicarbonate was not affected by the level of intake . Dietary intake appears to be a significant factor in determining the faecal output of fat and nitrogen in patients with pancreatic insufficiency and should be considered when determining the optimum amount of pancreatic supplementation Enteric‐coated microspheres of pancreatin were compared with non‐enteric‐coated pancreatin combined with cimetidine taken 40 min before meals in the treatment of patients with cystic fibrosis . Fourteen adults with steatorrhoea due to cystic fibrosis were investigated in an open , r and omized crossover study , over two consecutive 28‐day treatment periods . Lipase intake was adjusted to each patient 's previous requirements and was the same during both months ; they were instructed to continue with their normal diet . Patients collected faeces for 72 h at the end of each month and completed diary cards daily throughout . Bowel actions were less frequent on enteric‐coated microspheres of pancreatin than on non‐enteric‐coated pancreatin/cimetidine ( 1.7 vs. 2.4/day ; P < 0.001 ) and stool character was improved ( P < 0.001 ) . Mean daily faecal weight was similar on enteric‐coated microspheres of pancreatin to that on the combination ( 254 g vs. 291 g ; N.S. ) , whereas daily faecal fat excretion tended to be less on enteric‐coated microspheres of pancreatin ( 21 g vs. 27 g ; N.S. ) , and percentage fat absorption tended to be greater ( 81%vs . 73 % ; N.S. ) . Mean body weight increased by 0.3 kg on enteric‐coated microspheres of pancreatin and fell by 0.1 kg on the combination ( N.S. ) . These data indicate that enteric‐coated microspheres of pancreatin are at least as effective as non‐enteric‐coated pancreatin with cimetidine in the treatment of steatorrhoea in cystic fibrosis In a r and omised single blind crossover study in children with cystic fibrosis and pancreatic insufficiency , two enteric coated microsphere preparations of pancreatin were compared on a capsule for capsule basis , by measuring the coefficient of fat absorption , nitrogen excretion , weight change , and symptom scores after four weeks ' treatment with each preparation . Thirty nine subjects were r and omly allocated to receive Pancrease followed by Creon or vice versa . Each individual subject received the same number of capsules per day in each study period . Data from 27 children ( Pancrease/Creon , n = 13 and Creon/Pancrease , n = 14 ) wer suitable for analysis . Results showed no significant differences between the two preparations in any variable studied . We conclude that there is no significant difference between Pancrease and Creon when compared on a capsule for capsule basis BACKGROUND Pancreatic enzyme replacement therapy ( PERT ) is critical for correction of exocrine pancreatic insufficiency ( EPI ) in patients with cystic fibrosis ( CF ) . METHODS This was a r and omized , placebo-controlled PERT withdrawal study evaluating the efficacy and safety of PANCREAZE ® ( pancrelipase ) in CF patients with EPI . Participants ( n=49 ) entered an open-label , ≤ 14 day run-in phase , maintained a high-fat diet ( 100 ± 15 g/day ) , and received PANCREAZE ® ( 10.5 or 21 ) . Participants with a coefficient of fat absorption (CFA)≥ 80 % ( n=40 ) were then r and omized ( 1:1 ) to receive either PANCREAZE ® or placebo during a double-blind , ≤ 7 day withdrawal phase . RESULTS PANCREAZE ® improved fat absorption as shown by significantly lower mean ± SD change in CFA between open-label and double-blind phases for PANCREAZE ® ( -1.5 ± 5.88 % ; p<0.001 ) compared to placebo ( -34.1 ± 23.03 % ) . Protein absorption was similarly improved . No unexpected adverse events were reported . CONCLUSIONS This study demonstrated PANCREAZE ® was effective in treating EPI due to CF and was safe and well tolerated Objectives : Patients with cystic fibrosis ( CF ) who have exocrine pancreatic insufficiency ( EPI ) require treatment with pancreatic enzyme replacement therapy ( PERT ) to maintain adequate nutrition and age-appropriate growth and weight gain . Liprotamase , a nonporcine , highly purified biotechnology-derived PERT , has demonstrated significant efficacy in fat and protein malabsorption in patients with EPI compared to placebo . This study of liprotamase is the first ever long-term trial of a PERT to evaluate safety and nutritional parameters . Methods : This phase III 12-month open-label trial assessed the safety , tolerability , and long-term nutritional effects of liprotamase treatment in patients with CF and EPI 7 years and older . All of the patients were required to discontinue their long-term use of porcine PERTs at the time of enrollment . Dosing started at 1 capsule of liprotamase ( 32,500 US Pharmacopoeia ( USP ) units crystallized cross-linked lipase , 25,000 USP units crystallized protease , and 3,750 USP units amorphous amylase ) per meal or snack ; dose could be increased based on protocol -defined parameters . Results : A total of 215 subjects were enrolled and 214 received at least 1 dose of liprotamase ( mean 5.5 capsules per day ) . During the study period , height , weight , and body mass index z scores and lung function as measured by forced expiratory volume in 1 second were stable . There were no clinical ly meaningful changes in laboratory tests , including levels of fat-soluble vitamins . Liprotamase was well tolerated without any significant safety concerns . Adverse events , primarily gastrointestinal , led to treatment discontinuation for 36 subjects ( 16.8 % ) , most within the first 3 months . Conclusions : Treatment with a mean of 5.5 capsules of liprotamase per day , during meals and snacks , for up to 12 months was safe , well tolerated , and associated with age-appropriate growth and weight gain or weight maintenance in subjects with CF-related EPI Cotazym-S-Forte , a new pancreatic supplement containing 10,000 BP units of lipase activity per capsule , was compared with a st and ard dose pancreatin supplement ( Pancrease ) with 5000 BP units lipase activity in a r and omised crossover trial . The number of capsules of Cotazym-S-Forte administered was half the usual number of Pancrease capsules and was associated with the same degree of fat absorption as Pancrease Background . Pancreatic enzyme replacement therapy is the st and ard of care for treatment of malabsorption in patients with cystic fibrosis ( CF ) and exocrine pancreatic insufficiency ( PI ) . Aim . To evaluate efficacy and safety of a new formulation of pancrelipase ( Ultrase MT20 ) in patients with CF and PI . Coefficients of fat absorption ( CFA% ) and nitrogen absorption ( CNA% ) were the main efficacy parameters . Safety was evaluated by monitoring laboratory analyses , adverse events ( AEs ) , and overall signs and symptoms . Methods . Patients ( n = 31 ) were r and omized in a crossover design comparing this pancrelipase with placebo during 2 inpatient evaluation periods ( 6 - 7 days each ) . Fat and protein/nitrogen ingestion and excretion were measured from food diaries and 72-hour stool collection s. CFA% and CNA% were calculated for each period and compared . Results . Twenty-four patients provided analyzable data . This pancrelipase increased mean CFA% and CNA% ( + 34.7 % and + 25.7 % , resp . , P < .0001 for both ) , reduced stool frequency , and improved stool consistency compared with placebo . Placebo-treated patients reported more AEs , with gastrointestinal symptoms being the most frequently reported AE . Conclusions . This pancrelipase is a safe and effective treatment for malabsorption associated with exocrine PI in patients with CF A st and ard acid resistant microsphere pancreatic enzyme preparation was compared with identical capsules half filled with mini-tablets of a new high lipase preparation in a r and omised double blind crossover study in children with cystic fibrosis . Each patient received his/her usual number of capsules and the same dose of lipase during each period of the study . Eighteen patients completed the study . There were fewer gastrointestinal symptoms when pancreatic enzyme was supplied as the high lipase preparation . There was also a significant improvement in fat absorption ( 17 % , 95 % confidence interval ( CI ) 6 to 27 ) , reduction in faecal fat output ( 15.8 g/day , 95 % CI 6.4 to 22.5 ) , and faecal energy loss ( 789 kJ/day , 95 % CI 211 to 1384 ) . It is concluded that half filled capsules of the new high lipase preparation are more effective than the st and ard preparation and it is likely that filled capsules would allow patients to use fewer than half the number of pancreatic enzyme capsules BACKGROUND EUR-1008 ( Zenpep [ pancrelipase ] ) is a new , enteric-coated , porcine-derived pancreatic enzyme product ( PEP ) developed for the treatment of cystic fibrosis ( CF ) patients with malabsorption associated with exocrine pancreatic insufficiency ( EPI ) . Unlike currently marketed PEPs , EUR-1008 contains the label-cl aim ed lipase content . Safety and efficacy were assessed in younger ( < 7 years ) and older ( > or = 7 years ) CF patients with EPI . METHODS Two multicenter studies were conducted : a r and omized , double-blind , placebo-controlled , crossover trial in patients > or = 7 years of age ( N=34 ) and a supplemental , open-label study in children < 7 years of age ( N=19 ) . Use of any medications altering gastric pH/motility was prohibited during the studies . Outcome measures in the r and omized trial included changes in the coefficient of fat absorption ( CFA ) , coefficient of nitrogen absorption ( CNA ) , and signs/symptoms of malabsorption for EUR-1008 vs. placebo . Outcome measures in the supplemental study included safety and response ( defined as no steatorrhea and no overt signs/symptoms of malabsorption ) to EUR-1008 vs. previous enzyme treatment . RESULTS In the r and omized trial , EUR-1008 treatment compared to placebo result ed in a significantly higher mean CFA ( 88.3 % vs. 62.8 % , respectively ) and CNA ( 87.2 % vs. 65.7 % , respectively ) ( both p<0.001 ) and reduced the incidence of malabsorption signs and symptoms in 32 evaluable patients . In the supplemental study , 11 of 19 patients met the criteria for responder with EUR-1008 at the end of the study vs. 10 of 19 patients at screening ( previous PEP ) , and improvements in clinical symptoms were reported with EUR-1008 treatment . EUR-1008 was safe and well tolerated , and no serious drug-related AEs were reported in either study . CONCLUSIONS EUR-1008 was safe , well tolerated , and effective in CF patients of all ages with EPI-associated malabsorption in two clinical trials . Treatment led to clinical ly and statistically significant improvements in CFA and CNA in the r and omized study , and control of malabsorption and clinical symptoms in both studies BACKGROUND Most cystic fibrosis ( CF ) patients have exocrine pancreatic insufficiency ( EPI ) and need supplementation with pancreatic enzyme replacement therapy ( PERT ) . Liprotamase , a novel non-porcine PERT containing highly purified biotechnology-derived lipase , protease , and amylase , has successfully undergone initial efficacy and safety testing . METHODS In this international phase III parallel-group , r and omized-withdrawal , double-blind placebo-controlled trial , CF patients with EPI 7 years and older , including nutritionally and functionally compromised individuals , underwent baseline testing for coefficients of fat and nitrogen absorption ( CFA and CNA ) and stool weight and frequency while off PERT . After an open-label treatment period with liprotamase , subjects were r and omized 1:1 to one liprotamase or placebo capsule taken with 3 meals and 2 snacks per day . The dose was fixed and increases were not allowed . The same measurements were obtained again after treatment with double-blind study drug or placebo . RESULTS 138 subjects were r and omized . The adjusted least squares mean ( LSM ) difference between the treatment and placebo groups for change in CFA was 15.1 % ( p=0.001 ) for the subgroup with baseline CFA < 40 % , 8.6 % ( p=0.006 ) for subjects with baseline CFA ≥40 % , and 10.6 % ( p<0.001 ) for the overall intent-to-treat population . Similar results were seen for change in CNA . Stool weight was significantly decreased although not stool frequency . Liprotamase was well tolerated with no safety concerns identified . CONCLUSIONS In a CF patient population reflective of that encountered in clinical practice , this trial demonstrated that liprotamase at a fixed dose of one capsule per meal or snack ( 5 capsules per day ) was well tolerated and significantly increased fat absorption as measured by improvement in CFA , significantly increased protein absorption as measured by improvement in CNA , and significantly decreased stool weight Summary We evaluated three acid-resistant pancreatic enzyme preparations by in vitro assays , and by comparing degree of steatorrhea , creatorrhea , fecal wet weight , and stool energy losses in a r and omized crossover study of patients with pancreatic insufficient cystic fibrosis . Aims of the study were to assess ( a ) the most practicable and reliable indicator of malabsorption ; ( b ) the variation in enzyme batch potency ; ( c ) the decline in enzyme batch potency with prolonged shelf life ; and ( d ) the relative bioefficacy of the different preparations . In the in vivo study , absorption of energy , nitrogen , and fat did not differ when comparing the three preparations at roughly pharmaceutically equivalent doses , but when expressed per capsule of pancreatic supplement ingested , absorption reflected relative enzyme content , favoring the higher potency preparations . Although steatorrhea was reasonably controlled by these preparations , stool energy losses varied from 800 to 1,100 kJ per day , suggesting greater attention be paid to overall energy absorption rather than absorption of individual nutrients . In addition , fecal energy loss correlated more closely with fecal wet weight ( r = 0.81 ; p < 0.05 ) than with steatorrhea ( r = 0.40 ; ns ) , such that 1 g wet feces = 8.37 kJ ( ± 0.14 ) . In vitro enzyme potency varied markedly between batches of the same br and , and also a decline of up to 20 % in amylase , lipase , and trypsin activity was noted over an 8-month period for each batch . Both observations have clinical implication s at times of represcription . Finally , the higher potency preparations were more effective per capsule and reduced capsule dosage is therefore attainable Among cystic fibrosis ( CF ) centers , usual doses of enteric coated ( EC ) pancreatic enzymes vary from one to six capsules per meal based upon arbitrary criteria for stool and growth patterns . Large doses of non-EC enzymes are associated with increased serum urate ( SU ) and urinary uric acid ( UUA ) but data are unavailable for EC enzymes . This study compared the effectiveness and safety of a relatively large dose ( patient 's usual dose ) versus a small dose ( 1/4 usual dose ) of EC enzymes in nine nourished children with CF , regarding decreasing fecal fat and stool nitrogen losses and maintaining normal SU and UUA concentrations . A crossover study design r and omly assigned large or small doses to two consecutive 7 day treatment periods within each child . Large doses of EC enzymes reduced steatorrhea and increased SU and UUA . SU was normal with both treatments and UUA was normal , i.e. , 17 of 18 values were between the 10th and 95th percentiles for healthy children eating a normal diet . When fat excretion was greater than 10 % with small doses of EC enzymes , large doses result ed in reduced fat excretion and normal UUA . These data suggest that large doses of EC enzymes reduce steatorrhea and are safe in patients who have malabsorbtion with small doses BACKGROUND The trace metal zinc has a wide range of important physiologic roles . Indirect evidence suggests that fat malabsorption is associated with malabsorption of zinc . The objective of this study was to evaluate the effect of pancreatic enzyme replacement on zinc absorption in children and adolescents with cystic fibrosis . METHODS Subjects were four boys and four girls ranging in age from 7 to 17 years of age . All were pancreatic insufficient . Stable isotope labels , 70Zn and 67Zn , were administered orally in divided doses on consecutive days with meals . Meals were identical on the first 2 study days . Subjects were r and omized to have pancreatic enzyme replacement withheld on the first or second day . All fecal sample s were collected quantitatively for 10 days after label administration and were analyzed individually for total zinc and isotopic enrichment using atomic absorption spectrophotometry and fast atom bombardment mass spectrometry , respectively . Fractional absorption of zinc was calculated from cumulative fecal excretion of unabsorbed label . RESULTS Fractional absorption while receiving enzymes was 0.50 + /- 0.29 versus 0.38 + /- 0.24 while not taking enzymes ( p = 0.05 ) . CONCLUSIONS These results indicate that fractional absorption of zinc is impaired by pancreatic insufficiency in patients with cystic fibrosis , and is improved by exocrine pancreatic enzyme replacement High-strength pancreatic enzyme preparations have recently come into widespread use in some countries for treatment of pancreatic insufficiency in cystic fibrosis . However , the therapeutic equivalence of these preparations to the st and ard acid-resistant microsphere preparations , under the same lipase dosage , has not been demonstrated by appropriate clinical trials ; they are also considered responsible for severe colonic stricture . In a r and omized crossover study , 20 adolescent or adult cystic fibrosis patients were treated in hospital with both low-lipase ( A ) and high-lipase ( B ) enteric-coated microsphere preparations . The fat excretion coefficient , evaluated over two 72-h fat balance periods ( measured fat intake , 1.43 to 3 g/kg/day according to age ) , was the main response variable , secondary variables being stool wet and dry weight , fecal nitrogen output , and energy loss . With both preparations , patients were given a daily dose of 1,500 - 2,000 lipase BP U/g fat ingested , distributed across four meals . The low-strength preparation was divided into three doses during each meal , while the high-strength preparation was taken as a single dose in the middle of each meal . The considerable variability of results did not provide conclusive evidence of equivalence or significant differences between the two preparations in terms of steatorrhea and other variables . However , mean differences between the two treatments and their 95 % confidence intervals showed less satisfactory results with the high-lipase preparation . A high-strength preparation is thought to release relatively less enzyme activity in the small intestine , forcing patients to increase their dosage and possibly creating a dangerous enzyme hyperconcentration in the large intestine . For this reason , the occasional occurrence of colonic stricture should be borne in mind , as must the possible scope for division of dosage during each meal Creon 10,000 Minimicrospherestrade mark ( Creon ) 10,000 MMS ) is a pancreatic enzyme formulation that contains smaller spheres of pancreatin in a 50 % smaller capsule than conventional microspheres ( Creon ) 8,000 ) . This three-centre study investigated the preference of cystic fibrosis ( CF ) patients for these products . In one centre , 72 h stool fat excretion and coefficient of fat absorption ( CFA ) were also compared . Fifty-nine patients with a mean age 10 years ( range 3 - 17 ) took Creon 8,000 ms for 14 days and were then r and omised to 28 days of Creon 8,000 ms followed by 28 days of Creon 10,000 MMS , or vice versa . Dosing was lipase for lipase according to the labelled declaration . At the end of the second treatment period , 51 of 54 patients who completed the study expressed a preference , with a statistically significant preference in favour of Creon 10,000 MMS ( 47/51 ; 87 % ) vs. Creon 8,000 ms ( 4/51 ; 7.4 % ; P<0.0001 ) . Stool fat ( g/day ) and CFA ( % ) were measured in 24 patients at the end of each treatment period : the products were therapeutically equivalent ( Creon 10,000 : 8.4 g/day , 91.3 % CFA ; Creon 8,000 : 6.7 g/day , 93.5 % CFA ) . Both products were well tolerated . In conclusion , in CF children we found a clear preference for Creon 10,000 MMS compared with Creon 8,000 ms with no difference in fat absorption between the two products . Creon 10,000s smaller capsules are easier to take and should aid patient compliance To evaluate cl aims that enteric-coated pancreatic enzyme preparations are more effective than conventional digestants in managing malabsorption in cystic fibrosis ( CF ) , we conducted a trial comparing the efficacy of pancrealipase ( enzyme supplement containing lipase , amylase , and protease ) in the form of pH-sensitive microspheres ( Pancrease ) with that in the form of encapsulated enzyme powder ( Cotazym ) . Ten boys with CF received equivalent dosages in a controlled , double-blind fashion using a r and om sequence of capsule administration with crossover and " washout " periods . Patients experienced significantly enhanced nitrogen and fat absorption while receiving either enzyme when compared with placebo . The enteric-coated product promoted significantly improved fat absorption as compared with the conventional enzyme capsule . Both enzyme preparations caused significantly improved protein absorption as compared with placebo , but there as no significant difference between the two products in the degree of effect on azotorrhea Background : Cystic fibrosis causes exocrine pancreatic insufficiency , leading to malabsorption . Supplemental pancreatic enzyme therapy alleviates the concomitant malnutrition experienced by cystic fibrosis patients . It is recognized that patients experience variations in clinical response to different br and s of enzymes . This has prompted the US Food and Drug Administration to require that enzyme supplements be subjected to New Drug Applications Background : Malabsorption due to exocrine pancreatic insufficiency is the main gastrointestinal problem in cystic fibrosis . Despite high doses of pancreatic enzyme supplements it is often not possible to normalize fat absorption . We compared a new high lipase pancreatic enzyme preparation ( Pancrease‐HL ; Cilag , Brussels , Belgium ) , containing enteric coated microspheres with 25000 U of lipase , 22 500 U of amylase and 1250 U of protease per capsule , with regular Pancrease capsules , containing 5000 U of lipase , 2900 U of amylase and 330 U of protease per capsule Twenty-one stable hospitalized cystic fibrosis patients with malabsorption syndrome participated in an open-label crossover clinical trial to evaluate the efficacy of two-period dosing regimens of a pancreatic microtablet enzyme preparation in the treatment of steatorrhea . St and ard dosing consisted of 500 U lipase/kg body weight/ meal , 250 U lipase/kg body weight/snack ; high dosing consisted of 1,500 U lipase/kg body weight/meal , 750 U lipase/kg body weight/snack . Doses were determined by units of lipase/kg body weight to provide dosing consistency among patients of varying size . Each patient was on a regular diet of – 100 g of fat per day . Two separate , 72-h stool collection s were performed between markers . A significant difference in mean percentage fat absorbed between the st and ard dose and the high dose was found ( 86 % versus 91 % , p < 0.05 ) . Subjects were then stratified into two groups , based on the grams of fecal fat eliminated ( GFFE ) as follows : Group 1 with = s7 GFFE/24 h on both dosages ( n = 7 ) and Group 2 with > 7 GFFE/24 h on either dose ( n = 14 ) . A significant difference ( p < 0.05 ) between Group 1 ( 96 % ) and Group 2 ( 88 % ) was noted in the percentage fat absorbed while on the high dose . Fat absorption improved from 81 % to 88 % , ( p < 0.05 ) in Group 2 . During the study period , the adverse reactions of constipation or elevated serum uric acid levels were not observed . The increased doses of pancreatic enzymes result ed in improved correction of steatorrhea We investigated the therapeutic potential of an acid-resistant fungal lipase prepared from Aspergillus niger . We first demonstrated in vitro that it had a wide pH optimum of 2.5–5.5 and was resistant to pepsin and trypsin . We gave the enzyme or matching placebo in r and om order by mouth with a fatty meal to 10 adult patients with pancreatic steatorrhoea due to cystic fibrosis ( CF ) and sample d gastric contents for the following 2 h. Mean acid-resistant lipase activity was 330 nmol/ml/min free fatty acid released on placebo , compared with 896 nmol/ml/min on fungal lipase ( p = 0.006 for area under the curve ) . We compared this lipase 's clinical efficacy with that of two conventional pancreatin microsphere formulations in an open r and omised crossover fat-balance study in 10 similar patients . Each preparation was given for 2 weeks , and a fat-balance study , using a faecal recovery marker , was performed on the final 3 days ; a period without treatment was also included . The fungal lipase had no effect on faecal wet weight or on the coefficient of fat absorption ( 59.0 % vs. 52.3 % ; NS ) in comparison with placebo . The established enteric-coated microsphere preparation ( Creon ) produced a significant reduction in faecal wet weight and improvement in coefficient of fat absorption ( 81.4 % vs. 52.3 % ; p < 0.01 ) in comparison with placebo . The newer microsphere preparation ( Pancrex M ) was also effective , but perhaps less so than Creon ; there were no significant differences between the two preparations . We conclude that A. niger lipase is resistant to acid and protease and survives intact within the stomach postpr and ially but has no therapeutic effect when used alone , and we discuss why this might be In vitro data indicate that length of enzyme incubation with food critically affects enzyme dissolution and presumably effectiveness . This study compared the effectiveness of enteric coated ( EC ) pancreatic enzymes given before meals with those given during meals ( 15 minutes after beginning of meal ) in reducing steatorrhea in well-nourished children with cystic fibrosis . Eight children ( 6 years 11 months old to 14 years 7 months old ) were studied in the General Clinical Research Center at Indiana University Hospital , Indianapolis . A crossover study design r and omly assigned enzymes before or during meals during two consecutive 7-day treatment periods for each child . No difference in fat excretion was documented for the total group when the children who took enzymes before meals were compared with those who took enzymes during meals . However , a stepwise multiple regression analysis of the difference ( before minus during ) in fat excretion on sex , age , enzyme number , and treatment order documented a positive correlation of age with fat excretion ( r = .83 ) . Mean fat excretion in younger children ( less than 10 years old ) decreased significantly when enzymes were given before meals ( 7.14 + /- 1.95 % ) rather than during meals ( 9.92 + /- 1.61 % ) ( P = .004 ) . The difference in fat excretion ( mean = 2.78 + /- 0.55 % , range = 1.4 % to 4 % ) translates into a half to one full year 's growth potential . Younger children with cystic fibrosis may benefit clinical ly from taking EC enzymes before meals Two studies were performed in children with cystic fibrosis ( CF ) to compare the efficacy and tolerability of pancreatic enzymes prepared as enteric-coated microspheres with that of a conventional enzyme preparation . The parameters evaluated included the following : fecal fat excretion , coefficient of fat absorption , daily caloric intake , percent of diet as fats , proteins and carbohydrates , increase in height and weight , frequency and consistency of stools , palatability of the preparation , and patient compliance . The first study was an open r and omized crossover trial of an enteric-coated microsphere preparation ( Pancrease ) versus conventional pancreatin given alone or with cimetidine . With Pancrease compared to conventional pancreatin , a significant improvement was observed in all the digestive parameters in addition to better patient compliance . In the second study , the response of a group of CF patients given Pancrease for at least 3 months ( 3–67 months ) was retrospectively compared with the response to conventional pancreatin , which had been given to the same patients from 10 months to 8 years earlier . In comparison to conventional pancreatin , Pancrease provided better digestive efficacy and greater increases in the growth rate of teenage patients . With Pancrease , the number of daily dosage units is decreased even when fat intake is increased . No adverse reactions were seen with either of the enzyme preparations used in these studies New high dose pancreatic enzyme preparations could be potentially helpful to cystic fibrosis ( CF ) patients . The purpose of this study was to compare the efficacy of the new high dose pancreatic enzyme preparation , Nutrizym 22 with the st and ard preparation Nutrizym GR . Twenty-five CF children ( aged 7–16 years ) entered the study and 22 completed it ; 3 did not , due to non-compliance . All were taking Nutrizym GR for at least 2 weeks before entering the study . A r and omised double blind , crossover method using st and ard Nutrizym GR or double strength Nutrizym 22 capsules was carried out over two consecutive 14-day periods . Crossover analyses of variance showed no statistically significant differences in actual weight gain , appetite , abdominal pain , stool consistency or faecal fat during the pre study and study periods . It is concluded that half the capsule numbers of the high strength preparation are just as effective as the st and ard capsule dosage OBJECTIVE Enteric-coated ( EC ) high-buffered ( 2.5 mEq [ 2.5 mmol ] bicarbonate per capsule ) pancrelipase microsphere enzymes were compared to EC-nonbuffered pancreatic enzymes for efficacy in reducing steatorrhea in patients with cystic fibrosis . DESIGN Prospect i ve , r and omized , controlled trial using a crossover design with each subject as his/her own control . SUBJECTS/ SETTING Eighteen subjects with cystic fibrosis , who had pancreatic insufficiency and required large enzyme doses , were studied over two consecutive 7-day treatment periods . INTERVENTION Each 7-day period consisted of 3 days at home followed by 4 days in a general clinical research center for careful control of diets , enzyme lipase doses ( given at approximately 50 % of the subject 's usual lipase dose ) , and carmine red-labeled stool collection s for 72-hour fecal fat balance studies . MAIN OUTCOME MEASURE Fecal fat excretion . STATISTICAL ANALYSES PERFORMED Differences in fat excretion , when each subject received EC-high-buffered pancrelipase vs EC-nonbuffered enzymes , were compared using linear modeling . RESULTS Mean fat excretion decreased significantly in each subject during periods when given EC-high-buffered pancrelipase compared with periods when given EC-nonbuffered enzymes ( fat excretion 18.2 % vs 24.9 % or fat absorption 81.8 % vs 75.1 % , respectively ; P=0.01 ) . Thirteen of 18 subjects ( 72 % ) excreted less fat when receiving EC-high-buffered pancrelipase whereas 10 ( 56 % ) decreased fat excretion by more than 5 % , and five subjects did not respond . CONCLUSIONS EC-high-buffered pancrelipase decreased fat excretion , symbolizing improved fat absorption , when compared with EC-nonbuffered pancreatic enzymes given at equivalent , reduced ( approximately 50 % of usual ) lipase doses in nourished subjects with cystic fibrosis and mild pulmonary disease BACKGROUND Pancreatic enzyme replacement therapy ( PERT ) is used to treat exocrine pancreatic insufficiency in cystic fibrosis . RESULTS / METHODS Efficacy and safety of a unique enteric-coated ( EC ) bicarbonate-buffered PERT product ( PERTZYE ® /PANCRECARB ® ; Digestive Care , Inc. , Bethlehem , PA , USA ) was studied in a r and omized , double-blind , placebo-controlled cross-over design . Subjects were stabilized on EC-bicarbonate-buffered PERT and a high-fat diet . During two treatment periods , subjects were r and omized to EC-bicarbonate-buffered PERT or placebo , followed by a 72-h stool collection employing an ingested stool dye marker . Mean coefficient of fat absorption with EC-bicarbonate-buffered PERT was 82.5 % compared with 46.3 % with the placebo ( absolute difference 36.2 % ; p < 0.001 ) , a 78.2 % improvement for active over placebo . Similar improvements in nitrogen absorption were observed . Overall stool frequency and stool weight decreased ( p < 0.001 ) . No safety concerns were identified . SUMMARY EC-bicarbonate-buffered PERT is effective in treating cystic fibrosis-associated exocrine pancreatic insufficiency In an open , r and omised crossover study enteric coated microspheres of pancreatin were compared with a st and ard preparation of enteric coated pancreatin over two consecutive 28 day treatment periods in 23 adults with steatorrhoea due to cystic fibrosis . Lipase intake was equal to the patients ' previous requirements and was the same during the two months . Patients performed 72 hour faecal collection s at the end of each month and completed diary cards daily throughout . Comparison of the month of treatment with enteric coated microspheres with the month of st and ard enteric coated tablets showed a significant increase in body weight on microsphere capsules ( p less than 0.02 ) . There was also a reduced frequency of bowel actions ( p less than 0.001 ) and abdominal pain ( p less than 0.05 ) , and improvement in stool character ( p less than 0.001 ) on microsphere capsules . Faecal fat excretion was reduced by 44 % with the microsphere capsules ( p less than 0.01 ) , and 86 % of patients showed an increased coefficient of fat absorption ( mean increase 13 % , 95 % confidence limits 6.5 - 19.1 % ; p less than 0.001 ) . Eighty one per cent of patients preferred microsphere capsules of the two treatments . Thus enteric coated microsphere capsules are more effective in treating steatorrhoea in cystic fibrosis than st and ard enteric coated tablets UNLABELLED Maldigestion in cystic fibrosis ( CF ) affects approximately 90 % of patients . As soon as pancreatic insufficiency is identified , enzyme supplementation is prescribed even with breast fed infants . A pancreatic enzyme preparation developed particularly for infants , Creon for children ( CfC ) , contains smaller granules to be administered with a dosing spoon ( 5000 lipase units per scoop ) . PATIENTS AND METHODS In a prospect i ve , r and omised , multi-centre study , 40 infants and toddlers received both CfC and Creon 10000 ( C10 ) for two weeks each in a cross-over design . Dosing of pancreatic enzymes was continued as applied before the study . The primary endpoint was the parents ' treatment preference . Secondary endpoints included coefficient of fat absorption ( CFA ) , clinical symptoms and safety parameters . RESULTS 20 parents ( 51 % ) from the N=39 intent to treat sample preferred CfC , 9 ( 23 % ) preferred C10 , and 10 ( 26 % ) had no preference The applied doses led to a mean CFA with similar results for both treatments ( 77.8 % vs. 78.7 % ) . Gastrointestinal symptoms were reported on a number of study days , and some children had abnormal results for laboratory parameters of malabsorption . Safety and tolerability of the preparations were good and all these parameters were comparable for both treatments . CONCLUSION Those parents who had a preference favoured CfC over C10 . Both enzyme preparations improved malabsorption to a similar degree , although the applied dosages could have been too low in some children reflected in a suboptimal CFA . These data support the use of CfC for young patients with cystic fibrosis improving the daily care of this cohort detected mainly now through neonatal screening programmes BACKGROUND AND AIMS A simple non-invasive test not requiring the use of radioactive isotopes is required to assess fat malabsorption in adult cystic fibrosis ( CF ) patients . Breath tests using substrates labeled with 13C meet these conditions . The 14C-triolein breath test is sensitive and specific for measuring fat malabsorption , but involves radiation exposure . The aim of this study was to examine the utility of a test using a 13C label and to determine whether pancreatic replacement therapy would return the test to the values of a normal control group . METHODS 13CO2 recovery was assessed after an overnight fast in six adult patients with CF , both with and without pancreatic enzyme replacement therapy ( PERT ) in the usual dose for a light snack , in a r and omized order , on different days . Studies were also performed in eight healthy volunteers after oral ingestion . Subjects drank 50 mL of a liquid meal mixed with 200 microL 13C-triolein and breath sample s were collected by blowing through a straw into collection tubes every 30 min for 6 h. The effect of gastric emptying was assessed by comparison of oral ingestion with intraduodenal infusion . Intra-individual variability was assessed in nine volunteers by repeating the breath test after drinking the test meal on a separate day . RESULTS Compared with healthy subjects there was virtually no recovery of 13CO2 in CF patients without PERT . The median ( interquartile range ) cumulative percentage dose recovery ( cPDR ) at 6 h was 3 % ( 0 - 8 ) in CF patients compared with 28 % ( 22 - 41 ) in healthy controls ( P < 0.01 ) . Fat absorption was normalized ( 37 % ) ( 36 - 43 ) after ingestion of PERT . Gastric emptying delayed the peak in 13CO2 recovery , but there was no difference in the cPDR at 6 h. There was no difference in recovery between days 1 and 2 . CONCLUSIONS The 13C-triolein breath test is a simple and reproducible method to measure fat malabsorption . The test provides a screening technique for fat malabsorption in adult CF patients and may be useful for monitoring the lowest effective dose of PERT BACKGROUND Pancreatic enzyme replacement therapy is critical for adequate nutrition in cystic fibrosis ( CF ) patients with exocrine pancreatic insufficiency ( EPI ) . METHODS This was a double-blind , r and omised , placebo-controlled , two-period crossover study assessing efficacy and safety of Creon 24,000-unit capsules in CF subjects > or = 12 years with EPI . Patients were r and omised to one of two 5-day sequences , Creon/placebo or placebo/Creon ( target dose , 4000 lipase units/g fat ) . Primary outcome was the coefficient of fat absorption ( CFA ) ; secondary outcomes were coefficient of nitrogen absorption ( CNA ) , symptoms , and safety . RESULTS Thirty-two subjects were r and omised . Mean CFA and CNA were significantly greater with Creon than placebo ( CFA , 88.6 % vs. 49.6 % ; CNA , 85.1 % vs. 49.9 % ; p<0.001 for both ) . Symptoms were improved and fewer treatment-emergent adverse events were reported with Creon than placebo . One patient discontinued for weight loss unrelated to study drug . CONCLUSIONS This study demonstrated Creon was effective in treating EPI due to CF and was safe and well tolerated OBJECTIVE To evaluate the safety and efficacy of a novel microbial lipase ( NM-BL ) in a liquid formulation for the treatment of exocrine pancreatic insufficiency ( EPI ) in patients with cystic fibrosis ( CF ) in a phase IIa proof-of-concept study . STUDY DESIGN We conducted a double-blind , r and omized , placebo controlled crossover study in patients with cystic fibrosis and exocrine pancreatic insufficiency . Adolescent and adult patients with CF were r and omized to receive NM-BL or placebo for 1 week as replacement for their usual pancreatic enzyme formulation . They were subsequently crossed-over to the alternate study treatment . The coefficient of fat absorption was evaluated as the primary endpoint . Symptoms and adverse events were evaluated as secondary endpoints . RESULTS A total of 35 patients were r and omized into the study and 22 patients completed both treatment periods . During treatment with NM-BL , the coefficient of fat absorption was significantly greater ( 72.7 % ) compared with placebo ( 53.8 % ) with a difference between groups of 18.8 % ( P < .001 ) . Subjective assessment of stool fat and stool consistency also improved under treatment with NM-BL . Adverse events were mostly gastrointestinal in nature and were more common in the group receiving NM-BL . CONCLUSIONS Currently available pancreatic enzyme products are limited because of the lack of liquid formulations and being largely porcine based . The novel microbial lipase NM-BL was safe and effective in this short term trial . The trial provided clinical proof-of-concept for this novel microbial lipase as a treatment for EPI in CF . A larger phase 2 dose ranging trial is warranted . TRIAL REGISTRATION Clinical Trials.gov : NCT01710644 A cross-over trial of pancreatic enzyme replacement therapy has been conducted on 12 children with cystic fibrosis using Pancrex V forte and Nutrizym tablets in equivalent dosage . No differences were found in the effectiveness of these products as measured by stool volume , number of bowel actions , faecal fat excretion , and urine urea excretion . Neither product eliminated the steatorrhoea . Though there was no laboratory evidence to support their choice nine patients expressed a preference for Nutrizym at the conclusion of the trial . This preference was based partly on the smaller number of tablets which are required BACKGROUND Pancreatic exocrine insufficiency is a common condition in patients with cystic fibrosis . Large amounts of pancreatic enzyme supplements are required to reduce malabsorption but patient compliance is not always optimal . AIMS To compare patients ' preference and the efficacy of two enteric coated microsphere preparations in patients with cystic fibrosis . PATIENTS Patients with pancreatic exocrine insufficiency due to cystic fibrosis . METHODS Patients were assigned to the crossover treatment with Creon or Pancrease for 1 week and then to the alternative treatment . Patients had to follow a fixed diet ( at least 2 g fat/kg ) and had to assume 1000 units lipase/g fat . The evaluation parameters were : patients ' preference , acceptance of therapy , stool fat excretion , stool weight , gastrointestinal symptoms , and tolerance . RESULTS AND CONCLUSIONS Of the 33/60 patients who expressed a preference for one of the two treatments , 30 preferred Creon while only 3 patients preferred Pancrease ( p<0.001 ) . No difference between the two treatments was observed regarding stool characteristics , gastrointestinal symptoms and tolerance . The mean number of capsules taken daily was reduced by 35 % with Creon . The results of this study showed a preference in favour of Creon probably due to the reduction of daily capsule intake of 35 % , supporting digestion as well as Pancrease CONTEXT Postpr and ial hyperglycemia is an important clinical problem in cystic fibrosis ( CF ) , but the contribution of fat malabsorption , rapid gastric emptying , and the incretin axis has not been widely considered . OBJECTIVE The aim of this study was to evaluate these aspects of gut function in nondiabetic CF patients . DESIGN AND SETTING We conducted a r and omized , double-blind , placebo-controlled crossover study at a clinical research laboratory . PATIENTS Five nondiabetic CF patients ( three males ; age , 25.8 ± 1.0 yr ; body mass index , 20.2 ± 1.1 kg/m(2 ) ) with exocrine pancreatic insufficiency and six healthy subjects of similar age and body mass index participated in the study . INTERVENTIONS CF patients consumed a radiolabeled mashed potato meal on 2 separate days , together with four capsules of Creon Forte ( 100,000 IU lipase ) or placebo . Healthy subjects consumed the meal once , without pancreatic enzymes . MAIN OUTCOME MEASURES Gastric emptying was measured using scintigraphy , and blood was sample d frequently for blood glucose and plasma glucagon-like peptide-1 ( GLP-1 ) , glucose-dependent insulinotropic polypeptide ( GIP ) , and glucagon concentrations . RESULTS CF patients had more rapid gastric emptying ( P < 0.001 ) , impaired secretion of GLP-1 ( P < 0.01 ) and GIP ( P < 0.001 ) , and greater postpr and ial glycemic excursions ( P < 0.001 ) than healthy subjects . Pancreatic enzyme supplementation normalized gastric emptying and GLP-1 secretion and tended to increase glucagon ( P = 0.08 ) , but did not completely restore GIP secretion or normalize postpr and ial blood glucose . There was an excellent correlation between gastric emptying and blood glucose concentration at 60 min ( R = 0.75 ; P = 0.01 ) . CONCLUSIONS Pancreatic enzyme supplementation plays an important role in incretin secretion , gastric emptying , and postpr and ial hyperglycemia in CF Over the past 5 years , the Leeds Regional Cystic Fibrosis ( CF ) Unit has provided comprehensive annual assessment s of CF patients that include dietary assessment s and fat absorption studies . Enteric-coated microsphere pancreatic enzyme preparations ( micro-sphere preparations ) were compared to conventional enzymes as therapeutic agents for these patients . Presently in the U.K. , two microsphere preparations are licensed for use and a further two products are likely to receive licenses in the near future . The success of these preparations is dependent on the ability of the microsphere coating to resist dissolution until the pH exceeds approximately 5.5 and thus prevent inactivation of lipase in the acid environment of the stomach . A study comparing Pancrex V Forte , a conventional enzyme preparation , to three microsphere preparations , Pancrease , Creon , and pancreatin Merck , confirmed the superiority of Pancrease and Creon over Pancrex V Forte and pancreatin Merck with regard to control of symptoms , and nitrogen and fat absorption . Because of differences in the physical characteristics of various microsphere preparations , the dissolution rates of Pancrease , Creon , and pancreatin Merck were compared in vitro . In aqueous buffers , striking differences among the preparations were seen at pH 5.5 ; whereas only 25 % of available lipase was released from Creon , both Pancrease and pancreatin Merck show almost complete dissolution at this pH. Only at pH 6.5 and above do all three preparations show complete dissolution . In duodenal juice , as in aqueous buffers , lipase release from Creon takes place at a lower rate than with the other two preparations until pH 6.0 or higher is attained . Bile salts at pH 5.75 accelerate lipase release from Creon microspheres but not from those of Pancrease or pancreatin Merck . Albumin at pH 5.75 had no effect on the dissolution rate of any of the three microsphere preparations In an attempt to critically examine the therapeutic efficacy of pH-sensitive entericcoated pancreatic enzyme preparations in patients with pancreatic insufficiency due to cystic fibrosis , postpr and ial duodenal concentration and recovery of orally administered pancreatic enzymes , duodenal pH , and coefficient of fat absorption were determined in eight cases after ingestion of equivalent dosage of enteric-coated as well as conventional enzyme preparations . Ingestion of a pH-sensitive enteric-coated pancreatic enzyme preparation was accompanied with a significant ( P<0.05 ) reduction in steatorrhea , as well as a lower mean concentration and recovery of lipase and trypsin activity in the postpr and ial duodenal sample s. Furthermore , the intraluminal duodenal pH was noted to be below 4.0 during the postpr and ial period in all patients . These data suggest that in cystic fibrosis , the greater therapeutic efficacy of pH-sensitive enteric-coated preparations over conventional preparations may be related to the protection of pancreatic enzymes from the highly acidic milieu in the duodenum , allowing for possible bioavailability in the distal small intestine Four different pancreatin products , Pancrease , Creon , Pancrex V Forte , and Pancreatin Merck , were compared in a r and om crossover trial in children with cystic fibrosis . The results of our study showed that patients who received Creon and Pancrease had fewer gastrointestinal symptoms than patients who received Pancrex V Forte and Pancreatin Merck . Fat absorption was significantly improved with Pancrease when compared with Pancrex V forte and Pancreatin Merck . Also the fat absorption with Creon was superior to that with Pancrex V Forte . There was no significant difference in fat absorption between Pancrease and Creon . Pancrex V Forte and Pancreatin Merck , or Pancreatin Merck and Creon . Faecal nitrogen content was less with both Creon and Pancrease compared with Pancreatin Merck . Creon and Pancrease allow the patient with cystic fibrosis to take a high energy diet without any dietary restrictions OBJECTIVES To assess the efficacy of combining unprotected powder enzymes and oral enteric-coated microsphere ( ECM ) and to ECM alone in treating nutrient maldigestion in patients with cystic fibrosis . STUDY DESIGN Patients were r and omly assigned into 2 consecutive , 2-week phases ; ECM alone , and ECM plus unprotected powder enzymes . Fecal fat , energy , and nitrogen output were compared with intake at the end of each phase . Two-tailed , paired t tests were performed to compare outcomes . RESULTS The mean age of the 14 patients ( 3 girls ) was 5.7 + /- 3.2 years ( range , 1.9 to 13.4 years ) . There was no significant difference in percent malabsorption of fat ( 15.6 % vs 18.2 % ) , energy ( 13.3 % vs 13.4 % ) , or nitrogen ( 11.8 % vs 11.3 % ) between phases . CONCLUSIONS The addition of powder enzymes to ECM did not improve nutrient maldigestion compared with ECM alone Objectives : To compare the efficacy of an enteric-coated buffered pancreatic enzyme ( EC buffered PE ) containing 1.5 mEq of bicarbonate per capsule with a conventional enteric-coated enzyme ( EC-PE ) capsule in cystic fibrosis patients with signs or symptoms of moderate to severe malabsorption . Methods : In a double-blind crossover study , subjects were r and omly assigned to two consecutive , 2-week phases using an EC buffered PE product and conventional EC-PE product . Seventy-two hour stool collection s from each phase were analyzed for energy , fat , and nitrogen content and expressed as percent of estimated intake . Results : Twenty-one patients with cystic fibrosis and pancreatic insufficiency ( 14 female , mean age 20.6 ± 11.5 years , range 8.8 - 41.9 ) completed the study . There was no significant difference in percent malabsorption of energy ( 19.4 % vs. 19.0 % ) , fat ( 20.7 % vs. 20.2 % ) , or nitrogen ( 10.4 % vs. 10.7 % ) between the EC buffered PE product and the conventional EC-PE product . However , patients taking the EC buffered PE product received less enzyme based on actual enzyme activity measured in vitro ( 3,468 ± 1,434 U lipase/g fat vs. 3,978 ± 1,474 U lipase/g fat , P < 0.02 ) . Conclusions : In the doses used , nutrient absorption of patients taking EC buffered PE preparation offers no advantage over a conventional EC-PE preparation Background : Pancreatic enzyme replacement therapy ( PERT ) improves nutritional status and growth in patients with cystic fibrosis ( CF ) with pancreatic insufficiency ( PI ) . The current recommendation for infants and young children , who are not able to swallow the whole capsule , is to open the capsule and mix the beads in a spoon with some applesauce ; however , the efficacy and safety data of this approach are currently lacking . The aim of this study was to assess the efficacy , palatability ( ease of swallowing ) , and safety of 4 dose levels of pancrelipase microtablets ( Pancrease MT ) in infants and young children with CF-related PI . Patients and Methods : This study was a phase II r and omized , investigator-blinded , parallel-group pilot study in DNA-proven infants with CF and PI . The study design included a run-in period ( days 1–5 ) and an experimental period ( days 6–11 ) . Pancrelipase microtablets ( 2-mm , enteric coated ) were provided orally . Sixteen subjects , 6 to 30 months of age , were provided 500 U lipase/kg/meal for 5 days ( baseline period ) . Subsequently , subjects were r and omly assigned to 1 of 4 treatment groups ( each n = 4 ) , receiving 500 , 1000 , 1500 , or 2000 U ( Ph . EUR ) of lipase/kg/meal , respectively , for 5 days ( experimental period ) . The primary endpoint was medication efficacy assessed by the 72-hour fecal fat excretion , expressed as coefficient of fecal fat absorption ( CFA ) , and 13C mixed triglyceride breath test . Secondary endpoints were safety and palatability . Results : Overall compliance , defined as used study medication , was 89 % to 99 % for the entire study . None of the 4 dose regimens significantly influenced the CFA , relative to the baseline period ( median range 83%–93 % ) . During the run-in period the median cumulative % 13C was 11 ( range −8 to 59 ) . After r and omization the median cumulative % 13C was 18 ( range 14–23 ) in the 500-U , 14 ( range −1 to 17 ) in the 1000-U , 10 ( range 10–27 ) in the 1500-U , and 3 ( range 1–49 ) in the 2000-U groups . Palatability was scored fair to good by the parents in each of the treatment groups . Gastrointestinal symptoms were reported in some patients , including common adverse events reported in clinical trials involving pancreatic enzyme therapy . No serious or other adverse events were reported . Conclusion : Treatment with Pancrease MT at a dosage of 500 U lipase/kg/meal result ed in a CFA of approximately 89 % in pediatric subjects ages 6 to 30 months with PI result ing from CF . Pancrease MT doses were well tolerated and mean palatability was scored as fair to good . Present results do not indicate that a dosage higher than 500 U ( Ph . EUR ) lipase/kg/meal increases the coefficient of fat absorption in a cohort of infants 6 to 30 months of age During two treatment periods ( 4 weeks each ) , serum immunoreactive trypsin ( IRT ) , immunoreactive human lipase in stool ( IRL ) , and chymotrypsin ( CT ) activity in stool were determined in 16 cystic fibrosis patients and compared with fecal fat excretion ( 72-h sampling ) . Fecal fat estimation revealed mild to severe steatorrhea in all 16 patients ( X = 13.7 + /- 9.0 g/24 h ) in at least one study period . Stool fat excretion was highest in underweight adolescents and adults . Comparison of IRT and IRL with stool fat values showed no significant statistical correlation . IRT values revealed an inverse exponential correlation with age , with a steep decline at the age of 5 years . CT levels were very high in 14 of our 16 patients during supplementation therapy , whereas 2 patients showed subnormal CT values . We conclude that since indirect parameters of pancreatic function do not correlate with stool fat excretion , stool fat remains the best indirect parameter for the assessment of pancreatic insufficiency in cystic fibrosis . Leaving pancreatic enzyme supplementation in cystic fibrosis patients on the basis of normal serum trypsin or fecal lipase values does not appear to be adequate OBJECTIVES We studied a novel pancreatic enzyme product , ALTU-135 , a proprietary formulation of microbially derived lipase , protease , and amylase , to determine its efficacy and safety in treatment of pancreatic insufficiency ( PI ) in patients with cystic fibrosis ( CF ) . STUDY DESIGN Ambulatory subjects with CF-PI ( n = 117 ) had baseline coefficient of fat and nitrogen absorption ( CFA and CNA , respectively ) determined in an inpatient setting while not receiving pancreatic enzyme replacement therapy . Subjects were then r and omized to treatment with ALTU-135 containing 5000 ( low ) , 25,000 ( mid ) , or 100,000 ( highest ) units of lipase ( 1:1:0.15 of lipase : protease : amylase ) for 28 days . After 14 days , CFA and CNA were re-measured . The primary outcomes were change from baseline in CFA and CNA between treatments . RESULTS Treatment CFA was significantly greater in the mid and highest dose groups compared with that in the low dose group ( P = .0229 and P = .0041 , respectively ) ; findings were similar for CNA . Subjects with baseline CFA < or = 40 % and > 40 % in the 2 higher dose groups had a mean increase of 31 and 8 percentage points in CFA , respectively ( P < .0001 ) . CONCLUSION ALTU-135 was efficacious during the 1-month study period at the dose of 25,000 units of lipase , 25,000 units of protease , and 3750 units of amylase |
12,787 | 17,434,764 | The authors draw the conclusion , using defective review material , that removal of smear layer enhances the seal of the root filling . | In many areas of medicine the amount of published information is increasing at an exponential rate , making it difficult for the clinician to condense the data to a manageable amount of valuable and useful information .
Systematic review s have been suggested as a remedy for this information overload .
Such review s are regarded as the highest level of evidence .
Certain statistical methods , e.g. , meta- analysis , have also been introduced for the calculation of a more comprehensive summation of the compiled results from studies with small sample sizes .
These findings would then serve as an authoritarian guide for evidence -based practice .
Endodontists have lately jumped on the b and wagon of systematic review s and meta-analyses , and papers on various topics are being published .
Well done , such comprehensive information would be very useful and authoritative for the practitioner .
Alarmingly , the quality of these recent publications is negatively correlated to the frequency .
This can have serious consequences in the clinical arena if spurious information is given a seal of approval when communicated as facts in refereed journals .
In these studies , however , sources of bias are often not controlled .
Therefore , even the best review and meta- analysis becomes useless if it is based on poorly design ed research .
Furthermore , clinical protocol s often have many important “ proprietary ” modifications that make comparison difficult . | AIM The purpose of the present study is to evaluate the healing of periapical lesions of teeth with positive and negative canal cultures at the time of obturation , and to evaluate the periapical healing of teeth treated in one visit ( without ) or in two visits with an interappointment dressing of calcium hydroxide . METHODOLOGY Thirty-nine patients received root-canal treatment . In the first visit , teeth were instrumented , and 18 of these teeth were filled ( after microbiological sampling ) with calcium hydroxide in sterile saline . The other 21 teeth were obturated with gutta-percha and AH-26 sealer after microbiological sampling . Four weeks later , the teeth with calcium hydroxide were accessed again and after microbiological sampling they were obturated with gutta-percha and AH-26 sealer . Healing of periapical radiolucency was recorded over a period up to 4.5 years . RESULTS In both the treatment groups , the size of the periapical lesions reduced significantly during the follow-up period . Complete radiographic healing was observed in 81 % of the cases in the one-visit group , and in 71 % of the cases in the two-visit group . The probability of success increased continuously over time for both treatment groups . Seven out of eight cases ( 87.5 % ) that showed a positive root-canal culture at the time of obturation healed . The number of colony forming units ( CFU ) in six out of eight positive canals was < 10(2 ) CFU mL(-1 ) . CONCLUSIONS Within the limitations of this study , no significant differences in healing of periapical radiolucency was observed between teeth that were treated in one visit ( without ) and two visits with inclusion of calcium hydroxide for 4 weeks . The presence of a positive bacterial culture ( CFU<10(2 ) ) at the time of filling did not influence the outcome of treatment AIM This prospect i ve clinical study explored the influence of calcium hydroxide as an interappointment dressing on the healing of periapical lesions associated with pulpless teeth that had not been endodontically treated previously . This was achieved by comparing the prognosis after a two-visit root canal treatment with that following a one-visit treatment . METHODOLOGY Seventy-three patients were recruited having one tooth with an endodontically induced lesion . Of these patients , 67 could be re-examined . Calcium hydroxide was placed in the instrumented root canals of 31 teeth for at least one week and the treatment finished at the second visit . Thirty-six teeth were root canal treated at one visit . The criteria for success were the absence of signs and symptoms indicating an acute phase of periapical periodontitis and radiographically a periodontal ligament space of normal width . Methods for event time analysis were used to evaluate and compare the prognosis of both treatment approaches . RESULTS The probability that complete periapical healing will take place increased continuously with the length of the observation period . In both treatment groups the likelihood that the root canal treatment yields a success within an observation time of five years exceeded 90 % . A statistically significant difference between the two treatment groups could not be detected . CONCLUSIONS From a microbiological perspective , one-visit root canal treatment created favourable environmental conditions for periapical repair similar to the two-visit therapy when calcium hydroxide was used as antimicrobial dressing . One-visit root canal treatment is an acceptable alternative to two-visit treatment for pulpless teeth associated with an endodontically induced lesion This study was performed to evaluate radiographic healing of teeth with apical periodontitis , treated in one visit or in two visits ( a ) with or ( b ) without calcium hydroxide as an intracanal disinfecting medicament . The patients were assigned one of the three treatment groups by the throwing of a die . The Periapical Index ( PAI ) Scoring Method was used to compare differences in periapical status from the beginning of treatment to a 52-wk follow-up evaluation . Overall , the periapical status of the treated teeth improved significantly after 52 wk ( p < 0.0001 ) . A PAI score of 1 or 2 was considered as representing a " good " periapical status while 3 , 4 , or 5 was a " bad " status . When base line PAI scores were controlled for , the calcium hydroxide group showed the most improvement in PAI score ( 3 , 4 , or 5 to 1 or 2 ) , followed by the one-step group ( 74 % vs. 64 % ) . The teeth that were left empty between visits had clearly inferior healing results . Power statistics were conducted to determine the numbers required for significant differences between the groups , and it was shown that large experimental groups on the order of hundreds of patients would be required to show significant differences |
12,788 | 25,043,423 | Participants in GLP-1RA groups achieved a larger weight loss than those in control groups ( -2.85 kg , 95%CI -3.55 to -2.14 ) , and liraglutide may work in a dose-dependent fashion .
GLP-1RAs also reduced body mass index ( BMI ) and waist circumferences ( WC ) and benefited systolic blood pressure and triglyceride regulation .
But GLP-1RAs were associated with increased nausea and vomiting events .
GLP-1 mimetics induce a weight loss in addition to BMI and WC reduction in obese/overweight adults without diabetes . | BACKGROUND Glucagon-like peptide-1 receptor agonists ( GLP-1RAs ) benefit weight maintenance for diabetic patients .
