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1,800 | 32,212,412 | The effect of e-health educational interventions on HbA1c in patients with T1D is comparable to the st and ard care . | AIMS Patient-centered education improves glycemic control in subjects with type 1 diabetes ( T1D ) .
E-health technologies are widely used to support medical decision-making , patient advising or teleconsultations ; however , the active participation of a patient is missing .
Challenges remain whether e-health education can be effectively incorporated into clinical pathways .
The purpose of the study was to examine the effects of e-health education , compared to st and ard care , on HbA1c . | OBJECTIVE The objective of this study was to compare the relative effectiveness of two modes of delivering Behavioral Family Systems Therapy for Diabetes ( BFST-D ) to improve adherence and glycemic control among adolescents with type 1 diabetes with suboptimal glycemic control ( HbA1c ≥9.0 % [ ≥74.9 mmol/mol ] ) : face to face in clinic ( Clinic ) and Internet videoconferencing ( Skype ) conditions . RESEARCH DESIGN AND METHODS Adolescents aged 12 to 18 years and at least one adult caregiver were r and omized to receive BFST-D via the Clinic or Skype condition . Participants completed up to 10 therapy sessions within a 12-week period . Changes in youth- and parent-reported adherence and glycemic control were compared before and after the intervention and at follow-up assessment . RESULTS Using an intent-to-treat analytic approach , no significant between-group differences were identified between the before , after , and follow-up assessment s. Groups were collapsed to examine the overall effects of BFST-D on adherence and glycemic control . Results identified that statistically significant improvements in adherence and glycemic control occurred from before to after the intervention ; improvements were maintained at 3-month follow-up . CONCLUSIONS Delivery of BFST-D via Internet-based videoconferencing is viable for addressing nonadherence and suboptimal glycemic control in adolescents with type 1 diabetes , potentially reducing important barriers to care for youth and families The purpose of this report is to summarize and integrate the findings of the Diabetes Control and Complications Trial ( DCCT ) , a r and omized controlled clinical trial , and the succeeding observational follow-up of the DCCT cohort in the Epidemiology of Diabetes Interventions and Complications ( EDIC ) study , regarding the effects of intensive treatment on the microvascular complications of type 1 diabetes mellitus . The DCCT proved that intensive treatment reduced the risks of retinopathy , nephropathy , and neuropathy by 35 % to 90 % compared with conventional treatment . The absolute risks of retinopathy and nephropathy were proportional to the mean glycosylated hemoglobin ( HbA(1c ) ) level over the follow-up period preceding each event . Intensive treatment was most effective when begun early , before complications were detectable . These risk reductions , achieved at a median HbA(1c ) level difference of 9.1 % for conventional treatment vs 7.3 % for intensive treatment have been maintained through 7 years of EDIC , even though the difference in mean HbA(1c ) levels of the 2 former r and omized treatment groups was only 0.4 % at 1 year ( P<.001 ) ( 8.3 % in the former conventional treatment group vs 7.9 % in the former intensive treatment group ) , continued to narrow , and became statistically nonsignificant by 5 years ( 8.1 % vs 8.2 % , P = .09 ) . The further rate of progression of complications from their levels at the end of the DCCT remains less in the former intensive treatment group . Thus , the benefits of 6.5 years of intensive treatment extend well beyond the period of its most intensive implementation . Intensive treatment should be started as soon as is safely possible after the onset of type 1 diabetes mellitus and maintained thereafter , aim ing for a practicable target HbA(1c ) level of 7.0 % or less OBJECTIVE Widespread use of carbohydrate counting is limited by its complex education . In this study we compared a Diabetes Interactive Diary ( DID ) with st and ard carbohydrate counting in terms of metabolic and weight control , time required for education , quality of life , and treatment satisfaction . RESEARCH DESIGN AND METHODS Adults with type 1 diabetes were r and omly assigned to DID ( group A , n = 67 ) or st and ard education ( group B , n = 63 ) and followed for 6 months . A subgroup also completed the SF-36 Health Survey ( SF-36 ) and World Health Organization-Diabetes Treatment Satisfaction Question naire ( WHO-DTSQ ) at each visit . RESULTS Of 130 patients ( aged 35.7 ± 9.4 years ; diabetes duration 16.5 ± 10.5 years ) , 11 dropped out . Time for education was 6 h ( range 2–15 h ) in group A and 12 h ( 2.5–25 h ) in group B ( P = 0.07 ) . A1C reduction was similar in both groups ( group A from 8.2 ± 0.8 to 7.8 ± 0.8 % and group B from 8.4 ± 0.7 to 7.9 ± 1.1 % ; P = 0.68 ) . Nonsignificant differences in favor of group A were documented for fasting blood glucose and body weight . No severe hypoglycemic episode occurred . WHO-DTSQ scores increased significantly more in group A ( from 26.7 ± 4.4 to 30.3 ± 4.5 ) than in group B ( from 27.5 ± 4.8 to 28.6 ± 5.1 ) ( P = 0.04 ) . Role Physical , General Health , Vitality , and Role Emotional SF-36 scores improved significantly more in group A than in group B. CONCLUSIONS DID is at least as effective as traditional carbohydrate counting education , allowing dietary freedom for a larger proportion of type 1 diabetic patients . DID is safe , requires less time for education , and is associated with lower weight gain . DID significantly improved treatment satisfaction and several quality -of-life dimensions OBJECTIVE To conduct a 1-year r and omized clinical trial to evaluate a remote comprehensive diabetes self-management education ( DSME ) intervention , Diabetes TeleCare , administered by a dietitian and nurse/certified diabetes educator ( CDE ) in the setting of a federally qualified health center ( FQHC ) in rural South Carolina . RESEARCH DESIGN AND METHODS Participants were recruited from three member health centers of an FQHC and were r and omized to either Diabetes TeleCare , a 12-month , 13-session curriculum delivered using telehealth strategies , or usual care . RESULTS Mixed linear regression model results for repeated measures showed a significant reduction in glycated hemoglobin ( GHb ) in the Diabetes TeleCare group from baseline to 6 and 12 months ( 9.4 ± 0.3 , 8.3 ± 0.3 , and 8.2 ± 0.4 , respectively ) compared with usual care ( 8.8 ± 0.3 , 8.6 ± 0.3 , and 8.6 ± 0.3 , respectively ) . LDL cholesterol was reduced at 12 months in the Diabetes TeleCare group compared with usual care . Although not part of the original study design , GHb was reduced from baseline to 12 and 24 months in the Diabetes TeleCare group ( 9.2 ± 0.4 , 7.4 ± 0.5 , and 7.6 ± 0.5 , respectively ) compared with usual care ( 8.7 ± 0.4 , 8.1 ± 0.4 , and 8.1 ± 0.5 , respectively ) in a post hoc analysis of a subset of the r and omized sample who completed a 24-month follow-up visit . CONCLUSIONS Telehealth effectively created access to successfully conduct a 1-year remote DSME by a nurse CDE and dietitian that improved metabolic control and reduced cardiovascular risk in an ethnically diverse and rural population The CONSORT ( Consoli date d St and ards of Reporting Trials ) statement is used worldwide to improve the reporting of r and omized , controlled trials . Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . BACKGROUND The objective was to compare glycemic control between prepr and ial and postpr and ial bolus administration ( 15 min before [ PRE ] or immediately after the meal [ POST ] ) in patients with type 1 diabetes using insulin pump and real-time continuous glucose monitoring . METHODS Between September 2015 and February 2016 , a single-centre , open r and omized , 2-way crossover study of patients on bolus insulin aspart administration was conducted during two 14-day periods and according to 2 administration regimen schedules ( PRE/POST or POST/PRE ) . Inclusion criteria were as follows : patients with type 1 diabetes , ≥18 and ≤ 65 years old , treated with insulin aspart using a Medtronic ® insulin pump and trained on functional insulin therapy . Patients were r and omly assigned to either regimen schedule . At the beginning of each period , each patient was provided with a st and ardized high fat meal . Primary outcome was the area under the curve for interstitial glucose above 140 mg/dL per minute ( AUC > 140 mg/dL/min ) during each period . Secondary outcomes were time spent in hypo/eu/hyperglycemia , glycemic variability indices , and AUC during 4 hours after high fat meal calculated with continuous glucose monitoring data . RESULTS Twenty-two patients were included . Mean AUC > 140 mg/dL/min was statistically higher in patients on POST ( 43.70 mg/dL/min ; 95%CI : 34.08 to 53.31 ) versus PRE insulin aspart regimen ( 37.24 mg/dL/min 95%CI : 27.63 to 46.85 ) ( P = 0.03 ) . Mean interstitial glycemia and glycemic variability indices were also increased ( P < 0.05 ) on POST regimen . The mean AUC 4 hours after the high fat meal was higher on POST regimen but not statistically different ( P = 0.06 ) . CONCLUSIONS In our study , postpr and ial administration of insulin aspart appears to mildly increase glycemic excursion and glycemic variability OBJECTIVE To report results from YourWay , an Internet-based self-management intervention for adolescents with type 1 diabetes . RESEARCH DESIGN AND METHODS A total of 72 adolescents with type 1 diabetes , ages 13–17 years , were r and omized to a usual-care-plus-Internet support or a usual-care group . The intervention was design ed to enhance problem-solving barriers to self-management . A1C was obtained from medical records , and problem-solving and self-management were obtained via adolescent report . RESULTS Group differences were not statistically significant using intent-to-treat analyses . Using as-treated analyses , adolescents in the treatment condition showed statistically significant improvement in self-management ( d = 0.64 ; P = 0.02 ) and important improvements in problem-solving ( d = 0.30 ; P = 0.23 ) and A1C ( d = −0.28 ; P = 0.27 ) . Mean A1C for the intervention group remained constant ( −0.01 % ) , while the control group increased ( 0.33 % ) . CONCLUSIONS This brief trial suggests that self-management support delivered through a secure website may improve self-management and offset typical decreases in adolescent glycemic control OBJECTIVE DAFNE ( Dose Adjustment For Normal Eating ) , a structured education program in flexible insulin therapy , has been widely adopted in the U.K. after validation in a r and omized trial . To determine benefits in routine practice , we collected biomedical and psychological data from all participants attending during a 12-month period . RESEARCH DESIGN AND METHODS HbA1c , weight , self-reported hypoglycemia awareness , severe hypoglycemia frequency , PAID ( Problem Areas In Diabetes ) , HADS ( Hospital Anxiety and Depression Scale ) , and EuroQol Group 5-Dimension Self-Report Question naire scores were recorded prior to DAFNE and after 1 year . RESULTS Complete baseline and follow-up HbA1c data were available for 639 ( 54.9 % ) of 1,163 attendees . HbA1c fell from 8.51 ± 1.41 ( mean ± SD ) to 8.24 ± 1.29 % ( difference 0.27 [ 95 % CI 0.16–0.38 ] ; P < 0.001 ) , with a greater mean fall of 0.44 % from baseline HbA1c > 8.5 % . Severe hypoglycemia rate fell from 1.7 ± 8.5 to 0.6 ± 3.7 episodes per person per year ( 1.1 [ 0.7–1.4 ] ) and hypoglycemia recognition improved in 43 % of those reporting unawareness . Baseline psychological distress was evident , with a PAID score of 25.2 and HADS scores of 5.3 ( anxiety ) and 4.8 ( depression ) , falling to 16.7 ( 8.5 [ 6.6–10.4 ] ) , 4.6 ( 0.7 [ 0.4–1.0 ] ) , and 4.2 ( 0.6 [ 0.3–0.8 ] ) , respectively ( all P < 0.001 at 1 year ) . Clinical ly relevant anxiety and depression ( HADS ≥8 ) fell from 24.4 to 18.0 % and 20.9 to 15.5 % , respectively . CONCLUSIONS A structured education program delivered in routine clinical practice not only improves HbA1c while reducing severe hypoglycemia rate and restoring hypoglycemia awareness but also reduces psychological distress and improves perceived well-being Background Method ological guidelines for intervention reporting emphasise describing intervention content in detail . Despite this , systematic review s of quality improvement ( QI ) implementation interventions continue to be limited by a lack of clarity and detail regarding the intervention content being evaluated . We aim ed to apply the recently developed Behaviour Change Techniques Taxonomy version 1 ( BCTTv1 ) to trials of implementation interventions for managing diabetes to assess the capacity and utility of this taxonomy for characterising active ingredients . Methods Three psychologists independently coded a r and om sample of 23 trials of healthcare system , provider- and /or patient-focused implementation interventions from a systematic review that included 142 such studies . Intervention content was coded using the BCTTv1 , which describes 93 behaviour change techniques ( BCTs ) grouped within 16 categories . We supplemented the generic coding instructions within the BCTTv1 with decision rules and examples from this literature . Results Less than a quarter of possible BCTs within the BCTTv1 were identified . For implementation interventions targeting providers , the most commonly identified BCTs included the following : adding objects to the environment , prompts/cues , instruction on how to perform the behaviour , credible source , goal setting ( outcome ) , feedback on outcome of behaviour , and social support ( practical ) . For implementation interventions also targeting patients , the most commonly identified BCTs included the following : prompts/cues , instruction on how to perform the behaviour , information about health consequences , restructuring the social environment , adding objects to the environment , social support ( practical ) , and goal setting ( behaviour ) . The BCTTv1 mapped well onto implementation interventions directly targeting clinicians and patients and could also be used to examine the impact of system-level interventions on clinician and patient behaviour . Conclusions The BCTTv1 can be used to characterise the active ingredients in trials of implementation interventions and provides specificity of content beyond what is given by broader intervention labels . Identification of BCTs may provide a more helpful means of accumulating knowledge on the content used in trials of implementation interventions , which may help to better inform replication efforts . In addition , prospect i ve use of a behaviour change techniques taxonomy for developing and reporting intervention content would further aid in building a cumulative science of effective implementation interventions Background Persistently poor glycemic control in adult type 1 diabetes patients is a common , complex , and serious problem initiating significant damage to the cardiovascular , renal , neural , and visual systems . Currently , there is a plethora of low-cost and free diabetes self-management smartphone applications available in online stores . Objective The aim of this study was to examine the effectiveness of a freely available smartphone application combined with text-message feedback from a certified diabetes educator to improve glycemic control and other diabetes-related outcomes in adult patients with type 1 diabetes in a two-group r and omized controlled trial . Methods Patients were recruited through an online type 1 diabetes support group and letters mailed to adults with type 1 diabetes throughout Australia . In a 6-month intervention , followed by a three-month follow-up , patients ( n=72 ) were r and omized to usual care ( control group ) or usual care and the use of a smartphone application ( Glucose Buddy ) with weekly text-message feedback from a Certified Diabetes Educator ( intervention group ) . All outcome measures were collected at baseline and every three months over the study period . Patients ’ glycosylated hemoglobin levels ( HbA1c ) were measured with a blood test and diabetes-related self-efficacy , self-care activities , and quality of life were measured with online question naires . Results The mean age of patients was 35.20 years ( SD 10.43 ) ( 28 male , 44 female ) , 39 % ( 28/72 ) were male , and patients had been diagnosed with type 1 diabetes for a mean of 18.94 years ( SD 9.66 ) . Of the initial 72 patients , 53 completed the study ( 25 intervention , 28 control group ) . The intervention group significantly improved glycemic control ( HbA1c ) from baseline ( mean 9.08 % , SD 1.18 ) to 9-month follow-up ( mean 7.80 % , SD 0.75 ) , compared to the control group ( baseline : mean 8.47 % , SD 0.86 , follow-up : mean 8.58 % , SD 1.16 ) . No significant change over time was found in either group in relation to self-efficacy , self-care activities , and quality of life . Conclusions In adjunct to usual care , the use of a diabetes-related smartphone application combined with weekly text-message support from a health care professional can significantly improve glycemic control in adults with type 1 diabetes . Trial Registration Australian New Zeal and Clinical Trials Registry : ACTRN12612000132842 ; https://www.anzctr.org.au/Trial/ Registration /Trial Review .aspx?ACTRN=12612000132842 ( Archived by WebCite at http://www.webcitation.org/6Kl4jqn5u ) Abstract Objectives : To evaluate whether a course teaching flexible intensive insulin treatment combining dietary freedom and insulin adjustment can improve both glycaemic control and quality of life in type 1 diabetes . Design : R and omised design with participants either attending training immediately ( immediate DAFNE ) or acting as waiting list controls and attending “ delayed DAFNE ” training 6 months later . Setting : Secondary care diabetes clinics in three English health districts . Participants : 169 adults with type 1 diabetes and moderate or poor glycaemic control . Main outcome measures : Glycated haemoglobin ( HbA1c ) , severe hypoglycaemia , impact of diabetes on quality of life ( ADDQoL ) . Results : At 6 months , HbA1c was significantly better in immediate DAFNE patients ( mean 8.4 % ) than in delayed DAFNE patients ( 9.4 % ) ( t=6.1 , P<0.0001 ) . The impact of diabetes on dietary freedom was significantly improved in immediate DAFNE patients compared with delayed DAFNE patients ( t=−5.4 , P<0.0001 ) , as was the impact of diabetes on overall quality of life ( t=2.9 , P<0.01 ) . General wellbeing and treatment satisfaction were also significantly improved , but severe hypoglycaemia , weight , and lipids remained unchanged . Improvements in “ present quality of life ” did not reach significance at 6 months but were significant by 1 year . Conclusion : Skills training promoting dietary freedom improved quality of life and glycaemic control in people with type 1 diabetes without worsening severe hypoglycaemia or cardiovascular risk . This approach has the potential to enable more people to adopt intensive insulin treatment and is worthy of further investigation Intensification of insulin therapy in the Diabetes Control and Complications Trial led to an improvement in the quality of diabetes care , which was accompanied , however , by a threefold increase in the risk of severe hypoglycaemia . The present trial , a long-term evaluation of a structured 5-day treatment and teaching programme ( DTTP ) for intensified insulin therapy , was performed to clarify factors determining HbA1c , the incidence of severe hypoglycaemia , diabetes knowledge and quality of life . Ninety-four Type 1 diabetic patients were examined at baseline and 4 years after participation in a DTTP . Comparison of baseline data with measurements at the 4-year follow-up examination showed that relative HbA1c (= HbA1c/mean normal ) improved ( 1.9 + /- 0.51 vs 1.55 + /- 0.3 * , p < 0.001 , * excluding 4 patients with diabetes manifestation at baseline ) and that frequencies of daily insulin injections ( 3.73 + /- 1.23 vs 4.9 + /- 0.69 * , p < 0.001 ) and weekly blood glucose self-tests ( 6.6 + /- 10.1 vs 25.5 + /- 8.7 * , p < 0.001 ) increased , whereas the incidence of severe hypoglycaemia ( intravenous glucose , glucagon injection ) remained stable ( 0.19 vs 0.24 , p = 0.48 ) . Patients with less diabetes knowledge had higher HbA1c levels and a higher incidence of severe hypoglycaemia . In the group of patients with severe hypoglycaemia , certain crucial gaps in diabetes knowledge were identified concerning the effects of physical activity , nutrition and long-term complications of diabetes . In multivariate analysis . The most important factor associated with HbA1c was diabetes knowledge which , however , was not influenced by educational level or other factors . Interventions , such as the identification of psychosocial factors which may interact with diabetes knowledge , quality of life and successful self-management of diabetes by patients , are needed to improve the efficacy of DTTPs and to prevent severe side effects such as hypoglycaemia BACKGROUND To determine whether a Web-based diabetes case management program based in an electronic medical record can improve glycemic control ( primary outcome ) and diabetes-specific self-efficacy ( secondary outcome ) in adults with type 1 diabetes , a pilot r and omized controlled trial was conducted . METHODS A 12-month r and omized trial tested a Web-based case management program in a diabetes specialty clinic . Patients 21 - 49 years old with type 1 diabetes receiving multiple daily injections with insulin glargine and rapid-acting analogs who had a recent A1C > 7.0 % were eligible for inclusion . Participants were r and omized to receive either ( 1 ) usual care plus the nurse-practitioner-aided Web-based case management program ( intervention ) or ( 2 ) usual clinic care alone ( control ) . We compared patients in the two study arms for changes in A1C and self-efficacy measured with the Diabetes Empowerment Scale . RESULTS A total of 77 patients were recruited from the diabetes clinic and enrolled in the trial . The mean baseline A1C among study participants was 8.0 % . We observed a nonsignificant decrease in average A1C ( -0.48 ; 95 % confidence interval -1.22 to 0.27 ; P = 0.160 ) in the intervention group compared to the usual care group . The intervention group had a significant increase in diabetes-related self-efficacy compared to usual care ( group difference of 0.30 ; 95 % confidence interval 0.01 to 0.59 ; P = 0.04 ) . CONCLUSIONS Use of a Web-based case management program was associated with a beneficial treatment effect on self-efficacy , but change in glycemic control did not reach statistical significance in this trial of patients with moderately poorly controlled type 1 diabetes . Larger studies may be necessary to further clarify the intervention 's impact on health outcomes |
1,801 | 32,270,460 | Studies from some African countries suggest that fermented foods of probiotics relevance have effectively shown metal chelation properties .
Consumption of Nigerian fermented foods may hold a promise in checking the high body burden of heavy metals in Nigeria . | Probiotics are functional foods with a wide armamentarium of health benefits in man including metal chelation .
Given the unacceptable blood lead levels and the near ignorance or negligence of heavy metals in both diagnoses and management of diseases in Nigeria , it is feared that these metals are involved in the aetiogenesis of several ailments from preeclampsia , metabolic syndrome , cancer , etc .
This is an insight on Nigerian fermented foods and their possible role as metal chelators in the management of the chronic heavy metal exposure in Nigeria . | In a previous clinical study , a probiotic formulation ( PF ) consisting of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 ( PF ) decreased stress-induced gastrointestinal discomfort . Emerging evidence of a role for gut microbiota on central nervous system functions therefore suggests that oral intake of probiotics may have beneficial consequences on mood and psychological distress . The aim of the present study was to investigate the anxiolytic-like activity of PF in rats , and its possible effects on anxiety , depression , stress and coping strategies in healthy human volunteers . In the pre clinical study , rats were daily administered PF for 2 weeks and subsequently tested in the conditioned defensive burying test , a screening model for anti-anxiety agents . In the clinical trial , volunteers participated in a double-blind , placebo-controlled , r and omised parallel group study with PF administered for 30 d and assessed with the Hopkins Symptom Checklist ( HSCL-90 ) , the Hospital Anxiety and Depression Scale ( HADS ) , the Perceived Stress Scale , the Coping Checklist ( CCL ) and 24 h urinary free cortisol ( UFC ) . Daily subchronic administration of PF significantly reduced anxiety-like behaviour in rats ( P < 0·05 ) and alleviated psychological distress in volunteers , as measured particularly by the HSCL-90 scale ( global severity index , P < 0·05 ; somatisation , P < 0·05 ; depression , P < 0·05 ; and anger-hostility , P < 0·05 ) , the HADS ( HADS global score , P < 0·05 ; and HADS-anxiety , P < 0·06 ) , and by the CCL ( problem solving , P < 0·05 ) and the UFC level ( P < 0·05 ) . L. helveticus R0052 and B. longum R0175 taken in combination display anxiolytic-like activity in rats and beneficial psychological effects in healthy human volunteers Indigenous lactic acid fermented foods may have potential as probiotic treatment for diarrhoea , due to high levels of lactic acid bacteria . In this study the effect of a millet drink , spontaneously fermented by lactic acid bacteria , as a therapeutic agent among Ghanaian children with diarrhoea , was assessed . Children below 5 years of age coming to Northern Ghana health clinics for treatment of diarrhoea were r and omised to two groups . Children of both groups received treatment for diarrhoea given at the local clinic . The intervention group in addition received up to 300 ml fermented millet drink ( KSW ) daily for 5 days after enrolment . The clinical outcome of diarrhoea and reported well-being were registered every day for the 5-day intervention and again 14 days after diagnosis . Among 184 children ( mean age 17.4 , st and ard deviation 11.3 months ) included , no effects of the intervention were found with respect to stool frequency , stool consistency and duration of diarrhoea . However , KSW was associated with greater reported well-being 14 days after the start of the intervention ( P=0.02 ) . The fact that no effect of KSW on diarrhoea was observed could be because many children had a mild form of diarrhoea , and many were treated with antibiotics . Either this could have affected the lactic acid bacteria , or the lactic acid bacteria in KSW had no probiotic effects . It is speculated that the effect after two weeks could be due to a preventing effect of KSW on antibiotic-associated diarrhoea which could help reducing persistent diarrhoea Probiotics are live microorganisms that exert beneficial effects on the host , when administered in adequate amounts . Mostly , probiotics affect the gastrointestinal ( GI ) tract of the host and alter the composition of gut microbiota . Nowadays , the incidence of hip fractures due to osteoporosis is increasing worldwide . Ovariectomized ( OVX ) rats have fragile bone due to estrogen deficiency and mimic the menopausal conditions in women . Therefore , this study aim ed to examine the effects of Bifidobacterium longum ( B. longum ) on bone mass density ( BMD ) , bone mineral content ( BMC ) , bone remodeling , bone structure , and gene expression in OVX rats . The rats were r and omly assigned into 3 groups ( sham , OVX , and the OVX group supplemented with 1 mL of B. longum 108–109 colony forming units (CFU)/mL ) . B. longum was given once daily for 16 weeks , starting from 2 weeks after the surgery . The B. longum supplementation increased ( p < 0.05 ) serum osteocalcin ( OC ) and osteoblasts , bone formation parameters , and decreased serum C-terminal telopeptide ( CTX ) and osteoclasts , bone resorption parameters . It also altered the microstructure of the femur . Consequently , it increased BMD by increasing ( p < 0.05 ) the expression of Sparc and Bmp-2 genes . B. longum alleviated bone loss in OVX rats and enhanced BMD by decreasing bone resorption and increasing bone formation |
1,802 | 28,831,271 | This review indicates that there are sex differences in the placebo and nocebo effects , probably caused by sex differences in stress , anxiety , and the endogenous opioid system | OBJECTIVES The present review investigated whether there are systematic sex differences in the placebo and the nocebo effect . | Experimental challenge studies may generate and test hypotheses regarding the pathophysiology of panic disorder and may serve to identify pathophysiologically relevant subtypes . It has been suggested that gender-related differences may be relevant in the development and maintenance of panic disorder . In a r and omized double blind design the effects of placebo and sodium lactate administration in 14 female and 16 male patients with panic disorder and 23 healthy control subjects were compared using the Acute Panic Inventory ( API ) score and derived formal criteria for a panic attack . Panic attack frequency following sodium lactate was 76.6 % in the patient group . Although control subjects had a lactate-induced increase in the API score as well , this effect was much weaker . No panic attacks occurred in patients with panic disorder or healthy control subjects receiving a placebo . However , a gender effect was observed in the putative panicogenic placebo condition : female patients with panic disorder had more subthreshold panic anxiety as measured with the API score . The data give evidence for an increased nocebo response in female patients with panic disorder Nocebo hyperalgesia has received sparse experimental attention compared to placebo analgesia . The aim of the present study was to investigate if personality traits and fear of pain could predict experimental nocebo hyperalgesia . One hundred and eleven healthy volunteers ( 76 females ) participated in an experimental study in which personality traits and fear of pain were measured prior to induction of thermal heat pain . Personality traits were measured by the Big-Five Inventory-10 . Fear of pain was measured by the Fear of Pain Question naire III . Heat pain was induced by a PC-controlled thermode . Pain was measured by a computerized visual analog scale . Stress levels during the experiment were measured by numerical rating scales . The participants were r and omized to a Nocebo group or to a no-treatment Natural History group . The results revealed that pain and stress levels were significantly higher in the Nocebo group after nocebo treatment . Mediation analysis showed that higher levels of the Fear of Pain Question naire III factor “ fear of medical pain ” significantly increased stress levels after nocebo treatment and that higher stress levels were associated with increased nocebo hyperalgesic responses . There were no significant associations between any of the personality factors and the nocebo hyperalgesic effect . The results from the present study suggest that dispositional fear of pain might be a useful predictor for nocebo hyperalgesia and emotional states concomitant with expectations of increased pain . Furthermore , measurement of traits that are specific to pain experience is probably better suited for prediction of nocebo hyperalgesic responses compared to broad measures of personality OBJECTIVE This study investigated the impact of the social modeling of side effects following placebo medication ingestion on the nocebo and placebo effect . It also investigated whether medication br and ing ( br and or generic labeling ) moderated social modeling effects . METHOD Eighty-two university students took part in the study which was purportedly investigating the impact of fast-acting beta-blocker medications ( actually placebos ) on preexamination anxiety . After taking the medication , participants were r and omized to either witness a female confederate report experiencing side effects or no side effects after taking the same medication . Differences in symptom reporting , blood pressure , heart rate , and anxiety were assessed between the social modeling of side effects and no modeling groups . RESULTS Seeing a female confederate report side effects reduced the placebo effect in systolic ( p = .009 ) and diastolic blood pressure ( p = .033 ) . Seeing a female confederate report side effects also increased both total reported symptoms ( mean [ SE ] 7.35 [ .54 ] vs. 5.16 [ 0.53 ] p = .005 ) and symptoms attributed to the medication ( 5.27 [ 0.60 ] vs. 3.04 [ 0.59 ] p = .01 ) , although the effect on symptoms was only seen in female participants . Females who saw the confederate report side effects reported approximately twice the number of symptoms as those in the no modeling group . Social modeling did not affect heart rate or anxiety . Medication br and ing did not influence placebo or nocebo outcomes . CONCLUSIONS The social modeling of symptoms can substantially reduce or eliminate the placebo effect . Viewing a female confederate display symptoms after taking the same medication increases symptom reporting in females UNLABELLED Expectations and beliefs shape the experience of pain . This is most evident in context -induced , placebo analgesia , which has recently been shown to interact with the trait of magical thinking ( MT ) in adults . In children , placebo analgesia and the possible roles that MT and gender might play as modulators of placebo analgesia have remained unexplored . Using a paradigm in which heat pain stimuli were applied to both forearms , we investigated whether MT and gender can influence the magnitude of placebo analgesia in children . Participants were 49 right-h and ed children ( aged 6 - 9 years ) who were r and omly assigned-stratified for MT and gender-to either an analgesia-expectation or a control-expectation condition . For both conditions , the placebo was a blue-colored h and disinfectant that was applied to the children 's forearms . Independent of MT , the placebo treatment significantly increased both heat pain threshold and tolerance . The threshold placebo effect was more pronounced for girls than boys . In addition , independent of the expectation treatment , low-MT boys showed a lower tolerance increase on the left compared to the right side . Finally , MT specifically modulated tolerance on the right forearm side : Low-MT boys showed an increase , whereas high-MT boys showed a decrease in heat pain tolerance . This study documented a substantial expectation-induced placebo analgesia response in children ( girls > boys ) and demonstrated MT and gender-dependent laterality effects in pain perception . The findings may help improve individualized pain management for children . PERSPECTIVE The study documents the first experimental evidence for a substantial expectancy-induced placebo analgesia response in healthy children aged 6 to 9 years ( girls > boys ) . Moreover , the effect was substantially higher than the placebo response typically found in adults . The findings may help improve individualized pain management for children Background : Expectancy and modeling have been cited as factors in mass psychogenic illness ( MPI ) , which reportedly affects more women than men . Purpose : The purpose of the study is to assess the effects of expectancy and modeling in a controlled laboratory analogue of MPI . Methods : Students were r and omly assigned to inhale or not inhale an inert placebo described as a suspected environmental toxin that had been linked to four symptoms typical of reported instances of MPI . Half of the students observed a female confederate inhale the substance and subsequently display the specified symptoms . Results : Students who inhaled the placebo reported greater increases in symptoms , and the increase was significantly greater for the specified symptoms than for other symptoms . Observation of the confederate displaying symptoms increased specified symptoms significantly among women but not among men . Changes in reported symptoms were significantly associated with changes in unobtrusively observed behavior . Conclusions : Symptoms typical of clinical reports of MPI can be induced by manipulating response expectancies , and the effects are specific rather than generalized . Among women , this effect is enhanced by observing another participant ( who in this study is also female ) display symptoms . This suggests that the preponderance of women showing symptoms in outbreaks of MPI may be due to gender-linked differences in the effects of modeling on psychogenic symptoms We conjectured that individual differences in tension-reduction alcohol outcome expectancies ( TR-AOEs ) could produce widely varying responses to manipulations in alcohol-placebo studies and tested this idea by having individuals with social phobia give speeches in front of a group . One speech occurred before and one after participants consumed either a placebo beverage or a control beverage ( i.e. , a nonalcoholic drink described as containing no alcohol ) . Study results indicate that the placebo manipulation reduced cognitive and affective symptoms of anxiety to a greater extent for males with high TR-AOEs than for males with low TR-AOEs . This pattern was not found for women in the placebo group or for individuals in the control group . These findings demonstrate a moderating effect of TR-AOEs on the association between the consumption of a placebo beverage and response to an anxiety challenge and highlight the importance of accounting for gender and outcome expectancies when evaluating psychoactive substances Rationale In a r and omised placebo-controlled clinical trial it is assumed that psychosocial effects of the treatment , regression to the mean and spontaneous remission are identical in the drug and placebo group . Consequently , any difference between the groups can be ascribed to the pharmacological effects . Previous studies suggest that side effects of drugs can enhance expectancies of treatment effects in the drug group compared to the placebo group , and thereby increase placebo responses in the drug group compared to the placebo group . Objectives The hypothesis that side effects of drugs can enhance expectancies and placebo responses was tested . Method Painful laser stimuli were delivered to 20 healthy subjects before and after administration of a drink with 0 or 4 mg/kg caffeine . The drink was administered either with information that it contained a painkiller or that it was a placebo . Laser-evoked potentials and reports of pain , expectancy , arousal and stress were measured . Results Four milligrammes per kilogramme of caffeine reduced pain . Information that a painkiller was administered increased the analgesic effect of caffeine compared to caffeine administered with no drug information . This effect was mediated by expectancies . Information and expectancies had no effect on pain intensity when 0 mg/kg was administered . Conclusion The analgesic effect of caffeine was increased by information that a painkiller was administered . This was due to an interaction of the pharmacological action of the drug and expectancies . Hence , psychosocial effects accompanying a treatment can differ when an active drug is administered compared to a placebo The nocebo effect is the onset of untoward reactions following the administration of an indifferent substance . The oral challenge with alternative drugs plays a central role in the management of drug allergy and the use of inert substances is part of this procedure . We evaluated the occurrence and clinical characteristics of nocebo effect in patients with adverse drug reactions . Six hundred patients , seen in three different centres ( Genoa , Naples and Verona ) with a history of reactions to drugs , underwent a blind oral challenge with the administration of an indifferent substance and active drugs . The administration of an inert substance provoked untoward reactions in 54 patients ( 27 % ) in Verona , 60 ( 30 % ) in Naples and 48 ( 24 % ) in Genoa . The overall occurrence of nocebo effect was 27 % . The majority of reactions were subjective symptoms ( itching , malaise , headache etc ) , perceived as troublesome by all subjects . The occurrence was significantly higher in women than in men . Our data , collected in a large population , confirm that the nocebo effect occurs frequently in clinical practice . In managing adverse drug reactions through oral challenge the nocebo effect is m and atory to recognize false positive responses BACKGROUND Social cues and interpersonal interactions strongly contribute to evoke placebo effects that are pervasive in medicine and depend upon the activation of endogenous modulatory systems . Here , we explore the possibility to boost placebo effects by targeting pharmacologically the vasopressin system , characterized by a sexually dimorphic response and involved in the regulation of human and nonhuman social behaviors . METHODS We enrolled 109 healthy participants and studied the effects of intranasal administration of an arginine vasopressin 1A and 1B receptor agonist against 1 ) no treatment , 2 ) oxytocin , and 3 ) saline in a r and omized , placebo-controlled , double-blind , parallel design trial using a well-established model of placebo analgesia while controlling for sex differences . RESULTS Vasopressin agonists boosted placebo effects in women but had no effect in men . The effects of vasopressin on expectancy-induced analgesia were significantly larger than those observed in the no-treatment ( p < .004 ) , oxytocin ( p < .001 ) , and saline ( p < .015 ) groups . Moreover , women with lower dispositional anxiety and cortisol levels showed the largest vasopressin-induced modulation of placebo effects , suggesting a moderating interplay between pre-existing psychological factors and treatment cortisol changes . CONCLUSIONS This is the first study that demonstrates that arginine vasopressin boosts placebo effects and that the effect of vasopressin depends upon a significant sex by treatment interaction . These findings are novel and might open up new avenues for clinical ly relevant research due to the therapeutic potentials of vasopressin as well as the possibility to systematic ally control for influences of placebo responses in clinical trials We investigated the mechanisms underlying the activation of endogenous opioids in placebo analgesia by using the model of human experimental ischemic arm pain . Different types of placebo analgesic responses were evoked by means of cognitive expectation cues , drug conditioning , or a combination of both . Drug conditioning was performed by means of either the opioid agonist morphine hydrochloride or the nonopioid ketorolac tromethamine . Expectation cues produced placebo responses that were completely blocked by the opioid antagonist naloxone . Expectation cues together with morphine conditioning produced placebo responses that were completely antagonized by naloxone . Morphine conditioning alone ( without expectation cues ) induced a naloxone-reversible placebo effect . By contrast , ketorolac conditioning together with expectation cues elicited a placebo effect that was blocked by naloxone only partially . Ketorolac conditioning alone produced placebo responses that were naloxone-insensitive . Therefore , we evoked different types of placebo responses that were either naloxone-reversible or partially naloxone-reversible or , otherwise , naloxone-insensitive , depending on the procedure used to evoke the placebo response . These findings show that cognitive factors and conditioning are balanced in different ways in placebo analgesia , and this balance is crucial for the activation of opioid or nonopioid systems . Expectation triggers endogenous opioids , whereas conditioning activates specific subsystems . In fact , if conditioning is performed with opioids , placebo analgesia is mediated via opioid receptors , if conditioning is performed with nonopioid drugs , other nonopioid mechanisms result to be involved Expectancy or placebo effects on cognitive function have not been well studied . To determine the effect of taking pills on cognitive function , 40 participants were r and omly assigned to a pill or no-pill condition . Healthy seniors who took a 2-week supply of methylcellulose pills , which they were told was an experimental cognitive enhancer , were compared to seniors not taking any pills . There were 2 primary outcome measures defined prior to the study —Consortium to Establish a Registry for Alzheimer 's Disease ( CERAD ) Word List delayed recall and Stroop color word task time — as well as 7 other cognitive outcome measures . There was a significant effect of pill taking on the 2 primary outcome measures . There was also an effect of pill taking on choice reaction time and Word List immediate recall but not on the other 5 secondary cognitive outcome measures . In an exploratory analysis of potential predictors of the expectancy effect , perceived stress and self-efficacy but not personality traits interacted with the pill-taking effect on cognitive function . Further characterizing and underst and ing this observed expectancy effect is important to maximize cognitive health and improve clinical trial design Previous positron emission tomography ( PET ) studies have provided evidence that the psychological expectation of certain drugs combined to the placebo administration may lead to subjectively experienced placebo effects , which , in turn , are associated with dopamine ( DA ) release in the brain . Our recent study indicated that blind intravenous ( i.v . ) glucose induces DA release in male subjects . In the present study , we examined if the mere expectation of glucose ( i.v . placebo ) could similarly release DA in the basal ganglia . [(11)C]raclopride PET was performed for 12 lean [ mean body mass index ( BMI ) = 22 kg/m(2 ) ] and 12 overweight ( mean BMI = 33 kg/m(2 ) ) healthy subjects ( 12 men and 12 women ) . Each subject was imaged twice in a counter-balanced setting , after blind i.v . placebo and after open i.v . placebo . DA D2 receptor binding potentials ( BP ) were estimated . The results of the present study show that i.v . placebo administration with glucose expectation induces bilateral BP reduction in the ventral striatum in the male group , suggesting DA release . The stimulus did not induce dopaminergic placebo effect in the overweight or the lean group ( males and females combined ) . Voxel-based analysis also suggested regionally selective BP increases in the dorsal striatum in the male subjects , whereas women showed no significant changes in BPs . The results support previously reported gender differences in the DA function after a pharmacological challenge ( e.g. , amphetamine and glucose ) . Also , they suggest that the DA release in the ventral striatum mediates placebo responses in the context of glucose expectation The present study was design ed to determine the role of endogenous opioid mechanisms in the circulatory effects of relaxation training . Opioid mechanisms were assessed by examination of the effects of opioid receptor blockade with naltrexone on acute cardiovascular reactivity to laboratory stress before and after relaxation training . Thirty-two young men with mildly elevated casual arterial pressure were recruited for placebo-controlled naltrexone stress tests and relaxation training . The results indicated that relaxation training significantly reduced the diastolic pressure response to mental arithmetic stress . Opioid receptor blockade with naltrexone antagonized the effects of relaxation training . These findings suggest that some of the physiological effects of relaxation training are mediated by augmentation of inhibitory opioid mechanisms Abstract In patients who reported mild postoperative pain , we evoked a nocebo response , a phenomenon equal but opposite to placebo . Patients who gave informed consent to increase their pain for 30 min received a substance known to be non – hyperalgesic ( saline solution ) and were told that it produced a pain increase . A nocebo effect was observed when saline was administered . However , if a dose of 0.5 or 5 mg of the cholecystokinin antagonist proglumide was added to the saline solution , the nocebo effect was abolished . A dose of 0.05 mg of proglumide was ineffective . The blockade of the nocebo hyperalgesic response was not reversed by 10 mg of naloxone . These results suggest that cholecystokinin mediates pain increase in the nocebo response and that proglumide blocks nocebo through mechanisms not involving opioids . Since the nocebo procedure represents an anxiogenic stimulus and previous studies showed a role for cholecystokinin in anxiety , we suggest that nocebo hyperalgesia may be due to a cholecystokinin‐dependent increase of anxiety & NA ; Discovery of the involvement of endogenous opiates in placebo analgesia represents an important step in underst and ing the mechanisms underlying placebo response . In the present study , we investigated the effects of the opiate antagonist naloxone and the cholecystokinin antagonist proglumide on placebo analgesia in a human model of experimentally induced ischemic pain . First , we found that part of the placebo response was reversed by naloxone , confirming previous studies on the role of opioids in the placebo phenomenon . Second , since it was demonstrated that the action of exogenous and endogenous opiates is potentiated by proglumide , we analysed the effects of this cholecystokinin antagonist on placebo response and found that it enhanced placebo analgesia . The placebo effect can thus be modulated in two opposite directions : it can be partially abolished by naloxone and potentiated by proglumide . The fact that placebo potentiation by proglumide occurred only in placebo responders , but not in non‐responders , suggests that activation of an endogenous opiate system is a necessary condition for the action of proglumide . These results suggest an inhibitory role for cholecystokinin in placebo response , although the low affinity of proglumide for cholecystokinin receptors does not rule out the possibility of other mechanisms AIM To determine whether there is a sex difference in placebo and ibuprofen analgesia expectancy . METHODS We measured detection and tolerance thresholds for electrically induced pain in the ear lobe in healthy subjects ( 10 male , 10 female ) to study sex differences in expectancy following either ibuprofen 800 mg or placebo in four different expectancy states . Subjects took ibuprofen or placebo in a two-by-two factorial design ( the balanced placebo design ) . We r and omly assigned subjects to start in one of the four expectancy states . We analysed the results using analysis of variance for repeated measures with baseline pain as a covariate . RESULTS AND CONCLUSION We found no sex difference in baseline pain threshold or tolerance levels . When partitioned by sex and expectancy state , analgesia only occurred in males during positive expectancy states at 2 , 3 and 4 h post-placebo , and at 1 and 2 h post-ibuprofen . The time course of analgesic action in males was as expected considering the pharmacokinetic profile of ibuprofen . Our study found that dosages of 800 mg of ibuprofen are ineffective in producing analgesia in women regardless of their expectations . We hypothesize that ibuprofen analgesia is produced by a combination of specific pharmacological effects and a non-specific beta endorphin-mediated placebo effect . Whatever the mechanism responsible for the analgesic response seen in males , this research re-emphasizes the importance of psychological factors in determining drug response . It also shows that these factors can differ between men and women , and thus the contribution of psychological factors on analgesia needs to be seriously re-evaluated |
1,803 | 24,825,456 | There were significant benefits for the following outcomes : lower rates of failure to extubate and decreased risks of chronic lung disease at both 28 days and 36 weeks ' postmenstrual age , death or chronic lung disease at 28 days and 36 weeks ' postmenstrual age , patent ductus arteriosus and ROP , including severe ROP .
There were no significant differences in the rates of neonatal or subsequent mortality , infection , severe intraventricular haemorrhage , periventricular leukomalacia , necrotising enterocolitis or pulmonary haemorrhage .
Gastrointestinal bleeding and intestinal perforation were important adverse effects .
The risks of hyperglycaemia , hypertension , hypertrophic cardiomyopathy and growth failure were also increased .
In subgroup analyses by type of corticosteroid , most of the beneficial and harmful effects were attributable to dexamethasone ; hydrocortisone had little effect on any outcomes except for an increase in intestinal perforation and a borderline reduction in patent ductus arteriosus .
AUTHORS ' CONCLUSIONS The benefits of early postnatal corticosteroid treatment ( ≤ 7 days ) , particularly dexamethasone , may not outweigh the adverse effects of this treatment .
Although early corticosteroid treatment facilitates extubation and reduces the risk of chronic lung disease and patent ductus arteriosus , it causes short-term adverse effects including gastrointestinal bleeding , intestinal perforation , hyperglycaemia , hypertension , hypertrophic cardiomyopathy and growth failure .
Long-term follow-up studies report an increased risk of abnormal neurological examination and cerebral palsy .
Hydrocortisone in the doses and regimens used in the reported RCTs has few beneficial or harmful effects and can not be recommended for the prevention of chronic lung disease | BACKGROUND Chronic lung disease remains a major problem in neonatal intensive care units .
Persistent inflammation in the lungs is the most likely underlying pathogenesis .
Corticosteroids have been used to either prevent or treat chronic lung disease because of their potent anti-inflammatory effects .
OBJECTIVES To examine the relative benefits and adverse effects of postnatal corticosteroids commenced within the first seven days of life to preterm infants at risk of developing chronic lung disease . | To determine whether prenatal corticosteroid therapy would reduce the incidence of neonatal necrotizing enterocolitis ( NEC ) , we assigned a total of 466 women admitted in premature labor either to receive placebo ( group A , n = 256 ) , if delivery was expected to occur within 24 hours of admission , or to receive betamethasone ( group B , n = 210 ) if delivery was expected to take place more than 24 hours after admission . All women were free of severe medical complications or drug therapy ; cases of intrauterine growth retardation or premature rupture of the membranes were excluded . Their newborn infants , excluding malformed , congenitally infected , and growth-retarded infants , were enrolled in the study unless they had died before the age of 10 postnatal days . Babies born to group A mothers ( n = 248 ) were further assigned to a treatment group ( group A1 , n = 130 ) receiving dexamethasone , 2 mg/kg/day by intravenous injection during the first 7 days of life , or to a control group ( group A2 , n = 118 ) receiving 10 % dextrose solution placebo . Group B infants ( prenatal betamethasone , n = 205 ) received neither treatment nor placebo . The incidence of NEC in group A1 was 6.9 % ( 9/130 ) , and in group A2 it was 14.4 % ( 17/118 ) ( p less than 0.05 ) . In group B the incidence was 3.4 % ( 7/205 ) ; this was much lower than in group A2 ( p less than 0.01 ) and lower than in group A combined ( 10.4 % ) ( p less than 0.01 ) . There was no death from NEC and no surgical intervention among group B patients . The mortality rate for group A1 ( 11 % ) was lower than for group A2 ( 56 % ) ( p less than 0.02 ) . There were fewer indications for surgical intervention for NEC in group A1 than in group A2 . Histologic studies confirmed bowel ischemia in all specimens analyzed . These data support the hypothesis that the incidence of NEC is significantly reduced after prenatal steroid treatment . Although postnatal therapy with steroids does not decrease the incidence as effectively as prenatal therapy , it improves clinical outcome of NEC Early postnatal use of dexamethasone has recently been shown to be effective in improving the pulmonary status in premature infants with respiratory distress syndrome ( RDS ) . To study the effect of dexamethasone on pulmonary inflammatory responses , we studied ten infants treated with dexamethasone and ten infants without this treatment . Serial tracheal aspirates were obtained for cell counts , neutrophil counts , total protein concentrations , and leukotriene B4 ( LTB4 ) and 6-keto prostagl and in (PG)F(1 alpha ) levels before and after starting the study . Infants in the dexamethasone-treated group required significantly lower mean airway pressures for ventilation and had lower PaCO2 values from day 3 to day 14 than infants in the control group , suggesting better pulmonary function . For infants in the dexamethasone group , the tracheal aspirates showed significantly lower cell and neutrophil counts , protein concentrations , and 6-keto-PGF(1 alpha ) and LTB4 levels than in the control group . We conclude that early postnatal dexamethasone therapy may lessen lung inflammation and improve pulmonary function in infants with RDS Dexamethasone was compared with placebo in a double-blind , crossover , r and omised study of infants with severe bronchopulmonary dysplasia who had required mechanical ventilation for at least four weeks , despite treatment with diuretics , methylxanthines , bronchodilators , fluid restriction , nutritional supplementation , and ligation of the patent ductus arteriosus when indicated . Gestational age ranged from 27 to 33 weeks and birth weight from 800 to 1730 g. Patients received dexamethasone ( 0 . 5 mg/kg/day ) or normal saline for the first 3 days , then treatment was crossed over for the next 3 days . The study was terminated when sequential analysis showed that all six patients had improved during dexamethasone therapy . Significant improvements were seen in ventilator-determined respiratory rate , peak inspiratory pressure , fractional inspired oxygen concentration , and alveolar arterial oxygen gradients ( p less than 0 . 05 ) . Although dexamethasone hastened weaning from mechanical ventilation , infection occurred in a substantial proportion of patients Background . Although several trials of early dexamethasone therapy have been completed to determine if such therapy would reduce mortality and chronic lung disease ( CLD ) in infants with respiratory distress , optimal duration and side effects of such therapy remain unknown . Purpose . The purpose of this study was : 1 ) to determine if a 3-day course of early dexamethasone therapy would reduce CLD and increase survival without CLD in neonates who received surfactant therapy for respiratory distress syndrome and 2 ) to determine adverse effects associated with such therapy . Design . This was a prospect i ve multicenter r and omized trial comparing a 3-day course of dexamethasone therapy beginning at 24 to 48 hours of life to placebo therapy . Two hundred forty-one neonates ( dexamethasone n = 118 , placebon = 123 ) , who weighed between 500 g and 1500 g , received surfactant therapy , and were at significant risk for CLD or death using a model to predict CLD or death at 24 hours of life , were enrolled in the trial . Infants r and omized to receive early dexamethasone were given 6 doses of dexamethasone at 12-hour intervals beginning at 24 to 48 hours of life . The primary outcomes compared were survival without CLD and CLD . CLD was defined by the need for supplemental oxygen at the gestational age of 36 weeks . Complication rates and adverse effects of study drug therapy were also compared . Results . Neonates r and omized to early dexamethasone treatment were more likely to survive without CLD ( RR : 1.3 ; 95 % CI : 1.03 , 1.7 ) and were less likely to develop CLD ( RR : 0.6 ; CI : 0.3 , 0.98 ) . Mortality rates were not significantly different . Subsequent dexamethasone therapy use was less in early dexamethasone-treated neonates ( RR : 0.8 ; CI : 0.7 , 0.96 ) . Very early ( ≤7 days of life ) intestinal perforations were more common among dexamethasone-treated neonates ( 8 % vs 1 % ) . Conclusion . We conclude that an early 3-day course of dexamethasone therapy increases survival without CLD , reduces CLD , and reduces late dexamethasone therapy in high-risk , low birth weight infants who receive surfactant therapy for respiratory distress syndrome . Potential benefits of early dexamethasone therapy at the dosing schedule used in this trial need to be weighed against the risk for early intestinal perforation Background : Dexamethasone treatment is associated with an increased risk of cerebral palsy ( CP ) . Early hydrocortisone ( HC ) treatment may decrease the incidence of bronchopulmonary dysplasia ; however , the long-term effects are still under evaluation . Follow-up of r and omized studies concerning early HC treatment is essential to confirm the long-term safety . Objective : We hypothesized that early HC treatment in very preterm infants does not impair the neurologic outcome . Methods : We report follow-up data from a r and omized trial of early HC given for 10 days . Before the HC or placebo treatment , serum cortisol levels were measured . Receiver-operating characteristic was defined . Values below the median were classified as low endogenous cortisol and those above the median as high endogenous cortisol . A meta- analysis was performed . Results : Altogether 98 % of the 46 surviving infants participated in a follow-up study at a corrected age of 2 years . The growth characteristics were similar between the study groups . The developmental quotients ( DQs ) of the children with high endogenous cortisol and placebo treatment shortly after birth ( 100 ± 13 ) and those with low endogenous cortisol and HC ( 97 ± 7 ) were not lower than the DQs of the children with high endogenous cortisol and HC ( 92 ± 3 ) or low cortisol and placebo ( 96 ± 2 ) . According to a meta- analysis of three available trials ( 411 children ) , the rate of CP and survival without neurosensory or cognitive impairment was not influenced by HC . Conclusion : Early low-dose HC administration had no adverse effects at 2 years of age . Further studies are required to define the target group for neonatal HC BACKGROUND . Low cortisol concentrations in premature infants have been correlated with increased severity of illness , hypotension , mortality , and development of bronchopulmonary dysplasia . A total of 360 mechanically ventilated infants with a birth weight of 500 to 999 g were enrolled in a r and omized , multicenter trial of prophylaxis of early adrenal insufficiency to prevent bronchopulmonary dysplasia . Mortality and bronchopulmonary dysplasia were decreased in the hydrocortisone-treated patients exposed to chorioamnionitis . We now report outcomes at 18 to 22 months ' corrected age . PATIENTS AND METHODS . Surviving infants were evaluated with st and ardized neurologic examination and Bayley Scales of Infant Development-II . Neurodevelopmental impairment was defined as a Mental Developmental Index or Psychomotor Developmental Index of < 70 , cerebral palsy , blindness or deafness . RESULTS . A total of 252 ( 87 % ) of 291 survivors were evaluated . Cerebral palsy was diagnosed in 13 % of hydrocortisone-treated versus 14 % of placebo-treated infants . Fewer hydrocortisone-treated infants had a Mental Development Index < 70 , and more of the hydrocortisone-treated infants showed evidence of awareness of object permanence . Incidence of neurodevelopmental impairment was not different ( 39 % [ hydrocortisone ] vs 44 % [ placebo ] ) . There were no differences in physical growth measures . Chorioamnionitis-exposed infants treated with hydrocortisone were shorter and weighed less than controls but had no evidence of neurodevelopmental impairment . Among infants not exposed to chorioamnionitis , hydrocortisone-treated patients were less likely to have a Mental Development Index of < 70 or to be receiving glucocorticoids at follow-up . CONCLUSIONS . Early , low-dose hydrocortisone treatment was not associated with increased cerebral palsy . Treated infants had indicators of improved developmental outcome . Together with the short-term benefit previously reported , these data support additional studies of hydrocortisone treatment of adrenal insufficiency in extremely premature infants BACKGROUND Early administration of high doses of dexamethasone may reduce the risk of chronic lung disease in premature infants but can cause complications . Whether moderate doses would be as effective but safer is not known . METHODS We r and omly assigned 220 infants with a birth weight of 501 to 1000 g who were treated with mechanical ventilation within 12 hours after birth to receive dexamethasone or placebo with either routine ventilatory support or permissive hypercapnia . The dexamethasone was administered within 24 hours after birth at a dose of 0.15 mg per kilogram of body weight per day for three days , followed by a tapering of the dose over a period of seven days . The primary outcome was death or chronic lung disease at 36 weeks ' postmenstrual age . RESULTS The relative risk of death or chronic lung disease in the dexamethasone-treated infants , as compared with those who received placebo , was 0.9 ( 95 percent confidence interval , 0.8 to 1.1 ) . Since the effect of dexamethasone treatment did not vary according to the ventilatory approach , the two dexamethasone groups and the two placebo groups were combined . The infants in the dexamethasone group were less likely than those in the placebo group to be receiving oxygen supplementation 28 days after birth ( P=0.004 ) or open-label dexamethasone ( P=0.01 ) , were more likely to have hypertension ( P<0.001 ) , and were more likely to be receiving insulin treatment for hyperglycemia ( P=0.02 ) . During the first 14 days , spontaneous gastrointestinal perforation occurred in a larger proportion of infants in the dexamethasone group ( 13 percent , vs. 4 percent in the placebo group ; P=0.02 ) . The dexamethasone-treated infants had a lower weight ( P=0.02 ) and a smaller head circumference ( P=0.04 ) at 36 weeks ' postmenstrual age . CONCLUSIONS In preterm infants , early administration of dexamethasone at a moderate dose has no effect on death or chronic lung disease and is associated with gastrointestinal perforation and decreased growth OBJECTIVES To study whether early postnatal ( < 12 hours ) dexamethasone therapy reduces the incidence of chronic lung disease in preterm infants with respiratory distress syndrome . MATERIAL S AND METHODS A multicenter r and omized , double-blind clinical trial was undertaken on 262 ( saline placebo , 130 ; dexamethasone , 132 ) preterm infants ( < 2000 g ) who had respiratory distress syndrome and required mechanical ventilation shortly after birth . The sample size was calculated based on the 50 % reduction in the incidence of chronic lung disease when early dexamethasone is used , allowing a 5 % chance of a type I error and a 10 % chance of a type II error . For infants who received dexamethasone , the dosing schedules were : 0.25 mg/kg/dose every 12 hours intravenously on days 1 through 7 ; 0.12 mg/kg/dose every 12 hours intravenously on days 8 through 14 ; 0.05 mg/kg/dose every 12 hours intravenously on days 15 through 21 ; and 0 . 02 mg/kg/dose every 12 hours intravenously on days 22 through 28 . A st and ard protocol for respiratory care was followed by the participating hospitals . The protocol emphasized the criteria of initiation and weaning from mechanical ventilation . The diagnosis of chronic lung disease based on oxygen dependence and abnormal chest roentgenogram was made at 28 days of age . To assess the effect of dexamethasone on pulmonary inflammatory response , serial tracheal aspirates were assayed for cell counts , protein , leukotriene B4 , and 6-keto prostagl and in F1alpha . All infants were observed for possible side effects , including hypertension , hyperglycemia , sepsis , intraventricular hemorrhage , retinopathy of prematurity , cardiomyopathy , and alterations in calcium homeostasis , protein metabolism , and somatic growth . RESULTS Infants in the dexamethasone group had a significantly lower incidence of chronic lung disease than infants in the placebo group either judged at 28 postnatal days ( 21/132 vs 40/130 ) or at 36 postconceptional weeks ( 20/132 vs 37/130 ) . More infants in the dexamethasone group than in the placebo group were extubated during the study . There was no difference between the groups in mortality ( 39/130 vs 44/132 ) ; however , a higher proportion of infants in the dexamethasone group died in the late study period , probably attributable to infection or sepsis . There was no difference between the groups in duration of oxygen therapy and hospitalization . Early postnatal use of dexamethasone was associated with a significant decrease in tracheal aspirate cell counts , protein , leukotriene B4 , and 6-keto prostagl and in F1alpha , suggesting a suppression of pulmonary inflammatory response . Significantly more infants in the dexamethasone group than in the placebo group had either bacteremia or clinical sepsis ( 43/132 vs 27/130 ) . Other immediate , but transient , side effects observed in the dexamethasone group are : an increase in blood glucose and blood pressure , cardiac hypertrophy , hyperparathyroidism , and a transient delay in the rate of growth . CONCLUSIONS In preterm infants with severe respiratory distress syndrome requiring assisted ventilation shortly after birth , early postnatal dexamethasone therapy reduces the incidence of chronic lung disease , probably on the basis of decreasing the pulmonary inflammatory process during the early neonatal period . Infection or sepsis is the major side effect that may affect the immediate outcome . Other observable side effects are transient . In view of the significant side effects and the lack of overall improvement in outcome and mortality , and the lack of long term follow-up data , the routine use of early dexamethasone therapy is not yet recommended OBJECTIVE There is increasing concern in regard to the possible long-term adverse effects of postnatal dexamethasone treatment in preterm infants . The purpose of this study was to assess growth and neurodevelopmental outcome in preterm infants at high risk of chronic lung disease ( CLD ) , treated with early ( < 96 hours ) postnatal dexamethasone . DESIGN Three-year follow-up data of physical growth and neurodevelopmental outcome of preterm infants enrolled in a controlled trial to study the effectiveness of early postnatal dexamethasone administration for the prevention of CLD were review ed . The original trial included 25 treated neonates who received dexamethasone intravenously from the fourth day of life for 7 days ( 0.5 mg/kg/d for the first 3 days , 0.25 mg/kg/d the next 3 days , and 0.125 mg/kg/d on the seventh day ) , and 25 untreated neonates as controls . Forty-five surviving infants ( 22 untreated and 23 treated ) completed the 3-year follow-up . RESULTS At the end of follow-up , infants pertaining to both study groups had similar values for body weight , height , and head circumference , and a similar incidence of infants with anthropometrics data below the third percentile . Moreover , no differences were detected between the groups in regard to incidence of major cranial ultrasound abnormalities , cerebral palsy , major neurosensory impairment or IQ scores , and distribution . CONCLUSIONS Early ( < 96 hours ) postnatal dexamethasone administration at the doses employed in this study did not impair physical or neurodevelopmental outcome in preterm infants at high risk of CLD . However , the small sample size of our study was not tailored to look for long-term outcomes and our results are not in agreement with those of larger trials and systematic review s. The real risks of postnatal dexamethasone administration could be definitely assessed only when more well- design ed trials using long-term neurodevelopmental assessment as the primary outcome will be reported OBJECTIVES To investigate the effect of hydrocortisone treatment on survival without bronchopulmonary dysplasia ( BPD ) and to study whether serum cortisol concentrations predict the response . STUDY DESIGN We performed a r and omized , placebo-controlled trial on infants with gestation < or = 30 weeks , body weight of 501 to 1250 g , and respiratory failure . Hydrocortisone was started before 36 hours of age and given for 10 days at doses from 2.0 to 0.75 mg/kg per day . Shortly before hydrocortisone treatment , basal and stimulated ( ACTH , 0.1 microg/kg ) serum cortisols were measured . RESULTS The study was discontinued early , because of gastrointestinal perforations in the hydrocortisone group ( 4/25 vs 0/26 , P = .05 ) ; 3 of the 4 had received indomethacin/ibuprofen . The incidence of BPD ( 28 % vs placebo 42 % , P = 0.28 ) tended to be lower , and patent ductus arteriosus ( 36 % vs 73 % , P = .01 ) was lower in the hydrocortisone group . The hydrocortisone-treated infants with serum cortisol concentrations above the median had a high risk of gastrointestinal perforation . In infants with cortisol values below the median , hydrocortisone treatment increased survival without BPD . CONCLUSIONS Serum cortisol concentrations measured shortly after birth may identify those very high-risk infants who may benefit from hydrocortisone supplementation Aim : To evaluate the long‐term effects of postnatal dexamethasone treatment in high‐risk infants of very low birthweight . Methods The study included 16 children aged 7.8 to 9.2 y who had been born very prematurely at gestational ages of 24–29 wk and with birthweights of < 1500 g and who had participated in a r and omized study of dexamethasone or placebo treatment in ventilator‐dependent infants at 10 d of age . Flow‐volume spirometry , impulse oscillometry , skin‐prick tests and Doppler echocardiography were carried out at school age , and respiratory morbidity and overall neurological outcome evaluated . Controls were 18 non‐atopic children born at term , tested for lung function . Results : No significant differences were found in respiratory morbidity at school age between the dexamethasone ( n= 8) and placebo ( n= 8) groups . Six of the 16 children had moderate to severe neurosensory impairments , but all were able to walk without support and attended primary school . In prematurely born children , st and ardized height was significantly less than that in controls , but between the two study groups , no significant differences existed in somatic growth . Atopy was uncommon : skin‐prick tests were positive in only one child in the placebo group . In the dexamethasone group , forced vital capacity adjusted to height was significantly higher than that in the placebo group , but impairment of basic lung function and bronchial obstruction was evident in both study groups . No hypertrophic cardiomyopathy was apparent , and non‐invasive measurements of pulmonary arterial pressure did not reveal any significant difference between the study groups Objectives . To study neurologic , educational , and psychological status in adolescence of neonates enrolled in a double-blind , r and omized , controlled trial of dexamethasone therapy for chronic lung disease . Participants . A total of 287 infants who were chronically dependent on supplementary oxygen and were 2 to 12 weeks of age were recruited from 31 centers in 6 countries to a r and omized , controlled trial of dexamethasone base ( 0.5 mg/kg per day for 1 week ) ; 95 % of survivors were review ed at 3 years . Survivors from the 25 British and Irish centers were retraced at 13 to 17 years of age . Outcome Measures . Nonverbal reasoning , British Picture Vocabulary Scale , Goodman Strengths and Difficulties Question naire behavior scores , school national test results , teacher ability ratings , and parental and general practitioner question naires . Results . A total of 195 children were eligible for the follow-up study . Information was available for 150 children ( 77 % ) , with 142 ( 73 % ) being assessed in home visits . No baseline differences were detected between the children included in the follow-up study and those not included . There was a slight excess of cerebral palsy in the steroid group , which was not statistically significant ( relative risk : 1.58 ; 95 % confidence interval : 0.81–3.07 ) . Overall disability rates in both groups were high ( 21 % moderate and 14 % severe ) , but with no difference between the 2 groups ( for severe disability , relative risk : 0.84 ; 95 % confidence interval : 0.37–1.86 ) . Conclusions . Information was obtained for 150 adolescents r and omized to receive dexamethasone or placebo for neonatal chronic lung disease . Rates of disabilities and educational difficulties were high , but with no significant differences between the 2 groups . Some use of open-label steroids in the placebo group plus losses to long-term follow-up monitoring reduced the power of this study to detect clinical ly important differences , and this study can not rule out a real increase in cerebral palsy , as reported by others 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 assess the effectiveness of a “ stress dose ” of hydrocortisone for rescue treatment of refractory hypotension and adrenocortical insufficiency of prematurity in very low birth weight ( VLBW ) infants . We hypothesized that significantly more VLBW infants who were receiving dopamine ≥10 μg/kg per min could wean off vasopressor support 72 hours after treatment with hydrocortisone . Methods . A double-blind , r and omized , controlled study was conducted in a university neonatal center . Forty-eight VLBW infants who had refractory hypotension and required dopamine ≥10 μg/kg per min were r and omly assigned to receive a stress dose of hydrocortisone ( 1 mg/kg every 8 hours for 5 days ; n = 24 ) or an equivalent volume of the placebo solution ( isotonic saline ; n = 24 ) . Results . The baseline clinical characteristics were similar between the groups . Serum cortisol concentrations were very low immediately before r and omization in both groups of infants . Significantly more VLBW infants who were treated with hydrocortisone weaned off vasopressor support 72 hours after starting treatment . The use of volume exp and er , cumulative dose of dopamine , and dobutamine were significantly less in hydrocortisone-treated infants compared with control infants . In addition , the median duration of vasopressor treatment was halved in hydrocortisone-treated patients . Two versus 11 infants in the hydrocortisone and control groups required a second vasopressor for treatment of refractory hypotension . The trend ( linear and quadratic ) of the mean arterial blood pressure was also significantly and consistently higher in hydrocortisone-treated infants . Conclusions . A stress dose of hydrocortisone was effective in treating refractory hypotension in VLBW infants . Although routine and prophylactic use of systemic corticosteroids could not be recommended because of their potential adverse effects , this relatively low dose of hydrocortisone would probably be preferable to high-dose dexamethasone for treatment of refractory hypotension in emergency and life-threatening situations Objective : The purpose of this study was to evaluate the effect of early administration of dexamethasone on the incidence of chronic lung disease ( CLD ) in high risk preterm infants and to evaluate the side effects of the early steroid administration . Design : R and omised clinical trial . Setting : Neonatal intensive care unit . Patients : 50 infants at high risk of CLD were r and omly assigned after 72 h of life to the dexamethasone group ( n = 25 ) or to the control group ( n = 25 ) . The treated infants received dexamethasone intravenously from the 4th day of life for 7 days ( 0.5 mg/kg per day for the first 3 days , 0.25 mg/kg per day for the next 3 days and 0.125 mg/kg per day on the 7th day ) . The control group received no steroid treatment . Results : The incidence of CLD at 28 days of life and at 36 weeks ' postconceptional age was significantly lower in the dexamethasone group than in the control group ( p < 0.001 ) . Moreover , infants in the dexamethasone group remained intubated and required oxygen therapy for a shorter period than those in the control group ( p < 0.001 ) . Hyperglycaemia , hypertension , growth failure and mainly hypertrophy of the left ventricle were the transient side effects associated with early steroid administration . Conclusions : Early dexamethasone administration may be useful in preventing CLD , but its use should prudently be restricted to preterm infants at high risk of CLD A r and omized trial was conducted of dexamethasone therapy in infants with bronchopulmonary dysplasia who were dependent on respirators and were not progressing clinical ly despite conventional treatment . Babies were admitted to the study if they had a roentgenogram and clinical diagnosis of bronchopulmonary dysplasia , were 2 to 6 weeks in age , weighed less than 1,500 g , had made no progress in weaning for the preceding five days , and were free of sepsis , patent ductus arteriosus , and congenital heart disease , and had had no intravenous fat for at least 24 hours . After parental consent was obtained , infants were r and omly assigned to control or treatment groups . The study hypothesis was that with steroid treatment , babies could be weaned from the respirator within 72 hours and would show a significant improvement in lung compliance within that time . Sequential analysis exceeded criterion ( P less than .05 ) when seven consecutive untied pairs showed weaning with dexamethasone and failure to wean in control infants . Pulmonary compliance improved by 64 % in the treated group and 5 % in the control group ( P less than .01 ) . No significant intergroup differences were noted in mortality , length of hospital stay , sepsis , hypertension , hyperglycemia , or electrolyte abnormalities . Study design permits the conclusion that dexamethasone can produce substantial short-term improvement in lung function , often permitting rapid weaning from the respirator , but long-term efficacy and safety must be demonstrated by further investigations Corticosteroids are used to ameliorate bronchopulmonary dysplasia ( BPD ) . They also affect normal development , including the expression of growth factors such as vascular endothelial growth factor ( VEGF ) . Deep pulmonary lavage specimens were collected on days 1 , 3 , 7 and 28 of life in 40 infants of < 34 weeks of gestation at birth during a r and omized controlled trial of two doses of dexamethasone ( DEX ) at 12 and 24 h of age for BPD prophylaxis . VEGF was measured by enzyme-linked immunosorbent assay . The 18 DEX and 21 control subjects had similar gestations , birth weights and oxygen requirements at study entry . Lavage VEGF tripled between day 1 and 3 in both groups . The day 7 levels were higher in DEX subjects than in controls . DEX and control values were similar on day 28 . Higher lavage VEGF levels on days 1 and 3 were also correlated with lower gestational age at birth . Lavage VEGF levels were not associated with the development of BPD . We speculate that these DEX- and age-associated changes in VEGF may affect pulmonary angiogenesis OBJECTIVE . Low-dose dexamethasone facilitates extubation in chronically ventilator-dependent infants with no obvious short-term complications . The objective of this study was to determine the long-term effects of low-dose dexamethasone . METHODS . Very preterm ( < 28 weeks ' gestation ) or extremely low birth weight ( birth weight < 1000 g ) infants who were ventilator dependent after the first week of life for whom clinicians considered corticosteroids were indicated were eligible . After informed consent , infants were r and omly assigned to masked dexamethasone ( 0.89 mg/kg over 10 days ) or saline placebo . Survivors were assessed at 2 years ' corrected age by staff blinded to treatment group allocation to determine neurosensory outcome , growth , and health . RESULTS . The trial was ab and oned well short of its target sample size because of recruitment difficulties . Seventy infants were recruited from 11 centers , 35 in each group : 59 survived to 2 years of age , and 58 ( 98 % ) were assessed at follow-up , but data for cerebral palsy were available for only 56 survivors . There was little evidence for a difference in the major end point , the rate of the combined outcome of death , or major disability at 2 years of age ( dexamethasone group : 46 % ; controls : 43 % ) . Rates of mortality before follow-up ( 11 % vs 20 % ) , major disability ( 41 % vs 31 % ) , cerebral palsy ( 14 % vs 22 % ) , or of the combined outcomes of death or cerebral palsy ( 23 % vs 37 % ) were not substantially different between the groups . There were no obvious effects of low-dose dexamethasone on growth or readmissions to hospital after discharge . CONCLUSIONS . Although this trial was not able to provide definitive evidence on the long-term effects of low-dose dexamethasone after the first week of life in chronically ventilator-dependent infants , our data indicate no strong association with long-term morbidity OBJECTIVE To test the hypothesis that high-risk ventilator-dependent extremely low birth weight ( birth weight ≤1000 g ) infants treated with 7 days of hydrocortisone will have larger total brain tissue volumes than placebo treated infants . STUDY DESIGN A predetermined sample size of 64 extremely low birth weight infants , between 10 - 21 days old and ventilator-dependent with a respiratory index score ≥2 , were r and omized to systemic hydrocortisone ( 17 mg/kg cumulative dose ) or saline placebo . Primary outcome was total brain tissue volume . Volumetric magnetic resonance imaging was performed at 38 weeks postmenstrual age ; brain tissue regions were segmented and quantified automatically with a high degree of accuracy and 9 structures were segmented manually . All analyses of regional brain volumes were adjusted by postmenstrual age at magnetic resonance imaging scan . RESULTS The study groups were similar at baseline and 8 infants died in each arm . Unadjusted total brain tissue volume ( mean ± SD ) in the hydrocortisone ( N = 23 ) and placebo treated infants ( N = 21 ) was 272 ± 40.3 cm(3 ) and 277.8 ± 59.1 cm(3 ) , respectively ( adjusted mean difference : 6.35 cm(3 ) ( 95 % CI : ( -20.8 , 32.5 ) ; P = .64 ) . Three of the 31 hydrocortisone treated infants and 5 of the 33 placebo treated infants survived without severe bronchopulmonary dysplasia ( relative risk 0.62 , 95 % CI : 0.13 , 2.66 ; P = .49 ) . No significant differences were noted in prespecified secondary outcomes of regional structural volumes or days on respiratory support . No adverse effects of hydrocortisone were observed . CONCLUSIONS Low dose hydrocortisone in high-risk ventilator-dependent infants after a week of age had no discernible effect on regional brain volumes or pulmonary outcomes prior to neonatal intensive care unit discharge In order to assess the efficacy of a combination of systemic and nebulized corticosteroids in reducing the incidence and severity of chronic lung disease ( CLD ) in very low birthweight ( VLBW ) infants , 60 ventilator‐dependent infants ≤ 1500 g were r and omly assigned to receive either steroids or placebo as of 7d . The steroid group ( n= 30 , GA = 25:8 ± 1:6 weeks , BW = 731 ± 147 g ) received systemic dexamethasone for 3 d , followed by nebulized budesonide for 18 d. Control infants ( n= 30 , GA = 25:9 ± 1.8 weeks , BW = 796 ± 199 g ) received systemic and inhaled saline . Steroid‐treated infants required less ventilatory support between 9 and 17 d ( p < 0:01 ) , and had greater lung compliance at 10 d ( p= 0:01 ) , but not subsequently . CLD incidence at 36 weeks was 45.5 % vs 56.0 % in controls , and fewer steroid‐treated infants required dexamethasone rescue ( 23.3 % vs 56.7 % , p= 0:017 ) . Survival to discharge was similar ( 73.3 % vs 83.3 % ) , as were the duration s of mechanical ventilation , supplemental oxygen use , and hospitalization . Tracheal effluent elastase/albumin ratios and serum cortisol values did not differ between groups , and no adverse effects were noted . We conclude that early dexamethasone administration was associated with improved pulmonary function , which was not sustained with nebulized budesonide . However , the steroid regimen studied reduced the need for dexamethasone rescue in infants with CLD Objective . To assess the effect on duration of ventilator dependency of a 42-day tapering course of dexamethasone in very low birth weight neonates . Methods . Infants ( N = 118 ) were assigned r and omly , within birth weight/gender strata , to treatment with either a 42-day tapering course of dexamethasone or an equal volume of saline as placebo . Entry criteria were 1 ) birth weight < 1501 g ; 2 ) age between 15 and 25 days ; 3 ) < 10 % decrease in ventilator setting s for 24 hours and Fio 2 ≥0.3 ; 4 ) absence of patent ductus arteriosus , sepsis , major congenital malformation , congenital heart disease ; and 5 ) no evidence of maternal HIV or hepatitis B infection . The dosage schedule was 0.25 mg/kg bid for 3 days , then 0.15 mg/kg bid for 3 days , then a 10 % reduction in the dose every 3 days until a dose of 0.1 mg/kg had been given for 3 days , from which time a dose of 0.1 mg/kg qod was continued until 42 days after entry . The primary endpoint was the number of days on assisted ventilation after study entry . Secondary outcomes of interest included days on supplemental oxygen , days of hospitalization , and potential adverse effects , such as infection , gastrointestinal bleeding , left ventricular hypertrophy , and severe retinopathy of prematurity . Results . Infants in the dexamethasone- and placebo-treated groups were similar in terms of baseline attributes , including birth weight , gestational age , gender , race , and ventilator setting s at entry . Infants treated with dexamethasone were on assisted ventilation and supplemental oxygen for fewer days after study entry ( median days on ventilator , 5th and 95th percentiles , 13 [ 1–64 ] vs 25 [ 6–104 ] ; days on oxygen , 59 [ 6–247 ] vs 100 [ 11–346 ] ) . No differences were found in risk of death , infection , or severe retinopathy . In subgroup analyses , the association of dexamethasone with more rapid weaning from the ventilator was weaker among infants enrolled before the 16th day of life , infants with chest radiographs showing cystic changes and /or hyperinflation , and infants requiring an Fio 2 ≥0.7 or a peak inspiratory pressure ≥19 at study entry . Conclusions . A 42-day tapering course of dexamethasone decreases the duration of ventilator and oxygen dependency in very low birth weight infants and is not associated with an increased risk of short-term adverse effects Background : Several reports indicate a decreased cortisol response to adrenocorticotropic hormone in preterm infants developing chronic lung disease and in preterm infants with refractory hypotension . Low-dose hydrocortisone ( HC ) may allow for beneficial effects . Objective : Our aim was to assess whether HC is able to increase survival without chronic lung disease . Methods : We performed a double-blind , r and omized , placebo-controlled trial . Fifty mechanically ventilated infants ( birth weight : 500–1,249 g ) were r and omized to receive treatment ( HC 0.5 mg/kg/12 h for 9 days , then HC 0.5 mg/kg/24 h for 3 days ) or placebo . Major outcome was survival without oxygen dependence at 36 weeks of postconceptional age ( O2-free survival ) . Results : The basic characteristics were similar between the two groups . O2-free survival was higher in the HC group ( 64 vs. 32 % ) . The advantage was particularly evident among infants without antenatal steroids . The mortality rate was 16 % in the HC group versus 40 % in the control group ( difference not significant ) . Hypotension after recruitment was reduced by HC ( 0 vs. 30 % ) . The incidence of gastrointestinal perforation and other adverse effects was similar between the two groups . Conclusions : HC prophylaxis improved O2-free survival and early cardiocirculatory function in our population , without important short-term effects . The neurodevelopmental outcome will be assessed at 2 years Background . Infection is a major complication of preterm infants , result ing in increased morbidity and mortality . We recently reported the results of a multicenter trial of dexamethasone initiated at 14 or 28 days in very low birth weight ( VLBW ) infants who were at risk for chronic lung disease ; the results showed an increase in nosocomial bacteremia in the group receiving dexamethasone . This study is an in-depth analysis of bacteremia/sepsis and meningitis among infants enrolled in the trial . Methods . Data on cultures performed and antibiotic therapy were collected prospect ively . Infections were classified as definite or possible/ clinical . Results . A total of 371 infants were enrolled in the trial . There were no baseline differences in risk factors for infection . For the first 14 days of study , infants received either dexamethasone ( group I , 182 ) or placebo ( group II , 189 ) . During this period , infants in group I were significantly more likely than those in group II to have a positive blood culture result ( 48 % vs 30 % ) and definite bacteremia/sepsis/meningitis ( 22 % vs 14 % ) . Over the 6-week study period , 47 % of those cultured had at least one positive blood culture result ( 53 % in group I vs 41 % in group II ) and 25 % of the infants had at least one episode of definite bacteremia/sepsis/meningitis ( 29 % in group I vs 21 % in group II ) . Among infants with definite infections , 46.8 % were attributable to Gram-positive organisms , 26.6 % to Gram-negative organisms and 26.6 % to fungi . The factors present at r and omization were evaluated for their association with infection . Group I assignment and H2blocker therapy ( before study entry ) were associated with increased risk of definite infection , whereas cesarean section delivery and increasing birth weight were associated with decreased risk . Conclusions . Infants who received a 14-day course of dexamethasone initiated at 2 weeks of age were more likely to develop a bloodstream or cerebrospinal fluid infection while on dexamethasone therapy than were those who received placebo . Physicians must consider this increased risk of infection when deciding whether to treat VLBW infants with dexamethasone Background . Infants developing bronchopulmonary dysplasia ( BPD ) show decreased cortisol response to adrenocorticotropic hormone . A pilot study of low-dose hydrocortisone therapy for prophylaxis of early adrenal insufficiency showed improved survival without BPD at 36 weeks ’ postmenstrual age , particularly in infants exposed to histologic chorioamnionitis . Methods . Mechanically ventilated infants with birth weights of 500 to 999 g were enrolled into this multicenter , r and omized , masked trial between 12 and 48 hours of life . Patients received placebo or hydrocortisone , 1 mg/kg per day for 12 days , then 0.5 mg/kg per day for 3 days . BPD at 36 weeks ’ postmenstrual age was defined clinical ly ( receiving supplemental oxygen ) and physiologically ( supplemental oxygen required for O2 saturation ≥90 % ) . Results . Patient enrollment was stopped at 360 patients because of an increase in spontaneous gastrointestinal perforation in the hydrocortisone-treated group . Survival without BPD was similar , defined clinical ly or physiologically , as were mortality , head circumference , and weight at 36 weeks . For patients exposed to histologic chorioamnionitis ( n = 149 ) , hydrocortisone treatment significantly decreased mortality and increased survival without BPD , defined clinical ly or physiologically . After treatment , cortisol values and response to adrenocorticotropic hormone were similar between groups . Hydrocortisone-treated infants receiving indomethacin had more gastrointestinal perforations than placebo-treated infants receiving indomethacin , suggesting an interactive effect . Conclusions . Prophylaxis of early adrenal insufficiency did not improve survival without BPD in the overall study population ; however , treatment of chorioamnionitis-exposed infants significantly decreased mortality and improved survival without BPD . Low-dose hydrocortisone therapy did not suppress adrenal function or compromise short-term growth . The combination of indomethacin and hydrocortisone should be avoided OBJECTIVE To determine the changes in pulmonary mechanics before and during early dexamethasone therapy , and to evaluate the effect of dexamethasone on the duration of mechanical ventilation in very low birth weight ( VLBW ) ventilator-dependent infants at risk for chronic lung disease ( CLD ) . METHODS A prospect i ve r and omized trial was conducted . Forty-three patients ( birth weight 600 to 1500 g , gestational age 24 to 32 weeks ) who failed to be weaned from the respirator at 7 to 14 days of age were enrolled ; 23 infants received a 7-day course of dexamethasone ( 0.5 mg/kg/day intravenously for 3 days , 0.25 mg/kg/day for 3 days , and 0.1 mg/kg/day for 1 day ) , and 20 patients were in the control group . At similar mean airway pressure ( MAP ) and fractional inspired oxygen concentration ( FiO2 ) , respiratory system mechanics were measured before and on days 2 , 5 , and 7 of the study . Airway pressure , flow and tidal volume ( VT ) were recorded and only mechanical breaths were analyzed . Respiratory compliance ( Crs ) and respiratory resistance ( Rrs ) were calculated by two factor least mean square analysis . RESULTS Eighty-three percent of infants in the dexamethasone group and 90 % in the control group received surfactant in the first 24 hours of life . There was a significant increase in Crs and VT in the dexamethasone group as compared with the control group ( P < .001 ) . No major changes in Rrs were observed . Dexamethasone therapy significantly decreased FiO2 and MAP P < .001 ) and facilitated successful weaning from mechanical ventilation . In addition to a shorter duration of mechanical ventilation ( P < .01 ) , the occurrence of CLD ( FiO2 > 0.21 at 36 weeks of corrected gestational age , chest radiograph changes ) was significantly decreased in the dexamethasone group ( P < .01 ) . Except for a transient increase in blood pressure and serum glucose , there were no significant differences in infection rates , intraventricular hemorrhage , or retinopathy of prematurity . Thirteen patients in the control group received dexamethasone at a later age . CONCLUSIONS Our findings indicate that : 1 ) early dexamethasone therapy in VLBW infants markedly improves respiratory compliance and tidal volume , reduces FiO2 and MAP requirements , and facilitates extubation in these infants ; 2 ) early dexamethasone therapy reduces the duration of mechanical ventilation and decreases CLD ( at 28 days and 36 weeks ) in a population of VLBW infants largely treated with surfactant ABSTRACT : The mechanisms explaining the beneficial effects of glucocorticoid in ventilator-dependent preterm infants are not known . In the present r and omized trial , we evaluated the hypothesis that dexamethasone ( DEX ) treatment of small , preterm infants at risk for chronic lung disease favorably affects the surfactant system . Twenty-three ventilator-dependent infants , with a mean ± SD gestational age of 26 ± 2 wk and a mean birth weight of 836 ± 173 g , received 1 wk of treatment with either DEX ( dose 0.5 mg/kg/d ) or placebo beginning at 2 wk of age . The airway specimens were analyzed for surfactant components , surface activity , surfactant inhibitors , and inflammatory mediators . The concentrations of these parameters in epithelial lining fluid were calculated using the urea method . DEX treatment decreased the concentration of nonsedimentable protein in epithelial lining fluid within 3 d ( p < 0.05 ) . The nonsedimentable fraction of airway specimens decreased the surface activity of surfactant as a function of protein concentration . At a constant protein concentration , the protein from placebo-treated infants inhibited the surface activity of human surfactant in vitro more than protein from DEX-treated infants ( p < 0.05 ) . DEX transiently increased the concentration of surfactant protein-A in epithelial lining fluid but had no effect on surface activity of the sediment-able surfactant complex or on concentrations of phosphati-dylcholine , IL-ip , lactoferrin , or myeloperoxidase . We conclude that the acute beneficial effect of DEX treatment in preterm ventilator-dependent infants may in part be mediated through a decrease in the concentration of non-sedimentable protein and a decrease in the capacity of this protein to inhibit surface activity OBJECTIVE To test the hypothesis that early postnatal dexamethasone will reduce the incidence of death or chronic lung disease ( CLD ) in ventilated extremely low birth weight premature infants . DESIGN Multicenter r and omized double-blinded controlled clinical trial . SETTING A total of 42 neonatal intensive care units in the Vermont Oxford Network . PARTICIPANTS Infants weighing 501 to 1000 g were eligible for enrollment at 12 hours of age if they needed assisted ventilation , had received surfactant replacement therapy , were physiologically stable , had no obvious life-threatening congenital anomaly , and had blood cultures obtained and antibiotic therapy initiated . INTERVENTION Infants were r and omly assigned to dexamethasone or saline placebo . Intravenous dexamethasone was administered for 12 days according to the following dosing schedule : 0.5 mg/kg/d for 3 days , 0.25 mg/kg/d for 3 days , 0.10 mg/kg/d for 3 days , 0.05 mg/kg/d for 3 days . Infants in either group could receive treatment with selective late postnatal steroids beginning on day 14 of life if they were on assisted ventilation with supplemental oxygen greater than 30 % . OUTCOME MEASUREMENTS The primary outcome measure was CLD or death at 36 weeks postmenstrual age . RESULTS The study was stopped before completion of sample size goals because of concern about serious side effects in the early steroid treatment group . A total of 542 infants were enrolled ( early treatment N = 273 , control N = 269 ) . The 2 groups had similar demographic characteristics . No differences were noted in the primary outcome of CLD or death at 36 weeks postmenstrual age ( early treatment 50 % vs control : 53 % , relative risk : 0.93 ; 95 % confidence interval [ CI ] : 0.79 - 1.09 ) . Fewer infants who received early steroid treatment had a patent ductus arteriosus ( relative risk : 0.78 ; 95 % CI : 0.63 - 0.96 ) , and fewer infants in the early steroid group received indomethacin therapy ( relative risk : 0.74 ; 95 % CI : 0.64 - 0.86 ) or late steroid treatment ( relative risk : 0.69 ; 95 % CI : 0.58 - 0.81 ) . However , more infants who received early steroid treatment had complications associated with therapy including an increase in hyperglycemia ( relative risk : 1.29 ; 95 % CI : 1.13 - 1.46 ) and an increase in the use of insulin therapy ( relative risk : 1.62 ; 95 % CI : 1.36 - 1.94 ) . A trend toward increased gastrointestinal hemorrhage ( relative risk : 1.55 ; 95 % CI : 0.92 - 2.61 ) , gastrointestinal perforation ( relative risk : 1.53 ; 95 % CI : 0.89 - 2.61 ) , and an increased systolic blood pressure ( relative risk : 1.34 ; 95 % CI : 0.97 - 1.85 ) was noted . In infants receiving cranial ultrasound examinations , a marginal increase in periventricular leukomalacia was noted in the early steroid treatment group ( relative risk : 2.23 ; 95 % CI : 0.99 - 5.04 ) . Infants who received early steroid therapy had fewer days in supplemental oxygen but experienced poor weight gain . CONCLUSIONS A 12-day course of early postnatal steroid therapy given to extremely low birth weight infants did not decrease the risk of CLD or death at 36 weeks postmenstrual age and was associated with an increased risk of complications and poor weight gain Objective . To assess the effects of early postnatal dexamethasone therapy on hematologic values in preterm infants . Material s and Methods . We review ed the hematologic data of 179 preterm infants who participated in a double-blind clinical trial of early postnatal dexamethasone therapy ( < 12 hours after birth ) for the prevention of chronic lung disease . One group ( 86 infants ) received saline and the other group ( 93 infants ) received dexamethasone . Dexamethasone was given intravenously every 12 hours in tapering doses : 0.25 mg/kg on days 1 to 7 , 0.12 mg/kg on days 8 to 14 , 0.05 mg/kg on days 15 to 21 , and 0.02 mg/kg on days 21 to 28 . Blood sample s were obtained on days 0 , 3 , 7 , 10 , 14 , 21 , and 28 . None of the infants received prenatal steroid therapy . Results . Multiple regression analysis revealed significant differences in the values versus time curves of the white blood cell , neutrophil , lymphocyte , basophil , and eosinophil counts between the two groups . The white blood cell count was significantly higher in the dexamethasone group on days 7 through 14 , and this was associated with significantly higher numbers of segmented neutrophils and b and forms and significantly lower numbers of lymphocytes and eosinophils . The hematocrit and platelet counts were similar in the two groups throughout most of the trial . Except for platelet count , steroid therapy did not alter the hematologic values for infants with bacteremia . Conclusion . Dexamethasone affects white blood cell , segmented neutrophil , lymphocyte , basophil , and eosinophil counts in neonates . This should be taken into consideration when evaluating preterm infants who are receiving dexamethasone . early dexamethasone therapy ; neonatal blood count ; preterm infant ; respiratory distress syndrome OBJECTIVE To study the long term neurodevelopmental outcome of children who participated in a r and omised , double blind , placebo controlled study of early postnatal dexamethasone treatment for prevention of chronic lung disease . METHODS The original study compared a three day course of dexamethasone ( n = 132 ) with a saline placebo ( n = 116 ) administered from before 12 hours of age in preterm infants , who were ventilated for respiratory distress syndrome and had received surfactant treatment . Dexamethasone treatment was associated with an increased incidence of hypertension , hyperglycaemia , and gastrointestinal haemorrhage and no reduction in either the incidence or severity of chronic lung disease or mortality . A total of 195 infants survived to discharge and five died later . Follow up data were obtained on 159 of 190 survivors at a mean ( SD ) age of 53 ( 18 ) months . RESULTS No differences were found between the groups in terms of perinatal or neonatal course , antenatal steroid administration , severity of initial disease , or major neonatal morbidity . Dexamethasone treated children had a significantly higher incidence of cerebral palsy than those receiving placebo ( 39/80 ( 49 % ) v 12/79 ( 15 % ) respectively ; odds ratio ( OR ) 4.62 , 95 % confidence interval ( 95 % CI ) 2.38 to 8.98 ) . The most common form of cerebral palsy was spastic diplegia ( incidence 22/80 ( 28 % ) v 5/79 ( 6 % ) in dexamethasone and placebo treated infants respectively ; OR 4.45 , 95 % CI 1.95 to 10.15 ) . Developmental delay was significantly more common in the dexamethasone treated group ( 44/80 ( 55 % ) ) than in the placebo treated group ( 23/79 ( 29 % ) ; OR 2.87 , 95 % CI 1.53 to 5.38 ) . Dexamethasone treated infants had more periventricular leucomalacia and less intraventricular haemorrhage in the neonatal period than those in the placebo group , although these differences were not statistically significant . Eleven children with cerebral palsy had normal ultrasound scans in the neonatal period ; all 11 had received dexamethasone . Logistic regression analysis showed both periventricular leucomalacia and drug assignment to dexamethasone to be highly significant predictors of abnormal neurological outcome . CONCLUSIONS A three day course of dexamethasone administered shortly after birth in preterm infants with respiratory distress syndrome is associated with a significantly increased incidence of cerebral palsy and developmental delay To determine whether early ( less than or equal to 12 hours ) postnatal dexamethasone therapy would facilitate removal of the endotracheal tube and improve outcome in premature infants with severe respiratory distress syndrome , we conducted a double-blind , controlled study of 57 infants whose birth weights were less than 2000 gm . The placebo ( n = 29 ) and treated ( n = 28 ) groups were comparable in birth weight ( mean + /- SD : 1273 + /- 323 vs 1318 + /- 359 gm ) , gestational age ( 30.1 + /- 2.1 vs 30.8 + /- 2.7 weeks ) , postnatal age ( 8.7 + /- 3.1 vs 8.5 + /- 3.1 hours ) , and pulmonary function at the start of the study . The dose of dexamethasone was 1.0 mg/kg/day for 3 days and then was progressively decreased for 12 days . Infants in the dexamethasone group had significantly higher pulmonary compliance , tidal volume , and minute ventilation , and required lower mean airway pressure for ventilation than infants in the placebo group . The endotracheal tube was successfully removed from more infants in the dexamethasone group ( 16/28 vs 8/29 ; p less than 0.025 ) . Nineteen infants ( 65 % ) in the placebo group and 11 ( 39 % ) in the dexamethasone group ( p less than 0.05 ) had lung injuries . Dexamethasone therapy was associated with a temporary increase in blood pressure and plasma glucose concentration and a delay in somatic growth . We conclude that early postnatal dexamethasone therapy improves pulmonary status , facilitates removal of the endotracheal tube , and minimizes lung injuries in premature infants with severe respiratory distress syndrome Abstract . Patent ductus arteriosus ( PDA ) is believed to be a contributing factor in the etiopathogenesis of bronchopulmonary dysplasia ( BPD ) . We studied the effects of early dexamethasone therapy on persistent ductal patency and the role of PDA in the etiopathogenesis of BPD during the course of a r and omized double-blind trial of dexamethasone to prevent BPD . Infants , who weighed between 700 and 999 g , had severe RDS , and had been given surfactant , were r and omized to receive a 12-day course of dexamethasone ( n= 13 ) or placebo ( n= 17 ) starting within the first 12 hours of postnatal life . The diagnosis of PDA was made clinical ly and was confirmed by cardiac ultrasound . The incidence of clinical ly significant ductus in infants who weighed less than 1000 g was 23 % in the dexamethasone-treated group , as compared with 59 % in infants who were given placebo . This difference was marginally significant , p= 0.05 , odds ratio 0.21 , 95 % confidence interval 0.04–1.05 . None of the infants in the dexamethasone group had recurrence of PDA after indomethacin therapy as compared with three infants in the placebo group . Dexamethasone significantly reduced the number of days infants required ventilator and supplemental oxygen as compared with infants who received placebo . Dexamethasone , as compared with placebo , also reduced the incidence of BPD , p= 0.025 , odds ratio 0.08 , 95 % confidence interval 0.01–0.58 . Dexamethasone may reduce the incidence of PDA in premature infants who weigh less than 1000 g at birth and thereby reduce the incidence of BPD This r and omized controlled trial was design ed to answer the question : does administration of dexamethasone to neonates with bronchopulmonary dysplasia decrease the need for assisted ventilation ? Twenty‐five infants with a birth weight < 1501 g , requiring mechanical ventilation and FiO2 of ± 0.30 at 21‐35 days of age , were r and omized to treatment with iv dexamethasone or to sham injections for 12 days . The primary outcome criterion was extubation within seven days after study entry . Treatment ( n= 12 ) and control ( n= 13 ) groups were well matched at entry . Dexamethasone facilitated weaning from assisted ventilation ( p= 0.0154 ) . There was no increased incidence of infection . Dexamethasone treatment result ed in a significant increase in glucosuria ( p= 0.0002 ) and in systolic blood pressure ( p= 0.0034 ) . There was a significant decrease in heart rate ( p= 0.0001 ) and a significant weight loss ( p= 0.0002 ) following dexamethasone treatment . Dexamethasone treatment facilitated weaning from assisted ventilation but several systemic effects were noted that deserve further evaluation before dexamethasone becomes routine treatment BACKGROUND Methylxanthines reduce the frequency of apnea of prematurity and the need for mechanical ventilation during the first seven days of therapy . It is uncertain whether methylxanthines have other short- and long-term benefits or risks in infants with very low birth weight . METHODS We r and omly assigned 2006 infants with birth weights of 500 to 1250 g during the first 10 days of life to receive either caffeine or placebo , until drug therapy for apnea of prematurity was no longer needed . We evaluated the short-term outcomes before the first discharge home . RESULTS Of 963 infants who were assigned to caffeine and who remained alive at a postmenstrual age of 36 weeks , 350 ( 36 percent ) received supplemental oxygen , as did 447 of the 954 infants ( 47 percent ) assigned to placebo ( adjusted odds ratio , 0.63 ; 95 percent confidence interval , 0.52 to 0.76 ; P<0.001 ) . Positive airway pressure was discontinued one week earlier in the infants assigned to caffeine ( median postmenstrual age , 31.0 weeks ; interquartile range , 29.4 to 33.0 ) than in the infants in the placebo group ( median postmenstrual age , 32.0 weeks ; interquartile range , 30.3 to 34.0 ; P<0.001 ) . Caffeine reduced weight gain temporarily . The mean difference in weight gain between the group receiving caffeine and the group receiving placebo was greatest after two weeks ( mean difference , -23 g ; 95 percent confidence interval , -32 to -13 ; P<0.001 ) . The rates of death , ultrasonographic signs of brain injury , and necrotizing enterocolitis did not differ significantly between the two groups . CONCLUSIONS Caffeine therapy for apnea of prematurity reduces the rate of bronchopulmonary dysplasia in infants with very low birth weight . ( Clinical Trials.gov number , NCT00182312 . ) Objectives . To study the growth , health status , and respiratory outcomes at 13 to 17 years of infants enrolled in a double-blind , r and omized , controlled trial of dexamethasone for the treatment of neonatal chronic lung disease . Participants . A total of 287 infants who were chronically dependent on supplementary oxygen between 2 and 12 weeks of age were recruited from 31 centers in 6 countries to a double-blind , r and omized , controlled trial of dexamethasone base ( 0.5 mg/kg per day for 1 week ) or placebo , and survivors were evaluated at 3 years . Children from the 25 British and Irish centers were traced for re assessment at 13 to 17 years of age . Outcome Measures . Respiratory symptoms , lung-function testing , height , weight , head circumference , blood pressure , health re source usage , and school absences . Results . There was no significant difference in respiratory outcomes between the dexamethasone and placebo groups . Lung function was impaired but with no difference between the 2 groups . Growth was also impaired in both groups , with height z score of −0.7 , weight z score of −0.4 , and head circumference z score of −1.1 . Systolic blood pressure was > 95th percentile for age and height for 15 % of children , but with no difference between the 2 groups . There was no difference in the numbers of hospital admissions for respiratory causes or other causes . Conclusions . Despite a shorter duration of neonatal assisted ventilation , there is no evidence that dexamethasone use is associated with long-term improvement in lung function . Impaired growth and poor health status are long-term consequences of neonatal chronic lung disease , irrespective of exposure to neonatal dexamethasone AIM To determine whether treatment with inhaled nitric oxide ( NO ) and /or dexamethasone reduces the incidence of chronic lung disease ( CLD ) and /or death in high risk preterm infants . METHODS Infants below 32 weeks of gestation were recruited at 96 hours of age if they were deemed to be at high risk of developing CLD . Infants were r and omly assigned to one of four treatment groups using a factorial design : ( 1 ) 5–20 parts per million inhaled NO for 72 hours ; ( 2 ) 0.5–1 mg/kg/day intravenous dexamethasone for 6 days ; ( 3 ) both drugs together ; ( 4 ) continued conventional management . RESULTS Forty two infants were r and omised : 10 infants received inhaled NO alone ; 11 dexamethasone alone ; 10 both treatments ; and 11 neither treatment . There was no difference in the combined incidence of CLD and /or death before discharge from hospital between either infants treated with inhaled NO and controls ( RR 1.05 , 95 % CI 0.84–1.25 ) , or those treated with dexamethasone and controls ( RR 0.95 , 95 % CI 0.79–1.18 ) . CONCLUSIONS At 96 hours of age , neither treatment with inhaled NO nor dexamethasone prevented CLD or death OBJECTIVE We compared the effects of a policy of neonatal steroid administration versus placebo for babies chronically dependent on supplemental oxygen in terms of long-term health and development , judged at 3 years of age . DESIGN Double-blind r and omized controlled trial . SETTING Thirty-one centers in the United Kingdom , Irel and , Belgium , Germany , Canada , and the United States . PATIENTS Babies who were chronically dependent on supplemental oxygen between 2 and 12 weeks of age were recruited to the trial between 1986 and 1989 . Sixty-two children were known to have died , 23 before discharge from the hospital and 10 afterward in the active group , compared with 25 and 4 , respectively , in the placebo group . Information was available for 209 of the 212 eligible for follow-up ( 99 % ) . INTERVENTIONS A 1-week course of active dexamethasone phosphate 0.6 mg/kg/d ( dexamethasone base 0.5 mg/kg/d ) or saline placebo was given intravenously ( or orally , if no intravenous line ) . There was an option to give a second tapering 9-day course if relapse occurred after initial improvement . OUTCOME MEASURES Information about respiratory problems , growth , neurodevelopment and disability , infection , and health service use when the children were 3 years old was ascertained from question naires to general practitioners , health visitors , and parents ( and occasionally pediatricians ) . RESULTS About half the children in both groups had been admitted to the hospital for respiratory problems , with more in the active than the placebo group having at least five outpatient consultations for these problems over the 3 years . Overall , the children were below average in height , weight , and head circumference . About one fifth had cerebral palsy , 8 % some visual loss , and 16 % hearing loss ; 18 % needed or were anticipated to need special schooling . There were no clear differences between the r and omized groups . These overall conclusions were not altered by any of the prespecified secondary analyses . CONCLUSIONS Despite early benefits , there were no clear effects at 3 years of age . As 40 % of the placebo group eventually received open steroids , even a trial of this size has limited statistical power to detect a moderate effect of the policy . Regardless of r and om allocation , overall morbidity was high , confirming that babies with protracted dependence on supplemental oxygen are at high risk of childhood disability and poor health UNLABELLED BACKGROUND . Many extremely low birth weight infants ( < 1000 g ) show biochemical evidence of adrenal insufficiency in the first week of life , correlating with subsequent development of chronic lung disease ( CLD ) . METHODS We conducted a r and omized , double-masked , placebo-controlled pilot study to test whether early treatment with low-dose hydrocortisone for 12 days ( 1 mg/kg/day for 9 days followed by.5 mg/kg/day for 3 days ) , begun before 48 hours of life , would increase the likelihood of survival without CLD . RESULTS Forty patients were enrolled at two centers . Birth weight and gestation were similar for treatment and placebo groups : 732 + /- 135 g versus 770 + /- 135 g and 25.2 + /- 1.3 weeks versus 25.4 + /- 1.5 weeks . More infants treated with hydrocortisone achieved study success , defined as survival without supplemental oxygen at 36 weeks ' postconception ( 12/20 [ 60 % ] vs 7/20 [ 35 % ] ) . Lower birth weight , histologic chorioamnionitis , and preeclampsia were significant risk factors , whereas study center , prenatal steroids , sex , and ethnicity were not significant . Hydrocortisone treatment decreased days on > 40 % oxygen , days on > 25 % oxygen , days on ventilator , and oxygen at discharge . Among infants exposed to chorioamnionitis , hydrocortisone treatment also was associated with increased enteral intake during the first month of life and with increased weight at 36 weeks ' postconception . Five treated infants and 6 placebo infants developed sepsis ; 3 in each group died . CONCLUSIONS First , early treatment with low-dose hydrocortisone in this population of extremely low birth weight infants increased the likelihood of survival without CLD . Second , the benefit was particularly apparent in infants with chorioamnionitis . Third , a larger multicenter trial is needed to verify the primary outcome and to better evaluate risks and benefits A r and omized double-blind placebo-controlled trial was conducted to evaluate the effects of enterally administered dexamethasone on the hospital course of infants with bronchopulmonary dysplasia . A total of 23 infants with a birth weight less than 1500 g who were dependent on artificial ventilation 3 to 4 weeks of age received dexamethasone ( n = 12 ) or saline placebo ( n = 11 ) . Dexamethasone ( 0.5 mg/kg per day ) was given in tapering doses for 7 days followed by hydrocortisone ( 8 mg/kg per day ) which was progressively reduced for a total of 17 days of therapy . Infants who received dexamethasone required less oxygen on days 8 and 17 ( P less than .05 ) and were more likely to extubate 8 days after therapy than infants in the control group ( respectively 8/12 vs 3/11 infants , P less than .05 ; P = .12 after Yates correction ) . The use of dexamethasone significantly shortened median duration of mechanical ventilation ( 4 vs 22 days , P less than .05 ) but had no effect on length of oxygen therapy , hospitalization , home oxygen therapy , occurrence and severity of retinopathy of prematurity , rate of growth , and mortality . No significant complications result ed from dexamethasone therapy . Measurements of plasma dexamethasone levels confirmed the absorption of drug from the gastrointestinal tract ( 23.7 ng/mL in dexamethasone vs 4.6 ng/mL in the control group , P less than .05 ) . Dexamethasone administration result ed in short-term improvements in pulmonary function but did not ameliorate the hospital course of infants with bronchopulmonary dysplasia OBJECTIVE : Extremely low birth weight ( ELBW ) infants are at risk for hypotension . Abnormal adrenal function may play a role in the pathogenesis of hypotension , and therefore , the administration of hydrocortisone ( HC ) may be an effective treatment for hypotension in some infants . However , the efficacy of prophylactic HC to prevent the use of vasopressors for a defined hypotensive state has not been studied . We conducted a r and omized-controlled trial to determine the potential role on adrenal insufficiency in early neonatal hypotension and to determine the effectiveness of prophylactic HC in reducing treatment of hypotension in ELBW infants . STUDY DESIGN : Infants were assigned to receive either HC or placebo within the first 3 hours of life . Therapy was continued for 5 days . The presence of hypotension was based on an operational definition and treatment with vasopressors ( VP ) was st and ardized based on an a priori protocol . RESULTS : A total of 34 patients were enrolled . Baseline characteristics were similar between groups . Of the HC group 25 % received VP at 24 hours of age compared to 44 % of the placebo group . On day of life 2 , only 7 % of the HC group received VP compared to 39 % of the placebo group ( p<0.05 ) . CONCLUSION : Prophylactic treatment with HC reduces the incidence of hypotension , defined by treatment with VP , among ELBW infants during the first 2 days of life . However , the mounting evidence that prophylactic administration of glucocorticoids in the first days of life is harmful to ELBW infants makes HC prophylaxis unwise until the efficacy of treatment relative to safety can be clearly established To determine whether dexamethasone therapy altered the outcome of chronic lung disease in neonates , we conducted a prospect i ve , r and omized , placebo-controlled trial . Twenty-one 30-day-old oxygen- and ventilator-dependent infants were enrolled . The mean ( + /- SD ) birth weight was 808.1 + /- 141 gm and the mean gestational age was 26.0 + /- 1.5 weeks . There were 17 black and 12 male infants . Twelve received placebo and nine received dexamethasone . Neither severity of early illness , birth weight , gestational age , age when treated , gender and race distribution , nor frequency of diuretic therapy differed significantly between groups . The age at extubation , 57.2 days ( placebo ) versus 39.4 days ( steroid ) , was significantly different . The average oxygen requirements of the steroid-treated patients was significantly lower than for placebo-treated patients during the first 10 days of treatment . There were no differences for placebo-versus steroid-treated patients in age when weaned to room air ( 95.5 days vs 74.9 days ) , age at discharge ( 119 days vs 111 days ) , or number of deaths ( 2 ( 17 % ) vs 1 ( 11 % ] . Dexamethasone therapy was associated with a significantly increased incidence of hyperglycemia ( 89 % vs 8 % ) but did not influence the incidence of hypertension , intracranial hemorrhage , infection , or retinopathy of prematurity . The steroid-treated patients had a significant delay in weight gain during the first 3 weeks of treatment but recovered by discharge . Our results suggest that dexamethasone produces acute improvement in infants with lung disease but no long-term effect on mortality rate , duration of oxygen requirement or age at discharge OBJECTIVE . Postnatal corticosteroid therapy is controversial . The aim of this study was to determine the short-term effects of low-dose dexamethasone treatment among chronically ventilator-dependent neonates . METHODS . Very preterm ( gestational age : < 28 weeks ) or extremely low birth weight ( birth weight : < 1000 g ) infants who were ventilator dependent after the first 1 week of life were eligible and were assigned r and omly to receive masked dexamethasone ( 0.89 mg/kg over 10 days ) or saline placebo . Data on ventilator and oxygen requirements and deaths were recorded . RESULTS . Seventy infants were recruited from 11 centers , at a median age of 23 days . More infants were extubated successfully by 10 days of treatment in the dexamethasone group ( 60 % , 21 of 35 patients ) than in the control group ( 12 % , 4 of 34 patients ) ( odds ratio [ OR ] : 11.2 ; 95 % confidence interval [ CI ] : 3.2–39.0 ) . Ventilator and oxygen requirements improved substantially , and the duration of intubation was shorter . There was little evidence for a reduction in either the mortality rate ( dexamethasone group : 11 % ; control group : 20 % ; OR : 0.52 ; 95 % CI : 0.14–1.95 ) or the rate of oxygen dependence at 36 weeks ( dexamethasone group : 85 % ; control group : 91 % ; OR : 0.58 ; 95 % CI : 0.13–2.66 ) . There were no obvious effects of low-dose dexamethasone on blood glucose concentrations , blood pressure , or other complications . No infant experienced intestinal perforation . CONCLUSIONS . Low-dose dexamethasone treatment after the first 1 week of life clearly facilitates extubation and shortens the duration of intubation among ventilator-dependent , very preterm/extremely low birth weight infants , without any obvious short-term complications . Combined with recent evidence that infants at very high risk of bronchopulmonary dysplasia may benefit in the long term , our study reopens debate regarding the role of low-dose , late postnatal , corticosteroid therapy ABSTRACT : Bronchopulmonary dysplasia is an important complication of ventilation in babies for which treatment with steroids has been advocated . We report the results of a phase I study of early i.v . dexamethasone to prevent the development of bronchopulmonary dysplasia in a high-risk population of ventilated premature babies , < 30 wk gestation , with surfactant-treated respiratory distress syndrome . This study used a limited dexamethasone dosing regimen to minimize toxicity but used administration early in the course of acute lung disease to interrupt the injury cycle . Forty babies were enrolled ; 19 were r and omized to receive dexamethasone ( 0.5 mg/kg birth weight at 12–18 h of age and a second dose 12 h later ) and 21 were r and omized to receive placebo ( i.v . saline ) . The dexamethasone group required less ventilatory support ( mean airway , peak in-spiratory and end expiratory pressures , and intermittent m and atory ventilation ) and supplemental oxygen after study d 4 ( all p < 0.05 , repeated measures analysis of variance ) . Improved tidal volume in the dexamethasone group , as measured by pulmonary function testing of infants who remained intubated , was seen on study d 7 ( p = 0.02 , t test ) . The dexamethasone group required shorter hospitalizations ( median of 95 d versus 106 d , p = 0.01 ) ( proportional hazards regression ) . Survival in the dexa methasone group was 89 % versus 67 % in the placebo group ( p = 0.08 , x2 analysis ) . Survival without bronchopulmonary dysplasia , diagnosed at 36 wk corrected gestational age , was 68 % in the dexamethasone group versus 43 % in the placebo group ( p = 0.14 ) . Mean blood pressure was elevated on study d 4 through 7 in the dexamethasone group , but this difference resolved by study d 10 without pharmacologic intervention . No differences in hyperglycemia , incidence of intraventricular hemorrhage ( or its severity ) , or days to regain birth weight were seen . Early administration of dexamethasone result ed in short-term and suggested long-term benefits without significant complications . The results of this trial justify a large scale , broader-based ( phase II ) trial in premature babies with respiratory distress syndrome to determine the limits of effectiveness and the incidence of less-frequent potential side effects OBJECTIVE To test the efficacy of single-dose dexamethasone ( DXM ) in the management of severe arterial hypotension of newborn infants . Our hypothesis was that epinephrine infusions could be discontinued in 70 % of patients within 12 hours after DXM administration compared with 10 % in the placebo group . STUDY DESIGN Twenty preterm infants ( median birth weight 690 g , gestational age 28 weeks , age at intervention 2 days ) who did not respond to a st and ardized treatment protocol ( blood/colloid followed by dopamine infusion stepwise increased to 15 micrograms/kg and minute ) were started on an epinephrine infusion and were r and omly allocated to receive either DXM ( 0.25 mg/kg ) or placebo intravenously . The primary outcome criterion was the need for an epinephrine infusion 12 hours after treatment . RESULTS Three infants were excluded . Epinephrine infusion was discontinued in 5 of 8 infants with DXM but in only 1 of 9 infants in the control group . The duration of epinephrine infusion was significantly shorter in the DXM group ( exact log-rank test , P = . 