We performed a systematic review to evaluate its weight loss effect on obese/overweight patients without diabetes in r and omized controlled trials ( RCTs ) . | BACKGROUND Exenatide , an incretin mimetic for adjunctive treatment of type 2 diabetes ( T2DM ) , reduced hemoglobin A(1c ) ( A1C ) and weight in clinical trials . The objective of this study was to evaluate the effects of > or = 3 years exenatide therapy on glycemic control , body weight , cardiometabolic markers , and safety . METHODS Patients from three placebo-controlled trials and their open-label extensions were enrolled into one open-ended , open-label clinical trial . Patients were r and omized to twice daily ( BID ) placebo , 5 mug exenatide , or 10 mug exenatide for 30 weeks , followed by 5 mug exenatide BID for 4 weeks , then 10 mug exenatide BID for > or = 3 years of exenatide exposure . Patients continued metformin and /or sulfonylureas . RESULTS 217 patients ( 64 % male , age 58 + /- 10 years , weight 99 + /- 18 kg , BMI 34 + /- 5 kg/m(2 ) , A1C 8.2 + /- 1.0 % [ mean + /- SD ] ) completed 3 years of exenatide exposure . Reductions in A1C from baseline to week 12 ( -1.1 + /- 0.1 % [ mean + /- SEM ] ) were sustained to 3 years ( -1.0 + /- 0.1 % ; p < 0.0001 ) , with 46 % achieving A1C < or = 7 % . Exenatide progressively reduced body weight from baseline ( -5.3 + /- 0.4 kg at 3 years ; p < 0.0001 ) . Patients with elevated serum alanine aminotransferase ( ALT ) at baseline ( n = 116 ) had reduced ALT ( -10.4 + /- 1.5 IU/L ; p < 0.0001 ) and 41 % achieved normal ALT . Patients with elevated ALT at baseline tended to lose more weight than patients with normal ALT at baseline ( -6.1 + /- 0.6 kg vs. -4.4 + /- 0.5 kg ; p = 0.03 ) , however weight change was minimally correlated with baseline ALT ( r = -0.01 ) or ALT change ( r = 0.31 ) . Homeostasis Model Assessment B ( HOMA-B ) , blood pressure , and aspartate aminotransferase ( AST ) all improved . A subset achieved 3.5 years of exenatide exposure and had serum lipids available for analysis ( n = 151 ) . Triglycerides decreased 12 % ( p = 0.0003 ) , total cholesterol decreased 5 % ( p = 0.0007 ) , LDL-C decreased 6 % ( p < 0.0001 ) , and HDL-C increased 24 % ( p < 0.0001 ) . Exenatide was generally well tolerated . The most frequent adverse event was mild-to-moderate nausea . The main limitation of this study is the open-label , uncontrolled nature of the study design which does not provide a placebo group for comparison . CONCLUSION Adjunctive exenatide treatment for > or = 3 years in T2DM patients result ed in sustained improvements in glycemic control , cardiovascular risk factors , and hepatic biomarkers , coupled with progressive weight reduction OBJECTIVE To assess the effects of exenatide on body weight and glucose tolerance in nondiabetic obese subjects with normal or impaired glucose tolerance ( IGT ) or impaired fasting glucose ( IFG ) . RESEARCH DESIGN AND METHODS Obese subjects ( n = 152 ; age 46 ± 12 years , female 82 % , weight 108.6 ± 23.0 kg , BMI 39.6 ± 7.0 kg/m2 , IGT or IFG 25 % ) were r and omized to receive exenatide ( n = 73 ) or placebo ( n = 79 ) , along with lifestyle intervention , for 24 weeks . RESULTS Exenatide-treated subjects lost 5.1 ± 0.5 kg from baseline versus 1.6 ± 0.5 kg with placebo ( exenatide − placebo , P < 0.001 ) . Placebo-subtracted difference in percent weight reduction was −3.3 ± 0.5 % ( P < 0.001 ) . Both groups reduced their daily calorie intake ( exenatide , −449 cal ; placebo , −387 cal ) . IGT or IFG normalized at end point in 77 and 56 % of exenatide and placebo subjects , respectively . CONCLUSIONS Exenatide plus lifestyle modification decreased caloric intake and result ed in weight loss in nondiabetic obesity with improved glucose tolerance in subjects with IGT and IFG OBJECTIVE The aim was to evaluate the ability of liraglutide to augment weight loss and improve insulin resistance , cardiovascular disease ( CVD ) risk factors , and inflammation in a high-risk population for type 2 diabetes ( T2DM ) and CVD . RESEARCH DESIGN AND METHODS We r and omized 68 older individuals ( mean age , 58 ± 8 years ) with overweight/obesity and prediabetes to this double-blind study of liraglutide 1.8 mg versus placebo for 14 weeks . All subjects were advised to decrease calorie intake by 500 kcal/day . Peripheral insulin resistance was quantified by measuring the steady-state plasma glucose ( SSPG ) concentration during the insulin suppression test . Traditional CVD risk factors and inflammatory markers also were assessed . RESULTS Eleven out of 35 individuals ( 31 % ) assigned to liraglutide discontinued the study compared with 6 out of 33 ( 18 % ) assigned to placebo ( P = 0.26 ) . Subjects who continued to use liraglutide ( n = 24 ) lost twice as much weight as those using placebo ( n = 27 ; 6.8 vs. 3.3 kg ; P < 0.001 ) . Liraglutide-treated subjects also had a significant improvement in SSPG concentration ( −3.2 vs. 0.2 mmol/L ; P < 0.001 ) and significantly ( P ≤ 0.04 ) greater lowering of systolic blood pressure ( −8.1 vs. −2.6 mmHg ) , fasting glucose ( −0.5 vs. 0 mmol/L ) , and triglyceride ( −0.4 vs. −0.1 mmol/L ) concentration . Inflammatory markers did not differ between the two groups , but pulse increased after liraglutide treatment ( 6.4 vs. −0.9 bpm ; P = 0.001 ) . CONCLUSIONS The addition of liraglutide to calorie restriction significantly augmented weight loss and improved insulin resistance , systolic blood pressure , glucose , and triglyceride concentration in this population at high risk for development of T2DM and CVD Objective : Having demonstrated short-term weight loss with liraglutide in this group of obese adults , we now evaluate safety/tolerability ( primary outcome ) and long-term efficacy for sustaining weight loss ( secondary outcome ) over 2 years . Design : A r and omized , double-blind , placebo-controlled 20-week study with 2-year extension ( sponsor unblinded at 20 weeks , participants /investigators at 1 year ) in 19 European clinical research centers . Subjects : A total of 564 adults ( n=90–98 per group ; body mass index 30–40 kg m−2 ) enrolled , 398 entered the extension and 268 completed the 2-year trial . Participants received diet ( 500 kcal deficit per day ) and exercise counseling during 2-week run-in , before being r and omly assigned ( with a telephone or web-based system ) to once-daily subcutaneous liraglutide ( 1.2 , 1.8 , 2.4 or 3.0 mg , n=90–95 ) , placebo ( n=98 ) or open-label orlistat ( 120 mg × 3 , n=95 ) . After 1 year , liraglutide/placebo recipients switched to liraglutide 2.4 mg , then 3.0 mg ( based on 20-week and 1-year results , respectively ) . The trial ran from January 2007–April 2009 and is registered with Clinical trials.gov , number NCT00480909 . Results : From r and omization to year 1 , liraglutide 3.0 mg recipients lost 5.8 kg ( 95 % confidence interval 3.7–8.0 ) more weight than those on placebo and 3.8 kg ( 1.6–6.0 ) more than those on orlistat ( P⩽0.0001 ; intention-to-treat , last-observation-carried-forward ) . At year 2 , participants on liraglutide 2.4/3.0 mg for the full 2 years ( pooled group , n=184 ) lost 3.0 kg ( 1.3–4.7 ) more weight than those on orlistat ( n=95 ; P<0.001 ) . Completers on liraglutide 2.4/3.0 mg ( n=92 ) maintained a 2-year weight loss of 7.8 kg from screening . With liraglutide 3.0 mg , 20-week body fat decreased by 15.4 % and lean tissue by 2.0 % . The most frequent drug-related side effects were mild to moderate , transient nausea and vomiting . With liraglutide 2.4/3.0 mg , the 2-year prevalence of prediabetes and metabolic syndrome decreased by 52 and 59 % , with improvements in blood pressure and lipids . Conclusion : Liraglutide is well tolerated , sustains weight loss over 2 years and improves cardiovascular risk factors AIM We investigated the relationship between weight change and related factors in subjects with type 2 diabetes mellitus ( T2DM ) treated with liraglutide versus comparator diabetes therapies . METHODS Twenty-six-week data from seven phase 3 , r and omized trials in the liraglutide T2DM development programme were analysed by trial and treatment group : liraglutide ( 1.2 and 1.8 mg ) , active comparator and placebo . Outcome measures included proportions of subjects in various weight change categories and their percentage weight change from baseline ; impact of body mass index ( BMI ) and gastrointestinal ( GI ) adverse events ( AEs ) on weight change and correlation of weight change with change in glycosylated haemoglobin ( HbA1c ) . RESULTS A number of subjects experienced > 5 % weight loss during the trials ( 24.4 % liraglutide 1.8 mg and 17.7 % liraglutide 1.2 mg ; 17.7 % exenatide , 10.0 % sitagliptin , 3.6 - 7.0 % sulphonylurea , 2.6 % thiazolidinedione and 2.6 % glargine ; 9.9 % placebo ) . More weight loss was seen with liraglutide 1.2 and 1.8 mg than with active comparators except exenatide . Across trials , higher initial BMI was associated with slightly greater weight loss with liraglutide . Mean weight loss increased slightly the longer GI AEs persisted . Although HbA1c reduction was slightly larger in higher weight loss categories across treatments ( including placebo ) , sample sizes were small and no clear correlation could be determined . Liraglutide-treated subjects experienced additional HbA1c reduction beyond that which appeared weight induced ; thus , not all HbA1c-lowering effect appears weight mediated . CONCLUSIONS The majority of liraglutide-treated T2DM subjects experienced weight loss in this analysis . Weight loss was greater and occurred more in glucagon-like peptide-1 receptor agonist-treated subjects than in active comparator-treated subjects OBJECTIVE To investigate the effect of treatment with the glucagon-like peptide 1 receptor agonist exenatide on weight loss and metabolic parameters in obese nondiabetic women . RESEARCH DESIGN AND METHODS Forty-one obese women ( aged 48 ± 11 years and BMI 33.1 ± 4.1 kg/m2 ) participated in a 35-week r and omized , double-blind , placebo-controlled , crossover study , including two 16-week treatment periods separated by a 3-week washout period . There was no lifestyle intervention . The primary outcome was change in body weight . RESULTS Subjects treated with exenatide lost an average of 2.49 ± 0.66 kg compared with a 0.43 ± 0.63 kg weight gain during placebo treatment . Weight loss with exenatide treatment was noted at 2 weeks . The degree of weight loss could be stratified . A total of 30 % of subjects were high responders who lost ≥5 % body weight ( −7.96 ± 0.52 % ) , 39 % were moderate responders who lost < 5 % body weight ( −2.43 ± 0.45 % ) , and 31 % were nonresponders who gained weight ( 1.93 ± 0.53 % ) . Waist circumference also decreased significantly with exenatide treatment . Subjects experienced more nausea during exenatide treatment compared with placebo , but the severity decreased over time and did not correlate with weight loss . CONCLUSIONS Short-term exenatide treatment was associated with modest weight loss and decreased waist circumference in a cohort of obese nondiabetic women . A subset of individuals demonstrated robust weight loss that was detected very early in the course of treatment Background Glucagon like peptide-1 ( GLP-1 ) receptor agonist treatment may improve endothelial function via direct and indirect mechanisms . We compared the acute and chronic effects of the GLP-1 receptor agonist exenatide vs. metformin on endothelial function in patients with obesity and pre-diabetes . Methods We performed a r and omized , open-label , clinical trial in 50 non-diabetic individuals ( mean age 58.5 ± 10.0 ; 38 females ) with abdominal obesity and either impaired fasting glucose , elevated HbA1c , or impaired glucose tolerance ( IGT ) who were r and omized to receive 3-months of exenatide or metformin . Microvascular endothelial function , assessed by digital reactive hyperemia ( reactive hyperemic index : RHI ) , C-reactive protein ( CRP ) , circulating oxidized LDL ( oxLDL ) , and vascular cell adhesion molecule-1 ( VCAM-1 ) were measured at baseline and 3-months . Seven subjects with IGT participated in a sub- study comparing the effects of pre-administration of exenatide and metformin on postpr and ial endothelial function . Results There were no differences for the change in RHI ( Δ exenatide : 0.01 ± 0.68 vs. Δ metformin : -0.17 ± 0.72 , P = 0.348 ) , CRP , oxLDL , or VCAM-1 between exenatide and metformin treatment . Triglycerides were reduced more with exenatide compared to metformin ( Δ exenatide : -25.5 ± 45.7 mg/dL vs. Δ metformin : -2.9 ± 22.8 mg/dL , P = 0.032 ) . In the sub- study , there was no difference in postpr and ial RHI between exenatide and metformin . Conclusions Three months of exenatide therapy had similar effects on microvascular endothelial function , markers of inflammation , oxidative stress , and vascular activation , as metformin , in patients with obesity and pre-diabetes . Clinical trials registration This study is registered on http://www . clinical Objective The effect of metformin on weight reduction in polycystic ovary syndrome ( PCOS ) is often unsatisfactory . In this study , we investigated the potential add-on effect of treatment with the glucagon-like peptide-1 receptor agonist liraglutide on weight loss in obese nondiabetic women with PCOS who had lost < 5 % body weight during pretreatment with metformin . Methods A total of 40 obese women with PCOS , who had been pretreated with metformin for at least 6 months , participated in a 12-week open-label , prospect i ve study . They were r and omized to one of three treatment arms : metformin ( MET ) arm 1000 mg BID , liraglutide ( LIRA ) arm 1.2 mg QD s.c . , or combined MET 1000 mg BID and LIRA ( COMBI ) 1.2 mg QD s.c . Lifestyle intervention was not actively promoted . The primary outcome was change in body weight . Results Thirty six patients ( aged 31.3±7.1 years , BMI 37.1±4.6 kg/m2 ) completed the study : 14 on MET , 11 on LIRA , and 11 on combined treatment . COMBI therapy was superior to LIRA and MET monotherapy in reducing weight , BMI , and waist circumference . Subjects treated with COMBI lost on average 6.5±2.8 kg compared with a 3.8±3.7 kg loss in the LIRA group and a 1.2±1.4 kg loss in the MET group ( P<0.001 ) . The extent of weight loss was stratified : a total of 38 % of subjects were high responders who lost ≥5 % body weight , 22 % of them in the COMBI arm compared with 16 and 0 % in the LIRA and MET arm respectively . BMI decreased by 2.4±1.0 in the COMBI arm compared with 1.3±1.3 in LIRA and 0.5±0.5 in the MET arm ( P<0.001 ) . Waist circumference also decreased by 5.5±3.8 cm in the COMBI arm compared with 3.2±2.9 cm in LIRA and 1.6±2.9 cm in the MET arm ( P=0.029 ) . Subjects treated with liraglutide experienced more nausea than those treated with metformin , but severity of nausea decreased over time and did not correlate with weight loss . Conclusions Short-term combined treatment with liraglutide and metformin was associated with significant weight loss and decrease in waist circumference in obese women with PCOS who had previously been poor responders regarding weight reduction on metformin monotherapy CONTEXT Insulin resistance and obesity are common features of the polycystic ovary syndrome ( PCOS ) . Weight loss and use of insulin-lowering drugs have been shown to improve both reproductive and metabolic aspects of PCOS . OBJECTIVE We evaluated exenatide ( EX ) and metformin ( MET ) , alone and in combination ( COM ) , on menstrual cyclicity , hormonal parameters , metabolic profiles , and inflammatory markers in overweight , insulin-resistant women with PCOS . DESIGN , SETTING , AND PARTICIPANTS Sixty overweight oligoovulatory women with PCOS ( body mass index > 27 ; 18 - 40 yr ) were r and omized to one of three treatment groups : MET [ 1000 mg twice daily ( BID ) ] , EX ( 10 microg BID ) , or COM ( MET 1000 mg BID , EX 10 microg BID ) for 24 wk . The primary outcome was menstrual frequency ; secondary outcome measures included changes in ovulation rate , insulin action , anthropometric measures , and rogen levels , and inflammatory markers . RESULTS Forty-two ( 70 % ) patients completed the study . COM therapy was superior to EX or MET monotherapy in improving menstrual cyclicity , ovulation rate , free and rogen index , and insulin sensitivity measures and reducing weight and abdominal fat . Both EX arms were more effective in promoting weight loss than MET ( P = 0.003 ) . CONCLUSIONS COM appears better than either EX or MET alone on menstrual cycle frequency and hormonal and metabolic derangements . A marked decrease in central adiposity could partly explain the improvements in reproductive function , insulin-glucose parameters , and adiponectin observed in these overweight women with PCOS treated with COM therapy . Larger trials of longer duration are warranted to assess the long-term efficacy and safety of combined EX-MET therapy in overweight women with PCOS OBJECTIVE Chronic exenatide treatment in type 2 diabetes is associated with improved glucose control and fasting lipid levels , as well as weight loss . Less established is whether exenatide directly reduces postpr and ial lipid and lipoprotein levels without the reduction in body weight or fasting glucose and triglycerides levels that frequently occur with prolonged therapy . Therefore , the effect of a single injection of exenatide on postpr and ial lipids , remnant lipoproteins , and apolipoproteins was studied . METHODS A double-blinded , r and omized , placebo-controlled , crossover study was conducted in 35 subjects ( 31 men and 4 women ) with impaired glucose tolerance ( n=20 ) or recent onset type 2 diabetes ( n=15 ) . A single subcutaneous injection of exenatide ( 10 microg ) or normal saline was administered just prior to a high-calorie , fat-enriched breakfast meal . Concentrations of triglycerides ( TG ) , apolipoproteins B-48 and CIII , non-esterified fatty acids ( NEFA ) , and remnant lipoprotein ( RLP ) cholesterol and TG in serum or plasma were measured prior to the injection and for up to 8 h postpr and ially . RESULTS Exenatide markedly reduced postpr and ial elevation of TG , apolipoproteins B-48 and CIII , RLP-cholesterol and RLP-triglyceride ( all p<0.001 ) . Postpr and ial declines in NEFA were less pronounced but persisted longer with exenatide compared to placebo ( p<0.05 ) . These effects of exenatide were not affected either by glucose tolerance status or by treatment with statins . CONCLUSION These results demonstrate that exenatide acutely and profoundly inhibits postpr and ial excursions of proatherogenic lipids and lipoproteins and may offer additional cardiovascular risk reduction ( NCT00974272 ) BACKGROUND Our objective was to quantify and predict diabetes risk reduction during the Diabetes Prevention Program Outcomes Study ( DPPOS ) in participants who returned to normal glucose regulation at least once during the Diabetes Prevention Program ( DPP ) compared with those who consistently met criteria for prediabetes . METHODS DPPOS is an ongoing observational study of participants from the DPP r and omised trial . For this analysis , diabetes cumulative incidence in DPPOS was calculated for participants with normal glucose regulation or prediabetes status during DPP with and without stratification by previous r and omised treatment group . Cox proportional hazards modelling and generalised linear mixed models were used to quantify the effect of previous ( DPP ) glycaemic status on risk of later ( DPPOS ) diabetes and normal glucose regulation status , respectively , per SD in change . Included in this analysis were 1990 participants of DPPOS who had been r and omly assigned to treatment groups during DPP ( 736 intensive lifestyle intervention , 647 metformin , 607 placebo ) . These studies are registered at Clinical Trials.gov , NCT00004992 ( DPP ) and NCT00038727 ( DPPOS ) . FINDINGS Diabetes risk during DPPOS was 56 % lower for participants who had returned to normal glucose regulation versus those who consistently had prediabetes ( hazard ratio [ HR ] 0·44 , 95 % CI 0·37 - 0·55 , p<0·0001 ) and was unaffected by previous group assignment ( interaction test for normal glucose regulation and lifestyle intervention , p=0·1722 ; normal glucose regulation and metformin , p=0·3304 ) . Many , but not all , of the variables that increased diabetes risk were inversely associated with the chance of a participant reaching normal glucose regulation status in DPPOS . Specifically , previous achievement of normal glucose regulation ( odds ratio [ OR ] 3·18 , 95 % CI 2·71 - 3·72 , p<0·0001 ) , increased β-cell function ( OR 1·28 ; 95 % CI 1·18 - 1·39 , p<0·0001 ) , and insulin sensitivity ( OR 1·16 , 95 % CI 1·08 - 1·25 , p<0·0001 ) were associated with normal glucose regulation in DPPOS , whereas the opposite was true for prediction of diabetes , with increased β-cell function ( HR 0·80 , 95 % CI 0·71 - 0·89 , p<0·0001 ) and insulin sensitivity ( HR 0·83 , 95 % CI 0·74 - 0·94 , p=0·0001 ) having a protective effect . Among participants who did not return to normal glucose regulation in DPP , those assigned to the intensive lifestyle intervention had a higher diabetes risk ( HR 1·31 , 95 % CI 1·03 - 1·68 , p=0·0304 ) and lower chance of normal glucose regulation ( OR 0·59 , 95 % CI 0·42 - 0·82 , p=0·0014 ) than did the placebo group in DPPOS . INTERPRETATION We conclude that prediabetes is a high-risk state for diabetes , especially in patients who remain with prediabetes despite intensive lifestyle intervention . Reversion to normal glucose regulation , even if transient , is associated with a significantly reduced risk of future diabetes independent of previous treatment group . FUNDING US National Institutes of Health BACKGROUND Unlike most antihyperglycaemic drugs , glucagon-like peptide-1 ( GLP-1 ) receptor agonists have a glucose-dependent action and promote weight loss . We compared the efficacy and safety of liraglutide , a human GLP-1 analogue , with exenatide , an exendin-based GLP-1 receptor agonist . METHODS Adults with inadequately controlled type 2 diabetes on maximally tolerated doses of metformin , sulphonylurea , or both , were stratified by previous oral antidiabetic therapy and r and omly assigned to receive additional liraglutide 1.8 mg once a day ( n=233 ) or exenatide 10 microg twice a day ( n=231 ) in a 26-week open-label , parallel-group , multinational ( 15 countries ) study . The primary outcome was change in glycosylated haemoglobin ( HbA(1c ) ) . Efficacy analyses were by intention to treat . The trial is registered with Clinical Trials.gov , number NCT00518882 . FINDINGS Mean baseline HbA(1c ) for the study population was 8.2 % . Liraglutide reduced mean HbA(1c ) significantly more than did exenatide ( -1.12 % [ SE 0.08 ] vs -0.79 % [ 0.08 ] ; estimated treatment difference -0.33 ; 95 % CI -0.47 to -0.18 ; p<0.0001 ) and more patients achieved a HbA(1c ) value of less than 7 % ( 54%vs 43 % , respectively ; odds ratio 2.02 ; 95 % CI 1.31 to 3.11 ; p=0.0015 ) . Liraglutide reduced mean fasting plasma glucose more than did exenatide ( -1.61 mmol/L [ SE 0.20 ] vs -0.60 mmol/L [ 0.20 ] ; estimated treatment difference -1.01 mmol/L ; 95 % CI -1.37 to -0.65 ; p<0.0001 ) but postpr and ial glucose control was less effective after breakfast and dinner . Both drugs promoted similar weight losses ( liraglutide -3.24 kg vs exenatide -2.87 kg ) . Both drugs were well tolerated , but nausea was less persistent ( estimated treatment rate ratio 0.448 , p<0.0001 ) and minor hypoglycaemia less frequent with liraglutide than with exenatide ( 1.93 vs 2.60 events per patient per year ; rate ratio 0.55 ; 95 % CI 0.34 to 0.88 ; p=0.0131 ; 25.5%vs 33.6 % had minor hypoglycaemia ) . Two patients taking both exenatide and a sulphonylurea had a major hypoglycaemic episode . INTERPRETATION Liraglutide once a day provided significantly greater improvements in glycaemic control than did exenatide twice a day , and was generally better tolerated . The results suggest that liraglutide might be a treatment option for type 2 diabetes , especially when weight loss and risk of hypoglycaemia are major considerations . FUNDING Novo Nordisk |
12,789 | 30,483,405 | Results Despite the heterogeneity and general low quality of the identified literature , the review highlights a relatively high use of TCAM alone or in combination with orthodox medicine , in both general population and in specific health conditions in SSA .
TCAM users compared with non-TCAM users are more likely to be of low socioeconomic and educational status , while there were inconsistencies in age , sex , spatial location and religious affiliation between TCAM users and non-TCAM users .
Conclusion TCAM use in SSA is significant , although most studies emerge from a few countries . | Background The WHO estimates that a considerable number of people in Sub-Saharan Africa ( SSA ) rely on traditional , complementary and alternative medicine ( TCAM ) to meet their primary healthcare needs , yet there remains a dearth of research evidence on the overall picture of TCAM utilisation in the region . | Background Attention and interest in the use of Complementary and Alternative Medicine ( CAM ) has been reawakened globally . Evidence from studies carried out in different parts of the world has established that CAM use is very common and varies among population s. This study investigated the use of CAM among adults in Enugu urban , irrespective of their health status . It provided information on the prevalence of CAM use , forms of CAM remedies used and reasons for utilizing them Methods The study areas were three local government areas in Enugu urban of Enugu State . Cross-sectional survey using question naires were administered to r and omly selected households . All consenting participants were used for the study Results 732 participants ( 37.2 % males and 62.8 % females ) were used for the study . Ages ranged from 18 - 65 years . 620 ( 84.7 % ) of the adult population have used CAM ranging from one single type to twenty different types while 112 ( 15.3 % ) have not used any form of CAM . The most commonly used CAM product was the biological products , followed by prayer/faith healing . Major reasons for using CAM include their natural state and also for health promotion and maintenance . Conclusion There is need for adequate policy formulation and regulation to ensure safety and efficacy of CAM products . Measures to ensure rational use of CAM should be instituted Summary Background . Traditional bone setting ( TBS ) practice is an important part of health care delivery in many developing countries and has been in Nigeria for long . Despite the complications that arise from the cultural practice , TBS services is still in high dem and by a significant number of people . This study was conducted to determine the factors that influence the utilization of TBS practice . Methods . A descriptive cross-sectional study was carried out using a semi structured question naire to gather information from 400 r and omly selected residents of Ilorin West LGA in north central Nigeria . Multistage sampling technique was used in selecting the respondents . Results . The respondents were between the ages of 18 - 72 years with a mean age of 36.3 ± 12.3 . Three hundred and three ( 77.3 % ) of the respondents know of TBS practice as a way of getting treatment for bone injuries . More than two third 210 ( 69.3 % ) of the respondents who know TBS practice as a form of treatment for bone injuries think that TBS therapy is preferable to Orthodox medicine in h and ling bone injuries . Reasons for preference are that it is cheap 134 ( 63.8 % ) , acceptable 123 ( 58.6 % ) and accessible 109 ( 51.9 % ) to them . More than half ( 52.3 % ) of the respondents had patronized TBS treatment at one time or the other . Main reason for patronage of TBS was influence from family members and friends ( 53.6 % ) . However , factors that influence the respondents decision to utilize TBS treatment include attitude of health workers 310 ( 77.5 % ) , delay in hospitals 284(71.0 % ) fear of amputation 272 ( 54.35 ) and fear of operation 217(54.3 % ) in hospitals . There was a statistically significant ( p < 0.05 ) relationship between respondents age , sex , marital status , occupation , ethnicity as well as the income level of the respondents and the utilization of TBS . Conclusions . Utilisation of TBS is quite popular among the studied population because it is believed to be cheap , acceptable and accessible to them and a high proportion of the respondents utilize TBS notwithst and ing that they live in a community where they have better access to orthodox medical care . Influence from family and friends is the main reason for consulting TBS . Regulations should be made concerning the advertisement of TBS practice by relevant agencies and the public should be made aware through health education on the dangers of TBS treatment Background Traditional herbal medicines are commonly used in sub-Saharan Africa and some herbs are known to be hepatotoxic . However little is known about the effect of herbal medicines on liver disease in sub-Saharan Africa . Methods 500 HIV-infected participants in a rural HIV care program in Rakai , Ug and a , were frequency matched to 500 HIV-uninfected participants . Participants were asked about traditional herbal medicine use and assessed for other potential risk factors for liver disease . All participants underwent transient elastography ( FibroScan ® ) to quantify liver fibrosis . The association between herb use and significant liver fibrosis was measured with adjusted prevalence risk ratios ( adjPRR ) and 95 % confidence intervals ( CI ) using modified Poisson multivariable logistic regression . Results 19 unique herbs from 13 plant families were used by 42/1000 of all participants , including 9/500 HIV-infected participants . The three most-used plant families were Asteraceae , Fabaceae , and Lamiaceae . Among all participants , use of any herb ( adjPRR = 2.2 , 95 % CI 1.3–3.5 , p = 0.002 ) , herbs from the Asteraceae family ( adjPRR = 5.0 , 95 % CI 2.9–8.7 , p<0.001 ) , and herbs from the Lamiaceae family ( adjPRR = 3.4 , 95 % CI 1.2–9.2 , p = 0.017 ) were associated with significant liver fibrosis . Among HIV infected participants , use of any herb ( adjPRR = 2.3 , 95 % CI 1.0–5.0 , p = 0.044 ) and use of herbs from the Asteraceae family ( adjPRR = 5.0 , 95 % CI 1.7–14.7 , p = 0.004 ) were associated with increased liver fibrosis . Conclusions Traditional herbal medicine use was independently associated with a substantial increase in significant liver fibrosis in both HIV-infected and HIV-uninfected study participants . Pharmacokinetic and prospect i ve clinical studies are needed to inform herb safety recommendations in sub-Saharan Africa . Counseling about herb use should be part of routine health counseling and counseling of HIV-infected persons in Ug and OBJECTIVES Use of complementary and alternative medicines ( CAMs ) is widespread . Several studies have explored why individuals chose to use CAM but there are fewer data to explain how its use ' dovetails ' with conventional medicine . This study aim ed to determine the prevalence of CAM use in the adult population in Australia and the proportion that seek advice or tell their primary care physician after CAM use , and also to investigate which demographic characteristics , health behaviours and health status are associated with CAM use and disclosure . DESIGN A cross sectional survey . METHODS a r and om sample of 1261 adults was interviewed as part of 2010 Queensl and Social Survey , which contained questions about CAM use , frequency of use , types of CAM used , reasons for use , discussing and reporting CAM use with the doctor and confidence in CAM use . Relationships were explored using bivariate and multiple logistic regression . MAIN OUTCOME MEASURES use of CAM ; sought advice from doctor before CAM use ; informed doctor after CAM use . RESULTS 61.7 % of respondents had used self-prescribed CAM or visited a CAM practitioner . Being female and being younger predicted CAM use . Being male and in better health predicted seeking advice from the doctor before and also after CAM use . CONCLUSION Our results confirm the relatively high use of CAM in Queensl and , Australia and found that a significant proportion of people did not seek advice from their primary care physician before using CAM , or disclose its use afterwards . These factors should be taken into account in the doctor-patient consultation Background In Africa , herbal medicines are often used as primary treatment for Human immunodeficiency virus ( HIV ) related problems . Concurrent use of traditional herbal medicines ( THM ) with antiretroviral drugs ( ARVs ) is widespread among HIV infected patients . However , the extent of THM use is not known in most setting s in Sub-Saharan Africa . This study aim ed at determining the prevalence and factors associated with THM use among HIV infected patients on highly active antiretroviral therapy ( HAART ) attending The AIDS Support Organization ( TASO ) in Ug and a. TASO is a non-governmental organization devoted to offering HIV/AIDS care and treatment services in the population . Methods This was a cross-sectional study carried out in two TASO treatment centres in Ug and a among 401 r and omly selected eligible participants . We included participants who were 18 years and above , were enrolled on HAART , and consented to participate in the study . Data was collected using an interviewer-administered semi-structured question naire . THM use referred to someone who had ever used or was currently using herbal medicine while on highly active antiretroviral therapy ( HAART ) by the time of the study . Data was captured in Epi- data version 3.1 and exported to STATA version 9.0 for analysis . Results The prevalence of THM use was 33.7 % . Patients on HAART for < 4 years were more likely to use THM ( OR = 5.98 , 95 % CI 1.13 - 31.73 ) as well as those who experienced HAART side effects ( OR = 3.66 , 95 % CI : 1.15 - 11.68 ) . Older patients ( ≥39 years ) were less likely to use THM ( OR = 0.26 95 % CI : 0.08 - 0.83 ) . Participants with HAART adherence levels > 95 % were less likely to use THM ( OR = 0.09 , 95 % CI 0.01 - 0.65 ) . Conclusion The prevalence of THM use among participants on HAART was high . This raises clinical and pharmacological concerns that need attention by the health care service providers INTRODUCTION Traditional medicines are an important part of healthcare in sub-Saharan Africa , and building successful disease treatment programs that are sensitive to traditional medicine practice s will require an underst and ing of their current use and roles , including from a biomedical perspective . Therefore , we conducted a mixed- method study in Northern Tanzania in order to characterize the extent of and reasons for the use of traditional medicines among the general population so that we can better inform public health efforts in the region . METHODS Between December 2013 and June 2014 in Kilimanjaro , Tanzania , we conducted 5 focus group discussion s and 27 in-depth interviews of key informants . The data from these sessions were analyzed using an inductive framework method with cultural insider-outsider coding . From these results , we developed a structured survey design ed to test different aspects of traditional medicine use and administered it to a r and om sample of 655 adults from the community . The results were triangulated to explore converging and diverging themes . RESULTS Most structured survey participants ( 68 % ) reported knowing someone who frequently used traditional medicines , and the majority ( 56 % ) reported using them themselves in the previous year . The most common uses were for symptomatic ailments ( 42 % ) , chronic diseases ( 15 % ) , reproductive problems ( 11 % ) , and malaria/febrile illnesses ( 11 % ) . We identified five major determinants for traditional medicine use in Northern Tanzania : biomedical healthcare delivery , credibility of traditional practice s , strong cultural identities , individual health status , and disease underst and ing . CONCLUSIONS In order to better formulate effective local disease management programs that are sensitive to TM practice s , we described the determinants of TM use . Additionally , we found TM use to be high in Northern Tanzania and that its use is not limited to lower-income areas or rural setting s. After symptomatic ailments , chronic diseases were reported as the most common reason for TM use which may be particularly important in Northern Tanzania where non-communicable diseases are a rapidly growing burden OBJECTIVE To investigate the prevalence of use of traditional medicines amongst patients with HIV infection receiving therapies of antiretroviral ( ARV ) drugs at the Aminu Kano Teaching Hospital ( AKTH ) , Kano , Northwest Nigeria , and to assess the attitude of these patients to their ARV therapy . METHODS A cross sectional prospect i ve study using pretested structured question naires administered on 430 patients with antiretroviral therapy attending the AKTH between April and June 2009 . Data was collected on socio-demographic characteristics , use of traditional medicine and attitude to antiretroviral therapy . RESULTS A mean age of ( 33.6#20381;8.4 ) years old was found with 67.2 % females and 32.8 % males . A total of 29 % had no formal education while 10.5 % had postgraduate education ; 12 % earned above 35,000 naira ( 230 USD ) per month ; 63.8 % were married ; 39.8 % had at least 2 sexual partners ; 27.5 % used traditional medicine before commencement of antiretroviral therapy ( ART ) , but only 4.25 % of patients used ARV and traditional medicine concurrently . There was no significant difference in most of the socio-demographic indices between the concurrent users and other patients ( P>0.05 ) . A total of 28.8 % HIV patients , 14.6 % patients used traditional medicine before ART and 29.4 % concurrent users had missed at least a dose of their ARVs since commencement of therapy . 148 ( 37 % ) of the patients had their drug regimen changed at least once while 23 ( 20.90 % ) patients receiving traditional medicine before ART and 5 ( 29.41 % ) patients having two treatments had their drug regimen changed . CONCLUSIONS A total of 4.25 % patients used ARV and traditional medicine concurrently . In conclusion , the widespread use of traditional medicine by patients living with HIV/AIDS should be of concern to clinicians and policy makers Background In developing countries , most childbirth occurs at home and is not assisted by skilled attendants . This situation increases the risk of death for both mother and child and has severe maternal and neonatal health complications . The purpose of this study was to explore pregnant women ’s perceptions and utilization of traditional birth attendant ( TBA ) services in a rural Local Government Area ( LGA ) in Ogun State , southwest Nigeria . Methods A quantitative design was used to obtain information using a structured question naire from 250 pregnant women attending four r and omly selected primary health care clinics in the LGA . Data were analyzed using Epi Info ( v 3.5.1 ) statistical software . Results Almost half ( 48.8 % ) of the respondents were in the age group 26–35 years , with a mean age of 29.4 ± 7.33 years . About two-thirds ( 65.6 % ) of the respondents had been pregnant 2–4 times before . TBA functions , as identified by respondents , were : “ taking normal delivery ” ( 56.7 % ) , “ providing antenatal services ” ( 16.5 % ) , “ performing caesarean section ” ( 13.0 % ) , “ providing family planning services ” ( 8.2 % ) , and “ performing gynaecological surgeries ” ( 5.6 % ) . About 6/10 ( 61.0 % ) respondents believed that TBAs have adequate knowledge and skills to care for them , however , approximately 7/10 ( 69.7 % ) respondents acknowledged that complications could arise from TBA care . Services obtained from TBAs were : routine antenatal care ( 81.1 % ) , normal delivery ( 36.1 % ) , “ special maternal bath to ward off evil spirits ” ( 1.9 % ) , “ concoctions for mothers to drink to make baby strong ” ( 15.1 % ) , and family planning services ( 1.9 % ) . Reasons for using TBA services were : “ TBA services are cheaper ” ( 50.9 % ) , “ TBA services are more culturally acceptable in my environment ” ( 34.0 % ) , “ TBA services are closer to my house than hospital services ” ( 13.2 % ) , “ TBAs provide more compassionate care than orthodox health workers ” ( 43.4 % ) , and “ TBA service is the only maternity service that I know ” ( 1.9 % ) . Approximately 8/10 ( 79.2 % ) of the users ( past or current ) opined that TBA services are effective but could be improved with some form of training ( 78.3 % ) . More than three-quarters ( 77.1 % ) opposed the banning of TBA services . Almost 7/10 ( 74.8 % ) users were satisfied with TBA services . Conclusion Study findings revealed a positive perception and use of TBA services by the respondents . This underlines the necessity for TBAs ’ knowledge and skills to be improved within permissible st and ards through sustained partnership between TBAs and health systems . It is hoped that such partnership will foster a healthy collaboration between providers of orthodox and traditional maternity services that will translate into improved maternal and neonatal health outcomes in relevant setting Adherence to antiretroviral medication in the treatment of HIV is critical , both to maximize efficacy and to minimize the emergence of drug resistance . The aim of this prospect i ve study in three public hospitals in KwaZulu-Natal , South Africa , is to assess the use of Traditional Complementary and Alternative Medicine ( TCAM ) by HIV patients and its effect on antiretroviral ( ARV ) adherence 6 months after initiating ARVs . 735 ( 29.8 % male and 70.2 % female ) patients who consecutively attended three HIV clinics completed assessment s prior to ARV initiation and 519 after six months on antiretroviral therapy ( ART ) Results indicate that the use of herbal therapies for HIV declined significantly from 36.6 % prior to antiretroviral treatment ( ART ) initiation to 7.9 % after being on ARVs for 6 months . Faith healing methods , including spiritual practice s and prayer for HIV declined from 35.8 % to 22.1 % and physical/body-mind therapy ( exercise and massage ) declined from 5.0 % to 1.9 % . In contrast , the use of micronutrients ( vitamins , etc . ) significantly increased from 42.6 % to 87.4 % . In multivariate regression analyses , ARV non-adherence ( dose , schedule and food ) was associated with the use of herbal treatment , not taking micronutrients and the use of over-the-counter drugs . The use of TCAM declined after initiating ARVs . As herbal treatment for HIV was associated with reduced ARV adherence , patients ' use of TCAM should be considered in ARV adherence management Background Infantile colic is a self-limiting condition that is distributed worldwide . It is often misdiagnosed as an organic disease for which an infant is admitted to the hospital . Many studies have described the aetiopathogenesis , pharmacologic and non-pharmacologic management of colic but none has evaluated self-medication for infants with colic . The aim of this study was therefore to determine the knowledge of Nigerian mothers about colic , their home-based management , extent of self-medication for the infants with colic and the types of medicines involved . Methods It is a prospect i ve study conducted at the vaccination clinics of 20 primary health care centres , each from different Local Government Areas in Lagos , Nigeria . Eight hundred mothers that brought their infants for vaccination between April and September , 2006 were interviewed with open- and close-ended question naire . Results Six hundred and eighty three ( 85.4 % ) mothers cl aim ed they had a good knowledge of colic . Incessant and excessive cry was the main clinical feature of colic identified by 430(62.9 % ) mothers . Three hundred and seventy eight ( 67.7 % ) infants were treated by self-medication , 157 ( 28.1 % ) sought medical intervention and 17 ( 3.1 % ) were treated at a traditional birth attendant home . Herbal medicines constituted 51.8 % of the self-medicated medicines , of which 48 ( 26.2 % ) were " Ororo Ogiri " . Nospamin ® ( 49.5 % ) and Gripe water ® ( 43.0 % ) were the two frequently prescribed and self-medicated medicines for infants with colic . Conclusion Nigerian mothers are deficient in their knowledge of colic . Self-medication was the most frequently used home-based intervention . Health education would appear necessary to improve parental management of this self-limiting condition Background Over three-quarter of the world 's population is using herbal medicines with an increasing trend globally . Herbal medicines may be beneficial but are not completely harmless . This study aim ed to assess the extent of use and the general knowledge of the benefits and safety of herbal medicines among urban residents in Lagos , Nigeria . Methods The study involved 388 participants recruited by cluster and r and om sampling techniques . Participants were interviewed with a structured open- and close-ended question naire . The information obtained comprises the demography and types of herbal medicines used by the respondents ; indications for their use ; the sources , benefits and adverse effects of the herbal medicines they used . Results A total of 12 herbal medicines ( crude or refined ) were used by the respondents , either alone or in combination with other herbal medicines . Herbal medicines were reportedly used by 259 ( 66.8 % ) respondents . ' Agbo jedi-jedi ' ( 35 % ) was the most frequently used herbal medicine preparation , followed by ' agbo-iba ' ( 27.5 % ) and Oroki herbal mixture ® ( 9 % ) . Family and friends had a marked influence on 78.4 % of the respondents who used herbal medicine preparations . Herbal medicines were considered safe by half of the respondents despite 20.8 % of those who experienced mild to moderate adverse effects . Conclusions Herbal medicine is popular among the respondents but they appear to be ignorant of its potential toxicities . It may be necessary to evaluate the safety , efficacy and quality of herbal medicines and their products through r and omised clinical trial studies . Public enlightenment programme about safe use of herbal medicines may be necessary as a means of minimizing the potential adverse effects Research on unconventional medical practice s among students has proliferated lately in the global space , hitherto , little is known explicitly in Ghana . This paper teases out insights for recent utilisation patterns of traditional medical therapies at Kwame Nkrumah University of Science and Technology ( KNUST ) , Ghana . A sample of 754 , r and omly selected undergraduates were involved in a retrospective cross-sectional survey . Data were analysed using multivariate logistic regression and Pearson 's χ2 test with p < 0.05 as significant . Overall prevalence of traditional therapies consumption was 89.1 % in the last 12 months . Herbal-based products ( 67 % ) , prayer healing ( 15 % ) and body-mind therapies ( 11 % ) were principally used and , accessed through purchases from pharmacy shops ( 29 % ) and encounter with faith healers ( 26 % ) . Although students ' knowledge on traditional therapies was acquired through family members ( 50 % ) and media ( 23 % ) , literary material s remained significant information routes for Science related students compared to the Non-science related counterparts ( p < 0.001 ) . Pursuing Non-science-related programme [ odds ratio ( OR ) 6.154 ( 95 % confidence interval ( CI ) 3.745–10.111 ; p < 0.001 ) ] and having Christian faith [ OR 2.450 ( 95 % CI 1.359–4.415 ; p = 0.003 ) ] were strongly associated with students ' traditional therapies use . Although students exhibited positive attitude towards unconventional therapies , there is an urgent need to vali date the quality of traditional therapies through r and omised clinical trials and regulatory practice s to ensure quality control . Health forces should intensify efforts towards intercultural health care system in Ghana Diarrhea is a leading cause of child mortality worldwide . Early recognition of symptoms and referral to medical treatment are essential . In 2007 , we conducted a Healthcare Utilization and Attitudes Survey ( HUAS ) of 1,000 children r and omly selected from a population census to define care-seeking patterns for diarrheal disease in Bamako , Mali , in preparation for the Global Enteric Multicenter Study ( GEMS ) . We found that 57 % of caretakers sought care for their child 's diarrheal illness from traditional healers , and 27 % of caretakers sought care from the government health center ( GHC ) . Weighted logistic regression showed that seeking care from a traditional healer was associated with more severe reported diarrheal disease , like decreased urination ( odds ratio [ OR ] = 3.35 , 95 % confidence interval [ 95 % CI ] = 1.19–9.41 ) and mucus or pus in stool ( OR = 4.42 , 95 % CI = 1.35–14.51 ) , along with other indicators of perceived susceptibility . A locally design ed traditional healer referral system was , therefore , created that emphasized more severe disease . This system may serve as a model for health systems in West Africa This paper examines the relationship between national health insurance status and the pattern of traditional medicine ( TRM ) use among the general population in Ghana . A retrospective cross-sectional survey of r and omly sample d adults , aged ≥18 years ( N = 324 ) , was conducted . The results indicate that TRM use was high with prevalence of over 86 % . The study found no statistically significant association between national health insurance status and TRM utilisation ( P > 0.05 ) . Paradoxically , major sources of TRM , frequency of TRM use , comedical administration , and disclosure of TRM use to health care professionals differed significantly between the insured and uninsured subgroups ( P < 0.001 ) . Whereas effectiveness of TRM predicted its use for both insured [ odds ratio ( OR ) = 4.374 ( confidence interval ( CI ) : 1.753–10.913 ; P = 0.002 ) ] and uninsured [ OR = 3.383 CI : 0.869–13.170 ; P = 0.039 ) ] , work experience predicted TRM use for the insured [ OR = 1.528 ( 95 % CI : 1.309–1.900 ; P = 0.019 ) ] . Cultural specific variables and health philosophies rather than health insurance status may influence health care-seeking behaviour and TRM use . The enrollment of herbal-based therapies on the national health insurance medicine plan is exigent to ensure monitoring and rational use of TRM towards intercultural health care system in Ghana Background In South Africa , over 6 million people are hypertensive and the burden of disease shows that cardiovascular diseases ( CVDs ) are the leading cause of death among adults . Although treatments exist , few people comply or adhere to recommended treatment due to side effects or costs of the drugs , hence the reliance on alternative forms of treatment . Traditional herbal medicines ( THM ) are used for the management of hypertension but the prevalence of its use among hypertensive patients living in South African communities is not sufficiently known . Methods This was a cross-sectional descriptive study to determine the prevalence of THM use for hypertension , among 135 purpose fully selected South African participants of the Prospect i ve Urban and Rural Epidemiological ( PURE ) study , who are THM users . Data on THM use were collected by way of face to face interviews using structured question naires administered by trained field workers . St and ard descriptive measures were used to characterize the study sample and responses to the question naire . Chi-square test was used when making comparisons between groups . Results There were 135 THM users , 21 % of whom used THM to treat hypertension . Majority ( 82.1 % ) of the hypertensive THM users were females , only 29 % were married or co-habitating , virtually all ( 96 % ) were unemployed and 86 % were Christians . More than half ( 56 % ) of the respondents were aged between 55 and 64 years . THM was occasionally used ( 51.9 % ) as a combination of tea and other mixtures ( 63 % ) and prescribed by family/ friends/self-administered . There was a significant difference in the age , marital and employment status , as well as the form and frequency of THM use of hypertensive THM users compared to other THM users . Conclusions The study gives an insight into the prevalence of THM use by hypertensive patients in selected South African communities . The practice of self-medication was also observed which raises concern regarding the safety of medications taken by the participants . Health care providers should however be more aware of THM use and counsel patients regarding the combination of prescribed treatment regimen and herbal medicines and the potential of herb-drug interactions Background : The use of herbal medicines in Nigeria is on the increase . Documented Population based data on the use of herbal medicinal products and indigenous knowledge among the younger generations are lacking in Nigeria and Africa at large . Aim : The aim of this study is to investigate the extent of use and general knowledge of herbal medicines among adolescents in the Niger Delta Region of Nigeria . Methods : The study covered a total of Two hundred and twenty-eight adolescents r and omly selected in Senior Secondary Schools ( SSS 1 - 3 ) in Amassoma using a semi structured question naire/Interview and informal conversation on the respondents . Findings : Nearly all ( 97 % ) the respondents have had contact with herbs . Less than 1 % had contact with herbs through formal education ( teachers/ literature s ) . Stimulation of interest was majorly through parents ( 53 % ) . Gr and parents were the highest ( 46 % ) of custodian of indigenous knowledge . Parents were the next ( 39.7 % ) . Only 39 % of the respondents would prefer the use of herbal medicine to modern medicine . Fever was the main ailment mentioned followed by eye ailment and stomach ache . Vernonia amygdalina was the main plant for the treatment of fever . Conclusion : The study revealed that parents are the major custodians of knowledge being transferred to the younger generation and little or none is learnt from Schools . There is therefore the need to include the study of herbal medicines in School ’s curricula especially at SS 2 and SS 3 since they are matured enough to appreciate the importance of Herbal medicine so as to prepare them for the promotion of herbal medicine in future and to preserve our indigenous knowledge BACKGROUND The use of Traditional Medicines ( TM ) is common practice world over . Traditional Eye Medicine ( TEM ) use may be associated with various ocular complications including blindness . A study on the prevalence of TEM use was carried out at Sekuru Kaguvi Hospital Eye Unit ( SKHEU ) in Harare , with emphasis on the types ofTEM used and associated ocular complications . OBJECTIVES To evaluate the prevalence of TEM use among newly-presenting patients at SKHEU . To identify the ocular symptoms experienced by the new clinic-attendees who had used TEM for their current eye problem . To characterize the TEM used , in terms of type , source ( provider ) and routes of administration . To evaluate any association between TEM use and legal blindness at presentation , destructive eye procedures and other specific ocular complications among these patients . DESIGN Hospital-based , cross-sectional analytic study . METHODS All new patients attending one r and omly selected clinic per week were recruited for the study over a period of eight months . The patients had a full clinical examination and data collected . RESULTS The prevalence of TEM use among new patients at SKHEU was 61.5 % . The initial ocular symptoms prior to the use of TEM were mainly those of ocular surface inflammation : tearing ( 77.4 % ) , redness ( 74.9 % ) , itchiness ( 71.6 % ) and pain ( 70.3 % ) . The most common category of TEM used was plants and plant products . Most TEMs ( 92.4 % ) were administered as topical eye drops . In ninety-five percent of cases , the provider of TEM was not a formal traditional healer but rather relatives , friends and the patients self-medicated . The use of TEM was associated with specific ocular complications in 58.6 % of cases . There were significant associations between use of TEM and corneal ulceration , corneal vascularisation , endophthalmitis , evisceration , exenteration and legal blindness at presentation . CONCLUSION This study has shown that the use of TEM is common among new clinic-attendees at SKHEU and is associated with specific ocular complications The aim of this prospect i ve study ( 20 months ) was to assess HIV patients ' use of Traditional , Complementary and Alternative Medicine ( TCAM ) and its effect on ARV adherence at three public hospitals in KwaZulu-Natal , South Africa . Seven hundred and thirty-five ( 29.8 % male and 70.2 % female ) patients who consecutively attended three HIV clinics completed assessment s prior to ARV initiation , 519 after 6 months , 557 after 12 and 499 after 20 months on antiretroviral therapy ( ART ) . Results indicate that following initiation of ARV therapy the use of herbal therapies for HIV declined significantly from 36.6 % prior to ARV therapy to 8.0 % after 6 months , 4.1 % after 12 months and 0.6 % after 20 months on ARVs . Faith healing methods ( including spiritual practice s and prayer ) declined from 35.8 % to 22.1 % , 20.8 % and 15.5 % , respectively . In contrast , the use of micronutrients ( vitamins , etc . ) significantly increased from 42.6 % to 78.2 % . The major herbal remedies that were used prior to ART were unnamed traditional medicine , followed by imbiza ( Scilla natalensis planch ) , canova ( immune booster ) , izifozonke ( essential vitamins mixed with herbs ) , African potato ( Hypoxis hemerocallidea ) , stametta ( aloe mixed with vitamins and herbs ) and ingwe ( tonic ) . Herbal remedies were mainly used for pain relief , as immune booster and for stopping diarrhea . As herbal treatment for HIV was associated with reduced ARV adherence , patient 's use of TCAM should be considered in ARV adherence management BACKGROUND In order to institute preventive programmes against harmful traditional oral health practice s there is a need to identify targets . OBJECTIVES To investigate factors influencing awareness and attendance of traditional oral health practice s by residents of a peri-urban community in Ibadan , Nigeria . METHODS A cross-sectional study of adult residents selected by simple r and om sampling in a peri-urban community in Ibadan , Nigeria , was conducted over a period of six months . Information was obtained with interviewer administered question naires . Data were recorded using SPSS version 16 software . RESULTS A total of 172 ( 44.1 % ) respondents were aware of the existence of traditional healers for dental problems . Only 34 ( 8.7 % ) participants had been to traditional healers on account of toothache . About 76.5 % reported having relief after treatment with relapse occurring in 12 cases ( 46.2 % ) . Twenty ( 58.8 % ) of these ( 34 ) participants said they would not choose this option of treating dental problems in future . Significant associations existed between knowing that traditional healers provided dental treatment and gender ( p = 0.001 ) or history of dental problems ( p = 0.008 ) . CONCLUSION The study showed moderate awareness of traditional oral care practice s in Ibadan , Nigeria as influenced by gender and previous dental problems ETHNOPHARMACOLOGICAL RELEVANCE Whilst over three-quarters of the world׳s population continues to use traditional medicine ( TRM ) with an increasing trend globally , limited data exist in the Ashanti Region regarding TRM utilisation . This study espoused a retrospective cross-sectional quantitative approach to examine the prevalence and pattern of TRM use among the general population in the Kumasi Metropolis and Sekyere South District , Ghana . MATERIAL S AND METHODS A sample of 324 , drawn through systematic r and om sampling was used . The main instrument for data collection was formal face-to-face interviewer-administered question naire . Data were analysed using Chi-square and Fisher 's exact tests from the PASW ( V.17.0 ) with p ≤ 0.05 as significant . RESULTS The survey found that TRM use alongside conventional medicines was pervasive with prevalence of 86.1 % . Biologically-based therapies ( 88.5 % ) and distant prayer interventions ( 58.4 % ) were commonly used modalities through the influence of families ( 50.3 % ) , friends ( 19.4 % ) and the mass media ( 18.0 % ) . Whilst self-administration and purchases from pharmacy shops remained important sources of TRM , TMPs׳ consultation was less credible ( p<0.005 ) . The disclosure rate of TRM use to health care professionals remained low ( 12.2 % ; p<0.001 ) . CONCLUSION Concomitant TRM use with conventional therapies without disclosure may interfere with the potency of treatment regimen and result in drug interactions . Inclusion of alternative medicines on the National Health Insurance Scheme 's drug plan will fortify monitoring and professional administration of TRM . Information as regards TRM use needs to be incorporated into clinical and medical practice , hence the need to prioritise patient-physician communication Traditional medicine ( TRM ) use remains universal among individuals , families and communities the world over but the predictive variables of TRM use is still confounding . This population -based study analysed the predictors of TRM use in Ashanti Region , Ghana . A retrospective cross-sectional quantitative survey involving systematic r and om sample d participants ( N = 324 ) was conducted . Structured interviewer-administered question naires were used as research instruments . Data were analysed with logit regression , Pearson ’s Chi square and Fisher ’s exact tests from the PASW for Windows application ( V. 17.0 ) . Overall , 86.1 % ( n = 279 ) reported use of TRM with biologically-based and distant/prayer therapies as the major forms of TRM utilised in the previous 12 months . Among the general population , TRM use was predicted by having low-income levels [ odds ratio ( OR ) 2.883 , confidence interval ( CI ) 1.142–7.277 ] , being a trader ( OR 2.321 , CI 1.037–5.194 ) , perceiving TRM as effective ( OR 4.430 , CI 1.645–11.934 ) and safe ( OR 2.730 , CI 0.986–4.321 ) , good affective behaviour of traditional medical practitioner ( TMP ) ( OR 2.943 , CI 0.875–9.896 ) and having chronic ill-health ( OR 3.821 , CI 1.213–11.311 ) . The prevalence of TRM use is high . The study provides evidence that people ’s experience , personal attributes , health beliefs , attitude to TRM , attitude of TMP to clients and medical history are largely accountable for the upsurge use of TRM rather than socio-demographic factors . Underst and ing the health-seeking behaviour of individuals is exigent to ascribe appropriate medical care by health care providers Background In sub-Saharan Africa , chronic kidney disease ( CKD ) is being recognized as a non-communicable disease ( NCD ) with high morbidity and mortality . In countries like Tanzania , people access many sources , including traditional medicines , to meet their healthcare needs for NCDs , but little is known about traditional medicine practice s among people with CKD . Therefore , we sought to characterize these practice s among community members with CKD in northern Tanzania . Methods Between December 2013 and June 2014 , we administered a previously-developed survey to a r and om sample of adult community-members from the Kilimanjaro Region ; the survey was design ed to measure traditional medicine practice s such as types , frequencies , reasons , and modes . Participants were also tested for CKD , diabetes , hypertension , and HIV as part of the CKD-AFRiKA study . To identify traditional medicines used in the local treatment of kidney disease , we review ed the qualitative sessions which had previously been conducted with key informants . Results We enrolled 481 adults of whom 57 ( 11.9 % ) had CKD . The prevalence of traditional medicine use among adults with CKD was 70.3 % ( 95 % CI 50.0–84.9 % ) , and among those at risk for CKD ( n = 147 ; 30.6 % ) , it was 49.0 % ( 95 % CI 33.1–65.0 % ) . Among adults with CKD , the prevalence of concurrent use of traditional medicine and biomedicine was 33.2 % ( 11.4–65.6 % ) . Symptomatic ailments ( 66.7 % ; 95 % CI 17.3–54.3 ) , malaria/febrile illnesses ( 64.0 % ; 95 % CI 44.1–79.9 ) , and chronic diseases ( 49.6 % ; 95 % CI 28.6–70.6 ) were the most prevalent uses for traditional medicines . We identified five plant – based traditional medicines used for the treatment of kidney disease : Aloe vera , Commifora africana , Cymbopogon citrullus , Persea americana , and Zanthoxylum chalybeum . Conclusions The prevalence of traditional medicine use is high among adults with and at risk for CKD in northern Tanzania where they use them for a variety of conditions including other NCDs . Additionally , many of these same people access biomedicine and traditional medicines concurrently . The traditional medicines used for the local treatment of kidney disease have a variety of activities , and people with CKD may be particularly vulnerable to adverse effects . Recognizing these traditional medicine practice s will be important in shaping CKD treatment programs and public health policies aim ed at addressing CKD Background . In Ethiopia , up to 80 % of the population use traditional medicine for primary health care . Studies on the current knowledge and practice s of communities in the era of modern health care expansion are lacking . Therefore , this study is aim ed at assessing the knowledge , attitude , and practice of traditional medicine among communities in Merawi town . Methods . A descriptive cross-sectional study was carried out among 403 residents of Merawi town . A systematic r and om sampling was used to select households . Data was collected through house to house interview . Results . 392 out of 403 question naires were analysed . Among the participants , 220 ( 56.1 % ) were female . The mean ( ±s.d . ) age of the participants was 32.5 ( ±12.4 ) years . Nearly two-thirds , 241 ( 61.5 % ) , of study participants have good knowledge about traditional medicines . Three-quarters of participants prefer modern medicine to traditional drugs . 70.9 % of participants had the experience of personal use of traditional therapies . Conclusions . The population in Merawi has good knowledge with high acceptability and use of traditional medicine . The main reasons for high acceptability and practice were cultural acceptability , lesser cost , and good outcome of traditional medicine Objectives Examine factors associated with use of traditional medicine during childbirth and in management of childhood diarrhoea . Design Cross-sectional cluster survey , household interviews in a stratified last stage r and om sample of 90 census enumeration areas ; unstructured interviews with traditional doctors . Setting Oil-rich Cross River State in south-eastern Nigeria has 3.5 million residents , most of whom depend on a subsistence agriculture economy . Participants 8089 women aged 15–49 years in 7685 households reported on the health of 11 305 children aged 0–36 months in July – August 2011 . Primary and secondary outcome measures Traditional medicine used at childbirth and for management of childhood diarrhoea ; covariates included access to Western medicine and education , economic conditions , engagement with the modern state and family relations . Cluster-adjusted analysis relied on the Mantel-Haenszel procedure and Mantel extension . Results 24.1 % ( 1371/5686 ) of women reported using traditional medicine at childbirth ; these women had less education , accessed antenatal care less , experienced more family violence and were less likely to have birth certificates for their children . 11.3 % ( 615/5425 ) of young children with diarrhoea were taken to traditional medical practitioners ; these children were less likely to receive BCG , to have birth certificates , to live in households with a more educated head , or to use fuel other than charcoal for cooking . Education showed a gradient with decreasing use of traditional medicine for childbirth ( χ2 135.2 ) and for childhood diarrhoea ( χ2 77.2 ) . Conclusions Use of traditional medicine is associated with several factors related to cultural transition and to health status , with formal education playing a prominent role . Any assessment of the effectiveness of traditional medicine should anticipate confounding by these factors , which are widely recognised to affect health in their own right Background Diabetes is a growing burden in sub-Saharan Africa where traditional medicines ( TMs ) remain a primary form of healthcare in many setting s. In Tanzania , TMs are frequently used to treat non-communicable diseases , yet little is known about TM practice s for non-communicable diseases like diabetes . Methods Between December 2013 and June 2014 , we assessed TM practice s , including types , frequencies , reasons , and modes , among r and omly selected community members . To further characterize TMs relevant for the local treatment of diabetes , we also conducted focus groups and semi-structured interviews with key informants . Results We enrolled 481 adults of whom 45 ( 9.4 % ) had diabetes . The prevalence of TM use among individuals with diabetes was 77.1 % ( 95 % CI 58.5–89.0 % ) , and the prevalence of using TMs and biomedicines concurrently was 37.6 % ( 95 % CI 20.5–58.4 % ) . Many were using TMs specifically to treat diabetes ( 40.3 % ; 95 % CI 20.5–63.9 ) , and individuals with diabetes reported seeking healthcare from traditional healers , elders , family , friends , and herbal vendors . We identified several plant-based TMs used toward diabetes care : Moringa oleifera , Cymbopogon citrullus , Hagenia abyssinica , Aloe vera , Clausena anisata , Cajanus cajan , Artimisia afra , and Persea americana . Conclusions TMs were commonly used for diabetes care in northern Tanzania . Individuals with diabetes sought healthcare advice from many sources , and several individuals used TMs and biomedicines together . The TMs commonly used by individuals with diabetes in northern Tanzania have a wide range of effects , and underst and ing them will more effectively shape biomedical practitices and public health policies that are patient-centered and sensitive to TM preferences Background : The WHO estimates that more than 80 % of African population s attend traditional healers for health reasons and that 40%–60 % of these have some kind of mental illness . However , little is known about the profiles and outcome of this traditional approach to treatment . Objective : The purpose of this study was to describe the profiles and outcome of traditional healing practice s for severe mental illnesses in Jinja and Iganga districts in the Busoga region of Eastern Ug and a. Methods : Four studies were conducted . Study I used focus group discussion s ( FGDs ) with case vignettes with local community members and traditional healers to explore the lay concepts of psychosis . Studies II and III concerned a cross-sectional survey of patients above 18 years at the traditional healer 's shrines and study IV was made on a prospect i ve cohort of patients diagnosed with psychosis in study III . Manual content analysis was used in study I ; quantitative data in studies II , III , and IV were analyzed at univariate , bivariate , and multivariate levels to determine the association between psychological distress and socio-demographic factors ; for study IV , factors associated with outcome were analyzed . One-way ANOVA for independent sample s was the analysis used in Study IV . Results : The community gave indigenous names to psychoses ( mania , schizophrenia , and psychotic depression ) and had multiple explanatory models for them . Thus multiple solutions for these problems were sought . Of the 387 respondents , the prevalence of psychological distress was 65.1 % , where 60.2 % had diagnosable current mental illness , and 16.3 % had had one disorder in their lifetime . Over 80 % of patients with psychosis used both biomedical and traditional healing systems . Those who combined these two systems seemed to have a better outcome . All the symptom scales showed a percentage reduction of more than 20 % at the 3- and 6-month follow-ups . Conclusion : Traditional healers shoulder a large burden of care of patients with mental health problems . This calls for all those who share the goal of improving the mental health of individuals to engage with traditional healers Economic challenges associated with noncommunicable diseases ( NCDs ) and the sociocultural outlook of many patients especially in Africa have increased dependence on traditional herbal medicines ( THMs ) for these diseases . A cross-sectional descriptive study design ed to determine the prevalence of and reasons for THM use in the management of NCDs among South African adults was conducted in an urban , economically disadvantaged area of Cape Town , South Africa . In a cohort of 1030 participants recruited as part of the existing Prospect i ve Urban and Rural Epidemiological ( PURE ) study , 456 individuals were identified . The overall prevalence of THM use was 27 % , of which 61 % was for NCDs . Participants used THM because of a family history ( 49 % ) and sociocultural beliefs ( 33 % ) . Hypertensive medication was most commonly used concurrently with THM . Healthcare professionals need to be aware of the potential dualistic use of THM and conventional drugs by patients , as this could significantly influence health outcomes . Efforts should be made to educate patients on the potential for drug/herb interactions Background Clinical history-taking can be employed as a st and ardized approach to eluci date the use of herbal medicines and their linked suspected adverse drug reactions ( ADRs ) among hospitalized patients . We sought to identify herbal medicines nominated by Ug and an in patients ; compare nomination rates by ward and gender ; confirm the herbs ’ known pharmacological properties from published literature ; and identify ADRs linked to pre-admission use of herbal medicines . Methods Prospect i ve cohort of consented adult in patients design ed to assess medication use and ADRs on one gynaecological and three medical wards of 1790-bed Mulago National Referral Hospital . Baseline and follow-up data were obtained on patients ’ characteristics , including pre-admission use of herbal medicines . Results Fourteen percent ( 26/191 ) of females in Gynaecology nominated at least one specific herbal medicine compared with 20 % ( 114/571 ) of in patients on medical wards [ 20 % ( 69/343 ) of females ; 20 % ( 45/228 ) of males ] . Frequent nominations were Persea americana ( 30 ) , Mumbwa/multiple-herb clay rods ( 23 ) , Aloe barbadensis ( 22 ) , Beta vulgaris ( 12 ) , Vernonia amygdalina ( 11 ) , Commelina africana ( 7 ) , Bidens pilosa ( 7 ) , Hoslundia opposita ( 6 ) , Mangifera indica ( 4 ) , and Dicliptera laxata ( 4 ) . Four in patients experienced 10 suspected ADRs linked to pre-admission herbal medicine use including Commelina africana ( 4 ) , multiple-herb-mumbwa ( 1 ) , or unspecified local-herbs ( 5 ) : three ADR-cases were abortion-related and one kidney-related . Conclusions The named herbal medicines and their nomination rates generally differed by specialized ward , probably guided by local folklore knowledge of their use . Clinical elicitation from in patients can generate valuable safety data on herbal medicine use . However , larger routine studies might increase the utility of our method to assess herbal medicine use and detect herb-linked ADRs . Future studies should take testable sample s of ADR-implicated herbal medicines for further analysis This study aim ed to examine the factors associated with Chinese medicine use amongst a sample of 10,287 Australian women aged 56 - 61 years . Data was obtained from a cross-sectional postal question naire conducted in 2007 , this being the fifth survey of the Australian Longitudinal Study on Women 's Health . This representative sample of 10,287 women was r and omly selected from the Health Insurance Commission ( Medicare ) data base . The outcome measure was the use of Chinese medicine in the previous 12 months . The predictive factors included demographics , health status measures and health service utilization measures . Statistical analyses included univariate chi-square and ANOVA tests and backward stepwise multiple logistic regression modelling . The use of Chinese medicine amongst women aged 56 - 61 years appears to be strongly influenced by their country of birth , consultation with a range of CAM practitioners , and the use of some self-prescribed CAM . Interestingly , severe tiredness was the only symptom or diagnosis that predicted Chinese medicine use . Given the substantial prevalence of Chinese medicine use and the finding that the use of Chinese medicine is heavily integrated alongside the use of many other CAM and conventional treatments , it is imperative for the safety of patients that health professionals ( across complementary and conventional healthcare ) fully recognise the possible Chinese medicine use amongst their practice population s. In order to help inform relevant practice and policy development it is also important that future research further examining women 's decision-making , motivations and evaluations regarding Chinese medicine use considers such issues within the context of broader CAM and conventional health care utilization Despite the recognition for rising consumption rate of traditional medicine ( TRM ) in health and spatio-medical literature in the global scale , the impact of location in traditional therapy use has been explored least in Ghana . This paper analysed the role of spatial variation in TRM use in Kumasi Metropolis and Sekyere South District of Ashanti Region , Ghana . A retrospective cross-sectional and place-based survey was conducted in a representative sample ( N=324 ) selected through systematic r and om sampling technique . Structured interviewer-administered question naires were espoused as the main research instruments . Data were analysed with Pearson 's Chi-square and Fisher 's exact tests from the Predictive Analytics Software ( PASW ) version 17.0 . The study found that over 86 % reported TRM use . Whilst majority ( 59.1 % ) of the respondents had used TRM two or more times within the last 12 months , biologically-based therapies and energy healing were common forms of TRM accessed . Although , the use of TRM did not vary ( p>0.05 ) , knowledge about TRM , modalities of TRM and the sources of TRM differed significantly across geographically demarcated rural and urban splits ( p<0.005 ) . The study advances our underst and ing of the spatial dimensions as regards TRM utilisation Alternate medicine which has a long history has been relegated to the background by the evolution of modern medicine . In recent times , however , alternative medical therapy has been growing in popularity and getting increasing attention and interest . This study assessed the knowledge , attitude and use by urban dwellers of alternative medical therapies . This was a cross-sectional descriptive study which used a semi-structured question naire to gather information from 812 r and omly selected urban respondents . Majority 734 ( 90.4 % ) of the respondents were aware of an alternative way of getting treatment for their ailments apart from the orthodox medicine . The forms of alternative medical therapy ( AMT ) respondents were aware of include : concoction ( herbal preparations ) 683 ( 94.2 % ) ; herbalists/traditionalists 616 ( 85.0 % ) ; traditional bone setters therapy 434 ( 59.9 % ) ; among others . The main source of information was through radio 439 ( 70.9 % ) . About half 403 ( 54.9 % ) of the respondents were aware of side effects from AMT and these include diarrhea , abdominal pain and vomiting which accounts for 69.7 % ; 42.2 % and 40.2 % respectively . About 347 ( 47.3 % ) think AMT could be injurious to health . About a third 262 ( 35.7 % ) of the respondents who were aware of AMT prefers it to orthodox medicine . Reasons given for the preference were that : AMT is cheap 56 ( 21.4 % ) ; accessible 43 ( 16.4 % ) and acceptable 35 ( 13.4 % ) to them . About half 367 ( 50.0 % ) also believed AMT alone could cure their illness without resort to orthodox medical therapy ( OMT ) . Over half 401 ( 54.6 % ) of the 734 respondents that were aware of AMT had patronized or taken one form of alternative medical therapy or the other in the last 12 months prior to the study . Of these number , 323 ( 80.5 % ) had taken concoction ( herbal preparations ) . However , there was no relationship between respondents ' age , sex , educational level or religion and the patronage of AMT as all test of associations were not statistically significant p>0.05 . This study has revealed that the use of alternative medical therapies is quite popular among the studied population and a high proportion of the respondents use AMT notwithst and ing that they live in the urban communities where they have better access to orthodox medical care and medical practitioners . Regulations should be made concerning the advertisement of alternative medicine and practice s as orthodox medicine and practice s are usually not advertised Abstract : The predictors for seeking alternative therapies for HIV-infection in sub-Saharan Africa are unknown . Among a prospect i ve cohort of 442 HIV-infected patients in Moshi , Tanzania , 249 ( 56 % ) sought cure from a newly popularized religious healer in Loliondo ( 450 km away ) , and their adherence to antiretrovirals ( ARVs ) dropped precipitously ( odds ratio = 0.20 , 95 % confidence interval : 0.09 to 0.44 , P < 0.001 ) after the visit . Compared with those not attending Loliondo , attendees were more likely to have been diagnosed with HIV more remotely ( 3.8 vs. 3.0 years before , P < 0.001 ) , have taken ARVs longer ( 3.4 vs. 2.5 years , P < 0.001 ) , have higher median CD4 + lymphocyte counts ( 429 vs. 354 cells/mm3 , P < 0.001 ) , be wealthier ( wealth index : 10.9 vs. 8.8 , P = 0.034 ) , and receive care at the private versus the public hospital ( P = 0.012 ) . In multivariable logistic regression , only years since the start of ARVs remained significant ( odds ratio = 1.49 , 95 % confidence interval : 1.23 to 1.80 ) . Treatment fatigue may play a role in the lure of alternative healers OBJECTIVE To investigate the use of and expenditure on 17 of the most popular forms of complementary and alternative medicine ( CAM ) by adult Australians , sociodemographic characteristics of CAM users , and communication between CAM users and their doctors . METHODS In May-June 2005 , a sample of 1067 adults , 18 years and older , from all Australian states and territories , was recruited by r and om-digit telephone dialing and interviewed about their CAM use in the previous 12 months . RESULTS In the 12-month period , 68.9 % ( 95 % CI : 66.1%-71.7 % ) of those interviewed used at least one of the 17 forms of CAM and 44.1 % ( 95 % confidence interval : 41.1%-47.1 % ) visited a CAM practitioner . The estimated number of visits to CAM practitioners by adult Australians in the 12-month period ( 69.2 million ) was almost identical to the estimated number of visits to medical practitioners ( 69.3 million ) . The annual " out of pocket " expenditure on CAM , nationally , was estimated as 4.13 billion Australian dollars ( US $ 3.12 billion ) . Less than half of the users always informed their medical practitioners about their use of CAM . The most common characteristics of CAM users were : age , 18 - 34 ; female ; employed ; well-educated ; private health insurance coverage ; and higher-than-average incomes . CONCLUSIONS CAM use nationally in Australia appears to be considerably higher than estimated from previous Australian studies . This may reflect an increasing popularity of CAM ; however , regional variations in CAM use and the broader range of CAM included in the current study may contribute to the difference . Most frequently , doctors would not appear to be aware of their patient use of CAM Objective : To determine how knowledgeable physicians are regarding the toxic effects and drug interactions of herbal remedies . Methods : An anonymous voluntary demographic survey and 16- question , multiple-choice quiz was distributed at educational meetings of emergency medicine and internal medicine physicians . The primary outcome measures were to determine whether significant associations existed between quiz scores and the amount of clinical experience , or between quiz scores and self-assessed familiarity with the topic of herbal toxicities and adverse herb – drug interactions . Results : A total of 142 surveys and quizzes were completed by 59 attending physicians , 57 resident physicians , and 26 medical students . The mean subject score on the quiz was only slightly higher than would have occurred from r and om guessing . Neither the amount of the subjects ' clinical experience , nor their self-assessed familiarity with herbal toxicities and drug interactions correlated significantly with the score on the quiz . Conclusion : The physicians and medical students surveyed had little training in herbal toxicities and drug interactions . They generally rated their familiarity with these topics as ‘ poor ’ , and their scores on the quiz bore out this assessment as correct . Educational efforts might improve physician knowledge of the adverse effects of herbal remedies BACKGROUND Complementary medicine ( CM ) use is common among children with chronic illnesses such as epilepsy and asthma . Lack of data on the profile of CM use among children with human immunodeficiency virus ( HIV ) infection necessitated this study . METHODS Parents or caregivers of HIV-infected children attending the paediatric HIV-clinic in a teaching hospital in Lagos , Nigeria , were r and omly selected and interviewed with a semi-structured ( open- and close-ended ) question naire . Clinical details of the patients were extracted from their case files . RESULTS A total of 187 parents/caregivers were interviewed . Most of the parents/caregivers ( 181 ; 96.8 % ) have used CMs for their children . Mind-body interventions ( 181 ; 36.6 % ) and biological products ( 179 ; 36.2 % ) were frequently used . Relatives , friends and neighbours influenced CM use in 37.1 % of the children . CMs were used mostly to treat weight loss ( 79 ; 43.7 % ) , cold ( 40 ; 22.1 % ) , and fever ( 39 ; 21.6 % ) . CONCLUSION CM use is common among HIV-infected children in Lagos Objective To estimate recent prevalence data ( 2011–2013 ) on traditional , complementary and alternative medicine ( TCAM ) provider use and sociodemographic and health related correlates in nationally representative population sample s from 32 countries from all world regions . Methods This secondary analysis was based on the International Social Survey Program ( ISSP ) , 2011–2013 , Health and Health Care Module . In a cross-sectional population -based survey ( N=52,801 ) , simple or multi-stage stratified r and om sampling was used , result ing in representative sample s of the adult population of respective countries . Results Overall , the 12-month TCAM provider use prevalence was 26.4 % , ranging from under 10 % in Bulgaria , Pol and and Slovenia to over 50 % in China mainl and , the Philippines and Republic of Korea . Over 80 % TCAM treatment satisfaction was found in Europe in Denmark , Slovenia , Spain and Switzerl and , in Asia in Taiwan ( China ) and USA . Multivariate logistic regression found sociodemographic variables ( middle age , female sex , lower educational status , not having a religious affiliation , and lower economic indicators ) and health variables ( perceived poor or fair health status , being unhappy and depressed , having a chronic condition or disability , and having positive attitudes towards TCAM ) were associated with TCAM provider use . Conclusions A high prevalence TCAM provider use was found in all world regions and several sociodemographic and health related factors of its use were identified Purpose : The aim of this study was to determine the types and nature of traditional eye medications ( TEMs ) , their sources , and the ocular complications that may arise from use in a teaching hospital in Nigeria . Material s and Methods : A prospect i ve study of consecutive subjects who used TEM before presentation to the Eye Clinic of the University of Benin Teaching Hospital , Benin City , Nigeria between July 1 , 2004 and June 30 , 2008 . P < 0.05 was considered statistically significant . Results : A total of 113 subjects were evaluated of which 64 were males ( 56.6 % ) , females ( 43.4 % ) were females . There was no significant difference in the number of males and females ( P > 0.05 ) . Rural dwellers were more likely to use TEM than urban dwellers ( P < 0.0001 ) . The mean age of the subjects was 47.9 ± 22.3 years ( range , 4 - 90 years ) . The most common traditional medication was derived from plant extracts ( 54.9 % ) followed by concoctions ( 21.2 % ) . Complications occurred in 54.8 % of the subjects . Ocular complications included corneal opacities in 13.35 % of subjects , staphyloma in 9 % , and corneal ulcers in 8 % . Other complications were panophthalmitis , endophthalmitis , uveitis , cataract , and bullous keratopathy . Eleven subjects underwent evisceration or enucleation of the affected eye . There was no significant difference in the type of medication used and ocular complications ( P = 0.956 ) . Sources of TEM were self-medication in 38.9 % of subjects , relatives in 27.4 % , and traditional healers in 17.7 % . Conclusion : The use of TEM is a common practice that could be harmful and lead to blindness . Proper health education of the public and traditional healers can reduce the prevalence of preventable blindness BACKGROUND Despite the reported widespread use of herbal medicines globally and their benefits , they are not completely without potential to cause harm . The haphazard , irresponsible or non-regulated use of several herbal medicines may put the health of their users at risk of toxicity . OBJECTIVE This study aim ed to assess the general perception of the safety and occurrence of adverse effects of herbal medicines among residents of Ikorodu in Lagos , Nigeria . METHODS The study population included 400 r and omly selected and consented residents in Ikorodu . Data was collected using a st and ard closed and open-ended structured question naire with three ( 3 ) sections on socio-demography , safety and adverse effects of herbal medicines . Associations between the variables were determined using Chi square analysis . RESULTS The results showed that 333 respondents ( 82.4 % ) believed that herbal medicines are safe for use and only 39 ( 9.7 % ) held the view that they may not be safe . RESULTS also show that 51 ( 12.6 % ) of respondents had experienced adverse effects while 250 ( 61.9 % ) said they had never experienced adverse effects from the use of herbal medicines . CONCLUSION Herbal medicine is popular among the respondents but they appear to be ignorant of its potential toxicities . It may be necessary to educate the consumers of herbal medicines on the potentials for herbs-drugs interaction and adverse effects specially as a result of indiscriminate and unguided use of herbal medicines BACKGROUND Traditional bone setting is a practice that is common in our environment . This is a community based survey of opinions concerning orthodox and traditional fracture management in four states of the middle belt of Nigeria . We set out to ascertain the factors influencing preference of treatment of fractures among population s in the middle belt of Nigeria . METHODOLOGY A community based question naire survey of r and omly selected adults regarding preference of choice of treatment between orthodox and traditional fracture management . RESULTS One hundred and eighty-six question naires were found analyzable with a male to female ratio of 2:1 . There was a preponderance of preference for orthodox fracture management ( 70.4 % ) . Decisions were mainly collegiate , outside the influence of the individual ; only 9.9 % decided to attend traditional bone setters on their own . CONCLUSION Reasons adduced for preference of traditional bone setters were incongruous and inconsistent . A fixated cultural outlook was recognized as being the motivating factor for patronage of traditional bone setters . Need for enlightenment campaign of the public against patronage of traditional bone setters is emphasized . A gradual phasing out of traditional bone setting with a road map towards making orthodox fracture management available to all is advocated ETHNOPHARMACOLOGICAL RELEVANCE Most adults in West Africa treat acute febrile illnesses with local herbs , but the patterns of herbs used for malaria have not been recently described in Sierra Leone . MATERIAL S AND METHODS We used a population -based cross-sectional approach to interview 810 r and omly- sample d rural and urban adult residents of Bo , Sierra Leone , in December 2013 and January 2014 about their use of herbal remedies when they suspect they have malaria . RESULTS In total , 55 % of the participants reported taking one or more of seven herbs to treat symptoms of malaria . Among herb users , the most commonly used anti-malarial herbs were Moringa oleifera ( moringa , 52 % ) and Sarcocephalus latifolius ( yumbuyambay , 50 % ) . The other herbs used included Senna siamea ( shekutoure , 18 % ) , Cassia sieberiana ( gbangba , 18 % ) , Uvaria afzelii ( gone-botai , 14 % ) , Morinda chrysorhiza ( njasui , 14 % ) , and Craterispermum laurinum ( nyelleh , 7 % ) . Combination herbal therapy was common , with 37 % of herb users taking two or more herbs together when ill with suspected malaria . CONCLUSIONS Indigenous medical knowledge about herbal remedies and combinations of local herbs remains an integral part of malaria case management in Sierra Leone Background : Traditional medicine ( TM ) has maintained its popularity in all regions of the developing world . Even though , the wide acceptance of TM is a well-established fact , its status in a population with access to modern health is not well clear in the whole country . This study was carried out to assess the knowledge , attitudes , practice and management of TM among the community of Burka Jato Kebele , West Ethiopia . Methodology : A descriptive cross-sectional study was conducted on a total of 282 sample d individuals ’ selected using systematic r and om sampling from January 28 , 2013 to February 8 , 2013 in Burka Jato Kebele , Nekemte town , East Wollega Zone , West of Ethiopia . Results : The majority ( 94.22 % ) of people in the study area relied on TM . Most of them were aware of medicinal herbs ( 55.7 % ) . About half ( 40.79 % ) of the respondents were aware of the major side-effects of TM such as diarrhea ( 36.64 % ) . About 31.85 % of them prefer traditional medical practice s ( TMP ) because they are cheap . Most ( 50 % ) of the species were harvested for their leaves to prepare remedies , followed by seed ( 21.15 % ) and root ( 13.46 % ) and the methods of preparation were pounding ( 27.54 % ) , crushing ( 18.84 % ) , a concoction ( 15.95 % ) and squeezing ( 13.04 % ) . About 53.84 % of them were used as fresh preparations . Remedies were reported to be administered through oral ( 53.85 % ) , dermal or topical ( 36.54 % ) , buccal ( 3.85 % ) and anal ( 5.77 % ) . Conclusion : The study revealed that the use of TMs were quite popular among the population and a large proportion of the respondents not only preferred , but also used TMs notwithst and ing that they lived in the urban communities with better access to modern medical care and medical practitioners . To use TM as a valuable alternative to conventional western medicine , further investigation must be undertaken to determine the validity , efficacy of the plants to make it available as an alternative medicine to human beings |
12,790 | 30,899,427 | The absolute tumour blood flow ( TBF ) values can differentiate high- grade gliomas ( HGGs ) from low- grade gliomas ( LGGs ) and grade II from grade IV tumours .
However , it lacked the capacity to differentiate grade II from grade III tumours and grade III from grade IV tumours .
In contrast , the relative TBF ( rTBF ) is effective in differentiating HGG from LGG and in glioma grading .
The maximum rTBF ( rTBFmax ) demonstrated the best results in glioma grading .
Sensitivity and specificity analysis replicate these results as well .
This meta- analysis suggests that ASL is useful for glioma grading , especially when considering the rTBFmax parameter | This study aim ed to evaluate the diagnostic performance of arterial spin labelling ( ASL ) in grading of adult gliomas . | Objective : To assess the value of spectroscopic and perfusion MRI for glioma grading and for distinguishing glioblastomas from metastases and from CNS lymphomas . Methods : The authors examined 79 consecutive patients with first detection of a brain neoplasm on nonenhanced CT scans and no therapy prior to evaluation . Spectroscopic MRI ; arterial spin-labeling MRI for measuring cerebral blood flow ( CBF ) ; first-pass dynamic , susceptibility-weighted , contrast-enhanced MRI for measuring cerebral blood volume ; and T1-weighted dynamic contrast-enhanced MRI were performed . Receiver operating characteristic analysis was performed , and optimum thresholds for tumor classification and glioma grading were determined . Results : Perfusion MRI had a higher diagnostic performance than spectroscopic MRI . Because of a significantly higher tumor blood flow in glioblastomas compared with CNS lymphomas , a threshold value of 1.2 for CBF provided sensitivity of 97 % , specificity of 80 % , positive predictive value ( PPV ) of 94 % , and negative predictive value ( NPV ) of 89 % . Because CBF was significantly higher in peritumoral nonenhancing T2-hyperintense regions of glioblastomas compared with metastases , a threshold value of 0.5 for CBF provided sensitivity , specificity , PPV , and NPV of 100 % , 71 % , 94 % , and 100 % . Glioblastomas had the highest tumor blood flow values among all other glioma grade s. For discrimination of glioblastomas from grade 3 gliomas , sensitivity was 97 % , specificity was 50 % , PPV was 84 % , and NPV was 86 % ( CBF threshold value of 1.4 ) , and for discrimination of glioblastomas from grade 2 gliomas , sensitivity was 94 % , specificity was 78 % , PPV was 94 % , and NPV was 78 % ( CBF threshold value of 1.6 ) . Conclusion : Perfusion MRI is predictive in distinguishing glioblastomas from metastases , CNS lymphomas and other gliomas vs. MRI and magnetic resonance spectroscopy Background The treatment goal for recurrent malignant gliomas centers on disease stabilization while minimizing therapy-related side effects . Metronomic dosing of cytotoxic chemotherapy has emerged as a promising option to achieve this objective . Methods This phase I study was performed using metronomic temozolomide ( mTMZ ) at 25 or 50 mg/m2/day continuously in 42-day cycles . Correlative studies were incorporated using arterial spin labeling MRI to assess tumor blood flow , analysis of matrix metalloproteinase-2 ( MMP-2 ) and MMP-9 activities in the cerebrospinal fluid ( CSF ) as surrogates for tumor angiogenesis and invasion , as well as determination of CSF soluble interleukin-2 receptor alpha ( sIL-2Rα ) levels as a marker of immune modulation . Results Nine subjects were enrolled and toxicity consisted of primarily grade 1 or 2 hematological and gastrointestinal side effects ; only one patient had a grade 3 elevated liver enzyme level that was reversible . Tumor blood flow was variable across subjects and time , with two experiencing a transient increase before a decrease to below baseline level while one exhibited a gradual drop in blood flow over time . MMP-2 activity correlated with overall survival but not with progression free survival , while MMP-9 activity did not correlate with either outcome parameters . Baseline CSF sIL-2Rα level was inversely correlated with time from initial diagnosis to first progression , suggesting that subjects with higher sIL-2Rα may have more aggressive disease . But they lived longer when treated with mTMZ , probably due to drug-related changes in T-cell constituency . Conclusions mTMZ possesses efficacy against recurrent malignant gliomas by altering blood flow , slowing invasion and modulating antitumor immune function BACKGROUND AND PURPOSE : The purpose of this study was to determine whether qualitative and quantitative measures obtained with pulsed arterial spin-labeling ( PASL ) and apparent diffusion coefficients ( ADC ) improve glioma grading compared with conventional MR images . MATERIAL S AND METHODS : We prospect ively performed 2 qualitative consensus review s in 33 suspected gliomas : 1 ) conventional MR images alone and 2 ) conventional MR images with PASL and ADC . To calculate the diagnostic performance parameters of PASL and ADC , we used a qualitative scoring system on the basis of the tumor perfusion signal intensity ( sTP ) and visual ADC scoring ( sADC ) . We then analyzed quantitative regions of interest and calculated the ratio of the maximum tumor perfusion signal intensity ( rTPmax ) and the minimum ADC value ( mADC ) . RESULTS : Two observers diagnosed accurate tumor grade s in 23 of 33 ( 70 % ) lesions in the first review and in 29 of 33 ( 88 % ) lesions in the second review . The sensitivity , specificity , positive predictive value ( PPV ) , and negative predictive value ( NPV ) for determining a glioma grading by using combined sTP and sADC scoring were 90.9 , 90.9 , 95.2 , and 83.3 % , respectively . Statistical analysis gave a threshold value of 1.24 for rTPmax and 0.98 × 10–3 mm/s2 for mADC to provide a sensitivity , specificity , PPV , and NPV of 95.5 , 81.8 , 91.3 , and 90.1 % and 90.9 , 81.8 , 90.9 , and 81.8 % , respectively . The receiver operator characteristic curve analyses showed no significant difference between the quantitative and combined qualitative parameters . CONCLUSION : PASL and ADC significantly improve the diagnostic accuracy of glioma grading compared with conventional imaging |
12,791 | 22,972,094 | Early application of N-acetylcysteine to prevent the development of an oxidato-inflammatory response did not affect the outcome , nor did late application that is after 24 hours of developing symptoms .
Late application was associated with cardiovascular instability .
AUTHORS ' CONCLUSIONS Overall , this meta- analysis puts doubt on the safety and utility of intravenous N-acetylcysteine as an adjuvant therapy in SIRS and sepsis .
At best , N-acetylcysteine is ineffective in reducing mortality and complications in this patient population .
At worst , it can be harmful , especially when administered later than 24 hours after the onset of symptoms , by causing cardiovascular depression . | BACKGROUND Death is common in systemic inflammatory response syndrome ( SIRS ) or sepsis-induced multisystem organ failure and it has been thought that antioxidants such as N-acetylcysteine could be beneficial .
OBJECTIVES We assessed the clinical effectiveness of intravenous N-acetylcysteine for the treatment of patients with SIRS or sepsis . | BACKGROUND Glutathione ( GSH ) deficiency is common in HIV-infected individuals and is associated with impaired T cell function and impaired survival . N-acetylcysteine ( NAC ) is used to replenish GSH that has been depleted by acetaminophen overdose . Studies here test oral administration of NAC for safe and effective GSH replenishment in HIV infection . DESIGN Oral NAC administration in a r and omized , 8-week double-blind , placebo-controlled trial followed by optional open-label drug for up to 24 weeks . SUBJECTS HIV-infected , low GSH , CD4 T cells < 500 micro L(-1 ) , no active opportunistic infections or other debilitation ; n = 81 . Study conducted prior to introduction of protease inhibitors . RESULTS Whole blood GSH levels in NAC arm subjects significantly increased from 0.88 mM to 0.98 mM , bringing GSH levels in NAC-treated subjects to 89 % of uninfected controls ( P = 0.03 ) . Baseline GSH levels in the placebo group ( 0.91 ) remained essentially the same during the 8 week placebo-controlled trial . T cell GSH , adjusted for CD4 T cell count and beta2-microglobulin levels , also increased in the NAC-treated subjects ( P = 0.04 ) . Adverse effects were minimal and not significantly associated with NAC ingestion . CONCLUSION NAC treatment for 8 weeks safely replenishes whole blood GSH and T cell GSH in HIV-infected individuals . Thus , NAC offers useful adjunct therapy to increase protection against oxidative stress , improve immune system function and increase detoxification of acetaminophen and other drugs . These findings suggest that NAC therapy could be valuable in other clinical situations in which GSH deficiency or oxidative stress plays a role in disease pathology , e.g. rheumatoid arthritis , Parkinson 's disease , hepatitis , liver cirrhosis , septic shock and diabetes OBJECTIVE We aim ed to evaluate the efficacy of low dose N-acetylcysteine ( NAC ) against myocardial ischemia-reperfusion damage in coronary artery bypass surgery accompanied by cardiopulmonary bypass ( CPB ) . METHODS Thirty patients operated due to triple coronary artery disease were enrolled into this prospect i ve r and omized study ( control group -n=15 and NAC group - n=15 ) . N-acetylcysteine was added to induction cardioplegia solution in dose of 4 mmol/l and in dose of 2 mmol/l to maintenance cardioplegia solution in the NAC group . Hemodynamic measurements were performed before and after anesthesia with different intervals . Creatine kinase-MB ( CK-MB ) levels were analyzed during 24 hours postoperatively . Blood sample s were obtained from coronary sinus before CPB ( T1 ) , just before the cross-clamp removed ( T2 ) and 30 minutes later ( T3 ) . Malondialdehyde ( MDA ) , glutathione peroxidase ( GSH-Px ) , nitric oxide ( NO ) levels and neutrophil percentage were determined . Statistical analysis was performed using student 's t test , Chi-square and two-way ANOVA tests . RESULTS There were no significant differences between the two groups with regard to the hemodynamic parameters , and CK-MB levels . The MDA levels were significantly lower in NAC group than in control group during reperfusion period ( 0.75 nmol/l vs 0.88 nmol/l , p<0.05 ) . Neutrophil percentage in coronary sinus blood was significantly lower in NAC group than in control group during the reperfusion period ( 77.6 % vs 82.7 % , p<0.05 ) . The GSH-Px and NO levels were also not statistically different between groups . CONCLUSION Low dose NAC as an adjunct to cardioplegic solutions effectively reduces myocardial oxidative stress in coronary bypass surgery with cardiopulmonary bypass , but may not restore the myocardial injury In a r and omized , double – blind study , 131 consecutive patients , subjected to elective upper laparotomy , were prophylactically given the recommended dose of N – acetylcysteine ( NAC ) ( Mucomyst , ASTRA ) ( 200 mg × 3 ) or placebo against postoperative pulmonary complications . The effect was evaluated by lung function tests ( VC and FEV1 ) , arterial blood gas analyses and chest x – ray . No benefit could be demonstrated , either to postoperative pulmonary function or in the frequency of atelectasis in the recommended dose . However , no patients with preoperative bronchopulmonary disease dem and ing treatment with bronchodilatators were included in the study . A positive effect of NAC in this category of patients could not be excluded OBJECTIVE --To see whether intravenous acetylcysteine would improve outcome in patients with fulminant hepatic failure after paracetamol overdose . DESIGN --A prospect i ve r and omised controlled study . SETTING --The Institute of Liver Studies , King 's College Hospital , London . PATIENTS --50 consecutive patients ( 21 male ) aged 16 - 60 with fulminant hepatic failure after paracetamol overdose who had not previously received acetylcysteine . INTERVENTIONS --Conventional intensive liver care plus either acetylcysteine ( 25 patients ) in the same dose regimen as used early after a paracetamol overdose , except that the infusion was continued until recovery from encephalopathy or death , or an equivalent volume of 5 % dextrose ( 25 patients ) . MAIN OUTCOME MEASURES --Survival ; incidence of cerebral oedema , renal failure , and hypotension requiring inotropic support ; liver function as assessed by prolongation of the prothrombin time ; and degree of encephalopathy . RESULTS --The rate of survival was significantly higher in the acetylcysteine treated group than in the controls ( 48 % ( 12/25 patients ) v 20 % ( 5/25 ) ; p = 0.037 , 95 % confidence interval for difference in proportions surviving 3 % to 53 % ) . Acetylcysteine treated patients had a lower incidence of cerebral oedema ( 40 % ( 10/25 ) v 68 % ( 17/25 ) ; p = 0.047 , 95 % confidence interval for difference in incidence 2 % to 54 % ) , and fewer developed hypotension requiring inotropic support ( 48 % ( 12/25 ) v 80 % ( 20/25 ) ; p = 0.018 , 95 % confidence interval 7 % to 57 % ) . Rates of deterioration and recovery of liver function , however , were similar in the two groups . No adverse reactions to acetylcysteine were seen . CONCLUSIONS --Acetylcysteine is safe and effective in fulminant hepatic failure after paracetamol overdose The role of N-acetylcystein ( NAC ) administration on the oxidative response of neutrophils during cardiopulmonary bypass ( CPB ) was evaluated in a double-blind study . Twenty-four adult patients undergoing coronary artery bypass were included in the study . Twelve patients received NAC as a bolus of 100 mg/kg followed by a continuous infusion of 20 mg/kg/h in the bypass circuit from the beginning to the end of bypass . A further 12 patients received placebo . Citrated blood sample s for measurement of oxidative burst response of neutrophils were obtained at different time points during bypass . The oxidative burst response of neutrophils in the patients receiving NAC was significantly low at all times during bypass . Based on these findings NAC appears to act as an oxygen free radical scavenger during open-heart surgery BACKGROUND & AIMS N-acetylcysteine ( NAC ) , an antidote for acetaminophen poisoning , might benefit patients with non-acetaminophen-related acute liver failure . METHODS In a prospect i ve , double-blind trial , acute liver failure patients without clinical or historical evidence of acetaminophen overdose were stratified by site and coma grade and assigned r and omly to groups that were given NAC or placebo ( dextrose ) infusion for 72 hours . The primary outcome was overall survival at 3 weeks . Secondary outcomes included transplant-free survival and rate of transplantation . RESULTS A total of 173 patients received NAC ( n = 81 ) or placebo ( n = 92 ) . Overall survival at 3 weeks was 70 % for patients given NAC and 66 % for patients given placebo ( 1-sided P = .283 ) . Transplant-free survival was significantly better for NAC patients ( 40 % ) than for those given placebo ( 27 % ; 1-sided P = .043 ) . The benefits of transplant-free survival were confined to the 114 patients with coma grade s I-II who received NAC ( 52 % compared with 30 % for placebo ; 1-sided P = .010 ) ; transplant-free survival for the 59 patients with coma grade s III-IV was 9 % in those given NAC and 22 % in those given placebo ( 1-sided P = .912 ) . The transplantation rate was lower in the NAC group but was not significantly different between groups ( 32 % vs 45 % ; P = .093 ) . Intravenous NAC generally was well tolerated ; only nausea and vomiting occurred significantly more frequently in the NAC group ( 14 % vs 4 % ; P = .031 ) . CONCLUSIONS Intravenous NAC improves transplant-free survival in patients with early stage non-acetaminophen-related acute liver failure . Patients with advanced coma grade s do not benefit from NAC and typically require emergency liver transplantation Objective : Markers of oxidative stress are reported to be increased in severe malaria . It has been suggested that the antioxidant N-acetylcysteine ( NAC ) may be beneficial in treatment . We studied the efficacy and safety of parenteral NAC as an adjunct to artesunate treatment of severe falciparum malaria . Design : A r and omized , double-blind , placebo-controlled trial on the use of high-dose intravenous NAC as adjunctive treatment to artesunate . Setting : A provincial hospital in Western Thail and and a tertiary referral hospital in Chittagong , Bangladesh . Patients : One hundred eight adult patients with severe falciparum malaria . Interventions : Patients were r and omized to receive NAC or placebo as an adjunctive treatment to intravenous artesunate . Measurements and Main Results : A total of 56 patients were treated with NAC and 52 received placebo . NAC had no significant effect on mortality , lactate clearance times ( p = 0.74 ) , or coma recovery times ( p = 0.46 ) . Parasite clearance time was increased from 30 hours ( range , 6–144 hours ) to 36 hours ( range , 6–120 hours ) ( p = 0.03 ) , but this could be explained by differences in admission parasitemia . Urinary F2-isoprostane metabolites , measured as a marker of oxidative stress , were increased in severe malaria compared with patients with uncomplicated malaria and healthy volunteers . Admission red cell rigidity correlated with mortality , but did not improve with NAC . Conclusion : Systemic oxidative stress is increased in severe malaria . Treatment with NAC had no effect on outcome in patients with severe falciparum malaria in this setting OBJECTIVE To determine the effects of intravenous N-acetylcysteine ( NAC ) on the development of severe adult respiratory distress syndrome ( ARDS ) and mortality rate in patients with mild-to-moderate acute lung injury and to analyze the duration of ventilatory support and FIO2 required as well as the evolution of the lung injury score . SETTING Three university hospital ICUs and one regional ICU in Switzerl and . PATIENTS Sixty-one adult patients presenting with mild-to-moderate acute lung injury and various predisposing factors for ARDS received either NAC , 40 mg/kg/d , or placebo intravenously for 3 days . MEASUREMENTS Respiratory dysfunction was assessed daily according to the need for mechanical ventilation and FIO2 , the evolution of the lung injury score , and the PaO2/FIO2 ratio . The cardiovascular state , liver function , and kidney function were also monitored . Data were collected at admission ( day 0 ) , during the first 3 days , and on the day of discharge from the ICU . RESULTS The NAC and placebo groups ( 32 and 29 patients , respectively ) were comparable at ICU admission for severity of illness assessed by the simplified acute physiology score ( SAPS ) ( 10.8 + /- 4.6 vs 10.9 + /- 4.8 ) and lung injury score ( LIS ) ( 1.39 + /- 0.95 vs 1.11 + /- 1.08 ) ( mean + /- SD ) . Three patients in each group developed ARDS . The 1-month mortality rate was 22 percent for the NAC group and 35 percent for the placebo group ( difference not statistically significant ) . At admission , 22 of 32 patients ( 69 percent ) in the NAC group were mechanically ventilated compared with 22 of 29 ( 76 percent ) in the placebo group . At the end of the treatment period ( day 3 ) , 5 of 29 ( 17 percent ) in the NAC group and 12 of 25 ( 48 percent ) in the placebo group were still receiving ventilatory support ( p = 0.01 ) , The FIO2 was 0.37 less than admission value ( day 0 ) in the NAC group , and 0.20 less in the placebo group ( p < 0.04 ) ; the oxygenation index ( PaO2/FIO2 ) improved significantly ( p < 0.05 ) from day 0 to day 3 only in the NAC-treated group . The LIS showed a significant regression ( p = 0.003 ) in the NAC-treated group during the first 10 days of treatment : no change was observed in the placebo group . No adverse effects were observed during the treatment with NAC . CONCLUSIONS Intravenous NAC treatment during 72 h improved systemic oxygenation and reduced the need for ventilatory support in patients presenting with mild-to-moderate acute lung injury subsequent to a variety of underlying diseases . Development of ARDS and mortality were not reduced significantly by this therapy STUDY OBJECTIVE To assess the effects of adjunctive treatment with N-acetyl-L-cysteine ( NAC ) on hemodynamics , oxygen transport variables , and plasma levels of cytokines in patients with septic shock . DESIGN Prospect i ve , r and omized , double-blind , placebo-controlled study . SETTING A 24-bed medicosurgical ICU in a university hospital . PATIENTS Twenty-two patients included within 4 h of diagnosis of septic shock . INTERVENTIONS Patients were r and omly allocated to receive either NAC ( 150 mg/kg bolus , followed by a continuous infusion of 50 mg/kg over 4 h ; n= 12 ) or placebo ( n=10 ) in addition to st and ard therapy . MEASUREMENTS Plasma concentrations of tumor necrosis factor-alpha ( TNF ) , interleukin (IL)-6 , IL-8 , IL-10 , and soluble tumor necrosis factor-alpha receptor-p55 ( sTNFR-p55 ) were measured by sensitive immunoassays at 0 , 2 , 4 , 6 and 24 h. Pulmonary artery catheter-derived hemodynamics , blood gases , hemoglobin , and arterial lactate were measured at baseline , after infusion ( 4 h ) , and at 24 h. RESULTS NAC improved oxygenation ( PaO2/FIO2 ratio , 214+/-97 vs 123+/-86 ; p<0.05 ) and static lung compliance ( 44+/-11 vs 31+/-6 L/cm H2O ; p<0.05 ) at 24 h. NAC had no significant effects on plasma TNF , IL-6 , or IL-10 levels , but acutely decreased IL-8 and sTNFR-p55 levels . The administration of NAC had no significant effect on systemic and pulmonary hemodynamics , oxygen delivery , and oxygen consumption . Mortality was similar in both groups ( control , 40 % ; NAC , 42 % ) but survivors who received NAC had shorter ventilator requirement ( 7+/-2 days vs 20+/-7 days ; p<0.05 ) and were discharged earlier from the ICU ( 13+/-2 days vs 32+/-9 days ; p<0.05 ) . CONCLUSION In this small cohort of patients with early septic shock , short-term IV infusion of NAC was well-tolerated , improved respiratory function , and shortened ICU stay in survivors . The attenuated production of IL-8 , a potential mediator of septic lung injury , may have contributed to the lung-protective effects of NAC OBJECTIVES To investigate whether prolonged infusion of N-acetylcysteine ( NAC ) that is commenced immediately after admission to the intensive care unit could ameliorate the development or progression of multisystem organ failure and improve mortality . DESIGN Prospect i ve , r and omized , double-blinded clinical trial . SETTING Six-bed intensive care unit in a teaching hospital . PATIENTS Of the 100 patients recruited ( 14 withdrew ) , 86 patients were studied . INTERVENTIONS After r and omization , the treatment group ( n = 41 ) received NAC ( 150 mg/kg bolus followed by a continuous infusion of 12 mg/kg/hr ) and the placebo group ( n = 45 ) received 5 % dextrose , from a minimum of 3 days up to a maximum of 5 days . MEASUREMENTS AND MAIN RESULTS There was no statistically significant difference between the two groups regarding outcome as indicated by mortality and the required days of inotropic support , mechanical ventilation , and intensive care . The time interval between hospital and intensive care unit admission showed great variability , with a median of 24 hrs for the whole sample . By splitting the groups with this median value , the effect of NAC was examined on patients admitted within 24 hrs and after 24 hrs of arrival to the hospital . There was a nonsignificant difference in mortality in favor of NAC . Patients admitted after 24 hrs of hospital admission had a significantly worse mortality in the NAC-treated group ( 61 % vs. 32 % for controls ; p = .05 ) . CONCLUSIONS We found a nonsignificant difference in outcome between NAC and placebo-treated patients . Our results suggest that the initiation of NAC treatment > 24 hrs after hospital admission may potentially be harmful , and further studies should be undertaken to investigate the clinical use of the early application of NAC in critically ill patients Objective : When used to prevent perioperative inflammation and ischemia – reperfusion injury , N-acetylcysteine may inadvertently impair hemostasis . We , therefore , performed a post hoc analysis of a recent r and omized controlled trial in cardiac surgery to determine whether N-acetylcysteine was associated with increased blood loss and blood product transfusion . Design : Blinded ( patients , caregivers , outcome assessors ) placebo-controlled parallel group r and omized trial ( www . Clinical Trials.gov ID NCT00188630 ) . Setting : Tertiary care hospital in Toronto , Ontario , Canada ( September 2003 to October 2005 ) . Patients : A total of 177 patients with preexisting moderate renal insufficiency ( estimated glomerular filtration rate ≤60 mL/min ) and undergoing cardiac surgery . Interventions : Eighty-nine patients were r and omized to receive intravenous N-acetylcysteine ( 100 mg/kg bolus ; 20 mg·kg−1·hr−1 infusion until 4 hours after cardiopulmonary bypass ) , and 88 were r and omized to receive placebo . Measurements and Main Results : We used laboratory markers ( hemoglobin , platelets , coagulation ) , chest-tube blood loss , and blood product transfusion to evaluate hemostasis . Compared with placebo , patients who received N-acetylcysteine arm experienced a mean 24-hour chest-tube blood loss that was 261 mL higher ( 95 % confidence interval [ CI ] 93–488 mL , p = 0.008 ) , and were transfused 1.6 more units of red blood cells ( 95 % CI 0.4–3.1 units , p = 0.02 ) during hospitalization . The risk of receiving ≥5 units of red blood cells within 24 hours of surgery was significantly higher with N-acetylcysteine ( relative risk 1.85 , 95 % CI 1.06–3.21 , p = 0.03 ; adjusted relative risk 2.09 , 95 % CI 1.24–3.83 , p = 0.005 ) . Conclusions : In patients who have preexisting moderate renal insufficiency and are undergoing cardiac surgery , N-acetylcysteine was associated with important effects on blood loss and blood product transfusion . Clinicians and research ers should , therefore , consider the potential for impaired hemostasis when using N-acetylcysteine in the perioperative setting . Further research is needed to eluci date mechanisms by which N-acetylcysteine may impair hemostasis , and the risk – benefit profile of N-acetylcysteine for perioperative organ protection Reactive oxygen species and inflammation have been implicated in renal tubule cell injury . However , there is some controversy concerning whether antioxidants might attenuate oxidative damage and inflammation in humans after hypotension in the setting of critical illness . This study was a prospect i ve , r and omized , double-blinded , placebo-controlled study that included patients with hypotension . Patients were r and omized to receive either N-acetylcysteine ( NAC ; 50 mg/kg by 4 hours followed by 100 mg/kg/d for 48 hours diluted in 5 % glucose ) and deferoxamine ( DFX ; at a single dose of 1000 mg diluted in 5 % glucose ) or placebo . The primary study outcome was the serum levels of markers of oxidative damage and inflammatory response . Secondary outcomes included the incidence of acute renal failure , serum creatinine at hospital discharge , intensive care unit length of stay , and length of hospital stay . Thirty patients were enrolled in the study . The use of NAC plus DFX decreased the oxidative damage parameters but not plasma interleukin-6 levels . In contrast , plasma nitrite levels increased 24 hours after NAC plus DFX administration . On analysis of secondary outcomes , it was observed that creatinine levels at hospital discharge were lower in patients receiving NAC plus DFX when compared with placebo . NAC plus DFX administration was able to decrease plasma markers of oxidative damage and creatinine levels at hospital discharge Cancer of the esophagus has a poor long-term prognosis and a high peri-operative morbidity in which pulmonary complications play a major role . The combination of the surgical approach , pre-existing pulmonary disorders , poor nutritional status and the release of pro-inflammatory cytokines may be contributing factors . N-acetylcysteine ( ( NAC ) has been shown to have oxygen scavenging abilities . In severe sepsis and acute respiratory distress syndrome , positive effects of NAC on morbidity and mortality were discovered . In this observational study peri-operative high dose NAC was administered in 22 patients . The effects of this treatment on respiratory function , morbidity and survival were studied . These prospect ively collected data were compared with data of a matched , retrospective group without NAC treatment . There were no significant differences between the groups in terms of socio-demographic data , preoperative pulmonary function , intra-operative course and oncologic characteristics . The oxygenation indices at the postoperative hours 2 ( P = 0.019 ) , 4 ( P < 0.001 ) , 8 ( P = 0.035 ) , 12 ( P = 0.035 ) and 24 ( P = 0.046 ) were significantly higher in the NAC group . After 36 h , the difference between groups was no longer significant ( P = 0.064 ) . NAC-treated patients showed significant lower overall pulmonary morbidity , 45.5 % versus 81.8 % ( P = 0.027 ) . Surgical morbidity , intensive care unit and hospital stay were not significantly different between groups , mortality was zero . Kaplan-Meier curves showed no significant difference in survival 12 months postoperatively . These data indicate that postoperative oxygenation can be improved and rate of overall pulmonary complications is reduced using peri-operative high dose NAC in transthoracic esophagectomy STUDY OBJECTIVE The level of microalbuminuria is thought to reflect the severity of inflammation-induced systemic vascular permeability and may have prognostic value with regard to organ dysfunction and survival . N-acetylcysteine ( NAC ) has been shown to decrease capillary leakage in experimental sepsis . The present study investigated the effect of early treatment with NAC on microalbuminuria and organ dysfunction in severe clinical sepsis . DESIGN Prospect i ve , r and omized , placebo-controlled study . SETTING A 24-bed multidisciplinary ICU in a university teaching hospital . PATIENTS Thirty-five patients included within 4 h of fulfilling consensus criteria of severe sepsis . INTERVENTIONS Patients were r and omly assigned to receive either NAC ( continuous infusion starting with 50 mg/kg/4 h followed by 100 mg/kg/24 h for 44 h ; n = 18 ) or placebo ( n = 17 ) in addition to st and ard therapy . MEASUREMENTS AND RESULTS Urine sample s for measurement of microalbuminuria/creatinine ratio ( MACR ) were collected on inclusion and after 4 h , 24 h , and 48 h. Severity of illness and degree of organ failure were determined by using , respectively , the APACHE ( acute physiology and chronic health evaluation ) II score and the sequential organ failure assessment ( SOFA ) score . The MACR did not differ over time between the placebo- and the NAC-treated groups . SOFA scores were comparable between both treatment groups at baseline ( 6.2 + /- 3.9 vs 6.5 + /- 2.7 , NAC vs placebo ; p = 0.6 ) and increased during treatment in the NAC-treated patients but not in the placebo group ( 7.9 + /- 3.7 vs 5.9 + /- 2.5 , p = 0.09 and 7.7 + /- 3.8 vs 5.1 + /- 2.1 , p < 0.05 ; NAC vs placebo , respectively , at 24 h and at 48 h ) . The cardiovascular SOFA score progressively increased during NAC treatment , reaching higher values as compared to time-matched scores in the placebo group . CONCLUSIONS Early NAC administration does not influence the course of MACR in severe clinical sepsis , suggesting that NAC might not attenuate endothelial damage in this condition . NAC treatment even aggravated sepsis-induced organ failure , in particular cardiovascular failure Objective : To assess the preventive effect of the antioxidant N-acetylcysteine on postoperative acute renal failure in patients with renal insufficiency undergoing cardiac surgery . Design : R and omized , placebo-controlled , prospect i ve study . Setting : University cardiology center . Patients : Two hundred fifty-four consecutive patients with chronic renal insufficiency ( estimated creatinine clearance ≤60 mL/min ) undergoing elective cardiac surgery . Interventions : Patients were r and omized to receive N-acetylcysteine ( n = 129 ) or placebo ( n = 125 ) . Patients of the N-acetylcysteine group received four boluses of intravenous N-acetylcysteine ( 1200 mg every 12 hrs , starting immediately before cardiac surgery ) . Measurements and Main Results : The incidence of postoperative acute renal failure ( > 25 % increase in serum creatinine from baseline ) and the in-hospital clinical course were evaluated . Acute renal failure occurred in 46 % of patients and was associated with increased in-hospital mortality ( 7 % vs. 0.7 % ; p = .024 ) . It occurred in 52 % of control patients and 40 % of N-acetylcysteine-treated patients ( p = .06 ) . In-hospital mortality and need for renal replacement therapy were not affected by N-acetylcysteine , but a lower percentage of N-acetylcysteine-treated patients required mechanical ventilation prolonged for > 48 hrs ( 3 % vs. 18 % ; p < .001 ) and had an intensive care unit stay > 4 days ( 13 % vs. 33 % ; p < .001 ) . Conclusions : Intravenous administration of N-acetylcysteine does not clearly prevent postoperative acute renal failure in patients with renal insufficiency undergoing cardiac surgery PURPOSE Intravenous N-acetylcysteine ( NAC ) has been reported to improve systemic oxygenation and reduce the need for ventilatory support in patients with an acute lung injury . In the more serious form , namely established adult respiratory distress syndrome ( ARDS ) ( PaO2/FIO2 < or = 200 mm Hg ) , we tested the hypothesis that treatment with intravenous NAC may be beneficial . MATERIAL S AND METHODS Respiratory dysfunction was grade d daily according to the need for mechanical ventilation and FIO2 and to the evolution of the lung injury score ( LIS ) and the PaO2/FIO2 ratio in 42 patients with established ARDS receiving either NAC 190 mg/kg/day or placebo as a continuous intravenous infusion over the first 3 days of their clinical course . RESULTS NAC and placebo groups ( 22 and 20 patients , respectively ) were comparable for demographic characteristics , ARDS categories , severity of illness ( simplified acute physiology score [ SAPS II ] ) LIS and PaO2/FIO2 ratio . Mortality rate was 32 % for the NAC and 25 % for the placebo group ( difference not significant ) . At admission ( day 1 ) , 91 % of patients in the NAC and 95 % in the placebo group required ventilatory support ; at days 2 , 3 , 5 , and 7 after admission , the percentage of patients receiving ventilatory support was not significantly reduced for both groups in comparison with day 1 . Moreover , there were no differences between the two groups at the same observation days . In both groups , the FIO2 was significantly lower and the PaO2/FIO2 ratio was significantly higher than the initial values during the evolution ( FiO2 at day 3 , P < .01 for NAC and P < .05 for placebo ; PaO2/FIO2 at day 3 : P < .01 for NAC and P < .02 for placebo ) , but this improvement was similar for both groups and , moreover , the between-group comparison was never significantly different at the various collection days . The LIS decreased significantly in NAC group between days 1 and 3 ( 2.23 + /- 0.62 v 1.76 + /- 0.17 ; P < .05 ) , whereas no changes were observed in the placebo group ; at day 5 , there was a significant difference between the two groups ( 1.53 + /- 0.21 for the NAC v 2.15 + /- 0.19 for the placebo group ; P < .05 ) . In the prevalent sepsis category ( 10 patients in the NAC and 9 in the placebo group ) , the mortality rate , the need of ventilatory support , the intensive care unit stay , and the PaO2/FIO2 evolution did not differ significantly in both subgroups . CONCLUSIONS In this relatively small group of patients presenting with an established ARDS subsequent to a variety of underlying diseases , intravenous NAC treatment during 72 hours neither improved systemic oxygenation nor reduced the need for ventilatory support Objectives To determine the influence of N-acetylcysteine ( NAC ) in a treatment model , its effects on endotoxin-induced leukocyte-endothelial cell adhesion , vascular leakage , and venular micro-hemodynamics in postcapillary venules of rat mesentery . Design Prospect i ve , r and omized , controlled , experimental study . Setting Animal research laboratory . Subjects40 male Wistar rats . Interventions The rats r and omly received one of four treatments : infusion of saline ( SAL ) or Escherichia coli lipopolysaccharides ( LPS ) followed by treatment with saline ( SAL ) or NAC ( 150 mg · kg− body weight ) 30 min after induction of endotoxemia . Measurements and main results Leukocyte adherence , red blood cell velocity , and vessel diameters in postcapillary venules of rat mesentery were evaluated every 30 min over a period of 120 min using in vivo videomicroscopy . Vascular permeability was determined by measuring the extravasation of fluorescence-labeled albumin . Venular wall shear rate was calculated from red cell velocity , and vessel diameter . NAC in rats without endotoxemia ( SAL + NAC group ) compared to the control group ( SAL + SAL ) did not change microcirculatory parameters in postcapillary venules of rat mesentery . In both LPS-treated groups ( LPS + SAL and LPS + NAC ) , leukocyte adherence increased after just 30 min . NAC treatment