023 ) . CONCLUSIONS DXM was effective for the management of severe arterial hypotension in preterm infants not responding to st and ardized treatment The potential induction of cardiac effects by high-dose dexamethasone therapy was evaluated prospect ively in 13 respirator-dependent infants with bronchopulmonary dysplasia by means of two-dimensional and M-mode echocardiography . The initial divided dose of dexamethasone was 500 micrograms/kg per day , tapered progressively for as long as 6 weeks . Evaluations were made before treatment and at 3 , 7 , 14 , 21 , 28 , 35 , and 42 days after the start of dexamethasone therapy . This regimen was associated with a significant ( p less than 0.01 ) increase in thickness of the interventricular septum ( 2.60 + /- 0.09 to 4.00 + /- 0.16 mm ) , diastolic left ventricular free wall ( 2.80 + /- 0.13 to 4.06 + /- 0.20 mm ) , and diastolic right ventricular free wall ( 1.55 + /- 0.08 to 2.02 + /- 0.12 mm ) . In addition , seven dexamethasone-treated infants but no control infants had systolic anterior motion of the mitral valve ( p less than 0.001 ) . These effects were transient , reached their maximal degree by the third week of treatment , and approached pretreatment conditions by the sixth week of treatment . Ejection fraction was not affected ; heart rate and mean arterial pressure were transiently increased during dexamethasone therapy . We conclude that a transient absolute myocardial hypertrophy is associated with dexamethasone therapy in infants with bronchopulmonary dysplasia . The mechanism or mechanisms through which this hypertrophy arises and the cardiopulmonary implication s are unclear BACKGROUND : Early postnatal use of dexamethasone in infants with respiratory distress syndrome ( RDS ) has been shown effectively to improve pulmonary status and to allow early weaning off mechanical ventilation . However , the mechanisms to explain the beneficial effects of dexamethasone in ventilatory dependent preterm infants remain unclear . METHODS : A double blind , placebo controlled study was performed to determine the change in pulmonary ventilation of premature infants with RDS as a result of dexamethasone treatment , and to evaluate the effect of dexamethasone on the levels of surfactant-associated proteins A ( SP-A ) and D ( SP-D ) in the tracheal fluid from 34 premature infants with RDS and 29 control subjects . RESULTS : Dexamethasone treatment decreased fractional inspired oxygen concentration ( FIO2 ) , arterial carbon dioxide tension ( PCO2 ) , mean airway pressure ( MAP ) , and facilitated successful weaning from mechanical ventilation . SP-A concentrations in the tracheal aspirates were increased at days 7 and 14 , and SP-D concentrations were increased during the period from days 3 to 14 in the dexamethasone treated group compared with the control group . However , albumin levels in the tracheal aspirate sample s were decreased after dexamethasone treatment over the period from days 3 to 14 . There was an inverse correlation between PCO2 values and SP-A concentrations . CONCLUSIONS : These results suggest that early use of dexamethasone can improve pulmonary status and also increase SP-A and SP-D levels in the tracheal fluid in premature infants with RDS BACKGROUND We studied the outcomes at school age in children who had participated in a double-blind , placebo-controlled trial of early postnatal dexamethasone therapy ( initiated within 12 hours after birth ) for the prevention of chronic lung disease of prematurity . METHODS Of the 262 children included in the initial study , 159 lived to school age . Of these children , 146 ( 72 in the dexamethasone group and 74 in the control group ) were included in our study . All the infants had had severe respiratory distress syndrome requiring mechanical ventilation shortly after birth . In the dexamethasone group , 0.25 mg of dexamethasone per kilogram of body weight was given intravenously every 12 hours for one week , and then the dose was tapered . We evaluated the children 's growth , neurologic and motor function , cognition , and school performance . RESULTS Children in the dexamethasone group were significantly shorter than the controls ( P=0.03 for boys , P=0.01 for girls , and P=0.03 for all children ) and had a significantly smaller head circumference ( P=0.04 ) . Children in the dexamethasone group had significantly poorer motor skills ( P<0.001 ) , motor coordination ( P<0.001 ) , and visual-motor integration ( P=0.02 ) . As compared with the controls , children in the dexamethasone group also had significantly lower full IQ scores ( mean [ + /-SD ] , 78.2+/-15.0 vs. 84.4+/-12.6 ; P=0.008 ) , verbal IQ scores ( 84.1+/-13.2 vs. 88.4+/-11.8 , P=0.04 ) , and performance IQ scores ( 76.5+/-14.6 vs. 84.5+/-12.7 , P=0.001 ) . The frequency of clinical ly significant disabilities was higher among children in the dexamethasone group than among controls ( 28 of 72 [ 39 percent ] vs. 16 of 74 [ 22 percent ] , P=0.04 ) . CONCLUSIONS Early postnatal dexamethasone therapy should not be recommended for the routine prevention or treatment of chronic lung disease , because it leads to substantial adverse effects on neuromotor and cognitive function at school age OBJECTIVE To characterize the cardiac effects of dexamethasone in very low birth weight infants . DESIGN Prospect i ve , r and omized , placebo-controlled , double-blind trial . Enrolled subjects were r and omized to receive either a 42-day tapering course of dexamethasone or a saline placebo . Echocardiographic measurements were obtained on days 0 , 7 , 14 , 28 , and 42 . SUBJECTS Thirteen infants received dexamethasone and 13 a saline placebo . The two groups were similar in birth weight , gestational age , age at enrollment , and sex/ race composition . RESULTS Patients receiving dexamethasone had a significantly larger increase in septal thickness on days 7 , 14 , and 28 and left ventricle ( LV ) posterior wall thickness on day 14 . A significantly lower left ventricular end-diastolic dimension in the dexamethasone group was initially noted on day 7 and persisted until day 42 . With the reduced left ventricular end-diastolic dimension , no significant differences in LV mass were noted , despite the increased wall thickness . No differences in LV systolic function , as assessed by area shortening , were seen . Assessment of diastolic function showed a significant increase in the atrial portion of mitral inflow in dexamethasone patients on day 14 , as well as a significant prolongation in isovolumic relaxation time on days 7 , 14 , and 28 . CONCLUSIONS Infants receiving dexamethasone developed evidence for impaired LV filling with a lager increase in wall thickness but no increase in LV mass , asymmetric septal hypertrophy , or augmented systolic function . This suggests that alterations in left ventricular filling play an important role in the development of hypertrophy seen with dexamethasone administration Eighteen infants were entered into a r and omized , placebo-controlled trial of dexamethasone therapy for chronic lung disease . Initial ventilation requirements were similar in the two groups , although all infants were in headbox oxygen on entry to the trial . The dexamethasone-treated infants showed a significantly more rapid improvement during the 1st week of treatment , although the overall duration of oxygen therapy was similar in both groups . Cranial ultrasound examination revealed new periventricular abnormalities in three out of the five dexamethasone-treated infants who had previously normal scans , compared with none of four similar placebotreated infants . A large trial , focussing on potential complications , is now needed We evaluated the use of dexamethasone in preterm infants to decrease morbidity associated with bronchopulmonary dysplasia in a r and omized , double-blind , placebo-controlled trial . Thirty-six preterm infants ( birth weight , less than or equal to 1250 g and gestational age , less than or equal to 30 weeks ) who were dependent on oxygen and mechanical ventilation at two weeks of age received a 42-day course of dexamethasone ( n = 13 ) , an 18-day course of dexamethasone ( n = 12 ) , or saline placebo ( n = 11 ) . The starting dose of dexamethasone was 0.5 mg per kilogram of body weight per day , and it was progressively lowered during the period of administration . Infants in the 42-day dexamethasone group , but not those in the 18-day group , were weaned from mechanical ventilation significantly faster than control infants ( medians 29 , 73 , and 84 days , respectively ; P less than 0.05 ) , and from supplemental oxygen ( medians 65 , 190 , and 136 days , respectively ; P less than 0.05 ) . No clinical complications of steroid administration were noted . Follow-up of all 23 survivors at 6 and 15 months of age showed good outcome ( normal neurologic examinations and Bayley Developmental Indexes greater than or equal to 84 ) in 7 of the 9 infants in the 42-day dexamethasone group , but in only 2 of the 9 infants in the 18-day dexamethasone group and 2 of the 5 in the placebo group ( P less than 0.05 ) . We conclude that dexamethasone therapy for 42 days improves pulmonary and neurodevelopmental outcome in very-low-birth-weight infants at high risk for bronchopulmonary dysplasia OBJECTIVE A short course of moderately early dexamethasone therapy with a starting dose of 0.5 mg/kg/day improves lung compliance and shortens the duration of ventilatory support in preterm infants with respiratory distress syndrome ( RDS ) . We conducted a double-blind , r and omized study to evaluate whether a moderately early 14-day weaning course of low-dose dexamethasone affects adrenal function and facilitates weaning from the ventilator . PATIENTS AND METHODS Thirty-six preterm infants with a gestational age < or = 32 weeks who required ventilatory support for RDS on days 7 - 14 were r and omized to a 14-day treatment course with dexamethasone ( 0.2 mg/kg/day start , tapering doses ) or placebo ( equivalent amounts of normal saline ) . Prior to the first study treatment and the day after completion of the treatment course , adrenal function was assessed from serum cortisol levels drawn before and 30 min after intravenous administration of 0.1 mg Cortrosyn . Extubation rate during treatment in both groups was compared . RESULTS In both groups baseline serum cortisol levels decreased significantly during treatment , but stimulated cortisol levels did not change . After the 14-day treatment course , stimulated cortisol levels increased significantly from baseline levels in both groups ( p<0.001 ) , following Cortrosyn administration . More infants in the dexamethasone group were extubated within 7 - 14 days of study entry than in the placebo group ( p<0.05 ) . Hyperglycemia was more frequently diagnosed in the dexamethasone group and open-label dexamethasone treatment was given more frequently in the control group . CONCLUSIONS A moderately early 14-day weaning course of low-dose dexamethasone does not significantly suppress the adrenal function of very preterm infants with RDS , but accelerates weaning from the ventilator We conducted a prospect i ve , r and omized , double-blind trial to assess the efficacy and safety of pulse doses of dexamethasone on survival without supplemental oxygen in very low birth weight infants at high risk of having chronic lung disease . Seventy-eight infants with birth weights < or = 1500 gm who were ventilator dependent at 7 days of postnatal age were r and omly assigned to receive pulse doses of dexamethasone , 0.5 mg/kg per day , divided twice daily ( n = 39 ) , or an equivalent volume of saline solution placebo ( n = 39 ) , for 3 days at 10-day intervals until they no longer required supplemental oxygen or assisted ventilation , or reached 36 weeks of postmenstrual age . At study entry , the groups did not differ by birth weight , gestational age , or severity of lung disease . At 36 weeks of postmenstrual age , there was both a significant increase in survival rates without oxygen supplementation ( p = 0.03 ) and a significant decrease in the incidence of chronic lung disease ( p = 0.047 ) in the group that received pulse therapy . Supplemental oxygen requirements were less throughout the study period in the group that received repeated pulse doses of dexamethasone ( p = 0.013 ) . The total numbers of deaths and the duration s of supplemental oxygen , ventilator support , and hospital stay did not differ between groups . Recorded side effects in the pulse therapy group were minimal and included an increase in the use of insulin therapy for hyperglycemia ( p < 0.05 ) . We conclude that in this population of very low birth weight infants , treatment with pulse doses of dexamethasone result ed in improvement in pulmonary outcome without clinical ly significant side effects OBJECTIVE Evaluation of repeated pulses of dexamethasone ( PDEX ) , given to improve cardiopulmonary outcome , on growth of very low birth weight ( VLBW , < 1500 g ) infants . METHODS In this prospect i ve , double-blind , r and omized clinical trial , VLBW infants mechanically ventilated at 1 week of age received intravenous PDEX or saline placebo ( P ) for 3 days , every 10 days , until no supplemental oxygen or ventilation was required or 36 weeks postmenstrual age ( PMA ) . Weight gain , fluid intake , caloric intake , and serum glucose were monitored throughout the study . Nutritional assessment at 36 weeks PMA consisted of weight , length , head circumference , skinfold thickness measures , body composition by total body electrical conductance , and bone mineral content ( BMC ) by single beam photon absorptiometry . RESULTS 37 PDEX and 31 P infants survived at least 36 days and completed the protocol . Average daily weight gain , fluid intake and caloric intake were not different between groups . The pattern of weight gain ( g/kg/day , mean + /- SD ) was different : PDEX infants showed significant growth delay during ( 3.0 + /- 11.4 ) and immediately after ( 7.8 + /- 8.7 ) each pulse , with subsequent growth acceleration ( 18.3 + /- 8.2 ) until the next steroid pulse . In contrast , growth rate of P infants was constant ( 12.6 + /- 3.7 ) ( p = 0.04 ) . Hyperglycemia requiring insulin therapy occurred only in the PDEX group ( 10/37 ) . The catch-up growth noted between pulses in the PDEX group was explained only in part by insulin therapy . At 36 weeks PMA , there were no differences between groups in body size , composition , or BMC . CONCLUSION PDEX negatively affected glucose metabolism and growth patterns during and immediately after drug exposure . However , assessment near term gestational age showed similar body composition and size in both groups A r and omized study was design ed to evaluate the effects of two different dexamethasone courses on the growth of preterm infants . The first phase included 30 preterm infants at high risk for chronic lung disease ( CLD ) . 15 babies ( moderately early dexamethasone group ) were treated with dexamethasone for 14 days , from the 10th day of life , and received a total dose of 4.75 mg/kg ; 15 babies were assigned to the control group . The second phase included 30 preterm infants at high risk for CLD . 15 babies ( early dexamethasone group ) were treated with dexamethasone for 7 days , from the 4th day of life , and received a total dose of 2.38 mg/kg ; 15 babies were assigned to the control group . All the main clinical baseline characteristics were similar between the groups both in the first and in the second phase . Infants given the two dexamethasone courses showed significantly reduced weight gain during the period of treatment when compared to the respective control group , but they had a weight catch-up soon after the end of treatment . At 30 days of life the weight and length gain of each treated group were similar to those of control infants , but the moderately early dexamethasone group showed a significantly poorer head growth . No differences between the groups were observed at discharge . Dexamethasone treatment induces a slower weight gain which is time-limited to the period of treatment and is followed by a body weight catch-up . However , the poorer head growth detected at 30 days of life in the infants who received a higher dose of dexamethasone could indicate important adverse effects , possibly dose-related , on postnatal brain growth and development The changes induced on respiratory mechanics and on tracheobronchial aspirate fluid ( TAF ) cytology by dexamethasone courses started at two different postnatal ages in preterm infants at risk of chronic lung disease ( CLD ) were reported in this clinical trial design ed in two phases . The first phase of the study included 20 neonates with birth weight ≤1,250 g and gestational age ≤32 weeks , who were oxygen and ventilator dependent on the 10th day of life . They were r and omly assigned to the moderately early dexamethasone ( MED ) group or to the control group . The second phase of the study included 20 neonates with the same characteristics , oxygen and ventilator dependent on the 4th day of life , r and omly assigned to the early dexamethasone ( ED ) group or to the control group . Both treated groups received dexamethasone intravenously for 7 days ( 0.5 mg/kg/day for the first 3 days , 0.25 mg/kg/day for the next 3 days , and 0.125 mg/kg/day for the last day of treatment ) . The control groups received no steroid treatment . A significantly lower absolute cell count and percentage of neutrophils ( PMN ) in the TAF and significantly higher dynamic lung compliance ( Cdyn ) values were observed in both the MED treated compared to the untreated infants and the ED treated infants compared to the control group . Moreover these changes were more precocious in the ED Group compared to the MED Group . Our study suggests that dexamethasone could be more efficacious in reducing effects of ventilator-induced lung injury in preterm infants at high risk of CLD when started earlier Background . We previously demonstrated improved survival and early outcomes in a pilot trial of 2 doses of intravenous dexamethasone for infants with surfactant-treated respiratory distress syndrome.1 A multicenter , r and omized , double-blind trial was undertaken to confirm these results . Methods . Infants < 30 weeks ' gestation were eligible if they had respiratory distress syndrome , required mechanical ventilation at 12 to 18 hours of age , and had received at least 1 dose of exogenous surfactant . Infants were excluded if sepsis or pneumonia was suspected or if congenital heart disease or chromosomal abnormalities were present . A total of 384 infants were enrolled—189 r and omized to dexamethasone ( .5mg/kg birth weight at 12–18 hours of age and a second dose 12 hours later ) and 195 to an equal volume of saline placebo . Results . No differences were found in the dexamethasone versus placebo groups , respectively , regarding the primary outcomes of survival ( 79 % vs 83 % ) , survival without oxygen at 36 weeks ' corrected gestational age ( CGA ; both 59 % ) , and survival without oxygen at 36 weeks ' CGA and without late glucocorticoid therapy ( 46 % vs 44 % ) . No significant differences between the groups in estimates from Kaplan-Meier survival analyses were found for median days on oxygen ( 50 vs 56 days ) , ventilation ( 20 vs 27 days ) , days to regain birth weight ( 15.5 vs 14 days ) , or length of stay ( LOS ; 88 vs 89 days ) . Infants given early dexamethasone were less likely to receive later glucocorticoid therapy for bronchopulmonary dysplasia during their hospitalization ( 27 % vs 35 % ) . No clinical ly significant side effects were noted in the dexamethasone group , although there were transient elevations in blood glucose and blood pressure followed by a return to baseline by study day 10 . Among infants who died ( 40 vs 33 ) , there were no differences in the median days on oxygen , ventilation , nor LOS . However , in survivors ( 149 vs 162 ) , the following were observed : median days on oxygen 37 versus 45 days , ventilation 14 versus 19 days , and LOS 79 versus 81 days , for the dexamethasone versus placebo groups , respectively . Conclusions . This dose of early intravenous dexamethasone did not reduce the requirement for oxygen at 36 weeks ' CGA and survival was not improved . However , early dexamethasone reduced the use of later prolonged dexamethasone therapy , and among survivors , reduced the median days on oxygen and ventilation . We conclude that this course of early dexamethasone probably represents a near minimum dose for instituting a prophylactic regimen against bronchopulmonary dys- plasia We examined 26 preterm infants with respiratory distress syndrome in a r and omized controlled prospect i ve study to determine whether early postnatal dexamethasone therapy ( < 2h ; 0.5 mg/kg per day ) over 5 days in addition to substitution of surfactant ( 100 mg/kg ) facilitates extubation and the course of RDS . Control ( n= 12 ) and treated ( n= 14 ) groups were comparable in birthweight ( mean ± SD : 1219 ± 292 versus 1446 ± 442 g ) , gestational age ( 29.3 ± 2.2 versus 30.6 ± 2.7 weeks ) , prenatal characteristics and initial respiratory and blood gas parameters . In both groups one infant died . Infants in the dexamethasone group responded better to surfactant ( 12/14 versus 3/12 ; p < 0.01 ) , were extubated earlier ( 6.6 versus 14.2 days ; p < 0.02 ) and required less time on supplemental oxygen ( 4.2 versus 12.5 days ; p < 0.02 ) . Pulmonary complications tended to be lower in the dexamethasone group ( 1/14 versus 4/12 ) , as was the frequency of retinopathy ( 2/14 versus 6/12 ; p < 0.05 ) . We conclude that early postnatal dexamethasone therapy improves response to surfactant therapy result ing in better weaning and earlier extubation in premature infants BACKGROUND Ventilator-dependent premature infants are often treated with dexamethasone . However , the optimal timing of therapy is unknown . METHODS We compared the benefits and hazards of initiating dexamethasone therapy at two weeks of age and at four weeks of age in 371 ventilator-dependent very-low-birth-weight infants ( 501 to 1500 g ) who had respiratory index scores ( mean airway pressure x the fraction of inspired oxygen ) of 52.4 at two weeks of age . One hundred eighty-two infants received dexamethasone for two weeks followed by placebo for two weeks , and 189 infants received placebo for two weeks followed by either dexamethasone ( those with a respiratory-index score of > or = 2.4 on treatment day 14 ) or additional placebo for two weeks . Dexamethasone was given at a dose of 0.25 mg per kilogram of body weight twice daily intravenously or orally for five days , and the dose was then tapered . RESULTS The median time to ventilator independence was 36 days in the dexamethasone-placebo group and 37 days in the placebo-dexamethasone group . The incidences of chronic lung disease ( defined as the need for oxygen supplementation at 36 weeks ' postconceptional age ) were 66 percent and 67 percent , respectively . Dexamethasone was associated with an increased incidence of nosocomial bacteremia ( relative risk , 1.5 ; 95 percent confidence interval , 1.1 to 2.1 ) and hyperglycemia ( relative risk , 1.9 ; 95 percent confidence interval , 1.2 to 3.0 ) in the dexamethasone-placebo group , elevated blood pressure ( relative risk , 2.9 ; 95 percent confidence interval , 1.2 to 6.9 ) in the placebo-dexamethasone group , and diminished weight gain and head growth ( P < 0.001 ) in both groups . CONCLUSIONS Treatment of ventilator-dependent premature infants with dexamethasone at two weeks of age is more hazardous and no more beneficial than treatment at four weeks of ages Recent studies suggest that early dexamethasone therapy may lessen the pulmonary inflammation in preterm infants with respiratory distress syndrome ( RDS ) . To investigate whether early ( < 12 hr ) postnatal dexamethasone therapy would reduce the incidence of chronic lung disease ( CLD ) , a r and omized , double-blind , controlled trial was conducted in 40 infants ( birth weights from 500 to 1,999 gm ) who had severe RDS and required mechanical ventilation within 6 hr of birth . All infants received one dose of Survanta before they were r and omly assigned to control ( saline placebo ) or dexamethasone-treated groups ( 0.5 mg/kg/d for 1 week , then tapered over 3 weeks ) . Sequential analysis was performed with the end point of assessment being the presence or absence of CLD on postnatal Day 28 . Statistical significance favoring dexamethasone was reached when 12 consecutive pairs in which one infant had CLD and the other did not have CLD showed that ten pairs favored dexamethasone and two pairs favored control treatment . Among the survivors , 12/15 were extubated in the dexamethasone group and 9/16 in the control group at the end of study . Infants in the treated group had transient hyperglycemia and hypertension . There was no difference between the groups in mortality and in incidence of sepsis or intraventricular hemorrhage . We conclude that early postnatal dexamethasone therapy is potentially effective in the lessening of CLD in preterm infants . To substantiate our result , large r and omized controlled trials are needed and warranted The objective of the study was to test the hypothesis that early postnatal dexamethasone administration ( days 1 - 5 ) in preterm infants with respiratory distress syndrome would improve acute respiratory status and therefore decrease long-term neonatal morbidity . This was a prospect i ve , blind r and omized controlled trial . Eligible neonates were preterm infants with birthweight < or = 1500 g who developed respiratory distress syndrome requiring mechanical ventilation and surfactant . A 5-day course of dexamethasone or placebo was initiated within the first 6 h after birth . The starting dose of dexamethasone was 0.5 mg/kg/day and it was tapered progressively . Results were analysed with t-test chi 2 , Wilcoxon test , and ANOVA . Twenty-nine infants ( n = 15 of early dexamethasone and n = 14 of placebo group ) fulfilled the inclusion criteria . The dexamethasone group exhibited a significant improvement in arterial to alveolar oxygen ratio only between postnatal days 2 and 5 ( p = 0.02 ) . This initial improvement was not associated with long-term benefits . Infants who received dexamethasone had increased systolic blood pressure ( p = 0.0001 ) , diastolic blood pressure ( p = 0.001 ) , blood sugar ( p = 0.02 , serum urea ( p = 0.03 ) , and creatinine level ( p = 0.02 ) . All these side-effects were resolved by postnatal day 7 . We concluded that a 5-day course of early postnatal dexamethasone was associated with only a transient improvement in oxygenation with no long-term benefits . Side-effects were more common in the dexamethasone group OBJECTIVES This study was carried to evaluate the effect of early administration of dexamethasone on the incidence of bronchopulmonary dysplasia ( BPD ) and /or death in surfactant-treated preterm infants with respiratory distress syndrome ( RDS ) . STUDY DESIGN In a multicenter , double-blind , placebo-controlled trial , 109 preterm infants with RDS and birth weights between 700 and 1600 gm , who were treated with mechanical ventilation and surfactant , were r and omly assigned before 36 hours of life to receive dexamethasone ( n = 55 ) or placebo ( n = 54 ) for 12 days . RESULTS There were no differences in the incidence of BPD and /or death between groups . However , fewer patients in the dexamethasone group were oxygen-dependent at 36 weeks after conception ( 8 % vs 33 % , p < 0.05 ) . The dexamethasone group had a lower incidence of necrotizing enterocolitis ( 0 % vs 9 % , p < 0.05 ) . The incidence of arterial hypertension , hyperglycemia , and sepsis was not affected by the treatment . Basal and poststimulation serum cortisol levels did not differ between groups . CONCLUSION The administration of dexamethasone early in the course of RDS does not decrease the incidence of BPD and /or death in preterm infants . However , dexamethasone may reduce oxygen dependency at 36 weeks after conception A r and omised double blind placebo controlled study was conducted to determine whether a one week course of dexamethasone could reduce the severity of bronchopulmonary dysplasia in preterm infants without compromising their adrenal function . Forty one infants with a mean birth weight of 880 g and a gestational age of 27 weeks who were ventilator dependent at 10 days of age were enrolled . At the age of 28 days pulmonary outcome was significantly better in the girls treated with dexamethasone but not in all infants . There was no difference between the groups in the long term outcome , except for a shorter duration of supplemental oxygen in dexamethasone treated female infants . After the one week dexamethasone treatment there was a significant but short lived suppression of the basal cortisol concentrations and the adrenal response to corticotrophin ( ACTH ) . No serious side effects were observed . It is concluded that early one week dexamethasone treatment improves short term pulmonary outcome in premature infants , but there is no clear evidence of long term benefits OBJECTIVE To assess the feasibility of a r and omized placebo controlled trial ( RCT ) of blood pressure ( BP ) management for extremely preterm infants . STUDY DESIGN This was a prospect i ve pilot RCT of infants 23 - 0/7 to 26 - 6/7 weeks gestation who had protocol -defined low BP in the first 24 postnatal hours . Enrolled infants were administered a study infusion ( dopamine or placebo ) and a study syringe medication ( hydrocortisone or placebo ) . RESULTS Of the 366 infants screened , 119 ( 33 % ) had low BP , 58 ( 16 % ) met all entry criteria , and 10 ( 3 % ) were enrolled . A total of 161 infants ( 44 % ) were ineligible because they received early indomethacin . Only 17 % of eligible infants were enrolled . Problems with consent included insufficient time , parent unavailability , and physician unwillingness to enroll critically ill infants . Two infants were withdrawn from the study because of the potential risk of intestinal perforation with simultaneous administration of hydrocortisone and indomethacin . CONCLUSIONS This pilot RCT was not feasible because of low eligibility and consent rates . An RCT of BP management for extremely preterm infants may require a waiver of consent for research in emergency care . The frequent use of early indomethacin and the associated risk of intestinal perforation when used with hydrocortisone may limit future investigations to only inotropic medications OBJECTIVE To determine whether postnatal dexamethasone ( DEX ) exposure affects pulmonary outcomes at school age in children born with very low birth weight ( VLBW ) . STUDY DESIGN Follow-up study of 68 VLBW children who participated in a r and omized controlled trial of postnatal DEX . Pulmonary function was assessed by spirometry . Current asthma status was obtained from a parent . RESULTS Sixty-eight percent of the placebo group had below-normal forced expiratory volume in 1 second ( FEV1 ) , compared with 40 % of the DEX group ( chi2 = 4.84 ; P = .03 ) , with trends for lower forced vital capacity ( FVC ) and FEV1 values in the placebo group . Fifty percent of the placebo group and 34 % of DEX group had below normal FEV1/FVC ( chi2 = 1.59 ; P = .21 ) . Parent-reported prevalence of asthma did not differ between groups . Logistic regression analysis suggested that the positive effects of DEX on pulmonary function at follow-up were mediated in part by shortened exposure to mechanical ventilation . CONCLUSIONS Postnatal DEX exposure was associated with higher expiratory flow with no adverse effects on pulmonary outcomes at school age . The prevalences of asthma and impaired pulmonary function underscore the influence of neonatal illness on health at school age , and stress the importance of repeated follow-up examinations of these children Objective . Ventilator-dependent preterm infants are often treated with a prolonged tapering course of dexamethasone to decrease the risk and severity of chronic lung disease . The objective of this study was to assess the effect of this therapy on developmental outcome at 1 year of age . Methods . Study participants were 118 very low birth weight infants who , at 15 to 25 days of life , were not weaning from assisted ventilation and were then enrolled in a r and omized , placebo-controlled , double-blind trial of a 42-day tapering course of dexamethasone . Infants were examined at 1 year of age , adjusted for prematurity , by a pediatrician and a child psychologist . A physical and neurologic examination was performed , and the Bayley Scales of Infant Development were administered . All examiners were blind to treatment group . Results . Groups were similar in terms of birth weight , gestational age , gender , and race . A higher percentage of dexamethasone recipients had major intracranial abnormalities diagnosed by ultrasonography ( 21 % vs 11 % ) . Group differences were not found for Bayley Mental Development Index ( median [ range ] for dexamethasone-treated group , 94 [ 50–123 ] ; for placebo group , 90 [ 28–117 ] ) or Psychomotor Development Index Index ( median [ range ] ) for dexamethasone-treated group , 78 ( 50–109 ) ; for placebo-treated group , 81 [ 28–117 ] ) . More dexamethasone-treated infants had cerebral palsy ( 25 % vs 7 % ) and abnormal neurologic examination findings ( 45 % vs 16 % ) . In stratified analyses , adjusted for major cranial ultrasound abnormalities , these associations persisted ( OR values for cerebral palsy , 5.3 ; 95 % CI : 1.3–21.4 ; OR values for neurologic abnormality 3.6 ; 95 % CI : 1.2–11.0 ) . Conclusions . A 42-day tapering course of dexamethasone was associated with an increased risk of cerebral palsy . Possible explanations include an adverse effect of this therapy on brain development and /or improved survival of infants who either already have neurologic injury or who are at increased risk for such injury Clinical research must determine whether treatments enhance lives , make little difference , cause significant harm , or do several of these things . This is well illustrated by the epidemic of blindness due to retrolental fibroplasia that affected thous and s of preterm babies in the 1950s.1 Although oxygen was accepted as lifesaving in severe respiratory distress syndrome , r and omised controlled trials showed that its unrestricted use could also cause permanent visual impairment . The risk is minimised with modern oxygen therapy , which is strictly controlled . The lesson is that new treatments need to be tested with r and omised trials that are large enough and with follow ups long enough to provide robust data on all clinical ly important endpoints 12 Dexamethasone for chronic lung disease in preterm infants may be a similar case where we need better data from larger trials with longer follow up . View this table : Hospital mortality , and morbidity after 12 months , in r and omised studies of postnatal BACKGROUND Surfactant therapy now has a well-established role in the treatment of neonates with respiratory distress syndrome but has failed to reduce the incidence of bronchopulmonary dysplasia ( BPD ) . We conducted a double-blind , placebo-controlled trial to test the hypothesis that dexamethasone therapy given during the first 12 days of life to very low birth weight infants would be synergistic to surfactant in preventing BPD . METHODS Seventy surfactant-pretreated infants ( 700 - 1500 g ) who had severe respiratory distress syndrome ( a/A ratio , 0.18 + /- 0.10 ; mean airway pressure , 11.1 + /- 1.9 cm H2O ; fraction of inspired oxygen , 0.81 + /- 0.22 ) were enrolled to receive a 12-day course of dexamethasone ( n = 36 ) or saline placebo ( n = 34 ) starting within the first 12 hours after birth . The starting dose of dexamethasone was 0.5 mg/kg per day , and it was tapered progressively . RESULTS Ventilator variables at 5 to 14 days were significantly improved in those infants who received dexamethasone compared with those who received the placebo . The effect seem to be more marked in infants weighting less than 1250 g at birth . Significantly more infants could be extubated by 14 days of age in the dexamethasone group ( 26 of 32 vs 14 of 32 ) . Dexamethasone therapy reduced the incidence of BPD at 28 days ( odds ratio , 0.1 ; 95 % confidence interval , 0.03 to 0.3 ) and eliminated BPD at 36 weeks ' postconceptional age . Dexamethasone-treated infants had greater weight loss at 14 days ( 12.9 + /- 6.4 % vs 3.7 + /- 8.6 % , respectively ) and higher blood pressures from days 3 to 10 . However , no differences were seen in time to regain birth weight , hypertension ( 1 infant in each group ) , or incidence of intraventricular hemorrhage . CONCLUSIONS We found an additive effect between dexamethasone and surfactant in improving pulmonary status and reducing the incidence of BPD . Compared with the placebo , dexamethasone therapy was more effective in reducing the incidence of BPD in surfactant-pretreated very low birth weight infants OBJECTIVE : To study the effect of early postnatal dexamethasone ( days 1 - 3 ) on the incidence and severity of chronic lung disease in preterm infants with respiratory distress syndrome . METHODS : A multicentre , r and omised , placebo controlled , blinded study was carried out in 18 neonatal intensive care units in Israel . The primary outcome measure was survival to discharge without requirement for supplemental oxygen therapy beyond 28 days of life . The secondary outcome measures were requirement for mechanical ventilation at 3 and 7 days , duration of ventilation or oxygen therapy , need for subsequent steroids for established chronic lung disease and incidence of major morbidities . RESULTS : The study consisted of 248 infants ( dexamethasone n = 132 ; placebo n = 116 ) . No differences were found in the outcome variables except for a reduction in requirement for mechanical ventilation at age 3 days in treated infants ( dexamethasone 44 % , placebo 67 % ; P = 0.001 ) . Gastrointestinal haemorrhage , hypertension , and hyperglycaemia were more common in treated infants , but no life threatening complications , such as gastrointestinal perforation , were encountered . CONCLUSIONS : These data do no support the routine use of early postnatal steroids , but may justify further study in a selected , high risk group of infants OBJECTIVE To study the effect of early postnatal dexamethasone therapy on severity of hyaline membrane disease . DESIGN Prospect i ve , r and omized , controlled , unblinded study . SETTING Neonatal Intensive Care Unit . METHODS 19 babies who had hyaline membrane disease were included in this study . The inclusion criteria were clinical and radiographic diagnosis of RDS , requiring mechanical ventilation and FiO2 > 0.3 . Ten babies received injection dexamethasone 0.5 mg/kg/dose 12 hourly for 3 days starting within 6 hours of birth . The control group did not receive any drug . Babies with active infection , bleeding tendency and congenital malformation were excluded . None of the babies received surfactant . The duration of ventilation and AaDO2 and FiO2 requirements from day one to five were calculated . RESULTS The initial AaDO2 were similar in both the groups but on day 3 , 4 , 5 AaDO2 were low in study group ( 201 , 85 , 70 ) compared to control group ( 236 , 209 , 162 ) . The initial FiO2 were 0.66 and 0.63 in dexamethasone and control groups , respectively and remained high till day 2 and came down in study group on days 3 , 4 and 5 ( 0.41 , 0.27 , 0.27 ) compared to control group ( 0.53 , 0.34 , 0.42 ) . The mean duration of ventilation was shorter in dexamethasone group ( 87 hours ) vs control group ( 120 hours ) . CONCLUSION Early use of postnatal dexamethasone reduces the disease severity and oxygen requirement in RDS and hence would be useful in the Indian context OBJECTIVE . The purpose of this work was to evaluate the effects of a 42-day tapering course of dexamethasone on blood pressure and anthropometric measurements in school-age children who were born with very low birth weight . METHODS . Sixty-eight children , who as neonates participated in a r and omized placebo-controlled trial of a 42-day tapering course of dexamethasone ( n = 38 , dexamethasone ; n = 30 , placebo ) to facilitate weaning from the ventilator , were seen at a median of 9 years of age . Participants underwent measurements of systolic blood pressure , diastolic blood pressure , mid-arm circumference , triceps skinfold thickness , height , and weight . Mann-Whitney U tests were used to compare groups , and Spearman coefficients were used to examine correlations between variables . RESULTS . Comparing dexamethasone- and placebo-treated children , we found no differences in systolic blood pressure , mid-arm circumference , triceps skinfold thickness , height , weight , or body mass index . Twenty-nine percent of all subjects had systolic blood pressure and /or diastolic blood pressure ≥90th percentile for age and gender . Thirty percent of all subjects had body mass index ≥85th percentile for age and gender . CONCLUSIONS . In a group of preterm very low birth-weight infants at high risk for chronic lung disease , we found no effects of dexamethasone on blood pressure or anthropometric measurements at 8 to 11 years of age . Of concern is that a high proportion in this sample had blood pressure ≥90th percentile and /or body mass index ≥85th percentile OBJECTIVES To test the hypothesis that a single dose of dexamethasone given soon after delivery to infants < 28 weeks ' gestation leads to improved cardiopulmonary adaptation in the first week and lowers the risk of significant intraventricular hemorrhage . METHODS In a prospect i ve , blinded , placebo-controlled study , we r and omly assigned 70 infants < 28 weeks ' gestation who were born in the hospital to receive dexamethasone ( 0.2 mg/kg ) ( n = 37 ) or normal saline solution ( n = 33 ) within 2 hours of delivery . After an interim analysis showed that the incidence of intraventricular hemorrhage was much lower than expected , enrollment was stopped and we limited our analysis to a comparison of ventilator setting s , blood pressure , and pressor use during the first 7 days . RESULTS Clinical characteristics of the groups were comparable at study entry . Ventilator weaning occurred more rapidly in the patients who received dexamethasone : their intermittent m and atory ventilation rate was significantly lower on days 1 through 6 , and their peak inspiratory pressure was lower on days 3 through 7 compared with the control group . Mean blood pressures were higher in the dexamethasone group within 12 hours and remained higher through day 5 , but the use of pressors was not different . Fewer infants in the dexamethasone group received indomethacin to treat a patent ductus arteriosus ( 22 % vs 47 % , P < .03 ) . CONCLUSION Dexamethasone given within 2 hours of delivery to preterm infants < 28 weeks ' gestation result ed in lower ventilator setting s and higher mean blood pressures during the first 7 days . Fewer infants required indomethacin to treat a patent ductus arteriosus Objective : To assess the effect of moderately early postnatal dexamethasone treatment on growth and neurodevelopmental outcome in preterm infants . Methods : Thirty preterm infants enrolled in a r and omised clinical trial to investigate the effectiveness of moderately early dexamethasone administration in the treatment of chronic lung disease were routinely followed up . Fifteen babies received a total dose of 4.75 mg/kg over 14 days from the 10th day of life , and 15 babies were untreated . Five infants in each group received open label steroids to facilitate extubation later in their clinical course . Growth and neurodevelopmental outcome are reported . Results : The mean body weight , height , and head circumference as well as the number of babies with anthropometric measurements within normal range were similar in treated and untreated babies . There was no significant difference between treated and control groups with respect to incidence of cerebral palsy , major neurosensory impairment , mean intelligence quotient scores , and behavioural abnormalities . Conclusions : Postnatal dexamethasone treatment with the schedule used in this study did not impair growth and neurodevelopmental outcome in preterm infants . Data from larger trials have raised major concern that postnatal steroid treatment may increase neurodevelopmental impairment . The full extent of the risk will only be known when more trials have reported follow up data OBJECTIVE Our objective was to address the efficacy of 5 days of dexamethasone therapy in preterm infants dependent on ventilation and to measure adrenocorticotropic hormone-stimulated cortisol release after therapy . METHODS This was a r and omized , masked trial . Results were evaluated with Fisher 's exact test and Wilcoxon test . Fifteen preterm infants in a newborn intensive care unit who were dependent on ventilation were enrolled at 8 to 24 days of age . Dexamethasone or normal saline solution was used for treatment . The main outcome measure was ventilator independence . RESULTS Dexamethasone therapy correlated to successful extubation . Posttherapy peak adrenocorticotropic hormone-stimulated cortisol concentrations were lower in infants treated with dexamethasone than in infants treated with saline solution . CONCLUSIONS A 5-day course of dexamethasone may be adequate to achieve ventilator independence . The difference in peak cortisol concentrations may reflect suppression of the hypothalamic-pituitary-adrenal axis by dexamethasone or a higher peak cortisol response in the infants treated with saline solution who have higher ventilatory acuity after therapy |
1,804 | 28,759,284 | Studies were more likely to indicate beneficial effects where anxiety-focused ( rather than illness-focused ) intervention protocol s were utilised , asthma-related education was provided and where the trials focused on individuals with likely clinical levels of anxiety at baseline .
Whilst further high- quality research is needed , available evidence is supportive of anxiety-focused CBT interventions tailored to target the particular mechanisms thought to maintain this comorbidity in asthma | OBJECTIVE Asthma and anxiety are known to interact , leading to exacerbations for both conditions .