prevented a further increase in leukocyte adherence and attenuated the extravasation of fluorescence-labeled albumin during endotoxemia . Venular diameters remained unchanged , while erythrocyte velocity decreased in the LPS + SAL group . This led to a lower venular wall shear rate in this group . Conclusions Treatment with NAC attenuates endotoxin-induced leukocyte adherence and macromole-cular leakage in postcapillary venules of rat mesentery , showing that NAC is also effective after the onset of endotoxemia BACKGROUND All r and omized controlled trials of N-acetylcysteine ( NAC ) in contrast media-induced nephropathy used creatinine as a marker of renal function . However , it has been suggested that NAC may lower plasma creatinine levels independent of any effects on glomerular filtration rate ( GFR ) . METHODS At a tertiary hospital 110 cardiac surgical patients were r and omly allocated to peri-operative infusion of NAC ( 300 mg/kg over 24 h , N = 30 ) or placebo ( N = 80 ) . We compared the plasma concentrations of creatinine , cystatin C and urea , the plasma creatinine/plasma cystatin C ratio and the estimated GFR at baseline and at 24 and 72 h after commencement of the infusion . We measured urinary creatinine concentration at 24 h. RESULTS At baseline , the plasma creatinine/plasma cystatin C ratio did not differ between the NAC and placebo group ( 0.90 versus 0.92 ; P = 0.94 ) . There was no significant difference in the plasma creatinine/plasma cystatin C ratio for the NAC and placebo group either during or after NAC infusion at 24 h ( 1.03 versus 1.00 ; P = 0.78 ) and 72 h ( 0.94 versus 0.89 ; P = 0.09 ) . Those allocated to NAC showed no difference in urinary creatinine excretion when compared to placebo ( P = 0.24 ) . CONCLUSIONS The results of our study do not demonstrate that NAC artifactually lowers creatinine measured using the Jaffé method . ( Clinical Trials.gov , NCT00332631 , NCT00334191 ) Covert tissue hypoxia , particularly of the splanchnic region , appears important in the pathogenesis of multiple organ failure ( MOF ) . This investigation evaluates the effects of N-acetylcysteine ( NAC ) upon several measures of tissue oxygenation in 10 patients with severe MOF and evidence of splanchnic hypoxia ( as suggested by a pathologically low value ( < 7.32 ) of the pH of the gastric mucosa ( pHi ) ) . Patients were studied following a prospect i ve , r and omized , placebo-controlled , cross-over design . Measurements included pulmonary and systemic haemodynamics , cardiac output by thermodilution , arterial and mixed venous blood gas values , blood lactate concentration , whole-body oxygen uptake by analysis of the expired gases , and pHi by tonometry . A complete set of measurements was obtained before and 45 min after the infusion of NAC ( 150 mg.kg-1 in 250 mL of saline ) and , also , before and 45 min after the infusion of an equivalent volume of saline . NAC increased the cardiac index and vasodilated the systemic circulation ( p < 0.01 ) . However , O2 delivery to the tissues did not increase because the arterial oxygen content fell after NAC ( p < 0.01 ) . Mean O2 extraction or lactate concentration did not change after NAC , and pHi fell slightly ( from 7.11 + /- 0.21 to 7.07 + /- 0.21 ; p < 0.05 ) . The infusion of saline did not modify any variable significantly . The O2 extraction fraction increased exponentially in those patients with reduced O2 transport to the tissues . These results argue against a beneficial effect of N-acetylcysteine upon tissue oxygenation in patients with severe multiple organ failure and evidence of splanchnic hypoxia . Furthermore , they suggest that the mechanisms controlling the extraction of oxygen by the peripheral tissues in these patients were not impaired BACKGROUND Glutathione ( GSH ) acts as a free radical scavenger that may be helpful in preventing reperfusion injury . N-acetylcysteine ( NAC ) replenishes GSH stores . The aims of this study were to evaluate the efficacy of NAC in improving liver graft performance and reducing the incidence of post-operative acute kidney injury ( AKI ) . METHODS Our study was a r and omized , double-blind , placebo-controlled trial of 100 patients ; 50 received placebo and 50 received a loading dose of 140 mg/kg of intravenous ( IV ) NAC over 1 h followed by 70 mg/kg IV repeated every 4 h for a total of 12 doses . Both groups were followed up for 1 year post-orthotopic liver transplant ( OLT ) . We recorded liver function tests , renal function tests , graft survival , patient survival , plasma GSH and duration of hospital and ICU stay . In addition to serum creatinine ( SCr ) levels , we analysed cystatin C and beta-trace as independent measures of glomerular filtration . All clinical data were recorded daily for the first week after the surgery , then on Days 14 , 21 , 30 , 90 and 180 and at the end of the first year . RESULTS IV NAC did not affect survival , graft function or risk of AKI . However , GSH levels were highly variable with only 50 % of patients receiving NAC exhibiting increased levels and fewer patients developed AKI when GSH levels were increased . Additional risk factors for AKI in the post-transplant period were female gender ( P = 0.05 ) , increased baseline serum bilirubin ( P = 0.004 ) and increased baseline SCr levels ( P = 0.02 ) . CONCLUSIONS IV NAC was not effective in reducing renal or hepatic injury in the setting of liver transplantation . The dose and duration of NAC used , though higher than most renal protection studies , may have been ineffective for raising GSH levels in some patients Introduction The purpose of the present study was to evaluate the effects of continuously infused N-acetyl-L-cystein ( NAC ) on serum cytokine levels and gastric intramucosal pH in humans suffering from severe sepsis . Methods Fifty-three patients were included in the study . In the NAC group ( n = 27 ) , after an initial intravenous bolus of NAC ( 150 mg/kg over 5 min ) , a continuous intravenous infusion of 12.5 mg/kg per hour was given for 6 hours . Patients in the control group ( n = 26 ) were administered dextrose ( 5 % solution ) at the same dosage . We recorded the following : haemodynamic parameters , nasopharyngeal temperature , arterial blood gas changes , plasma cytokine levels , biochemical parameters , intramucosal pH , length of stay in the intensive care unit , duration of of mechanical ventilation and mortality . All measurements were taken at baseline ( 15 min before the start of the study ) and were repeated immediately after the bolus infusion , and at 24 and 48 hours after initiation of the continuous NAC infusion . Results No differences were found between groups in levels of the major cytokines , duration of ventilation and intensive care unit stay , gastric intramucosal pH and arterial oxygen tension/inspired fractional oxygen ratio ( P > 0.05 ) . Conclusion We found that NAC infusion at the doses given did not affect cytokine levels , outcomes , or gastric intramucosal pH in patients with severe sepsis . Because of the limited number of patients included in the study and the short period of observation , our findings need confirmation in larger clinical trials of NAC infused in a dose-titrated manner . However , our results do not support the use of NAC in patients with severe sepsis BACKGROUND Pre-existing chronic renal failure is a significant risk factor for acute renal failure ( ARF ) after cardiac surgery . N-acetylcysteine ( NAC ) has been shown to prevent contrast media-induced ARF . Our objective was to evaluate whether i.v . NAC has renoprotective effects in patients with mild renal failure undergoing cardiac surgery . METHODS In this prospect i ve , r and omized , double-blind study , 80 patients with mild to moderate renal failure undergoing elective heart surgery with cardiopulmonary bypass were recruited . All received either i.v . NAC ( n=38 ) or placebo ( n=39 ) at induction of anaesthesia and then up to 20 h. Urine N-acetyl-beta-D-glucosaminidase ( NAG ) and urine creatinine ratio , plasma creatinine , and serum cystatin C levels indicated renal function . RESULTS Levels of urinary NAG/creatinine ratio , plasma creatinine and serum cystatin C did not significantly differ between NAC and placebo groups during five postoperative days . Urine NAG/creatinine ratio increased over 30 % in 100 % of patients in the NAC group vs 92.3 % in the placebo group ( P=0.081 ) . Plasma creatinine increased by 25 % from baseline or over 44 mumol litre(-1 ) in 42.1 % in NAC group vs 48.7 % in placebo group ( P=0.560 ) . Serum cystatin C exceeded 1.4 mg litre(-1 ) in 78.9 % in NAC group vs 61.5 % in placebo group ( P=0.096 ) . CONCLUSIONS Prophylactic treatment with i.v . N-acetylcysteine had no renoprotective effect in patients with pre-existing renal failure undergoing cardiac surgery Objective To determine the prevalence and mortality of ICU patients with severe sepsis in Germany , with consideration of hospital size . Design Prospect i ve , observational , cross-sectional 1-day point-prevalence study . Setting 454 ICUs from a representative nationwide sample of 310 hospitals stratified by size . Data were collected via 1-day on-site audits by trained external study physicians . Visits were r and omly distributed over 1 year ( 2003 ) . Patients Inflammatory response of all ICU patients was assessed using the ACCP/SCCM consensus conference criteria . Patients with severe sepsis were followed up after 3 months for hospital mortality and length of ICU stay . Measurements and results Main outcome measures were prevalence and mortality . A total of 3,877 patients were screened . Prevalence was 12.4 % ( 95 % CI , 10.9–13.8 % ) for sepsis and 11.0 % ( 95 % CI , 9.7–12.2 % ) for severe sepsis including septic shock . The ICU and hospital mortality of patients with severe sepsis was 48.4 and 55.2 % , respectively , without significant differences between hospital size . Prevalence and mean length of ICU stay of patients with severe sepsis were significantly higher in larger hospitals and universities ( ≤ 200 beds : 6 % and 11.5 days , universities : 19 % and 19.2 days , respectively ) . Conclusions The expected number of newly diagnosed cases with severe sepsis in Germany amounts to 76–110 per 100,000 adult inhabitants . To allow better comparison between countries , future epidemiological studies should use st and ardized study method ologies with respect to sepsis definitions , hospital size , and daily and monthly variability ABSTRACT Objective : Renal function impairment is a common complication in cardiac surgery patients . Because cardiopulmonary bypass and cardioplegic arrest are associated with formation of free radicals , which have been shown to impair various organs including the kidneys , radical scavenging may protect renal function . Therefore , the purpose of our study was to evaluate the impact of the radical scavenger N-acetylcysteine ( NAC ) versus placebo on peri-operative renal function in cardiac surgery patients . Research design and methods : We reanalyzed the data of our previous study in which 40 coronary artery surgery patients ( 66 ± 9 [ SD ] years , 9 women and 31 men ) with normal pre-operative renal function had been r and omized in a double-blind fashion to receive either NAC ( 100 mg/kg into the cardiopulmonary bypass prime followed by infusion at 20 mg/kg/h ; n = 20 ) or placebo ( n = 20 ) . We determined serum creatinine levels as an indicator for renal function pre- and at 1 day post-surgery as well as peri-operative urinary output and diuretic medication . Creatinine clearance was calculated according to Cockcroft and Gault . Results : Biometric and intra-operative patient data were similar between both groups . In the placebo group , serum creatinine increased from 93.1 ± 35.4 µmol/L pre-operatively to 115.9 ± 47.2 µmol/L on post-op day 1 ( p < 0.001 ) . In contrast , serum creatinine in the NAC group remained unchanged ( 92.3 ± 31.3 µmol/L pre-op ; 99.3 ± 25.4 µmol/L on post-op day 1 ; p = 0.084 ) . Accordingly , creatinine clearance decreased by 16.9 ± 14.3 mL/min in the placebo group as compared to 7.5 ± 17.7 mL/min in the NAC group ( p = 0.039 ) . Urinary output and diuretic medication were similar between NAC and placebo . Conclusions : Our data suggest that free radical-scavenging using NAC protects renal function in patients subjected to cardiac surgery on cardiopulmonary bypass Background : Acute renal failure is a common complication in critically ill patients and carries an increased morbidity and mortality . N-acetylcysteine is an antioxidant and anti-inflammatory agent that may counteract some of the pathophysiologic derangements in shock states . Objective : To test whether the administration of N-acetylcysteine , compared with placebo , reduces the incidence of acute renal failure in hypotensive patients . Design : Prospect i ve , r and omized , double-blinded , placebo-controlled study . Setting : Intensive care units of a university tertiary care hospital . Patients : One hundred forty-two patients with new onset ( within 12 hrs ) of at least ≥30 consecutive minutes of hypotension and /or vasopressor requirement . Interventions : Patients were r and omized to receive either N-acetylcysteine or placebo for 7 days , in addition to st and ard supportive therapy . Measurements and Main Results : Patients who received N-acetylcysteine had an incidence of acute renal failure ( ≥0.5 mg/dL increase in creatinine ) of 15.5 % , compared with 16.9 % in those receiving placebo ( p = .82 , not significant ) . There were no significant differences between treatment arms in any of the secondary outcomes examined , including incidence of a 50 % increase in creatinine , maximal rise in creatinine , recovery of renal function , length of intensive care unit and hospital stay , requirement for renal replacement therapy , and mortality . Among patients receiving N-acetylcysteine , there were trends toward reduced incidence of acute renal failure in patients with baseline Sequential Organ Failure Assessment ( SOFA ) score > 8 ( p = .12 ) , lower SOFA scores during the first 4 days of treatment ( p = .28 ) , and reduced mortality in patients < 65 yrs of age ( p = .20 ) . Conclusions : There were no significant differences in any of our primary or secondary end points between patients treated with N-acetylcysteine or placebo . Trends toward reduced incidence of acute renal failure in patients with baseline SOFA score > 8 , reduced SOFA scores during the first 4 days , and reduced mortality in patients < 65 yrs of age are provocative but require further study to determine their clinical significance Hyperoxic ventilation , used to prevent hypoxemia during potential periods of hypoventilation , has been reported to paradoxically decrease whole body oxygen consumption ( VO2 ) . Reduction in nutritive blood flow due to oxygen radical production is one possible mechanism . We investigated whether pretreatment with the sulfhydryl group donor and O2 radical scavenger N-acetylcysteine ( NAC ) would preserve whole body VO2 and prevent deterioration of oxygenation in gastric mucosal tissue during hyperoxia . Thirty-eight patients , requiring hemodynamic monitoring ( radial and pulmonary artery catheters ) due to sepsis syndrome , were included in this r and omized experiment . All patients exhibited stable clinical conditions ( hemodynamics , body temperature , hemoglobin , FIO2 < 0.5 ) . A gastric tonometer was placed to measure the gastric intramucosal pH ( pHi ) , which indirectly assesses nutritive blood flow to the mucosa . Cardiac output was determined by thermodilution and VO2 by cardiovascular Fick . After baseline measurements , patients r and omly received either 150 mg.kg-1 NAC ( n = 19 ) or placebo ( n = 19 ) in 250 ml 5 % dextrose intravenously over a period of 15 min . Measurements were repeated 30 min after starting NAC or placebo infusion , 30 min after starting hyperoxia ( FIO2 = 1.0 ) , and 60 min after re setting the original FIO2 . There were no significant differences between groups in any of the measurements before treatment and after the return to baseline FIO2 at the end of the study . NAC , but not placebo infusion , caused a slight but significant increase in cardiac output and decrease in systemic vascular resistance . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To determine antioxidant vitamin concentrations , lipid peroxidation , and an index of nitric oxide production in patients in the intensive care unit ( ICU ) with septic shock and relate the findings to the presence of secondary organ failure . DESIGN A prospect i ve , observational study . SETTING A nine-bed ICU in a University teaching hospital . PATIENTS Sixteen consecutive patients with septic shock , defined as : a ) clinical evidence of acute infection ; b ) hypo- or hyperthermia ( < 35.6 degrees C or > 38.3 degrees C ) ; c ) tachypnea ( > 20 breaths/min or being mechanically ventilated ) ; d ) tachycardia ( > 90 beats/min ) ; e ) shock ( systolic pressure < 90 mm Hg ) or receiving inotropes . Fourteen patients also had secondary organ dysfunction . INTERVENTIONS None . MEASUREMENTS AND MAIN RESULTS Antioxidant vitamin concentrations were significantly lower in the patients than the reference range obtained from a comparable group of healthy controls . The mean plasma retinol ( vitamin A ) concentration was 26.5 + /- 19.3 micrograms/dL compared with 73.5 + /- 18.3 micrograms/dL in healthy subjects ( p < .01 ) . Additionally , 13 ( 81 % ) patients had retinol values below the lower limit of our reference range ( < 37.0 micrograms/dL ) . Tocopherol ( vitamin E ) plasma concentrations were below the reference range in all patients ( < 9.0 mg/L ) , with a mean value of 3.6 + /- 2.0 mg/L compared with 11.5 + /- 1.3 mg/L in healthy subjects ( p < .001 ) . Plasma beta carotene and lycopene concentrations were undetectable ( < 15 micrograms/L ) in eight ( 50 % ) patients , and below our reference range ( < 101 micrograms/L and < 154 micrograms/L , respectively ) in the remaining patients . In the five patients with three or more dysfunctional secondary organs , plasma thiobarbituric acid-reactive substances were significantly increased ( p < .05 ) , suggesting increased lipid peroxidation . Concentrations of thiobarbituric acid-reactive substances correlated negatively with both plasma retinol and plasma tocopherol ( r2 = .42 , p < .01 and r2 = .48 , p < .005 , respectively ) . In the five patients from whom we were able to collect urine , nitrite excretion was increased approximately 400-fold ( p < .001 ) . CONCLUSIONS These data indicate decreased antioxidant status in the face of enhanced free radical activity , and suggest potential therapeutic strategies involving antioxidant repletion Cardiopulmonary bypass ( CPB ) has been implicated in causing poor pulmonary gas exchange postoperatively in patients undergoing coronary artery bypass grafting ( CABG ) procedures . In this prospect i ve , r and omized , double-blind , placebo-controlled study , we examined the pulmonary effects of N-acetylcysteine ( NAC ) in patients undergoing CABG . Twenty patients undergoing elective CABG and early tracheal extubation were r and omized into two groups . Group I ( ten patients ) received a physiologic salt solution as a placebo in a continuous intravenous infusion for one hour before CPB and 24 hours after CPB ; Group II ( ten patients ) received 100 mg/kg NAC intravenously for one hour before CPB and 40 mg/kg/day at 24 hours after CPB . Perioperative hemodynamic and pulmonary data were recorded . Postoperative tracheal extubation was accomplished at the earliest appropriate time . The postoperative clinical course was similar in the two groups . Both groups exhibited significant postoperative increases in A-a oxygen gradient ( p<0.01 ) , but patients in Group II exhibited significantly lower increases in postoperative A-a oxygen gradient ( p<0.006 ) . Other hemodynamic and pulmonary data ( pulmonary capillary wedge pressure , pulmonary vascular resistance ( PVR ) , cardiac index ( CI ) , shunt flow , dynamic lung compliance and static lung compliance ) exhibited no differences between the groups . There was no significant difference in terms of intubation time . The malondialdehyde ( MDA ) increase in Group II following CPB was found to be significantly lower than in Group I ( p=0.043 ) . This clinical study reveals that administration of NAC to patients undergoing elective CABG with CPB improves systemic oxygenation . There was no effect in other pulmonary parameters and in terms of intubation time Myocardial ischemia – reperfusion injury may complicate coronary artery bypass grafting ( CABG ) operations . N-Acertylcysteine ( NAC ) had antioxidant and microcirculatory effects , and inhibits neutrophil aggregation . The aim of this study was to determine the effects of NAC in limiting myocardial ischemia – reperfusion injury in CABG operations . Twenty patients undergoing elective coronary bypass operation with cardiopulmonary bypass were enrolled and r and omly assigned to two groups : a control group operated with a routine CABG protocol , and one where NAC was administered intravenously during the operation ( NAC group ) . Blood sample s from coronary sinus for tumor necrosis factor-α assay , myocardial biopsy specimens for chemiluminescent luminol , and lucigenin measurements of reactive oxygen species were taken . The luminol ( specific for •OH , H2O2 , and HOCl− radicals ) and lucigenin ( specific for O2•− ) levels and the difference ratios after reperfusion were significantly lower in the NAC group . Tumor necrosis factor-α levels increased in the control group but , in contrast , a significant decrease was detected in the NAC group ( P < 0.01 ) . Creatine kinase-MB levels at 6 and 12 hours were singnificantly lower in the NAC group ( P = 0.02 ) . N-Acetylcysteine has potential effects to limit ischemia reperfusion injury during CABG operations . We believe that its effects on clinical outcome may be more apparent in patients prone to ischemia – reperfusion injury OBJECTIVE To determine the plasma antioxidant potential of patients in the intensive care unit ( ICU ) with severe sepsis and secondary organ dysfunction and relate these findings to outcome . DESIGN A prospect i ve , cohort study . SETTING A nine-bed ICU in a university teaching hospital . PATIENTS Fifteen consecutive patients , who were within 16 hrs of development of severe sepsis and secondary organ dysfunction . INTERVENTIONS Plasma sample s were obtained within 16 hrs of the onset of secondary organ dysfunction and subsequently on days 2 , 3 , 4 , 6 , 8 , 10 , and 15 until patients either left the ICU or died . Plasma antioxidant potential was determined by an ultraviolet spectrophotometric technique . MEASUREMENTS AND MAIN RESULTS The mean initial plasma antioxidant potential was lower than our range for healthy volunteers ( p < .05 ) . Survivors had an initial plasma antioxidant potential that was greater than nonsurvivors ( p < .01 ) , and serial subset analysis demonstrated that survivors , despite having a low initial plasma antioxidant potential rapidly attained normal or supranormal values . While plasma antioxidant potential also increased in nonsurvivors over time , values in this subset never reached the normal range and remained below values in survivors at all time points studied ( p < .05 ) . CONCLUSIONS Plasma antioxidant potential is initially decreased in patients with sepsis who develop organ dysfunction , and it increases over time . While we have no clear evidence to prove that this reduction has a causal relationship , failure to achieve a normal plasma antioxidant potential is strongly associated with an unfavorable outcome Sepsis and respiratory dysfunction leading to multiple system organ failure remains the leading cause of postoperative morbidity and mortality following major surgical procedures . It has been suggested the oxygen free radicals might play a pivotal role in this process . The aim of this study was to investigate whether short-term infusion of N-acetylcysteine ( N-acetylcysteine ) , a potent antioxidant , administered before and during extensive abdominal surgery , could ameliorate the progression of early postoperative organ dysfunction and improve oxygenation . Out of the 93 patients , 47 received N-acetylcysteine and 46 were given placebo in a r and omized , controlled , double-blinded fashion . Patients received N-acetylcysteine ( 150 mg.kg -1 bolus followed by a continuous infusion of 12 mg.kg -1 .h -1 ) or the same volume of placebo ( 5 % dextrose ) during surgery . Treatment effect on organ function was assessed by organ dysfunction scores according to physiological parameters of six main organ systems : respiratory , cardiovascular , renal , hepatic , haematological and central nervous system . The scores were obtained on admission , then daily during the first three postoperative days . For statistical analysis Mann-Whitney U and Chi-squared tests were used . There was no significant difference between the two groups in any of the six organ dysfunction parameters , length of intensive care stay , days of mechanical ventilation and mortality . Our results do not support the routine use of N-acetylcysteine as a prophylactic measure during surgery , and reinforce previous evidence which challenges the indication of N-acetylcysteine in the critically ill AIMS Oxidative stress has recently been implicated in the pathophysiology of atrial fibrillation ( AF ) . The aim of the present study was to evaluate the effects of antioxidant agent N-acetylcysteine ( NAC ) on postoperative AF . METHODS AND RESULTS The population of this prospect i ve , r and omized , double-blind , placebo-controlled study consisted of 115 patients undergoing coronary artery bypass and /or valve surgery . All the patients were treated with st and ard medical therapy and were r and omized to NAC group ( n = 58 ) or placebo ( saline , n = 57 ) . An AF episode > 5 min during hospitalization was accepted as endpoint . During follow-up period , 15 patients ( 15/115 , 13 % ) had AF . The rate of AF was lower in NAC group compared with placebo group ( three patients in NAC group [ 5.2 % ] and 12 patients in placebo group [ 21.1 % ] had postoperative AF ; odds ratio [ OR ] 0.20 ; 95 % confidence interval [ CI ] 0.05 to 0.77 ; P = 0.019 ) . In the multivariable logistic regression analysis , independent predictors of postoperative AF were left atrial diameter ( OR , 1.18 ; 95 % CI , 1.06 - 1.31 ; P = 0.002 ) and the use of NAC ( OR , 0.20 ; 95 % CI , 0.04 - 0.91 ; P = 0.038 ) . CONCLUSION The result of this study indicates that NAC treatment decreases the incidence of postoperative AF Background : Based on equivocal clinical data , intravenous antioxidant therapy has been used for the treatment of severe acute pancreatitis . To date there is no r and omised comparison of this therapy in severe acute pancreatitis . Methods : We conducted a r and omised , double blind , placebo controlled trial of intravenous antioxidant ( n-acetylcysteine , selenium , vitamin C ) therapy in patients with predicted severe acute pancreatitis . Forty-three patients were enrolled from three hospitals in the Manchester ( UK ) area over the period June 2001 to November 2004 . R and omisation stratified for APACHE-II score and hospital site , and delivered groups that were similar at baseline . Results : Relative serum levels of antioxidants rose while markers of oxidative stress fell in the active treatment group during the course of the trial . However , at 7 days , there was no statistically significant difference in the primary end point , organ dysfunction ( antioxidant vs placebo : 32 % vs 17 % , p = 0.33 ) or any secondary end point of organ dysfunction or patient outcome . Conclusions : This study provides no evidence to justify continued use of n-acetylcysteine , selenium , vitamin C based antioxidant therapy in severe acute pancreatitis . In the context of any future trial design , careful consideration must be given to the risks raised by the greater trend towards adverse outcome in patients in the treatment arm of this study Purpose N-acetylcysteine may prevent acute kidney injury after cardiac surgery . To determine if N-acetylcysteine warrants definitive evaluation in a large multicentre trial , we evaluated its effects on a surrogate outcome , estimated glomerular filtration rate ( eGFR ) , in a r and omized trial . Methods One-hundred-seventy-seven cardiac surgery patients with moderate pre-existing renal insufficiency ( eGFR ≤ 60 mL.min-1 ) were recruited in a blinded ( patients , clinicians , data -collectors ) placebo-controlled r and omized trial . Eighty-nine were r and omized to N-acetylcysteine ( 100 mg·kg-1 iv bolus , 20 mg·kg-1hr·-1 infusion until four hours after cardiopulmonary bypass ) , and 88 to placebo . The primary outcome was the percent change in eGFR during the first 72 postoperative hours . Secondary outcomes included renal replacement therapy , mortality , atrial fibrillation , vasoactive medications , and adverse effects . A future multicentre trial was deemed to be warranted if N-acetylcysteine was associated with a percent change in eGFR that was 3.8 better ( small benefit ) , and with an upper 95 % confidence interval including 9.5 ( moderate benefit ) . Results The median percent change in eGFR was 5.2 % better ( absolute difference ) in the N-acetylcysteine arm ( 95 % confidence interval 2.4 % worse to 12.1 % better ; P = 0.22 ) . With regard to secondary outcomes , all-cause mortality was lower in the N-acetylcysteine arm ( 0 % vs 8 % ; P = 0.007 ) . Conclusion N-acetylcysteine did not cause a statistically significant improvement in postoperative eGFR in this single-centre study . Nonetheless , its treatment effect was consistent with a plausible small-to-moderate benefit . Given this finding , N-acetylcysteine should be definitively evaluated in a large r and omized trial . RésuméObjectifLa N-acétylcystéine pourrait empêcher une atteinte rénale aiguë après une chirurgie cardiaque . Afin de déterminer si la N-acétylcystéine mérite une évaluation définitive menée par une étude multi-centrique étendue , nous avons évalué ses effets sur un pronostic de remplacement , le taux de filtration glomérulaire estimé ( eGFR ) , dans une étude r and omisée . MéthodeCent soixante-dix-sept patients de chirurgie cardiaque souffrant d’insuffisance rénale modérée préexistante ( eGFR ≤ 60 mL·min-1 ) ont été recrutés dans le cadre d’une étude en aveugle ( patients , cliniciens , collecteurs de données ) , r and omisée et contrôlée par placebo . Quatre-vingt-neuf patients ont été r and omisés à recevoir de la N-acétylcystéine ( bolus 100 mg·kg-1 iv , perfusion 20 mg·kg-1 · h-1 jusqu’à quatre heures après la circulation extracor-porelle ) , et 88 ont reçu un placebo . Le changement en pourcentage du eGFR durant les premières 72 h postopératoires a constitué le résultat primaire . Les résultats secondaires comptaient la dialyse , la mortalité , la fibrillation atriale , les médicaments vasomoteurs administrés , ainsi que les effets secondaires . Une étude multi-centrique ultérieure a été considérée nécessaire si la N-acétylcystéine était associée à une modification en pourcentage du eGFR qui était meilleure de 3,8 ( bénéfice modeste ) , avec un intervalle de confiance de 95 % supérieur comprenant 9,5 ( bénéfice modéré).RésultatsLe changement en pourcentage moyen du eGFR était meilleur de 5,2 % ( différence absolue ) dans le groupe N-acétylcystéine ( intervalle de confiance 95 % 2,4 % moins bon à 12,1 % meilleur ; P = 0,22 ) . En ce qui concerne les résultats secondaires , la mortalité — toutes causes — était plus basse dans le groupe N-acétylcystéine ( 0 % vs 8 % ; P = 0,007 ) . Conclusion La N-acétylcystéine n’a pas causé d’amélioration statistiquement significative dans l’eGFR postopératoire dans cette étude uni-centrique . Néanmoins , son effet thérapeutique pouvait correspondre à un bénéfice plausible modeste à modéré . Au vu de cette découverte , la N-acétylcystéine devrait être évaluée de manière définitive dans une étude r and omisée étendue Objective In septic shock , decreased splanchnic blood flow is reported , despite adequate systemic hemodynamics . N-acetylcysteine ( NAC ) was found to increase hepatosplanchnic blood flow in experimental setting s. In septic shock patients , NAC improved the clearance of indocyanine green and the relationship of systemic oxygen consumption to oxygen dem and . We investigated the influence of NAC on liver blood flow , hepatosplanchnic oxygen transport-related variables , and liver function during early septic shock . Design Prospect i ve , r and omized , double-blind study . Setting Septic shock patients admitted to an interdisciplinary surgical intensive care unit . Patients We examined 60 septic shock patients within 24 hrs after onset of sepsis . They were conventionally resuscitated with volume and inotropes and were in stable condition . A gastric tonometer was inserted into the stomach and a catheter into the hepatic vein . Microsomal liver function was assessed by using the plasma appearance of monoethylglycinexylidide ( MEGX ) . Interventions Subjects r and omly received either a bolus of 150 mg/kg iv NAC over 15 mins and a subsequent continuous infusion of 12.5 mg/kg/hr NAC over 90 mins ( n = 30 ) or placebo ( n = 30 ) . Measurements and Main Results Measurements were performed before ( baseline ) and 60 mins after beginning the infusion ( infusion ) . After NAC , a significant increase in absolute liver blood flow index ( 2.7 vs. 3.3 L/min/m2;p = .01 ) and cardiac index ( 5.0 vs. 5.7 L/min/m2;p = .02 ) was observed . Fractional liver blood flow index ( cardiac index-related liver blood flow index ) did not change . The difference between arterial and gastric mucosal carbon dioxide tension decreased ( p = .05 ) and MEGX increased ( p = .04 ) . Liver blood flow index and MEGX correlated significantly ( rs = .57;p ≤ .01 ) . Conclusions After NAC treatment , hepatosplanchnic flow and function improved and may , therefore , suggest enhanced nutritive blood flow . The increase of liver blood flow index was not caused by redistribution to the hepatosplanchnic area , but by an increase of cardiac index . Because of its correlation with liver blood flow index , MEGX may be helpful in identifying patients who benefit from NAC treatment in early septic shock Objective : To assess the effect of high-dose N-acetylcysteine on renal function in cardiac surgery patients at higher risk of postoperative renal failure . Design : Multiblind , placebo-controlled , r and omized , phase II clinical trial . Setting : Operating rooms and intensive care units of two tertiary referral hospitals . Patients : A total of 60 cardiac surgery patients at higher risk of postoperative renal failure . Interventions : Patients were allocated to either 24 hrs of high-dose N-acetylcysteine infusion ( 300 mg/kg body weight in 5 % glucose , 1.7 L ) or placebo ( 5 % glucose , 1.7 L ) . Measurements and Main Results : The primary outcome measure was the absolute change in serum creatinine from baseline to peak value within the first five postoperative days . Secondary outcomes included the relative change in serum creatinine , peak serum creatinine level , serum cystatin C , and in urinary output . Further outcomes were needed for renal replacement therapy , length of ventilation , and length of stay in the intensive care unit and hospital . R and omization was successful and patients were well balanced for preoperative and intraoperative characteristics . There was no significant attenuation in the increase in serum creatinine from baseline to peak when comparing N-acetylcysteine with placebo ( 64.5 ± 91.2 and 38.0 ± 42.4 & mgr;mol/L , respectively ; p = .15 ) . Also , there was no attenuation in the increase in serum cystatin C from baseline to peak for N-acetylcysteine compared with placebo ( 0.45 ± 0.43 and 0.30 ± 0.33 mg/L , respectively ; p = .40 ) . Likewise , there was no evidence for differences in any other clinical outcome . Conclusions : In this phase II , r and omized , controlled trial , high-dose N-acetylcysteine was no more effective than placebo in attenuating cardiopulmonary bypass – related acute renal failure in high-risk cardiac surgery patients In this prospect i ve , r and omized , placebo-controlled , double-blind trial we studied the effects of IV N-acetylcysteine for prevention of renal injury in patients undergoing abdominal aortic surgery . Seventy patients without previously documented renal dysfunction were r and omly allocated to receive either N-acetylcysteine ( 150 mg/kg mixed in 250 mL of 5 % dextrose infused in 20 min , followed by an infusion of 150 mg/kg in 250 mL of 5 % dextrose over 24 h ) or placebo . The infusion was started after the induction of anesthesia . The primary outcome measure was renal injury as measured by the increases in urinary N-acetyl-β-d-glucosaminidase (NAG)/creatinine ratio ( indicator of renal tubular injury ) and urinary albumin/creatinine ratio ( indicator of glomerular injury ) . Renal function was assessed by measuring plasma creatinine and serum cystatin C concentrations . The urinary NAG/creatinine ratio increased significantly from baseline to before crossclamp and remained increased on day 5 in both groups . The urinary albumin/creatinine ratio increased significantly from baseline to 6 h after declamping in the N-acetylcysteine group . However , the changes in the NAG/creatinine ratio and the albumin/creatinine ratio were not significantly different between the two groups . Plasma creatinine and serum cystatin C values remained unchanged during the study period in both groups . In conclusion , N-acetylcysteine did not offer any significant protection from renal injury during elective aortic operation in patients with normal preoperative renal function , and some degree of tubular injury seems to occur before aortic crossclamp This study investigates the effects of N-acetylcysteine ( NAC ) and rutin on the lung oxidative burden of patients with early adult respiratory distress syndrome ( ARDS ) . The protection was evaluated by measuring expired ethane and malondialdehyde ( MDA ) , and oxidized ( GSSG ) and reduced glutathione ( GSH ) in the epithelial lining fluid of 36 patients who developed ARDS less than 24 hours before enrollment in the study . The patients were r and omly assigned to 3 groups , receiving 250 mL 5 % dextrose in water ( group 1 ) , NAC 50 mg/kg body weight in 5 % dextrose ( group 2 ) , and NAC 50 mg/kg + rutin 5 mg/kg in 5 % dextrose ( group 3 ) . Ethane and MDA concentrations were significantly reduced in the treatment groups after day 6 . GSH was 30 % increased in the treatment groups . No significant variations were observed in the control group until day 9 . The trial confirms that NAC and rutin are efficient in protecting the lungs of patients with ARDS Background : Temporary occlusion of blood flow is used during arthroscopic knee surgery in order to provide a bloodless surgical field . The result ing ischaemia‐reperfusion causes lipid peroxidation , which contributes to tissue injury . The aim of the study was to investigate the effect of low‐dose n‐acetyl cysteine ( NAC ) infusion on oxidative stress by determining malondialdehyde ( MDA ) levels during arthroscopic knee surgery The release of toxic oxidative free radicals induced by ischemia and reperfusion may jeopardize liver graft function . N-acetylcysteine ( NAC ) has shown protective effects on hypothermic and warm ischemia reperfusion liver injury in animals . NAC improves hemodynamics and survival rates in patients with fulminant hepatic failure . The aim of this study was to investigate whether intraoperative treatment with NAC would improve hemodynamics and postoperative graft function in liver transplantation . Sixty patients with chronic end-stage liver disease were included in a prospect i ve r and omized placebo-controlled study . NAC or the same volume of 5 % glucose was started during the anhepatic phase . Hemodynamic data and calculated tissue oxygenation parameters were compared throughout the procedure . Postoperative graft function was assessed by measurements of aminotransferases , prothrombin time , and monoethylglycinexylidide test over the 3 first postoperative days . Patient demographics were similar before the infusion of NAC or glucose . Hemodynamic parameters , oxygen consumption , oxygen delivery , oxygen extraction ratio , and lactates were not different throughout the procedure . One hour after the revascularization of the hepatic artery , the oxygen extraction ratio by the liver was similar ( 17 % + /- 7.6 % v 17 % + /- 6.2 % ) in both groups . Postoperative graft function was comparable within the 3 first postoperative days . This study failed to show any beneficial effect of the intraoperative administration of NAC on hemodynamics and graft function in liver transplantation in patients with chronic liver disease OBJECTIVE To determine the influence of N-acetylcysteine on endotoxin-induced leukocyte-endothelial cell adhesion , vascular leakage , and venular microhemodynamics . DESIGN R and omized , blinded , controlled trial . SETTING Experimental laboratory . SUBJECTS Thirty male Wistar rats . INTERVENTIONS After pretreatment with N-acetylcysteine ( 150 mg/kg ; n = 40 ; group A ) or 0.9 % saline solution ( n = 10 ; group B ) animals were given an intravenous infusion of endotoxin ( Escherichia coli lipopolysaccharide 026:B6 ; 2 mg/kg/hr ) over 120 mins . Animals in the control group ( n = 10 ; group C ) received a volume-equivalent infusion of 0.9 % saline solution . MEASUREMENTS AND MAIN RESULTS Leukocyte adherence , red cell velocity ( VRBC ) , vessel diameters , venular wall shear rate , and macromolecular leakage were determined in mesenteric postcapillary venules using in vivo videomicroscopy at baseline and at 30 , 50 , 90 , and 120 mins after the start of the endotoxin challenge . Endotoxin exposure induced a marked increase in adherent leukocytes ( group B : baseline , 391 + /- 24 cells/mm2 ; 120 mins , 1268 + /- 131 cells/mm2 ; p < .01 ) . N-acetylcysteine pretreatment attenuated the adherence of leukocytes during endotoxemia ( baseline , 366 + /- 28 cells/mm2 ; 120 mins , 636 + /- 49 cells/mm2 ; p < .01 vs. baseline ; p < .01 vs. group B ) . Leukocyte adherence in control animals ( group C ) did not increase significantly . Administration of N-acetylcysteine did not influence the decrease in VRBC observed during endotoxemia . In group B1 VRBC decreased during the infusion of endotoxin from 2.0 + /- 0.2 mm/sec at baseline to 1.1 + /- 0.2 mm/ sec after 120 mins ( p < .01 vs. baseline ; p < .05 vs. group C ) , and in group A from 2.2 + /- 0.2 mm/sec to 1.1 + /- 0.1 mm/sec after 120 mins ( p < .01 vs. baseline ; p < .05 vs. group C ) . In group C , VRBC remained unchanged ( baseline , 1.7 + /- 0.2 mm/sec ; at 120 mins , 1.5 + /- 0.2 mm/sec ) . The venular diameters remained unchanged in all groups during the entire study period . After 120 mins , the venular wall shear rate decreased from 502 + /- 62 secs-1 at baseline to 272 + /- 46 sec-1 in group B ( p < .01 ) , and from 563 + /- 45 secs-1 at baseline to 283 + /- 31 secs-1 in group A ( p < .01 ) . No differences in venular wall shear rate were observed between these groups . In group C , the venular wall shear rate remained unchanged ( baseline , 457 + /- 54 secs-1 ; at 120 mins , 409 + /- 51 secs-1 ) . Macromolecular leakage , expressed as perivenular/intravenular fluorescence intensity after injection of fluorescence-labeled albumin , increased from 0.29 + /- 0.03 to 0.58 + /- 0.03 ( p < .01 ) during the infusion of endotoxin in group B. In contrast , pretreatment with N-acetylcysteine diminished the extravasation of albumin ( baseline , 0.27 + /- 0.01 ; at 120 mins , 0.37 + /- 0.02 ; p < .01 vs. baseline ; p < .01 vs. group B ) . CONCLUSION These results demonstrate that N-acetylcysteine attenuates endotoxin-induced alterations in leukocyte-endothelial cell adhesion and macromolecular leakage , suggesting N-acetylcysteine might be therapeutic in the prevention of endothelial damage in sepsis OBJECTIVES To investigate whether short-term N-acetylcysteine ( NAC ) infusion administered before and during extensive abdominal surgery could modify the progression of early postoperative organ dysfunction and systemic inflammatory response . METHODS After r and omisation the treatment group ( n = 47 ) received NAC ( 150 mg kg-1 bolus followed by a continuous infusion of 12 mg kg-1 h-1 ) and the placebo group ( n = 46 ) received the same volume of 5 % dextrose during surgery . Clinical progress was monitored by the Multiple organ dysfunction score , systemic inflammatory response by serum procalcitonin ( PCT ) , C-reactive protein ( CRP ) and microalbuminuria during the first 3 postoperative days . Mann-Whitney and chi 2 tests were used for statistical analysis . RESULTS There was no significant difference between the two groups regarding the MODS , organ dysfunction , length of intensive care stay , days of mechanical ventilation and mortality . PCT and microalbuminuria did not differ significantly . Significantly lower CRP levels were found in the NAC group on day one and two [ t24 : median : 84.5 interquartile range : ( 62.48 - 120.25 ) vs. 118 ( 86 - 137 ) mg/l ; p = 0.020 ; t48 : 136 ( 103 - 232 ) vs. 195 ( 154.5 - 252 ) mg/l p = 0.013 , NAC vs. placebo ] . CONCLUSION The results of this study do not support the routine use of NAC as a prophylactic drug during surgery , and reinforce previous evidence which challenge the indication of NAC in the critically ill patient AIM Acute pancreatitis ( AP ) is the most common and often severe complication of endoscopic retro grade cholangiopancreatography ( ERCP ) . The early step in the pathogenesis of acute pancreatitis is probably the capillary endothelial injury mediated by oxygen-derived free radicals . N-acetylcysteine - a free radical scavenger may be potentially effective in preventing post-ERCP acute pancreatitis and it is also known that N-acetylcysteine ( ACC ) can reduce the severity of disease in experimental model of AP . METHODS One hundred and six patients were r and omly allocated to two groups . Fifty-five patients were given N-acetylcysteine ( two 600 mg doses orally 24 and 12 h before ERCP and 600 mg was given iv , twice a day for two days after the ERCP ) . The control group consisted of 51 patients who were given iv . isotonic saline twice a day for two days after the ERCP . Serum and urine amylase activities were measured before ERCP and 8 and 24 h after the procedure . The primary outcome parameter was post-ERCP acute pancreatitis and the secondary outcome parameters were differences between groups in serum and urine amylase activity . RESULTS There were no significant differences in the rate of post-ERCP pancreatitis between two groups ( 10 patients overall , 4 in the ACC group and 6 in the control group ) . There were also no significant differences in baseline and post-ERCP serum and urine amylase activity between ACC group and control group . CONCLUSION N-acetylcysteine fails to demonstrate any significant preventive effect on post-ERCP pancreatitis , as well as on serum and urine amylase activity OBJECTIVE To investigate the effects of adjunctive therapy with parenteral N-acetyl-L-cysteine in patients with newly diagnosed septic shock . DESIGN Prospect i ve , r and omized , double-blind , placebo-controlled study . SETTING Multidisciplinary intensive care unit at a university teaching hospital . PATIENTS Twenty patients ( N-acetyl-L-cysteine group [ n = 10 ] , placebo group [ n = 10 ] ) , 15 male and five female , of mean age 64 + /- 15 ( SD ) yrs and Acute Physiology and Chronic health Evaluation ( APACHE ) II score 33 + /- 6 , with septic shock within 24 hrs of diagnosis . INTERVENTIONS After a 2-hr stabilization period ( time-zero minus 2 hrs to time-zero ) , patients received either N-acetyl-L-cysteine in 5 % dextrose ( 150 mg/kg in 100 mL over 15 mins , followed by 50 mg/kg in 250 mL over 4 hrs , and then 100 mg/kg/24 hrs in 500 mL for 44 hrs ; N-acetyl-L-cysteine group ) or the equivalent volume of 5 % dextrose ( placebo group ) . MEASUREMENTS AND MAIN RESULTS Hemodynamic and oxygen transport indices were measured at time-zero minus 2 hrs and time-zero , and at multiple time points thereafter until completion of the trial infusion ( time-zero plus 48 hrs ) . A daily Organ Failure Score was recorded for 14 days . Treatment group demographics and hemodynamic variables did not differ significantly between the two groups at time-zero . Mean ( SD ) , pooled mean arterial pressure ( MAP ) , and cardiac index were 75 + /- 15 mm Hg and 3.9 + /- 1.2 L/min/m2 , respectively . Over the next 48 hrs , in the N-acetyl-L-cysteine group , there was a progressive decrease , relative to both time-zero and the placebo group , in MAP , cardiac index , and left ventricular stroke work index ( p < .01 , repeated- measures analysis of variance ) . Percentage reductions in these values relative to the placebo group at 48 hrs were 23 % , 18 % , and 43 % , respectively Oxygen transport indices , arterial blood gas analyses , Pao2/Fio2 ratio , and shunt did not differ over time between the groups . There was no difference in either daily Organ Failure Score over time ( p > .01 , repeated- measures analysis of variance ) or hospital mortality rate ( 90 % N-acetyl-L-cysteine group , 50 % placebo group ) ( p > .1 , logistic regression ) between the two groups . CONCLUSION Adjunctive therapy with N-acetyl-L-cysteine in newly diagnosed septic shock was associated with a depression in cardiovascular performance , as indicated by progressive reductions in cardiac index , left ventricular stroke work index , and MAP OBJECTIVE Reactive oxygen species have been shown to contribute to myocardial stress in patients undergoing cardiac surgery , as demonstrated by myocardial 8-iso-prostagl and in-F(2)alpha and nitrotyrosine formation . We hypothesized that the reactive oxygen species scavenger N-acetylcysteine attenuates reactive oxygen species-mediated myocardial stress in patients undergoing cardiac surgery . METHODS Forty patients undergoing coronary artery surgery ( mean age + /- SD , 66 + /- 9 years ; 9 women and 31 men ) were r and omized to receive either N-acetylcysteine ( 100 mg/kg into cardiopulmonary bypass prime followed by infusion at 20 mg.kg(-1).h(-1 ) , n = 20 ) or placebo ( n = 20 ) . Patients and clinical staff were blinded to group assignment . Transmural left ventricular biopsy specimens collected before and at the end of cardiopulmonary bypass were subjected to immunocytochemical staining against 8-iso-prostagl and in-F(2)alpha ( primary measure ) as an indicator for reactive oxygen species-mediated lipid peroxidation and nitrotyrosine ( co primary measure ) as a marker for peroxynitrite-mediated tissue injury . Cardiomyocyte staining was quantitatively determined by using densitometry ( in gray units ) . Global left ventricular function was measured on the basis of fractional area of contraction by using transesophageal echocardiography . RESULTS Patient characteristics in both groups were comparable . The change in left ventricular cardiomyocyte staining ( end of cardiopulmonary bypass -- before cardiopulmonary bypass ) differed significantly between groups for both primary measures : 8-iso-prostagl and in-F(2)alpha , -1.8 + /- 7.5 gray units ( mean + /- SD , N-acetylcysteine group ) versus 5.0 + /- 4.1 gray units ( placebo group ; 95 % confidence interval , 2.6 - 11.0 , P = .003 ) ; nitrotyrosine , -6.4 + /- 10.0 gray units ( N-acetylcysteine group ) versus 9.2 + /- 8.4 gray units ( placebo group ; 95 % confidence interval , 9.4 - 21.7 , P < .001 ) . Hemodynamics and clinical outcomes were comparable in both groups . CONCLUSIONS Reactive oxygen species scavenging with N-acetylcysteine attenuates myocardial oxidative stress in the hearts of patients subjected to cardiopulmonary bypass and cardioplegic arrest BACKGROUND N-acetylcysteine ( NAC ) is an antioxidant drug largely tested in different clinical situations . Recently , NAC has been employed with variable success in the prevention of radiocontrast nephropathy . Since aortic aneurysm surgical repair is a condition that is frequently accompanied by acute renal failure ( ARF ) , we sought to investigate whether NAC has any role in preventing ARF in this scenario . METHODS A r and omized , placebo-controlled , double-blind trial with the following inclusion criteria : elective aortic aneurysm repair in patients with stable renal function . The groups were r and omly matched for age , gender , presence of diabetes and pre-existent renal failure . NAC or placebo ( control ) was administered p.o . for 24 h before operation and maintained i.v . for 48 h after operation . The dose of NAC was 1200 mg b.i.d . the day before surgery and 600 mg b.i.d . after . The primary endpoint was the development of ARF up to the third post-operative day , defined as an increase in SCr > or = 25 % from baseline . Secondary endpoints were : ICU mortality and ICU length of stay . RESULTS Forty-two patients ( n = 18 for NAC group and n = 24 for control ) were studied . The baseline SCr and calculated GFR did not differ between the groups ( 1.19 + /- 0.33 vs 1.37 + /- 0.49 mg/dl ; and 64.6 + /- 26.22 vs 65.7 + /- 28.32 ml/min , NAC vs control , respectively , P = 0.17 and P = 0.90 ) . Need for suprarenal aortic cross-clamping and its duration , occurrence of major bleeding , intra-operative hypotension and the post-operative peak of CPK did not differ between NAC and control groups . The overall incidence of ARF in the study was 36 % ( 13/36 ) , but it was not significantly different between groups ( 7/14 , 50 % in NAC vs 6/22 , 27.3 % in control , P = 0.16 ) . The overall mortality was 23 % ( 10/42 ) and was not different ( P = 0.209 ) in NAC group ( 33.3 % ) when compared with control ( 16.7 % ) , the same occurring with the length of ICU stay ( 2.93 + /- 1.53 vs 2.52 + /- 1.36 days , P = 0.40 ) . CONCLUSION This study suggests that the putative beneficial effects of NAC on radiocontrast nephropathy might not be applicable to other situations , such as ARF associated with elective aortic aneurysm repair Both the hyperproduction of oxygen free radicals ( OFR ) and the weakening of natural scavenging mechanisms have been implicated as contributors to multiple organ failure in septic shock . This study examined whether the antioxidants glutathione ( GSH ) and N-acetyl-L-cysteine ( NAC ) play a protective role against damage by OFR in early septic shock . We r and omly entered 30 patients with septic shock into one of three groups within 24 h of diagnosis . All of the patients received septic shock therapy , including parenteral nutrition , antibiotics , and volume-exp and ing and inotropic agents . One group ( Group B ) also received 70 mg/kg/d of intravenous GSH , and a second group ( Group C ) , 70 mg/kg/d of intravenous GSH and 75 mg/kg/d of intravenous NAC . The protection against OFR damage was evaluated by measuring expired ethane , plasma malondialdehyde , erythrocyte deformability , complement activation , and clinical scores at admission and on Days 3 and 5 of treatment . A significant decrease in peroxidative indexes was observed at Day 5 in Group B as compared with both the control group and basal values . The decrease in peroxidative indexes was even more marked in Group C. Clinical scores in this group were also significantly improved . In conclusion , the administration of high doses of NAC added to GSH significantly decreased the peroxidative stress of patients with septic shock Objective Controversial data have been reported on the effects of N-acetylcysteine in patients with septic shock . We therefore investigated the systemic , pulmonary , and hepatosplanchnic hemodynamic , gas exchange , and metabolic effects of N-acetylcysteine during long-term , volume-resuscitated , hyperdynamic porcine endotoxemia , which mimics the features of hyperdynamic human sepsis . Design Prospect i ve , r and omized , controlled experimental study . Setting Investigational animal laboratory . SubjectsEighteen pigs were r and omized to receive endotoxin alone ( controls , n = 9 ) or endotoxin plus N-acetylcysteine ( n = 9 ) . Interventions Anesthetized , mechanically ventilated , and instrumented animals received continuous intravenous endotoxin and were resuscitated with hydroxyethylstarch to keep mean arterial pressure > 60 mm Hg . After 12 hrs of endotoxemia , they were r and omized to receive either placebo or N-acetylcysteine ( 150 mg/kg loading dose over 1 hr followed by 20 mg·kg−1·hr−1 for 11 hrs ) . Measurements and Main Results Before as well as 12 , 18 , and 24 hrs after starting the endotoxin infusion , systemic , pulmonary , and hepatosplanchnic hemodynamics , oxygen exchange , and metabolism as well as nitric oxide , glutathione , and 8-isoprostane concentrations were assessed . N-acetylcysteine failed to improve any of the variables of the systemic , pulmonary , or hepatosplanchnic hemodynamics , gas exchange , and metabolism . Although N-acetylcysteine significantly elevated glutathione concentration , it did not influence the 8-isoprostane concentrations and even further reduced hepatic venous pH. Conclusions Despite the increased glutathione concentration , N-acetylcysteine did not improve systemic , pulmonary , and hepatosplanchnic hemodynamics , oxygen exchange , and metabolism . When compared with previous reports in the literature , a different timing of N-acetylcysteine administration and /or an ongoing or even N-acetylcysteine-induced aggravation of oxidative stress may account for this result ObjectiveS tudy of leukocyte activation and release of toxic mediators during extracorporeal circulation ( ECC ) . ECC can be used to study the potential protective effect of a pharmacon against neutrophil-mediated lung injury . Clinical studies have indicated that N-acetylcysteine ( NAC ) may improve systemic oxygenation and reduce the need for ventilatory support when given to patients with acute lung injury . Design Cardiac surgery patients were pretreated with high-dose NAC in order to assess the potential role of NAC to interfere with neutrophil-mediated inflammation and lung injury . Patients 18 patients who underwent ECC : group 1 ( n=8 ) no premedication ( only placebo ) ; group 2 ( n=10 ) NAC ( 72 mg/kg i.v . as a bolus , later 72 mg/kg over 12 h ) . Measurements and results In group 2 , the partial pressure of oxygen in arterial blood/fractional inspired oxygen 4 h after surgery was significantly higher than in group 1 ( 213±31 vs 123±22;p=0.044 ) . NAC pretreatment prevented an increase in plasma neutrophil elastase activity ( 18.9±6.9 vs 49.9±5.6 ng/ml in group 1 at the end of ECC;p=0.027 ) . Release of myeloperoxidase ( MPO ) was not affected ( group 1 : 1105±225 ng/ml vs group 2 : 1127±81 at the end of ECC;p=0.63 ) . At the end of ECC , total antigenic human neutrophil elastase ( group 1 : 671±72 ng/ml vs group 2 : 579±134;p=0.37 ) and complex formation between elastase and α1-proteinase inhibitor were no different in the two groups . There were no significant differences in cellular composition and mediators in the lavage fluid , although values for total number of neutrophils , elastase , MPO and interleukin-8 were lower in group 2 . Conclusion Pretreatment with NAC may prevent lung injury by diminishing elastase activity . Since the release of mediators , especially MPO , is not affected , this diminished activity of elastase may be achieved by enhanced inactivation by antiproteases after initial treatment In acute respiratory distress syndrome ( ARDS ) , there is extensive overproduction of free radicals to the extent that endogenous anti-oxidants are overwhelmed , permitting oxidative cell damage . The present study examined the benefit of the anti-oxidant compound N-acetylcysteine ( NAC ) in the management of ARDS by measuring patient 's intracellular glutathione ( inside red blood cells ) and extracellular ( plasma ) anti-oxidant defense biomarkers and outcome . Twenty-seven ARDS patients were recruited from the intensive care unit of a teaching Hospital and r and omly divided into two groups . Both groups were managed similarly by regular treatments but 17 patients received NAC 150 mg/kg at the first day that followed by 50 mg/kg/day for three days and 10 patients did not receive NAC . Treatment by NAC increased extracellular total anti-oxidant power and total thiol molecules and also improved intracellular glutathione and the outcome of the patients . In conclusion , patients with ARDS are in a deficient oxidant — anti-oxidant balance that can get a significant benefit if supplemented with NAC . Human & Experimental Toxicology ( 2007 ) 26 , N-acetylcysteine ( NAC ) may offer renal and hepatic protection during surgery , but in experimental studies it has been shown to impair coagulation . Since very little is known about the effects of NAC on blood coagulation in surgical patients , we studied its effects during abdominal aortic reconstruction . NAC ( a bolus of 150 mg/kg followed by a continuous 24-h infusion of 150 mg/kg ) or the same volume of placebo was given intravenously , in a r and omized double-blinded fashion , to 20 patients undergoing abdominal aortic aneurysm repair . The haematocrit , platelet count , prothrombin time , thromboelastometry , and platelet aggregation were studied during and after surgery . Total blood loss was also measured . The median ( 25th–75th percentiles ) decrease of the prothrombin time value was 33.0 % ( 30–37 % ) after NAC treatment and 6.5 % ( 4–8 % ) after placebo ( P < 0.001 ) . Postoperative prothrombin time values remained lower in the patients receiving NAC . In thromboelastometry tracings the coagulation time was more prolonged after the bolus of NAC ( P = 0.02 ) . Platelet aggregation induced with adenosine diphosphate decreased after NAC but not after placebo . Low prothrombin time values before and after bolus infusions were associated with increased blood loss ( P = 0.008 and P = 0.015 , respectively ) . NAC has anticoagulant and platelet-inhibiting properties in patients undergoing major vascular surgery . This abnormal haemostatic activity should be considered when NAC is administered to patients with increased bleeding risk UNLABELLED Hyperoxic ventilation , used to prevent hypoxia during potential periods of hypoventilation , has been reported to paradoxically decrease whole-body oxygen consumption ( VO2 ) . Reduction in nutritive blood flow due to oxygen radical production is one possible mechanism . We investigated whether pretreatment with the sulfhydryl group donor and O2 radical scavenger N-acetylcysteine ( NAC ) would preserve VO2 and other clinical indicators of tissue oxygenation in cardiac risk patients . METHODS Thirty patients , requiring hemodynamic monitoring ( radial and pulmonary artery catheters ) because of cardiac risk factors , were included in this r and omized investigation . All patients exhibited stable clinical conditions ( hemodynamics , body temperature , hemoglobin , F1O2 < 0.5 ) . Cardiac output was determined by thermodilution and VO2 by cardiovascular Fick . After baseline measurements , patients r and omly received either 150 mg kg-1 NAC ( n = 15 ) or placebo ( n = 15 ) in 250 ml 5 % dextrose i.v . over a period of 30 min . Measurements were repeated 30 min after starting NAC or placebo infusion , 30 min after starting hyperoxia ( F1O2 = 1.0 ) , and 30 min after re setting the original F1O2 . RESULTS There were no significant differences between groups in any of the measurements before treatment and after the return to baseline F1O2 at the end of the study , respectively . NAC , but not placebo infusion , caused a slight but not significant increase in cardiac index ( CI ) , left ventricular stroke work index ( LVSWI ) and a decrease in systemic vascular resistance . Significant differences between groups during hyperoxia were : VO2 ( NAC : 108 + /- 38 ml min-1m-2 vs placebo : 79 + /- 22 ml min-1m-2 ; P < or = 0.05 ) , CI ( NAC : 4.6 + /- 1.0 vs placebo : 3.7 + /- 1.11 min-1m-2 ; P < or = 0.05 ) and LVSWI ( NAC : 47 + /- 12 vs placebo : 38 + /- 9 ; P < or = 0.05 ) . The mean decrease of VO2 was 22 % in the NAC group vs 47 % in the placebo group ( P < or = 0.05 ) and the mean difference between groups in venoarterial carbon dioxide gradient ( PvaCO2 ) was 14 % ( P < or = 0.05 ) . ST segment depression ( > 0.2 mV ) was significantly less marked in the NAC group ( NAC : -0.02 + /- 0.17 vs placebo : -0.23 + /- 0.15 ; P < or = 0.05 ) . CONCLUSIONS NAC helped preserve VO2 , oxygen delivery , CI , LVSWI and PvaCO2 during brief hyperoxia in cardiac risk patients . Clinical signs of myocardial ischemia did not occur such as ST-depression if patients were prophylactically treated with NAC . This suggests that pretreatment with NAC could be considered to attenuate impaired tissue oxygenation and to preserve myocardial performance better in cardiac risk patients during hyperoxia Abstract Objective : To investigate the effects of N-acetylcysteine ( NAC ) when given as an early treatment to critically ill patients on the serum total anti-oxidant potential ( TAP ) and urine micro-albumin : creatinine ( M : Cr ) ratio . Design : Prospect i ve , placebo controlled , double blinded clinical trial . Setting : General intensive care unit in a teaching hospital . Patients : Sixty critically ill patients were recruited but ten were withdrawn due to less than 48 h of ICU stay . Interventions : After envelope r and omisation , patients received either NAC ( n=23 ) : a bolus of 150 mg/kg in 250 ml of 5 % dextrose followed by a continuous infusion of 12 mg/kg per h in 500 ml of 5 % dextrose over 24 h or , as controls ( n= 27 ) , the equal volume of placebo . Treatment lasted for a minimum of 3 , up to a maximum of 5 , days . Blood and urine sample s were collected on admission ( 0 h ) and then 6 hourly up 18 h. Measurements and results : There was no significant difference between NAC and placebo groups regarding the required length of inotropic support , mechanical ventilation and ICU stay . There was no significant difference in TAP or M : Cr ratio over 18 h or between the groups . Conclusions : Our results suggest that NAC had no significant effects on the progress of the TAP and the urinary albumin excretion in our patients , which may suggest that NAC at the given dose has no clinical relevance as an early treatment in the critically ill Oxidative stress and inflammatory processes generate edema in burns . Treatment of consequent hypovolemia is a challenge . The aim of study was to assess if glutathione pro-drug N-acetylcysteine ( NAC ) can influence inflammation and fluid requirement . We also aim ed to compare organ functions scores and vasoactive drug requirement . This prospect i ve r and omised study involved 28 patients with burn injury affecting more than 20 % of body surface area . Fourteen patients were on st and ard therapy , whereas for other 14 patients