This systematic review summarised evidence regarding the effectiveness of cognitive behavioural therapy ( CBT ) in reducing anxiety in individuals with asthma , with results presented separately for adults and children . | An educational training program for children with asthma , aged between 8 and 13 years , was evaluated in an 18-month r and omized , controlled experiment , including three follow-up evaluations . The objective of the program is to improve coping with asthma in daily life . The program , ten 1-hour sessions , is a combination of self-management training and cognitive behaviour therapy in a group , using games and learning material s specifically design ed for this age group . From 195 asthmatic children , 112 with inadequate self-management abilities were selected ; these children were r and omly divided into an experimental group and two control groups . The results indicated highly significant differences in favor of the experimental group on the psychological and medical variables . There were no drop-outs during the program . The conclusion is that this multi-faceted program is an effective method of teaching children how to cope with their asthma and helping them to achieve a less anxious and more realistic attitude towards their illness AIM This article describes a study that aim ed to investigate the effect of nurse-delivered behaviour therapy on anxiety levels and quality of life in children with asthma and coexistent anxiety . METHOD A prospect i ve cohort pilot study in which ten children , aged between seven and ten years , with asthma and diagnosed with health-related anxiety took part . Data were collected over a two-year period , cognitive behaviour therapy sessions were provided , and asthma , anxiety and quality of life scores were measured . FINDINGS The Child and Adolescent Mental Health Services-devised , respiratory nurse-delivered , cognitive behaviour therapy programme was associated with an increase in quality of life for children with asthma and a decrease in anxiety levels and hyperventilation scores . CONCLUSION All nursing staff need to be aware of the detrimental effects of anxiety on asthma control , so that early symptoms of anxiety can be identified and addressed quickly The hierarchy of evidence in assessing the effectiveness of interventions or treatments is explained , and the gold st and ard for evaluating the effectiveness of interventions , the r and omised controlled trial , is discussed . Issues that need to be considered during the critical appraisal of r and omised controlled trials , such as assessing the validity of trial methodology and the magnitude and precision of the treatment effect , and deciding on the applicability of research results , are discussed . Important terminologies such as r and omisation , allocation concealment , blinding , intention to treat , p values , and confidence intervals are explained This study examined whether cognitive behavioural therapy ( CBT ) could prevent the development or worsening of panic-spectrum psychopathology and anxiety symptoms in chronic obstructive pulmonary disease ( COPD ) . 41 patients with COPD , who had undergone pulmonary rehabilitation , were r and omised to either a four-session CBT intervention condition ( n = 21 ) or a routine care condition ( n = 20 ) . Assessment s were at baseline , post-intervention , and at 6- , 12- and 18-month follow-ups . Primary outcomes were the rates of panic attacks , panic disorder and anxiety symptoms . Secondary outcomes were depressive symptoms , catastrophic cognitions about breathing difficulties , disease-specific quality of life and hospital admission rates . There were no significant differences between the groups on outcome measures at baseline . By the 18-month follow-up assessment , 12 ( 60 % ) routine care group participants had experienced at least one panic attack in the previous 6 months , with two ( 17 % ) of these being diagnosed with panic disorder , while no CBT group participants experienced any panic attacks during the follow-up phase . There were also significant reductions in anxiety symptoms and catastrophic cognitions in the CBT group at all three follow-ups and a lower number of hospital admissions between the 6- and 12-month follow-ups . The study provides evidence that a brief , specifically targeted CBT intervention can treat panic attacks in COPD patients and prevent the development and worsening of panic-spectrum psychopathology and anxiety symptoms Abstract Several behavioral medicine interventions ( eg , relaxation training and written emotional expression ) have been proposed as effective supplemental treatments for individuals with chronic illnesses such as asthma . Whether these treatments are feasible or effective in a manual-based , self-administered format is unclear , and few studies have examined the effectiveness of such treatments presented in a complementary format . We examined the feasibility and effectiveness of a 4 week stress management treatment compared with a matched placebo intervention in young adults with asthma . Both groups considered the workbooks credible treatment interventions and completed them conscientiously . The treatment group showed significant improvement in measures of lung function compared with the placebo group , but analysis revealed no differences in measures of perceived stress . These findings provide initial support for the feasibility of self-administered manual-based interventions and some evidence that they can produce health benefits in individuals with asthma and , perhaps other chronic conditions There is evidence that educational programmes may improve patient 's compliance with asthma treatment and control symptoms . Whilst medical parameters have been thoroughly studied , few data are available concerning psychological intervention . The aim of our open pilot study was to verify whether any difference in perceived illness and response style to asthma existed in the patients enrolled in an Asthma Rehabilitation Group ( ARG ) and in a Control Group ( CG ) . Forty consecutive asthmatics were r and omly enrolled , all of whom were diagnosed , treated and followed-up according to the International Guidelines . Both groups underwent a psychological assessment at baseline and after one year . A battery of question naires was used to obtain data relating to baseline characteristics ( anxiety , depression , psychophysiological disorders ) , emotional reactions to asthma attacks ( panic-fear , etc , ) and cognitive variables ( external control , psychological stigma , internal beliefs , external chance , etc . ) involved in the perceived illness . In addition , the Asthma Rehabilitation Group patients underwent an educational programme and a cognitive-behavioural intervention . In both groups , a reduction of anxiety and depression scores was observed , as well as a significant improvement of the medical parameters evaluated . Only the Asthma Rehabilitation Group reported lower scores on the Psychophysiological Question naire and on the External Control Subscale after 1 year . The Control Group reported higher score on the External Chance Scale . The data of our study seem to confirm the effectiveness of psychological intervention on the cognitive skills involved in the perception and management of asthma . Larger scale studies on this topic are suggested This study tested the efficacy of a nurse-administered 8-week group treatment program for adults with asthma suffering from coexisting panic disorder . The program consisted of cognitive behavioral treatment ( CBT ) for panic disorder combined with asthma education ( AE ) . Forty-eight women with a confirmed diagnosis of asthma and panic disorder were r and omly allocated to a treatment condition ( n=25 ) and a wait-list control condition ( n=23 ) . Twenty-five participants —15 in the treatment group and 10 in the wait-list control group— completed treatment . Repeated measures ANOVA procedures were used to compare the groups on panic and asthma outcomes at posttreatment and 6-month follow-up . The results demonstrate that the CBT-AE program is capable of producing substantial and durable antipanic and antianxiety treatment effects and led to substantial but nonsustained improvement in morning peak-flow expiratory rate and asthma-related quality of life . Implication s of these findings for this clinical population are addressed Confusion between panic and asthma symptoms can result in serious self-management errors . A cognitive behavior psychophysiological therapy ( CBPT ) intervention was culturally adapted for Latinos consisting of CBT for panic disorder ( PD ) , asthma education , differentiation between panic and asthma symptoms , and heart rate variability biofeedback . An RCT compared CBPT to music and relaxation therapy ( MRT ) , which included listening to relaxing music and paced breathing at resting respiration rates . Fifty-three Latino ( primarily Puerto Rican ) adults with asthma and PD were r and omly assigned to CBPT or MRT for 8 weekly sessions . Both groups showed improvements in PD severity , asthma control , and several other anxiety and asthma outcome measures from baseline to post-treatment and 3-month follow-up . CBPT showed an advantage over MRT for improvement in adherence to inhaled corticosteroids . Improvements in PD severity were mediated by anxiety sensitivity in CBPT and by depression in MRT , although earlier levels of these mediators did not predict subsequent improvements . Attrition was high ( 40 % ) in both groups , albeit comparable to CBT studies targeting anxiety in Latinos . Additional strategies are needed to improve retention in this high-risk population . Both CBPT and MRT may be efficacious interventions for comorbid asthma-PD , and CBPT may offer additional benefits for improving medication adherence An individualised asthma programme directed at behavioural change was evaluated in asthmatic subjects who reported complaints and impairment , despite adequate medical treatment . Mild-to-moderate asthma patients ( n=23 ) were r and omly assigned to a programme or waiting list condition . Outcome measures were : McMaster Asthma Quality of Life Question naire , Asthma Symptom Checklist , Negative Emotionality Scale , Knowledge , Attitude and Self-Efficacy Asthma Question naire , Adherence Scale , and peak flow measurements . Both groups were evaluated at three consecutive moments , each separated by 3 months ; the programme was delivered between the first two evaluations . At onset the patient received a workbook containing information , exercises and homework assignments . Psycho-education , behavioural and cognitive techniques were introduced during six 1‐h individual sessions . Compared with controls the programme group reported less symptoms ( obstruction , fatigue ) , better quality of life ( activity , symptoms , emotions ) , decreased negative affectivity , and increased adherence , immediately after finishing the programme and at 3 months follow-up . All three cognitive variables ( knowledge , attitude towards asthma , self-efficacy ) and day and night peak flow ratings improved in the programme group but not in the waiting list group . Participation in an individualised programme result ed in improvement of asthma morbidity , and asthma-related behaviour and cognitions , in subjects reporting symptoms and impairment despite adequate medical therapy BACKGROUND High levels of asthma-related fear and panic exacerbate asthma symptoms and complicate the management of asthma . Asthma-specific fear may be reduced by a cognitive behavioural intervention . We aim ed to test if there is a reduction in asthma-specific fear after cognitive behavioural intervention compared with routine treatment . METHODS Adults with asthma registered with family doctors in Sheffield UK were screened for anxiety and 94 highly anxious patients were r and omly allocated to receive either a cognitive behavioural intervention to improve self-management of their anxiety ( n = 50 ) or routine clinical care ( n = 44 ) . Asthma-specific fear at the end of treatment and at six month follow up were the primary endpoints . Service usage in the six months prior to and six months following the intervention was monitored to allow estimation of costs . Data were analysed by intention to treat . FINDINGS At the end of treatment , there was a significantly greater reduction in asthma-specific fear for people in the CBT group compared with controls . At six months after treatment the reduction in asthma-specific fear in the CBT group was increased and the difference between treatment and control group was statistically significant . Service use costs were not reduced in the CBT group . INTERPRETATION A brief cognitive behavioural intervention was found to have efficacy in reducing asthma-specific panic fear immediately after treatment and at 6 months follow up . There was no cost advantage to cognitive behavioural treatment ABSTRACT Objectives : Evidence for the efficacy of Cognitive Behavioural Therapy ( CBT ) in asthma is developing but it is not known if this translates to benefits in severe asthma or if a group approach is acceptable to this patient group . This study aim ed to assess the feasibility and acceptability of Group-CBT in severe asthma . Method : This was a two-centre , r and omised controlled parallel group feasibility study . Eligible participants ( patients with severe asthma and a clinical ly significant diagnosis of anxiety and /or depression – Hospital Anxiety and Depression Scale ( HAD ) score greater than 8 for the anxiety or depression sub-scale ) received Group-CBT in weekly sessions for eight consecutive weeks and usual care or usual care only . Follow-up was for 16 weeks and end points were : Asthma Quality of Life Question naire , Asthma Control Question naire , HAD , Dyspnoea-12 , EuroQual-5D and EuroQuol-VAS . Results : 51 patients were r and omised : 36 % ( 51 out of 140 ) consent rate and attrition at week 16 was 12 . Screening logs indicated that study take-up was influenced by patients living long distances from the treatment centre and inability to commit to the weekly dem and s of the programme . Drop-out was higher in Group-CBT compared due to inability to commit to the weekly programme because of poor health . Participants who contributed to focus group discussion s reported that Group-CBT contributed to a better underst and ing of their illness and related approaches to anxiety management and acceptance of their asthma condition . Although weekly face-to-face sessions were challenging , this was the preferred method of delivery for these participants . Conclusions : This feasibility study shows that Group-CBT warrants further investigation as a potentially promising treatment option for patients with severe asthma . It has been possible but not easy to recruit and retain the sample . Options for a less dem and ing intervention schedule , such as less frequent face-to-face visits and the use of web-based interventions , require careful consideration |
1,805 | 14,576,245 | Metformin has an effect in reducing fasting insulin concentrations , blood pressure , and low density lipoprotein cholesterol .
We found no evidence of any effect on body mass index or waist : hip ratio .
Metformin was associated with a higher incidence of nausea , vomiting , and other gastrointestinal disturbance .
CONCLUSIONS Metformin is an effective treatment for anovulation in women with polycystic ovary syndrome .
No data are available regarding the safety of metformin in long term use in young women and only limited data on its safety in early pregnancy . | OBJECTIVE To assess the effectiveness of metformin in improving clinical and biochemical features of polycystic ovary syndrome . | BACKGROUND Obese women with the polycystic ovary syndrome are relatively unresponsive to the induction of ovulation by clomiphene . We hypothesized that reducing insulin secretion by administering metformin would increase the ovulatory response to clomiphene . METHODS We performed oral glucose-tolerance tests before and after the administration of 500 mg of metformin or placebo three times daily for 35 days in 61 obese women with the polycystic ovary syndrome . Women who did not ovulate spontaneously were then given 50 mg of clomiphene daily for five days while continuing to take metformin or placebo . Serum progesterone was measured on days 14 , 28 , 35 , 44 , and 53 , and ovulation was presumed to have occurred if the concentration exceeded 8 ng per milliliter ( 26 nmol per liter ) on any of these days . RESULTS Twenty-one women in the metformin group and 25 women in the placebo group were given clomiphene because they did not ovulate spontaneously during the first phase of the study . Among the 21 women given metformin plus clomiphene , the mean ( + /-SE ) area under the serum insulin curve after oral glucose administration decreased from 6745+/-2021 to 3479+/-455 microU per milliliter per minute ( 40.5+/-12.1 to 20.9+/-2.7 nmol per liter per minute , P=0.03 ) , but it did not change significantly in the 25 women given placebo plus clomiphene . Nineteen of the 21 women ( 90 percent ) who received metformin plus clomiphene ovulated ( mean peak serum progesterone concentration , 23.8+/-3.4 ng per milliliter [ 7.6+/-10.9 nmol per liter ] ) . Two of the 25 women ( 8 percent ) who received placebo plus clomiphene ovulated ( P<0.001 ) . Overall , 31 of the 35 women ( 89 percent ) treated with metformin ovulated spontaneously or in response to clomiphene , as compared with 3 of the 26 women ( 12 percent ) treated with placebo . CONCLUSIONS The ovulatory response to clomiphene can be increased in obese women with the polycystic ovary syndrome by decreasing insulin secretion with metformin Abdominal obesity and hyperinsulinemia play a key role in the development of the polycystic ovary syndrome ( PCOS ) . Dietary-induced weight loss and the administration of insulin-lowering drugs , such as metformin , are usually followed by improved hyper and rogenism and related clinical abnormalities . This study was carried out to evaluate the effects of combined hypocaloric diet and metformin on body weight , fat distribution , the glucose-insulin system , and hormones in a group of 20 obese PCOS women [ body mass index ( BMI ) > 28 kg/m2 ] with the abdominal phenotype ( waist to hip ratio > 0.80 ) , and an appropriate control group of 20 obese women who were comparable for age and pattern of body fat distribution but without PCOS . At baseline , we measured sex hormone , sex hormone-binding globulin ( SHBG ) , and leptin blood concentrations and performed an oral glucose tolerance test and computerized tomography ( CT ) at the L4-L5 level , to measure sc adipose tissue area ( SAT ) and visceral adipose tissue area . All women were then given a low-calorie diet ( 1,200 - 1,400 kcal/day ) alone for one month , after which anthropometric parameters and CT scan were newly measured . While continuing dietary treatment , PCOS women and obese controls were subsequently placed , in a r and om order , on metformin ( 850 mg/os , twice daily ) ( 12 and 8 , respectively ) or placebo ( 8 and 12 , respectively ) , according to a double-blind design , for the following 6 months . Blood tests and the CT scan were performed in each woman at the end of the study while they were still on treatment . During the treatment period , 3 women of the control group ( all treated with placebo ) were excluded because of noncompliance ; and 2 PCOS women , both treated with metformin , were also excluded because they became pregnant . Therefore , the women cohort available for final statistical analysis included 18 PCOS ( 10 treated with metformin and 8 with placebo ) and 17 control women ( 8 treated with metformin and 9 with placebo ) . The treatment was well tolerated . In the PCOS group , metformin therapy improved hirsutism and menstrual cycles significantly more than placebo . Baseline anthropometric and CT parameters were similar in all groups . Hypocaloric dieting for 1 month similarly reduced BMI values and the waist circumference in both PCOS and control groups , without any significant effect on CT scan parameters . In both PCOS and control women , however , metformin treatment reduced body weight and BMI significantly more than placebo . Changes in the waist-to-hip ratio values were similar in PCOS women and controls , regardless of pharmacological treatment . Metformin treatment significantly decreased SAT values in both PCOS and control groups , although only in the latter group were SAT changes significantly greater than those observed during the placebo treatment . On the contrary , visceral adipose tissue area values significantly decreased during metformin treatment in both PCOS and control groups , but only in the former was the effect of metformin treatment significantly higher than that of placebo . Fasting insulin significantly decreased in both PCOS women and controls , regardless of treatment , whereas glucose-stimulated insulin significantly decreased only in PCOS women and controls treated with metformin . Neither metformin or placebo significantly modified the levels of LH , FSH , dehydroepi and rosterone sulphate , and progesterone in any group , whereas testosterone concentrations decreased only in PCOS women treated with metformin . SHBG concentrations remained unchanged in all PCOS women ; whereas in the control group , they significantly increased after both metformin and placebo . Leptin levels decreased only during metformin treatment in both PCOS and control groups . ( ABSTRACT TRUNCATED BACKGROUND Insulin resistance and increased ovarian cytochrome P450c17 alpha activity are both features of the polycystic ovary syndrome . P450c17 alpha , which is involved in and rogen bio synthesis , has both 17 alpha-hydroxylase and 17,20-lyase activities . Increased activity of this enzyme results in exaggerated conversion of progesterone to 17 alpha-hydroxyprogesterone in response to stimulation by gonadotrophin . We hypothesized that hyperinsulinemia stimulates ovarian P450c17 alpha activity . METHODS We measured fasting serum steroid concentrations and the response of serum 17 alpha-hydroxyprogesterone to leuprolide , a gonadotrophin-releasing hormone agonist , and performed oral glucose-tolerance tests before and after oral administration of either metformin ( 500 mg three times daily ) or placebo for four to eight weeks in 24 obese women with the polycystic ovary syndrome . RESULTS In the 11 women given metformin , the mean ( + /- SE ) area under the serum insulin curve after oral glucose administration decreased from 9303 + /- 1603 to 4982 + /- 911 microU per milliliter per minute ( 56 + /- 10 to 30 + /- 6 nmol per liter per minute ) ( P = 0.004 ) . This decrease was associated with a reduction in the basal serum 17 alpha-hydroxyprogesterone concentration from 135 + /- 21 to 66 + /- 7 ng per deciliter ( 4.1 + /- 0.6 to 2.0 + /- 0.2 nmol per liter ) ( P = 0.01 ) and a reduction in the leuprolide-stimulated peak serum 17 alpha-hydroxyprogesterone concentration from 455 + /- 54 to 281 + /- 52 ng per deciliter ( 13.7 + /- 1.6 to 8.5 + /- 1.6 nmol per liter ) ( P = 0.01 ) . The serum 17 alpha-hydroxyprogesterone values increased slightly in the placebo group . In the metformin group , the basal serum luteinizing hormone concentration decreased from 8.5 + /- 2.2 to 2.8 + /- 0.5 mlU per milliliter ( P = 0.01 ) , the serum free testosterone concentration decreased from 0.34 + /- 0.07 to 0.19 + /- 0.05 ng per deciliter ( 12 + /- 3 to 7 + /- 2 pmol per liter ) ( P = 0.009 ) , and the serum sex hormone-binding globulin concentration increased from 0.8 + /- 0.2 to 2.3 + /- 0.6 microgram per deciliter ( 29 + /- 7 to 80 + /- 21 nmol per liter ) ( P < 0.001 ) . None of these values changed significantly in the placebo group . CONCLUSIONS In obese women with the polycystic ovary syndrome , decreasing serum insulin concentrations with metformin reduces ovarian cytochrome P450c17 alpha activity and ameliorates hyper and rogenism BACKGROUND This study aims to evaluate the impact of metformin on ovarian response when co-administered during recombinant (r)FSH using the low-dose step-up protocol in clomiphene citrate-resistant polycystic ovarian syndrome ( PCOS ) patients with normal glucose tolerance . METHODS AND RESULTS Thirty-two patients were r and omized to metformin ( n = 16 ) and placebo ( n = 16 ) groups . Hormonal assessment , a 75 g oral glucose tolerance test ( OGTT ) and a frequently sample d i.v . glucose tolerance test ( FSIGTT ) were performed before and after oral administration of metformin ( 850 mg twice daily ) or placebo for 6 weeks . Recombinant FSH treatment was undertaken , thereafter , in women who did not ovulate on metformin ( n = 10 ) or placebo ( n = 15 ) . There was no significant change in all insulin sensitivity indices in both groups . The only change noted was a decline in mean serum free testosterone concentration in the metformin group ( P = 0.049 ) . One patient on placebo and six patients on metformin ovulated spontaneously ( P < 0.05 ) . All parameters of ovarian response were comparable between the two groups during rFSH treatment . Combining the 6 week placebo or metformin-only period with a single rFSH treatment cycle , the overall ovulation rates were 75 and 94 % in the placebo and metformin groups respectively ( P > 0.05 ) . The respective figures for pregnancy were 6.3 and 31.3 % ( P > 0.05 ) . CONCLUSIONS Metformin may restore ovulation with no improvement on insulin resistance in clomiphene citrate-resistant PCOS patients with normal glucose tolerance , but has no significant effect on ovarian response during rFSH treatment OBJECTIVE To evaluate the effect of metformin therapy on hyper and rogenism , insulin resistance , cervical scores , ovulation , and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome ( PCOS ) . DESIGN Prospect i ve , r and omized , double-blind , placebo-controlled study . SETTING Infertility clinic of a tertiary referral center . PATIENT(S ) Fifty-six women with clomiphene citrate-resistant PCOS . INTERVENTION(S ) Two cycles of oral metformin therapy ( 850 mg , twice daily ) in group I and placebo therapy ( twice daily ) in group II . Clomiphene citrate ( 100 mg/day ) on cycle days 3 - 7 of the second cycle in both groups . MAIN OUTCOME MEASURE(S ) Insulin , T , DHEAS , FSH , LH , body mass index ( BMI ) , waist-to-hip ratio , endometrial thickness , cervical score , ovulation , and pregnancy rates in clomiphene-induced cycles after metformin therapy . RESULT ( S ) Metformin therapy result ed in a significant decrease in total T , LH level , LH/FSH ratio , insulin resistance , and mean BMI . No difference in waist-to-hip ratio , DHEAS level , and fasting insulin level was observed . Clomiphene citrate induction result ed in higher ovulation rates and thicker endometrium in the metformin group than in the placebo group . There was higher cumulative pregnancy rate in the metformin group ; however , there was no significant difference in the pregnancy rate between the two groups . CONCLUSION ( S ) Metformin therapy not only decreases hyper and rogenism and insulin resistance but also improves ovulation rates , cervical scores , and pregnancy rates in clomiphene citrate-resistant women with PCOS We hypothesized that hyperinsulinemia contributes to early pregnancy loss in the polycystic ovary syndrome by adversely affecting endometrial function and environment . Serum glycodelin , a putative biomarker of endometrial function , is decreased in women with early pregnancy loss . Insulin-like growth factor-binding protein-1 may also play an important role in pregnancy by facilitating adhesion processes at the feto-maternal interface . We studied 48 women with polycystic ovary syndrome before and after 4 weeks of administration of 500 mg metformin ( n = 26 ) or placebo ( n = 22 ) 3 times daily . Oral glucose tolerance tests were performed , and serum glycodelin and insulin-like growth factor-binding protein-1 were measured during the follicular and clomiphene-induced luteal phases of menses . In the metformin group , the mean ( + /-SE ) area under the serum insulin curve after glucose administration decreased from 62 + /- 6 to 19 + /- 2 nmol/L.min ( P < 0.001 ) . Follicular phase serum glycodelin concentrations increased 20-fold from 150 + /- 46 to 2813 + /- 1192 pmol/L ( P < 0.001 ) , and serum insulin-like-growth factor-binding protein-1 concentrations increased from 936 + /- 152 to 2396 + /- 300 pmol/L ( P < 0.001 ) . Similarly , luteal phase serum glycodelin concentrations increased 3-fold from 3434 + /- 1299 to 10624 + /- 1803 pmol/L ( P < 0.001 ) , and serum insulin-like growth factor-binding protein-1 concentrations increased from 1220 + /- 136 to 4916 + /- 596 pmol/L ( P < 0.001 ) . Uterine vascular penetration also increased in the metformin group , as did blood flow of spiral arteries , as demonstrated by a 20 % decrease in the resistance index from 0.71 + /- 0.02 to 0.57 + /- 0.03 ( P < 0.001 ) . These variables did not change in the placebo group . We conclude that insulin reduction with metformin increases follicular and luteal phase serum glycodelin and insulin-like growth factor-binding protein-1 concentrations and enhances luteal phase uterine vascularity and blood flow in the polycystic ovary syndrome . These changes may reflect an improved endometrial milieu for the establishment and maintenance of pregnancy AIMS To determine whether metformin pretreatment has beneficial effects in clomiphene resistant infertile women with polycystic ovary syndrome ( PCOS ) in an infertility clinic . METHODS This was a r and omized placebo controlled double-blind crossover study of 3 months metformin ( 1500 mg day-1)/placebo , followed by 3 months metformin/placebo together with clomiphene ( 50 - 100 mg for 5 days ) for three cycles in clomiphene resistant women with PCOS . The primary outcomes were restoration of spontaneous menses , ovulation induction ( spontaneous or clomiphene induced ) and pregnancy . Secondary endpoints were changes in biochemical parameters related to and rogens and insulin . RESULTS Twelve women completed the metformin arm and 14 the placebo arm . Spontaneous menstruation resumed in five metformin treated patients and in six placebo treated women , P=0.63 . No women given metformin spontaneously ovulated , although one patient given placebo did , P=0.30 . There was no difference in the efficacy of clomiphene between the two groups with ovulation being induced in five ( out of 12 ) metformin treated women and four ( out of 14 ) placebo treated women , P=0.63 . Pregnancy occurred in three ( out of 12 ) women given metformin and two ( out of 14 ) women given placebo , P=0.59 . CONCLUSIONS Metformin is not always beneficial when given to clomiphene resistant infertile women with PCOS in clinical practice Obesity affects ovulation , response to fertility treatment , pregnancy rates and outcome . In this prospect i ve study , a weight loss programme was assessed to determine whether it could help obese infertile women , irrespective of their infertility diagnosis , to achieve a viable pregnancy , ideally without further medical intervention . The subjects underwent a weekly programme aim ed at lifestyle changes in relation to exercise and diet for 6 months ; those that did not complete the 6 months were treated as a comparison group . Women in the study lost an average of 10.2 kg/m2 , with 60 of the 67 anovulatory subjects resuming spontaneous ovulation , 52 achieving a pregnancy ( 18 spontaneously ) and 45 a live birth . The miscarriage rate was 18 % , compared to 75 % for the same women prior to the programme . Psychometric measurements also improved . None of these changes occurred in the comparison group . The cost savings of the programme were considerable . Prior to the programme , the 67 women had had treatment costing a total of A$ 550,000 for two live births , a cost of A$ 275,000 per baby . After the programme , the same women had treatment costing a total of A$ 210,000 for 45 babies , a cost of A$ 4600 per baby . Thus weight loss should be considered as a first option for women who are infertile and overweight OBJECTIVE To determine whether metformin treatment increases the ovulation and pregnancy rates in response to clomiphene citrate ( CC ) in women who are resistant to CC alone . DESIGN R and omized , double-blind , placebo-controlled trial . SETTING Multicenter environment . PATIENT(S ) Anovulatory women with the polycystic ovary syndrome ( PCOS ) who were resistant to CC . INTERVENTION(S ) Participants received placebo or metformin , 500 mg three times daily , for 7 weeks . Information on reproductive steroids , gonadotropins , and oral glucose tolerance testing was obtained at baseline and after treatment . Metformin or placebo was continued and CC treatment was begun at 50 mg daily for 5 days . Serum P level > or = 4 ng/mL was considered to indicate ovulation . With ovulation , the daily CC dose was not changed , but with anovulation it was increased by 50 mg for the next cycle . Patients completed the study when they had had six ovulatory cycles , became pregnant , or experienced anovulation while receiving 150 mg of CC . MAIN OUTCOME MEASURE(S ) Ovulation and pregnancy rates . RESULT ( S ) In the metformin and placebo groups , 9 of 12 participants ( 75 % ) and 4 of 15 participants ( 27 % ) ovulated , and 6 of 11 participants ( 55 % ) and 1 of 14 participants ( 7 % ) conceived , respectively . Comparisons between the groups were significant . CONCLUSION ( S ) In anovulatory women with PCOS who are resistant to CC , metformin use significantly increased the ovulation rate and pregnancy rate from CC treatment OBJECTIVE To study the effect of metformin in combination with clomiphene citrate , as compared with placebo plus clomiphene citrate , on the ovulation and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome . METHODS This study was carried out at King Hussein Medical Center , Amman , Jordan , during the period January 2001 through to July 2001 . Twenty-eight clomiphene citrate-resistant polycystic ovary syndrome women were evaluated prospect ively for 6 treatment cycles by receiving metformin , 850 mg twice daily throughout the cycle along with 50 mg clomiphene citrate , starting on day 5 - 9 of the same cycle ( N=16 ) , or by taking placebo with clomiphene citrate ( N=12 ) . During cycles 2 - 6 , clomiphene citrate was added with increments of 50 mg ( up to 200 mg/day ) for both groups . Progesterone level on day 21 and 28 > 5ng/dl was indicative of ovulation . RESULTS A statistically significant increase in the rates of ovulation ( 68.6 % versus 25 % , p<0.05 ) and pregnancy ( 56.3 % versus 16.6 % , p<0.05 ) were observed in the metformin-clomiphene citrate group as compared with the placebo-clomiphene citrate controls . Insignificant increase in the rate of ovarian hyperstimulation was noted in the placebo-clomiphene citrate group . CONCLUSION Metformin-clomiphene citrate regimen in resistant-clomiphene citrate polycystic ovary syndrome women significantly increases the ovulation and pregnancy rates , and decreases the occurrence of ovarian hyperstimulation syndrome |
1,806 | 19,821,429 | AUTHORS ' CONCLUSIONS In the absence of evidence of efficacy , at present , for oral meloxicam in acute postoperative pain , its use in this indication is not justified . | BACKGROUND Meloxicam is a non-steroidal anti-inflammatory drug ( NSAID ) used mainly in treating pain associated with arthritis .
The usual oral dose for osteoarthritis is 15 mg daily , but lower doses of 7.5 mg are advised in older patients .
This review sought to evaluate the efficacy and safety of oral meloxicam in acute postoperative pain , using clinical studies of patients with established pain , and with outcomes measured primarily over 6 hours using st and ard methods .
This type of study has been used for many decades to establish that drugs have analgesic properties .
OBJECTIVES To assess the efficacy of single dose oral meloxicam in acute postoperative pain , and any associated adverse events . | Abstract Variability in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size Successful management of endodontic pain represents a continuing challenge . The purpose of this r and omized , double-blind , placebo-controlled , parallel-group trial was to compare the pain reducing effect of oral preparations of meloxicam , piroxicam , and placebo in endodontic emergency patients . A total of 51 patients who presented to the Tehran University endodontic clinic and one private dental clinic were invited to participate . Patients were asked to evaluate their pretreatment pain with a visual-analog scale . After root canal therapy they were r and omly assigned to one of three groups : meloxicam , piroxicam , or placebo . Each patient was sent home with a visual-analog scale to fill out at 8 and 24 h after completion of therapy . The results of this study showed no significant differences between efficacy of meloxicam , piroxicam , and placebo , but a significant effect of the time factor in reducing postoperative pain in all treatment groups was observed Abstract A previously established relationship for deriving dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics has been tested using an independent data set . Individual patient information from 18 RCTs of parallel‐group design in acute postoperative pain ( after abdominal , gynaecological and oral surgery ) was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with > 50%maxTOTPAR for the different treatments . The relationship between the measures was investigated in 85 treatments with over 3400 patients . In 80 of 85 treatments ( 94 % ) agreement between calculated and actual number of patients with > 50%maxTOTPAR was within four patients per treatment and in 72 ( 85 % ) was within three ( average of 40 patients per treatment , range 21–58 patients ) . Summing the positive and negative differences between actual and calculated numbers of patients with > 50%maxTOTPAR gave an average difference of 0.30 patients per treatment arm . Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events , such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data in acute pain studies enables data published as means to be used for quantitative systematic review s which require data in dichotomous form & NA ; Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events — such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean data , at least in acute pain models , indicates that more meaningful overviews or meta‐ analysis may be possible . This study investigated the relationship between continuous and dichotomous analgesic measures in a set of individual patient data , and then used that relationship to derive dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics . Individual patient information from 13 RCTs of parallel‐group and crossover design in acute postoperative pain was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with greater than 50 % pain relief ( > 50%maxTOTPAR ) for the different treatments . The relationship between the measures was investigated in 45 actual treatments and 10 000 treatments simulated using the underlying actual distribution ; 1283 patients had 45 separate treatments . Mean % maxTOTPAR correlated with the proportion of patients with > 50%maxTOTPAR ( r2 = 0.90 ) . The relationship calculated from all the 45 treatments predicted to within three patients the number of patients with more than 50 % pain relief in 42 of 45 treatments , and 98.8 % of 10 000 simulated treatments . For seven effective treatments , actual numbers‐needed‐to‐treat ( NNT ) to achieve > 50%maxTOTPAR compared with placebo were very similar to those derived from calculated data AIM To investigate the effect of the administration of a single dose of meloxicam pre-emptively on postoperative pain management in patients who underwent inguinal hernia repair under local anaesthesia . SUBJECTS AND METHOD Fifty patients who underwent inguinal hernia repair under local anaesthesia during the period November 2005 to May 2006 were recruited into the study prospect ively . The patients were r and omized to two groups regarding administration and non-administration of pre-emptive meloxicam . The postoperative visual analogue pain scale ( VAS ) values at 4 , 8 , 12 and 24 hours and analgesic needs of the patients were recorded RESULTS No difference was found between the groups in terms of age , gender , hernia localization and type . The VAS values of the patients regarding their pain severity were evaluated at 4 , 8 , 12 and 24 hours and were significantly lower in the group which received meloxicam pre-emptively ( p = 0.001 , 0.0001 , 0.003 and 0.0001 respectively ) . The need for non-steroidal anti-inflammatory drug was also found to be significantly lower ( p = 0.0001 ) . CONCLUSION Postoperative pain severity and hence analgesic requirement were significantly decreased in the patients who received meloxicam pre-emptively . Single dose pre-emptive meloxicam seems to be an effective analgesic therapy for patients undergoing inguinal hernia repair under local anaesthesia . It thereby improves patients comfort and should be considered for use in outpatient surgery We studied 36 patients , allocated r and omly to receive meloxicam 15 mg rectally ( n = 18 ) or placebo suppository ( n = 18 ) before total abdominal hysterectomy in a double-blind study . Visual analogue scores for pain at rest ( P < 0.005 ) , on movement ( P < 0.05 ) and on coughing ( P < 0.05 ) were significantly decreased in the meloxicam group during the first 24 h after surgery . Mean 24-h PCA morphine requirements were 33.2 ( SD 16.9 ) mg and 38.2 ( 20.8 ) mg in the meloxicam and placebo groups , respectively ( ns ) . There was no difference in the incidence of nausea , vomiting or sedation between groups & NA ; A data base of r and omised clinical trials ( RCTs ) in pain research published from 1950 to 1990 was created following an extensive literature search . By applying a refined MEDLINE search strategy from 1966 to 1990 and by h and ‐ search ing more than 1 000 000 pages of a total of 40 biomedical journals published during the period 1950–1990 , more than 8000 RCTs were identified . The RCTs were published in more than 800 journals and over 85 % appeared between 1976 and 1990 . If the trend of the last 15 years persists , a total of more than 15 000 RCTs will be published in pain relief by the year 2000 . A detailed description of methods to ensure efficient use of re sources during the identification , retrieval and management of the information in pain relief and other fields is given . Emphasis is made on the importance of refining MEDLINE search strategies , on the use of volunteers to h and ‐ search journals and on careful monitoring of each of the steps of the process . The potential uses of the data base to guide clinical and research decisions are discussed Abstract One way to ensure adequate sensitivity for analgesic trials is to test the intervention on patients who have established pain of moderate to severe intensity . The usual criterion is at least moderate pain on a categorical pain intensity scale . When visual analogue scales ( VAS ) are the only pain measure in trials we need to know what point on a VAS represents moderate pain , so that these trials can be included in meta‐ analysis when baseline pain of at least moderate intensity is an inclusion criterion . To investigate this we used individual patient data from 1080 patients from r and omised controlled trials of various analgesics . Baseline pain was measured using a 4‐point categorical pain intensity scale and a pain intensity VAS under identical conditions . The distribution of the VAS scores was examined for 736 patients reporting moderate pain and for 344 reporting severe pain . The VAS scores corresponding to moderate or severe pain were also examined by gender . Baseline VAS scores recorded by patients reporting moderate pain were significantly different from those of patients reporting severe pain . Of the patients reporting moderate pain 85 % scored over 30 mm on the corresponding VAS , with a mean score of 49 mm . For those reporting severe pain 85 % scored over 54 mm with a mean score of 75 mm . There was no difference between the corresponding VAS scores of men and women . Our results indicate that if a patient records a baseline VAS score in excess of 30 mm they would probably have recorded at least moderate pain on a 4‐point categorical scale Fifty patients were scheduled to undergo removal of symmetrically positioned lower third molars in two separate appointments . Meloxicam 7.5 or 15 mg was once daily administered in a double-blind , r and omized and crossover manner after the surgery for 4 days . Objective and subjective parameters were recorded for comparison of postoperative courses . Patients treated with 7.5 mg meloxicam who underwent osteotomy reported higher pain scores at 1.5 , 3 , 4 , 10 , 12 and 16 h ( P<0.05 ) and ingested a greater amount of rescue analgesic medication ( P<0.05 ) than those who did not require osteotomy . A higher percentage of patients who underwent osteotomy medicated with 7.5 mg meloxicam needed rescue medication as compared to those who did not require osteotomy ( P<0.05 ) . There was a similar mouth opening at suture removal compared with preoperative values for both doses ( P>0.05 ) . There were no significant differences concerning swelling observed on the 2nd or 7th postoperative days in comparison with baseline ( P>0.05 ) between the two doses . Pain , trismus and swelling after lower third molar removal not requiring osteotomy can be successfully controlled by a dose regimen of 7.5 mg meloxicam once daily . For more aggressive extraction s 15 mg meloxicam is advisable OBJECTIVES To investigate pain relieving efficacy of six agents which are used in postoperative pain management after otolaryngologic operations . PATIENTS AND METHODS 120 adult patients ( 63 females , 57 males ; mean age 36 ; range 18 to 76 years ) were included in the study . The same intraoperative anesthesia was applied to all the patients . The following medications were r and omly given to the patients who declared pain in the sixth hour after the operation : naproxen sodium , meloxicam , rofecoxib , paracetamol , dipyrone , and etodolac in proper dosage to form groups of 20 for each medication . Before and after the application of pain reliever tablets , visual analog scale ( VAS ) and numerical rating scale ( NRS ) were used to inquire whether the agents were effective in relieving pain . ANOVA ( one way ) , paired t-test , Kruskal-Wallis , and Student 's t-test were used as statistical methods . p values < 0.05 were considered to indicate statistical significance . RESULTS All the groups had similar VAS values before medication ( p>0.05 ) . When VAS values of each group were assessed after medication , it was recorded that naproxen sodium ( p=0.020 ) and meloxicam ( p=0.001 ) were effective . When the difference of NRS values between " before medication " and " after medication " was compared among the groups , all the agents significantly changed NRS values , but no inter-group differences were found ( p>0.05 ) . CONCLUSION In terms of NRS scores , the effectiveness of six different analgesic agents which had been used to reduce postoperative pain was confirmed . Moreover , naproxen sodium and meloxicam were found to be more effective than the other agents when taken in the postoperative period for the adult patients according to VAS values |
1,807 | 15,932,360 | Intermittent proton pump inhibitor or H2-receptor antagonist therapy is not effective in maintaining control in oesophagitis patients .
H2-receptor antagonists are effective for relief of heartburn episodes .