NAC was supplemented . Blood sample s were taken on admission and on the next five consecutive mornings . Leukocyte surface marker expressions were determined , multiple organ function scores , use of vasopressor agents and fluid requirements were recorded daily . Expression of CD11a ( p < 0.05 ) , CD18 ( p < 0.05 ) and CD97 ( p < 0.01 ) on the granulocytes were significantly lower in the NAC treated group , similarly to lymphocyte CD 49d ( p < 0.05 ) and monocyte CD 49d ( p < 0.01 ) and CD 97 ( p < 0.05 ) expression . No significant difference was found in the fluid requirement between groups but patients the NAC group required less vasopressor and inotropic drugs from day 4 . NAC treatment is associated with a less pronounced inflammation reflected in lower CD marker expression and vasopressor requirement BACKGROUND Acute kidney injury ( AKI ) after heart surgery is associated with increased mortality . We sought to determine whether prophylactic perioperative administration of N-acetylcysteine ( NAC ) prevents postoperative AKI in patients with chronic kidney disease undergoing cardiac surgery ( clinical trials.gov identifier NCT00211653 ) . METHODS In this prospect i ve , r and omized , placebo-controlled , double-blinded clinical trial , 102 patients with chronic kidney disease who underwent heart surgery at the Minneapolis Veterans Affairs Medical Center were r and omized to either NAC ( n = 50 ) 600 mg PO twice daily or placebo ( n = 52 ) for a total of 14 doses ( 3 preoperative ) . The primary outcome was maximum change in creatinine from baseline within 7 days after surgery . Secondary outcome was AKI ( ie , > 0.5 mg/dL or > or=25 % increase in creatinine from baseline ) . RESULTS Creatinine increased in both groups ( 0.45 + /- 0.7 mg/dL in NAC vs 0.55 + /- 0.9 mg/dL in placebo , P = .53 ) and peaked on postoperative day 5 . Acute kidney injury occurred in 41 patients ( 22 NAC vs 19 placebo , P = .44 ) by postoperative day 5 , but persisted in only 14 ( 7 NAC vs 7 placebo , P = .94 ) by day 30 . In multivariable analysis , perioperative NAC was unassociated with AKI ( relative risk 1.2 , 95 % CI , 0.8 - 1.9 , P = .34 ) . Five patients ( 3 NAC vs 2 placebo , P = .68 ) underwent hemodialysis , and 5 ( 2 NAC vs 3 placebo , P = 1.0 ) died perioperatively . There was no difference in lengths of stay in the intensive care unit ( 4.9 + /- 7 days in NAC vs 6.5 + /- 9 days in placebo , P = .06 ) and the hospital ( 13.2 + /- 13 days in NAC vs 16.7 + /- 17 days in placebo , P = .12 ) . CONCLUSION Prophylactic perioperative NAC administration does not prevent AKI after cardiac surgery OBJECTIVE N-acetylcysteine , a potent anti-inflammatory and antioxidant agent , is known to decrease the production of reactive oxygen species after cardiac surgery . The objective of this study was to evaluate the effects of intravenous N-acetylcysteine on clinical and biochemical outcomes after coronary artery bypass surgery with cardiopulmonary bypass . METHODS One hundred patients ( mean age 60.5 years , range 43 - 78 years , 89 % male ) undergoing coronary artery bypass grafting at the Montreal Heart Institute were r and omized to receive either N-acetylcysteine ( 600 mg orally the day before and the morning of the operation , a bolus of 150 mg/kg of intravenous N-acetylcysteine before skin incision , followed by perfusion at 12.5 mg x kg(-1 ) x h(-1 ) over 24 hours ; n = 50 ) or placebo ( n = 50 ) . The patients and clinical team were blinded to group assignments . Preoperative characteristics were similar between the two groups . Postoperative clinical data ( death , myocardial infa rct ion , low-output syndromes , arrhythmias , bleeding , transfusion requirements , and intensive care unit and hospital lengths of stay ) and biochemical markers ( creatine kinase MB , troponin T , creatinine , hemoglobin , and platelet levels ) were evaluated serially over 4 days . RESULTS Clinical outcomes were not significantly different between the two groups with regard to the incidence of death , myocardial infa rct ion , bleeding , transfusion requirements , intubation time , and hospital length of stay . No differences were found in postoperative biochemical markers ( troponin T , creatine kinase MB , creatinine , hemoglobin , and platelets ) between the groups . No differences were observed between the groups in interleukin-6 production ( P = not significant ) . CONCLUSIONS Prophylactic use of N-acetylcysteine in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass does not lead to improvement in clinical results or biochemical markers . Further strategies to decrease reperfusion injury should be devised Objectives : Deactivation of endotheliumderived relaxing factor due to an increased oxygen radical load during sepsis may contribute to an impairment in microcirculatory blood flow . We investigated whether treatment with the sulfhydryl donor and oxygen radical scavenger , N‐acetylcysteine , would improve wholebody oxygen consumption ( & OV0312;o2 ) , gastric intramucosal pH , and veno‐arterial CO2 gradient ( veno‐arterial Pco2 ) during septic shock . Design : Prospect i ve , r and omized , doubleblind study conducted over 2 yrs . Setting : Septic shock patients admitted to the intensive care unit . Patients : Fifty‐eight patients requiring hemodynamic monitoring ( radial and pulmonary artery catheters ) due to septic shock , were included in this study . All patients were examined within 72 hrs after the onset of sepsis . They were optimally resuscitated by conventional means with volume and inotropic agents , and exhibited stable clinical conditions ( hemodynamic values , body temperature , hemoglobin , Fio2 ) . Interventions : A gastric tonometer was inserted to measure the gastric intramucosal pH. Subjects r and omly received either 150 mg/kg of intravenous N‐acetylcysteine or placebo over a 15‐min period , then a continuous infusion of 12.5 mg/hr of N‐acetylcysteine or placebo over ˜90 mins . Measurements : Infusion measurements were begun 60 mins after the beginning of infusion and lasted ˜30 mins . The infusion was then discontinued and 2 hrs later the final measurements were taken . Main Results : Basic patient characteristics ( age , sex , Acute Physiology and Chronic Health Evaluation [ APACHE ] II scores , Multiple Organ Failure scores ) did not differ significantly , nor did pre‐ and 2‐hr postinfusion measurements differ between any of the groups . Thirteen ( 45 % ) patients responded ( i.e. , showed an increase in & OV0312;o2 > 10 % , reaching a mean of 19 % ) to the N‐acetylcysteine infusion . The N‐acetylcysteine responders also showed an increase in gastric intramucosal pH , a decrease in veno‐arterial Pco2 , an increase in oxygen delivery , cardiac index , stroke index , and left ventricular stroke work index , as well as a significant decrease in systemic vascular resistance in comparison to baseline . The N‐acetylcysteine nonresponders , as well as the patients in the placebo group , did not show any significant changes in any of these variables . The N‐acetylcysteine responders had a higher survival rate ( 69 % ) than the nonresponders ( 19 % ) and were studied earlier after onset of sepsis ( 37 hrs ) than the nonresponders ( 61 hrs ) . The only significant difference between the entire N‐acetylcysteine group ( which included responders plus nonresponders ) and the placebo group was an increased & OV0312;o2 in the entire N‐acetylcysteine group during infusion measurements . Conclusions : N‐acetylcysteine provided a transient improvement in tissue oxygenation in about half of the septic shock patients , as indicated by an increase in & OV0312;o2 and gastric intramucosal pH and a decrease in veno‐arterial Pco2 . The higher survival rate in the N‐acetylcysteine responders and the fact that half of the patients receiving N‐acetylcysteine did not respond , suggests that , in some patients , sepsis irreversibly damages the microvasculature to the extent that N‐acetylcysteine has no effect . If analyzed by intention to treat , the N‐acetylcysteine did not produce effects that were significantly different from the placebo . Whether the N‐acetylcysteine challenge was merely diagnostic or whether N‐acetylcysteine can be effective in the treatment of sepsis deserves further investigation . ( Crit Care Med 1994 ; 22:1738–1746 Presently , only hydration and N-acetylcysteine have been shown to be effective in decreasing the incidence of radiographic contrast-induced nephropathy . We investigated the role of N-acetylcysteine and various hydration protocol s in vascular surgery patients undergoing angiography . A single-center , r and omized , placebo-controlled trial was conducted in patients with stable , preexisting renal dysfunction undergoing elective , outpatient angiography . Patients were r and omized to outpatient oral hydration and N-acetylcysteine , inpatient hydration plus N-acetylcysteine , or our st and ard therapy of inpatient intravenous hydration alone . Two of twenty-eight ( 7 % ) patients who received outpatient oral hydration and N-acetylcysteine developed contrast-induced nephropathy , while two of 25 ( 8 % ) who recieved inpatient hydration plus N-acetylcysteine developed contrast-induced nephropathy and two of 25 ( 8 % ) who received st and ard therapy of inpatient intravenous hydration alone developed contrast-induced nephropathy . There was no statistical difference in incidence of contrast-induced nephropathy between the groups . No statistically significant independent risk factors were identified among the patients who developed contrast-induced nephropathy . N-Acetylcysteine did not confer additional benefit to patients treated with inpatient intravenous hydration . Outpatient oral hydration plus N-acetylcysteine was as effective at preventing contrast-induced nephropathy as inpatient therapies and avoided costly hospital admission Objective To examine whether the antioxidant N-acetylcysteine could ameliorate the course of the adult respiratory distress syndrome ( ARDS ) in man . Design R and omized , double-blind , placebo-controlled study . Setting Medical and surgical ICU in a regional hospital . Patients Sixty-six ICU patients with ARDS . Interventions Patients with ARDS ( Pao2/FIO2 ratio < 250 torr ) were treated with either the antioxidant N-acetylcysteine 150 mg/kg as a loading dose and then 20 mg/kg/hr , or with placebo for 6 days . Measurements and Main Results No improvement could be demonstrated in the Pao2/FIO2 ratio in the study group as compared with the control group on any day . Pulmonary compliance was higher in the N-acetylcysteine group than in the placebo group on all days , but this difference did not reach the chosen 5 % level of significance . No difference between the two groups could be demonstrated on chest radiograph or on survival rate . We documented that N-acetylcysteine acts as an anticoagulant and perhaps decreases pulmonary fibrin uptake during ARDS . Conclusions N-acetylcysteine might be of benefit in ARDS . Before further clinical studies are started , problems with N-acetylcysteine and coagulation have to be eluci date d in order to find out whether N-acetylcysteine could have a beneficial effect in the treatment of ARDS Objective : To determine whether fenoldopam and N-acetylcysteine prevent renal deterioration and improve hospital outcome for patients with chronic renal insufficiency undergoing cardiac surgery . Design : Prospect i ve , r and omized , double-blinded , placebo-controlled trial . Setting : A community hospital that is a cardiac referral center . Patients : Seventy-nine adult patients with chronic renal insufficiency ( creatinine clearance ≤40 mL/min ) who underwent cardiac surgery . Interventions : Group 1 received intravenous fenoldopam 0.1 & mgr;g/kg/min started at surgical induction and continued for 48 hrs . Group 2 received N-acetylcysteine 600 mg orally twice a day , from preoperative day 1 to postoperative day 1 . Group 3 received both fenoldopam and N-acetylcysteine , and group 4 patients served as controls . Measurements and Main Results : Using multiple comparisons ( analysis of variance ) with change scores , and statistically adjusting for group differences in aortic cross-clamp time , use of intraoperative aprotinin , and preoperative use of statin , we found that the change in creatinine clearance from preoperative to postoperative day 3 was statistically less for group 1 ( −1.47 mL/min ± 2.06 se , p = .0286 ) and for group 2 ( −0.67 mL/min ± 2.11 se , p = .0198 ) and less but not quite significant for group 3 ( −3.08 mL/min ± 1.95 se , p = .0891 ) compared with controls ( −8.15 mL/min ± 2.18 se ) . Furthermore , the adjusted weight gain on postoperative day 3 was 5.55 kg ± 1.00 se ( p = .0988 ) for group 1 , 5.06 kg ± 1.06 se ( p = .0631 ) for group 2 , and 5.14 kg ± .91 se ( p = .0445 ) for group 3 compared with 8.03 kg ± 1.07 se for group 4 . However , there was no decrease in length of critical care or hospital stay or hospital costs . Finally , fenoldopam contributed to perioperative hypotension . Conclusions : Perioperative fenoldopam and N-acetylcysteine abrogate the early postoperative decline in renal function of patients who have chronic renal insufficiency , although these agents do not affect other parameters of cardiac surgical outcome The production of cytotoxic oxygen radicals by activated granulocytes is a proposed mechanism of lung injury in ARDS . Protective effects of N-acetylcysteine ( NAC ) have been described in experimental and clinical ARDS . NAC could act in part by replenishing the intracellular stores of glutathione ( GSH ) in activated granulocytes , leading to detoxification of oxygen radicals produced by these cells . To test this hypothesis , 16 patients in the early phase of ARDS were r and omized to receive either NAC ( n = 8) or placebo ( n = 8) ; granulocyte GSH , granulocyte oxygen radical production , and plasma levels of granulocyte elastase were measured in blood sample s drawn sequentially within 8 h after the onset of ARDS ( day 0 ) , and then 24 ( day 1 ) , 72 ( day 3 ) , and 120 h ( day 5 ) after the first sample ; treatment with NAC or placebo was started immediately after day 0 and stopped just after day 3 . Granulocyte GSH was significantly higher on days 1 and 3 when NAC was received by the patient . Unstimulated oxygen radical production , as measured ex vivo by luminol- and lucigenin-amplified chemiluminescence ( CL ) , was higher in granulocytes from ARDS patients than from healthy control subjects , but was not influenced by NAC . The plasma levels of granulocyte elastase were five to eight times above the upper normal limit on day 0 , decreased steadily until day 5 , and were uninfluenced by NAC . In summary , parenteral NAC treatment started within 8 h of diagnosis increases the intracellular GSH in the granulocytes of ARDS patients without decreasing spontaneous oxidant production by these cells . The mechanisms of the protective effects of this drug previously reported in experimental and clinical ARDS remain to be established Purpose To investigate the effect of N-acetylcysteine on preventing pump-induced oxidoinflammatory response during cardiopulmonary bypass ( CPB ) . Methods Forty patients undergoing coronary artery bypass grafting ( CABG ) were r and omly divided into a study group ( n = 20 ) , given 50 mg kg−1N-acetylcysteine intravenously for 3 days , and a control group ( n = 20 ) given saline . Serum sample s were collected for measurement of myeloperoxidase ( MPO ) , malondialdehyde ( MDA ) , interleukin-6 , Α1-acid glycoprotein ( AAGP ) , and C-reactive protein ( CRP ) during surgery and postoperatively . Results The MPO and MDA values showed a similar pattern during and after CPB in the study group , with significantly less variance than in the control group . Interleukin-6 showed similar patterns in the two groups , but the data from 30 min after the start of CPB and from 6 h post-CPB were significantly different . The AAGP and CRP values were both elevated during CPB in the two groups without a significant difference , but 6 and 24 h post-CPB , the values were significantly higher in the control group than in the study group . Conclusions N-Acetylcysteine decreased pump-induced oxidoinflammatory response during CPB , suggesting that it could be a novel therapy for assisting in the prevention of CBP-induced oxidoinflammatory damage OBJECTIVE To determine the levels of glutathione and cysteine in patients with ARDS and examine the effect of treatment with N-acetylcysteine ( NAC ) and L-2-oxothiazolidine-4-carboxylate ( Procysteine ; Clintec Technologies Inc ; Chicago [ OTZ ] ) on these levels and on common physiologic abnormalities , and organ dysfunction associated with ARDS . DESIGN R and omized , double-blind , placebo-controlled , prospect i ve clinical trial . SETTING ICUs in five clinical centers in the United States and Canada . PATIENTS Patients meeting a predetermined definition of ARDS and requiring mechanical ventilation . INTERVENTION St and ard care for ARDS and I.V. infusion , every 8 h for 10 days , of one of the following : NAC ( 70 mg/kg , n=14 ) , OTZ ( 63 mg/kg , n=17 ) , or placebo ( n=15 ) . MAIN RESULTS Both antioxidants effectively repleted RBC glutathione gradually over the 10-day treatment period ( 47 % and 49 % increases from baseline values for NAC and OTZ , respectively ) . There was no difference in mortality among groups ( placebo , 40 % ; NAC , 36 % ; OTZ , 35 % ) . However , the number of days of acute lung injury was decreased and there was also a significant increase in cardiac index in both treatment groups ( NAC/OTZ [+]14 % ; placebo [-]6 % ) . CONCLUSIONS Our findings suggest that repletion of glutathione may safely be accomplished with NAC or OTZ in patients with acute lung injury/ARDS . Such treatment may shorten the duration of acute lung injury , but larger studies are needed to confirm this Objective Expression of inflammatory mediators is controlled in part at the transcriptional level via nuclear factor-&kgr;B. Inhibition of nuclear factor-&kgr;B activation may be beneficial in critically ill patients . N-acetylcysteine is an antioxidant that inhibits nuclear factor-&kgr;B activation in vitro . In this pilot study we investigated the effect of N-acetylcysteine on nuclear factor-&kgr;B activation and circulating cytokine and adhesion molecules in patients with sepsis . Design Prospect i ve , r and omized , double blind , placebo-controlled pilot trial . Setting Eight-bed intensive care unit in a university teaching hospital . Patients Twenty consecutive patients within 12 hrs of fulfilling the consensus criteria for sepsis . Interventions A bolus of 150 mg/kg N-acetylcysteine in 100 mL of 0.9 % saline over 15 mins , then 50 mg/kg in 100 mL of 0.9 % saline over 4 hrs as a loading dose , and then a maintenance infusion of 50 mg/kg in 200 mL of 0.9 % saline over each 24-hr period for a total of 72 hrs , or an equivalent volume of saline . Measurements and Main Results Nuclear factor-&kgr;B activation was measured in mononuclear leukocytes using electrophoretic mobility shift assay , at baseline and 24 , 48 , 72 , and 96 hrs later . Activation decreased significantly in patients treated with N-acetylcysteine ( p = .016 ) but not placebo and was significantly reduced at 72 hrs compared with both preinfusion values ( p = .028 ) and patients receiving placebo ( p = .01 ) . Plasma interleukin-6 , interleukin-8 , and soluble intercellular adhesion molecule-1 concentrations were measured using enzyme immunoassay . Interleukin-6 concentrations were high initially and then decreased in all patients , regardless of whether they received N-acetylcysteine or placebo . Interleukin-8 decreased significantly only in those who received N-acetylcysteine ( p = .0081 ) . Soluble intercellular adhesion molecule-1 concentrations remained unchanged in all patients . Conclusions Administration of N-acetylcysteine results in decreased nuclear factor-&kgr;B activation in patients with sepsis , associated with decreases in interleukin-8 but not interleukin-6 or soluble intercellular adhesion molecule-1 . These pilot data suggest that antioxidant therapy with N-acetylcysteine may be useful in blunting the inflammatory response to sepsis . Further studies are warranted We have investigated the effect of N-acetylcysteine on hemodynamic variables , oxygen delivery ( DO2 ) , oxygen consumption ( VO2 ) , and oxygen extraction in patients with fulminant hepatic failure using independent methods of determining DO2 and VO2 , thereby eliminating the effect of mathematical coupling , which may have biased previous studies . In 11 patients with severe fulminant hepatic failure , we documented the hemodynamic effects of N-acetylcysteine during the first 5 hours of a st and ard infusion regime and simultaneously measured VO2 using a method based on respiratory gas analysis . We related physiological changes to plasma N-acetylcysteine concentrations , and compared this group with 7 patients who received placebo infusions . A variable hemodynamic response to N-acetylcysteine was observed that did not differ significantly in comparison with the placebo group , and did not correlate with plasma drug concentrations . The most significant relationship observed between DO2 and VO2 in any patient predicted a 13-mL x min(-1 ) x m(-2 ) increase in VO2 when DO2 increased by 100 mL x min(-1 ) x m(-2 ) ; in 8 patients , VO2 was independent of DO2 over the range observed . In the group that received N-acetylcysteine , a small ( mean 6 [ SD 6 ] mL x min(-1 ) x m[-2 ] ) increase in VO2 occurred in comparison with baseline after 1 hour of infusion ( P < .01 ) , but changes were not significantly different from the placebo group and were not sustained . N-Acetylcysteine infusion did not increase oxygen extraction or result in an improvement in whole-blood lactate levels or base excess during the study period . We conclude that N-acetylcysteine infusion does not result in clinical ly relevant improvements in global VO2 , or in clinical markers of tissue hypoxia in patients with severe fulminant hepatic failure Objective The antioxidant N-acetylcysteine ( NAC ) has been shown to attenuate septic tissue injury . To evaluate whether NAC affects host defense mechanisms in critically ill patients , thus predisposing to increased risk of infection , the current study focuses on neutrophil phagocytotic and burst activity after treatment with NAC . Design Prospect i ve , r and omized , clinical trial . Setting Twelve-bed operative intensive care unit in a university hospital . Patients Thirty patients diagnosed with sepsis/systemic inflammatory response syndrome , or multiple trauma . Interventions Patients were r and omly assigned to receive either NAC ( n = 15 ) for 4 days in increasing dosages ( day 1 : 6 g ; day 2 : 12 g ; days 3 and 4 : 18 g ) or a mucolytic basis dosage of NAC ( 3 × 300 mg/day [ control ] ; n = 15 ) , respectively . Measurements and Main Results Blood sample s were taken before NAC high-dose infusion ( day 1 ) , after increasing doses of NAC ( days 3 and 5 ) and 4 days after the last high-dose treatment ( day 8) . Neutrophil oxidative burst activity after stimulation with Escherichia coli and polymorphonuclear phagocytosis were determined in a flow cytometric assay . Baseline values of polymorphonuclear functions were comparable in both groups . NAC high-dose treatment result ed in a significantly improved phagocytosis activity compared with control patients . In contrast to this , polymorphonuclear burst activity was significantly reduced in the NAC high-dose treated group on day 3 . Conclusion These findings suggest that infusion of NAC in high doses affects granulocyte functions in critically ill patients . Antimicrobial host defense requires the effective sequence of cell adhesion , phagocytosis , and bactericidal respiratory burst . The enhanced phagocytotic activity might be a compensatory mechanism in states of impaired respiratory burst to maintain tissue sterility . For certain mechanisms of disease , the effects observed might be favorable ( e.g. , ischemia/reperfusion , endothelial cell activation ) , for others ( infection ) this might be detrimental AIM Myocardial ischemia/reperfusion injury in patients undergoing coronary artery by-pass grafting ( CABG ) involves the reperfusion-induced conversion of reversible injured myocardial and endothelial cells . N-acetylcysteine ( NAC ) has a potential being the minimization of the impact of reperfusion injury . The aim of this study was to evaluate the effects of intravenous NAC on periprocedural myocardial injury after CABG . METHODS The population of this prospect ive-r and omized , double blind , placebo controlled study consisted of 40 patients undergoing on-pump CABG . All the patients were treated with st and ard medical therapy and eligible patients were r and omized to NAC group ( N.=19 ; intravenous infusion for 1 hour before the procedure at a dose of 50 mg/kg , followed by intravenous infusion for 48 hours after the operation at a dose of 50 mg/kg/day ) and placebo ( saline ) group ( N.=21 ) . The study drug and placebo infusions were set to infuse at the same rate . RESULTS Demographic and procedural variables were similar in the both groups ( All P>0.05 ) . Creatine kinase MB isoform ( CK-MB ) mass levels did not significantly differ between the groups at both preoperative and postoperative periods . Similarly , cTnT levels were similar in the groups at all periods . Eight patients in the NAC group and 7 in the placebo group had increased CK-MB > 3 times normal value . However , only 3 patients in the NAC group experienced CK-MB>5 times normal value . CONCLUSION Results of this study indicated that periprocedural use of NAC as intravenously did not attenuate myocardial damage after on-pump CABG surgery Objective Our objective was to investigate whether short-term infusion of the oxygen free radical scavenger N-acetylcysteine ( NAC ) administered before and during extensive abdominal surgery could ameliorate the progression of early systemic inflammatory response . Design Prospect i ve , r and omised , double-blinded , placebo-controlled clinical trial . Setting Twenty-bed intensive care unit in a university hospital . Patients Following written informed consent , 100 patients were r and omised into NAC and placebo groups . Three patients from the NAC group and four from the placebo group withdrew before the final analysis .InterventionThe treatment group ( n=47 ) received NAC ( 150 mg/kg–1 bolus followed by a continuous infusion of 12 mg/kg–1/h–1 ) and the placebo group ( n=46 ) received the same volume of 5 % dextrose during surgery . Measurements and results Serum procalcitonin ( PCT ) , C-reactive protein ( CRP ) and microalbuminuria was monitored preoperatively , on admission to ICU , then daily during the first 3 postoperative days . For statistical analysis Mann Whitney and Chi-squared tests were used . Patients ' clinical course was similar in each group as monitored by the Multiple Organ Dysfunction Scores . There was no significant difference between the two groups regarding PCT and microalbuminuria at any assessment point . Significantly lower CRP levels were found in the NAC group on days 1 and 2 ( t24 : median : 84.5 interquartile range : [ 62–120 ] vs. 118 [ 86–137 ] mg/l ; p=0.020 ; t48 : 136 [ 103–232 ] vs. 195 [ 154–252 ] mg/l ; p=0.013 , NAC vs. placebo respectively ) . Conclusion In this study , short-term NAC treatment decreased CRP levels , but failed to attenuate any other inflammatory response , as monitored by serum PCT and microalbuminuria . Overall , our results do not support the routine prophylactic use of NAC as a free radical scavenger in abdominal surgery BACKGROUND Cold-blood cardioplegia is a well-known method in coronary artery bypass graft surgery , and several authors have used various agents in the enrichment of cold-blood cardioplegia to decrease ischemia-reperfusion injury seen during surgery . N-acetylcysteine , which can increase glutathione levels , is one of the agents added to cardioplegic solutions to decrease myocardial injury . This study was planned to assess the efficiency of N-acetylcysteine-enriched cold-blood cardioplegia on early reperfusion injury in patients with ischemic heart disease undergoing coronary artery bypass grafting , using measurements of cardiac troponin I and malondialdehyde release . METHODS Thirty patients ( 11 women and 19 men ) with left ventricular ejection fraction greater than 0.40 scheduled for coronary artery bypass grafting were r and omly divided into two groups . We used cold-blood cardioplegia enriched with N-acetylcysteine ( 50 mg per kilogram of body weight ) in the first group and cold-blood cardioplegia alone in the second group . Hemodynamic variables and clinical properties of the patients were preoperatively and postoperatively evaluated . Enzyme releases were measured in the early hours after the operation . RESULTS In the N-acetylcysteine-enriched group cardiac troponin I levels were lower than in the N-acetylcysteine-free group , and this difference was statistically significant . Cardiac troponin I levels increased in both groups in the 6th and 12th hours postoperatively , but there was a statistically significant difference between the two groups . Malondialdehyde levels were significantly higher in the N-acetylcysteine-free group after the 6th , 12th , 24th , and 48th hours postoperatively when compared with the N-acetylcysteine-enriched group . CONCLUSIONS N-acetylcysteine-supplemented cold-blood cardioplegia minimizes myocardial injury in the early hours after and during the cardiac surgery N-acetylcysteine ( NAC ) is an antioxidant agent which has been shown to benefit patients with fulminant hepatic failure . We have examined its effect in patients with chronic liver disease undergoing orthotopic liver transplantation by giving NAC during operation . In a prospect i ve , r and omized , double-blind , placebo-controlled study of 50 patients , NAC appeared to induce mild vasodilatation , improve oxygen delivery and consumption , and reduce base deficit , but data interpretation was difficult . There were no significant effects on mortality , morbidity or postoperative graft function |
12,792 | 29,476,794 | The remaining articles were reports of prospect i ve cohort studies from Denmark and the Netherl and s. CONCLUSIONS there is currently insufficient evidence to recommend one tooth replacement strategy over another in adult patients with reduced dentitions . | OBJECTIVES A systematic review of r and omised and non-r and omised controlled trials was conducted to evaluate studies of the effectiveness of different tooth replacement strategies in adult patients with shortened dental arches .
The objectives of the review were to determine the survival rates of different prosthodontic interventions , the risk of tooth loss with and without prosthodontic interventions , and the impact of different tooth replacement strategies on oral-health related quality of life ( OHRQoL ) . | Objective To analyse the factors affecting the clinical performance and those influencing the survival of resin-retained bridgework provided at a UK dental teaching hospital between 1994 and 2001 . Design A prospect i ve analysis of restorations provided at a single centre using case notes with all patients invited for review to corroborate findings . Setting Department of Restorative Dentistry , University of Bristol Dental Hospital and School , Bristol , United Kingdom . Subjects and methods Between January 1994 and December 2001 , data regarding 1,000 consecutive resin-retained bridges provided at Bristol Dental Hospital and School were recorded . Data was available for 805 patients at the time of the study . Following invitation , 621 patients attended for a review appointment . Life table and Kaplan-Meir survival analysis were carried out for all restorations provided . Results The five-year and ten-year survival rates estimated by the life-table method are 80.8 % ( 95 % confidence interval 78.0–83.6 % ) and 80.4 % ( 95 % confidence interval 77.6–83.2 % ) respectively . The median survival can not be estimated for this study as the survival probability remains above 80 % even at the longest follow-up . Analysis of clinical variables influencing survival revealed that design of the restoration and experience of the operator providing the restoration were significant factors . Resin-retained bridges made with minimal tooth preparation are shown to be superior in terms of longevity than those for which other types of tooth preparation is made . Patient satisfaction with their treatment was high In a multicentre r and omised trial ( German Research Association , grants DFG WA 831/2 - 1 to 2 - 6 , WO 677/2 - 1.1 to 2 - 2.1 . ; controlled-trials.com IS RCT N97265367 ) , patients with complete molar loss in one jaw received either a partial removable dental prosthesis ( PRDP ) with precision attachments or treatment according to the SDA concept aim ing at pre-molar occlusion . The objective of this current analysis was to evaluate the influence of different treatments on periodontal health . Linear mixed regression models were fitted to quantify the differences between the treatment groups . The assessment at 5 years encompassed 59 patients ( PRDP group ) and 46 patients ( SDA group ) . For the distal measuring sites of the posterior-most teeth of the study jaw , significant differences were found for the plaque index according to Silness and Löe , vertical clinical attachment loss ( CAL-V ) , probing pocket depth ( PPD ) and bleeding on probing . These differences were small and showed a slightly more unfavourable course in the PRDP group . With CAL-V and PPD , significant differences were also found for the study jaw as a whole . For CAL-V , the estimated group differences over 5 years amounted to 0.27 mm ( 95 % CI 0.05 ; 0.48 ; P = 0.016 ) for the study jaw and 0.25 mm ( 95 % CI 0.05 ; 0.45 ; P = 0.014 ) for the distal sites of the posterior-most teeth . The respective values for PPD were 0.22 mm ( 95 % CI 0.03 ; 0.41 ; P = 0.023 ) and 0.32 mm ( 95 % CI 0.13 ; 0.5 ; P = 0.001 ) . It can be concluded that even in a well-maintained.patient group statistically significant although minor detrimental effects of PRDPs on periodontal health are measurable 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 BACKGROUND General dental care can effectively control disease and restore damaged tissue , yet little is known about its impact on patients ' subjective oral health , namely treatment goals and oral health-related quality of life ( OHRQoL ) . This study aim ed to evaluate change in both aspects of subjective oral health among elderly adults receiving publicly-funded , general dental care . METHODS We conducted a prospect i ve , single-group intervention study of adults aged 75 + years receiving care through the South Australian Dental Service ( SADS ) . Before receiving dental care , subjects completed the Oral Health Impact Profile ( OHIP-14 ) question naire which evaluates OHRQoL. In this question naire , subjects rated the extent to which they had attained a self-nominated oral health goal . Dentists provided st and ard-of-care treatment and six months later the OHIP-14 and goal attainment questions were re-administered . RESULTS Among the 253 adults studied , overall improvements in OHRQoL were observed ( p < 0.05 ) , although the effect was dependent on pre-treatment goal : mean OHIP-14 scores did not change significantly for subjects whose goal was less pain/discomfort while significant improvements were observed for subjects with other treatment goals . In contrast , mean goal attainment ratings improved significantly ( P < 0.05 ) , regardless of treatment goal categories . CONCLUSIONS Dental care was associated with improvements in subjective oral health , although different patterns of improvement were observed for OHRQoL compared with goal attainment ratings OBJECTIVES This study aim ed to compare two different tooth replacement strategies for partially dentate older patients ; namely functionally orientated treatment according to the principles of the shortened dental arch ( SDA ) and conventional treatment using removable partial dentures ( RPDs ) using a r and omised controlled clinical trial . The primary outcome measure for this study was impact on oral health-related quality of life ( OHRQoL ) measured using the short form of the oral health impact profile ( OHIP-14 ) . METHODS Patients aged 65 years and older were r and omly allocated to two different treatment groups : the RPD group and the SDA group . For the RPD group each patient was restored to complete arches with cobalt-chromium RPDs used to replace missing teeth . For the SDA group , patients were restored to a premolar occlusion of 10 occluding pairs of natural and replacement teeth using resin bonded bridgework ( RBB ) . OHRQoL was measured using the OHIP-14 question naire administered at baseline , 1 month , 6 months and 12 months after treatment intervention . RESULTS In total , 89 patients completed the RCT : 44 from the RPD group and 45 from the SDA group . Analysis using a mixed model of covariance ( ANCOVA ) illustrated that treatment according to the SDA concept result ed in significantly better mean OHIP-14 scores compared with RPD treatment ( p<0.05 ) . This result was replicated in both treatment centres used in the study . CONCLUSIONS In terms of impact on OHRQoL , treatment based on the SDA concept achieved significantly better results than that based on RPDs 12 months after treatment intervention ( trial registration no. IS RCT N26302774 ) . CLINICAL SIGNIFICANCE Functionally orientated treatment delivery result ed in significantly better outcomes compared to removable dentures in terms of impact on Objectives Although the shortened dental arch ( SDA ) concept is a widely accepted strategy to avoid overtreatment , little is known on its impact on oral health-related quality of life ( OHRQoL ) . This multicenter r and omized controlled trial aim ed to investigate the OHRQoL for removable partial dental prostheses ( RPDP ) with molar replacement versus the SDA concept . Material and methods In both groups , missing anterior teeth were replaced with fixed dental prosthesis . Two hundred fifteen patients with bilateral molar loss in at least one jaw were included . The Oral Health Impact Profile ( OHIP-49 ) was completed before ; 6 weeks ( baseline ) , 6 months , and 12 months after treatment ; and thereafter annually until 5 years . Results Of the initial cohort , 81 patients were assigned to the RPDP group and 71 to the SDA group ( age , 34 to 86 years ) . Before treatment , the median OHIP score was similar in both groups ( RPDP , 38.0 ; SDA , 40.0 ; n.s . ) . Results indicate marked improvements in OHRQoL in both groups between pretreatment and baseline ( RPDP , 27.0 ; SDA , 19.0 ; p ≤ 0.0001 ) which continued in the RPDP group until the 1-year follow-up ( p = 0.0002 ) . These significant reductions in OHIP scores are reflected in its subscales . No further differences were seen within and between groups during the remainder observation period . Conclusion Both treatments show a significant improvement in OHRQoL which continued in the RPDP group until the 1-year follow-up . No significant differences were seen between groups . Clinical relevance For improving OHRQoL , it is not necessary to replace missing molars with a RPDP OBJECTIVE To conduct a cost-effectiveness analysis comparing two different tooth replacement strategies for partially dentate older patients , namely partial removable dental prostheses ( RDP ) and functionally orientated treatment based on the shortened dental arch concept ( SDA ) . METHODS Ninety-two partially dentate older patients completed a r and omized controlled clinical trial . Patients were r and omly allocated to two treatment groups : the RDP group and the SDA group . Treatment effect was measured using impact on oral health-related quality of life ( OHrQOL ) , and the costs involved in providing and maintaining care were recorded for all patients . Patients were followed for 12 months after treatment intervention . All treatment was provided by a single operator . RESULTS The total cost of achieving the minimally important clinical difference ( MID ) in OHrQOL for an average patient in the RDP group was € 464.64 . For the SDA group , the cost of achieving the MID for an average patient was € 252.00 . The cost-effectiveness ratio was therefore 1:1.84 in favour of SDA treatment . CONCLUSION With an increasingly ageing population , many patients will continue to benefit from removable prostheses to replace their missing natural teeth . From a purely economic st and point , the results from this analysis suggest that the treatment of partially dentate older adults should be focused on functionally orientated treatment because it is simply more cost-effective PURPOSE Removable partial dentures ( RPD ) used to restore the severely shortened m and ible may adversely affect the remaining natural teeth and are associated with a low prevalence of use . This pilot study investigated patient satisfaction following restoration of m and ibular shortened dental arches . MATERIAL S AND METHODS Sixty subjects with m and ibular shortened dental arches entered a r and omized controlled trial comparing two types of m and ibular prostheses : bilateral free-end saddle RPDs and distal cantilever resin-bonded fixed partial dentures ( FPD ) . Patient satisfaction was assessed using self-administered question naires before ( baseline ) , 3 months after , and 1 year after provision of new prostheses . RESULTS Improvements in levels of general satisfaction with teeth , appearance of teeth , and perceived masticatory ability were significant for the FPD group . Significant improvements in perceived masticatory ability were noted for both groups . There were also significant improvements in perceived levels of comfort of m and ibular prostheses in both groups . Changes in summary satisfaction scores indicated improved satisfaction for both treatment groups but suggested a larger clinical effect for the FPD group . Significant differences between treatment groups were not established . CONCLUSION Patient-based outcomes reported suggested that resin-bonded cantilever FPDs are an effective means of restoring the shortened m and ibular dental arch in terms of patient comfort and acceptance A multi-centre r and omized clinical trial is under way at 14 university dental schools in Germany to compare prosthodontic treatments for the shortened dental arch ( SDA ) . One of the aims of this pilot- study was to measure the effect of two treatment options of the SDA on oral health-related quality of life and on the Research Diagnostic Criteria ( RDC ) for temporom and ibular disorders ( TMD ) . Thirty-four patients participated in the pilot- study . Inclusion criteria were : all molars were missing and the presence of at least both canines and one premolar in each quadrant . Participants were r and omly assigned to receive either removable partial dentures including molar replacement ( RPD_group ) or retain a premolar occlusion ( PROC_group ) . The Oral Health Impact Profile ( OHIP-49 ) and the RDC for TMD were completed by participants before treatment ( pre-treatment ) , 6 weeks ( 6 wks ) , 6 months ( 6 m ) and 12 months ( 12 m ) after treatment . At the 12-month follow up , data of 10 women and 11 men ( mean age : 62 + /- 10 years ) were available . Medians of the OHIP total-scores were as follows : RPD ( n = 10 ) , 43.5 ( pre-treatment ) , 18.2 ( 6 wks ) , 13.3 ( 6 m ) , 14.7 ( 12 m ) . PROC ( n = 11 ) : 31.8 ( pre-treatment ) , 27.1 ( 6 wks ) , 8.8 ( 6 m ) , 8.3 ( 12 m ) . Significant differences were shown for RPD_group between pre-treatment and 6m/12 m and for PROC_group between pre-treatment and 6 m . There were no significant differences between treatment groups at any time . Within each group , an improvement of life- quality was observed . No significant difference could be reported between the two therapy concepts . This may be due to the low sample size within the pilot study OBJECTIVES To assess sustainability of shortened dental arches ( SDA ) by determining time to ' first restorative intervention ' of teeth and time to ' tooth loss ' and comparing these outcomes with complete dental arches ( CDA ) and SDA plus removable dental prostheses ( RDP ) . METHODS Data ( follow-up time ranged from 27.4 ( SD 7.1 ) to 35.0 ( SD 5.6 ) years ; max . follow up : 45.8 years ) from patient records of 59 subjects ( 23 SDA , 23 CDA , and 13 SDA plus RDP ) participating in a prospect i ve cohort study on shortened dental arches ( SDA ) were analysed . Group effects on survival were analysed using Cox regression models ; where appropriate Kaplan-Meier analyses were done . RESULTS Compared to SDA subjects , CDA subjects had a lower risk to receive a first restorative intervention in anterior teeth ( HR=0.377 ; 95 % CI [ 0.205 - 0.695 ] ) and premolars ( HR=0.470 ; 95 % CI [ 0.226 - 0.977 ] ) . CDA subjects had a lower risk to lose premolars compared to SDA subjects ( HR=0.130 ; 95 % CI [ 0.053 - 0.319 ] ) . Risk for ' first restorative intervention ' and for ' tooth loss ' did not significantly differ between SDA with and without RDP . CONCLUSIONS SDA subjects had an increased risk to lose premolars and to receive a first time restoration in anterior teeth and premolars compared to CDA subjects . SDA subjects with RDP had no increased risk to receive a first restorative intervention or for tooth loss compared to SDA without RDP . CLINICAL RELEVANCE Subjects with shortened dental arches can be discerned as enduring at-risk patients . It is therefore recommended that shortened dental arch subjects receive intensive and continuous care to prevent further tooth loss Objectives The study was design ed to provide clinical outcome data for two treatments of the shortened dental arch ( SDA ) . Material and Methods In a multicenter r and omized controlled clinical trial , patients with complete molar loss in one jaw were provided with either a partial removable dental prosthesis ( PRDP ) retained with precision attachments or treated according to the SDA concept preserving or restoring a premolar occlusion . No implants were placed . The primary outcome was tooth loss . Results Of 152 treated patients , 132 patients reached the 5-year examination . Over 5 years , 38 patients experienced tooth loss . For the primary outcome tooth loss , the Kaplan – Meier survival rates at 5 years were 0.74 ( 95 % CI 0.64 , 0.84 ) in the PRDP group and 0.74 ( 95 % CI 0.63 , 0.85 ) in the SDA group . For tooth loss in the study jaw , the survival rates at 5 years were 0.88 ( 95 % CI 0.80 , 0.95 ) in the PRDP group and 0.84 ( 95 % CI 0.74 , 0.93 ) in the SDA group . The differences were not significant . No Cox regression models of appropriate fit explaining tooth loss on the patient level could be found . Conclusions The overall treatment goals of a sustainable oral rehabilitation and the avoidance of further tooth loss over longer periods were not reliably achievable . The influence of the type of prosthetic treatment on tooth loss might have been overestimated . Clinical Relevance Regarding our results , the patient ’s view will gain even more importance in the clinical decision between removable and fixed restorations in SDAs Removable partial dentures may adversely affect remaining tissues and have a low prevalence of use . This r and omized controlled trial was design ed to compare the time to survival of cantilever resin-bonded fixed partial dentures and conventional removable partial dentures to restore shortened lower dental arches . We r and omly allocated 25 male and 35 female patients ( median age , 67 years ) to fixed or removable partial denture groups of 30 persons , matched for age and sex . Survival of the prostheses was assessed , based on listed criteria , at each review or when problems arose . Although the removable partial denture group required rather more maintenance visits , the difference in survival rates was not statistically significant ( hazard ratio = 0.59 , with 95 % CI 0.27 , 1.29 ) . In the absence of significant differences in five-year survival , the reported advantages of fixed partial dentures , including reduced maintenance frequency , offer positive support for the use of resin-bonded fixed partial dentures CONTEXT Removable partial dentures used to restore the shortened lower dental arch may adversely affect the remaining natural teeth and are associated with a low prevalence of use . OBJECTIVE To report the findings for caries incidence 2 years after restoration of lower shortened arches with bilateral cantilever resin-bonded bridges ( RBBs ) and conventional partial dentures ( RPDs ) . DESIGN R and omised controlled trial . SETTING Secondary care PATIENTS 25 male and 35 female subjects of median age 67 years . were r and omly allocated to ' bridge ' and ' denture ' treatment groups of 30 patients each matched for age and sex . Caries incidence was recorded during dental examinations 3 months , 1 and 2 years after insertion of new lower prostheses . INTERVENTIONS Cantilever RBBs and conventional RPDs with cast metal frameworks . RESULTS There was a highly significant difference in the frequency of new caries lesions , 11 and 51 in the bridge and denture groups respectively ( P < 0.01 ) . 20 out of 27 bridge patients and 9 of 23 denture patients had no caries experience . Multivariate modeling identified treatment group as the only significant predictor of caries occurrence . CONCLUSIONS Two years after restoration of lower shortened arches for an elderly sample of patients , there was a significantly greater incidence of new and recurrent caries lesions in subjects restored with RPDs compared with cantilever RBBs OBJECTIVE To compare the cost-effectiveness of conventional treatment using partial dentures with functionally orientated treatment to replace missing teeth for partially dentate elders using a r and omised controlled clinical trial . BACKGROUND In many countries , including the Republic of Irel and , the only publically funded treatment option offered to partially dentate older patients is a removable partial denture . However , evidence suggests that these removable prostheses are unpopular with patients and can potentially increase the risk of further dental disease and subsequent tooth loss . MATERIAL S AND METHODS Fourty-four partially dentate patients aged 65 years and older were recruited . Patients were r and omly assigned to the two treatment arms of the study . The conventional treatment group received removable partial dentures to replace all missing natural teeth . The functionally orientated group was restored to a Shortened Dental Arch ( SDA ) of 10 occluding contacts using resin-bonded bridgework ( RBB ) . The costs associated with each treatment were recorded . Effectiveness was measured in terms of the impact on oral health-related quality of life ( OHRQoL ) using OHIP-14 . RESULTS Both groups reported improvements in OHRQoL 1 month after completion of treatment . The conventional treatment group required 8.3 clinic visits as compared to 4.4 visits for the functionally orientated group . The mean total treatment time was 183 min 19 s for the conventional group vs. 124 min 8 s for the functionally orientated group . The average cost of treatment for the conventional group was 487.74 Euros compared to 356.20 Euros for the functional group . CONCLUSIONS Functionally orientated treatment was more cost-effective than conventional treatment in terms of treatment effect and opportunity costs to the patients ' time Between 1994 and 1999 , 515 Astra st and ard implants were placed and documented prospect ively in 107 patients . Of these implants , 364 were placed in original jawbone , 38 in areas augmented with local osteoplasty , and 113 in bone grafts from the iliac crest . The main indications for implantation were an atrophic edentulous alveolar crest ( n = 361 ) and a shortened dental arch ( n = 113 ) . Single-tooth implants were excluded . In a special clinical examination , 56 patients with 258 implants were investigated . The average in situ time of the implants was 34.2 months . Failing osseointegration ( n = 10 ) , peri-implantitis ( n = 10 ) , and implant fracture ( n = 1 ) in 15 patients result ed in the failure of 21 implants ( 4.1 % ) . Three patients with 8 implants died from malignant tumor . Currently , 27 implants have been lost to follow-up , and 488 implants remain in situ ( 95.9 % ) . Under analyses with different implant success criteria , the success rate decreased to 85 % . Based on the results in this patient population , this implant was found to be a useful alternative to established implant systems for the indications analyzed Prosthesis function and dental conditions were observed for 5 years in 27 elderly patients treated with m and ibular cantilevered fixed partial dentures ( FPDs ) and in 26 elderly patients treated with distal-extension removal partial dentures ( RPDs ) . All patients were treated with a complete upper denture . The patients were assigned r and omly into two treatment groups that had the same composition with regard to sex , age , and distribution of teeth . The patients were under supervised oral hygiene and prosthodontic care . Clinical examination of prostheses , masticatory system , periodontal status , and caries was carried out yearly . Oral hygiene was good , and the periodontal status was maintained in both groups . Caries was observed six times more frequently in the RPD group than in the group with fixed restorations , however . Occlusal and functional conditions deteriorated in the RPD group only . Eight of 42 fixed partial dentures ( 19 % ) failed ; of these , six were recemented with composite resin . Generally the need for dental and prosthetic follow-up treatment was more pronounced in the RPD group than in the FPD group OBJECTIVES This article is part of a r and omized clinical trial on different treatments in the shortened dental arch ( SDA ) . It focused on the abutment tooth prognosis with cantilevered fixed dental prostheses ( CFDPs ) . METHODS Sixty-two patients with a bilaterally SDA up to the first or second premolar in the m and ible or maxilla were evaluated . In 57 of 124 quadrants , second premolars were replaced by a CFDP ( cantilever group ) . In the remaining 67 quadrants , a natural second premolar was present and thus no need for a CFDP was given ( non-cantilever group ) . Patients were recalled annually up to 5 years . RESULTS The mean observation period was 56.3 months ( min . 3.0 , max . 76.2 , SD 16.1 ) . Kaplan-Meier survival rates concerning tooth loss and tooth fracture were 93.9%/94.0 % in the cantilever group and 91.9%/92.8 % in the non-cantilever group . Differences between both groups were not significant . The survival rate concerning loss of retention of CFDP retainers was 92.1 % in the cantilever group . CONCLUSION After 5 years of clinical service , CFDPs for the replacement of the second premolar showed no negative impact on the abutment tooth prognosis . CLINICAL SIGNIFICANCE Cantilevered fixed dental prostheses present a viable treatment option in the shortened dental arch without compromising the medium-term abutment tooth prognosis The aim of this multicentre prospect i ve study was to investigate the effect of prosthetic restoration for missing posterior teeth in patients with shortened dental arches ( SDAs ) . SDA patients with 2 - 12 missing occlusal units ( a pair of occluding premolars corresponds to one unit , and a pair of occluding molars corresponds to two units ) were consecutively recruited from seven university-based dental hospitals in Japan . Patients chose no replacement of missing teeth or prosthetic treatment with removable partial dentures ( RPDs ) or implant-supported fixed partial dentures ( IFPDs ) . Oral health-related quality of life ( OHRQoL ) was measured using the oral health impact profile ( Japanese version - OHIP-J ) at baseline and follow-up/post-treatment evaluation . Of the 169 subjects who completed baseline evaluation , 125 subjects ( mean age ; 63.0 years ) received follow-up/post-treatment evaluation . No-treatment was chosen by 42 % ( 53/125 ) of the subjects , and 58 % ( 72/125 ) chose treatment with a RPD ( n = 53 ) or an IFPD ( n = 19 ) . In the no-treatment ( NT ) group , the mean OHIP summary score at baseline was similar to that at follow-up evaluation ( P = 0.69 ) . In the treatment ( TRT ) group , the mean OHIP summary score decreased significantly after the RPD treatment ( P = 0.002 ) , and it tended to decrease , though not statistically significant ( P = 0.18 ) , after the IFPD treatment . The restoration of one occlusal unit was associated with a 1.2-point decrease in OHIP summary score ( P = 0.034 ) . These results suggest that the replacement of missing posterior teeth with RPDs or IFPDs improved OHRQoL. Prosthetic restoration for SDAs may benefit OHRQoL in patients needing replacement of missing posterior teeth |
12,793 | 32,258,835 | All study design s defined by the Oxford Centre for Evidence -Based Medicine will be included in the search . " | Introduction Wide Awake Local Anaesthetic No Tourniquet ( WALANT ) technique has been developed to eliminate tourniquet pain during upper limb and h and surgery whilst also improving utilisation of operating theatre time and inpatient stay , however inconclusive data still limits the techniques uptake .
Here presents a protocol for a systematic review to collate findings to produce conclusive data on efficacy of WALANT . | PURPOSE Wide-awake , local anesthesia , no tourniquet ( WALANT ) h and surgery was developed to improve access to h and surgery care while optimizing medical re sources . H and surgery in the clinic setting may result in substantial cost savings for the United States Military Health Care System ( MHS ) and provide a safe alternative to performing similar procedures in the operating room . METHODS A prospect i ve cohort study was performed on the first 100 consecutive clinic-based WALANT h and surgery procedures performed at a military medical center from January 2014 to September 2015 by a single h and surgeon . Cost savings analysis was performed by using the Medical Expense and Performance Reporting System , the st and ard cost accounting system for the MHS , to compare procedures performed in the clinic versus the operating room during the study period . A study specific question naire was obtained for 66 procedures to evaluate the patient 's experience . RESULTS For carpal tunnel release ( n = 34 ) and A1 pulley release ( n = 33 ) , there were 85 % and 70 % cost savings by having the procedures performed in clinic under WALANT compared with the main operating room , respectively . During the study period , carpal tunnel release , A1 pulley release , and de Quervain release performed in the clinic instead of the operating room amounted to $ 393,100 in cost savings for the MHS . There were no adverse events during the WALANT procedure . CONCLUSIONS A clinic-based WALANT h and surgery program at a military medical center results in considerable cost savings for the MHS . TYPE OF STUDY /LEVEL OF EVIDENCE Economic/Decision Analysis IV Background The purpose of this study was to provide prospect i ve independently analyzed evidence on how patients feel about a carpal tunnel release ( CTR ) performed under local anesthesia only ( no sedation or tourniquet ) versus with local anesthesia , intravenous ( IV ) sedation , and a tourniquet . Methods This prospect i ve cohort study compared 100 consecutive CTRs done with only lidocaine and epinephrine in Saint John , New Brunswick to 100 consecutive CTRs done with IV sedation in Davenport , Iowa . Patient perspectives on the anesthesia were captured in a blinded question naire 1 week postoperatively . Results For subsequent surgery , 93 % of wide awake patients would choose local anesthesia only and 93 % of se date d patients would choose sedation . Wide awake patients spent less time at the hospital ( M = 2.6 h ) than se date d patients ( M = 4.0 h ; p < .001 ) . Preoperative blood work , electrocardiograms , and /or chest radiographs were done for 3 % of wide awake patients and 48 % of se date d patients ( p < 0.001 ) . Preoperative anxiety levels for wide awake patients were lower than for se date d patients ( p = 0.007 ) ; postoperative anxiety was similar . There were no anesthesia complications in either group . Narcotics were used by 5 % of unse date d patients and 67 % of se date d patients ( p < 0.001 ) . Adequate pain control was reported by 89 % and 90 % of patients , respectively . Conclusions The majority of patients from both cohorts liked whichever method of anesthesia they received and would choose it again . However , se date d patients spent more time at the hospital , required more preoperative testing , and reported greater preoperative anxiety Purpose : Minor h and surgeries can be done under field sterility in procedure rooms . Surgeons are still sceptical about the usage of wide awake local anaesthesia no tourniquet ( WALANT ) technique . They perceive that patients can tolerate tourniquet for a brief period while they perform minor surgeries under local anaesthesia ( LA ) . We compared the perceived comfort experienced by patients during minor h and surgeries with WALANT and LA/tourniquet . We investigated the difference in preoperative preparation time , operating time and blood loss between the two groups . Methods : Between July and October 2016 , a total of 72 patients were diagnosed with carpal tunnel syndrome , trigger finger or ganglion , at the University Malaya Medical Centre . Forty patients consented to participate in this study and were r and omized into WALANT and LA/tourniquet groups . Anaesthesia was administered accordingly and tourniquet was applied . The time taken for preoperative preparation and surgery was recorded . Each surgeon estimated the blood loss . The perceived comfort level of each patient was quantified using a visual analogue score ( VAS ) . Data were analysed using SPSS . Results : The mean VAS for the WALANT group was 2.33 ± 1.94 , whereas it was 4.72 ± 3.05 for the LA/tourniquet group , and the difference was statistically significant ( p < 0.05 ) . The mean time for preoperative preparation in WALANT group was 19.17 ± 12.61 min and LA/tourniquet group was 7.05 ± 3.44 min . The difference between these groups was statistically significant ( p < 0.01 ) . There was no significant difference in operating time and blood loss . Conclusion : WALANT technique was associated with better patient comfort . Tourniquet was the main reason for discomfort during surgeries . WALANT is an alternative in minor h and surgeries for a bloodless surgical field without the discomfort of tourniquet application Background : We prospect ively evaluated opioid consumption postoperatively following trigger finger release ( TFR ) and open carpal tunnel release ( CTR ) , and hypothesized that cases performed wide awake with local anesthesia and no tourniquet ( WALANT ) would result in increased opioid consumption compared with cases performed under monitored anesthesia care ( MAC ) . Methods : Postoperative opioid consumption following CTR and TFR was prospect ively collected over 6 months . The primary end points of the study were : ( 1 ) total opioid consumption ; and ( 2 ) the number of days an opioid was used for both groups . Results : Mean opioid use and number of days the opioid was used for all MAC cases were 3.95 pills and 1.8 days , respectively . The results for WALANT were 3.85 pills and 1.6 days . Conclusions : These results suggest that effective pain control postoperatively may be independent of anesthesia type for soft tissue procedures of the h and . Specifically , average opioid consumption and days of utilization were similar in both the MAC and WALANT groups . Average postoperative opioid consumption was approximately only 4 opioid pills . Consideration should be given to prescribing fewer opioids for surgeries such as CTR and TFR BACKGROUND Most minor h and operations can be performed with local anesthesia and tourniquet . Some literature supports this concept based on the believe that the " patient can tolerate it " . Nowadays , the wide-awake technique with epinephrine- contained lidocaine is safe . This technique does not need a tourniquet because epinephrine provides local vasoconstriction . OBJECTIVE The present study was design ed to compare patients ' comfort and effectiveness of local anesthesia as well as bleeding at the surgical site between wide-awake anesthesia and local lidocaine with tourniquet application . MATERIAL AND METHOD Prospect i ve Clinical Trial was performed in 60 patients who received outpatient surgery for common h and problems at Maharaj Nakorn Chiang Mai Hospital . With r and omization , 30 patients were in wide-awake group , who received adrenaline-contained lidocaine as a local anesthetic agent , with tourniquet wrapping but with no pressure applied ( group 1 ) . The other 30 patients were in the conventional group that received lidocaine ( no adrenaline ) and a 250-mmHg tourniquet application ( group 2 ) . Operations were performed with st and ard methods . Visual analog scores , surgical field bleeding , amount of bleeding , any complications within 4 weeks were recorded . RESULTS There are no significant differences between the two groups in terms of patient profiles ( sex , age and diseases ) , injected site pain and surgeon 's opinion of surgical site bleeding . Tourniquet 's pain and the amount of blood loss in the conventional group were significantly higher than the wide-awake group . CONCLUSION Wide-awake technique ( no tourniquet applied ) offers better comfort for patients and less total blood loss while providing effective anesthesia and patient safety as with the conventional technique We conducted a prospect i ve r and omized controlled trial to investigate carpal tunnel decompression under local anaesthesia . Carpal tunnel decompression was performed in 37 wrists using local anaesthesia and an arm tourniquet and 36 without tourniquet but with a local anaesthetic mixture containing adrenaline . Patients who underwent carpal tunnel decompression using a tourniquet experienced a significantly greater degree of pain when compared with those who did not have a tourniquet . Pain and h and function improved to a similar degree in both groups . We conclude that carpal tunnel decompression performed with a tourniquet causes patients unnecessary pain with no additional benefit as compared with the wide-awake carpal tunnel decompression without use of a tourniquet . Level of evidence : |
12,794 | 28,617,209 | Risk assessment methods have been shown to be sensitive predictors of suicide and suicide attempts , but the frequency of false positives limits their clinical utility . | OBJECTIVE Suicide rates in veteran and military population s in the United States are high .
This article review s studies of the accuracy of methods to identify individuals at increased risk of suicide and the effectiveness and adverse effects of health care interventions relevant to U.S. veteran and military population s in reducing suicide and suicide attempts . | OBJECTIVE The SAD PERSONS scale is a widely used risk assessment tool for suicidal behavior despite a paucity of supporting data . The objective of this study was to examine the ability of the scale in predicting suicide attempts . METHOD Participants consisted of consecutive referrals ( N=4,019 ) over 2 years ( January 1 , 2009 to December 31 , 2010 ) to psychiatric services in the emergency departments of the 2 largest tertiary care hospitals in the province of Manitoba , Canada . SAD PERSONS and Modified SAD PERSONS ( MSPS ) scale scores were recorded for individuals at their index and all subsequent presentations . The 2 main outcome measures in the study included current suicide attempts ( at index presentation ) and future suicide attempts ( within the next 6 months ) . The ability of the scales to predict suicide attempts was evaluated with logistic regression , sensitivity and specificity analyses , and receiver operating characteristic curves . RESULTS 566 people presented with suicide attempts ( 14.1 % of the sample ) . Both SAD PERSONS and MSPS showed poor predictive ability for future suicide attempts . Compared to low risk scores , high risk baseline scores had low sensitivity ( 19.6 % and 40.0 % , respectively ) and low positive predictive value ( 5.3 % and 7.4 % , respectively ) . SAD PERSONS did not predict suicide attempts better than chance ( area under the curve = 0.572 ; 95 % confidence interval [ CI ] , 0.51 - 0.64 ; P value nonsignificant ) . Stepwise regression identified 5 original scale items that accounted for the greatest proportion of future suicide attempt variance . High risk scores using this model had high sensitivity ( 93.5 % ) and were associated with a 5-fold higher likelihood of future suicide attempt presentation ( odds ratio = 5.58 ; 95 % CI , 2.24 - 13.86 ; P<.001 ) . CONCLUSION In their current form , SAD PERSONS and MSPS do not accurately predict future suicide attempts Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items BACKGROUND Rates of self-harm are high and have recently increased . This trend and the repetitive nature of self-harm pose a significant challenge to mental health services . AIMS To determine the efficacy of a structured group problem-solving skills training ( PST ) programme as an intervention approach for self-harm in addition to treatment as usual ( TAU ) as offered by mental health services . METHOD A total of 433 participants ( aged 18 - 64 years ) were r and omly assigned to TAU plus PST or TAU alone . Assessment s were carried out at baseline and at 6-week and 6-month follow-up and repeated hospital-treated self-harm was ascertained at 12-month follow-up . RESULTS The treatment groups did not differ in rates of repeated self-harm at 6-week , 6-month and 12-month follow-up . Both treatment groups showed significant improvements in psychological and social functioning at follow-up . Only one measure ( needing and receiving practical help from those closest to them ) showed a positive treatment effect at 6-week ( P = 0.004 ) and 6-month ( P = 0.01 ) follow-up . Repetition was not associated with waiting time in the PST group . CONCLUSIONS This brief intervention for self-harm is no more effective than treatment as usual . Further work is required to establish whether a modified , more intensive programme delivered sooner after the index episode would be effective The 2013 US Veterans Administration/Department of Defense Clinical Practice Guidelines ( VA/DoD CPG ) require comprehensive suicide risk assessment s for VA/DoD patients with mental disorders but provide minimal guidance on how to carry out these assessment s. Given that clinician-based assessment s are not known to be strong predictors of suicide , we investigated whether a precision medicine model using administrative data after outpatient mental health specialty visits could be developed to predict suicides among out patients . We focused on male nondeployed Regular US Army soldiers because they account for the vast majority of such suicides . Four machine learning classifiers ( naive Bayes , r and om forests , support vector regression and elastic net penalized regression ) were explored . Of the Army suicides in 2004–2009 , 41.5 % occurred among 12.0 % of soldiers seen as outpatient by mental health specialists , with risk especially high within 26 weeks of visits . An elastic net classifier with 10–14 predictors optimized sensitivity ( 45.6 % of suicide deaths occurring after the 15 % of visits with highest predicted risk ) . Good model stability was found for a model using 2004–2007 data to predict 2008–2009 suicides , although stability decreased in a model using 2008–2009 data to predict 2010–2012 suicides . The 5 % of visits with highest risk included only 0.1 % of soldiers ( 1047.1 suicides/100 000 person-years in the 5 weeks after the visit ) . This is a high enough concentration of risk to have implication s for targeting preventive interventions . An even better model might be developed in the future by including the enriched information on clinician-evaluated suicide risk m and ated by the VA/DoD CPG to be recorded OBJECTIVE The authors evaluated the effectiveness of brief cognitive-behavioral therapy ( CBT ) for the prevention of suicide attempts in military personnel . METHOD In a r and omized controlled trial , active-duty Army soldiers at Fort Carson , Colo. , who either attempted suicide or experienced suicidal ideation with intent , were r and omly assigned to treatment as usual ( N=76 ) or treatment as usual plus brief CBT ( N=76 ) . Assessment of incidence of suicide attempts during the follow-up period was conducted with the Suicide Attempt Self-Injury Interview . Inclusion criteria were the presence of suicidal ideation with intent to die during the past week and /or a suicide attempt within the past month . Soldiers were excluded if they had a medical or psychiatric condition that would prevent informed consent or participation in outpatient treatment , such as active psychosis or mania . To determine treatment efficacy with regard to incidence and time to suicide attempt , survival curve analyses were conducted . Differences in psychiatric symptoms were evaluated using longitudinal r and om-effects models . RESULTS From baseline to the 24-month follow-up assessment , eight participants in brief CBT ( 13.8 % ) and 18 participants in treatment as usual ( 40.2 % ) made at least one suicide attempt ( hazard ratio=0.38 , 95 % CI=0.16 - 0.87 , number needed to treat=3.88 ) , suggesting that soldiers in brief CBT were approximately 60 % less likely to make a suicide attempt during follow-up than soldiers in treatment as usual . There were no between-group differences in severity of psychiatric symptoms . CONCLUSIONS Brief CBT was effective in preventing follow-up suicide attempts among active-duty military service members with current suicidal ideation and /or a recent suicide attempt Context Persons with depression are more likely to die , but studies have not shown that treatment of depression reduces mortality . Contribution Investigators observed a 45 % reduction in the hazard of death among patients with major depression cared for in primary care practice s that were r and omly assigned to a depression care management program . Caution s The reduction in deaths occurred almost exclusively among patients who died of cancer . The mechanism for the effect is unclear and might be due to misclassification of cause of death or vital status . Implication A practice -level depression care management program seemed to reduce deaths due to cancer in older patients with major depression . The Editors Prospect i ve , observational studies from many setting s have shown that depression is independently associated with an increased risk for death ( 15 ) . However , few studies have evaluated whether an intervention focused on depression can modify this risk . Intervention studies that have reported on death in patients with depression have serious limitations : They lacked r and omization to the intervention condition ( 68 ) , focused only on patients after cardiovascular events ( 912 ) , or adjusted for treatment in examining the association of depression with death rather than study ing the effect of treatment ( 6 , 13 ) . In our study , we analyzed the relationship between a depression care management intervention and the risk for death among older primary care patients during a 5-year interval . We used data from the Prevention of Suicide in Primary Care Elderly : Collaborative Trial ( PROSPECT ) , which we supplemented with data from the National Death Index ( NDI ) . The PROSPECT was an effectiveness study design ed to assess the effect of care management on reducing risk factors for late-life suicide ( 14 ) . It integrated a r and omized trial with a population -based , public health model . The study intervention was implemented at the practice level and involved a depression care manager working with physicians to provide algorithm-based care ( 14 ) . The primary care practice was the unit of r and omization , and practice s that were not r and omly assigned to the intervention were expected to provide usual care . Patients were not assigned to receive specific treatments , so patients and their physicians in the intervention and usual care practice s decided whether patients would receive depression treatment . Our research question focused on whether this practice -level intervention influenced a patient-level outcome , namely survival . We hypothesized that older adults with depression in practice s r and omly assigned to a depression management intervention would experience an attenuated risk for death compared with those patients in usual care practice s. Guided by published criteria for performing and reporting subgroup analyses ( 15 , 16 ) , we were particularly interested in whether the effects of care management were specific to patients meeting st and ard criteria for major depression ( Diagnostic and Statistical Manual for Mental Disorders , fourth edition [ DSM-IV ] [ 17 ] ) . Methods Study Sample The PROSPECT was conducted in 20 primary care practice s located in greater New York , New York , and Philadelphia and Pittsburgh , Pennsylvania , from May 1999 to August 2001 , with individual patients followed for 2 years . After being paired by urban location , academic affiliation , size , and population type , practice s were r and omly assigned to the intervention or to usual care by coin flip ( cluster r and omization by practice ) . Patients were recruited from an age-stratified ( 60 to 74 years and 75 years ) , r and om sample of patients with upcoming appointments . Research associates confirmed study eligibility ( age 60 years , Mini-Mental State Examination score 18 [ 18 ] , and English-speaking ) of consenting patients and screened patients for depression by using the Centers for Epidemiologic Studies Depression scale ( 19 ) . Eligibility Criteria All patients scoring greater than 20 on the Centers for Epidemiologic Studies Depression scale were invited to enroll . Patients from a 5 % sample with lower scores were also invited for assessment of false-negative results on screening . To increase the sensitivity of screening , the PROSPECT investigators also recruited patients with scores less than 20 and positive responses to questions about previous depression episodes or treatment . Research associates met patients at the practice , obtained written consent , and administered a baseline interview ( 20 ) . The sampling strategy yielded a cohort that approximated a representative sample of attendees of the PROSPECT practice s , with oversampling of patients with depression symptoms . Depression Assessment We conducted a Structured Clinical Interview for DSM-IV Disorders Axis I ( SCID-I ) and allowed for the full range of DSM-IV diagnoses for depression disorders ( 17 , 21 ) . Our investigation focused on patients targeted by the intervention , that is , patients who met DSM-IV criteria for major depression ( 17 ) or who had clinical ly significant minor depression , defined by DSM-IV criteria for minor depression that we modified by requiring 4 depression symptoms , Hamilton Depression Rating Scale ( HDRS ) score of 10 or more , and duration of 4 weeks or more ( 22 ) . To minimize variation in applying criteria for depression , the Cornell Advanced Center for Intervention and Services Research , White Plains , New York , conducted regular teleconferences with research associates to review diagnostic practice s and conduct reliability assessment s. Ongoing monitoring indicated excellent reliability within and across sites for SCID-I assessment s ( intraclass correlation , 0.78 to 1.00 ) . Assessment of Patient Characteristics We obtained baseline information on age , sex , marital status , self-reported ethnicity , educational attainment , and smoking status ( according to tobacco use within the past 6 months ) . We included ethnicity in describing our sample because it has been associated with patterns of mental health service use ( 23 , 24 ) . Patients self-reported having a medical comorbid condition according to the Charlson Comorbidity Index ( 25 ) . The 24-item HDRS measured depression severity ( 26 ) , and the Scale for Suicidal Ideation indicated the presence of suicidal ideation ( 27 ) . Description of Usual Care and Intervention Groups Practice s r and omly assigned to usual care received educational sessions for primary care physicians and notification of the depression status of their patients . No specific recommendations were given to physicians about individual patients , except for psychiatric emergencies . The following were made available to practice s r and omly assigned to the intervention : educational sessions for primary care physicians , education for patients ' families , and a depression care manager who worked within the practice . The care manager implemented the intervention by review ing patients ' depression status , medical history , and medication use and subsequently worked with the primary care physician to recommend treatment according to st and ard guidelines . Care managers had psychiatric backup , including on-dem and consultation , weekly supervision by psychiatrist- investigators , and monthly interpersonal therapy cross-site supervision . They were introduced to patients by research associates immediately after the baseline interview . The 15 care managers included social workers , nurses , and psychologists who interacted with patients in person or by telephone at scheduled intervals and as necessary . Care managers focused efforts on depression treatment ( not on care for medical conditions or preventive services ) by monitoring symptoms , adverse effects of medications , and treatment adherence . All patients with depression received citalopram for first-line treatment . Citalopram therapy was initiated at 10 mg before bedtime on the first day , 20 mg/d for the next 6 days , and 30 mg/d subsequently . After 6 weeks , the target dosage was maintained if the patient exhibited a substantial improvement ( 50 % reduction in the HDRS score ) ( 26 ) and was increased if the patient exhibited a partial improvement ( 30 % to 50 % reduction in the HDRS score ) . Nonresponders , for whom guidelines called for switching to another antidepressant , were defined as patients who did not demonstrate either minimal improvement after 6 weeks of treatment at the target dosage or substantial improvement after the dose was increased to the maximum recommended dose after 12 weeks of treatment ( 28 ) . For patients who had not responded at 12 weeks , the health specialist followed guidelines for switching antidepressants ( 28 ) . Health specialists informed patients and their family members about the possible occurrence of specific side effects and to contact them if side effects occurred . When side effects occurred , health specialists provided support and , if warranted , asked primary care physicians to adjust doses or time of administration or to institute symptomatic treatment ( 28 ) . The PROSPECT treatment algorithm also took account whether patients were already being treated for depression . For example , for patients already receiving pharmacotherapy who remained symptomatic , the care manager optimized the current antidepressant before switching patients to another antidepressant ( 28 ) . Interpersonal therapy could be used alone or as an augmentation strategy , depending on whether the patient tolerated the antidepressant therapy and on the presence or absence of a partial response . Care managers from each site , all of whom had some experience in psychotherapy for depression , participated in interpersonal therapy training at the University of Pittsburgh Medical Center , Pittsburgh . In both study groups , physicians were informed by letter if patients reported any suicidal ideation and immediately when patients were identified as being at high risk for suicide according to prespecified guidelines . Other sources detail the PROSPECT treatment algorithm and implementation , including the role of IMPORTANCE Dialectical behavior therapy ( DBT ) is an empirically supported treatment for suicidal individuals . However , DBT consists of multiple components , including individual therapy , skills training , telephone coaching , and a therapist consultation team , and little is known about which components are needed to achieve positive outcomes . OBJECTIVE To evaluate the importance of the skills training component of DBT by comparing skills training plus case management ( DBT-S ) , DBT individual therapy plus activities group ( DBT-I ) , and st and ard DBT which includes skills training and individual therapy . DESIGN , SETTING , AND PARTICIPANTS We performed a single-blind r and omized clinical trial from April 24 , 2004 , through January 26 , 2010 , involving 1 year of treatment and 1 year of follow-up . Participants included 99 women ( mean age , 30.3 years ; 69 [ 71 % ] white ) with borderline personality disorder who had at least 2 suicide attempts and /or nonsuicidal self-injury ( NSSI ) acts in the last 5 years , an NSSI act or suicide attempt in the 8 weeks before screening , and a suicide attempt in the past year . We used an adaptive r and omization procedure to assign participants to each condition . Treatment was delivered from June 3 , 2004 , through September 29 , 2008 , in a university-affiliated clinic and community setting s by therapists or case managers . Outcomes were evaluated quarterly by blinded assessors . We hypothesized that st and ard DBT would outperform DBT-S and DBT-I. INTERVENTIONS The study compared st and ard DBT , DBT-S , and DBT-I. Treatment dose was controlled across conditions , and all treatment providers used the DBT suicide risk assessment and management protocol . MAIN OUTCOMES AND MEASURES Frequency and severity of suicide attempts and NSSI episodes . RESULTS All treatment conditions result ed in similar improvements in the frequency and severity of suicide attempts , suicide ideation , use of crisis services due to suicidality , and reasons for living . Compared with the DBT-I group , interventions that included skills training result ed in greater improvements in the frequency of NSSI acts ( F1,85 = 59.1 [ P < .001 ] for st and ard DBT and F1,85 = 56.3 [ P < .001 ] for DBT-S ) and depression ( t399 = 1.8 [ P = .03 ] for st and ard DBT and t399 = 2.9 [ P = .004 ] for DBT-S ) during the treatment year . In addition , anxiety significantly improved during the treatment year in st and ard DBT ( t94 = -3.5 [ P < .001 ] ) and DBT-S ( t94 = -2.6 [ P = .01 ] ) , but not in DBT-I. Compared with the DBT-I group , the st and ard DBT group had lower dropout rates from treatment ( 8 patients [ 24 % ] vs 16 patients [ 48 % ] [ P = .04 ] ) , and patients were less likely to use crisis services in follow-up ( ED visits , 1 [ 3 % ] vs 3 [ 13 % ] [ P = .02 ] ; psychiatric hospitalizations , 1 [ 3 % ] vs 3 [ 13 % ] [ P = .03 ] ) . CONCLUSIONS AND RELEVANCE A variety of DBT interventions with therapists trained in the DBT suicide risk assessment and management protocol are effective for reducing suicide attempts and NSSI episodes . Interventions that include DBT skills training are more effective than DBT without skills training , and st and ard DBT may be superior in some areas . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00183651 Evidence for the effectiveness of psychological therapies for people who self-harm is limited . Personal construct theory provides a model of self-harm and a framework for therapeutic intervention , which was evaluated in the present study . Sixty-four adults presenting to Accident and Emergency departments following self-harm were allocated to a personal construct psychotherapy or a ' normal clinical practice ' condition . They completed various measures at assessment points pre- and post-therapy . Repetition of self-harm was assessed over a 3-year period . Participants in the intervention condition showed significantly greater reduction in suicidal ideation , hopelessness and depression post-treatment than the control group ; and significantly more reconstruing at this point and 6-month follow-up . There was some evidence suggestive of a lower frequency of repetition of self-harm in the intervention than in the control group . It is concluded that brief personal construct psychotherapy may be effective for people who self-harm and merits further exploration Background : Despite the ubiquity of suicidality in behavioral health setting s , empirically supported interventions for suicidality are surprisingly rare . Given the importance of resolving suicidality and therapists ' anxieties about treating suicidal patients , there is a clear need for innovative services and clinical approaches . The purpose of the current study was an attempt to address some of these needs by examining the feasibility and use of a new intervention called the “ Collaborative Assessment and Management of Suicidality ” ( CAMS ) within a “ Next‐Day Appointment ” ( NDA ) outpatient treatment setting . Methods : As part of a larger feasibility study , n = 32 suicidal patients were r and omly assigned to CAMS care versus Enhanced Care as Usual ( E‐CAU ) in an outpatient crisis intervention setting attached to a safety net hospital . Intent to treat suicidal patients were seen and assessed before , during , and after treatment ( with follow‐up assessment s conducted at 2 , 4 , 6 , and 12 months ) . Results : The feasibility of using CAMS in the NDA setting was clear ; both groups appeared to initially benefit from their respective treatments in terms of decreased suicidal ideation and overall symptom distress . Although patients rated both treatments favorably , the CAMS group had significantly higher satisfaction and better treatment retention than E‐CAU . At 12 months post‐treatment , CAMS patients showed significantly better and sustained reductions in suicidal ideation , overall symptom distress , and increased hope in comparison to E‐CAU patients . Conclusions : CAMS was both feasible in this NDA setting and effective in treating suicidal ideation , distress , and hopelessness ( particularly at 12 months followup ) . Depression and Anxiety , 2011 . © 2011 Wiley Periodicals , BACKGROUND Self-harm is a common reason for Emergency Department ( ED ) attendance . We aim ed to develop a clinical tool to help identify patients at higher risk of repeat self-harm , or suicide , within 6 months of an ED self-harm presentation . METHOD The tool , the ReACT Self-Harm Rule , was derived using multicentre data from a prospect i ve cohort study . Binary recursive partitioning was applied to data from two centres , and data from a separate centre were used to test the tool . There were 29 571 self-harm presentations to five hospital EDs between January 2003 and June 2007 , involving 18 680 adults aged ⩾16 years . We estimated sensitivity , specificity and positive and negative predictive values to measure the performance of the tool . RESULTS A self-harm presentation was classified as higher risk if at least one of the following factors was present : recent self-harm ( in the past year ) , living alone or homelessness , cutting as a method of harm and treatment for a current psychiatric disorder . The rule performed with 95 % sensitivity [ 95 % confidence interval ( CI ) 94 - 95 ] and 21 % specificity ( 95 % CI 21 - 22 ) , and had a positive predictive value of 30 % ( 95 % CI 30 - 31 ) and a negative predictive value of 91 % ( 95 % CI 90 - 92 ) in the derivation centres ; it identified 83/92 of all subsequent suicides . CONCLUSIONS The ReACT Self-Harm Rule might be used as a screening tool to inform the process of assessing self-harm presentations to ED . The four risk factors could also be used as an adjunct to in-depth psychosocial assessment to help guide risk formulation . The use of multicentre data helped to maximize the generalizability of the tool , but we need to further verify its external validity in other localities Mental health related hospitalizations and suicide are both significant public health problems within the United States Department of Defense ( DoD ) . To date , few evidence -based suicide prevention programs have been developed for delivery to military personnel and family members admitted for psychiatric inpatient care due to suicidal self-directed violence . This paper describes the rationale and detailed methodology for a study called Safety Planning for Military ( SAFE MIL ) which involves a r and omized controlled trial ( RCT ) at the largest military treatment facility in the United States . The purpose of this study is to test the efficacy of a brief , readily accessible , and personalized treatment called the Safety Planning Intervention ( Stanley and Brown , 2012 ) . Primary outcomes , measured by blinded assessors at one and six months following psychiatric discharge , include suicide ideation , suicide-related coping , and attitudes toward help seeking . Additionally , given the study 's focus on a highly vulnerable patient population , a description of safety considerations for human subjects ' participation is provided . Based on this research team 's experience , the implementation of an infrastructure in support of RCT research within DoD setting s and the processing of regulatory approvals for a clinical trial with high risk suicidal patients are expected to take up to 18 - 24 months . Recommendations for expediting the advancement of clinical trials research within the DoD are provided in order to maximize cost efficacy and minimize the research to practice gap Several post-suicide prevention strategies such as sending postcards or making phone calls have been used to keep in contact with suicide attempters . The continuity of care has been beneficial to the prevention of post-acute suicidal behaviors . The aim of the study was to evaluate the technical feasibility and acceptability of text messaging outreach in post-acute suicide attempters . Eighteen post-suicidal patients were included in a prospect i ve , monocentric , open-label , 2 months pilot study . The text messages were sent from the intranet program that we specially developed for the study . Technical feasibility of this text message intervention was evaluated by the analysis of text message reports . Acceptability of such intervention was evaluated by a st and ardized phone interview . Our study showed that receiving text messages sent from an intranet program after a suicide attempt is technically possible . This post-crisis outreach program was accepted by the patients who found it to have a positive preventive impact . Text messaging outreach offers several advantages such as lower cost , and easier utilization compared to current post-acute care strategies . We suggest further r and omized controlled trials in a large sample of suicidal patients to assess the efficacy of this novel outreach tool for prevention of post-acute suicide OBJECTIVE The Prevention of Suicide in Primary Care Elderly : Collaborative Trial ( PROSPECT ) evaluated the impact of a care management intervention on suicidal ideation and depression in older primary care patients . This is the first report of outcomes over a 2-year period . METHOD Study participants were patients 60 years of age or older ( N=599 ) with major or minor depression selected after screening 9,072 r and omly identified patients of 20 primary care practice s r and omly assigned to provide either the PROSPECT intervention or usual care . The intervention consisted of services of 15 trained care managers , who offered algorithm-based recommendations to physicians and helped patients with treatment adherence over 24 months . RESULTS Compared with patients receiving usual care , those receiving the intervention had a higher likelihood of receiving antidepressants and /or psychotherapy ( 84.9%-89 % versus 49%-62 % ) and had a 2.2 times greater decline in suicidal ideation over 24 months . Treatment response occurred earlier on average in the intervention group and increased from months 18 to 24 , while no appreciable increase in treatment response occurred in the usual care group during the same period . Among patients with major depression , a greater number achieved remission in the intervention group than in the usual-care group at 4 months ( 26.6 % versus 15.2 % ) , 8 months ( 36 % versus 22.5 % ) , and 24 months ( 45.4 % versus 31.5 % ) . Patients with minor depression had favorable outcomes regardless of treatment assignment . CONCLUSIONS Sustained collaborative care maintains high utilization of depression treatment , reduces suicidal ideation , and improves the outcomes of major depression over 2 years CONTEXT Dialectical behavior therapy ( DBT ) is a treatment for suicidal behavior and borderline personality disorder with well-documented efficacy . OBJECTIVE To evaluate the hypothesis that unique aspects of DBT are more efficacious compared with treatment offered by non-behavioral psychotherapy experts . DESIGN One-year r and omized controlled trial , plus 1 year of posttreatment follow-up . SETTING University outpatient clinic and community practice . PARTICIPANTS One hundred one clinical ly referred women with recent suicidal and self-injurious behaviors meeting DSM-IV criteria , matched to condition on age , suicide attempt history , negative prognostic indication , and number of lifetime intentional self-injuries and psychiatric hospitalizations . INTERVENTION One year of DBT or 1 year of community treatment by experts ( developed to maximize internal validity by controlling for therapist sex , availability , expertise , allegiance , training and experience , consultation availability , and institutional prestige ) . MAIN OUTCOME MEASURES Trimester assessment s of suicidal behaviors , emergency services use , and general psychological functioning . Measures were selected based on previous outcome studies of DBT . Outcome variables were evaluated by blinded assessors . RESULTS Dialectical behavior therapy was associated with better outcomes in the intent-to-treat analysis than community treatment by experts in most target areas during the 2-year treatment and follow-up period . Subjects receiving DBT were half as likely to make a suicide attempt ( hazard ratio , 2.66 ; P = .005 ) , required less hospitalization for suicide ideation ( F(1,92 ) = 7.3 ; P = .004 ) , and had lower medical risk ( F(1,50 ) = 3.2 ; P = .04 ) across all suicide attempts and self-injurious acts combined . Subjects receiving DBT were less likely to drop out of treatment ( hazard ratio , 3.2 ; P < .001 ) and had fewer psychiatric hospitalizations ( F(1,92 ) = 6.0 ; P = .007 ) and psychiatric emergency department visits ( F(1,92 ) = 2.9 ; P = .04 ) . CONCLUSIONS Our findings replicate those of previous studies of DBT and suggest that the effectiveness of DBT can not reasonably be attributed to general factors associated with expert psychotherapy . Dialectical behavior therapy appears to be uniquely effective in reducing suicide attempts There are no evidence -based , brief interventions to reduce suicide risk in Veterans . Death by suicide is a major public health problem . This article describes a protocol , Suicide Assessment and Follow-up Engagement : Veteran Emergency Treatment [ SAFE VET ] , developed for testing the effectiveness of a brief intervention combining a Safety Planning Intervention with structured follow-up ( SPI-SFU ) to reduce near-term suicide risk and increase outpatient behavioral health treatment engagement among Veterans seeking treatment at Veteran Affairs Medical Center ( VAMC ) emergency departments ( EDs ) who are at risk for suicide . In addition to describing study procedures , outcome measures , primary and secondary hypotheses , and human subjects ' protection issues , the rationale for the selection of SPI-SFU as the intervention is detailed , as are safety considerations for the unique study setting and sample OBJECTIVE The authors conducted a 2-year prospect i ve naturalistic follow-up study to evaluate posttreatment clinical outcomes in out patients who were r and omly selected to receive 1 year of either dialectical behavior therapy or general psychiatric management for borderline personality disorder . METHOD Patients were assessed by blind raters 6 , 12 , 18 , and 24 months after treatment . The clinical effectiveness of treatment was assessed on measures of suicidal and nonsuicidal self-injurious behaviors , health care utilization , general symptom distress , depression , anger , quality of life , social adjustment , borderline psychopathology , and diagnostic status . The authors conducted between-group comparisons using generalized estimating equation , mixed-effects models , or chi-square statistics , depending on the distribution and nature of the data . RESULTS Both treatment groups showed similar and statistically significant improvements on the majority of outcomes 2 years after discharge . The original effects of treatment did not diminish for any outcome domain , including suicidal and nonsuicidal self-injurious behaviors . Further improvements were seen on measures of depression , interpersonal functioning , and anger . However , even though two-thirds of the participants achieved diagnostic remission and significant increases in quality of life , 53 % were neither employed nor in school , and 39 % were receiving psychiatric disability support after 36 months . CONCLUSIONS One year of either dialectical behavior therapy or general psychiatric management was associated with long-lasting positive effects across a broad range of outcomes . Despite the benefits of these specific treatments , one important finding that replicates previous research is that participants continued to exhibit high levels of functional impairment . The effectiveness of adjunctive rehabilitation strategies to improve general functioning deserves additional study IMPORTANCE Suicide is one of the top 10 leading causes of mortality among middle-aged women . Most work in the field emphasizes the psychiatric , psychological , or biological determinants of suicide . OBJECTIVE To estimate the association between social integration and suicide . DESIGN , SETTING , AND PARTICIPANTS We used data from the Nurses ' Health Study , an ongoing nationwide prospect i ve cohort study of nurses in the United States . Beginning in 1992 , a population -based sample of 72 607 nurses 46 to 71 years of age were surveyed about their social relationships . The vital status of study participants was ascertained through June 1 , 2010 . EXPOSURES Social integration was measured with a 7-item index that included marital status , social network size , frequency of contact with social ties , and participation in religious or other social groups . MAIN OUTCOMES AND MEASURES The primary outcome of interest was suicide , defined as deaths classified using the codes E950 to E959 from the International Classification of Diseases , Eighth Revision . RESULTS During more than 1.2 million person-years of follow-up ( 1992 - 2010 ) , there were 43 suicide events . The incidence of suicide decreased with increasing social integration . In a multivariable Cox proportional hazards regression model , the relative hazard of suicide was lowest among participants in the highest category of social integration ( adjusted hazard ratio , 0.23 [ 95 % CI , 0.09 - 0.58 ] ) and second-highest category of social integration ( adjusted hazard ratio , 0.26 [ 95 % CI , 0.09 - 0.74 ] ) . Increasing or consistently high levels of social integration were associated with a lower risk of suicide . These findings were robust to sensitivity analyses that accounted for poor mental health and serious physical illness . CONCLUSIONS AND RELEVANCE Women who were socially well integrated had a more than 3-fold lower risk for suicide over 18 years of follow-up BACKGROUND The tryptophan hydroxylase 1 ( TPH1 ) gene is reported to be associated with suicidal behavior . This has not been confirmed by prospect i ve studies of suicide and clinical or biological mediators of this genetic risk have not been identified . METHODS 343 subjects ( Caucasian , African-American , Hispanic ) presenting with a Major Depressive Episode were genotyped for polymorphisms A218C in intron 7 and A-6526 G in the promoter region of TPH1 , and monitored for suicide attempts for up to one year . Clinical correlates of suicidal behavior and CSF-HIAA , HVA and MHPG levels were explored as possible mediators of genetic risk . Analyses were adjusted for ethnicity . RESULTS The AA genotype on intron 7 and the AA genotype on the promoter ( both more prevalent in Caucasians ) predicted suicide attempts during the 1 year follow-up , and were associated with past attempts of high medical lethality , regardless of ethnicity . The intron 7 genotype was associated with fewer reported reasons for living , and lower impulsivity . Haplotype analysis indicated significant increase in risk of suicide attempts for subjects with four risk alleles . TPH1 genotype was not associated with CSF metabolite levels . LIMITATIONS The TPH1 gene is likely one of several genes associated with suicidal behavior . Power to detect differential genotype effects by ethnicity is low . CONCLUSIONS Polymorphisms of TPH1 may assist in identifying a subgroup of mood disorder patients that is at higher risk for suicidal behavior OBJECTIVES The Veterans Health Administration ( VHA ) evaluated the use of predictive modeling to identify patients at risk for suicide and to supplement ongoing care with risk-stratified interventions . METHODS Suicide data came from the National Death Index . Predictors were measures from VHA clinical records incorporating patient-months from October 1 , 2008 , to September 30 , 2011 , for all suicide decedents and 1 % of living patients , divided r and omly into development and validation sample s. We used data on all patients alive on September 30 , 2010 , to evaluate predictions of suicide risk over 1 year . RESULTS Modeling demonstrated that suicide rates were 82 and 60 times greater than the rate in the overall sample in the highest 0.01 % stratum for calculated risk for the development and validation sample s , respectively ; 39 and 30 times greater in the highest 0.10 % ; 14 and 12 times greater in the highest 1.00 % ; and 6.3 and 5.7 times greater in the highest 5.00 % . CONCLUSIONS Predictive modeling can identify high-risk patients who were not identified on clinical grounds . VHA is developing modeling to enhance clinical care and to guide the delivery of preventive interventions |
12,795 | 28,131,006 | In summary , the current analysis revealed that we can restrict the energy intake by consuming an LED preload .
Moreover , consuming an LED preload could favorably affect preload+meal energy intake | OBJECTIVE To conduct a systematic review and meta- analysis of the effects of preload/meal energy density on energy intake in a subsequent meal(s ) . | BACKGROUND Increases in both the portion size and energy density of food have both been shown to increase energy intake , but the combined effects of such increases have not been investigated . OBJECTIVE The objective was to determine the combined effects of energy density and portion size on energy intake in women . DESIGN This study used a within-subjects design . Once a week for 6 wk , 39 women were served breakfast , lunch , and dinner ad libitum . The main entrée at lunch was formulated in 2 versions that varied in energy density ( 5.23 or 7.32 kJ/g ) , each of which was served in 3 different portion sizes ( 500 , 700 , or 900 g ) . The 2 versions were matched for macronutrient composition and palatability . Breakfast and dinner were st and ard meals . RESULTS Increases in portion size and energy density led to independent and additive increases in energy intake ( P < 0.0001 ) . Subjects consumed 56 % more energy ( 925 kJ ) when served the largest portion of the higher energy-dense entrée than when served the smallest portion of the lower energy-dense entrée . Subjects did not compensate for the additional intake by eating less at the subsequent meal . Despite substantial differences in energy intake , no systematic differences in ratings of hunger and fullness across conditions were observed . CONCLUSIONS The energy density and the portion size of a food act independently to affect energy intake . The findings indicate that large portions of foods with a high energy density may facilitate the overconsumption of energy BACKGROUND An impaired ability to compensate for calories and increased eating in the absence of hunger ( EAH ) has been associated with increased energy intake and weight gain in unrelated children . OBJECTIVE The aims of this study were to compare caloric compensation [ the percentage compensation index ( % COMPX ) ] and EAH in weight-discordant siblings aged 5 - 12 y. DESIGN In a crossover , behavioral genetics design , 47 same-sex sibling pairs ( 53 % female , 55 % full siblings ) were served dinner once a week for 3 wk . Across conditions , siblings were served the same dinner , but 25 min before dinner , they either consumed in full or did not consume 1 of 2 preloads that varied in energy density ( ED ; 0.57 or 0.97 kcal/g ) . On the day when no preload was consumed , EAH was assessed after dinner and defined as the number of calories consumed from snacks . RESULTS Overweight/obese siblings undercompensated [ % COMPX : -48.8 ± 56.3 ( mean ± SEM ) ] and therefore overate after the high-ED preload , whereas normal-weight siblings showed accurate compensation ( % COMPX : 101.3 ± 51.9 ; P = 0.03 ) . Furthermore , overweight/obese siblings consumed 34 % more calories ( 93 kcal ) in the absence of hunger than did normal-weight siblings ( P = 0.01 ) . Within-pair resemblances for % COMPX and EAH were stronger for full siblings ( P < 0.049 ) than for half siblings ( P > 0.23 ) . CONCLUSIONS An impaired ability to regulate short-term energy intake , which includes incomplete adjustment for calorie differences in a preload and eating when satiated , may represent a behavioral phenotype for obesity in children . Future studies should test whether teaching children to focus on internal satiety cues may prevent at-risk children from overeating Background The purpose of this study was to determine whether a high-protein afternoon yogurt snack improves appetite control , satiety , and reduces subsequent food intake compared to other commonly-consumed , energy dense , high-fat snacks . Findings Twenty , healthy women ( age : 27 ± 2 y ; BMI : 23.4 ± 0.7 kg/m2 ) completed the r and omized crossover design study which included 3 , 8-h testing days comparing the following 160 kcal afternoon snacks : high-protein yogurt ( 14 g protein/25 g CHO/0 g fat ) ; high-fat crackers ( 0 g protein/19 g CHO/9 g fat ) ; and high-fat chocolate ( 2 g protein/19 g CHO/9 g fat ) . Participants were acclimated to each snack for 3 consecutive days . On day 4 , the participants consumed a st and ardized breakfast and lunch ; the respective snack was consumed 3-h post-lunch . Perceived hunger and fullness were assessed throughout the afternoon until dinner was voluntarily requested . An ad libitum dinner was then provided . The consumption of the yogurt snack led to greater reductions in afternoon hunger vs. chocolate ( p < 0.01 ) . No differences in afternoon fullness were detected . The yogurt snack also delayed eating initiation by approximately 30 min compared to the chocolate snack ( p < 0.01 ) and approximately 20 min vs. crackers ( p = 0.07 ) . The yogurt snack led to approximately 100 fewer kcals consumed at dinner vs. the crackers ( p = 0.08 ) and chocolate ( p < 0.05 ) . No other differences were detected . Conclusion These data suggest that , when compared to high-fat snacks , eating less energy dense , high-protein snacks like yogurt improves appetite control , satiety , and reduces subsequent food intake in healthy women This study tested the hypothesis that the amount ( weight or volume ) of food consumed affects the satiating potency of a food , independent of its energy content . Normal-weight young men ( n = 20 ) were tested in a within-subjects design . Subjects were served a milk-based drink or no drink ( control ) , followed 30 min later by a self-selected lunch and > 4 h later by a self-selected dinner . Milk drinks were equal in energy content ( 2088 kJ , or 499 kcal ) and had similar proportions of fat ( 30.3 % ) , carbohydrate ( 54.7 % ) , and protein ( 15 % ) across three volumes : 300 , 450 , and 600 mL. Ratings of palatability , sensory properties , and energy content of the drinks and of hunger completed before consumption of the preloads were not significantly different among conditions . The results showed that preload volume affected energy intake at lunch ( P < or = 0.009 ) such that energy intake was less after the 600-mL preload than after the 300-mL preload . This effect was still present when energy intake at dinner was included ( P < or = 0.022 ) . At lunch , including energy from the preload , subjects overate relative to the control condition ( 4323 + /- 322 kJ ) after the 300- ( 5263 + /- 321 kJ ) and 450-mL ( 5011 + /- 300 kJ ) preloads but not after the 600-mL ( 4703 + /- 353 kJ ) preload . Thus , the best adjustment for the energy in the preloads was with the largest , least energy-dense drink . Consistent with the effects on intake , the volume of the drinks affected ratings of hunger and fullness . These results indicate that the volume consumed is an important determinant of satiety after milk drinks under these conditions BACKGROUND The results of previous studies indicated that energy density , independent of fat content , influences energy intake . In most studies , however , both fat content and energy density were lower than in typical American diets . OBJECTIVE We examined the influence of energy density on intake when fat content was above , below , or similar to the amount of fat typically consumed and when energy density was closer to that of American diets . DESIGN Lean ( n = 19 ) and obese ( n = 17 ) women consumed all meals daily in our laboratory during 6 experimental sessions . The main entrées , consumed ad libitum , were formulated to vary in fat content ( 25 % , 35 % , and 45 % of energy ) and energy density ( 5.23 kJ/g , or low energy density , and 7.32 kJ/g , or high energy density ) but to have similar palatability . RESULTS Energy density influenced energy intake across all fat contents in both lean and obese women ( P < 0.0001 ) . Women consumed less energy in the low ( 7531 kJ ) than in the high ( 9414 kJ ) energy density condition . Despite this 20 % lower energy intake , there were only small differences in hunger ( 7 % ) and fullness ( 5 % ) . Women consumed a similar volume , but not weight , of food daily across conditions . Differences in intake by weight , but not volume , occurred because for some versions of manipulated foods , weight and volume were not directly proportional . CONCLUSIONS Energy density affected energy intake across different fat contents and at levels of energy density comparable with those in typical diets . Furthermore , our findings suggest that cues related to the amount of food consumed have a greater influence on short-term intake than does the amount of energy consumed BACKGROUND Studies have shown that energy intake increases when both the fat content and energy density of the entire diet increases . When the fat content and energy density vary independently of one another , however , energy density , but not fat content , influences intake . OBJECTIVE The present study examined whether energy intake in lean and obese women is affected when either the energy density or the fat content of a portion of the diet is manipulated and palatability is held constant . DESIGN In a within-subjects design , 17 lean and 17 obese women consumed meals in the laboratory for four , 4-d test periods . In 3 of these test periods the energy density ( 4.4 and 6.7 kJ/g ) or the fat content ( 16 % and 36 % of energy ) of compulsory entrees representing 50 % of each subject 's usual energy intake was manipulated . Additional self-selected foods were consumed ad libitum at meals and as snacks . RESULTS There were no systematic differences in palatability of the manipulated foods across conditions . Obese and lean participants responded similarly to the dietary manipulations . Intake of self-selected foods at meals was reduced significantly by 16 % for both lean and obese subjects in the low- compared with the high-energy-density condition . The fat content of the compulsory foods had no significant effect on energy intake . Ratings of hunger did not differ between diets . CONCLUSION These results indicate that when a portion of the diet was manipulated , the energy density , but not the fat content , of the foods affected total energy intake at meals in both lean and obese women BACKGROUND Little is known about the long-term effects of dietary energy density ( ED ) on weight gain . OBJECTIVE The objective was to assess the long-term relation between changes in dietary ED and age-related weight gain . DESIGN We conducted a prospect i ve study of 50 026 women ( x + /- SD age : 36.5 + /- 4.6 y ) in the Nurses ' Health Study II followed from 1991 to 1999 . Dietary ED and body weight were ascertained in 1991 , 1995 , and 1999 . Total dietary ED was calculated by dividing each subject 's daily energy intake ( kcal ) by the reported weight ( g ) of all foods consumed . RESULTS Dietary ED was positively correlated with saturated fat ( r = 0.16 ) , trans fat ( r = 0.15 ) , and the glycemic index ( r = 0.16 ) , but was inversely correlated with vegetable protein ( r = -0.30 ) , vegetables ( r = -0.27 ) , and fruit ( r = -0.17 ) . ED was not significantly correlated with total fat intake as a percentage of energy ( r = 0.08 ) . Women who increased their dietary ED during follow-up the most ( 5th quintile ) had a significantly greater multivariate-adjusted weight gain than did those who decreased their dietary ED ( 1st quintile ) ( 8-y time period : 6.42 kg compared with 4.57 kg ; P for trend < 0.001 ) . However , the amount of weight change over time varied considerably according to the ED values of individual foods and beverages . CONCLUSION A high dietary ED reflects a dietary pattern higher in saturated and trans fats and refined carbohydrates . Increases in dietary ED were associated with greater weight gain among middle-aged women during 8 y of follow-up . However , public health recommendations can not be made simply on the basis of ED values of individual foods and beverages Although several studies have assessed the influence of the glycemic index on body weight and blood pressure among adults , limited evidence exists for the pediatric age population . In the current study , we compared the effects of low glycemic index ( LGI ) diet to the healthy nutritional recommendation (HNR)-based diet on obesity and blood pressure among adolescent girls in pubertal ages . This 10-week parallel r and omized clinical trial comprised of 50 overweight or obese and sexually mature girls less than 18 years of age years , who were r and omly assigned to LGI or HNR-based diet . Macronutrient distribution was equivalently prescribed in both groups . Blood pressure , weight and waist circumference were measured at baseline and after intervention . Of the 50 participants , 41 subjects ( include 82 % ) completed the study . The GI of the diet in the LGI group was 42.67 ± 0.067 . A within-group analysis illustrated that in comparison to the baseline values , the body weight and body mass index ( not waist circumference and blood pressure ) decreased significantly after the intervention in both groups ( P = 0.0001 ) . The percent changes of the body weight status , waist circumference and blood pressure were compared between the two groups and the findings did not show any difference between the LGI diet consumers and those in the HNR group . In comparison to the HNR , LGI diet could not change the weight and blood pressure following a 10-week intervention . Further longitudinal studies with a long-term follow up should be conducted in this regard This study investigated the effect of high- and low-energy density preloads on gastrointestinal and metabolic factors , which act to regulate acute energy intake . Sixteen overweight and obese men ( BMI range : 27.2 - 36.5 kg/m2 ) each received 3 oral preloads in r and omised order : i ) high-energy-density , high-fat ( 1.5 kcal/g ) , ii ) low-energy density , high-fat ( 1.1 kcal/g ) , and iii ) low-energy-density , high-protein ( 1.1 kcal/g ) . Over 180 min , gastric emptying , plasma glucagon-like peptide-1 concentrations , and diet-induced thermogenesis were assessed , and subsequent energy intake was determined . Total energy intake did not differ between preloads ( high-energy-density , high-fat , 2059±72 kilocalories ( kcal ) ; low-energy-density , high-fat , 1876±91 kcal ; and low-energy-density , high protein , 1867±63 kcal ) . Gastric emptying was slower following the high-energy-density , high-fat preload ( 158±8 min ) compared with the low-energy-density , high-protein preload ( 130±9 min ) ( p=0.05 ) , but did not differ between the high-energy-density , high-fat and low-energy-density , high-fat ( 147±8 min ) preloads . Plasma glucagon- like peptide-1 did not differ substantially between preloads . Diet-induced thermogenesis was lower following high-energy-density , high-fat ( 10.4±0.7 % ) than low-energy-density , high-fat ( 14.9±1.2 % ) and low-energy density , high-protein ( 18.1±1.1 % ) preloads ( p<0.01 for both ) . We conclude that an increased energy density slows gastric emptying and reduces thermogenesis , but that a high fat content overrides the effect of energy density on gastric emptying . The counter-regulatory modulation of these gastric and metabolic factors may explain , at least in part , the lack of differences in subsequent energy intake in response to oral preloads with increasing energy density OBJECTIVE The purpose of the study was to examine the effect of energy density and food weight ( volume ) on subsequent intake . DESIGN Sixteen lean men were each studied four times during a 2-d protocol at the Rowett 's Human Nutrition Unit . On day 1 , subjects were fed a m and atory diet at 1.6 x resting metabolic rate ( RMR ) . On day 2 , during the m and atory morning period ( 08.30 - 12.30 ) subjects consumed a fixed breakfast ( 08.30 ) plus a snack ( 10.30 ) in one of four treatments [ with values in weight ( kg ) , ED ( kJ/100 g ) , Energy ( MJ ) ] : ( i ) zero intake , 0:0:0 ( ii ) low energy density ( LED ) , 0.615 : 400 : 2.46 ; ( iii ) high energy density ( HED ) , 0.615 : 800 : 4.92 ; ( iv ) 2 x LED , 1.225 : 400 : 4.91 . From 12.30 , throughout the remainder of the day , subjects had ad libitum access to 15 high-protein , 15 high-fat and 15 high-carbohydrate foods . Motivation to eat was tracked hourly using 100 mm line scales . RESULTS ANOVA showed subjects were hungrier after the zero and LED treatments in the m and atory period ( p<0.001 ) . Lunch time EI was 5.0 , 3.1 , 4.2 and 3.2 MJ on the zero , HED , LED and 2 x LED treatments , respectively ( p<0.001 ) . Total ad libitum EI was 11.7 , 9.6 , 10.3 and 9.5 MJ/d , respectively ( p=0.033 ) . Total ad libitum plus m and atory intakes amounted to 11.7 , 14.5 , 12.6 and 14.4 MJ/d , respectively ( p=0.001 ) . Corresponding food intakes were 2.18 , 2.39 , 2.51 and 3.06 kg/d , respectively ( p<0.001 ) . CONCLUSIONS The present study showed that subjects respond to both the amount of food eaten in the morning and to the energy density of those foods . However , compensation was only partial and short-term . Subjects only compensated EI by approximately 40 % and that compensation only occurred at the next meal Background and Objective . Few data are available linking fast food intake to diet quality in developing countries . This study was conducted to determine the association between fast food consumption and diet quality as well as obesity among Isfahani girls . Methods . This cross-sectional study was done among 140 Iranian adolescents selected by the use of systematic cluster r and om sampling . Dietary intakes were assessed using a vali date d food frequency question naire . Diet quality was defined based on energy density and nutrient adequacy ratios ( NARs ) . Results . Individuals in the highest quartile of fast food intake had significantly lower NARs for vitamin B1 ( P = 0.008 ) , phosphorus ( P = 0.0250 ) , selenium ( P < 0.001 ) and vitamin B2 ( P = 0.012 ) compared with those in the lowest quartile . Those in top quartile of fast food intake consumed more energy-dense diets than those in the bottom quartile ( P = 0.022 ) . High intakes of fast foods were significantly associated with overweight ( top quartile : 40 % versus bottom quartile : 0 % , P = 0.0001 ) and obesity ( 11.4 % versus 2.9 % , P = 0.0001 ) . Conclusion . Fast food consumption is associated with poor diet quality and high prevalence of overweight and obesity among Isfahani adolescents . Prospect i ve data are required to confirm these findings Background Previous studies show that dietary fibre-rich foods with low energy density have a stronger effect on satiety per calorie compared to more energy dense foods . Objective To investigate subjective appetite and voluntary energy intake ( 24 h ) after consumption of rye porridge breakfast and pasta lunch made from whole grain compared to iso-energetic reference meals made from refined cereals : wheat bread breakfast and wheat pasta lunch . Subjects In all , 22 healthy subjects , 14 females and 8 males , aged 21–64 years , BMI ranging from 18.7 to 27.5 kg/m2 , participated . Design A r and omised , crossover design was used . Appetite was rated by visual analogue scales ( VAS ) regularly from just before breakfast ( 08:00 ) until bedtime . An ad libitum dinner was served at 16:00 . After leaving the clinic and in the morning day 2 , subjects recorded foods consumed . Results Whole grain rye porridge gave a significantly prolonged satiety , lowered hunger and desire to eat ( p<0.05 in most point estimates ) up to 8 h after consumption compared to the refined wheat bread . The two pasta lunch meals did not vary in their effects on appetite ratings . There was no significant effect on ad libitum energy intake at 16:00 or self-reported energy and macronutrient intake in the evening and breakfast meal on day 2 . Conclusions Whole grain rye porridge at breakfast has prolonged satiating properties up to 8 h after consumption compared to refined wheat bread , but did not diminish subsequent food intake We previously reported that a eucaloric , low fat , liquid formula diet enriched in simple carbohydrate markedly increased the synthesis of fatty acids in lean volunteers . To examine the diet sensitivity of obese subjects , 7 obese and 12 lean volunteers were given two eucaloric low fat solid food diets enriched in simple sugars for 2 weeks each in a r and om-order , cross-over design ( 10 % fat , 75 % carbohydrate vs. 30 % fat , 55 % carbohydrate , ratio of sugar to starch 60:40 ) . The fatty acid compositions of both diets were matched to the composition of each subject 's adipose tissue and fatty acid synthesis measured by the method of linoleate dilution in plasma VLDL triglyceride . In all subjects , the maximum % de novo synthesized fatty acids in VLDL triglyceride 3;-9 h after the last meal was higher on the 10 % versus the 30 % fat diet . There was no significant difference between the dietary effects on lean ( 43+/-13 vs. 12+/-13 % ) and obese ( 37+/-15 vs. 6+/-6 % ) subjects , despite 2-fold elevated levels of insulin and reduced glucagon levels in the obese . Similar results were obtained for de novo palmitate synthesis in VLDL triglyceride measured by mass isotopomer distribution analysis after infusion of [(13)C]acetate . On the 10 % fat diet , plasma triglycerides ( fasting and 24 h ) were increased and correlated with fatty acid synthesis . Triglycerides were higher when fatty acid synthesis was constantly elevated rather than having diurnal variation . Thus , eucaloric , solid food diets which are very low in fat and high in simple sugars markedly stimulate fatty acid synthesis from carbohydrate , and plasma triglycerides increase in proportion to the amount of fatty acid synthesis . However , this dietary effect is not related to body mass index , insulin , or glucagon levels Expectations about a food ’s satiating capacity predict self-selected portion size , food intake and food choice . However , two individuals might have a similar expectation , but one might be extremely confident while the other might be guessing . It is unclear whether confidence about an expectation affects adjustments in energy intake at a subsequent meal . In a r and omized cross-over design , 24 subjects participated in three separate breakfast sessions , and were served a low-energy-dense preload ( 53 kcal/100 g ) , a high-energy-dense preload ( 94 kcal/100 g ) , or no preload . Subjects received ambiguous information about the preload ’s satiating capacity and rated how confident they were about their expected satiation before consuming the preload in its entirety . They were served an ad libitum test meal 30 min later . Confidence ratings were negatively associated with energy compensation after consuming the high-energy-dense preload ( r = −0.61 ; p = 0.001 ) . The same relationship was evident after consuming the low-energy-dense preload , but only after controlling for dietary restraint , hunger prior to , and liking of the test meal ( p = 0.03 ) . Our results suggest that confidence modifies short-term controls of food intake by affecting energy compensation . These results merit consideration because imprecise caloric compensation has been identified as a potential risk factor for a positive energy balance and weight gain In two experiments , 2 - 5-year-old children 's responsiveness to caloric density cues was examined . In a preloading protocol , consumption of fixed volumes of drinks ( 205 ml in Experiment 1 ; 150 ml in Experiment 2 ) , sweetened with sucrose , aspartame , aspartame plus low glucose maltodextrin , or a water control , was followed by ad lib consumption from among a variety of foods . Caloric drinks had about 90 kcal in Experiment 1 , 65 kcal in Experiment 2 . The delay interval between the preload and the ad lib consumption was 0 , 30 or 60 minutes . In Experiment 1 , 24 4- and 5-year-old children participated in only one delay interval , while in Experiment 2 , all 20 2- and 3-year-old children were seen in all conditions . Results revealed evidence of caloric compensation , but no evidence of preload x time delay interaction . In both experiments , aspartame also produced a significant suppression of intake relative to water , primarily due to the pattern at 30 min following the preload . Across conditions , the suppression following aspartame was usually significantly less than that produced by the caloric sweet drinks , providing evidence for postingestive effects . In Experiment 1 , suppression of intake was related to the children 's preferences for the foods , not to macronutrient content ; consumption of nonpreferred foods was most suppressed . Consumption of sweetened drinks as long as 1 hour prior to eating suppressed food intake , and this common feeding practice may also reduce dietary variety Previous research suggests that enhancing the volume of a food preload without altering energy content can result in reduced appetite , although the limited evidence means that the conditions under which this effect will occur are not yet clear . In the present study , we used a Universal Eating Monitor ( UEM ) to record test meal intake constantly , in parallel with appetite ratings , following soup-based preloads that varied both in volume ( 150 vs. 450 ml ) and energy density ( 1.4 vs. 4.2 kJ/ml ) . Healthy young men ( n=20 ) received four different preload conditions ( repeated measures ) followed by unlimited hot pasta test meals ( interval 30 min ) . They completed appetite ratings during and after each laboratory session , and food diaries for the afternoon and evening following each session . Subjective appetite after the preloads was reduced by the high-volume preloads relative to low-volume preloads , with no difference between the two at each volume level . This indicates an effect of volume , but no effect of energy . Test meal intake in the high-volume , high-energy-density condition was reduced relative to the other conditions , which did not differ from one another . This indicates an effect of total energy , but no effect of volume . The dissociation between these different measures of appetite might be explained in terms of largely cognitive influences on subjective appetite between preload and test meal , contrasted with stronger physiological influences on actual intake during the test meal . With regard to previous studies , it is argued that food volume is more influential under circumstances where gastric volume is closer to its normal limits Observational studies suggest that increased fruit and vegetable consumption can contribute to weight maintenance and facilitate weight loss when substituted for other energy dense foods . Therefore , the purpose of the present study was to assess the effect of berries on acute appetite and energy intake . Twelve unrestrained pre-menopausal women ( age 21 ± 2 y ; BMI 26.6 ± 2.6 kg m(-2 ) ; body fat 23 ± 3 % ) completed a familiarisation trial and two r and omised experimental trials . Subjects arrived in the evening ( ~5pm ) and consumed an isoenergetic snack ( 65 kcal ) of mixed berries ( BERRY ) or confectionary sweets ( CONF ) . Sixty min later , subjects consumed a homogenous pasta test meal until voluntary satiation , and energy intake was quantified . Subjective appetite ( hunger , fullness , desire to eat and prospect i ve food consumption ) was assessed throughout trials , and for 120 min after the test meal . Energy intake was less ( P<0.001 ) after consumption of the BERRY snack ( 691 ± 146 kcal ) than after the CONF snack ( 824 ± 172 kcal ) ; whilst water consumption was similar ( P=0.925 ) . There were no trial ( P>0.095 ) or interaction ( P>0.351 ) effects for any subjective appetite ratings . Time taken to eat the BERRY snack ( 4.05 ± 1.12 min ) was greater ( P<0.001 ) than the CONF snack ( 0.93 ± 0.33 min ) . This study demonstrates that substituting an afternoon confectionary snack with mixed berries decreased subsequent energy intake at dinner , but did not affect subjective appetite . This dietary strategy could represent a simple method for reducing daily energy intake and aiding weight management Volume has been shown to be an important direct control of food intake , since larger volumes of food consumed prior to a meal can inhibit subsequent intake . Variety of food is known to stimulate food intake . The present study was design ed to examine the relative effects of manipulating the volume of a soup preload in the context of providing either a single or a variety of s and wich fillings . Thirty participants ( 15 females ; 15 males ) attended the laboratory on 4 occasions to receive a low ( f=240 ml , 3.6 kJ/g ; m=300 ml , 3.6 kJ/g ) or high ( f=480 ml , 1.8 kJ/g ; m=600 ml , 1.8 kJ/g ) volume tomato soup preload 30 min before a s and wich lunch with either single or a variety of fillings . Overall , subjects reported significant differences in hunger and fullness as a function of volume manipulations but the satiety quotient ( SQ : change in ratings divided by weight of soup ) calculated just before lunch indicated a smaller SQ for high than for the low volume soup . Therefore , although subjective ratings were influenced by volume this was not sufficient to affect intake at lunch . Variety ( 2344+/-200 kJ ) increased food intake at lunch compared to the single filling condition ( 2062+/-171 kJ ) , an enhancement by variety of 14 % . In conclusion , lowering energy density and increasing volume by adding water failed to reduce intake at lunch . Clearly volume effects on intake rely both on amount consumed and energy density . As predicted , variety stimulated food intake and this occurred across volume conditions The relative effects of energy density and palatability on energy intake , and whether there are familial influences on these effects , are not known . We investigated this issue in 7 pairs of healthy , male monozygotic twins ( mean+/-SD age 26.3+/-8.6 years , BMI 23.7+/-3.2 kg/m(2 ) ) in a clinical study involving covert ad libitum feeding of high-fat ( HF , approximately 40 % ) and low-fat ( LF , approximately 20 % ) diets in two 9-day phases . Diets were matched for average energy density , protein , fiber , and initial reported taste pleasantness , but these factors varied among the individual foods . Relationships between energy density , palatability , and energy intake were explored using regression and path analyses . Food energy density was positively associated with average taste pleasantness ( r=0.46 , P=0.03 ) independent of fat content , while energy intake from individual foods was positively associated with both energy density ( r=0.56 , P=0.007 ) and taste pleasantness ( r=0.73 , P<0.0001 ) . In path analysis , both energy density and taste pleasantness directly influenced energy intake , and energy density also indirectly influenced energy intake by influencing taste pleasantness . In addition , there were significant within-twin pair similarities for the energy density-taste pleasantness and energy density-energy intake relationships ( P<0.03 ) with the result that some twin pairs but not others identified foods high in energy density as more pleasant tasting and consumed relatively more energy from them compared to foods low in energy density . These results suggest that there are familial influences on the extent to which high energy density foods are preferred and contribute to total energy intake Dietary energy density ( DED ) might be associated with the quality of the consumed diet . Therefore , this study was conducted to report the relationship between dietary energy density and diet quality index in Iranian youths . In this cross-sectional study we enrolled 410 female young adults in Isfahan-Iran who were selected according to the stratified r and om sampling method from among students of Isfahan University of Medical Sciences . A vali date d semi quantitative food frequency question naire was used to assess the usual dietary intakes . Dietary energy density was calculated as each individual 's reported daily energy intake ( kcal/d ) into total weight of foods ( excluding beverages ) consumed ( g/d ) . Diet quality was assessed by healthy eating index ( HEI ) , nutrient adequacy ratio ( NAR ) , and mean adequacy ratio ( MAR ) . For calculating the NAR the ratio of daily individual intakes to st and ard recommended amounts for the subject 's sex and age category was used . MAR was calculated as the sum of NARs divided by the number of nutrients ( n=10 ) . Mean dietary energy density was 1.5±0.2 kcal/g and mean HEI was 57.5±16.0 . Those in the highest quartile of DED had the lowest value for HEI , MAR , and NAR of zinc , calcium , vitamin C , vitamin B12 and vitamin B2 ( p<0.05 ) . Those in the highest quartile of DED had the highest prevalence of calcium , zinc , vitamin B2 , vitamin B12 , and vitamin C deficiency ( p<0.05 ) . Dietary energy density was inversely associated with the diet quality indices among Iranian young women adults This experiment examined whether food volume and energy content affected satiety in lean and obese women , when visual and oral cues were bypassed by infusing food intragastrically . The effects of volume and energy content were examined separately by using liquid foods that differed in energy density ( kcal/g ) . On 5 separate days , 25 lean and 29 obese women consumed all of their meals in the laboratory . A nasogastric tube was inserted 30 min before lunch on 4 days ; on three of these occasions , a liquid preload was infused for 15 min and , on the fourth occasion ( control ) , the preload was diverted covertly . On the remaining day , no tube was inserted . The three preloads varied two-fold in volume and energy content : 200 ml/200 kcal , 400 ml/200 kcal and 400 ml/400 kcal . The results showed that increasing the volume of infused food , but not the energy content , affected satiety in both lean and obese women . There was a mean decrease in energy intake at lunch of 77 kcal ( 13 % ) after the 400-ml preload compared with the iso-energetic 200-ml preload ( P=.013 ) . Increasing the energy content of infused food , but not the volume , did not affect satiety . Thus , when sensory cues were bypassed , the volume of liquid food infused intragastrically affected subsequent energy intake in both lean and obese women . These results suggest that gastric and postgastric mechanisms are involved in the effects of high-volume , low-energy-dense foods on satiety The effects of food unit size ( FU ) and energy density ( ED ) on food consumption were explored in 20 adults using a within subjects 2 x 2 design study . The four food treatment combinations were provided in the laboratory in r and om order on four non-consecutive days . The foods differed in FU ( small food unit ( SFU ) or customary food unit ( CFU ) ) and energy density , by manipulating fat content ( low ( LED ) or high ( HED ) ) . Appetitive responses and total grams and kilocalories consumed were monitored . Hunger , fullness , desire to eat and prospect i ve consumption ratings were not significantly different between treatments . Gram weight of food consumed was constant across all treatments . Energy intake of HED foods was greater than LED foods independent of food unit size for breakfast ( F(1,17 ) = 11.77 , p < 0.001 ) , lunch ( F(1,17 ) = 4.70 , p < 0.05 ) and the 24 h period ( F(1,17 ) = 8.99 , p < 0.001 ) but only tended to be increased at dinner . In summary , appetitive sensations were not markedly altered by food unit size or energy density . The daily gram weight of food consumed and appetitive ratings were relatively consistent across treatments result ing in higher energy intake with HED foods Cumulative food intake curves have been obtained by monitoring eating from a plate , placed on a scale built into a table , and connected to a digital computer . They describe and integrate parameters of consumption of an ad lib single course meal , i.e. meal size , meal duration , eating rate , change in eating rate , bite size and bite frequency . It is concluded that they are an adequate tool for analyzing dietary and clinical interventions on meal size , because the cumulative food intake curve parameters : are stable and consistent within subjects ; show a clear relationship with the subject characteristics dietary restraint and obesity ; show a clear relationship with the physiological parameters satiation , diet-induced thermogenesis and body-temperature near the liver , and with the cognitive parameter : estimating forthcoming ingestion ; are sensitive to instructions , clinical and dietary interventions ( preloads , palatability , energy density , macronutrient composition ) , and to a state of negative energy balance . Because of possible compensatory post-pr and ial effects , it is suggested that assessment of meal size should be part of a 24 h appetite profile and food intake observation Preloads ( 250 ml ) of 2 % or 10 % fructose containing 1 % soluble fibre and 1 % insoluble fibre or 10 % fructose with 3 % soluble fibre and 1 % insoluble were administered 60 min before lunch to 24 healthy women , who were slightly overweight and considerably weight concerned . The fibre consisted of guar gum , partly hydrolysed for the soluble form . The placebo consisted of a solution of sweeteners ( cyclamate and saccharin ) . After the experiment with three preload-types and a placebo , a r and om subset of 15 subjects returned for an experiment with one preload-type and a placebo , given 30 or 60 min before lunch . Food intake during the subsequent lunch was only significantly different from after the placebo in this subset of 15 subjects after the 10 % fructose/3 % soluble and 1 % insoluble fibre preload after intervals of 30 or 60 min . However , energy intake of preload and meal was significantly higher than energy intake of placebo and meal . At the 30-min delay , eating rate was significantly lower after the preload than after the placebo ; also , hunger ratings were lower after intake of a preload and meal than after intake of the placebo+meal , from immediately after lunch until 5 hours later . Energy intake over 24 h was not affected by administration of fructose/fibre or placebo 30 or 60 minutes before lunch in the 24 women This study evaluated the effect of adding fruit or oats to the diet of free-living women on energy consumption and body weight . Fruit and oat cookies had the same amount of fiber and total calories ( approximately 200 kcal ) , but differed in energy density . We analyzed data from a clinical trial conducted in a primary care unit in Rio de Janeiro , Brazil . Forty-nine women , ages ranging from 30 to 50 years , with body mass index ( BMI ) > 25 kg/m2 , were r and omly chosen to add three apples ( 0.63 kcal/g energy density ) or three pears ( 0.64 kcal/g energy density ) or three oat cookies ( 3.7 kcal/g energy density ) to their usual diet for 10 weeks . Fiber composition was similar ( approximately 6 g ) . Statistical analysis of the repeated measures of dietary composition and body weight were analyzed using mixed model procedures . Results showed a significant decrease in the energy density during the follow-up ( -1.23 kcal/g , p<0.04 , and -1.29 kcal/g , p<0.05 ) for apples and pears , respectively , compared to the oat group . The energy intake also decreased significantly ( -25.05 and -19.66 kcal/day ) for the apple and pear group , respectively , but showed a small increase ( + 0.93 ) for the oat group . Apples and pears were also associated ( p<0.001 ) with weight reduction ( -0.93 kg for the apple and -0.84 for the pear group ) , whereas weight was unchanged ( + 0.21 ; p=0.35 ) in the oat group . Results suggest that energy densities of fruits , independent of their fiber amount can reduce energy consumption and body weight over time OBJECTIVE We tested the effect on meal intake of varying the energy density and portion size of a compulsory first-course salad . DESIGN The study used a r and omized crossover design . SUBJECTS/ SETTING Forty-two women from the State College , PA , university community ate lunch in the laboratory once per week for 7 weeks . INTERVENTION Lunch comprised one of six first-course salads , or no salad in the control condition , followed by a main course of pasta . Subjects were required to consume the entire salad , but ate as much pasta as they wanted . The salads varied in energy density ( 0.33 , 0.67 , or 1.33 kcal/g ) and portion size ( 150 or 300 g ) . The energy density of the salad was reduced by changing the amount and type of dressing and cheese . MAIN OUTCOME MEASURES Energy intake and ratings of hunger , satiety , and food characteristics were measured . STATISTICAL ANALYSES PERFORMED Outcomes were analyzed using a linear mixed model with repeated measures . RESULTS Compared with having no first course , consuming the low-energy-dense salads reduced meal energy intake ( by 7 % for the small portion and 12 % for the large ) , and consuming the high-energy-dense salads increased intake ( by 8 % for the small portion and 17 % for the large ) . When two salads with the same number of calories were compared , meal intake was decreased when the large portion of the lower-energy-dense salad was consumed . CONCLUSIONS Eating a low-energy-dense first course enhances satiety and reduces meal energy intake . Consuming a large portion of a low-energy-dense food at the start of a meal may be an effective strategy for weight management BACKGROUND & AIMS Texture modified diets may be enriched to optimise the opportunity for individuals to meet their required energy intakes ; however there is insufficient evidence supporting this strategy . Thus we sought to investigate the effect of texture and energy density on food ( g ) and energy intakes ( kcal ) , appetite ( satiation and satiety ) , and palatability in healthy adults . METHODS A single blind within-subjects r and omised crossover design , where 33 healthy adults consumed a test meal with either its texture and /or energy density altered , until satiation was reached whilst rating their appetite parameters . Subsequent intakes were recorded in a food diary to determine the effect of the treatments on satiety and identify any evidence of energy compensation . RESULTS Test meal energy intakes ( kcal ) were significantly higher with energy enrichment of both meals ( st and ard texture ; 315 kcal and texture modified ; 303 kcal ( p = 0.001 ) ) and remained higher over the day for both ( 260 kcal/d and , 225 kcal/d respectively ( p < 0.05 ) ) . Area under the curve ( AUC ) did not differ between meals for hunger , fullness , or desire to eat however palatability was significantly reduced with texture modification . CONCLUSIONS Enriching meals ( st and ard texture and texture modified ) is an effective method to increase short term energy intakes in healthy adults over a 24 h period and may have application to optimise energy intakes in a clinical setting |
12,796 | 24,731,074 | Results indicate that deficits in withholding are insufficiently sensitive or specific to be used individually as a diagnostic measure or biomarker in most disorders | Response inhibition , defined as the ability to withhold a response , is considered to be a core deficit in various mental illnesses .