On-dem and proton pump inhibitor therapy may work in a proportion of non-erosive gastro-oesophageal reflux disease patients | AIM To perform a systematic review on the efficacy of intermittent and on-dem and therapy with either histamine H2-receptor antagonists or proton pump inhibitors for patients with erosive oesophagitis or symptomatic heartburn . | On-dem and therapy is effective for maintaining symptoms control in nonerosive gastroesophagealreflux disease ( GERD ) . Our aim was to assess the clinical effectiveness of on-dem and therapy witha proton pump inhibitor ( PPI ) in mild GERD ( nonerosive and low- grade esophagitis ) , its impact onhealth-related quality of life ( HRQoL ) , and the degree of patient satisfaction . Fifty-five patients ( 17with nonerosive GERD and 38 with low- grade esophagitis ) were treated with rabeprazole , 20 mg/day . The healed patients started on-dem and therapy . We evaluated symptoms ( clinical question naire),HRQoL ( SF-36 question naire ) , and patient satisfaction ( visual analogue scale ) . Of the 55 patients included , 51 started on-dem and therapy for 6 months . Symptom control ( heartburn < twice a week)was achieved in over 85 % of the patients . The mean ( SD ) amount of PPI used was 0.3 (0.19)tablet/day . The patient satisfaction score at the end of the acute phase was 98 ( range , 0 - 100 ) and remained high ( 90 ; range , 10 - 100 ) and stable during on-dem and therapy . Short-term treatmentnormalized the HRQoL scores , which were subsequently maintained during on-dem and therapy . On-dem and therapy is useful for the clinical management of patients with mild GERD , allowingadequate symptoms control , limiting PPI consumption , and affording important patient satisfactionwith normalization of BACKGROUND & AIMS Gastroesophageal reflux is considered a common condition , but detailed population -based data on reflux in the United States are lacking . The aim of this study was to determine the prevalence and clinical spectrum of gastroesophageal reflux in Olmsted County , Minnesota . METHODS A reliable and valid self-report question naire was mailed to an age- and sex-stratified r and om sample of 2200 Olmsted County residents aged 25 - 74 years . RESULTS The prevalence per 100 of heartburn and /or acid regurgitation experienced at least weekly was 19.8 ( 95 % confidence interval [ 95 % CI ] , 17.7 - 21.9 ) . Heartburn and acid regurgitation were associated with noncardiac chest pain ( odds ratio [ OR ] , 4.2 ; 95 % CI , 2.9 - 6.0 ) , dysphagia ( OR , 4.7 ; 95 % CI , 2.9 - 7.4 ) , dyspepsia ( OR , 3.1 ; 95 % CI , 1.9 - 5.0 ) , and globus sensation ( OR , 1.9 ; 95 % CI , 1.0 - 3.6 ) but not with asthma , hoarseness , bronchitis , or a history of pneumonia . Among subjects with reflux symptoms , 1.0 % reported an episode of hematemesis and 1.3 % had a past esophageal dilatation . CONCLUSIONS Symptoms of reflux are common among white men and women who are 25 - 74 years of age . Heartburn and acid regurgitation are significantly associated with chest pain , dysphagia , dyspepsia , and globus sensation . The percentage of patients reporting complications is low , but the absolute number is probably considerable given the high prevalence of the condition in the community To compare the efficacy of conventional versus on-dem and ( symptomatic ) treatment of duodenal ulcer , 81 patients were r and omized into two groups . Group A ( n = 40 ) patients were treated with ranitidine 150 mg twice daily until complete ulcer healing was achieved . Group B ( n = 41 ) received a similar dose of ranitidine until complete relief of pain was achieved , irrespective of ulcer healing . Recurrence of ulcer in group A was treated with a full course of treatment until complete healing of the ulcer was achieved again , whereas , in group B , treatment was given only until pain recurrence was symptomatically controlled . Endoscopic examination was performed each month . Analysis of the results at 8 wk and 28 wk showed that 1 ) ulcer healing in group A was significantly superior to that in group B up to 24 wk , but at 28 wk the difference was no longer statistically significant ( 95 % vs 70 % ) , 2 ) the number of painful days were similar in the two groups , 3 ) group A patients took treatment for a significantly longer period than those in group B , 4 ) the cost of treatment per patient in group A was significantly greater than that in group B , 5 ) the recurrence rate assessed in patients followed for 28 wk after complete ulcer healing was similar in the two groups , and 6 ) the ulcer-related complications were not significantly different in the two groups . These findings indicate that , although on-dem and treatment results in slower ulcer healing , it is not associated with an increase in the duration of pain and incidence of complications . A major advantage of this approach was a significant reduction in the cost of treatment . It is concluded that on-dem and treatment is an attractive alternative therapeutic approach in the management of duodenal ulcer disease The present study was performed to compare pain-related oesophageal motility , gastro-oesophageal reflux and ST-segment deviations in patients with intermittent chest pain and normal or pathological coronary angiography . Thirty patients ( 11 males , 19 females ; mean age 54.8 years ) with normal and 15 patients ( 12 males , 3 females ; mean age 66.7 years ) with pathological coronary angiography were investigated by 24-h oesophageal pressure , pH and ECG recording . Chest pain correlated with motility abnormalities or gastro-oesophageal reflux occurred in 33 % ( 10/30 ) of patients with normal coronary arteries and in 26 % of patients with pathological coronary angiography . Symptomatic and asymptomatic ST-segment changes were less frequently observed in patients with normal angiography ( 4/30 ) than in patients with pathological coronary angiography ( 7/14 ; P = 0.02 ) . Oesophageal dysfunction coincided with ST-segment deviation in 6.7 % ( 2/30 ) of patients with normal and 40 % ( 6/15 ) of patients with pathological coronary angiography ( P = 0.02 ) . The conclusions reached were : ( 1 ) pain-correlated abnormal motility or gastro-oesophageal reflux occurred in patients with normal and pathological coronary angiography at the same frequency ; ( 2 ) ambulatory motility and pH recording alone does not appear to differentiate between cardiac and non-cardiac chest pain ; ( 3 ) simultaneous ECG recording reveals a significant correlation of ST-segment deviation and gastro-oesophageal reflux or abnormal motility in patients with coronary artery stenosis The efficacy of fundoplication operations in the long-term management of gastroesophageal reflux disease ( GERD ) has been documented . However , only a few prospect i ve controlled series support the longterm ( > 10 years ) efficacy of these procedures , and further data are required to also determine whether the type of fundoplication affects the frequency of postfundoplication complaints . The aim of this study was to conduct a r and omized , controlled clinical trial to assess the long-term symptomatic outcome of a partial posterior fundoplication as compared to a total fundic wrap . During the years 1983 to 1991 , a total of 13 7 patients with chronic gastroesophageal reflux disease were enrolled in the study ; 72 were r and omized to semifundoplication ( Toupet ) and 65 to total fundoplication ( Nissen-Rossetti ) . A st and ardized symptom question naire was used for follow-up of these patients . A total of 110 patients completed a median follow-up of 11.5 years ; 54 had a total wrap and 56 underwent a partial posterior fundoplication . During this period , seven patients required reoperation ( Nissen-Rossetti in 5 and Toupet in 2 ) , 11 patients died , and nine patients were lost to follow-up or did not comply with the follow-up program . Control of heartburn ( no symptoms or mild , intermittent symptoms ) was achieved in 88 % and 92 % in the total and partial fundoplication groups , respectively , and the corresponding figures for control of acid regurgitation were 90 % and 94 % . We observed no difference in dysphagia scoring between the two groups , although odynophagia was somewhat more frequently reported in those undergoing a total fundoplication . On the other h and , a significant difference was observed in the prevalence of rectal flatus and postpr and ial fullness , which were recorded significantly more often in those undergoing a total fundoplication ( P < 0.001 and P < 0.03 , respectively ) . Posterior partial fundoplication seems to maintain the same high level of reflux control as total fundoplication . Earlier observations demonstrating the advantages of a partial fundoplication , which included fewer complaints associated with gas-bloat , continue to be valid after more than 10 years of follow-up Patients undergoing anaesthesia for cataract surgery were anaesthetized and their lungs ventilated by intermittent positive pressure ventilation . In one group , ventilation was facilitated by tracheal intubation and in the other group by laryngeal mask airway ( LMA ) . Reflux of stomach contents into the oesophagus was monitored continuously using an indwelling oesophageal pH electrode . The number of discrete episodes of reflux was higher in the LMA group ( P = 0.0178 ) , as was the incidence of reflux at antagonism of neuromuscular block ( P = 0.0349 ) Two hundred and sixty seven patients with duodenal ulceration were entered into a five year study of two strategies of treatment with cimetidine . Two thirds were treated continuously with 400 mg at bedtime supplemented by temporary increases in dosage if they had symptomatic relapses ( group 1 ) , and the remaining third were given intermittent “ healing ” doses for four to eight weeks if a symptomatic recurrence was judged to have occurred ( group 2 ) . Life table analysis showed that the probability of remaining free of clinical ly important symptoms five years after the start of treatment was 24 % ( 95 % confidence interval ( CI ) 15·5 % to 32·6 % ) in group 1 compared with nil in group 2 ( p<0·0001 ) . The median values for the longest periods free from relapse for each patient were 108 weeks in group 1 and 32 weeks in group 2 , respectively ( p<0·0001 ; 95 % CI of the median difference 36 to 76 ) . Over the five years 10 patients suffered major complications , two requiring emergency surgery , while a further nine had elective surgery because of the failure of medical treatment . There were no deaths that could be attributed either to ulceration or to treatment with cimetidine . Medical management was therefore very satisfactory for most patients , though those treated continuously with cimetidine suffered considerably less from their ulcer symptoms . As 80 % of patients studied relapsed during the two years after a healing course of cimetidine , continuous treatment will benefit many patients treated in general practice The head-downwards tipped position for physiotherapy has been cl aim ed to exacerbate gastro-oesophageal reflux ( GOR ) in infants with cystic fibrosis ( CF ) . This was investigated using lower oesophageal pH monitoring during physiotherapy . Twenty-one infants ( age range 1 - 27 months ) with respiratory disorders ( CF=11 ) , undergoing lower oesophageal pH monitoring were recruited . Subjects received two physiotherapy episodes in r and om order , A/B or B/A , 12 h apart . A began the gravity-assisted positioning head downward tip for : right lower lobe , middle lobe , left lower lobe and lingula ; then supine with no tip for anterior segments of the upper lobes followed by apical segments of upper lobes in a sitting position . B was in the reverse order . Intermittent chest clapping was carried out for 4 min in each position by a physiotherapist blinded to the pH data . During episode A , the median change in pH from baseline was -0.32 ( range -2.07 to + 1.0 ) in non-CF subjects ( NS ) and -0.52 ( range -2.7 to + 0.52 ) in CF subjects ( p<0.02 ) . During episode B , the median change in non-CF subjects was -0.1 ( NS ; range - 1.7 to -0.15 ) and in CF subjects was -0.05 ( NS ; range -0.67 to + 0.5 ) . There was no order effect for positioning . In the CF subjects the sitting position was twice as likely to have the lowest pH measurement during physiotherapy than the other positions ( p<0.04 ) . In conclusion , the head-downward tipped positioning for physiotherapy treatment neither induces nor aggravates gastro-oesophageal reflux . There is no justification for routinely changing the way in which infant physiotherapy is carried out BACKGROUND The length of time until symptom relief and the consistency of response are important aspects of the management of episodes of gastro-oesophageal reflux disease ( GORD ) . METHODS In an open , r and omized , crossover study 98 patients treated 3 episodes of GORD with ranitidine effervescent formulation and 3 with ranitidine st and ard formulation . The patients filled in a diary card during the 1st h after each study medication . Satisfaction with the formulations and the formulation of choice were determined at the end of the study . RESULTS A higher percentage of episodes with acceptable symptom relief ( 82.4 % versus 73.1 % P=0.024 ) and a shorter time to acceptable symptom relief ( 27 min versus 36 min ; P < 0.001 ) were achieved with the effervescent formulation . Sixty-five per cent preferred the effervescent formulation ( P < 0.01 ) . CONCLUSIONS An increased consistency of response and a more rapid symptom relief were achieved with treatment with the ranitidine effervescent formulation , indicating it may be more appropriate for on-dem and treatment in patients with episodes of GORD Background : A prospect i ve , open , r and omized multi‐centre study with parallel group design was conducted in 155 general practice clinics , and included 1357 endoscopically uninvestigated patients with symptoms suggestive of gastro‐oesophageal reflux disease . Summary The gastroduodenal tolerance of Tenoxicam and Diclofenac Na has been evaluated in a double-blind , parallel group study in 36 healthy male volunteers . The doses used were 20 mg Tenoxicam and 100 mg Diclofenac Na daily in a retard formulation for 14 days . Gastric tolerance was assessed by endoscopy , which was performed at base-line , after the 14 day dosing period and after a 14 day follow-up period without treatment . The mucosal lesions were scored using modified Lanza criteria .Tenoxicam was significantly better tolerated at the end of the 14 day dosing period ( mean gastric score : Tenoxicam 1.3 ; Diclofenac Na 2.2 ) . The two treatment groups had comparable scores at the base-line and post study assessment s . Tenoxicam and Diclofenac Na were generally well tolerated . Only two volunteers reported intermittant lack of appetite , heartburn and a feeling of pressure in the stomach : To observe the natural course of gastro‐oesophageal reflux disease ( GERD ) in patients without oesophagitis following effective symptom relief , and to determine the place of acid pump inhibitor therapy in the long‐term management of these patients Double-blind r and omized controlled trials in single subjects ( N of 1 RCTs ) have demonstrated a beneficial symptomatic effect of cimetidine in reflux- or ulcer-like non-ulcer dyspepsia ( NUD ) . However , spontaneous fluctuations in symptoms reduce the validity of such trials when performed as continuous trials with fixed dosages . This study was carried out to identify individual responders to cimetidine in NUD , peptic ulcer disease , and oesophagitis and to confirm the beneficial average effect of cimetidine in these clinical entities . We evaluated N of 1 multi-crossover trial design s , which compare the effects of single doses of cimetidine and placebo taken on-dem and for symptomatic relief . Each trial consisted of six cimetidine ( 400 mg or 800 mg ) and six placebo tablets r and omized in successive pairs . The symptomatic effect of each tablet was measured 1/2 - 6 h after the intake . Outcomes were assessed by individual p values and confidence intervals . A minimal clinical ly important difference was defined , to assess the clinical significance as demonstrated by the confidence intervals . Thirteen of 25 patients ( 52 % ) with reflux- and ulcer-like NUD obtained individual p values below 0.20 . Similarly , 7 of 9 patients ( 78 % ) with oesophagitis and 6 of 12 patients ( 50 % ) with peptic ulcer obtained such p values . On the basis of the 80 % confidence intervals the corresponding numbers of subjects with clinical ly significant effect were six ( NUD ) , three , and three . The combined data showed a significantly better effect of cimetidine than of placebo ( p less than 0.0001 ) in each of the three diagnostic groups studied . Cimetidine taken on-dem and may have a rapid symptom-relieving effect in dyspepsia . ( ABSTRACT TRUNCATED AT 250 WORDS Background : The aim of this study was to compare omeprazole 10 mg o.m . ( daily ) with omeprazole 20 mg o.m . on Friday to Sunday inclusive ( weekend ) in the prevention of duodenal ulcer relapse over a 6‐month period : Episodic heartburn is a common problem , affecting over 40 million Americans . Although omeprazole provides excellent acid suppression when used daily , the use of omeprazole as on‐dem and therapy for episodic symptoms has not been extensively studied Gastrointestinal cytomegalovirus ( CMV ) disease occurs in a significant proportion of patients with AIDS . A series of 66 AIDS patients with first-episode gastrointestinal CMV disease diagnosed on the basis of clinical and histopathologic findings were treated with foscarnet as first-line therapy at our institution between January 1987 and January 1991 . Primary sites of infection were the colon ( 28 patients ) and the esophagus ( 22 patients ) . Foscarnet was administered as a continuous infusion of 200 mg/kg ( prior to 1988 ) or as an intermittent infusion of 60 mg/kg t.i.d . or 90 mg/kg b.i.d . , with saline hyperhydration accompanying each infusion . Patients were treated initially for 2 weeks , with an additional 1 - 2 weeks of treatment being given in those not having a complete response during initial treatment ; maintenance therapy was given only in cases of concurrent CMV retinitis . Complete response to foscarnet therapy ( resolution of symptoms and endoscopic findings ) was observed in 17 esophagitis patients ( 77 % ) within 3 weeks , with only 4 patients relapsing ( at 1 - 7 months ) and none developing colitis or retinitis . Complete response was observed in 16 colitis patients ( 57 % ) within 3 weeks , with relapse occurring in 5 . Asymptomatic hypocalcemia occurred in 19.7 % of patients and penile ulceration occurred in 6.1 % ; increases in serum creatinine were observed in five patients ( 7.6 % ) , but did not require discontinuation of treatment . These findings indicate that foscarnet is an effective first-line treatment for gastrointestinal CMV infection . They also suggest that maintenance therapy with foscarnet may not be required in all patients BACKGROUND Data are limited on the value of effective antisecretory therapy in the relief of heartburn in patients without oesophagitis . METHODS Patients with heartburn , without endoscopic signs of oesophagitis , were r and omized to double-blind treatment with omeprazole , 20 or 10 mg once daily , or placebo , for 4 weeks ( n = 509 ) . Pre-treatment oesophageal acid exposure was assessed using 24-h intra-oesophageal pH monitoring . Heartburn was assessed at 2 and 4 weeks . RESULTS At 4 weeks the proportion of patients with complete absence of heartburn was 46 % ( 95 % confidence interval , 39 - 53 % ) with 20 mg omeprazole , 31 % ( 25 - 38 % ) with 10 mg omeprazole , and 13 % ( 7 - 20 % ) with placebo . Satisfaction with therapy was reported by 66 % , 57 % , and 31 % of the patients , respectively . CONCLUSION Omeprazole , 20 and 10 mg once daily , provides rapid relief of heartburn in patients without endoscopic oesophagitis The aim of this study was to determine the prevalence of upper gastrointestinal symptoms ( UGIS ) in a general population and quantify the relationship of those symptoms to healthcare utilization and quality of life . In-person interviews were conducted with 2056 United States and Canadian residents selected at r and om . Subjects reported frequency and severity for 11 symptoms , prescription and over-the-counter medication use , primary care and specialty physician visits in prior three months , and completed the Psychological General Well-Being Scale . For analyses , subjects were classified into four mutually exclusive symptom groups : gastroesophageal reflux disease ( GERD ) -like , GERD plus motility-like ( GERD+ ) , ulcerlike , and motility-like . Of the total sample , 51.4 % reported the occurrence of at least one UGIS in the prior three months . Subjects in the GERD+ and ulcer groups used more prescription medications and were more likely to see a physician about the symptoms ( P<0.001 ) . Subjects with symptoms demonstrated poorer quality of life compared to subjects with no symptoms . The prevalence of UGIS in the general population is high and symptoms are associated with significant health-care utilization and poorer quality of life The aim of this study was to compare recurrence rates of reflux oesophagitis ( after endoscopic healing with omeprazole ) over a 12 month period of r and omised , double blind , maintenance treatment with either daily omeprazole ( 20 mg every morning ; n = 53 ) , weekend omeprazole ( 20 mg on three consecutive days a week , n = 55 ) or daily ranitidine ( 150 mg twice daily , n = 51 ) . Patients were assessed for relapse by endoscopy ( with gastric biopsy ) at six and 12 months , or in the event of symptomatic recurrence , and serum gastrin was monitored . At 12 months , the estimated proportions of patients in remission ( actuarial life table method ) were 89 % when receiving daily omeprazole compared with 32 % when receiving weekend omeprazole ( difference 57 % , p < 0.001 , 95 % confidence intervals : 42 % to 71 % ) and 25 % when receiving daily ranitidine ( difference 64 % , p < 0.001 , 95 % confidence intervals : 50 % to 78 % ) . Median gastrin concentrations increased slightly during the healing phase , but remained within the normal range and did not change during maintenance treatment . No significant pathological findings were noted , and no adverse events were attributable to the study treatments . In conclusion , for patients who respond favourably to acute treatment with omeprazole 20 mg every morning , the drug is a safe and highly effective maintenance treatment for preventing relapse of reflux oesophagitis and its associated symptoms over 12 months . By contrast , weekend omeprazole and daily ranitidine were ineffective Most patients with gastro‐oesophageal reflux disease ( GERD ) , regardless of endoscopic status , suffer symptomatic relapse within 6 months of stopping acid suppressant therapy Background : Symptom relief , through adherence to appropriate maintenance therapy , is the sole objective of treatment for patients with endoscopy‐negative gastro‐oesophageal reflux disease BACKGROUND AND AIMS An ideal medication for heartburn should have the rapid onset of action needed for on-dem and treatment . However , assessment of the onset of action of proton pump inhibitors has been largely subjective . We compared the inhibitory effect on gastric acid secretion of a single oral dose of omeprazole with that of rabeprazole . METHODS Fourteen Helicobacter pylori-negative men participated in this r and omized , double-masked , two-way cross-over study . Intragastric pH was monitored continuously for 6 h after a single , r and omly assigned 20 mg oral dose of either omeprazole or rabeprazole . After a 7-day washout period , the other drug was administered . Each patient 's S-mephenytoin 4'-hydroxylase ( CYP2C19 ) genotype was determined by polymerase chain reaction-restriction fragment length polymorphism . RESULTS Intragastric pH and pH holding time did not differ between treatments when the data were analyzed for the whole group without stratifying for CYP2C19 status . In CYP2C19 homozygous and heterozygous extensive metabolizers ( 10 subjects ) , rabeprazole maintained the intragastric at pH > 3 and > 4 for longer than omeprazole during both the 5 and 6 h study periods , and the average pH during the 6 h study period was higher with rabeprazole than with omeprazole . In these extensive metabolizers , rabeprazole maintained the pH > 2 , > 3 , > 3.5 and > 4 for longer during the 6 h study period than did omeprazole . CONCLUSIONS In H. pylori-negative men who are CYP2C19 homozygous or heterozygous extensive metabolizers , the intragastric pH after a single dose of 20 mg rabeprazole is higher during first 5 - 6 h than that after a single dose of 20 mg omeprazole Background Heartburn , a common symptom , is self-treated with oral antacids . Efficacy of antacids has not been demonstrated for individual , spontaneous heartburn episodes . Methods We conducted a double-blind , r and omized , placebo-controlled , parallel-group study of self-directed treatment for episodic heartburn comparing famotidine ( FAM ) 5 , 10 , or 20 mg and antacid ( 11 mEq ANC ) to placebo ( PBO ) during a 4-week period . Twenty-nine US investigators enrolled a total of 565 out patients , ages 18–81 years ( mean 44.1 years ) with heartburn but not seeking care for heartburn . Treatment of spontaneous heartburn episodes was permitted as needed , up to twice daily , with self-administered test drug . An open-label , backup antacid was provided to use if test drug did not provide adequate relief . Patients assessed heartburn relief hourly and recorded use of backup antacid . Relief was defined as complete relief of symptoms without the use of backup antacid . Results The median proportion of episodes relieved was : PBO , 41 % ; FAM 5 mg , 59 % , 0.05 ≤ p < 0.10 ; FAM 10 mg , 70 % , p < 0.001 ; FAM 20 mg , 69 % , p < 0.001 ; antacid , 62 % , p < 0.05 ( p-values versus PBO ) . Supplemental analyses incorporating time to relief confirmed that famotidine and antacid provided more rapid and more frequent relief than placebo ( odds ratio for relief relative to PBO : FAM 5 mg , 1.55 , p = 0.003 ; FAM 10 mg , 1.94 , p < 0.001 ; FAM 20 mg , 2.13 , p < 0.001 ; antacid 1.57 , p = 0.003 ) . The tolerability profile was similar with famotidine , antacid , and placebo . Conclusions The positive results with antacid demonstrated for the first time the efficacy of antacid in self-treatment of individual heartburn episodes and provided internal validation of this study paradigm . Patients in this study self-medicated effectively using low doses of famotidine on an as needed basis for spontaneous episodes of heartburn Forty-eight patients with chronic duodenal ulcers which were healed with cimetidine were allocated at r and om into two equal groups to assess different ways of using cimetidine during one year of treatment . Twenty-four patients received intermittent six-week courses of cimetidine for each relapse , and 24 patients were treated with maintenance administration of cimetidine ( 400 mg twice a day ) continuously . Only one patient in the group receiving continuous therapy suffered clinical recurrence , but asymptomatic ulceration was found in four others . The group of patients who were receiving intermittent therapy suffered a total of 36 clinical recurrences . Three of these patients required prolonged treatment to heal their ulcers , and seven developed asymptomatic ulcer . The number of relapses varied from none to five . No way of predicting the individual prognosis was found . Intermittent treatment was an acceptable alternative in approximately half of the patients treated in this way , and was a failure in one-quarter of the group OBJECTIVE To assess the efficacy of omeprazole in patients presenting with troublesome reflux symptoms . DESIGN R and omized , double-blind , parallel-group , placebo-controlled comparison . SETTING Primary care . SUBJECTS Patients were recruited using a symptom-based question naire for diagnosis of gastro-oesophageal reflux disease . INTERVENTIONS After endoscopy , patients without endoscopic oesophagitis were r and omized to omeprazole 20 mg ( Ome20 ) , omeprazole 10 mg ( Ome10 ) or placebo once daily for 4 weeks ( n = 261 ) and those with oesophagitis ( except circumferential/ulcerative ) were r and omized to receive either Ome20 or Ome10 once daily for 4 weeks ( n = 277 ) . Patients not symptom-free at 4 weeks received open treatment with Ome20 once daily for a further 4 weeks . Those symptom-free at 4 - 8 weeks were followed up for 6 months off treatment , to see whether their symptoms recurred . MAIN OUTCOME MEASURE Complete upper GI symptom relief during week 4 on Ome20 or Ome10 in patients with or without endoscopic oesophagitis . RESULTS Forty one percent of all patients on Ome20 and 35 % on Ome10 reported complete relief from upper GI symptoms during week 4 , whilst 73 % of the patients on Ome20 and 62 % on Ome10 obtained sufficient control . Complete relief during week 4 was reported by 19 % of endoscopy-negative patients on placebo , and sufficient control by 35 % . Endoscopic healing at 4 weeks occurred in 76 % of oesophagitis patients on Ome20 and in 56 % on Ome10 . After 6 months off treatment , 90 % of patients with oesophagitis and 75 % of endoscopy-negative patients reported symptomatic relapse . CONCLUSION Both 10 mg and 20 mg of omeprazole gave effective relief of symptoms , although 20 mg gave superior healing in patients with oesophagitis . After cessation of treatment , symptomatic relapse was rapid and frequent in both endoscopy-positive and endoscopy-negative patients Introduction : Relapse of erosive oesophagitis occurs in almost all patients if treatment is stopped after initial healing To compare the onset of action of the local antacid Maalox and the systemic H2‐antagonist ranitidine , during ‘ on dem and ’ ambulant treatment of a single heartburn episode , using a r and omized , parallel group , double‐blind , double‐dummy design Background On-dem and therapy may offer an effective approach to the long-term management of gastro-oesophageal reflux disease ( GORD ) without oesophagitis . Aim To examine the efficacy of the novel proton pump inhibitor esomeprazole as on-dem and therapy in endoscopy-negative GORD . Patients and methods Endoscopy-negative GORD patients who achieved complete resolution of heartburn after short-term esomeprazole or omeprazole treatment ( n = 721 ) were r and omized to esomeprazole 20 mg ( n = 282 ) , 40 mg ( n = 293 ) or placebo ( n = 146 ) on dem and ( maximum one dose/day ) for 6 months . The primary and secondary efficacy endpoints were time to study discontinuation due to ( i ) unwillingness to continue and ( ii ) inadequate control of heartburn , respectively . Results Both doses of esomeprazole were more effective than placebo . During the 6-month period , 42 % of placebo recipients discontinued treatment due to unwillingness to continue , compared with 8 % and 11 % of esomeprazole 20 mg and 40 mg recipients , respectively . Overall , more patients treated with esomeprazole were free from gastrointestinal symptoms after 6 months of on-dem and therapy . Conclusions Esomeprazole 20 mg was superior to placebo for on-dem and treatment of GORD ; a higher dose did not confer additional clinical benefit . Over 90 % of patients were willing to continue on-dem and treatment with esomeprazole 20 mg over a 6-month period Background : There are few data on how patients on maintenance treatment of reflux oesophagitis take their medication . This study was design ed to investigate the dosing patterns of patients on on-dem and treatment and to compare lansoprazole with omeprazole in this regard . Methods : Patients with reflux oesophagitis , initially treated until absence of symptoms , took capsules of either lansoprazole ( 30 mg ) or omeprazole ( 20 mg ) for 6 months ; they were instructed to take the medication only when reflux symptoms occurred . In order to document dosing patterns , the medication was dispensed in bottles supplied with a Medication Event Monitoring System recording date and time the bottles were opened . There were regular follow-up visits with assessment of symptoms . Results : Three-hundred patients were eligible for analysis according to ' all patients treated ' . A dosing pattern was found of an increased intake mornings and evenings and constant intervals between intakes . Although there was no correlation between oesophagitis grade or initial symptoms and the amount of medication consumed , the patients had significantly fewer reflux symptoms the more medication they consumed . There was no difference in the number of capsules consumed between the lansoprazole ( 0.73 capsules/day ) and omeprazole groups ( 0.71 capsules/day ) . Nor was there any difference between the groups in reflux symptoms during the course of the study . Conclusion : Despite rigorous instructions to take medication on dem and , the results suggest that it is patient habits more so than symptoms that determine the frequency and interval of medication intake . Symptoms are not therefore decisive for the amount of medication consumed Background : Compliance studies have shown that patients with reflux symptoms generally take their medication only when experiencing these symptoms This study aim ed to evaluate whether or not the use of intermittent positive pressure ventilation via the laryngeal mask airway is associated with a higher risk of gastro‐oesophageal reflux when compared with intermittent positive pressure ventilation via a tracheal tube in patients undergoing day case gynaecological laparoscopy in the head down position . Sixty healthy women were r and omly allocated to receive either the laryngeal mask or cuffed tracheal tube for intra‐operative airway maintenance . Using continuous oesophageal pH monitoring , four patients in the tracheal tube group and none in the laryngeal mask group had evidence of gastro‐oesophageal reflux ( as indicated by a decrease in oesophageal pH to below 4 ) . The difference in the incidence of reflux did not achieve statistical significance ( p = 0.11 ) . In conclusion , we found no evidence to suggest that the use of intermittent positive pressure ventilation via the laryngeal mask increases the risk of gastro‐oesophageal reflux in patients undergoing elective day case gynaecological laparoscopy Abstract Objective : To assess intermittent treatment over 12 months in patients with symptomatic gastro-oesophageal reflux disease . Design : R and omised , multicentre , double blind , controlled study . Patients with heartburn and normal endoscopy results or mild erosive changes received omeprazole 10 mg or 20 mg daily or ranitidine 150 mg twice daily for 2 weeks . Patients remaining symptomatic had omeprazole 10 mg or ranitidine dose doubled for another 2 weeks while omeprazole 20 mg was continued for 2 weeks . Patients who were symptomatic or mildly symptomatic were followed up for 12 months . Recurrences of moderate or severe heartburn during follow up were treated with the dose which was successful for initial symptom control . Setting : Hospitals and primary care practice s between 1994 and 1996 . Subjects : 677 patients with gastro-oesophageal reflux disease . Main outcome measures : Total time off active treatment , time to failure of intermittent treatment , and outcomes ranked from best to worst . Results : 704 patients were r and omised , 677 were eligible for analyses ; 318 reached the end of the study with intermittent treatment without recourse to maintenance antisecretory drugs . The median number of days off active treatment during follow up was 142 for the entire study ( 281 for the 526 patients who reached a treatment related end point ) . Thus , about half the patients did not require treatment for at least 6 months , and this was similar in all three treatment groups . According to outcome , 378 ( 72 % ) patients were in the best outcome ranks ( no relapse or one ( or more ) relapse but in remission until 12 months ) ; 630 ( 93 % ) had three or fewer relapses in the intermittent treatment phase . Omeprazole 20 mg provided faster relief of heartburn . The results were similar in patients with erosive and non-erosive disease . Conclusions : Intermittent treatment is effective in managing symptoms of heartburn in half of patients with uncomplicated gastro-oesophageal reflux disease . It is simple and applicable in general practice , where most patients are seen BACKGROUND AND PURPOSE Reflux esophagitis of Los Angeles grade A or B is more common than grade s C and D disease among Taiwanese . This study compared the efficacy of esomeprazole 40 mg and omeprazole 20 mg for starting on-dem and therapy for grade A and B reflux esophagitis . METHODS 100 patients with grade A and B reflux esophagitis were r and omized to receive either esomeprazole 40 mg once daily ( n = 50 ) or omeprazole 20 mg once daily ( n = 50 ) for the first 4 weeks . Sustained symptomatic response ( SSR ) was defined as freedom from symptoms for the last 7 days of the 4-week treatment duration . On-dem and therapy was used for the next 4 weeks in patients with SSR ; patients without SSR continued with the same proton pump inhibitor regimen . Patients were asked to record their daily severity of acid regurgitation ( AR ) and heartburn ( HB ) . Medication usage during on-dem and therapy was recorded . RESULTS Forty six patients in the esomeprazole group and 45 patients in the omeprazole group completed the study protocol . The rate of SSR was higher in the esomeprazole group than in the omeprazole group ( per- protocol : 73.9 % vs 51.1 % , p < 0.05 ; intent-to-treat : 68 % vs 46 % , p < 0.05 ) . The symptomatic scores for AR and HB were similar between patients taking medication continuously and those taking medication on-dem and with both esomeprazole and omeprazole . For patients starting on-dem and therapy , the total number of tablets used during 4 weeks was lower in the esomeprazole group than in the omeprazole group ( 13.5 vs 18.5 , p < 0.05 ) . CONCLUSIONS In patients with grade A and B reflux esophagitis , esomeprazole 40 mg was more effective than omeprazole 20 mg for the initiation of on-dem and therapy Abstract Objective : This 1-year study compared the cost effectiveness of omeprazole and ranitidine when used as initial therapy in an intermittent treatment strategy for the management of patients with symptomatic gastro-oesophageal reflux disease with or without erosive oesophagitis . Design and setting : A prospect i ve health economic analysis was conducted alongside an international multicentre r and omised , double-blind clinical study . The economic analysis was performed from a societal perspective . Patients : A total of 704 patients in the UK , the Republic of Irel and , Germany , France , Italy and Spain were r and omised to 1 of the 3 treatment groups . Interventions : Patients were r and omised to receive either omeprazole 20 mg once daily , omeprazole 10 mg once daily or ranitidine 150 mg twice daily . Initial treatment failure result ed in dose titration and drug switching from ranitidine to omeprazole , and subsequently open maintenance treatment . Main outcome measures and results : The estimated mean direct medical costs ( medication and number of visits and endoscopies ) were found to be lower for both dosages of omeprazole than for ranitidine in all countries except Germany . However , none of the differences were statistically significant . The differences between omeprazole 10 mg and omeprazole 20 mg were small and nonsignificant . With regard to numbers of symptom-free days , both omeprazole 20 mg and omeprazole 10mgwere found to be more effective than ranitidine . However , none of the differences were statistically significant . Conclusions : Following a pragmatic interpretation , incorporating intermediate short term results , the results in this study give no support to the notion that a step-up approach , either as dose titration from omeprazole 10 mg to omeprazole 20 mg or as drug switching from ranitidine to omeprazole , will result in cost savings and thereby be cost BACKGROUND A multicentric , r and omized , placebo-controlled double-blind study on ginkgo biloba special extract EGb 761 ( Tebonin forte ) in patients suffering from peripheral occlusive arterial disease ( POAD ) in Fontaine stage II b was carried out in order to prove its clinical efficacy in this indication according to guidelines of European Community authorities and the German Angiological Society and to confirm the results of former clinical studies with EGb 761 . PATIENTS AND METHODS In total , 111 patients with angiographically proven POAD in Fontaine stage II b and intermittent claudication ( pain-free walking distance < 150 m on the treadmill ) were recruited in 5 centers and treated with either EGb 761 or placebo at a daily dose of 3 times 1 film-coated tablet over a duration of 24 weeks following a 2-week placebo run-in period . The primary response variable was the difference of the pain-free walking distance between the start of treatment and after 8 , 16 and 24 weeks as measured on the treadmill ( walking speed 3 km/h and slope of 12 % ) under st and ardized conditions . RESULTS At the start of the treatment period , the mean pain-free walking distances were very similar with 108.5 m in the EGb 761 group and 105.2 m in the placebo group . At the end of the treatment period these values increased to 153.2 m and 126.6 m , respectively . The group differences were statistically significant at all three control visits with p = 0.017 , p = 0.007 , and p = 0.016 . The differences for the maximum walking distance and the relative increases of the pain-free walking distance and the maximum distance were also significantly higher in the EGb 761 group with p-values < 0.05 each . In both groups Doppler indices remained nearly unchanged during therapy . The subjective assessment of the patients demonstrated an amelioration of complaints in both groups . Tolerability was very good with no adverse events under EGb 761 and one case of heartburn and gastric pain in the placebo group . CONCLUSIONS It can be concluded from the results of this study that treatment with EGb 761 in POAD patients with Fontaine stage II b is very safe and causes a significant and therapeutically relevant prolongation of the patients ' walking distance OBJECTIVE Although combined modality therapy appears to be superior to radiotherapy alone for the treatment of locally advanced non-small cell lung cancer ( NSCLC ) , the optimal treatment regimen has not been determined . We design ed this trial to determine the maximal tolerated doses ( MTD ) of continuous intravenous infusion ( CI ) cisplatin and etoposide that could be administered concurrently with thoracic irradiation . METHODS 19 patients with stage IIIA or IIIB NSCLC were treated at three different dose levels of CI cisplatin and etoposide with concurrent single daily fraction thoracic radiotherapy to 4500 cGy . This chemoradiotherapy phase of treatment was followed by a 1500 - 2000 cGy radiotherapy boost and three cycles of st and ard intermittent bolus cisplatin 80 mg/m2 i.v . on day 1 and etoposide 80 mg/m2 i.v . on days 1 , 2 and 3 . RESULTS The MTD of CI chemotherapy was determined to be cisplatin 5 mg/m2/day plus etoposide 18 mg/m2/day for 5 days per week over 5 weeks along with thoracic irradiation . Overall , 37 % of patients required breaks in the chemoradiotherapy course and 32 % required attenuation of the planned duration of CI chemotherapy . Only 42 % of patients received all three planned cycles of bolus chemotherapy and 16 % received < 6000 cGy of thoracic irradiation . The major toxicities during concurrent chemoradiotherapy were grade 3 - 4 esophagitis ( 42 % ) and myelosuppression ( 47 % ) . Subsequent chemotherapy was complicated by grade 3 - 4 myelosuppression in 38 % of patients . An objective response was documented in 58 % of patients ( CR 11 % , PR 47 % ) . Median survival was 18 months with 2- and 5-year survival rates of 42 and 11 % , respectively . CONCLUSIONS These results demonstrate that CI cisplatin and etoposide can be administered safely to patients with locally advanced NSCLC , and that such potentially radiosensitizing strategies deserve further evaluation in this setting More than half the number of patients who report troublesome heartburn symptoms suggestive of gastro-oesophageal reflux disease ( GORD ) to their doctor present with no obvious oesophageal lesions at endoscopy ( 1–3 ) . They do require medical therapy , however , and the objective of treatment in this endoscopy-negative group is symptom improvement and relief to a level where the symptoms are perceived as being under control . In clinical trials , the therapeutic response to treatment is usually assessed by asking patients to define the frequency and severity of their heartburn symptoms . While this may give reasonably accurate information about a very subjective outcome measure , it fails to address the question as to whether the patients perceive that they experienced sufficient heartburn control from their therapy , which is the aim of treatment in clinical practice . This analysis of data from a clinical trial relates pre and post-treatment heartburn assessment s to a st and ardized question to the patient : ‘ Does the study medication give sufficient control of your heartburn ? ’ This relationship may guide the choice of a clinical ly relevant efficacy measure based on heartburn severity and frequency Quality of life ( QoL ) is commonly assessed for evaluating the process and outcome of treatment but has not been studied in duodenal ulcer ( DU ) disease . The recently developed and vali date d Quality of Life in Duodenal Ulcer Patients ( QLDUP ) question naire allowed the study of various dimensions according to treatment regimens . This study was conducted to compare QoL over a one-year follow-up period in DU patients r and omized to two treatment regimens : maintenance versus intermittent ( no maintenance ) treatment with nizatidine . A total of 581 patients with endoscopic evidence of DU healing were r and omly allocated to receive either nizatidine 150 mg/day for one year ( Group A ) or intermittent treatment ( Group B ) . In both groups , symptomatic relapses were treated with nizatidine 300 mg/day for 6 weeks . The QLDUP question naire , which provides a QoL profile from 54 items divided up into 15 dimensions , was completed by all patients at entry and again at the time of a visit every 2 months for one year . The one-year symptomatic relapse rates were 8.0 % and 33.5 % in Group A and Group B , respectively ( p < 0.001 ) . The intent-to-treat analysis showed that patients in Group A had better QoL scores than those in Group B as regards 8 QoL dimensions , including ulcer-specific and non-specific dimensions . Differences between treatments were significant after 4 months , and this was sustained until the one-year assessment . The overall gain in QoL was significantly greater in Group A than in Group B with respect to 11 QoL dimensions . In conclusion , maintenance treatment with nizatidine for DU improved QoL to a larger extent than when intermittent therapy was used In this double-masked , double-dummy , r and omized , single crossover study , we compared single doses of a fast-dissolving wafer formulation of famotidine with a conventional tablet formulation of ranitidine in patients with gastroesophageal reflux disease ( GERD ) . Patient preference time until symptomatic relief , and predictive characteristics of early responders were assessed . Eligible patients had a clinical diagnosis of GERD and symptoms of GERD of sufficient severity to require relief . The study treatment was one dose of famotidine ( 20-mg wafer ) and one dose of ranitidine ( 150-mg tablet ) , which were given in a r and omized order and taken as needed . The patients were instructed to measure the symptomatic effects on a seven-point categorical scale ( 1 = worse to 7 = free of symptoms ) at 15 , 30 , 45 , 60 , 120 , and 180 minutes . After the clinical phase of the trial , the patients indicated their global assessment of efficacy and their preference for the wafer or the tablet . Of the 829 patients who completed the study , significantly more preferred the wafer to the tablet . While there was no significant difference in the global assessment of efficacy , the famotidine wafer provided significantly better relief than the ranitidine tablet during the first hour after dosing . However , at 120 and 180 minutes , the degree of relief was similar for the two drugs . The time until a clinical ly significant effect was also similar for the two drugs , and approximately one half of the patients experienced such improvement within 3 hours . Multivariate analyses disclosed no predictive characteristics of early symptomatic effect To compare the effects of ranitidine 75 mg with those of either cimetidine 200 mg or placebo given on dem and for relief of typical symptoms of gastro‐oesophageal reflux disease during a 15‐day period UNLABELLED We performed an open , prospect i ve , r and omized , three-cell , 6-month clinical trial on the prevention of duodenal ulcer ( DU ) relapse , comparing three omeprazole schedules , i.e. 20 mg daily , 20 mg every other day ( e.o.d . ) and 40 mg on Saturdays and Sundays ( S/S ) . Diagnosis of either healed or relapsed DU was on an endoscopic basis . Follow-up visits were performed at 3-monthly intervals with endoscopy at the baseline , after 6 months and at every symptomatic relapse . STATISTICS chi 2 test with st and ardized deviates , Yates ' corrected chi 2 test and analysis of variance ( one-way ) . One hundred and fifteen patients were r and omized to receive omeprazole 20 mg/day , 123 omeprazole 20 mg e.o.d . and 115 40 mg S/S. Twenty-eight dropped out ( 11 , 8 and 9 , respectively ) . Demonstrated ulcer relapse rates were 5.7 % with omeprazole 20 mg/day , 18.1 % with 20 mg e.o.d . and 17.6 % with 40 mg S/S ( p = 0.0124 , ' per- protocol ' analysis ) . No clinical ly significant adverse effects were recorded . In conclusion , of the three schedules studied , omeprazole 20 mg/day proved the most effective maintenance treatment for healed DU |
1,808 | 22,623,602 | The findings from this descriptive review suggest that multilevel interventions have positive effects on several health behavior outcomes , including cancer prevention and screening , as well improving the quality of health-care system processes . | To examine the impact of multilevel interventions ( with three or more levels of influence ) design ed to reduce health disparities , we conducted a systematic review and meta- analysis of interventions for ethnic/racial minorities ( all except non-Hispanic whites ) that were published between January 2000 and July 2011 .
The primary aims were to synthesize the findings of studies evaluating multilevel interventions ( three or more levels of influence ) targeted at ethnic and racial minorities to reduce disparities in their health care and obtain a quantitative estimate of the effect of multilevel interventions on health outcomes among these subgroups . | OBJECTIVE To improve health outcomes of children , the US Maternal and Child Health Bureau has recommended more effective organization of preventive services within primary care practice s and more coordination between practice s and community-based agencies . However , applying these recommendations in communities is challenging because they require both more complex systems of care delivery within organizations and more complex interactions between them . To improve the way that preventive health care services are organized and delivered in 1 community , we design ed , implemented , and assessed the impact of a health care system-level approach , which involved addressing multiple care delivery processes , at multiple levels in the community , the practice , and the family . Our objective was to improve the processes of preventive services delivery to all children in a defined geographic community , with particular attention to health outcomes for low-income mothers and infants . DESIGN Observational intervention study in 1 North Carolina county ( population 182 000 ) involving low- income pregnant mothers and their infants , primary care practice s , and departments of health and mental health . An interrupted time-series design was used to assess rates of preventive services in office practice s before and after the intervention , and a historical cohort design was used to compare maternal and child health outcomes for women enrolled in an intensive home visiting program with women who sought prenatal care during the 9 months before the program 's initiation . Outcomes were assessed when the infants reached 12 months of age . INTERVENTIONS Our primary objective was to achieve changes in the process of care delivery at the level of the clinical interaction between care providers and patients that would lead to improved health and developmental outcomes for families . We selected interventions that were directed toward major risk factors ( eg , poverty , ineffective care systems for preventive care in office practice s ) and for which there was existing evidence of efficacy . The interventions involved community- , practice - , and family-level strategies to improve processes of care delivery to families and children . The objectives of the community-level intervention were : 1 ) to achieve policy level changes that would result in changes in re sources available at the level of clinical care , 2 ) to engage multiple practice organizations in the intervention to achieve an effect on most , if not all , families in the community , and 3 ) to enhance communication between , among , and within public and private practice organizations to improve coordination and avoid duplication of services . The objective of the practice -level interventions was to overcome specific barriers in the process of care delivery so that preventive services could be effectively delivered . To assist the health department in implementing the family-level intervention , we provided assistance in hiring and training staff and ongoing consultation on staff supervision , including the use of structured protocol s for care delivery , and regular feedback data about implementation of the program . Interventions with primary care practice s focused on the design of the delivery system within the office and the use of teamwork and data in an " office systems " approach to improving clinical preventive care . All practice s ( N = 8) that enrolled at least 5 infants/month received help in assessing performance and developing systems ( eg , preventive services flow sheets ) for preventive services delivery . Family-level interventions addressed the process of care delivery to high-risk pregnant women ( < 100 % poverty ) and their infants . Mothers were recruited for the home visiting intervention when they first sought prenatal care at the community health center , the county 's largest provider of prenatal care to underserved women . The home visiting intervention involved teams of nurses and educators and involved 2 to 4 visits per month through the infant 's first year of life to provide parental education on fetal and infant health and development , enhance parents ' informal support systems , and link parents with needed health and human services . We included training in injury prevention and discipline , and home visitors assisted mothers in obtaining care from one of the primary care offices . RESULTS There were high levels of participation , changes in the organization of the delivery system , and improvements in preventive health outcomes . Agencies cooperated in joint contracting , staff training , and defining program eligibility . All 8 eligible practice s agreed to participate and 7/8 implemented at least 1 new office system element . Of eligible women , 89 % agreed to participate , and outcome data were available on 80 % ( 180/225 ) . After adjusting for differences in baseline characteristics , intervention group women were significantly more likely than comparison group women to use contraceptives ( 69 % vs 47 % ) , not smoke tobacco ( 27 % vs 54 % ) and have a safe and stimulating home environment for their children . Intervention group children were more likely to have had an appropriate number of well-child care visits ( 57 % vs 37 % ) and less likely to be injured ( 2 % vs 7 % ) . Intervention mothers also received Aid to Families with Dependent Children for fewer months after the birth of their child ( 7.7 months vs 11.3 months ) . CONCLUSIONS We observed a number of positive effects at all 3 levels of intervention . Policy-level changes at the state and community led to lasting changes in the organization and financing of care , which enabled changes in clinical services to take place . These changes have now been exp and ed beyond this community to other communities in the state . We were also able to engage multiple practice organizations , reduce duplication , and improve the coordination of care . Changes in the process of preventive services delivery were noted in participating practice s. Finally , the outcomes of the family-level intervention were comparable in direction and magnitude to the outcomes of previous r and omized trials of the intervention . All the changes were achieved over a relatively brief 3-year study period , and many have been sustained since the project was completed . Tiered , interrelated interventions directed at an entire population of mothers and children hold promise to improve the effectiveness and outcomes of health care for families and children BACKGROUND Community Action Against Asthma ( CAAA ) is a community-based participatory research ( CBPR ) project that assesses the effects of outdoor and indoor air quality on exacerbation of asthma in children , and tests household- and neighborhood-level interventions to reduce exposure to environmental asthma triggers . Representatives of community-based organizations , academia , an integrated health system , and the local health department work in partnership on CAAA 's Steering Committee ( SC ) to design and implement the project . OBJECTIVE To conduct a process evaluation of the CAAA community-academic partnership . DESIGN In-depth interviews containing open-ended questions were conducted with SC members . Analysis included established methods for qualitative data , including focused coding and constant comparison methods . SETTING Community setting in Detroit , Michigan . PARTICIPANTS Twenty-three members of the CAAA SC . MEASUREMENTS Common themes identified by SC members relating to the partnership 's ability to achieve project goals and the successes and challenges facing the partnership itself . MAIN RESULTS Identified partnership accomplishments included : successful implementation of a complex project , identification of children with previously undiagnosed asthma , and diverse participation and community influence in SC decisions . Challenges included ensuring all partners ' influence in decision-making , the need to adjust to " a different way of doing things " in CBPR , constraints and costs of doing CBPR felt by all partners , ongoing need for communication and maintaining trust , and balancing the needs of science and the community through intervention . CONCLUSIONS CBPR can enhance and facilitate basic research , but care must be given to trust issues , governance issues , organizational culture , and costs of participation for all organizations involved In this paper we describe a successful multi-level participatory intervention grounded in principles of individual and group empowerment , and guided by social construction theory . The intervention addressed known and persistent inequities in influenza vaccination among African American and Latino older adults , and associated infections , hospitalizations and mortality . It was design ed to increase resident ability to make informed decisions about vaccination , and to build internal and external infrastructure to support sustainability over time . The intervention brought a group of social scientists , vaccine research ers , geriatricians , public health nurses , elder services providers and advocates together with senior housing management and activist African American and Latino residents living in public senior housing in a small east coast city . Two buildings of equal size and similar ethnic composition were r and omized as intervention and control buildings . Pre and post intervention surveys were conducted in both buildings , measuring knowledge , attitudes and peer norms . Processes and outcomes were documented at four levels : Influenza Strategic Alliance ( macro and exo levels ) , building management ( meso level ) , building resident committee ( meso level ) and individual residents . The Influenza Strategic Alliance ( I.S.A. ) provided ongoing re sources , information and vaccine ; the building management provided economic and other in-kind re sources and supported residents to continue flu clinics in the building . The V.I.P. Resident Committee conducted flu campaigns with flu clinics in English and Spanish . The vaccination rate in the intervention building at post test exceeded the study goal of 70 % and showed a significant improvement over the control building . The intervention achieved desired outcomes at all four levels and result ed in a significant increase in influenza vaccination , and improvements in pro-vaccination knowledge , beliefs , and underst and ing of health consequences Lay Health Promoters ( LHPs ) are widely used in community health education , but their use and evaluation in occupational health has been limited to farm workers . Evaluation data were collected from 30 r and omly selected Latino poultry processing workers who had an encounter with an LHP who delivered Maria 's Story , an occupational health lesson about cumulative trauma disorders ( CTDs ) . Participants had good recall of Maria 's Story . Most participants ( n = 18 , 60 % ) could identify the primary occupational health exposure linked to CTDs , more than 50 % of participants ( n = 16 ) could recall one or more ways of preventing CTDs , and 43.3 % ( n = 13 ) described in detail recommended treatments . Nearly one-half ( n = 12 ) reported an occupational health behavior change after hearing Maria 's Story . The results of this study suggest that LHPs may be effective in promoting occupational health and reducing occupational health disparities among ethnic minorities in high-risk occupations BACKGROUND The National Cancer Institute funded an 8-year , nonr and omized demonstration project for tobacco prevention and control , the American Stop Smoking Intervention Study ( ASSIST ) . To evaluate ASSIST , we compared changes in adult smoking prevalence , per capita cigarette consumption , and tobacco control policies between the 17 ASSIST states and the 33 non-ASSIST states and the District of Columbia . METHODS The strength of tobacco control index was used to measure state-level program elements directed at tobacco control , and the initial outcomes index ( IOI ) was used to measure states ' tobacco control policy outcomes . Prevalence data were obtained from the Tobacco Use Supplement to the Current Population Survey , and consumption data were obtained from the Tobacco Institute 's bimonthly sales figures for cigarette packs moved from wholesale warehouses . Two-stage regression and mixed-effects linear modeling were used to analyze the various outcomes . Statistical analyses for testing individual regression coefficients were one-sided . RESULTS ASSIST states had a greater decrease in adult smoking prevalence than non-ASSIST states , with an adjusted difference of -0.63 % ( P = .049 ) . Per capita cigarette consumption was not statistically significantly different between ASSIST and non-ASSIST states . However , an increase in the IOI of a state from the 25th to the 75th percentile was associated with a reduction in per capita cigarette consumption by 0.57 packs per person per month . State IOI was also inversely , albeit not statistically significantly , associated with smoking prevalence ( regression coefficient = -0.11;P = .06 ) . CONCLUSIONS The reduction in adult smoking prevalence associated with ASSIST could have translated into approximately 278 700 fewer smokers nationwide if all states had implemented ASSIST . Investment in building state-level tobacco control capacity and promoting changes in tobacco control policies are effective strategies for reducing tobacco use Objective : To evaluate changes in the worksite environment in response to a multilevel intervention over a 2-year period . Methods : Worksites were recruited in the greater Seattle area , and 34 were r and omized to intervention or comparison condition . The intervention was based on the ecological model , with a framework of defined phases of intervention that included worksite-wide events implemented in partnership with employee-based advisory boards . The assessment of the worksite environment used a modification of the Checklist of Health Promotion Environments at Worksites . Subscales were developed using baseline data only . The intervention effect on different aspects of the worksite environment was estimated using logistic regression with robust estimating procedures . Results : Only changes in the physical activity and nutrition information environments were significantly associated with the intervention . Conclusions : This article provides one of the first attempts at using environmental assessment in the evaluation of worksite interventions OBJECTIVES The North Carolina WISEWOMAN project was initiated to evaluate the feasibility of exp and ing an existing cancer screening program to include a cardiovascular disease ( CVD ) screening and intervention program among low-income women . METHODS Seventeen North Carolina county health departments were design ated as minimum intervention ( MI ) , and 14 as enhanced intervention ( EI ) . The EI included three specially constructed counseling sessions spanning 6 months using a structured assessment and intervention program tailored to lower income women . RESULTS Of the 2,148 women screened , 40 % had elevated total cholesterol ( > or = 240 mg/dL ) , 39 % had low high-density lipoprotein cholesterol ( HDL-C ) levels ( < 45 mg/dL ) , and 63 % were hypertensive ( systolic blood pressure 140 and /or diastolic blood pressure > or = 90 mm Hg or on hypertensive medication ) . The majority of women ( 86 % ) had at least one of these three risk factors . Seventy-six percent were either overweight or obese . After 6 months of follow-up in the EI health departments , changes in total cholesterol levels , HDL-C levels , diastolic blood pressure , and BMI were observed ( -5.8 mg/dL , -0.9 mg/dL , -1.7 mm Hg , and -0.3 kg/m(2 ) , respectively ) , but were not significantly different from MI health departments . A dietary score that summarized fat and cholesterol intake improved by 2.1 units in the EI group , compared with essentially no change in the MI group . CONCLUSIONS Exp and ing existing cancer screening programs to include CVD intervention was feasible and may be an effective means for promoting healthful dietary practice s among low-income women BACKGROUND African American men with hypertension ( HTN ) in low socioeconomic urban environments continue to achieve poor rates of HTN control . METHODS In a 5-year r and omized clinical trial with 309 hypertensive urban African American men aged 21 to 54 years , the effectiveness of a more intensive educational/behavioral/pharmacologic intervention provided by a nurse practitioner/community health worker/physician team was compared to less intensive information and referral intervention . Changes in behavioral factors , health care utilization , blood pressure ( BP ) control , left ventricular hypertrophy ( LVH ) , and renal insufficiency were evaluated . RESULTS Follow-up rates exceeded 89 % of available men . The ranges of mean annual systolic BP/diastolic BP change from the baseline to each year follow-up were -3.7 to -10.1/-4.9 to -12.3 mm Hg for the more intensive group and + 3.4 to -3.0/-1.8 to -8.7 mm Hg for the less intensive group . The annual proportion of men with controlled BP ( < 140/90 mm Hg ) ranged from 17 % to 44 % in the more intensive group and 21 % to 36 % in the less intensive group . At 5 years the more intensive group had less LVH than the less intensive group and 17 % of the men were deceased primarily due to narcotic or alcohol intoxication ( 36 % ) and cardiovascular causes ( 19 % ) . CONCLUSIONS An appropriate educational/behavioral intervention significantly improved BP control and reduced some sequelae of HTN in a young African American male population . Improvement in risk factors other than HTN was limited and sustained control of HTN was difficult to maintain during 5 years Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists INTRODUCTION This article describes the development of a community-based participatory research ( CBPR ) process conducted in the context of a r and omized community health education trial utilizing community health workers ( CHWs ) . OBJECTIVES To present lessons learned from the utilization of CBPR methodology in a cardiovascular disease ( CVD ) prevention trial among Mexican American adults in a U.S.-Mexico border community and to disseminate the baseline results associated with risk factors for CVD and their associated demographic and psychosocial characteristics . METHODS Participants were 328 Hispanic adults ages 30 - 75 with at least one risk factor for CVD ( overweight , smoking , high cholesterol , diabetic or hypertensive ) , who were recruited through approaching households in r and omly selected census tracts within a specified zip code area . RESULTS CBPR methods were applied during the different stages of the research enterprise to support the development and implementation of the intervention trial aim at reducing cardiovascular risk factors for Mexican American adults . Data from baseline were used as an important component of dialogue with the community . DISCUSSION CBPR proved to be a good learning process for all partners involved . The risk profile of the participants demonstrated the " epidemic " nature of CVD morbidity conditions associated with Mexican origin population s living in a U.S.-Mexico border community . The CBPR dialogue was instrumental as a process to help disseminate to the community the need for projects like the one described in this article 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 BACKGROUND Underutilization of breast and cervical cancer screening has been observed in many ethnic groups and underserved population s. Effective community-based interventions are needed to eliminate disparities in screening rates and thus to improve prospect s for survival . METHODS The Breast and Cervical Cancer Intervention Study was a controlled trial of three interventions in the San Francisco Bay Area from 1993 to 1996 : ( 1 ) community-based lay health worker outreach ; ( 2 ) clinic-based provider training and reminder system ; and ( 3 ) patient navigator for follow-up of abnormal screening results . Study design and a description of the interventions are reported along with baseline results of a household survey conducted in four language s among 1599 women , aged 40 - 75 . RESULTS Seventy-six percent of women ages 40 and over had had at least one mammogram , and most had had a clinical breast examination ( 88 % ) and Pap smear ( 89 % ) . Rates were significantly lower for non-English-speaking Latinas and Chinese women ( 56 and 32 % , respectively , for mammography ) , and maintenance screening ( three mammograms in the past 5 years ) varied from 7 % ( non-English-speaking Chinese ) to 53 % ( Blacks ) . Pap smear screening in the past 3 years was low among non-English-speaking Latinas ( 72 % ) and markedly lower among non-English-speaking Chinese women ( 24 % ) . The strongest predictors of screening behavior were having private health insurance and frequent use of medical services . Having a regular clinic and speaking English were also important . Race/ethnicity , education , household income , and employment status were , overall , not significant predictors of screening behavior . CONCLUSIONS These baseline results support the importance of cancer screening interventions targeted to persons of foreign origin , particularly those less acculturated OBJECTIVES We analyzed outcomes from a study that examined social- context ual factors in cancer prevention interventions for working class , multiethnic population s. METHODS Ten community health centers were r and omized to intervention or to control . Patients who resided in low-income , multiethnic neighborhoods were eligible ; the intervention targeted fruit and vegetable consumption , red meat consumption , multivitamin intake , and physical activity . Outcomes were measured at 8 months . RESULTS The intervention led to significant increases in fruit and vegetable consumption and multivitamin intake and reductions in red meat consumption ; no change was found in physical activity levels . The intervention effect was not changed when context ual variables that may function as confounders or effect modifiers ( e.g. , gender , education , race/ethnicity , respondent and parents ' country of birth , and poverty status ) were included in the analyses . CONCLUSIONS The intervention led to significant improvements in health behaviors among a working class , multiethnic population , regardless of race/ ethnicity and socioeconomic status . Interventions that respond to the social context of working class individuals across racial/ethnic categories hold promise for improving cancer-related risk behaviors Background : In 1998 , the Health Re sources and Services Administration ’s Bureau of Primary Health Care began the Health Disparities Collaboratives ( HDC ) to improve chronic disease management in community health centers ( HCs ) nationwide . The HDC incorporates rapid quality improvement , a chronic care model , and best practice learning sessions . Objectives : To determine whether the HDC improves diabetes care in HCs over 4 years and whether more intensive interventions enhance care further . Subjects : Chart review of 2364 , 2417 , and 2212 r and omly selected patients with diabetes from 34 HCs in 17 states in 1998 , 2000 , and 2002 , respectively . Measures : American Diabetes Association st and ards . Research Design : We performed a r and omized controlled trial with an embedded prospect i ve longitudinal study . We r and omized 34 HCs that had undergone 1–2 years of the HDC . The st and ard-intensity arm continued the baseline HDC intervention . High-intensity arm centers received 4 additional learning sessions , provider training in behavioral change , and patient empowerment material s. To assess the impact of the HDC , we analyzed changes in clinical processes and outcomes in the st and ard-intensity centers . To determine the effect of more intensive interventions , we compared the st and ard- and high-intensity centers . Results : Between 1998 and 2002 , HCs undertaking the st and ard HDC improved 11 diabetes processes and lowered hemoglobin A1c [ −0.45 % ; 95 % confidence interval ( CI ) , −0.72 to −0.17 ] and low-density lipoprotein cholesterol ( −19.7 mg/dL ; 95 % CI , −25.8 to −13.6 ) . High-intensity intervention centers had greater use of angiotensin converting enzyme inhibitors [ adjusted odds ratio ( OR ) , 1.47 ; 95 % CI , 1.07–2.01 ] and aspirin ( OR , 2.20 ; 95 % CI , 1.28–3.76 ) , but lower use of dietary ( OR , 0.24 ; 95 % CI , 0.08–0.68 ) and exercise counseling ( OR , 0.34 ; 95 % CI , 0.15–0.75 ) . Conclusions : Diabetes care and outcomes improved in HCs during the first 4 years of the HDC quality improvement collaborative . More intensive interventions helped marginally OBJECTIVE : To obtain an early estimate of the effectiveness of the American Stop Smoking Intervention Study ( ASSIST ) . DESIGN , SETTING , AND PARTICIPANTS : Seventeen American states funded through ASSIST are compared with 32 others regarding per capita cigarette consumption from 1989 to 1995 . California , which already had an extensive tobacco control programme , was omitted . ASSIST states were selected competitively ( not r and omly ) based on their proposals ' merit , state smoking prevalence , and geographical distribution . INTERVENTIONS : Comprehensive tobacco control programmes , emphasising policy interventions , were implemented in the ASSIST states beginning in 1993 . MAIN OUTCOME MEASURES : Trends in aggregated per capita cigarette consumption and inflation-adjusted average price/pack of cigarettes in the intervention states were compared . Percentage change in per capita consumption is also compared with percentage change in inflation-adjusted cigarette price by state in each group from 1992 to 1994 . RESULTS : Per capita consumption and inflation-adjusted cigarette price were nearly identical in both groups of states before 1993 , when full funding for the ASSIST interventions began . However , by 1996 smokers in the intervention states were consuming about 7 % less cigarettes per capita ( P<0.05 , beginning in 1994 ) , and in 1994 the average price was over $ 0.12/pack higher in the intervention states . All but three states ( all intervention ) showed decreases in cigarette price . Nonetheless , 76 % of the intervention and 55 % of the comparison states showed some decrease in consumption despite decreases in price . The relationship between changes in price and consumption was considerably diminished in the intervention group . CONCLUSIONS : These interim results suggest that the ASSIST programme is associated with a substantial difference in tobacco consumption in a third of the United States , and that increased price from taxation may not be the only programme influence CONTEXT By improving the process of care , quality improvement efforts have the potential to reduce race and sex disparities . However , little is known about whether reductions actually occur . National quality improvement activities targeting hemodialysis patients provide an opportunity to examine this issue . OBJECTIVE To determine the effect of quality improvement efforts on race and sex disparities among hemodialysis patients . DESIGN , SETTING , AND SUBJECTS Longitudinal study of 58 700 r and omly selected hemodialysis patients from throughout the United States in 1993 through 2000 . INTERVENTION Medicare-funded quality improvement project involving monitoring of patient outcomes , feedback of performance data , and education of clinicians at dialysis centers . MAIN OUTCOME MEASURES Changes in hemodialysis dose ( Kt/V ) , anemia management ( hemoglobin level ) , and nutritional status ( albumin level ) . RESULTS The proportion of all patients with an adequate hemodialysis dose increased 2-fold . In 1993 , 46 % of white patients and 36 % of black patients received an adequate hemodialysis dose compared with 2000 when the proportions were 87 % and 84 % , respectively . Thus , the gap between white and black patients decreased from 10 % to 3 % ( P<.001 ) . The gap between female and male patients decreased from 23 % to 9 % over the same period ( P = .008 ) . The proportion of all patients with adequate hemoglobin levels increased 3-fold . The proportion of all patients with adequate albumin levels remained unchanged . Race and sex disparities in anemia management and nutritional status did not change significantly . CONCLUSIONS Quality improvement efforts have a variable impact on race and sex disparities in health outcomes . Further work is needed to determine how quality improvement methods can be targeted to reduce health disparities BACKGROUND This report presents the effectiveness of the Massachusetts Well-Integrated Screening and Evaluation for Women Across the Nation ( WISEWOMAN ) Project ( MWWP ) in reducing the cardiovascular disease ( CVD ) risk of uninsured and underinsured women aged > or = 50 . METHODS Healthcare sites were r and omly assigned to an enhanced intervention ( EI ) or minimum intervention ( MI ) . Women enrolled at all sites received CVD risk factor screening , onsite counseling , education , referral , and follow-up as needed . Women enrolled at EI sites received additional services and specially design ed interventions , including one-on-one nutritional and physical activity counseling and group activities , such as walking groups , nutrition classes , and cultural festivals . We report results for 1443 women who attended the initial screening in 10 study sites . Blood pressure , total cholesterol , number of servings of fruits and vegetables , and level of moderate or vigorous physical activity were assessed at baseline and 12-month follow-up screenings . Baseline data were collected between March and June 1996 ; follow-up data were collected 12 months later . RESULTS The comprehensive screenings significantly lowered the overall prevalence of hypertension , result ing in a 7 % reduction in high blood pressure among women at the EI sites ( p = 0.02 ) and a 9 % reduction at MI sites ( p = 0.009 ) . A significantly greater percentage of women became physically active at the EI sites ( 18 % ) than at the MI sites ( 6 % ) ( p = 0.04 ) . CONCLUSIONS MWWP is a promising model for providing comprehensive preventive healthcare to uninsured and underinsured women |
1,809 | 28,103,890 | However , subgroup analysis revealed no difference between the type and duration of diabetes and other health related factors , indicating that diabetes per se causes the microvascular dysfunction .
Conclusion Our meta- analysis shows that diabetes is associated with a large reduction of dermal microvascular function in diabetic patients . | Background / Introduction Diabetes and cardiovascular disease develop in concert with metabolic abnormalities mirroring and causing changes in the vasculature , particularly the microcirculation .
The microcirculation can be affected in different parts of the body of which the skin is the most easily accessible tissue .
Purpose The association between diabetes and dermal microvascular dysfunction has been investigated in observational studies .
However , the strength of the association is unknown .
Therefore we conducted a systematic review with meta- analysis on the association between diabetes and dermal microvascular dysfunction as assessed by laser Doppler/laser speckle contrast imaging with local thermal hyperaemia as non-invasive indicator of microvascular functionality . | The mechanisms underlying the skin blood flow ( SkBF ) response to local heating are complex and poorly understood . Our goal was to examine the role of axon reflexes and nitric oxide ( NO ) in the SkBF response to a local heating protocol . We performed 40 experiments following a st and ardized heating protocol with different interventions , including blockade of the axon reflex ( EMLA cream ) , antebrachial nerve blockade ( 0.5 % bupivacaine injection ) , and NO synthase ( NOS ) inhibition ( > or = 10 mM N(G)-nitro-L-arginine methyl ester ; microdialysis ) . Appropriate controls were performed to verify the efficacy of the various blocks . Values are expressed as a percentage of maximal SkBF ( SkBF(max ) ; 50 mM sodium nitroprusside ) . At the initiation of local heating , SkBF rose to an initial peak , followed by a brief nadir , and a secondary , progressive rise to a plateau . Axon reflex block decreased the initial peak from 75 + 3 to 32 + /- 2 % SkBF(max ) ( P < 0.01 vs. control ) but did not affect the plateau . NOS inhibition before and throughout local heating reduced the initial peak from 75 + /- 3 to 56 + /- 3 % SkBF(max ) ( P < 0.01 ) and the plateau from 87 + /- 4 to 40 + /- 5 % . NOS inhibition during axon reflex block did not further reduce the initial SkBF peak compared with axon reflex block alone . Antebrachial nerve block did not affect the local heating SkBF response . The primary finding of these studies is that there are at least two independent mechanisms contributing to the rise in SkBF during nonpainful local heating : a fast-responding vasodilator system mediated by the axon reflexes and a more slowly responding vasodilator system that relies on local production of NO OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity OBJECTIVE To evaluate the vasodilation induced by topical application of methyl nicotinate ( MN ) and to compare it with the vasodilatory response to acetylcholine ( ACh ) and sodium nitroprusside ( SNP ) in healthy subjects and diabetic neuropathic patients . RESEARCH DESIGN AND METHODS Ten diabetic patients with peripheral neuropathy ( DN ) and 10 age- and sex-matched healthy control subjects ( C ) were enrolled . The vasodilatory response to topical application of 1 % MN and a placebo emulsion at the forearm and dorsum of the foot skin at 5 , 15 , 30 , 60 and 120 min was measured using Laser Doppler Perfusion Imaging . The vasodilatory response to iontophoresis of 1 % ACh and 1 % SNP solutions was also evaluated . RESULTS The maximal vasodilatory response to ACh , SNP and MN was similar at the forearm and foot level in the diabetic patients . In the control group , the responses to MN , ACh and SNP were similar on the forearm but in the foot , the MN vasodilatory response was higher when compared to the ACh and SNP responses . MN-related vasodilation was present 5 min after the application , reached its peak at 15 - 30 min and declined to pre-application levels 120 min afterward . CONCLUSIONS Topical application of MN at the forearm and foot levels of diabetic neuropathic patients results in skin vasodilation that is comparable to the maximal vasodilation that can be induced by iontophoresis of ACh or SNP and lasts for less than 2 h. Further studies will be required to explore the potential of MN to increase blood flow and to prevent diabetic foot problems in clinical practice The aim of the present study was to examine the relationship among water diuresis-induced changes in renal oxygenation , endothelial function , and various metabolic parameters in type 2 diabetic patients and healthy subjects at risk of type 2 diabetes . Thirty-eight subjects with type 2 diabetes ( D : age , 54 + /- 10 years , mean + /- SD , 24 men ) and 7 healthy subjects with parental history of type 2 diabetes or with impaired glucose tolerance ( IGT ) ( relatives [ R ] : age 46 + /- 11 years , 4 men ) were included . Laser Doppler imaging scanning was used to measure vasodilatation in the forearm skin in response to iontophoresis of 1 % acetylcholine ( Ach ) and 1 % sodium nitroprusside ( SNP ) , and ultrasound was used to measure the flow-mediated dilation ( FMD ) and nitroglycerin-induced dilation ( NID ) in the brachial artery . Renal oxygenation was assessed by magnetic resonance imaging ( MRI ) before and during water diuresis . A decrease in the magnetic parameter R2 * implies an increase in oxygenation . Renal medullary oxygenation did not improve with diuresis in either group ( D : -0.5 + /- 1.9 , R : -0.4 + /- 2.1 , P = not significant [ NS ] ) . The renal cortical oxygenation showed a small , but statistically significant , improvement after diuresis in the 2 groups ( D : -0.6 + /- 1.1 , R : -0.5 + /- 0.5 , P < .05 ) . There were no correlations between the change in cortical R2 * ( R2 * post-minus R2 * prewater diuresis ) and the micro- and macrovascular reactivity . The postdiuresis renal cortical R2 * was negatively correlated with both the Ach- and SNP-induced skin vasodilation ( % change over baseline)(r = -.40 , P < .01 and r = -.39 , P < .05 , respectively ) , while no correlation existed with the FMD and NID . The baseline renal cortical oxygenation was also negatively correlated with the SNP-induced skin vasodilation ( r = -.36 , P < .05 ) and positively correlated with the fasting plasma glucose , total cholesterol , and vascular cell adhesion molecule ( VCAM ) concentrations ( r = .34 , P < .05 , r = .31 , P < .05 and r = .37 , P < .05 , respectively ) . These preliminary findings suggest an association between the kidney cortical oxygenation and the skin microvascular reactivity , glycemia , and lipidemia . Water diuresis failed to produce an improvement in renal medullary oxygenation in both patients with diabetes and subjects at risk for diabetes OBJECTIVES Capillary rarefaction is a hallmark of untreated hypertension . Recent data indicate that rarefaction may be reversed by antihypertensive treatment in nondiabetic hypertensive patients . Despite the frequent association of diabetes with hypertension , nothing is known on the capillary density of treated diabetic patients with hypertension . METHODS We enrolled 21 normotensive healthy , 25 hypertensive only , and 21 diabetic ( type 2 ) hypertensive subjects . All hypertensive patients were treated with a blocker of the renin-angiotensin system , and a majority had a home blood pressure ≤135/85 mmHg . Capillary density was assessed with videomicroscopy on dorsal finger skin and with laser Doppler imaging on forearm skin ( maximal vasodilation elicited by local heating ) . RESULTS There was no difference between any of the study groups in either dorsal finger skin capillary density ( controls 101 ± 11 capillaries/mm(2 ) , nondiabetic hypertensive 99 ± 16 , diabetic hypertensive 96 ± 18 , p > 0.5 ) or maximal blood flow in forearm skin ( controls 666 ± 114 perfusion units , nondiabetic hypertensive 612 ± 126 , diabetic hypertensive 620 ± 103 , p > 0.5 ) . CONCLUSIONS Irrespective of the presence or not of type 2 diabetes , capillary density is normal in hypertensive patients with reasonable control of blood pressure achieved with a blocker of the renin-angiotensin system OBJECTIVE To examine the effect of a 12-week daily treatment with 160 mg of valsartan , an angiotensin II receptor blocker , on the microcirculation and macrocirculation of type 2 diabetic patients ( T2DM ) and healthy subjects . METHODS This was a prospect i ve , r and omized , double-blind , placebo-controlled crossover study . Thirteen T2DM with no severe complications and 13 healthy subjects completed the trial . RESULTS Treatment with valsartan in T2DM improved the resting forearm skin blood flow and increased the resting brachial artery diameter but had no effects on arterial blood pressure , large vessel vascular reactivity , or carotid intima-media thickness . Resting skin blood flow increased by 60 % ( 2%-90 % ; median and 25th-75th percentiles ) during valsartan treatment and by only 2 % ( -22 % to 27 % ) during placebo treatment ( P < .05 ) . No changes were observed in the nondiabetic subjects . Immunostaining studies of forearm skin biopsy sample s from T2DM and healthy subjects showed that valsartan reduced poly(adenosine diphosphate-ribose ) polymerase ( PARP ) activity in 50 % ( 6/12 ) of the subjects . PARP activity remained unchanged in placebo-treated subjects ( P < .02 ) . In addition , valsartan treatment increased CD31 staining in 33 % ( 4/12 ) of the subjects , whereas no change was noted in sequential skin biopsy sample s of placebo-treated subjects ( P = .057 ) . Valsartan had no effect on the biochemical markers of endothelial cell activation and other cytokines , including CAMs , interleukin 6 , tumor necrosis factor alpha , C-reactive protein , adiponectin , and plasma activator inhibitor 1 . CONCLUSIONS Valsartan increases the resting skin blood flow in T2DM , likely through reduction of PARP activity We have investigated the effect of atorvastatin on the endothelial function of patients with diabetes and subjects at risk for type 2 diabetes in a 12-wk , prospect i ve , r and omized , placebo-controlled , double-blind clinical trial . The flow- mediated dilation ( FMD ; endothelium dependent ) and nitroglycerin-induced dilation ( endothelium independent ) in the brachial artery and the vascular reactivity at the forearm skin were measured . FMD improved in the atorvastatin-treated , at-risk subjects [ median ( 25 - 75 percentile ) , 7.2 % ( 2.9 - 9.6 % ) at exit visit vs. 6.6 % ( 2.9 - 9.5 % ) at baseline ; P < 0.05 ] . A similar improvement of FMD was found in atorvastatin-treated diabetic patients [ median ( 25 - 75 percentile ) , 5.6 ( 3.9 - 7.9 ) at exit visit vs. 4.2 ( 3.2 - 7.2 ) at baseline ; P = 0.07 ] . No changes were observed in nitroglycerin-induced dilation and the microcirculation reactivity measurements in either group . In the at-risk group , there was a decrease in the C-reactive protein [ median ( 25 - 75 percentile ) , 0.12 mg/dl ( 0.07 - 0.27 mg/dl ) at exit visit vs. 0.24 mg/dl ( 0.07 - 0.35 mg/dl ) at baseline ; P < 0.05 ] and TNF alpha [ median ( 25 - 75 percentile ) , 2.6 pg/ml ( 1.8 - 4.1 pg/ml ) at exit visit vs. 4.4 pg/ml ( 3.6 - 6.0 pg/ml ) at baseline ; P < 0.05 ] in the atorvastatin-treated patients , whereas in the diabetes group , a decrease in endothelin-1 ( mean + /- SD , 0.97 + /- 0.29 pg/ml at exit visit vs. 1.19 + /- 0.42 pg/ml at baseline ; P < 0.05 ) and plasminogen activator inhibitor-1 [ median ( 25 - 75 percentile ) , 18 ng/ml ( 9 - 24 ng/ml ) at exit visit vs. 27 ng/ml ( 7 - 41 ng/ml ) at baseline ; P < 0.05 ] were observed . We conclude that atorvastatin improves endothelial function and decreases levels of markers of endothelial activation and inflammation |
1,810 | 22,324,302 | The results showed that as a person fatigues , slow wave activity increased over the entire cortex , in theta and in alpha 1 and 2 b and s , while no significant changes were found in delta wave activity .
Substantial increases also occurred in fast wave activity , though mostly in frontal sites .
The results suggest that as a person fatigues , the brain loses capacity and slows its activity , and that attempts to maintain vigilance levels lead to increased beta activity | Assessing brain wave activity is a viable strategy for monitoring fatigue when performing tasks such as driving , and numerous studies have been conducted in this area .
However , results of a systematic review on changes in brain wave activity associated with fatigue have revealed equivocal findings .