Measures of response inhibition have been used to define functional deficits , as markers of genetic risk , in neuroimaging studies , and for diagnostic purpose s in these disorders .
However , the magnitude of the deficit across psychopathologies has not been systematic ally assessed . | CONTEXT Attention-deficit/hyperactivity disorder ( ADHD ) is a highly prevalent and impairing psychiatric disorder that affects both children and adults . There are Food and Drug Administration-approved stimulant and nonstimulant medications for treating ADHD ; however , little is known about the mechanisms by which these different treatments exert their therapeutic effects . OBJECTIVE To contrast changes in brain activation related to symptomatic improvement with use of the stimulant methylpheni date hydrochloride vs the nonstimulant atomoxetine hydrochloride . DESIGN Functional magnetic resonance imaging before and after 6 to 8 weeks of treatment with methylpheni date ( n = 18 ) or atomoxetine ( n = 18 ) using a parallel-groups design . SETTING Specialized ADHD clinical research program at Mount Sinai School of Medicine , New York , New York . PARTICIPANTS Thirty-six youth with ADHD ( mean [ SD ] age , 11.2 [ 2.7 ] years ; 27 boys ) recruited from r and omized clinical trials . MAIN OUTCOME MEASURES Changes in brain activation during a go/no-go test of response inhibition and investigator-completed ratings on the ADHD Rating Scale-IV-Parent Version . RESULTS Treatment with methylpheni date vs atomoxetine was associated with comparable improvements in both response inhibition on the go/no-go test and mean ( SD ) improvements in ratings of ADHD symptoms ( 55 % [ 30 % ] vs 57 % [ 25 % ] ) . Improvement in ADHD symptoms was associated with common reductions in bilateral motor cortex activation for both treatments . Symptomatic improvement was also differentially related to gains in task-related activation for atomoxetine and reductions in activation for methylpheni date in the right inferior frontal gyrus , left anterior cingulate/supplementary motor area , and bilateral posterior cingulate cortex . These findings were not attributable to baseline differences in activation . CONCLUSIONS Treatment with methylpheni date and atomoxetine produces symptomatic improvement via both common and divergent neurophysiologic actions in frontoparietal regions that have been implicated in the pathophysiology of ADHD . These results represent a first step in delineating the neurobiological basis of differential response to stimulant and nonstimulant medications for ADHD This study examined effects of reward and response costs on the ability of 19 attention-deficit hyperactivity disorder ( ADHD ) and 17 control children to inhibit responding . Children were tested under 4 reinforcement conditions on a go/no-go learning task developed by J. P. Newman , C. S. Widom , and S. Nathan ( 1985 ) . Two conditions involved both reward and response costs . 1 response costs only , and 1 reward only . ADHD children made more commission errors than controls across the 4 conditions . Analyses of learning curves indicated that group differences became larger on later trials . Thus , impaired inhibition was more generalized in ADHD children than in the psychopaths and extraverts studied by Newman and colleagues , and it became most evident when the children were required to improve learning across trials A disturbed functioning of the prefrontal cortex , the anterior cingulate cortex , and an accordingly reduced P300 presumably underlies executive function deficits of children with attention deficit hyperactivity disorder ( ADHD ) . Using a combined classification and Go/NoGo task paradigm , the present study investigated whether medication with methylpheni date ( MPH ) modulates the P300 as measured by a high-density electroencephalogram ( EEG ) and facilitates response inhibition in children with ADHD . Further , effects of MPH were compared with effects of self-regulation by if-then plans ( Gollwitzer in Am Psychol 54 : 493–503 , 1999 ) . MPH as well as if-then plans modulated the P300 and improved inhibition of an unwanted response on a Go/NoGo task to the same level observed in children without ADHD . Importantly , self-regulation strategies might be a valuable alternative to medication with MPH in children with ADHD The go-no go test requires a subject to emit a simple motor response to one cue while inhibiting the response in the presence of another cue . This test has been effective in demonstrating impulsivity ( elevated commission error rate ) in children with attention deficit disorder ( ADD ) . In this study , we examined the effects on go-no go test performance of two doses of methylpheni date ( 0.15 mg/kg and 0.3 mg/kg ) administered in double-blind placebo-controlled fashion to children with ADD . Our results indicate that even modest doses of methylpheni date improve the go-no go performance of these children by decreasing their tendency to make impulsive commission errors . Thus the test is sensitive to the effects of methylpheni date and can be used to monitor a response to therapy . ( J Child Neurol 1991 ; 6(Suppl):S126-S129 ) |
12,797 | 16,926,357 | Effective strategies that addressed impaired mobility included the use of support surfaces , mattress overlays on operating tables , and specialized foam and specialized sheepskin overlays .
While repositioning is a mainstay in most pressure ulcer prevention protocol s , there is insufficient evidence to recommend specific turning regimens for patients with impaired mobility .
In patients with nutritional impairments , dietary supplements may be beneficial .
The incremental benefit of specific topical agents over simple moisturizers for patients with impaired skin health is unclear .
Given current evidence , using support surfaces , repositioning the patient , optimizing nutritional status , and moisturizing sacral skin are appropriate strategies to prevent pressure ulcers . | CONTEXT Pressure ulcers are common in a variety of patient setting s and are associated with adverse health outcomes and high treatment costs .
OBJECTIVE To systematic ally review the evidence examining interventions to prevent pressure ulcers . | BACKGROUND AND OBJECTIVE To develop a checklist of items measuring the quality of reports of r and omized clinical trials ( RCTs ) assessing nonpharmacological treatments ( NPTs ) . STUDY DESIGN AND SETTING The Delphi consensus method was used to select and reduce the number of items in the checklist . A total of 154 individuals were invited to participate : epidemiologists and statisticians involved in the field of methodology of RCTs ( n = 55 ) , members of the Cochrane Collaboration ( n = 41 ) , and clinicians involved in planning NPT clinical trials ( n = 58 ) . Participants ranked on a 10-point Likert scale whether an item should be included in the checklist . RESULTS Fifty-five experts ( 36 % ) participated in the survey . They were experienced in systematic review s ( 68 % were involved in the Cochrane Collaboration ) and in planning RCTs ( 76 % ) . Three rounds of the Delphi method were conducted to achieve consensus . The final checklist contains 10 items and 5 subitems , with items related to the st and ardization of the intervention , care provider influence , and additional measures to minimize the potential bias from lack of blinding of participants , care providers , and outcome assessors . CONCLUSIONS This tool can be used to critically appraise the medical literature , design NPT studies , and assess the quality of trial reports included in systematic review A comparison of pressure reducing properties of alternating air , static air , and water mattress overlays was conducted with 57 patients in a surgical intensive care unit . Sacral and heel pressures in both recumbent and semi-Fowler 's positions were tested for each surface using a repeated measures design . Mean pressures for the alternating air mattress were significantly higher than pressures with other surfaces , regardless of position or site . There were significant main effects for position and site , with higher pressures in the semi-Fowler 's position and at the sacral site . A significant interaction between surface , site , and position was found . Pressure sores developed in eight patients , but the incidence was not significantly different across groups . A pressure measuring device constructed from available clinical material s proved to be both sensitive and reliable . The findings suggest alternating air overlays should be avoided , and that positioning and periodic position change to reduce sacral pressures for patients requiring prolonged upper body elevation is important OBJECTIVE To estimate the effectiveness of a new high-performance Australian medical sheepskin ( meeting Australian St and ard 4480.1 - 1998 ) in preventing pressure ulcers in a general hospital population at low to moderate risk of these ulcers . DESIGN Open-label r and omised controlled clinical trial . SETTING A large metropolitan teaching hospital in Melbourne , Victoria , in 2000 . PARTICIPANTS 441 patients aged over 18 years admitted between 12 June and 30 November 2000 , with expected length of stay over 2 days and assessed as at low to moderate risk of developing pressure ulcers . INTERVENTION Patients were r and omly allocated to receive a sheepskin mattress overlay for the duration of their hospital stay ( 218 patients ) or usual treatment , as determined by ward staff ( referent group , 223 patients ) . MAIN OUTCOME MEASURES Incidence rate and cumulative incidence of pressure ulcers , assessed daily throughout hospital stay . RESULTS 58 patients developed pressure ulcers ( sheepskin group , 21 ; referent group , 37 ) . Cumulative incidence risk was 9.6 % in the sheepskin group ( 95 % CI , 6.1%-14.3 % ) versus 16.6 % in the referent group ( 95 % CI , 12.0%-22.1 % ) . Patients in the sheepskin group developed new pressure ulcers at a rate less than half that of referent patients ( rate ratio , 0.42 ; 95 % CI , 0.26 - 0.67 ) . CONCLUSIONS The Australian Medical Sheepskin is effective in reducing the incidence of pressure ulcers in general hospital in patients at low to moderate risk of these ulcers Pressure sores are a frequent problem , especially in elderly patients . Nutritional status may influence the incidence , progression and severity of pressure sores , data , however , are contradictory ( 1 ) . The purpose of this study was to determine the effect of supplemental feeding on the nutritional status and the development and severity of pressure sores . The effect of supplemental feeding overnight ( tube + ) on patients with a fracture of the hip and a high pressure-sore risk score , was studied in a r and omized clinical trial . The control group ( tube - ) had no supplemental feeding . After informed consent , 140 patients were r and omized , and 129 of these took part in the trial ( 62 tube + , and 67 tube - ) . Protein and energy intake , haemoglobin , serum albumin , total serum protein and pressure-sore grade were measured at admission and after 1 and 2 weeks . Of the 62 patients r and omized for tube feeding ( tube + ) , only 25 tolerated their tube for more than 1 week and 16 for 2 weeks . Nevertheless , energy and protein intake was significantly higher in the tube + group ( P < 0.001 ) . This , however , did not significantly influence total serum protein , serum albumin and development and severity of pressure sores after 1 and 2 weeks . Comparison of the actually tube fed group ( n=25 at 1 week , n = 16 at 2 weeks ) and the control group showed a 2 - 3 times higher protein and energy intake ( P < 0.0001 ) , and a significantly higher total serum protein and serum albumin after 1 and 2 weeks in the actually tube fed group ( all P < 0.001 ) . Pressure-sore development and severity were not significantly influenced in the actually tube fed group . We conclude that we were not able to show a significant decrease in development and severity of pressure sores , because the nasogastric tube for supplemental feeding was not well tolerated in this patient group . Nevertheless , tube feeding overnight does result in a significant higher protein and energy intake , and has a significant effect on nutritional status in the actually tube-fed group . Other means of supplemental feeding will have to be used in order to answer the question of whether supplemental feeding can decrease development and severity of pressure sores 59 elderly patients ( mean age 82 ) with femoral neck fractures were r and omised into two groups . 27 patients received daily an oral nutrition supplement ( 250 ml , 20 g protein , 254 kcal ) for a mean of 32 days ; 32 patients acted as controls . On admission most patients had nutritional deficiencies . Despite being offered adequate quantities , nutritional requirements were not met during the hospital stay . Clinical outcome was significantly better in the supplemented group ( 56 % favourable course vs 13 % in controls ) during the stay in the convalescent hospital . The rates of complications and deaths were also significantly lower in supplemented patients ( 44 % vs 87 % ) . 6 months after the fracture the rates of complications and mortality were significantly lower in supplemented patients ( 40 % vs 74 % ) . The median duration of hospital stay was significantly shorter in the supplemented group ( 24 vs 40 days ) . Thus the clinical outcome of elderly patients with femoral neck fracture can be improved by once daily dietary oral supplementation Six hundred patients at risk for pressure sores were r and omized in either a control group or one of two experimental groups placed on alternating-pressure air-mattresses and water-mattresses . The groups remained comparable throughout the 10-day study period . Twenty-one patients from the control group developed decubitus ulcers , compared with 7 in each of the other groups . Patient and ward personnel opinions on the acceptability of the three types of mattresses were registered OBJECTIVES To examine skin health outcomes of an exercise and incontinence intervention . DESIGN R and omized controlled trial with blinded assessment s of outcomes at three points over 8 months . SETTING Four nursing homes ( NHs ) . PARTICIPANTS One hundred ninety incontinent NH residents . INTERVENTION In the intervention group , research staff provided exercise and incontinence care every 2 hours from 8:00 a.m. to 4:30 p.m. ( total of four daily care episodes ) 5 days a week for 32 weeks . The control group received usual care from NH staff . MEASUREMENTS Perineal skin wetness and skin health outcomes ( primarily blanchable erythema and pressure ulcers ) as measured by direct assessment s by research staff , urinary and fecal incontinence frequency , and percentage of behavioral observations with resident engaged in st and ing or walking . RESULTS Intervention subjects were significantly better in urinary and fecal incontinence , physical activity , and skin wetness outcome measures than the control group . However , despite these improvements , differences in skin health measures were limited to the back distal perineal area , which included the sacral and trochanter regions . There was no difference between groups in the incidence rate of pressure ulcers as measured by research staff , even though those residents who improved the most on fecal incontinence showed improvement in pressure ulcers in one area . CONCLUSION A multifaceted intervention improved four risk factors related to skin health but did not translate into significant improvements in most measures of skin health . Even if they had adequate staffing re sources , NHs might not be able to improve skin health quality indicators significantly if they attempt to implement preventive interventions on all residents who are judged at risk because of their incontinence status Pressure sores are a problem , especially in elderly patients . Our study was design ed to determine the effectiveness in pressure-sore prevention of a new interface-pressure decreasing mattress . In a prospect i ve r and omised controlled clinical trial we tested the Comfortex DeCube mattress ( Comfortex , Winona , USA ) against our st and ard hospital mattress in 44 patients with femoral-neck fracture and concomitant high pressure-sore risk score . In addition both groups were treated according to the Dutch consensus protocol for the prevention of pressure sores . On admission and 1 and 2 weeks after admission , pressure sores were grade d. The two groups were similar in patient characteristics and pressure-sore risk factors . At 1 week , 25 % of the patients nursed on the DeCube mattress and 64 % of the patients nursed on the st and ard mattress had clinical ly relevant pressure sores ( grade 2 or more ) . At 2 weeks the figures were 24 % and 68 % , respectively . The maximum score over the several body regions of the pressure-sore grading , measured on a 5-point sale , was significantly different in favour of the DeCube mattress at 1 week ( p = 0.0043 ) and 2 weeks ( p = 0.0067 ) postoperatively . We show that the occurrence of pressure sores and their severity can be significantly reduced when patients at risk are nursed on an interface-pressure decreasing mattress OBJECTIVE To evaluate the impact of in-hospital pressure ulcer development on mortality among older , high-risk , hospitalized patients up to 1 year post-hospital discharge , after adjusting for baseline patient characteristics , disease severity , hospital complications , and discharge activity level . DESIGN A prospect i ve , inception , cohort study . SETTING An urban , tertiary , acute care , university teaching hospital . PATIENTS A total of 286 patients aged 55 or older , expected to be confined to bed or chair for at least 5 days , who were admitted to the hospital without a Stage 2 or greater pressure ulcer . MEASUREMENTS The primary outcome measurement was time to death from admission to 1-year post-hospital discharge . Baseline information included demographic , medical , functional , and nutritional variables known to be associated with increased mortality . Measures of global disease severity and co-morbidity included the admitting physician 's estimate of illness severity and life expectancy , the acute physiology score of APACHE II , the Co-morbidity Damage Index , and the Medicus Nursing Classification Score . Baseline infections , incident infections , and noninfectious hospital complications were determined . Functional activity level was determined at hospital discharge . Post-discharge vital status was determined by telephone interviews at 3,6,9 , and 12 months after discharge and confirmed by death certificate review . MAIN RESULTS Development of an in-hospital pressure ulcer was associated with greater risk of death at 1 year ( 59.5 % vs 38.2 % , P = .02 ) . However , pressure ulcer development did not remain independently associated with decreased survival after adjusting for other predictors of mortality . Predictors of mortality at hospital admission by multivariate Cox regression analysis included weight loss in the 6 months before admission ( RR 2.4 , CI 1.6 , 3.6 ) , physician estimate of life expectancy ( RR 2.1 , CI 1.7 , 2.6 ) , and the Co-morbidity Damage Index ( RR 1.1 , CI 1.0 , 1.2 ) . Multivariate predictors of 1-year mortality at discharge included physician estimate of life expectancy ( RR 2.2 , CI 1.8,2.6 ) , weight loss in the 6 months before admission ( RR 2.2 , CI 1.5,3.2 ) , remaining confined to bed or chair ( RR 1.9 , CI 1.2,3.1 ) , and the total number of hospital complications ( RR 1.3 , CI 1.2,1.5 ) . CONCLUSIONS Pressure ulcers that develop during acute hospitalization are not associated with reduced 1-year survival among high risk older persons after adjusting for nutritional and functional status , global measures of disease severity and co-morbidity , and noninfectious hospital complications This study had three aims : to investigate if visco-elastic foam mattresses are more effective than st and ard hospital mattresses in reducing the incidence of pressure ulcers in patients with hip fractures ; to compare pressure ulcer grade and location and documented nursing prevention and treatment interventions in patients using the two types of mattresses ; to identify possible predictors of pressure ulcer development . Using a prospect i ve r and omised controlled trial design 101 patients ( mean age : 84 years ) were r and omly allocated either a visco-elastic foam mattress or a st and ard mattress . There was no significant difference in the incidence of pressure ulcers between the two groups , but patients on st and ard mattresses tended to develop more severe pressure ulcers . Furthermore , according to the documentation , patients with grade I pressure ulcers who were allocated a st and ard mattress received more preventive interventions , which may have reduced the differences in outcomes between the two groups . The research ers concluded that the results support the use of the test mattress . Significant predictors of pressure ulcer development were long waiting times for surgery and low haemoglobin levels at hospital admission The Pegasus Airwave mattress has been used for many years in the Eastbourne NHS Trust and has proven its efficiency in the prevention of pressure sores . Pegasus has now produced a new , improved , model : the Cairwave Therapy System . This article looks at criteria that may be used to determine whether the new model is suitable for patient care . The evaluation took the form of a r and omized controlled study in which 12 mattresses were r and omly allocated to patients --six Airwave mattresses and six Cairwave Therapy Systems -- over a 4-month period . The results of the evaluation showed that patients found the mattress comfortable . An encompassing cover reduced the risk of cross-infection , rehabilitation was supported by the firm edges of the bed and patient movement was easier due to the soft cover . During the trial all patients remained free from pressure sores This experimental study was design ed to identify the etiology of pressure ulcers in a surgical sample and to evaluate a special OR mattress overlay in preventing pressure ulcer development . Surgical patients ( N = 413 ) were r and omized to receive " usual perioperative care " or the new mattress overlay . Over six postoperative days , 89 patients ( 21.5 % ) developed pressure ulcers , primarily stage I. Only 2 % developed stage II or IV ulcers . Patients with ulcers were statistically older , had diabetes , were smaller in body mass , had lower Braden Scale scores on admission , and used the new mattress overlay ( P < .02 ) . Pressure ulcers that presented as " burns " or ecchymosis did not deteriorate to stage III or IV ulcers during the study . The mattress overlay was not effective in preventing pressure ulcer development Abstract Objective To assess the cost effectiveness of alternating pressure mattresses compared with alternating pressure overlays for the prevention of pressure ulcers in patients admitted to hospital . Design Cost effectiveness analysis carried out alongside the pressure relieving support surfaces ( PRESSURE ) trial ; a multicentre UK based pragmatic r and omised controlled trial . Setting 11 hospitals in six UK NHS trusts . Participants Intention to treat population comprising 1971 participants . Main outcome measures Kaplan Meier estimates of restricted mean time to development of pressure ulcers and total costs for treatment in hospital . Results Alternating pressure mattresses were associated with lower overall costs ( £ 283.6 per patient on average , 95 % confidence interval - £ 377.59 to £ 976.79 ) mainly due to reduced length of stay in hospital , and greater benefits ( a delay in time to ulceration of 10.64 days on average , - 24.40 to 3.09 ) . The differences in health benefits and total costs for hospital stay between alternating pressure mattresses and alternating pressure overlays were not statistically significant ; however , a cost effectiveness acceptability curve indicated that on average alternating pressure mattresses compared with alternating pressure overlays were associated with an 80 % probability of being cost saving . Conclusion Alternating pressure mattresses for the prevention of pressure ulcers are more likely to be cost effective and are more acceptable to patients than alternating pressure overlays Polyurethane foam cushions in a slab form or a customized contoured form are commonly used in wheelchairs to prevent the development of decubitus ulcers ( DU ) in elderly chronically ill persons . Sixty-two consenting subjects , 60 years or older , were r and omly assigned to sit on one of the two types of cushions for 3 or more hours daily for 5 months . A total of 72 DU developed in the 52 subjects who completed the study . These were mostly in the areas of ischial tuberosities , buttocks , and thighs ; were of persistent erythema level in severity ; and took an average of 6 to 8 weeks to heal . No statistically significant differences were found in the incidence , location , severity , or healing time of the sores that developed in the subjects who used the slab ( N = 26 ) and those who used the contoured ( N = 26 ) cushions . But , more severe sores did develop among the slab cushion group in the area of ischial tuberosities . It appears that foam customization for elderly persons could be justified only if DU have been a particular problem in this region . Incontinence as a contributory factor to DU formation should receive careful attention with respect to prevention . The trials described are being continued , using a larger number of subjects OBJECTIVE To identify specific demographic , medical , functional status , and nutritional characteristics that predict the development of stage 2 or greater pressure ulcers among patients whose activity is limited to bed or chair . DESIGN Prospect i ve inception cohort study . SETTING Tertiary care , urban , university teaching hospital . PATIENTS A total of 286 patients fulfilling the following criteria : admitted to the hospital within the previous 3 days , age 55 years or more , expected to be confined to bed or chair for at least 5 days or had a hip fracture , and without a stage 2 or greater pressure ulcer . MAIN OUTCOME MEASURE Time to in-hospital development of a stage 2 or greater pressure ulcer . RESULTS Total cumulative incidence of pressure ulcers was 12.9 % ( n = 37 ) after a median time of 9 days from admission to final skin examination . Age of 75 years or more , dry skin , nonblanchable erythema ( a stage 1 pressure ulcer ) , previous pressure ulcer history , immobility , fecal incontinence , depleted triceps skinfold , lymphopenia ( lymphocyte count < 1.50 x 10(9)/L ) , and decreased body weight ( < 58 kg ) were significantly associated with pressure ulcer development by univariate Kaplan-Meier survival analyses ( P < .05 by log-rank test ) . Risk ratios ( and 95 % confidence intervals ) for predictors ( P < or = .05 ) of pressure ulcer development after multivariable Cox regression analysis included the following : nonblanchable erythema , 7.52 ( 1.00 to 59.12 ) ; lymphopenia , 4.86 ( 1.70 to 13.89 ) ; immobility , 2.36 ( 1.14 to 4.85 ) ; dry skin , 2.31 ( 1.02 to 5.21 ) ; and decreased body weight , 2.18 ( 1.05 to 4.52 ) . The 3-week cumulative incidence of pressure ulcers with none , one , two , or three or more of these characteristics was 0 % , 11.4 % , 39.6 % , and 67.9 % , respectively ( P < .001 by log-rank test ) . CONCLUSIONS These results suggest that nonblanchable erythema , lymphopenia , immobility , dry skin , and decreased body weight are independent and significant risk factors for pressure ulcers in hospitalized patients whose activity is limited to bed or chair Thirty-two chronic neurologic patients between 19 and 60 years of age were r and omly assigned , for a period of three months , to either an alternating air mattress or a silicore mattress to test the preventive qualities of special mattresses in the occurrence of decubitus ulcers . The two groups were comparable on the variables of age , weight , diagnoses , history of disease process , history of being wheelchair bound , history of previous pressures , and mean scores on Norton 's scale of risk , which is based on the subject 's physical condition , mental alertness , ambulation , mobility and incontinence . No significant differences were observed in the preventive qualities of the two types of special mattresses in terms of the incidence , location , severity , or healing duration of the subjects ' decubitus ulcers . Improved studies of common special mattresses are suggested Patients with chronic neurological diseases who were at high risk of decubitus ulcers were r and omly assigned to alternating air on silicore mattress overlays for a period of 3 months . Of 148 subjects who completed the trial , more than 50 % in each group developed one or more ulcers . No statistically significant differences between groups were found in the incidence , severity , healing duration or the location of the ulcers ; with the exception of a significant difference ( p less than 0.001 ) in the categorical location of the trochanters OBJECTIVE To identify the independent effect of pressure ulcers on excess length of stay and control for all observable factors that may also contribute to excess length of stay . Hospitalized patients who develop a pressure ulcer during their hospital stay are at a greater risk for increased length of stay as compared with patients who do not . DESIGN Cross-sectional , observational study . SETTING Tertiary-care referral and teaching hospital in Australia . PATIENTS Two thous and hospitalized patients 18 years and older who had a minimum stay in the hospital of 1 night and admission to selected clinical units . METHODS Two thous and participants were r and omly selected from 4,500 patients enrolled in a prospect i ve survey conducted between October 2002 and January 2003 . Quantile median robust regression was used to assess risk factors for excess length of hospital stay . RESULTS Having a pressure ulcer result ed in a median excess length of stay of 4.31 days . Twenty other variables were statistically significant at the 5 % level in the final model . CONCLUSIONS Pressure ulcers make a significant independent contribution to excess length of hospitalization beyond what might be expected based on admission diagnosis . However , our estimates were substantially lower than those currently used to make predictions of the economic costs of pressure ulcers ; existing estimates may overstate the true economic cost BACKGROUND Little is known about physicians ' knowledge , attitudes , and practice preferences with regard to pressure ulcers . Clinical practice guidelines on pressure ulcers from the Agency for Health Care Policy and Research ( AHCPR ) have been publicized , but their impact on family physicians has not been assessed . METHODS A question naire was sent to a r and om sample of active members of the Minnesota Academy of Family Physicians . Information was collected on respondent demographics practice characteristics , training , and awareness of AHCPR guidelines . Knowledge about pressure ulcers was assessed with a 43-item test . Attitudes about pressure ulcer treatment were measured on a Likert-type scale . Four case scenarios were used to explore preferences . RESULTS Of 292 potential respondents after exclusion , 155 ( 53.1 % ) returned question naires . Regression analysis revealed that taking care of more elderly patients , completing a residency , being board-certified , and being aware of the AHCPR guidelines were independently associated with higher knowledge scores . Virtually all ( 99 % ) the respondents felt that it was the family physician 's role to provide pressure ulcer care , whereas 70 % felt that they had not been adequately trained to do so . There was a wide variety of practice preferences . Approximately 70 % of physicians were not aware of the AHCPR guidelines . CONCLUSIONS Most family physicians fell ill-prepared to manage pressure ulcers , suggesting a need to increase educational efforts for this important problem . Knowledge about pressure ulcers could possibly be enhanced by more clinical exposure to older patients , rigorous residency training , and review of AHCPR guidelines The purpose of this study was to determine the efficacy and safety of a multi-cell pulsating dynamic mattress system in comparison with conventional management for the prevention of pressure ulcers in the operative and postoperative period in patients having cardiovascular surgery . The study was a single center , prospect i ve , r and omized , controlled trial . Patients who were having cardiovascular surgery for a duration of at least 4 hours were r and omly assigned , prior to surgery , to dynamic mattress system or conventional management -- both of which were initiated in the operating room and continued for up to 7 days postoperatively . Patients were assessed daily using a st and ardized scoring system . The results of the study showed that 198 patients in the dynamic pressure system ( n = 98 ) or conventional management group ( n = 100 ) were similar at baseline . A strong trend of decreased pressure ulcers existed in the dynamic pressure system group ( n = 2 ) compared to the conventional management group ( n = 7 ) . The study concluded that a multi-cell pulsating dynamic mattress system is safe and mitigates risks for and decreases incidence of pressure ulcers in patients who undergo cardiovascular surgery OBJECTIVE To determine the incidence of pressure ulcers in varied population s , and whether demographic characteristics ( age , gender , race ) and primary diagnosis are factors in pressure ulcer development when the level of risk for developing ulcers is considered . To determine if there is a difference in the type of preventive services prescribed for persons who do or do not develop pressure ulcers when risk is controlled and whether differences can be related to demographic characteristics . DESIGN Cohort study . SETTING Two skilled nursing homes , two university operated tertiary care hospitals , and two Veteran 's Administration Medical Centers ( VAMCs ) in Omaha , NE , Durham , NC , and Chicago , IL . PATIENTS A total of 843 r and omly selected patients more than 19 years of age who did not have pressure ulcers on admission to their place of care . Subjects were 63 % male , 79 % white , and had a mean age of 63 ( + /- 16 ) years . MEASURES A head-to-toe skin assessment for pressure ulcers recording site and stage of ulcers , scores for the Braden Scale for Predicting Pressure Sore Risk , demographic characteristics ( age , sex , race ) , and primary diagnosis and preventive interventions ( turning or repositioning orders and pressure reduction surface ) were documented on the patient record . Observations were made every 48 to 72 hours for a minimum of 1 to a maximum of 4 weeks . MAIN OUTCOME MEASURES Presence/absence and stage of pressure ulcers . MAIN RESULTS One hundred eight of 843 ( 12.8 % ) subjects developed pressure ulcers . The incidence was 8.5 % , 7.4 % , and 23.9 % in tertiary care , VAMCs , and nursing homes , respectively . Logistic regression demonstrated that lower Braden Scale scores , older age and white race predicted pressure ulcers ; gender was not predictive . Primary diagnoses were not significant predictors of pressure ulcer risk when the Braden Scale score was entered into the regression . Prescription of turning was predicted by Braden Scale scores and by white race , whereas prescription of pressure reduction was predicted by Braden Scale scores , white race , and female sex . CONCLUSIONS Risk assessment , rather than diagnoses or demographic characteristics , is recommended as the basis for prescriptive decisions . Risk assessment should cue health care providers to make more judicious use of turning and support surfaces to prevent pressure ulcers . Persons who are at risk for pressure ulcers should have turning and pressure reduction surfaces consistently prescribed and implemented . The costs and goals of preventive prescription for those not at risk for pressure ulcers should be considered AIMS AND OBJECTIVES In this experimental study , a 4-cm thermoactive viscoelastic foam overlay and a heating source on the operating room table was compared with the st and ard operating room table with a heating source for the effect on the postoperative pressure ulcer incidence in cardiac surgery patients . BACKGROUND Pressure ulcer incidence in the cardiac surgery population is reported to be up to 29.5 % . The prolonged compressive forces from lying on the operating room table are one source of pressure ulcer development in this population . Pressure-reducing devices on the operating room (OR)-table should reduce the patients ' interface pressure and thus the hazard of skin breakdown . METHODS A r and omized controlled trial was performed to test the effect of a 4-cm thermoactive viscoelastic foam overlay with a water-filled warming mattress on the OR-table ( test OR-table ) compared with the st and ard OR-table ( a water-filled warming mattress , no pressure-reducing device ) on the postoperative pressure ulcer incidence in cardiac surgery patients . INSTRUMENTS The pressure ulcer classification system of the European Pressure Ulcer Advisory Panel ( EPUAP ) was used for pressure ulcer grading . RESULTS The results show that patients lying on the 4-cm thermoactive viscoelastic foam overlay suffer slightly more pressure ulcer ( 17.6 % ) than patients on the st and ard OR-table without the foam overlay ( 11.1 % ) . Because of the clinical relevance of the results , the r and omized controlled trial was terminated after 175 patients at the interim analysis although the power calculation stated 350 patients . CONCLUSIONS The combination of a 4-cm viscoelastic foam overlay and a warming source can not be recommended for pressure ulcer prevention on the operating room table . RELEVANCE TO CLINICAL PRACTICE Foam overlays are used to prevent pressure ulcers in patients . It is necessary to use such devices according to patient safety and use of re sources OBJECTIVE To determine , in critically ill patients at risk , both the clinical utility and cost-effectiveness of using an air suspension bed in the prevention of pressure ulcers . DESIGN R and omized , parallel group , controlled clinical trial with accompanying cost-effectiveness analysis . SETTING 30-bed multidisciplinary intensive care unit . PATIENTS 100 consecutive patients at risk for the development of pressure ulcers r and omly assigned to receive treatment on either an air suspension bed or a st and ard intensive care unit bed . Patients considered at risk were those at least 17 years of age with an Acute Physiology and Chronic Health Evaluation II ( APACHE II ) score greater than 15 who had an expected intensive care unit stay of at least 3 days . MAIN OUTCOME MEASURES The development of pressure ulcers by site and severity and the costs associated with each of the two programs . RESULTS The air suspension bed was associated with fewer patients developing single , multiple , or severe pressure ulcers . In patients at risk , the use of an air suspension bed in the prevention of pressure ulcers was a cost-effective therapy . CONCLUSIONS Despite intense nursing care , pressure ulcers are more prevalent in the critically ill patient population than in the general hospital population . Air suspension therapy provides a clinical ly effective means of preventing pressure ulcers in these patients . In patients at risk , air suspension therapy was a cost-effective means of managing pressure ulcers compared with the st and ard hospital bed This r and omised controlled trial of two dry-flotation pressure-reducing surfaces evaluates pressure sore incidence , patient comfort and the appropriate use of equipment in 100 orthopaedic patients . The trial involved five full Roho mattresses , five Sofflex mattresses and 10 Roho Quatro cushions to be used to complement the beds . Given the low rate of pressure sore incidence in this high-risk group it is not possible to determine whether there is any difference in effectiveness between the two mattresses . Both appear to provide similar levels of comfort , with the majority of patients finding them either comfortable or very comfortable . The initial setting of the equipment was , however , unsatisfactory Abstract Objective To compare whether differences exist between alternating pressure overlays and alternating pressure mattresses in the development of new pressure ulcers , healing of existing pressure ulcers , and patient acceptability . Design Pragmatic , open , multicentre , r and omised controlled trial . Setting 11 hospitals in six NHS trusts . Participants 1972 people admitted to hospital as acute or elective patients . Interventions Participants were r and omised to an alternating pressure mattress ( n = 982 ) or an alternating pressure overlay ( n = 990 ) . Main outcome measures The proportion of participants developing a new pressure ulcer of grade 2 or worse ; time to development of new pressure ulcers ; proportions of participants developing a new ulcer within 30 days ; healing of existing pressure ulcers ; and patient acceptability . Results Intention to treat analysis found no difference in the proportions of participants developing a new pressure ulcer of grade 2 or worse ( 10.7 % overlay patients , 10.3 % mattress patients ; difference 0.4 % , 95 % confidence interval - 2.3 % to 3.1 % , P = 0.75 ) . More overlay patients requested change owing to dissatisfaction ( 23.3 % ) than mattress patients ( 18.9 % , P = 0.02 ) . Conclusion No difference was found between alternating pressure mattresses and alternating pressure overlays in the proportion of people who develop a pressure ulcer . Trial registration IS RCT N This paper summarizes the results of the trial of the Beaufort Bead Bed system design ed to reduce the incidence and severity of pressure sores . Elderly orthopaedic admissions were allocated alternately to the Beaufort system and to the usual trolley , table and bed surfaces , and followed from admission to hospital until separation . The incidence of pressure sores was 15.6 % in the 32 ' trial ' patients , which was significantly less than the 48.8 % in the 43 ' control ' patients , as was the mean maximum diameter of the pressure sores incurred : 6.4 mm for the ' trials ' as against 29.5 mm for the ' controls ' . In particular the trial group were free from pressure lesions to the heel , which affected 32.6 % of the control group . The groups were well matched on a variety of criteria on admission , and we conclude that the Beaufort system successfully reduces the incidence and severity of pressure sores for elderly orthopaedic patients . The system -- renamed recently the ' Neumark-Macclesfield Support System'--is now in regular and satisfactory use BACKGROUND & AIMS Malnutrition is a risk factor for development of pressure ulcers ( PU ) . Nutritional supplementation may thus reduce the incidence of PU . We investigated the effect of nutritional supplementation on incidence of PU in hip-fracture patients at risk of developing PU . METHODS Hip-fracture patients ( n=103 ) were included in this double-blind , r and omised , placebo-controlled trial . They received 400 ml daily of a supplement enriched with protein , arginine , zinc and antioxidants ( n=51 ) or a non-caloric , water-based placebo supplement ( n=52 ) . Presence and stage of PU were assessed daily for 28 days or until discharge ( median : 10 days during supplementation ) . RESULTS Incidence of PU was not different between supplement ( 55 % ) and placebo ( 59 % ) , but incidence of PU stage II showed a 9 % difference ( difference : 0.091 ; 95 % CI : 0.07 - 0.25 ) between supplement ( 18 % ) and placebo ( 28 % ) . Of patients developing PU 57 % developed it by the second day . Time of onset ( days ) showed a trend ( P=0.090 ) towards later onset of PU with supplement ( 3.6+/-0.9 ) than placebo ( 1.6+/-0.9 ) . CONCLUSIONS Hip-fracture patients develop PU at an early stage . Nutritional supplementation may not prevent PU at this stage , but contributes possibly to a delayed onset and progression of PU . Nutritional supplementation may be more effective if initiated earlier The methodology of r and omized control trials ( RCTs ) of the primary treatment of early breast cancer has been review ed using a quantitative method . Sixty-three RCTs comparing various treatment modalities tested on over 34,000 patients and reported in 119 papers were evaluated according to a st and ardized scoring system . A percentage score was developed to assess the internal validity of a study ( referring to the quality of its design and execution ) and its external validity ( referring to presentation of information required to determine its generalizability ) . An overall score was also calculated as the combination of the two . The mean overall score for the 63 RCTs was 50 % ( 95 % confidence interval [ CI ] = 46 % to 54 % ) with small and nonstatistically significant differences between types of trial . The most common method ologic deficiencies encountered in these studies were related to the r and omization process ( only 27 of the 63 RCTs adopted a truly blinded procedure ) , the h and ling of withdrawals ( only 26 RCTs included all patients in the analyses ) , the description of the follow-up schedule ( only 12 RCTs reported adequately ) , the report of side effects ( adequate information given in 33 RCTs ) , and the description of the patient population ( satisfactory in 29 RCTs ) . Telephone calls to the principal investigators improved the quality scores by seven points on a scale of 100 , indicating that some of the deficiencies lay in reporting rather than performance . There was evidence that quality has improved over time and that the increasing tendency of involving a biostatistician in the research team was positively associated with the improvement of the internal validity but not with the external The effectiveness of hospital pillows versus a commercial heel elevation device ( the Foot Waffle [ EHOB incorporated ] ) in preventing heel pressure ulcers was examined using an experimental balanced factorial design with repeated measures on 52 patients ( ages 27 to 90 ) in r and omized groups . Heel interface pressures were taken with patients in supine and right lateral tilt positions . Logistic regression demonstrated a statistically significant difference between interface pressures on left and right heels ( p = .004 ) and a trend toward significance between the pillow and Foot Waffle ( p = .069 ) . The Generalized Estimating Equations ( GEE ) method revealed the Foot Waffle was four times more likely not to suspend the heel off the bed than the pillow , and the left heel was four- and -a-half times more likely to have higher interface pressures than the right . There was no significant difference between groups in incidence of lower-extremity pressure ulcers , but patients using the Foot Waffle developed pressure ulcers significantly sooner ( 10 days versus 13 days for the pillow ) . Heels require additional protection beyond the use of specially beds and mattress overlays . In order to provide continuous heel suspension , clinicians must consider proper fit , turning schedules , patient position , patient activity , and presence of additional equipment when selecting heel protection products . This study illustrates how difficult it is to control for all these factors when doing clinical research . Note : This study was done with a Foot Waffle model that has since been re design ed . No research is available on the new model The purpose of this study was to identify prospect ively risk factors for pressure sores and to compare these results with a cross-sectional analysis in the same population . Medical records on all admissions to a chronic care hospital over a 13-month period were review ed . Data on potential risk factors were abstract ed from the initial history , physical examination , nursing assessment , and laboratory studies . Pressure sore status on admission and at three weeks was determined from a st and ardized from completed on all patients with a score . The cross-sectional analysis was performed by comparing patients with and without a pressure sore at the time of admission . The cohort analysis used patients initially without a pressure sore and monitored for a new sore at three weeks . Factors associated with pressure sores on univariate testing were entered into a stepwise logistic regression model . One hundred of the 301 admissions presented with a pressure sore . Factors significantly associated with the presence of a sore were altered level of consciousness ( OR = 4.1 ) , bed- or chair-bound ( OR = 2.4 ) , impaired nutritional intake ( OR = 1.9 ) , and hypoalbuminemia ( OR = 1.8 for 10 mg/mL decrease ) . Of the 185 patients without a pressure sore , 20 ( 10.8 % ) developed a sore . Factors significantly associated with the development of a new pressure sore were a history of cerebrovascular accident ( OR = 5.0 ) , bed- or chair-bound ( OR = 3.8 ) , and impaired nutritional intake ( OR = 2.8 ) . Neither urinary nor fecal incontinence , nor the presence of hypoalbuminemia , was associated with sore development . We have prospect ively identified risk factors for pressure sores . ( ABSTRACT TRUNCATED AT 250 WORDS Manual repositioning of patients by nursing staff is a recognised technique for preventing pressure ulcer formation . The 30 degree tilt is a method of positioning patients that , in the laboratory setting , reduced the contact pressure between the patient and the support surface . A r and omised controlled trial was used to examine the effects of the 30 degree tilt position in reducing the incidence of non-blanching erythema ( i.e. established pressure damage ) in a hospital inpatient population ( n=23 ) when compared to the use of the 90 degree lateral and supine position ( n=23 ) . The primary outcome of the trial was the incidence of pressure damage , defined as non-blanching erythema . In this study no subject developed pressure damage that presented with visible breaks in the epidermis , but all damage was restricted to areas of non-blanching erythema ( five of the 39 subjects who completed the study exhibited such injury ) . The main findings of this study were that patient positioning using the 30 degree tilt method did not reduce the incidence of pressure damage compared with either the 90 degree lateral or supine positions . This study also investigated the feasibility of using the 30 degree tilt position with medical in patients ; it found that 78 % of subjects experienced difficulty in adopting and maintaining the position . This finding seriously questions the practicality of using the 30 degree tilt method with a predominantly ill population Research indicates that 8.5 % of all patients undergoing surgical procedures for more than 3 hours develop pressure ulcers . In some types of surgery , incidence rates in excess of 25 % have been reported . An 11-month study was conducted on the safety and efficacy of an experimental alternating air device in comparison with a tertiary care facility 's conventional practice . A series of 217 patients undergoing surgical procedures scheduled for a minimum of 3 hours were enrolled . No ulcers developed in the experimental group and 11 ulcers developed in seven patients in the control group ( 8.75 % incidence rate ) . Of the 11 ulcers , one was Stage I , four were Stage II , and six were unstageable secondary to eschar . The difference between the groups is significant at the P = 0.005 level . Individuals who developed ulcers had a length of stay approximately 7 days longer than the hospital average for comparable patients who did not develop ulcers The aims of the study were to investigate the relationship between nutritional state and the development of pressure sores and to test the hypothesis that supplementary nutritional support might prevent pressure sore development and improve healing . Newly admitted long-term care patients hospitalised for more than 3 weeks were included and r and omised into an experimental and a control group . The nutritional state was evaluated using serum protein analyses , anthropometry and the delayed hypersensitivity skin test . Further , the patients ' condition was assessed weekly using a modified Norton scale . The experimental group received extra nutritional support . Significantly more patients with protein-energy malnutrition had , or developed , pressure sores . Regression analyses indicated albumin , mobility , activity and food intake as predictors for pressure sores . Patients who received extra nutritional support tended to develop fewer pressure sores and to heal existing pressure sores to a greater extent than the control group , although this did not reach statistical significance Underst and ing the efficacy of patient support surfaces is essential if pressure sore management is to be both efficient and effective . However , laboratory and clinical studies in this area are fraught with well recognized problems . This investigation reports a combination of laboratory , r and omized controlled trial ( efficacy data ) and measures of effectiveness to illustrate the beneficial role of a new dynamic integrated mattress and seat cushion system : the Pegasus Trinova . Successful prevention of sores among a vulnerable patient population , along with positive comments regarding the system 's comfort and ' user-friendliness ' are supported by laboratory measures of interface pressure to provide a hierarchy of data . Such an approach may present one solution to the lack of timeliness of most mattress clinical trials , thus allowing decisions regarding new support surfaces to be made upon the basis of evidence , not on anecdote or solely upon marketing cl aims This study determines the effectiveness of a new low-unit-cost support system in patients at very high risk of developing pressure sores . In a prospect i ve r and omised controlled trial , a low-pressure inflatable mattress and cushion system ( Repose ) was compared to a dynamic support mattress ( Nimbus II ) used in conjunction with an alternating-pressure cushion ( Alpha TranCell ) in 80 patients with fractured neck of femur and high scores on a pressure sore risk assessment scale . All patients received best st and ard care , including turning at regular intervals . Skin condition was assessed in 17 locations on admission , preoperatively , and seven and 14 days postoperatively . No difference was found between the groups in skin condition or the occurrence and severity of pressure sores at any time point The purpose of this study was to assess the effect of nutritional supplementation on dietary intake and on pressure ulcer development in critically ill older patients . The multi-center trial involved 19 wards stratified according to specialty and recruitment for critically ill older patients ; 9 wards were r and omly selected for nutritional intervention ( nutritional intervention group ) , consisting of the daily distribution of two oral supplements , with each supplement containg 200 kcal , for 15 d. Pressure ulcer incidence was prospect ively recorded for grade s I ( erythema ) , II ( superficial broken skin ) , and III ( subcutaneous lesion ) for 15 d. Nutritional intake was monitored by using estimates in units of quarters vali date d by comparison with weight measurement . There were 672 subjects older than 65 y , and 295 were in the nutritional intervention group versus 377 in the control group . The patients were similar for age , sex ratio , and C-reactive protein . In comparison with the control group , the nutritional intervention group included more patients with stroke , heart failure , and dyspnea and fewer with antecedent falls , delirium , lower limb fractures , and digestive disease . The nutritional intervention group had a lower risk of pressure ulcers according to the Norton score but was less dependent ( Kuntzman score ) and had a lower serum albumin level . During the trial , energy and protein intakes were higher in the nutritional intervention group ( day 2 : 1081 + /- 595 kcal versus 957 + /- 530 kcal , P = 0.006 ; 45.9 + /- 27.8 g protein versus 38.3 + /- 23.8 g protein in the control group , P < 0.001 ) . At 15 d , the cumulative incidence of pressure ulcers was 40.6 % in the nutritional intervention group versus 47.2 % in the control group . The proportion of grade I cases relative to the total number of cases was 90 % . Multivariate analysis , taking into account all diagnoses , potential risk factors , and the intra-ward correlation , indicated that the independent risk factors of developing a pressure ulcer during this period were : serum albumin level at baseline , for 1 g/L decrease : 1.05 ( 95 % confidence interval : 1.02 to 1.07 , P < 0.001 ) ; Kuntzmann score at baseline , for 1-point increase : 1.22 ( 0.32 to 4.58 , P = 0.003 ) ; lower limb fracture : 2.68 ( 1.75 to 4.11 , P < 0.001 ) ; Norton score < 10 versus > 14 : 1.28 ( 1.01 to 1.62 , P = 0.04 ) ; and belonging to the control group : 1.57 ( 1.03 to 2.38 , P = 0.04 ) . In conclusion , it was possible to increase the dietary intake of critically ill elderly subjects by systematic use of oral supplements . This intervention was associated with a decreased risk of pressure ulcer incidence Most st and ard hospital beds are flat based with a pull-out backrest , result ing in a tendency for the patient to slide down the bed . This study aim ed to compare the outcome for patients at high risk of developing pressure ulcers nursed on either this type of bed or an electrically operated , multi-sectioned profiling bed . A total of 100 patients were r and omly assigned either to the profiling bed with a pressure-reducing foam mattress ( experimental group ) or a flat-based bed with an appropriate pressure-redistributing mattress ( control group ) for a maximum of 10 days . Risk status and pressure damage were assessed daily . Both a patient and a nurse question naire were completed . Data from 70 patients who participated in the study for five days or more were included in the analysis . Pressure ulcer incidence was 0 % in both groups . All patients ( 35 ) in the experimental group were able to maintain a sitting position compared with only 12/35 in the control group ( p = 0.0001 ) . While the question naire results suggest there were significant differences in postural control and ease of transfer between patients in the two groups , it was not possible to map this to pressure ulcer formation . Poor recruitment into the study was due to the ' blocking ' of electric beds by heavily dependent patients who did not meet the inclusion criteria , precluding a significant result in terms of pressure ulcer outcomes . This nurse-led use of the profiling beds was examined alongside the main study to investigate why they were allocated in this way Assessing the quality of r and omized controlled trials ( RCTs ) is important and relatively new . Quality gives us an estimate of the likelihood that the results are a valid estimate of the truth . We present an annotated bibliography of scales and checklists developed to assess quality . Twenty-five scales and nine checklists have been developed to assess quality . The checklists are most useful in providing investigators with guidelines as to what information should be included in reporting RCTs . The scales give readers a quantitative index of the likelihood that the reported methodology and results are free of bias . There are several shortcomings with these scales . Future scale development is likely to be most beneficial if questions common to all trials are assessed , if the scale is easy to use , and if it is developed with sufficient rigor A clinical evaluation of eight base foam pressure-reducing mattresses was undertaken at Addenbrooke 's NHS Trust , Cambridge . Data were collected on the medical and nutritional status , skin condition , medication , weight and Waterlow score for each patient , together with ratings on mattress comfort . At the beginning and end of the study , mattresses were assessed for interface pressures and the general condition of each mattress and its cover was evaluated AIM This paper reports a study to identify risk factors associated with pressure ulcer development among a mixed group of adult patients undergoing surgery . BACKGROUND Few studies have been carried out with patients undergoing surgery to assess the risk of pressure ulcer development , and so there is a little knowledge of the risk factors for this group . However , studies among non-surgical patients have shown that nutritional predictors such as low serum albumin level and low body mass index ( BMI ) are of great importance . An additional predictive factor may be low blood pressure . It is important to study these predictors further among patients undergoing surgery , using techniques such as multiple regression techniques , design ed to identify the most important predictors for pressure ulcer development . METHODS A prospect i ve comparative study was carried out in 1996 - 1998 with 286 adult patients undergoing surgical treatment . The data were collected from patient records by Registered Nurses preoperatively , for seven days postoperatively and thereafter once a week for up to 12 weeks . Perioperative data were also collected . The Risk Assessment Pressure Sore Scale was used , and data were collected on general physical condition , activity , mobility , moisture , food intake , fluid intake , sensory perception , friction and shear , body temperature and serum albumin . RESULTS Forty-one ( 14.3 % ) patients developed pressure ulcers during the observation period . The most common type was non-blanchable erythema . Those who developed pressure ulcers were significantly older , weighed less , and had a lower BMI and serum albumin . More women than men developed pressure ulcers . Risk factors identified in multiple stepwise regression analyses were female gender , American Society of Anaesthesiologists ( ASA ) status or New York Heart Association ( NYHA ) status and food-intake . CONCLUSION Special attention , with regard to risk of pressure ulcer development , should be paid to patients undergoing surgery who have low ASA or NYHA scores , low food intake and /or are women OBJECTIVE To determine if the use of pressure-reducing wheelchair cushions for elderly nursing home resident wheelchair users who are at high risk for developing sitting-acquired pressure ulcers would result in a lower incidence rate of pressure ulcers , a greater number of days until ulceration , and lower peak interface pressures compared with the use of convoluted foam cushions over a 12-month period . To determine the feasibility of conducting a subsequent full-scale definitive trial to evaluate the use of pressure-reducing seat cushions for elderly nursing home resident wheelchair users . DESIGN R and omized control trial SETTING 2200-bed skilled nursing facilities ( 1 suburban and 1 urban academic medical center ) PATIENTS 32 male and female at-risk nursing home residents who were wheelchair users > or = 65 years of age . Participants had Braden Scale scores < or = 18 , Braden Activity and Mobilitysubscale scores < or = 5 , no sitting surface pressure ulcers , and a daily wheelchair sitting tolerance of more than 6 hours . All met criteria for using the ETAC Twin wheelchair . INTERVENTIONS Seating evaluation with pressure-mapping and subsequent seating prescription . Subjects were assigned to either a foam ( n=17 ) or pressure-reducing cushion ( n=15 ) group and weekly assessment s of skin and pressure ulcer risk were made . MAIN OUTCOME MEASURES Incidence of pressure ulcers , days to ulceration , and peak interface pressure . MAIN RESULTS At a 95 % confidence interval , a 2-tailed analysis showed no differences between the FOAM and pressure-reducing cushion groups for pressure ulcer incidence , total days to pressure ulcer , or initial peak interface pressure . Pressure-reducing cushions were more effective in preventing sitting-acquired ( ischial ) pressure ulcers ( P<.005 ) . Higher interface pressures were associated with a higher incidence of pressure ulcers ( P<.001 ) . CONCLUSIONS A definitive r and omized control multicenter cushion trial is feasible with a sample size of 50 to 100 per study group . In the definitive trial , the definition of sitting-acquired pressure ulcers should be limited to lesions occurring over the ischial tuberosities Recurrence of pressure ulcers is a serious problem following myocutaneous flap surgery and can lead to prolonged and expensive hospitalization . One of the most important aspects of patient care after surgery is the monitoring of reduced pressure in the area of the flap . Usually reducing pressure requires an expensive high-tech support surface . The purpose of this study was to evaluate the effectiveness of a less expensive support surface . There were 12 patients involved in a clinical trial that lasted 14 days and compared the effectiveness of the ROHO dry-floatation mattress to that of the Clinitron bed . Findings indicated that post-operative patients were effectively treated on either support surface Four hundred and forty-six general , vascular and gynaecological surgical patients were recruited to a two centre , double triangular sequential r and omised controlled trial to compare the post-operative pressure sore incidence in patients positioned on the st and ard operating table mattress with those positioned on the dry visco-elastic polymer pad ( Action Products Inc. ) . Two hundred and twenty two patients were r and omised to the experimental group and 224 to the st and ard mattress . The main endpoint failure rate ( a pressure sore ) was found to be 11 % ( 22/205 ) for patients allocated to the dry visco-elastic polymer pad and 20 % ( 43/211 ) for patients allocated to the st and ard operating table mattress . There was a significant reduction in the odds of developing a pressure sore on the dry visco-elastic polymer pad as compared to the st and ard , [ symbol see text ] = 0.46 with 95 % confidence interval of ( 0.26 , 0.82 ) , P = 0.010 . The adjusted point estimates of the probability of developing a pressure sore on the dry visco-elastic polymer pad and the st and ard operating table mattress were 0.11 and 0.21 respectively OBJECTIVE To determine whether low airloss hydrotherapy reduces the incidence of new skin lesions associated with incontinence in hospitalized patients and results in more rapid healing of existing pressure sores compared with st and ard care . To assess subjectively patient and nursing satisfaction related to using low airloss hydrotherapy beds . DESIGN R and omized , prospect i ve , unblinded study . SETTING Acute and chronic hospital wards . PARTICIPANTS A total of 116 newly admitted , incontinent , hospitalized patients with and without existing pressure sores . INTERVENTION Low airloss hydrotherapy compared with treatment on hospital beds and mattresses ordered by the patient 's attending physician . MEASUREMENTS Incidence rates of new skin lesion development , e.g. , pressure sores , c and idiasis , and chemical irritation ; improvement in existing pressure sore size , volume , and status ; subjective assessment of patient and nursing satisfaction . RESULTS Possible hypothermia was identified in two patients during the first week of the study , and patient and nursing dissatisfaction with low airloss hydrotherapy remained high throughout the first months of the study . Therefore , two major modifications in the initial protocol were made : ( 1 ) increased patient temperature monitoring for hypothermia was initiated in Week 2 of the study and ( 2 ) increased staff re sources for in-service training on bed use began in Week 18 of the study . After the latter change , 58 subjects were r and omized to low airloss hydrotherapy and 58 to st and ard care . Subjects were old ( median age > or = 80 years ) , and almost all were bedbound or nonambulatory . The median ( range ) length of follow-up for subjects in the treatment group was significantly shorter than for those in the control group ( 4 ( 1 - 60 ) days versus 6 ( 1 - 62 ) days , respectively , P = .017 ) because there were more dropouts from the treatment group ( 24 ( 36 % ) of 58 versus 2 ( 3 % ) of 58 , P = .0001 ) . The major reasons dropout occurred were patient or family dissatisfaction ( 12 ( 21 % ) ) , new or worsened skin lesions thought to be related to bed use ( 4 ( 7 % ) ) , and hypothermia < 97 degrees F ( 4 ( 7 % ) ) . The total cumulative incidence of new truncal skin lesions within 9 days of enrollment was greater in the treatment than in the control group ( 48 % versus 14 % , respectively , P < 0.01 ) . Too few patients with existing pressure sores were treated for too short a period of time to assess the effect of low airloss hydrotherapy on pressure sore healing . Because only 10 patients treated on low airloss hydrotherapy beds were able to complete satisfaction surveys meaningfully , interpretation of these data is difficult . Only nine ( 21 % ) of 44 nurses subjectively reported overall satisfaction using the low airloss hydrotherapy bed . CONCLUSIONS This study shows the value of a rigorously design ed clinical ly based evaluation of a new product developed for older patients . The results of the study led to re-engineering of the prototype low airloss hydrotherapy bed as well as a change in marketing strategy . Studies of products targeted to the prevention and treatment of pressure sores in older patients should be undertaken before generalized marketing begins STUDY OBJECTIVE To compare the effectiveness and adverse effects of air-fluidized beds and conventional therapy for patients with pressure sores . DESIGN R and omized trial with both masked and unmasked comparisons of outcome after a median follow-up of 13 days ( range , 4 to 77 days ) . SETTING Urban , academic referral , and primary care medical center . PATIENTS Of 140 potentially eligible hospitalized patients with pressure sores , 72 consented to r and omization ; 65 ( 90 % ) completed the study . INTERVENTIONS Thirty-one patients on air-fluidized beds ( Clinitron Therapy , Support Systems International , Inc. , Charleston , South Carolina ) repositioned every 4 hours from 0700h to 2300h without use of other antipressure devices . Thirty-four patients on conventional therapy used an alternating air-mattress covered by a foam pad ( Lapidus Air Float System , American Pharmaceal Company , Cincinnati , Ohio ) on a regular hospital bed ; were repositioned every 2 hours ; and had elbow or heel pads as needed . Topical therapy was st and ardized for both groups . MEASUREMENTS AND MAIN RESULTS Pressure sores showed a median decrease in total surface area ( -1.2 cm2 ) on air-fluidized beds , but showed a median increase ( + 0.5 cm2 ) on conventional therapy ; 95 % confidence interval ( CI ) for the difference between medians , -9.2 to -0.6 cm2 ( p = 0.01 ) . Improvement , as assessed from serial color photographs by investigators masked to treatment group , occurred in 71 % and 47 % , respectively ; 95 % CI for the difference , 1 % to 47 % ( p = 0.05 ) . For pressure sores 7.8 cm2 or greater , outcome differences between air-fluidized beds and conventional therapy were greater : median total surface area change was -5.3 and + 4.0 cm2 , respectively ; 95 % CI for the difference , -42.2 to -3.2 cm2 ( p = 0.01 ) . Improvement rates were 62 % and 29 % respectively ; 95 % CI for difference , 1 % to 65 % ( p = 0.05 ) . After adjusting for other factors associated with sore outcome , the estimated relative odds of showing improvement with air-fluidized beds were 5.6-fold ( 95 % CI , 1.4 to 21.7 ) greater than with conventional therapy ( p = 0.01 ) . No significant increase in adverse effects was seen with air-fluidized beds . CONCLUSIONS Our findings suggest that air-fluidized beds are more effective than conventional therapy , particularly for large pressure sores . Studies are needed to determine the effectiveness of air-fluidized beds in long-term care setting Abstract The effectiveness of a new method of preventing pressure sores , the ' Air Wave System ' ( AWS ) , has been compared with that of the conventional large-cell ripple mattress . 31 matched pairs of patients at high risk of sores developing took part in the trial . The AWS was significantly more effective in preventing and reducing the severity of pressure sores and in promoting recovery from existing sores . Moreover , it was reliable and free from mechanical breakdown during the trial Pressure sores are a potential complication of intensive care . Modern methods of pressure sore prevention centre around the use of pressure‐relieving devices . Few studies exist that confirm the effectiveness of these devices . This study evaluates the effectiveness of two devices , the Hill‐Rom Duo ® mattress and the KCI TheraPulse ® . High‐risk patients were r and omly assigned to receive one of two devices . We excluded those patients who had pressure sores upon admission . Those patients that did develop a pressure sore had their wound digitally photographed and grade d by two independent tissue viability nurses . Sixty‐two patients were included ( 30 TheraPulse ® , 32 Duo ® ) . Nine developed a pressure sore ( 6 Duo ® , 3 TheraPulse ® ) . No statistical differences between the two devices could be found . The longer a patient was nursed on a device , the greater the risk of pressure sore development . Despite the use of these devices , pressure sores can still develop in the Intensive Care patient population This study evaluates pressure ulcer incidence rates and comfort perceptions in 100 subjects admitted to a district general hospital . Subjects were divided into two groups , Group A using the st and ard hospital mattress ( Transfoam ) , which had been in use in the hospital for three years , and Group B using the study mattress ( Transfoamwave ) , which was new at the beginning of the trial . Due to the low observed incidence of pressure ulcers , it has not been possible to determine whether there is a difference in the clinical performance of the mattresses . Both appear to provide similar levels of comfort . Seat cushions were provided for each trial subject but staff failed to make good use of them , which suggests that more education is required in this area BACKGROUND studies of the effectiveness of alternating pressure air mattresses ( APAMs ) for the prevention of pressure ulcers are scarce and in conflict . OBJECTIVE evaluating whether an APAM is more or equally effective as the st and ard prevention . DESIGN r and omised controlled trial . SETTING AND SUBJECTS patients admitted to 19 surgical , internal , or geriatric wards in seven Belgian hospitals were included if they were in need of prevention of pressure ulcers . To define this need , two methods were used r and omly : the Braden Scale or the presence of non-blanchable erythema ( NBE ) . METHODS 447 patients were r and omised into either an experimental or a control group . In the experimental group , 222 patients were lying on an APAM ( Alpha-X-Cell , Huntleigh Healthcare , UK ) . In the control group , 225 patients were lying on a visco-elastic foam mattress ( Tempur , Tempur-World Inc. , USA ) in combination with turning every 4 hours . Both groups had identical sitting protocol s. RESULTS there was no significant difference in incidence of pressure ulcers ( grade 2 - 4 ) between the experimental ( 15.6 % ) and control group ( 15.3 % ) ( P = 1 ) . There were significantly more heel pressure ulcers in the control group ( P = 0.006 ) . There was an interaction effect between the risk assessment method and preventive measures for the development of all pressure ulcers and sacral pressure ulcers . CONCLUSION fewer patients developed heel pressure ulcers on an APAM . Patients identified as being in need of prevention based on the presence of NBE had a tendency to develop fewer pressure ulcers on an APAM . Patients identified as being in need of prevention , based on the Braden Scale , appeared to develop more sacral pressure ulcers on an APAM BACKGROUND Turning is considered to be an effective way of preventing pressure ulcers , however almost no research has been undertaken on this method . AIM The aim of the study was to investigate the effect of four different preventative regimes involving either frequent turning ( 2 , 3 hourly ) or the use of a pressure-reducing mattress in combination with less frequent turning ( 4 , 6 hourly ) . SUBJECTS 838 geriatric nursing home patients participated in the study . METHODS During 28 days , four different turning schemes were used : turning every 2 h on a st and ard institutional ( SI ) mattress ( n = 65 ) , turning every 3 h on a SI mattress ( n = 65 ) , turning every 4 h on a viscoelastic foam ( VE ) mattress ( n = 67 ) , and turning every 6h on a VE mattress ( n = 65 ) . The remaining patients ( n = 576 ) received st and ard preventive care . MAIN RESULTS The incidence of non-blanchable erythema ( 34.8 - 38.1 % ) was not different between the groups . The incidence of grade II and higher pressure ulcers in the 4h interval group was 3.0 % , compared with incidence figures in the other groups varying between 14.3 % and 24.1 % . CONCLUSIONS Turning every 4 h on a VE mattress result ed in a significant reduction in the number of pressure ulcer lesions and makes turning a feasible preventive method in terms of effort and cost We analyzed prospect i ve data from 19,889 elderly residents of 51 nursing homes from 1984 to 1985 to determine the prevalence , incidence , and natural history of pressure ulcers . Among all residents admitted to nursing homes , 11.3 % possessed a stage II through stage IV pressure ulcer . For those residents admitted to the nursing home without pressure ulcers during the study period , the 1-year incidence was 13.2 % . This increased to 21.6 % by 2 years of nursing home stay . People already residing in a nursing home at the start of the study had a 1-year incidence of 9.5 % , which increased to 20.4 % by 2 years . Pressure ulcers were associated with an increased rate of mortality , but not hospitalization . Longitudinal follow-up of residents with pressure ulcers demonstrated that a majority of their lesions were healed by 1 year . Most of the improvement occurred early in a person 's nursing home stay . Although nursing home residents with pressure ulcers have a higher mortality , with good medical care pressure ulcers can be expected to heal The risk of nosocomial pneumonia and atelectasis is high among critically ill immobilized patients . We hypothesized that continuous turning on the kinetic treatment table would reduce their incidence . Sixty-five critically ill patients , immobilized because of head injury or traction , were prospect ively r and omized for treatment in a conventional bed ( n = 38 ) or the kinetic treatment table ( n = 27 ) . Patients were well matched for baseline demographic and pulmonary risk factors . Patients in the conventional bed group had a higher incidence of cigarette smoking . The combined incidence of significant atelectasis or pneumonia was higher ( 66 % ) in the conventional vs. kinetic treatment table ( 33 % ) groups ( p less than .01 ) . Atelectasis , pneumonia , adult respiratory distress syndrome , requirements for ventilator treatment , for PEEP , and for an FIO2 greater than 0.50 were not significantly different , but tended to be higher in the control group . Survival and the incidence of decubitus ulcers were similar The purpose of this study was to compare the incidence of pressure ulcers in 40 newly admitted at-risk ( Braden Scale score < 18 ) skilled-nursing-facility residents , r and omly assigned to Iris 3000 ( Bio Clinic of Sunrise Medical Corp , Ontario , CA ) foam mattress overlays ( n = 20 ) or a MAXIFLOAT ( BG Industries , Northridge , CA ) foam mattress replacements ( n = 20 ) . Head-to-toe skin assessment s were done 3 times weekly for a maximum of 21 days , using Bergstrom Skin Assessment Tool . Subjects on MAXIFLOAT had fewer pressure ulcers ( chi 2[1 , N = 40 ] = 5.013 , p = .025 ) despite heavier body mass ( t[35 ] = 2.60 , p = .013 ) and more days on the surface ( t[38 ] = 2.24 , p = .03 ) . MAXIFLOAT proved to be more effective in preventing pressure ulcers in an at-risk skilled-care population and was cost-effective . Research findings on efficacy , adequate feedback from nursing staff , residents , and ancillary staff regarding issues of patient comfort , ease of use , and cost are important factors in decision-making when considering product changes Nurses caring for elderly patients often need to select support surfaces that reduce the likelihood of pressure ulcers , but there is little information about the effectiveness of different support surfaces . This r and omized trial compared two support surfaces and investigated patient attributes related to the risk of developing a pressure ulcer . Eighty-four elderly patients were nursed on a convoluted or solid foam overlay and assessed three times a week for pressure ulcers . Stepwise Cox proportional hazards regression revealed a statistically significant relationship between the risk of developing a pressure ulcer and the variables mobility and type of support surface |
12,798 | 25,325,563 | Based on the clinical results obtained in VE-treated chronic HBV carriers , we provide a reliable hypothesis for the possible role of this vitamin in the modulation of host miRNA profiles perturbed by this viral pathogen and in the regulation of some cellular miRNA with a suggested potential anti-HBV activity . | Hepatitis B virus ( HBV ) infection represents a serious global health problem and persistent HBV infection is associated with an increased risk of cirrhosis , hepatocellular carcinoma and liver failure .
Recently , the study of the role of microRNA ( miRNA ) in the pathogenesis of HBV has gained considerable interest as well as new treatments against this pathogen have been approved .
A few studies have investigated the antiviral activity of vitamin E ( VE ) in chronic HBV carriers .
Herein , we review the possible role of tocopherols in the modulation of host miRNA with potential anti-HBV activity .
The keywords used were ' HBV therapy ' , ' HBV treatment ' , ' VE antiviral effects ' , ' tocopherol antiviral activity ' , ' miRNA antiviral activity ' and ' VE microRNA ' . | The effect of daily supplementation of 800 mg dl alpha-tocopheryl acetate for 30 d on general health , nutrient status , hepatic and renal function , intermediary metabolism , hematological status , plasma nutrients and antioxidant status , thyroid hormones , and urinary creatinine concentrations was studied in 32 healthy elderly ( > 60 y ) people who participated in a double-blind , placebo-controlled , residential trial . The subjects reported no side effects due to the supplements . Supplementation had no effect on body weight , plasma total protein , albumin , glucose , total cholesterol and triglycerides , conjugated and unconjugated bilirubin , alkaline phosphatase , indicators of hepatic and renal function , hematologic status , thyroid hormones , or serum and urinary creatinine concentrations and creatinine clearance . Supplementation did cause a significant increase in serum vitamin E , and a small ( 5 % ) but significant ( P < 0.05 ) increase in plasma zinc in the vitamin E-supplemented group . Thus , short-term supplementation with 800 mg vitamin E/d has no adverse effect on healthy older adults BACKGROUND It has been suggested that vitamin E can counteract the age-associated decline in cellular immune responsiveness ( CIR ) . Particularly , T helper cell type 1 ( Th1 ) activity , ie , interferon ( IFN ) gamma-producing Th1 activity and , hence , delayed-type hypersensitivity ( DTH ) would be enhanced by vitamin E supplementation . OBJECTIVE Our aim was to study the effects of 6 mo supplementation with 50 and 100 mg vitamin E on CIR in the elderly . DESIGN A double-blind , placebo-controlled trial was conducted in 161 healthy elderly subjects aged 65 - 80 y. CIR was measured in vivo by means of DTH skin tests and in vitro by assessing the production of interleukin ( IL ) 2 , IFN-gamma ( a typical Th1 cytokine ) , and IL-4 ( a typical Th2 cytokine ) by peripheral blood mononuclear cells after stimulation with phytohemagglutinin . RESULTS Both DTH and IL-2 production showed a trend toward increased responsiveness with increasing dose of vitamin E. However , IFN-gamma production decreased whereas IL-4 production increased in the groups receiving vitamin E. Only the change in the number of positive DTH reactions was borderline significantly larger in the 100-mg vitamin E group than in the placebo group ( P = 0.06 , Bonferroni adjusted ) . Subjects receiving 100 mg vitamin E with low baseline DTH reactivity or who were physically less active had a significantly larger increase in the cumulative diameter of the skin in duration result ing from the DTH test than did the placebo group ( P = 0.03 ) , although this difference was not significant after Bonferroni correction ( P = 0.07 ) . CONCLUSION Possible beneficial effects of 100-mg vitamin E supplementation may be more pronounced in particular subgroups of elderly subjects AIM To evaluate the safety and efficacy of Vitamin E in children with chronic hepatitis B. METHODS We r and omly assigned patients with chronic hepatitis B , positive for hepatitis B e antigen ( HBeAg ) , to receive either Vitamin E or placebo once daily for 6 mo in a 3:1 ratio and double-blind manner . The primary end point was HBeAg seroconversion , defined as the loss of HBeAg , undetectable levels of serum hepatitis B virus DNA , and the appearance of antibodies against HBeAg 12 mo after therapy . RESULTS At baseline visit , 49 patients had normal and 43 had increased serum aminotransferase levels . Twenty-nine patients did not respond to previous treatment with interferon-alpha or lamivudine . Seventy-six children completed the study ; 16 were non-compliant ( n = 7 ) , lost to follow-up ( n = 7 ) , or started another antiviral treatment ( n = 3 ) . Intention-to-treat analysis showed HBeAg seroconversion in 16 children ( 23.2 % ) treated with Vitamin E and two ( 8.7 % ) in the placebo group ( P = 0.13 ) . Vitamin E was well tolerated . CONCLUSION There is only a tendency that Vitamin E may promote HBeAg seroconversion . Therefore larger studies are needed to clarify the role of antioxidants in the therapy of chronic hepatitis BACKGROUND & AIMS Insulin resistance and oxidative stress contribute to the pathogenesis of nonalcoholic steatohepatitis ( NASH ) . We conducted a pilot study for the following reasons : ( 1 ) to test the hypothesis that a combination of an antioxidant ( vitamin E ) and an insulin sensitizer ( pioglitazone ) would be superior to vitamin E alone for the treatment of NASH , and ( 2 ) to define the effects of these interventions on insulin-sensitive metabolic functions and correlate the effects with changes in liver histology . METHODS A r and omized prospect i ve trial was performed to compare the efficacy and safety of vitamin E alone ( 400 IU/day ) vs. vitamin E ( 400 IU/day ) and pioglitazone ( 30 mg/day ) in nondiabetic , noncirrhotic subjects with NASH . Metabolic functions were assessed by a 2-step , hyperinsulinemic ( 10 and 40 mU/m2/min ) euglycemic clamp . RESULTS A total of 10 patients were r and omized to each arm . Two patients on combination therapy discontinued treatment ; one because of pregnancy and the other because of hepatotoxicity . Treatment with vitamin E only produced a significant decrease in steatosis ( mean grade , 2.2 vs. 1.4 ; P < .02 ) . Compared with baseline , combination therapy produced a significant decrease in steatosis ( mean , 2.3 vs. 1 ; P < .002 ) , cytologic ballooning ( 1.3 vs. 0.2 ; P < .01 ) , Mallory 's hyaline ( 0.7 vs. 0.2 ; P < .04 ) , and pericellular fibrosis ( 1.2 vs. 0.6 ; P < .03 ) . Although vitamin E had no significant effects , combination therapy produced a significant increase in metabolic clearance of glucose and a decrease in fasting free fatty acid ( FFA ) and insulin . The decrease in fasting FFA and insulin independently predicted improvement in hepatic steatosis and cytologic ballooning . CONCLUSIONS A combination of vitamin E and pioglitazone produces a greater improvement in NASH histology . The improvement in steatosis and cytologic ballooning are related to treatment-associated decreases in fasting FFA and insulin levels CONTEXT Nonalcoholic fatty liver disease ( NAFLD ) is the most common chronic liver disease in US children and adolescents and can present with advanced fibrosis or nonalcoholic steatohepatitis ( NASH ) . No treatment has been established . OBJECTIVE To determine whether children with NAFLD would improve from therapeutic intervention with vitamin E or metformin . DESIGN , SETTING , AND PATIENTS R and omized , double-blind , double-dummy , placebo-controlled clinical trial conducted at 10 university clinical research centers in 173 patients ( aged 8 - 17 years ) with biopsy-confirmed NAFLD conducted between September 2005 and March 2010 . Interventions Daily dosing of 800 IU of vitamin E ( 58 patients ) , 1000 mg of metformin ( 57 patients ) , or placebo ( 58 patients ) for 96 weeks . MAIN OUTCOME MEASURES The primary outcome was sustained reduction in alanine aminotransferase ( ALT ) defined as 50 % or less of the baseline level or 40 U/L or less at visits every 12 weeks from 48 to 96 weeks of treatment . Improvements in histological features of NAFLD and resolution of NASH were secondary outcome measures . RESULTS Sustained reduction in ALT level was similar to placebo ( 10/58 ; 17 % ; 95 % CI , 9 % to 29 % ) in both the vitamin E ( 15/58 ; 26 % ; 95 % CI , 15 % to 39 % ; P = .26 ) and metformin treatment groups ( 9/57 ; 16 % ; 95 % CI , 7 % to 28 % ; P = .83 ) . The mean change in ALT level from baseline to 96 weeks was -35.2 U/L ( 95 % CI , -56.9 to -13.5 ) with placebo vs -48.3 U/L ( 95 % CI , -66.8 to -29.8 ) with vitamin E ( P = .07 ) and -41.7 U/L ( 95 % CI , -62.9 to -20.5 ) with metformin ( P = .40 ) . The mean change at 96 weeks in hepatocellular ballooning scores was 0.1 with placebo ( 95 % CI , -0.2 to 0.3 ) vs -0.5 with vitamin E ( 95 % CI , -0.8 to -0.3 ; P = .006 ) and -0.3 with metformin ( 95 % CI , -0.6 to -0.0 ; P = .04 ) ; and in NAFLD activity score , -0.7 with placebo ( 95 % CI , -1.3 to -0.2 ) vs -1.8 with vitamin E ( 95 % CI , -2.4 to -1.2 ; P = .02 ) and -1.1 with metformin ( 95 % CI , -1.7 to -0.5 ; P = .25 ) . Among children with NASH , the proportion who resolved at 96 weeks was 28 % with placebo ( 95 % CI , 15 % to 45 % ; 11/39 ) vs 58 % with vitamin E ( 95 % CI , 42 % to 73 % ; 25/43 ; P = .006 ) and 41 % with metformin ( 95 % CI , 26 % to 58 % ; 16/39 ; P = .23 ) . Compared with placebo , neither therapy demonstrated significant improvements in other histological features . CONCLUSION Neither vitamin E nor metformin was superior to placebo in attaining the primary outcome of sustained reduction in ALT level in patients with pediatric NAFLD . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00063635 BACKGROUND The purpose of the present paper was to investigate the efficacy of vitamin E in children with immunotolerant-phase chronic hepatitis B virus ( CHB ) infection . METHODS Fifty-eight immunotolerant children were prospect ively and r and omly recruited into two groups . Group 1 ( study group ) included 30 patients who received vitamin E at a dose of 100 mg/day throughout 3 months ; group 2 ( control group ) contained 28 patients who did not receive any medication . Comparison of serological , virologic , and biochemical response ratios were done at the end of the therapy and after 6 months of vitamin E discontinuation . RESULTS Mean alanine transaminase ( ALT ) values in group 1 at the beginning of the therapy , 3 months after the therapy initiation and 6 months after discontinuation were 30.4 + /- 7.3 IU/L , 31.3 + /- 7.8 IU/L and 32.1 + /- 8.5 IU/L , respectively . The mean hepatitis B virus (HBV)-DNA load of group 1 at onset , and at the third and ninth months of the treatment were 3106 + /- 718 pg/mL , 3530 + /- 137 pg/mL and 3364 + /- 1246 pg/mL , respectively . These changes in both ALT and HBV-DNA values did not reach significant levels ( P > 0.05 ) . In group 2 , mean ALT values at the beginning of therapy , and at the third and ninth months were 28.0 + /- 1.8 IU/L , 34.6 + /- 8.1 IU/L , and 34.1 + /- 7.0 IU/L , respectively ( P > 0.05 ) , and mean viral load of HBV-DNA was 4227 + /- 1435 pg/mL , 3368 + /- 2673 pg/mL , and 3018 + /- 2814 pg/mL , respectively ( P > 0.05 ) . There was no statistically significant difference between group 1 and group 2 at the third and ninth months in the mean ALT values and viral load of HBV-DNA ( P > 0.05 ) . Hepatitis B s antigen and hepatitis B e antigen clearance or hepatitis B s antibody and hepatitis B e antibody seroconversion were not observed in either group . CONCLUSION As a first study investigating the effect of vitamin E in children with immunotolerant CHB infection , no beneficial effect could be demonstrated . Different immunomodulator protocol s should be considered for future investigations |
12,799 | 9,554,897 | This meta- analysis of 15 years of clinical research suggests that antibiotic prophylaxis with a combination of topical and systemic drugs can reduce respiratory tract infections and overall mortality in critically ill patients . | OBJECTIVE To determine whether antibiotic prophylaxis reduces respiratory tract infections and overall mortality in unselected critically ill adult patients . | To evaluate the use of selective decontamination of the digestive tract ( SDD ) ( polymyxin , amphotericin , tobramycin , and intravenous cefotaxime ) in a mixed intensive care unit , we performed a stratified , r and omized , prospect i ve study . The 331 patients were recruited over an 18-month period , with 256 patients remaining more than 48 hours . Stratification by acute physiology and chronic health evaluation ( APACHE II ) preceded r and omization to control ( st and ard antibiotic therapy ) or treatment ( SDD ) groups . Nosocomial infection was significantly reduced in the SDD group ( 16.7 % ; 21 of 126 patients ) compared with the control group ( 30.8 % ; 40 of 130 patients ; p = 0.008 ) . No difference was found in overall mortality rate or length of stay between the two groups . Those patients with admission APACHE II scores 10 to 19 demonstrated the most significant reduction in nosocomial infection ( 23 of 70 control vs 13 of 76 SDD ; p = 0.03 ) and mortality ( 15 of 70 control vs 8 of 76 SDD ; p = 0.07 ) . Emergence of multiresistant microorganisms was not a clinical problem , but a definite change occurred in the ecology of environmental and colonizing bacteria . With the exception of cefotaxime , a reduction was noted in systemic antibiotic usage in the SDD group . We conclude that SDD is useful in selected patients in a mixed intensive care unit Selective decontamination of the oropharynx and gastrointestinal tract with nonabsorbable antimicrobials and sucralfate , a stress ulcer prophylactic that maintains the normal gastric acid bacterial barrier , were compared for prevention of pneumonia in a cardiac surgery intensive care unit . Over 8 months , 51 patients received selective decontamination and 56 received sucralfate . The selective decontamination regimen included polymyxin , gentamicin , and nystatin given as an oral paste and as a solution ; patients also received st and ard antacid or histamine2 blocker stress ulcer prophylaxis . Patients in the selective decontamination group had significantly less colonization of the oropharynx and stomach by gram-negative bacilli ( 12 % vs. 55 % , P less than .001 ) , significantly fewer infections due to gram-negative bacilli ( 6 % vs. 20 % , P = .02 ) , and fewer infections overall ( 12 % vs. 27 % , P = .04 ) . There was one episode of pneumonia in the selective decontamination group and five in the sucralfate group . Mortality and length of stay did not differ between the groups , but those receiving selective decontamination had less than one-third as many days of systemic antibiotic therapy with no increase in colonization or infection with resistant gram-negative bacilli . Thus , selective decontamination appeared to reduce both extrapulmonary and pulmonary infections BACKGROUND Reduction of potential pathogens by selective intestinal decontamination has been proposed to improve intensive care . Despite large scientific interest in this method , little is known about its benefit in homogeneous trauma population s. METHODS In a prospect i ve , controlled study , we enrolled non-infected trauma patients ( age over 18 years , mechanical ventilation > or = 48 hours , intensive care for more than 3 days ) who primarily were admitted to our university medical center . We r and omized patients to be treated with two different topical regimens ( polymyxin , tobramycin , and amphotericin ( PTA ) or polymyxin , ciprofloxin , amphotericin ( PCA ) ) or the carrier only ( placebo ) , administered four times daily both to the oropharynx and to the gastrointestinal tract . All patients received intravenous ciprofloxacin ( 200 mg , bd ) for 4 days . FINDINGS Of 357 enrolled patients , 310 ( age 38.0 + /- 16.5 years , Injury Severity Score 35.2 + /- 12.7 ) met all inclusion criteria . Selective decontamination successfully reduced intestinal bacterial colonization . However , we did not identify significant differences between groups regarding pneumonia ( PTA 47.5 % , PCA 39.0 % , placebo 45.3 % ) , sepsis ( PTA 47.5 % , PCA 37.8 % , placebo 42.6 % ) , multiple organ failure ( PTA 56.3 % ; PCA 52.4 % , placebo 58.1 % ) , and death ( PTA 11.3 % , PCA 12.2 % , placebo 10.8 % ) . Total costs per patient were highest with the PTA regimen . CONCLUSIONS We found no benefit of selective decontamination in trauma patients . Apparently , bacterial overgrowth in the intestinal tract is not the sole link between trauma , sepsis , and organ failure 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 In a prospect i ve r and omized study to determine whether prevention of colonization of Gram-negative bacteria results in prevention of Gram-negative bacterial infections , 96 intensive care patients were r and omly allocated into a control group and a study group . The study group received oral nonabsorbable antimicrobial agents ( i.e. , tobramycin , amphotericin B , and polymyxin E ) in addition to parenteral antibiotics . Colonization with Gram-negative microorganisms in the oropharynx , and respiratory and digestive tracts increased in the control group during their stay , while the study group did not tend to colonize with Gram-negative bacteria . In the control group , 107 nosocomial infections were diagnosed , vs. 42 nosocomial infections in the study group . Nosocomial infections caused by Gram-negative bacteria were significantly less frequent in the study group . Mortality due to an acquired infection was significantly less frequent in the study group . We conclude that colonization , infection , and subsequent mortality by nosocomial Gram-negative bacteria can be prevented by a regime of topically applied nonabsorbable antibiotics Selective decontamination of the digestive tract ( SDD ) , by means of non-absorbable antibiotics , to prevent infection in intensive-care units ( ICUs ) remains controversial ; there is evidence that the regimen reduces the incidence of secondary infection , but no convincing reduction in morbidity or mortality has been shown and the costs and effect on microbial resistance patterns need further study . In a double-blind , placebo-controlled trial , we have tried to find out whether SDD should be used routinely in all ICU patients at high risk of secondary infection . All patients admitted to the ICU who were thought likely to stay in the unit for at least 5 days and to need intubation for longer than 48 h were enrolled and r and omly allocated to groups receiving placebo or SDD ( amphotericin , colistin , and tobramycin applied to the oropharynx and enterally ) ; all patients received intravenous cefotaxime for 72 h. Of 322 patients r and omised , 83 were withdrawn ( 80 ICU stay or duration of intubation too short , 3 protocol violations ) . 239 medical , trauma , and surgical patients completed the trial period ( 114 SDD , 125 placebo ) . There were no differences between SDD and placebo groups in incidence of infection ( 30 [ 26 % ] vs 43 [ 34 % ] patients ; p = 0.22 ) , duration of ICU stay ( mean 16.2 [ 14.3 ] vs 16.8 [ 12.3 ] days ) , hospital stay ( 29.9 [ SD 25.0 ] vs 31.9 [ 22.2 ] days ) , or mortality ( 21 [ 18 % ] vs 21 [ 17 % ] ) . SDD substantially increased the costs of intensive care . Mechanisms other than bacterial colonisation of the gut may bring about substantial numbers of secondary infections in ICUs . Routine use of SDD in multidisciplinary ICUs can not be recommended A comparative , prospect i ve study was made of the incidence of infection in the lower airway ( purulent tracheobronchitis and pneumonia ) in long-term patients who were mechanically ventilated due to respiratory failure of noninfectious origin . Twenty-eight patients were r and omly allocated into a study group ( A , n = 13 ) in which a nonabsorbable paste containing 2 % tobramycin , 2 % amphotericin B , and 2 % polymyxin E was administered locally to decontaminate the oropharynx , and a control group ( B , n = 15 ) in which a paste without antibiotics was also applied to the oropharynx . We studied the effectiveness of the prophylactic technique in decontaminating the oropharynx and trachea of organisms potentially pathogenic for the respiratory system . Decontamination was successful in ten of 13 patients in group A vs. one of 15 patients in group B ( p less than .001 ) . The results demonstrated a lower rate of infection in the lower respiratory tract in the study group ( three patients with tracheobronchitis and no pneumonias ) than in the control group ( three patients with tracheobronchitis and 11 with pneumonia ) , the difference between both being highly significant ( p less than .001 ) . Two ( 15 % ) patients in group B developed sepsis of pulmonary origin . None of the patients on prophylactic treatment developed this complication . Although the overall mortality was similar in both groups ( group A , 30 % vs. group B , 33 % ) , we believe that infection contributed to a great extent to the death of two of five patients in group B. We conclude that nosocomial pneumonia , which is a frequent complication in critically ill patients on mechanical ventilation , could be prevented by local application of nonabsorbable antibiotics to the oropharynx Suppression of the gut luminal aerobic flora to reduce nosocomial infections was tested in a prospect i ve , r and omized , double-blind , placebo-controlled clinical trial in patients in a surgical intensive care unit who had persistent hypermetabolism . Forty-six patients were r and omized to receive either norfloxacin , 500-mg suspension every 8 hours , together with nystatin , 1 million units every 6 hours , or matching placebo solutions administered through a nasogastric tube within 48 hours of surgical intensive care unit admission . Selective gut decontamination with the experimental therapy or placebo solutions continued for at least 5 days or until the time of surgical intensive care unit discharge . Patients were monitored with routine surveillance cultures for the development of nosocomial infections , as defined by criteria from the Centers for Disease Control . All other therapy was given as clinical ly indicated , including systemic antibiotics . The selective gut decontamination group experienced a significant reduction in the incidence of nosocomial infections and a reduced length of stay . However , these results were not associated with a concomitant decrease in progressive multiple organ failure syndrome , adult respiratory distress syndrome , or mortality Nosocomial pneumonia is a frequent complication of prolonged mechanical ventilation [ 1 - 3 ] . Oropharyngeal and gastric colonization , because of potentially pathogenic microorganisms and their subsequent aspiration to the lower airways , play a substantial role in the pathogenesis of ventilator-associated nosocomial pneumonia [ 4 , 5 ] . Selective digestive decontamination has been widely used as a prophylactic regimen for ventilator-associated nosocomial pneumonia . The first to describe this complication , Stoutenbeek and colleagues [ 6 ] suggested that the best combination for preventing nosocomial pneumonia was the use of topical nonabsorbable antibiotics in the oropharynx and stomach together with systemic antibiotics . Most studies have shown a substantial decrease in the carriage of gram-negative bacilli of the upper and lower airways and also in the incidence of nosocomial pneumonia [ 7 , 8 ] , and a few studies have shown a substantial decrease in the overall mortality rate [ 9 - 11 ] . Several important considerations in most of the studies still make selective digestive decontamination a controversial issue . First , several studies were not r and omized or used historical controls [ 6 , 12 - 19 ] . Second , most of the r and omized studies used only nonspecific methods to diagnose nosocomial pneumonia [ 9 , 11 , 20 - 28 ] . Finally , despite the apparent decrease in the incidence of nosocomial pneumonia , mortality did not change in most of the studies [ 12 - 28 ] , including two recent r and omized and double-blind studies [ 29 , 30 ] of a large population sample of patients in an intensive care unit . We did a r and omized , double-blind study of selective digestive decontamination in a general population of patients requiring mechanical ventilation . The main end points of this study were to assess the effect of selective digestive decontamination in decreasing nosocomial pneumonia and mortality . Additional end points of this study were to determine the effect of selective digestive decontamination on the morbidity ( length of stay and duration of mechanical ventilation ) and the mortality rate . Methods Patients The study was done in the Respiratory Intensive Care Unit of the Hospital Clinic of Barcelona , Spain , a 1000-bed teaching hospital , during a period of 12 months . All mechanically ventilated patients admitted to the respiratory intensive care unit and expected to remain intubated for more than 3 days were included in the study . The only exclusion criterion was the presence of immunosuppression ( human immunodeficiency virus [ HIV ] infection , HIV-related diseases , patients who received transplants , and patients treated with antineoplastic chemotherapy ) . Patients who were extubated or who died before receiving 72 hours of selective digestive decontamination or placebo were also excluded from the analysis . Study Design Patients were r and omly allocated to either the selective digestive decontamination or the placebo group . The r and omization was done using a computer-generated table , and the patients were enrolled consecutively . Severity of illness was evaluated by means of the Simplified Acute Physiologic Score after r and omization . The authors of the study were blinded in the recovery of the results . The study ended after extubation or death of the patient in the intensive care unit . Administration of Antibiotics After sample s for the bacteriologic assessment were obtained , antibiotics were administered for selective digestive decontamination . An aqueous suspension of 10 mL containing polymyxin E , 100 mg ( Dumex ; Dumex Limited , Denmark ) ; tobramycin , 80 mg ( Tobradistin ; Dista SA , Madrid , Spain ) ; and amphotericin B , 500 mg ( Fungizona ; Squibb Industria Farmaceutica SA , Madrid ) was administered through a nasogastric tube to patients in the selective digestive decontamination group . Carboxymethyl-cellulose with pectin and with gelatin ( 0.5 mL , Orabase ; Drogfesa , Mollet del Valles , Spain ) containing polymyxin E , tobramycin , and amphotericin B , at 2 % concentration , was applied four times a day . In the placebo group , an aqueous suspension of Maxipro ( Scientific Hospital Supplies Limited , Liverpool , United Kingdom ) and Orabase , both colored with tartrazine , were administered through the nasogastric tube and in the oropharynx at the same dosage as for patients who received selective digestive decontamination . Systemic Antibiotic and Stress Ulcer Prophylaxis Patients were treated with 2 g of intravenous cefotaxime four times a day ( Primafen , Hoechst Iberica SA , Barcelona , Spain ) for the first 4 days of mechanical ventilation if they did not have infection on admission . Infected patients who were admitted to the intensive care unit received other parenteral antibiotics according to clinical decisions . Prophylaxis for stress ulcers was done using 1 g of sucralfate every 4 hours ( Urbal ; Merck-Igoda SA , Mollet del Valles ) through a nasogastric tube , except in patients with paralytic ileus or with upper gastrointestinal bleeding , who were treated with 50 mg of intravenous ranitidine , four times a day ( Zantac ; Glaxo SA-Allen Farmaceutica SA , Madrid ) . Bacteriologic Assessment Endotracheal aspirates , pharyngeal swabs , and gastric juice sample s were obtained three times a week for quantitative cultures . Endotracheal aspirate sample s were obtained by means of sterile tubes ( Mocstrap ; Productes Clinics , SA , La Llagosta , Barcelona ) . Sample s obtained were diluted and homogenized in distilled water to 1/2 concentration using a vortex-style shaker ( Reax 2000 ; Heidolph , Germany ) and were rediluted in distilled water to 1/20 and 1/200 concentrations . Pharyngeal swabs were obtained using sterile swabs with Amies transport media ( Eurotubo ; Industrias Aulabor SA , Barcelona ) , were homogenized in 1 mL of distilled water , and were diluted to concentrations of 1/10 , 1/102 , and 1/103 . Gastric juice sample s were obtained by aspiration through a nasogastric tube using a sterile feeding syringe . The pH was determined in all the sample s using paper indicators ( Acilit , pH 0 to 6 and Spezialindikator , pH 6.5 to 10 ; Merck , Darmstadt , Germany ) . The sample s were homogenized using a vortex-style shaker and were diluted in distilled water to concentrations of 1/10 and 1/100 . All sample s were plated on the following agar media : blood ; chocolate ; McConkey-2 ; buffered , charcoal , and yeast extract ( BCYEa ) ; Sabouraud-dextrose ; Sabouraud with nalidixic acid ; and blood with nalidixic acid . If negative , the plates were discarded after 5 days of testing for aerobic bacteria , after 10 days of testing for Legionella and anaerobic bacteria , and after 4 weeks of testing for fungi . If positive , counts of colony-forming units per milliliter and identification using st and ard methods [ 31 ] were done for the microorganisms . Definitions Potentially pathogenic microorganisms were defined [ 32 ] as those causing infection in a person with impaired defense mechanisms . They can be classified into community microorganisms , which cause infections in previously healthy persons with intact carriage defense , and nosocomial microorganisms , which cause infections in persons with impaired carriage defense . Colonization was defined as the isolation of the same strain of a potentially pathogenic microorganism from at least two consecutive surveillance sample s in any concentration . The clinical diagnosis of pneumonia was based on the presence of all of the following criteria : new or progressive pulmonary radiologic infiltrate or both for 48 hours or more , purulent tracheal secretions , temperature of 38.5 C or more , and leukocytosis ( 12 109/L ) or leukopenia ( 4 109/L ) . The diagnosis of pneumonia was confirmed by the isolation of a potentially pathogenic microorganism in a protected specimen brush sample in concentrations of 103 CFU/mL or more or in a bronchoalveolar lavage sampling in concentrations of 104 CFU/mL or more [ 33 ] . We defined definite pneumonia when all the clinical criteria and one bacteriologic criterion were present or by the presence of histologic signs of pneumonia at autopsy . Probable pneumonia was defined when only clinical criteria were present . Primary endogenous pneumonia was diagnosed when pneumonia developed within the first 4 days of mechanical ventilation and when etiologic microorganisms were isolated previously or concomitantly in pharyngeal swabs or in gastric juice . Secondary endogenous pneumonia was pneumonia that developed after the fourth day of mechanical ventilation . Exogenous pneumonia was diagnosed when the etiologic microorganism was not isolated in pharyngeal swabs or in gastric juice before the development of pneumonia . Community flora was defined as the isolation of normal buccal flora ( Neisseria species , Streptococcus viridans , among others ) , Streptococcus pneumoniae , or Haemophilus influenzae . A catheter-related infection was diagnosed when inflammatory signs occurred in a catheterized blood vessel together with a temperature of 38.3 C or more , irrespective of the isolation of a potentially pathogenic microorganism in the culture of the removed catheter . Likewise , this diagnosis was considered if the fever improved within 12 hours after removing the catheter . A urinary tract infection was diagnosed after fresh-voided catheter urine containing five or more leukocytes per high-power light-microscopic field were identified and a potentially pathogenic microorganism was isolated in urine culture in concentrations of 105 CFU/mL or more . A wound infection was diagnosed if purulent secretions from wounds occurred with signs of inflammation and the isolation of a potentially pathogenic microorganism in concentrations of 105 CFU/mL or more from the purulent wound secretions . Septicemia was diagnosed if clinical signs of systemic infection occurred , such as fever , leukocytosis , increased percentage of b and forms , and metabolic acidosis , combined with a positive blood culture . Multiple organ system failure was defined as three or more organ systems failing for more than 2 consecutive days . Objective : To evaluate the effect of selective digestive decontamination on endotoxemia and cytokine activation during the ischemic phase of cardiopulmonary bypass surgery . Design : Prospect i ve , open , r and omized , controlled trial . Setting : Two multidisciplinary intensive care units in tertiary care hospitals . Patients : Eighty consecutive patients r and omly allocated to two groups : selective digestive decontamination ( group 1 , n = 40 ) and controls ( group 2 , n = 40 ) . Interventions : Preoperative administration of oral antibiotics ( polymyxin E , tobramycin , and amphotericin B ) vs. untreated controls . Measurements and Main Results : Assessment of decontamination by bacteriologic evaluation of rectal swabs ( colony-forming units [cfu]/mL ) were made in each group , along with circulating endotoxin , tumor necrosis factor and interleu-kin-6 ( IL-6 ) determinations before surgery , during ischemic and reperfusion phases of bypass , and at 4 hrs and at 24 hrs after surgery . Group 1 patients showed that rectal bacteria decreased ten-fold after treatment for 24 hrs , thous and -fold after 48 hrs , and registered 0 cfu/mL after digestive decontamination was administered for > 72 hrs . Endotoxin and IL-6 assays showed significantly lower values in this latter group vs. those circulating concentrations of control patients . On the other h and , both endotoxin and IL-6 concentrations correlated positively with the duration of surgical ischemia . Conclusions : Selective digestive decontamination reduces the gut content of enterobacteria , with complete elimination after 3 days of treatment . This fact could explain the lower endotoxin and cytokine concentrations found in the blood sample s of patients who had been fully decontaminated . Duration of aortic cross-clamping is an important factor in generating endotoxemia and in the activation of cytokines.(Crit Care Med 1993 ; 21:1684–1691 In a r and omized clinical trial the prophylactic effects of locally administered antimicrobials on quantitative colonization and respiratory infections were studied in intubated patients with an expected period of mechanical ventilation of > 6 days . Nineteen patients received 50 mg of polymyxin B and 80 mg of gentamicin distributed among nose , oropharynx and stomach at 6-h intervals , as well as 300 mg of amphotericin B in the oropharynx . Twenty untreated patients served as controls . In the control group colonization by respiratory pathogens was more common ( oropharynx 19 vs 6 patients ( p(0.001 ) ; trachea 19 vs 11 ( p(0.01 ) ) , and the number as well as the count of the colonizing species was usually higher . Fourteen patients of the control group developed respiratory infections , including nine cases of pneumonia , as compared to four patients with prophylaxis , including one case of pneumonia ( p(0.01 ) . Pneumonia-associated deaths were prevented with prophylaxis ; however , the overall mortality remained unchanged . Respiratory infections in the prophylaxis group were associated with organisms resistant to the agents used , but the overall occurrence of resistance was not increased , as compared to the control group . We conclude that unrestrained upper airway colonization by respiratory pathogens and respiratory tract infection were causally related . Local antimicrobial prophylaxis proved to be a highly effective strategy for the prevention of potentially life-threatening pneumonias in critically ill patients but in the present study the host setting appeared to be the major determinant of outcome The incidence of nosocomial pneumonia in long-term ventilated patients has been reduced by stress ulcer prophylaxis with sucralfate . In a double-blind trial we studied whether gentamicin administered topically to the oropharynx ( OPG ) had additional clinical benefits in these patients . 67 critically ill adult patients fulfilled entry criteria for > or = 5 days on ventilation . The OPG group received 40 mg gentamicin , the control group received 5 % dextrose topically administered to the oropharynx 4 times a day . During OPG , pharyngeal colonization rate ( 21 vs 44 % ) and tracheal secretion colonization rate ( 12 vs 41 % ) were significantly lower than during placebo ( p < 0.05 ) . Despite these differences nosocomial pneumonia rate ( 3 vs 12 % ) , duration of mechanical ventilation [ 15.8 + /- 11.1 vs 19.9 + /- 37.5 days ( means + /- SD ) ] and mortality ( 27 vs 41 % ) were not significantly affected by OPG . Moreover , 13 of 15 bacteria ( 87 % ) that occurred during OPG were resistant to gentamicin . Despite its reduction of bacterial colonization rates of pharyngeal and tracheal secretions , OPG did not seem to offer additional clinical benefits in long-term mechanically ventilated patients on stress ulcer prophylaxis with sucralfate Objective A r and omized , controlled , multicenter trial was undertaken in 102 patients with objective evidence of severe acute pancreatitis to evaluate whether selective decontamination reduces mortality . Summary Background Data Secondary pancreatic infection is the major cause of death in patients with acute necrotizing pancreatitis . Controlled clinical trials to study the effect of selective decontamination in such patients are not available . Methods Between April 22 , 1990 and April 19 , 1993 , 102 patients with severe acute pancreatitis were admitted to 16 participating hospitals . Patients were entered into the study if severe acute pancreatitis was indicated , on admission , by multiple laboratory criteria ( Imrie score ≥ 3 ) and /or computed tomography criteria ( Balthazar grade D or E ) . Patents were r and omly assigned to receive st and ard treatment ( control group ) or st and ard treatment plus selective decontamination ( norfloxacin , colistin , amphotericin ; selective decontamination group ) . All patients received full supportive treatment , and surveillance cultures were taken in both groups . Results Fifty patients were assigned to the selective decontamination group and 52 were assigned to the control group . There were 18 deaths in the control group ( 35 % ) , compared with 11 deaths ( 22 % ) in the selective decontamination group . ( adjusted for Imrie score and Balthazar grade : p = 0.048 ) . This difference was mainly caused by a reduction of late mortality ( > 2 weeks ) due to significant reduction of gram-negative pancreatic infection ( p = 0.003 ) . The average number of laparotomies per patient was reduced in patients treated with selective decontamination ( p < 0.05 ) . Failure of selective decontamination to prevent secondary gram-negative pancreatic infection with subsequent death was seen in only three patients ( 6 % ) and transient gram-negative pancreatic infection was seen in one ( 2 % ) . In both groups of patients , all gram-negative aerobic pancreatic infection was preceded by colonization of the digestive tract by the same bacteria Objective : To determine the influence of selective oropharyngeal decontamination ( SOD ) on the rate of colonization and infection of the respiratory tract in intensive care patients requiring mechanical ventilation for more than 4 days . A financial assessment was also performed . Design : R and omized , prospect i ve , controlled study using amphotericin B , colistin sulfate ( polymyxin E ) , and tobramycin applied to the oropharynx and systemic cefotaxime prophylaxis . Setting : Anesthesiology intensive care unit ( ICU ) of a 1500-bed hospital . Patients : A total of 88 patients admitted as emergencies and intubated within less than 24 h were enrolled . Fifty- eight patients received SOD and 30 patients served as controls . R and omization was in the proportion of 2 : 1 study patients to controls . Interventions : Microbiological sample s from the oropharynx and other infected sites were taken at the time of admission , then twice a week and after extubation . Measurements and results : With the use of SOD , colonization was significantly reduced . Furthermore , the infection rate decreased from 77 % in the controls to 22 % in the study patients . Staphylococcus aureus was the main potential pathogen causing colonization and pneumonia . Number of days in the ICU , duration of ventilation , and mortality were not significantly decreased . The total cost of antibiotics was reduced . Development of resistance was not observed . Conclusions : The use of SOD significantly reduced the colonization and pneumonia and the total charge for antibiotics . The length of stay in the ICU , duration of ventilation , and mortality were similar . No resistance was observed . Staphylococcus aureus was selected by SOD in some patients and the clinical relevance needs further observation Objective : To examine the effect of selective antibiotic decontamination of the digestive tract in patients undergoing elective orthotopic liver transplantation . Design : Prospect i ve , r and omized , concurrent allocation to either selective decontamination or st and ard antibiotic prophylaxis . Setting : Operating theater and intensive care unit at a tertiary referral , university teaching hospital . Patients : Fifty‐nine adult patients were recruited into the study and underwent liver transplantation . Interventions : Thirty‐two patients were r and omized to st and ard treatment ( control group ) and 27 patients were r and omized to receive selective decontamination . After early deaths and exclusions , 31 controls and 21 decontamination patients were available for analysis . Measurements and Main Results : Portal and systemic endotoxemia , colonization and infection rates , severity of illness ( organ system failures , Acute Physiology and Chronic Health Evaluation II score , Therapeutic Intervention Scoring System score ) , antibiotic costs , and hospital survival rates were measured . Selective decontamination significantly reduced pulmonary infections and enteric , aerobic , and Gram‐negative bacillary colonization without facilitating the emergence of resistant organisms , but selective decontamination had no effect on endotoxemia or the development of organ system failures . The financial costs of the selective decontamination regimen outweighed the advantages gained from an associated reduction in antibiotic usage . Conclusion : The failure of selective decontamination to enhance survival rates in many studies of the regimen in critically ill patients may , in part , be related to the inability of selective decontamination to abolish endotoxemia . ( Crit Care Med 1994 ; 22:40‐49 OBJECTIVE To evaluate the efficacy of two regimens of selective decontamination of the digestive tract in mechanically ventilated patients . DESIGN Prospect i ve , r and omized , concurrent trial . SETTING Multidisciplinary intensive care unit ( ICU ) in a 1,800-bed university hospital . PATIENTS Consecutive patients ( n = 660 ) who were likely to require mechanical ventilation for at least 48 hrs were r and omized to one of three groups : conventional antibiotic regimen ( control group A ) ; oral and enteral ofloxacin-amphotericin B ( group B ) ; and oral and enteral polymyxin E-tobramycin-amphotericin B ( group C ) . Both treatment groups received systemic antibiotics for 4 days ( ofloxacin in group B and cefotaxime in group C ) . INTERVENTIONS Patients were r and omized to receive st and ard treatment ( control group A , n = 220 ) , selective decontamination regimen B ( group B , n = 220 ) , and selective decontamination regimen C ( group C , n = 220 ) . After early deaths and exclusions from the study , 185 controls ( group A ) and 193 ( group B)/200 ( group C ) selective decontamination regimen patients were available for analysis . MEASUREMENTS AND MAIN RESULTS Measurements included colonization and primary / secondary infection rate , ICU mortality rate , emergence of antibiotic resistance , length of ICU stay , and antimicrobial agent costs . The study duration was 19 months . The patient groups were fully comparable for age , diagnostic category , and severity of illness . One third of patients in each group suffered a nosocomial infection at the time of admission . There was a significant difference between treatment group B and control group A in the number of infected patients ( odds ratio of 0.42 , 95 % confidence interval of 0.27 to 0.64 ) , secondary lower respiratory tract infection ( odds ratio of 0.47 , 95 % confidence interval of 0.26 to 0.82 ) , and urinary tract infection ( odds ratio of 0.47 , 95 % confidence interval of 0.27 to 0.81 ) . Significantly more Gram-positive bacteremias occurred in treatment group C vs. group A ( odds ratio of 1.22 , 95 % confidence interval 0.72 to 2.08 ) . Infection at the time of admission proved to be the most significant risk factor for subsequent infection in control and both treatment groups . ICU mortality rate was almost identical ( group A 16.8 % , group B 17.6 % , and group C 15.5 % ) and was not significantly related to primary or secondary infection . Increased antimicrobial resistance was recorded in both treatment groups : tobramycin-resistant enterobacteriaceae ( group C 48 % vs. group A 14 % , p < .01 ) , ofloxacin-resistant enterobacteriaceae ( group B 50 % vs. group A 11 % , p < .02 ) , ofloxacin-resistant nonfermenters ( group B 81 % vs. group A 52 % , p < .02 ) , and methicillin-resistant Staphylococcus aureus ( group C 83 % vs. group A 55 % , p < .05 ) . Antimicrobial agent costs were comparable in control and group C patients ; one third less was spent for group B patients . CONCLUSIONS In cases of high colonization and infection rates at the time of ICU admission , the preventive benefit of selective decontamination is highly debatable . Emergence of multiple antibiotic-resistant microorganisms creates a clinical problem and a definite change in the ecology of environmental , colonizing , and infecting bacteria . The selection of multiple antibiotic-resistant Gram-positive cocci is particularly hazardous . No beneficial effect on survival is observed . Moreover , selective decontamination adds substantially to the cost of ICU care Although it has been suggested that selective decontamination of the digestive tract ( SDD ) decreases postoperative aerobic Gram-negative and fungal infections in orthotopic liver transplantation ( OLT ) , no controlled trials exist in pediatric patients . This prospect i ve , r and omized controlled study of 36 pediatric OLT patients examines the effect of short-term SDD on postoperative infection and digestive tract flora . Patients were r and omized into two groups . The control group received perioperative parenteral antibiotics only . The SDD group received in addition polymyxin E , tobramycin , and amphotericin B enterally and by oropharyngeal swab postoperatively until oral intake was tolerated ( 6 + /- 4 days ) . Indications for operation , preoperative status , age , and intensive care unit and hospital length of stay were no different in SDD ( n = 18 ) and control ( n = 18 ) groups . A total of 14 Gram-negative infections ( intraabdominal abscess 7 , septicemia 5 , pneumonia 1 , urinary tract 1 ) developed in the 36 patients studied . Mortality was not significantly different in the two groups . However , there were significantly fewer patients with Gram-negative infections in the SDD group : 3/18 patients ( 11 % ) vs. 11/18 patients ( 50 % ) in the control group , P < 0.001 . There was also significant reduction in aerobic Gram-negative flora in the stool and pharynx in patients receiving SDD . Gram-positive and anaerobic organisms were unaffected . We conclude that short-term postoperative SDD significantly reduces Gram-negative infections in pediatric OLT patients 181 patients undergoing resection of the oesophagus for carcinoma were r and omised to receive selective decontamination ( test group ) or conventional perioperative antibiotic prophylaxis ( controls ) . 114 patients were finally included in the study : 12 of 56 test patients had 18 infections , whereas 32 of 58 controls acquired 51 infections . Colonisation with aerobic gram-negative microorganisms , and the number of postoperative respiratory tract infections were significantly lower in the test patients . The postoperative therapeutic use of antibiotics was significantly lower in the test group . No endogenous infections were caused by gram-negative bacilli in the test group . Selective decontamination reduces colonisation with gram-negative bacilli and postoperative infections after resection of the oesophagus BACKGROUND Selective decontamination of the digestive tract with topical nonabsorbable antibiotics has been reported to prevent nosocomial infections in patients receiving mechanical ventilation , and the procedure is used widely in Europe . However , it is unclear whether selective decontamination improves survival . METHODS We conducted a r and omized , double-blind multicenter study in which 445 patients receiving mechanical ventilation in 15 intensive care units were given either prophylactic nonabsorbable antibiotics ( n = 220 ) or a placebo ( n = 225 ) . Topical antibiotics ( tobramycin , colistin sulfate , and amphotericin B ) or a placebo was administered through a nasogastric tube and applied to the oropharynx throughout the period of ventilation . The main end points were the mortality rate in the intensive care unit and within 60 days of r and omization . RESULTS A total of 142 patients died in the intensive care unit ; 75 ( 34 percent ) in the treatment group and 67 ( 30 percent ) in the placebo group ( P = 0.37 ) . Mortality within 60 days of r and omization was similar in the two groups ( P = 0.40 ) , even after adjustment for factors that were either unbalanced or individually predictive of survival in the two groups ( P = 0.70 ) . Pneumonia developed in 59 patients ( 13 percent ) in the intensive care unit within 30 days of enrollment in the study ( 33 in the placebo group and 26 in the treatment group , P = 0.42 ) . Pneumonia acquired in the intensive care unit and due to gram-negative bacilli was less frequent ( P = 0.01 ) in the treatment group than in the placebo group . The total charges for antibiotics were 2.2 times higher in the treatment group . CONCLUSIONS Selective decontamination of the digestive tract does not improve survival among patients receiving mechanical ventilation in the intensive care unit , although it substantially increases the cost of their care Nosocomial infection is a major problem in intensive therapy units ( ITUs ) and a significant cause of mortality . Selective decontamination of the digestive tract ( SDD ) has been advocated as a means to reduce ITU morbidity and mortality . Ninety-one patients in a general ITU underwent SDD , consisting of topical polymyxin E , tobramycin and amphotericin B administered throughout the unit stay together with parenteral ceftazidime for the first three days , and were compared with 84 historical and 92 contemporaneous control patients who were treated conventionally . Twenty-seven historical and 32 contemporaneous control patients developed unit-acquired infections , in comparison with only three patients in the SDD group ( P less than 0.01 ) . Mortality in the SDD group ( 36 % ) was not significantly different from that in the other two groups ( historical control 40 % , contemporaneous control 43 % ) . Screening specimens revealed a significantly higher rate of colonization with resistant Acinetobacter spp . in the contemporaneous control than in the other two groups of patients ; infection caused by resistant bacteria did not occur . SDD did not lead to a significant reduction in the use of systemically-administered antibiotics when compared with either control group . SDD may be used selectively in an ITU without ill effects on those patients not receiving SDD ; nevertheless , microbiological monitoring is needed to detect emergence of resistant bacteria in the unit A r and omized , double-blind , placebo-controlled trial of selective decontamination of the oropharynx and gastrointestinal tract was conducted on 61 intubated patients in a medical-surgical intensive care unit ( ICU ) to determine the impact on nosocomial pneumonia , other infections , and emergence of colonization or infection with antibiotic-resistant bacteria . Over 8 months , 30 patients received an oral paste and solution containing polymyxin , gentamicin , and nystatin ; 31 patients received a placebo paste and solution . At study entry , patients in both groups were seriously ill ( mean acute physiologic score , 27.2 ) , frequently had pulmonary infiltrates ( 73.8 % ) , and were likely to be receiving systemic antibiotics ( 86.9 % ) . There were no differences between study patients and control patients in these characteristics or in frequency of any nosocomial infection ( 50 % vs. 55 % ) , nosocomial pneumonia ( 27 % vs. 26 % ) , febrile days ( 2.3 vs. 2.0 ) , duration of antibiotic therapy ( 14.0 vs. 13.4 ) , or mortality rates ( 37 % vs. 48 % ) . There was no difference in infections caused by antibiotic-resistant gram-negative bacilli , although a trend towards more frequent infection with gentamicin-resistant enterococci was found for study patients . Selective decontamination did not appear to be effective in our very ill medical-surgical ICU patients , although the number of patients in our trial was sufficient to detect only a 50 % or greater reduction in pneumonia rates Long-term beta blockade for perhaps a year or so following discharge after an MI is now of proven value , and for many such patients mortality reductions of about 25 % can be achieved . No important differences are clearly apparent among the benefits of different beta blockers , although some are more convenient than others ( or have slightly fewer side effects ) , and it appears that those with appreciable intrinsic sympathomimetic activity may confer less benefit . If monitored , the side effects of long-term therapy are not a major problem , as when they occur they are easily reversible by changing the beta blocker or by discontinuation of treatment . By contrast , although very early IV short-term beta blockade can definitely limit infa rct size , more reliable information about the effects of such treatment on mortality will not be available until a large trial ( ISIS ) reports later this year , with data on some thous and s of patients entered within less than 4 hours of the onset of pain . Our aim has been not only to review the 65-odd r and omized beta blocker trials but also to demonstrate that when many r and omized trials have all applied one general approach to treatment , it is often not appropriate to base inference on individual trial results . Although there will usually be important differences from one trial to another ( in eligibility , treatment , end-point assessment , and so on ) , physicians who wish to decide whether to adopt a particular treatment policy should try to make their decision in the light of an overview of all these related r and omized trials and not just a few particular trial results . Although most trials are too small to be individually reliable , this defect of size may be rectified by an overview of many trials , as long as appropriate statistical methods are used . Fortunately , robust statistical methods exist -- based on direct , unweighted summation of one O-E value from each trial -- that are simple for physicians to use and underst and yet provide full statistical sensitivity . These methods allow combination of information from different trials while avoiding the unjustified direct comparison of patients in one trial with patients in another . ( Moreover , they can be extended of such data that there is no real need for the introduction of any more complex statistical methods that might be more difficult for physicians to trust . ) Their robustness , sensitivity , and avoidance of unnecessary complexity make these particular methods an important tool in trial overviews |
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