This study investigated brain wave activity associated with fatigue in 48 nonprofessional healthy drivers as they participated in a simulated driving task until they fatigued . | Eye movements , eye blinks , cardiac signals , muscle noise , and line noise present serious problems for electroencephalographic ( EEG ) interpretation and analysis when rejecting contaminated EEG segments results in an unacceptable data loss . Many methods have been proposed to remove artifacts from EEG recordings , especially those arising from eye movements and blinks . Often regression in the time or frequency domain is performed on parallel EEG and electrooculographic ( EOG ) recordings to derive parameters characterizing the appearance and spread of EOG artifacts in the EEG channels . Because EEG and ocular activity mix bidirectionally , regressing out eye artifacts inevitably involves subtracting relevant EEG signals from each record as well . Regression methods become even more problematic when a good regressing channel is not available for each artifact source , as in the case of muscle artifacts . Use of principal component analysis ( PCA ) has been proposed to remove eye artifacts from multichannel EEG . However , PCA can not completely separate eye artifacts from brain signals , especially when they have comparable amplitudes . Here , we propose a new and generally applicable method for removing a wide variety of artifacts from EEG records based on blind source separation by independent component analysis ( ICA ) . Our results on EEG data collected from normal and autistic subjects show that ICA can effectively detect , separate , and remove contamination from a wide variety of artifactual sources in EEG records with results comparing favorably with those obtained using regression and PCA methods . ICA can also be used to analyze blink-related brain activity Driver fatigue is associated with risks of road accidents that result in injury and death . Research has been limited by several issues such as confusion over definitions , how best to measure fatigue , and the contribution of psychological factors to fatigue . This study addressed these limitations by investigating the relationship between psychological factors and fatigue . Participants were assessed and were required to perform a monotonous task till they tired . Results found few psychological factors to be related to physiological and performance decrement fatigue outcome measures . However , psychological factors were found to correlate consistently with self-reported fatigue . The results suggest that fatigue is associated with a predisposition to be anxious , depressive , less self-assured , more conscientious ( rule bound ) , less socially bold , less adaptable and low vigour . The results indicate that future research should employ a range of fatigue outcome measures in order to best underst and what factors contribute to fatigue Behavioral effects of alcohol are known to be greater when the blood alcohol is rising , known as the Mellanby effect ; however , research investigating the cortical changes during this period is scarce . The objective of this study was to investigate the effects of consumption of alcohol on cortical activity measured by the electroencephalogram ( EEG ) during the absorption or rising phase of alcohol . EEG signals were recorded using the entire 10/20 montage system . The experimental design consisted of a repeated measures r and omized crossover design in which subjects acted as their own control . This involved recording two EEG baseline measures , each of which was followed by a placebo or alcohol condition , delivered over two days for ten subjects . All subjects had a 50 % chance of receiving the alcohol first . All subjects were shown to have mean peak blood alcohol concentration ( BAC ) levels of around . 03 % . No significant differences were found between the two baselines . Significant increases in EEG magnitude occurred in the theta ( 4 - 7.75 Hz ) , alpha 1 ( 8 - 9.75 Hz ) , and beta 1 ( 13.25 - 19.75 Hz ) spectrum in the frontal EEG regions , and alpha 1 ( 8 - 9.75 Hz , ) in the central and posterior regions . No significant changes were found in the theta ( 4 - 7.75 Hz ) or beta ( 13.5 - 30 Hz ) spectrums in the central and posterior regions . There were also no significant results for alpha 2 ( 10 - 13 Hz , ) in any of the regions . These results suggest that rapid cortical changes occur within the first 35 min after alcohol consumption OBJECTIVE Cognitive behavior therapy for chronic fatigue syndrome was compared with relaxation in a r and omized controlled trial . METHODS Sixty patients with chronic fatigue syndrome were r and omly assigned to 13 sessions of either cognitive behavior therapy ( grade d activity and cognitive restructuring ) or relaxation . Outcome was evaluated by using measures of functional impairment , fatigue , mood , and global improvement . RESULTS Treatment was completed by 53 patients . Functional impairment and fatigue improved more in the group that received cognitive behavior therapy . At final follow-up , 70 % of the completers in the cognitive behavior therapy group achieved good outcomes ( substantial improvement in physical functioning ) compared with 19 % of those in the relaxation group who completed treatment . CONCLUSIONS Cognitive behavior therapy was more effective than a relaxation control in the management of patients with chronic fatigue syndrome . Improvements were sustained over 6 months of follow-up It is still controversial whether the pineal hormone melatonin can be characterized as a hypnotic . We therefore measured subjective sleepiness and waking EEG power density in the range of 0.25 - 20 Hz after a single dose of melatonin ( 5 mg ) . During an 8 h mini-constant routine protocol , melatonin administered in a double blind cross-over design to healthy young men at 1300 h or 1800 h increased subjective sleepiness , as rated half-hourly on three different scales ( Visual Analogue Scale , Akerstedt Sleepiness Symptoms Check List , Akerstedt Sleepiness Scale ) and objective fatigue as evidence d by augmented waking EEG power density in the theta/alpha range ( 5.25 - 9 Hz ) . The increase in subjective sleepiness reached significance 40 min and 90 min after melatonin administration ( at 1300 h and 1800 h , respectively ) and lasted for 3 h ( at 1300 h ) and 5 h ( at 1800 h ) . The increase in the theta/alpha frequencies of the waking EEG occurred immediately after melatonin ingestion and stayed significantly higher parallel to the higher sleepiness ratings . However , the EEG changes appeared before the subjective symptoms of sleepiness became manifest . There was a significant correlation between salivary melatonin levels and the timing of increased subjective sleepiness . Melatonin had no effects on mood The aim was to assess the suitability of EEG-based techniques to recording activity during a driving simulation task . To achieve this , an inexpensive driving simulator ( comprising a steering wheel , pedals and gear shift ) were made to function with a personal computer running ' Need for Speed ' simulation software . Simulators of this type are both inexpensive and relatively realistic . The EEG was recorded from four sites on the scalp ( P3 , P4 , F3 , F4 ) for two laps during the driving task , and during a replay task . The driving task involved participants driving a vehicle on a simulated undulating , sealed surface circuit , without any other vehicles present . Two men were participants in this experiment . Power spectra were computed and integrated to produce values of relative alpha activity for each channel and recording epoch , a time-series of alpha activity during each recorded segment . Overall values for alpha activity indicated an increase for replay compared to driving , and also driving on lap 5 compared to driving on lap 2 . The EEG changes are consistent with the notion of overall reduction of attention during the later laps and the replay task and indicate the potential of such measures for complex motor behaviour The effects of mental fatigue on planning and preparation for future actions were examined , using a task switching paradigm . Fatigue was induced by " time on task , " with subjects performing a switch task continuously for 2 hr . Subjects had to alternate between tasks on every second trial , so that a new task set was required on every second trial . Manipulations of response-stimulus intervals ( RSIs ) were used to examine whether subjects prepared themselves for the task change . Behavioral measurements , event-related potentials ( ERPs ) , and mood question naires were used to assess the effects of mental fatigue . Reaction times ( RTs ) were faster on trials in which no change in task set was required in comparison with switch trials , requiring a new task set . Long RSIs were used efficiently to prepare for the processing of subsequent stimuli . With increasing mental fatigue , preparation processes seemed to become less adequate and the number of errors increased . A clear poststimulus parietal negativity was observed on repetition trials , which reduced with time on task . This attention-related component was less pronounced in switch trials ; instead , ERPs elicited in switch trials showed a clear frontal negativity . This negativity was also diminished by time on task . ERP differences between repetition and switch trials became smaller with increasing time on task Cortical oscillations in the beta b and ( 13 - 35 Hz ) are known to be modulated by the GABAergic agonist benzodiazepine . To investigate the mechanisms generating the approximately 20-Hz oscillations in the human cortex , we administered benzodiazepines to healthy adults and monitored cortical oscillatory activity by means of magnetoencephalography . Benzodiazepine increased the power and decreased the frequency of beta oscillations over rol and ic areas . Minimum current estimates indicated the effect to take place around the h and area of the primary sensorimotor cortex . Given that previous research has identified sources of the beta rhythm in the motor cortex , our results suggest that these same motor-cortex beta sources are modulated by benzodiazepine . To explore the mechanisms underlying the increase in beta power with GABAergic inhibition , we simulated a conductance-based neuronal network comprising excitatory and inhibitory neurons . The model accounts for the increase in the beta power , the widening of the spectral peak , and the slowing down of the rhythms with benzodiazepines , implemented as an increase in GABAergic conductance . We found that an increase in IPSCs onto inhibitory neurons was more important for generating neuronal synchronization in the beta b and than an increase in IPSCs onto excitatory pyramidal cells During long and monotonous driving at night , most drivers progressively show signs of visual fatigue and loss of vigilance . Their capacity to maintain adequate driving performance usually is affected and varies with the age of the driver . The main question is to know , on one h and , if occurrence of fatigue and drowsiness is accompanied by a modification in the driving performance of the driver and , on the other h and , if this relationship partially depends on the driver 's age . Forty-six male drivers , divided into three age categories : 20 - 30 , 40 - 50 , and 60 - 70 years , performed a 350-km motorway driving session at night on a driving simulator . Driving errors were measured in terms of number of running-off-the-road incidents ( RORI ) and large speed deviations . The evolution of physiological vigilance level was evaluated using electroencephalography ( EEG ) recording . In older drivers , in comparison with young and middle-aged drivers , the degradation of driving performance was correlated to the evolution of lower frequency waking EEG ( i.e. , theta ) . Contrary to young and middle-aged drivers , the deterioration of the vigilance level attested by EEG correlated with the increase in gravity of all studied driving errors in older drivers . Thus , depending on the age category considered , only part of the driving errors would constitute a relevant indication as for the occurrence of a state of low arousal Fatigue is one of the most common psychophysiological symptoms that interact with the control mechanisms regulating task behaviour . The cortical processes involved in preparation and feedback control of voluntary movement are associated with EEG activity time-locked to movement onset : a pre-movement Movement-Related Cortical Potential ( MRCP ) is followed by a post-movement potential ( PMP ) . The aim of this study was to determine whether changes in subjective fatigue which arise in the course of a simple repetitive motor task affect cortical information processing as measured by MRCPs or PMPs . MRCPs/PMPs were recorded in 33 healthy subjects while they made 100 self-paced unilateral button presses with their left or right index finger , and then continued with the other index finger for another 100 movements . Before and after the motor tasks , subjective fatigue was assessed via question naire . ( 1 ) Subjects who reported a higher increase of fatigue when they had finished the motor tasks showed smaller ( more negative ) amplitudes of the PMP . ( 2 ) This increase of negativity was strongest during the initial part of the tasks . ( 3 ) Physical aspects of perceived fatigue had a stronger effect on PMP amplitude than cognitive aspects . Smaller amplitudes of the PMP in more fatigued subjects might be explained by reduced attention to somatosensory feedback . Adaptation of this effect may result from more automatic performance at later stages of the task when all subjects required a lower degree of attentional control . In conjunction with previous studies , effects of fatigue could be separated from habituation The present study systematic ally compared the effects of fatigue and alcohol intoxication on a range of neurobehavioural tasks . By doing so , it was possible to quantify the performance impairment associated with fatigue and express it as a blood alcohol impairment equivalent . Twenty-two healthy subjects aged 19 - 26 years participated in three counterbalanced conditions . In the sustained wakefulness condition , subjects were kept awake for 28 h. In the alcohol and placebo conditions , subjects consumed either an alcoholic or non-alcoholic beverage at 30 min intervals , until their blood alcohol concentration reached 0.10 % . In each session , performance was measured at hourly intervals using four tasks from a st and ardised computer-based test battery . Analysis indicated that the placebo beverage did not significantly effect mean relative performance . In contrast , as blood alcohol concentration increased performance on all the tasks , except for one , significantly decreased . Similarly , as hours of wakefulness increased performance levels for four of the six parameters significantly decreased . More importantly , equating the performance impairment in the two conditions indicated that , depending on the task measured , approximately 20 - 25 h of wakefulness produced performance decrements equivalent to those observed at a blood alcohol concentration ( BAC ) of 0.10 % . Overall , these results suggest that moderate levels of fatigue produce performance equivalent to or greater than those observed at levels of alcohol intoxication deemed unacceptable when driving , working and /or operating dangerous equipment Correlations between subjective , conscious , spontaneous cognitions and EEG power spectral profiles were investigated in 20 normal volunteers ( 2 sessions each ) during relaxation-drowsiness-sleep onset . Four-channel EEG ( temporal-parietal and parietal- central , left and right ) was continuously recorded . The subjects were prompted 15 times per session to give brief reports of their ongoing thoughts . The reports were rated on 23 scales , and the 16 seconds of EEG recording preceding the prompts were spectral analyzed . Canonical correlation analysis was applied to the data ( 23 cognition ratings and 124 EEG spectral values for each of the 538 prompts ) . Four of the 23 pairs of canonical EEG variables and cognition variables were significant ( p < 0.016 ) with correlation coefficients ranging from 0.78 to 0.62 . The four pairs of canonical variables showed distinctive features in EEG spectra and cognition styles . The results demonstrate ruleful correspondences between EEG states and spontaneous , conscious , covert , cognitive-emotional states in a no-input , no-task , no-response paradigm Drowsiness and increased tendency to fall asleep during daytime is still a generally underestimated problem . An increased tendency to fall asleep limits the efficiency at work and substantially increases the risk of accidents . Reduced alertness is difficult to assess , particularly under real life setting s. Most of the available measuring procedures are laboratory-oriented and their applicability under field conditions is limited ; their validity and sensitivity are often a matter of controversy . The spontaneous eye blink is considered to be a suitable ocular indicator for fatigue diagnostics . To evaluate eye blink parameters as a drowsiness indicator , a contact-free method for the measurement of spontaneous eye blinks was developed . An infrared sensor clipped to an eyeglass frame records eyelid movements continuously . In a series of sessions with 60 healthy adult participants , the validity of spontaneous blink parameters was investigated . The subjective state was determined by means of question naires immediately before the recording of eye blinks . The results show that several parameters of the spontaneous eye blink can be used as indicators in fatigue diagnostics . The parameters blink duration and reopening time in particular change reliably with increasing drowsiness . Furthermore , the proportion of long closure duration blinks proves to be an informative parameter . The results demonstrate that the measurement of eye blink parameters provides reliable information about drowsiness/sleepiness , which may also be applied to the continuous monitoring of the tendency to fall asleep EEG spectral power and coherence estimates in the individually defined delta , theta , alpha-1 , alpha-2 , and alpha-3 b and s were used to identify and characterize brain regions involved in meditative states , in which focused internalized attention gives rise to emotionally positive " blissful " experience . Blissful state was accompanied by increased anterior frontal and midline theta synchronization as well as enhanced theta long-distant connectivity between prefrontal and posterior association cortex with distinct " center of gravity " in the left prefrontal region ( AF3 site ) . Subjective scores of emotional experience significantly correlated with theta , whereas scores of internalized attention with both theta and alpha lower synchronization . Our results propose selective associations of theta and alpha oscillating networks activity with states of internalized attention and positive emotional experience Fatigue has major implication s for transportation system safety ; therefore , investigating the psychophysiological links to fatigue could enhance our underst and ing and management of fatigue in the transport industry . This study examined the psychophysiological changes that occurred during a driver simulator task in 35 r and omly selected subjects . Results showed that significant electroencephalographic changes occur during fatigue . Delta and theta activity were found to increase significantly during fatigue . Heart rate was significantly lower after the driving task . Blink rate also changed during the fatigue task . Increased trait anxiety , tension-anxiety , fatigue-inertia and reduced vigor-activity were shown to be associated with neurophysiological indicators of fatigue such as increased delta and theta activity . The results are discussed in light of directions for future studies and for the development of a fatigue countermeasure device |
1,811 | 28,695,008 | We conclude that both dietary components and pharmacological approaches can be used to increase apoA-I concentrations or functionality .
For the dietary components in particular , more knowledge about the underlying mechanisms is necessary , as increasing apoA-I per se does not necessarily translate into a reduced CHD risk | The incidence of CHD is still increasing , which underscores the need for new preventive and therapeutic approaches to decrease CHD risk .
In this respect , increasing apoA-I concentrations may be a promising approach , especially through increasing apoA-I synthesis .
This review first provides insight into current knowledge on apoA-I production , clearance , and degradation , followed by a systematic review of dietary and novel pharmacological approaches to target apoA-I metabolism . | This double-blind , r and omized crossover study investigated the effects of 6 weeks of treatment with prescription omega-3-acid ethyl esters ( POM3 , 4 g/day ) versus placebo ( soy oil ) on low-density lipoprotein cholesterol ( LDL-C ) and other aspects of the fasting lipid profile in 31 men and women with primary , isolated hypercholesterolemia ( LDL-C 130 - 220 mg/dL and triglycerides less than 150 mg/dL while free of lipid-altering therapies ) . Mean ± st and ard error of the mean baseline concentrations of total cholesterol , LDL-C , high-density lipoprotein cholesterol ( HDL-C ) , very-low-density lipoprotein cholesterol , and triglycerides were 229 ± 3 , 146 ± 3 , 60 ± 2 , 23 ± 2 , and 113 ± 8 mg/dL , respectively . POM3 produced a modest increase from baseline in LDL-C ( 3.4 % ) versus the placebo response ( -0.7 % , P = 0.010 ) . Significant changes ( P < 0.05 ) for POM3 ( placebo-corrected ) were observed for very-low-density lipoprotein cholesterol ( -18.8 % ) , triglycerides ( -18.7 % ) , and HDL-C ( 3.3 % ) . Nuclear magnetic resonance-determined very-low-density lipoprotein particle concentration and size and HDL particle concentration decreased significantly more with POM3 versus placebo , whereas LDL and HDL particle sizes increased significantly more with POM3 versus placebo . Total cholesterol , non-HDL-C , apolipoproteins A1 and B , and LDL particle concentration responses did not differ between treatments . These results did not confirm the hypothesis that POM3 treatment would lower LDL-C in primary , isolated hypercholesterolemia . Effects on other variables were consistent with prior results in mixed dyslipidemia High doses of n-3 PUFA found in fish oils can reduce the circulating concentration of triacylglycerol ( TG ) , which may contribute to the positive impact of these fatty acids on the risk of CVD . The present study aim ed to establish the differential impact of EPA and docosahexaenoic ( DHA ) on plasma lipids and apo in adults . Forty-two normolipidaemic adult subjects completed a double-blind placebo controlled parallel study , receiving an EPA-rich oil ( 4.8 g EPA/d ) , DHA-rich oil ( 4.9 g DHA/d ) or olive oil as control , for a period of 4 weeks . No effects of treatment on total cholesterol , LDL-cholesterol or HDL-cholesterol were evident . There was a significant 22 % reduction in TG level relative to the control value following the DHA treatment ( P=0.032 ) , with the 15 % decrease in the EPA group failing to reach significance ( P=0.258 ) . There were no significant inter-group differences in response to treatment for plasma apoA1 , -C3 or -E levels , although a significant 15 % within-group increase in apoE was evident in the EPA ( P=0.006 ) and DHA ( P=0.003 ) groups . In addition , a within-group decrease in the apoA1:HDL-cholesterol ratio was observed in the DHA group , suggesting a positive impact of DHA on HDL particle size . The DHA intervention result ed in a significant increase in the proportion of EPA P=0.000 and DHA P=0.000 in plasma phospholipids , whilst significant increases in EPA P=0.000 and docosapentaenoic acid P=0.002 , but not DHA P=0.193 , were evident following EPA supplementation ( P<0.05 ) . Our present results indicate that DHA may be more efficacious than EPA in improving the plasma lipid profile CONTEXT High-density lipoprotein ( HDL ) cholesterol is an inverse predictor of coronary atherosclerotic disease . Preliminary data have suggested that HDL infusions can induce atherosclerosis regression . OBJECTIVE To investigate the effects of reconstituted HDL on plaque burden as assessed by intravascular ultrasound ( IVUS ) . DESIGN AND SETTING A r and omized placebo-controlled trial was conducted at 17 centers in Canada . Intravascular ultrasound was performed to assess coronary atheroma at baseline and 2 to 3 weeks after the last study infusion . PATIENTS Between July 2005 and October 2006 , 183 patients had a baseline IVUS examination and of those , 145 had evaluable serial IVUS examinations after 6 weeks . INTERVENTION Sixty patients were r and omly assigned to receive 4 weekly infusions of placebo ( saline ) , 111 to receive 40 mg/kg of reconstituted HDL ( CSL-111 ) ; and 12 to receive 80 mg/kg of CSL-111 . MAIN OUTCOME MEASURES The primary efficacy parameter was the percentage change in atheroma volume . Nominal changes in plaque volume and plaque characterization index on IVUS and coronary score on quantitative coronary angiography were also prespecified end points . RESULTS The higher-dosage CSL-111 treatment group was discontinued early because of liver function test abnormalities . The percentage change in atheroma volume was -3.4 % with CSL-111 and -1.6 % for placebo ( P = .48 between groups , P<.001 vs baseline for CSL-111 ) . The nominal change in plaque volume was -5.3 mm3 with CSL-111 and -2.3 mm3 with placebo ( P = .39 between groups , P<.001 vs baseline for CSL-111 ) . The mean changes in plaque characterization index on IVUS ( -0.0097 for CSL-111 and 0.0128 with placebo ) and mean changes in coronary score ( -0.039 mm for CSL-111 and -0.071 mm with placebo ) on quantitative coronary angiography were significantly different between groups ( P = .01 and P = .03 , respectively ) . Administration of CSL-111 40 mg/kg was associated with mild , self-limiting transaminase elevation but was clinical ly well tolerated . CONCLUSIONS Short-term infusions of reconstituted HDL result ed in no significant reductions in percentage change in atheroma volume or nominal change in plaque volume compared with placebo but did result in statistically significant improvement in the plaque characterization index and coronary score on quantitative coronary angiography . Elevation of HDL remains a valid target in vascular disease and further studies of HDL infusions , including trials with clinical end points , appear warranted . TRIAL REGISTRATION clinical trials.gov Identifier : In a r and omized , cross-over feeding trial involving 10 men with polygenic hypercholesterolemia , a control , Mediterranean-type cholesterol-lowering diet , and a diet of similar composition in which walnuts replaced approximately 35 % of energy from unsaturated fat , were given for 6 weeks each . Compared with the control diet , the walnut diet reduced serum total and LDL cholesterol by 4.2 % ( P = 0.176 ) , and 6.0 % ( P = 0.087 ) , respectively . No changes were observed in HDL cholesterol , triglycerides , and apolipoprotein A-I levels or in the relative proportion of protein , triglycerides , phospholipids , and cholesteryl esters in LDL particles . The apolipoprotein B level declined in parallel with LDL cholesterol ( 6.0 % reduction ) . Whole LDL , particularly the triglyceride fraction , was enriched in polyunsaturated fatty acids from walnuts ( linoleic and alpha-linolenic acids ) . In comparison with LDL obtained during the control diet , LDL obtained during the walnut diet showed a 50 % increase in association rates to the LDL receptor in human hepatoma HepG2 cells . LDL uptake by HepG2 cells was correlated with alpha-linolenic acid content of the triglyceride plus cholesteryl ester fractions of LDL particles ( r(2 ) = 0.42 , P < 0.05 ) . Changes in the quantity and quality of LDL lipid fatty acids after a walnut-enriched diet facilitate receptor-mediated LDL clearance and may contribute to the cholesterol-lowering effect of walnut consumption Clinical trials have shown that soya protein reduces the concentrations of some atherogenic lipids in subjects with normal renal function . The present study examined the effects of soya protein on serum lipid concentrations and lipoprotein metabolism in patients on hypercholesterolaemic haemodialysis . Twenty-six hypercholesterolaemic ( total cholesterol > or = 6.21 mmol/l ) patients on haemodialysis were studied in a r and omized , double-blind , placebo-controlled clinical trial . After a 4-week run-in phase , the subjects were r and omly assigned to two groups . Isolated soya protein or milk protein 30 g was consumed daily as a beverage at breakfast or post-dialysis for 12 weeks . Soya protein substitution result ed in significant reductions in total cholesterol ( 17.2 ( sd 8.9 ) % ) , LDL-cholesterol ( 15.3 ( sd 12.5 ) % ) , apo B ( 14.6 ( sd 12.1 ) % ) and insulin ( 23.8 ( sd 18.7 ) % ) concentrations . There were no significant changes in HDL-cholesterol or apo A-I. These results indicate that replacing part of the daily protein intake with soya protein has a beneficial effect on atherogenic lipids and favourably affects lipoprotein metabolism in hypercholesterolaemic patients undergoing haemodialysis BACKGROUND In observational analyses , higher levels of high-density lipoprotein ( HDL ) cholesterol have been associated with a lower risk of coronary heart disease events . However , whether raising HDL cholesterol levels therapeutically reduces cardiovascular risk remains uncertain . Inhibition of cholesteryl ester transfer protein ( CETP ) raises HDL cholesterol levels and might therefore improve cardiovascular outcomes . METHODS We r and omly assigned 15,871 patients who had had a recent acute coronary syndrome to receive the CETP inhibitor dalcetrapib , at a dose of 600 mg daily , or placebo , in addition to the best available evidence -based care . The primary efficacy end point was a composite of death from coronary heart disease , nonfatal myocardial infa rct ion , ischemic stroke , unstable angina , or cardiac arrest with resuscitation . RESULTS At the time of r and omization , the mean HDL cholesterol level was 42 mg per deciliter ( 1.1 mmol per liter ) , and the mean low-density lipoprotein ( LDL ) cholesterol level was 76 mg per deciliter ( 2.0 mmol per liter ) . Over the course of the trial , HDL cholesterol levels increased from baseline by 4 to 11 % in the placebo group and by 31 to 40 % in the dalcetrapib group . Dalcetrapib had a minimal effect on LDL cholesterol levels . Patients were followed for a median of 31 months . At a prespecified interim analysis that included 1135 primary end-point events ( 71 % of the projected total number ) , the independent data and safety monitoring board recommended termination of the trial for futility . As compared with placebo , dalcetrapib did not alter the risk of the primary end point ( cumulative event rate , 8.0 % and 8.3 % , respectively ; hazard ratio with dalcetrapib , 1.04 ; 95 % confidence interval , 0.93 to 1.16 ; P=0.52 ) and did not have a significant effect on any component of the primary end point or total mortality . The median C-reactive protein level was 0.2 mg per liter higher and the mean systolic blood pressure was 0.6 mm Hg higher with dalcetrapib as compared with placebo ( P<0.001 for both comparisons ) . CONCLUSIONS In patients who had had a recent acute coronary syndrome , dalcetrapib increased HDL cholesterol levels but did not reduce the risk of recurrent cardiovascular events . ( Funded by F. Hoffmann-La Roche ; dal- OUTCOMES Clinical Trials.gov number , NCT00658515 . ) Objective —To determine mechanisms contributing to decreased high-density lipoprotein cholesterol ( HDL-C ) and increased low-density lipoprotein cholesterol ( LDL-C ) concentrations associated with hydrogenated fat intake , kinetic studies of apoA-I , apoB-100 , and apoB-48 were conducted using stable isotopes . Methods and Results —Eight postmenopausal hypercholesterolemic women were provided in r and om order with 3 diets for 5-week periods . Two-thirds of the fat was soybean oil ( unsaturated fat ) , stick margarine ( hydrogenated fat ) , or butter ( saturated fat ) . Total and LDL-C levels were highest after the saturated diet ( P < 0.05 ; saturated versus unsaturated ) whereas HDL-C levels were lowest after the hydrogenated diet ( P < 0.05 ; hydrogenated versus saturated ) . Plasma apoA-I levels and pool size ( PS ) were lower , whereas apoA-I fractional catabolic rate ( FCR ) was higher after the hydrogenated relative to the saturated diet ( P < 0.05 ) . LDL apoB-100 levels and PS were significantly higher , whereas LDL apoB-100 FCR was lower with the saturated and hydrogenated relative to the unsaturated diet . There was no significant difference among diets in apoA-I or B-100 production rates or apoB-48 kinetic parameters . HDL-C concentrations were negatively associated with apoA-I FCR ( r=−0.56 , P=0.03 ) and LDL-C concentrations were negatively correlated with LDL apoB-100 FCR ( r=−0.48 , P=0.05 ) . Conclusions —The mechanism for the adverse lipoprotein profile observed with hydrogenated fat intake is determined in part by increased apoA-I and decreased LDL apoB-100 catabolism Background / Objectives : There has been growing interest in using dietary intervention to improve the lipid profile . This work aims at analyzing the effects and the comparison of the enrichment of a diet with beta-glucans or rice bran in mildly hypercholesterolemic men . Subjects/ Methods : The subjects initially consumed a 3-week Step 1 American Heart Association diet with rice bran-enriched foods . After this adaptation period , volunteers were r and omly assigned to follow a crossover , controlled trial that consisted of two treatment with beta-glucan- or rice bran-enriched foods , each of 4 weeks , with a 3-week wash-out , like the adaptation period , between periods . Fasted blood sample s were collected on days 0 , 21 , 49 , 70 and 98 in both study arms for measuring low-density lipoprotein (LDL)-cholesterol ( primary outcome ) , total cholesterol , high-density lipoprotein (HDL)-cholesterol , triglycerides , apolipoprotein ( apo ) A-I , apo B and glucose levels . Results : Twenty-four men ( mean age : 50.3±5.3 , mean body mass index : 24.9±1.9 ) completed the 14-week trial . Subjects in the 3-week adaptation period experienced significant reductions in the mean level of LDL cholesterol , total cholesterol , total cholesterol/HDL cholesterol , LDL cholesterol/HDL cholesterol , apo A-I , apo A-I/apo B and glucose . During the intervention diet periods , a difference was found between treatment groups for the mean change in LDL ( 0.21 ( 95 % confidence interval ( CI ) : 0.02–0.40 ) , P=0.033 ) and total cholesterol ( 0.34 ( 95 % CI : 0.20–0.47 ) , P<0.001 ) . Other parameters evaluated were not significantly affected by the diet consumed . Conclusions : The results of the present crossover clinical trial showed that beta-glucan-enriched foods are more effective in lowering serum LDL levels , compared with rice bran-enriched foods To determine if the ratio of eicosapentaenoic ( EPA ) and docosahexaenoic ( DHA ) acids in fish oil had an effect on plasma lipid responses , we r and omly fed eight normolipidemic men three 36%-fat diets containing primarily butter , EPA-rich pollock oil , or DHA-rich tuna or salmon-blend oils . Plasma EPA and DHA reflected the amounts in the diets . Compared with values for the butter diet , very-low-density lipoprotein ( VLDL ) triglycerides decreased equally ( 71 - 78 % ) with all diets ; low-density lipoprotein ( LDL ) cholesterol ( LDL-C ) and apolipoprotein B decreased 26 % and 13 % , respectively , on the tuna and salmon-blend oil but did not change ( -1 % ) and increased 19 % with the pollock diet ; high-density lipoprotein cholesterol ( HDL-C ) and lipoproteins A-I and A-II decreased with all diets but more with the pollock diet than with the tuna and salmon diets . The 23 - 31 % decrease in total cholesterol on the tuna and salmon diets result ed mostly from decreased LDL-C whereas the 16 % decrease on pollock oil result ed mostly from a decrease in The aim of this study was to examine the effect of Max EPA ( a commercially available fish oil preparation ) on serum cholesterol lipoproteins and apolipoproteins in insulin-dependent diabetic ( IDDM ) men with dosages that were likely to be acceptable to patients . Twenty-two male IDDM patients aged 20–41 yr , 6 of whom had retinopathy , were recruited from the Royal Perth Hospital diabetic clinic . After screening , subjects were divided into three groups . Six of the subjects without retinopathy were r and omly selected and allocated to a control group . The remaining 16 patients ( 10 without and 6 with retinopathy ) received a fish oil supplement . All subjects were advised to maintain their usual dietary patterns . Sixteen patients , including the 6 with retinopathy , were instructed to take 15 Max EPA fish oil capsules/day with meals . Patients in the control group did not take Max EPA . Three weeks of Max EPA supplementation without other dietary modification led to a significant rise in total cholesterol ( P < 0.01 ) , which could be accounted for by increases in low-density lipoprotein ( LDL ) and high-density lipoprotein ( HDL ) cholesterol . The increase in HDL cholesterol was explained by a 33 % rise ( P < 0.001 ) in its HDL2 subclass . Changes in apolipoproteins were examined and showed that the level of apolipoprotein A-l increased after ingestion of fish oil and correlated significantly ( P < 0.05 ) with the rise in HDL cholesterol . Apolipoprotein A-ll showed a significant fall at the end of Max EPA intake in a subgroup of patients with retinopathy , and this correlated significantly ( P < 0.05 ) with the fall in HDL3 cholesterol observed at this time . A significant rise in apolipoprotein B ( P < 0.05 ) was correlated with the rise in LDL cholesterol . Possible adverse effects of the increase in both total and LDL cholesterol after 15 g/day Max EPA may be compensated for by a rise in the protective HDL2 subclass . However , in view of this hypercholesterolemic effect and evidence that suggests that LDL apolipoprotein B may be a risk factor for coronary heart disease , these findings raise questions regarding the safety of fish oils in patients with IDDM CONTEXT Although low levels of high-density lipoprotein cholesterol ( HDL-C ) increase risk for coronary disease , no data exist regarding potential benefits of administration of HDL-C or an HDL mimetic . ApoA-I Milano is a variant of apolipoprotein A-I identified in individuals in rural Italy who exhibit very low levels of HDL . Infusion of recombinant ApoA-I Milano-phospholipid complexes produces rapid regression of atherosclerosis in animal models . OBJECTIVE We assessed the effect of intravenous recombinant ApoA-I Milano/phospholipid complexes ( ETC-216 ) on atheroma burden in patients with acute coronary syndromes ( ACS ) . DESIGN The study was a double-blind , r and omized , placebo-controlled multicenter pilot trial comparing the effect of ETC-216 or placebo on coronary atheroma burden measured by intravascular ultrasound ( IVUS ) . SETTING Ten community and tertiary care hospitals in the United States . PATIENTS Between November 2001 and March 2003 , 123 patients aged 38 to 82 years consented , 57 were r and omly assigned , and 47 completed the protocol . INTERVENTIONS In a ratio of 1:2:2 , patients received 5 weekly infusions of placebo or ETC-216 at 15 mg/kg or 45 mg/kg . Intravascular ultrasound was performed within 2 weeks following ACS and repeated after 5 weekly treatments . MAIN OUTCOME MEASURES The primary efficacy parameter was the change in percent atheroma volume ( follow-up minus baseline ) in the combined ETC-216 cohort . Prespecified secondary efficacy measures included the change in total atheroma volume and average maximal atheroma thickness . RESULTS The mean ( SD ) percent atheroma volume decreased by -1.06 % ( 3.17 % ) in the combined ETC-216 group ( median , -0.81 % ; 95 % confidence interval [ CI ] , -1.53 % to -0.34 % ; P = .02 compared with baseline ) . In the placebo group , mean ( SD ) percent atheroma volume increased by 0.14 % ( 3.09 % ; median , 0.03 % ; 95 % CI , -1.11 % to 1.43 % ; P = .97 compared with baseline ) . The absolute reduction in atheroma volume in the combined treatment groups was -14.1 mm3 or a 4.2 % decrease from baseline ( P<.001 ) . CONCLUSIONS A recombinant ApoA-I Milano/phospholipid complex ( ETC-216 ) administered intravenously for 5 doses at weekly intervals produced significant regression of coronary atherosclerosis as measured by IVUS . Although promising , these results require confirmation in larger clinical trials with morbidity and mortality end points BACKGROUND Many of the benefits of soy have been attributed to soy isoflavones . OBJECTIVE The objective was to determine the effects of high- and low-isoflavone soy-protein foods on both lipid and nonlipid risk factors for coronary artery disease ( CAD ) . METHODS Forty-one hyperlipidemic men and postmenopausal women participated in a study with three 1-mo diets : a low-fat dairy food control diet and high- ( 50 g soy protein and 73 mg isoflavones daily ) and low- ( 52 g soy protein and 10 mg isoflavones daily ) isoflavone soyfood diets . All 3 diets were very low in saturated fat ( < 5 % of energy ) and cholesterol ( < 50 mg/d ) . Fasting blood sample s were drawn and blood pressure was measured at the start and end of each diet . RESULTS No significant differences were seen between the high- and low-isoflavone soy diets . Compared with the control diet , however , both soy diets result ed in significantly lower total cholesterol , estimated CAD risk , and ratios of total to HDL cholesterol , LDL to HDL cholesterol , and apolipoprotein B to A-I. No significant sex differences were observed , except for systolic blood pressure , which in men was significantly lower after the soy diets than after the control diet . On the basis of blood lipid and blood pressure changes , the calculated CAD risk was significantly lower with the soy diets , by 10.1 + /- 2.7 % . CONCLUSION Substitution of soyfoods for animal products , regardless of isoflavone concentration , reduces the CAD risk because of both modest reductions in blood lipids and reductions in oxidized LDL , homocysteine , and blood pressure Aims Apolipoprotein A-1 ( ApoA-1 ) , based on epidemiology , is inversely associated with cardiovascular ( CV ) events . Human carriers of the ApoA-1 Milano variant have a reduced incidence of CV disease . Regression of atherosclerotic plaque burden was previously observed on intravascular ultrasound ( IVUS ) with ETC-216 , a predecessor of MDCO-216 . MDCO-216 , a complex of dimeric ApoA-1 Milano and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine , is being developed to reduce atherosclerotic plaque burden and CV events . We investigated the efficacy and safety of a single infusion of MDCO-216 in healthy volunteers and in patients with coronary artery disease ( CAD ) . Methods and results Twenty-four healthy volunteers and 24 patients with documented CAD received a 2-h infusion of MDCO-216 in a r and omized , placebo controlled , single ascending dose study . Five cohorts of healthy volunteers and four cohorts of CAD patients received ApoA-1 Milano doses ranging from 5 to 40 mg/kg . Subjects were followed for 30 days . Dose-dependent increases in ApoA-1 , phospholipid , and pre-beta 1 HDL and decreases in ApoE were observed . Prominent and sustained increases in triglyceride , and decreases in HDL-C , endogenous ApoA-1 and ApoA-II occurred at doses > 20 mg/kg and profound increases in ABCA1-mediated cholesterol efflux were observed . Other lipid and lipoprotein parameters were generally unchanged . MDCO-216 was well tolerated . Conclusions MDCO-216-modulated lipid parameters profoundly increased ABCA1-mediated cholesterol efflux and was well tolerated . These single-dose data support further development of this agent for reducing atherosclerotic disease and subsequent CV events Studies examining the effect of soy protein on cardiovascular disease ( CVD ) risk factors have not taken advantage of the postpr and ial state as an adjunct to the fasting lipid profile . The American Heart Association has acknowledged the efficacy of soy protein in reducing CVD risk factors to be limited . We hypothesized that the postpr and ial state would be more sensitive to any favorable changes associated with consuming soy protein compared with the fasting lipid profile . Furthermore , the presence of isoflavones in soy would enhance this effect . Thirty sedentary males aged 18–30 years were r and omly assigned to milk protein ( Milk ) , isoflavone-poor soy ( Soy− ) , or isoflavone-rich soy ( Soy+ ) . Usual diets were supplemented with 25 g/day of protein for 28 days . Serum sample s were collected before and after supplementation in a fasted state and postpr and ially at 30 , 60 , 120 , 240 , and 360 min after a high-fat , 1,000 kcal shake . Triacylglycerol ( TAG ) , total cholesterol , non-esterified fatty acids , apolipoproteins B-100 and A-I and glucose concentrations were quantified . Fasting concentrations were not different after any protein supplementation . Postpr and ial TAG and TAG AUC increased after Soy-consumption supporting the postpr and ial state as a more sensitive indicator of soy ingestion effects on CVD risk factors compared with the fasting lipid profile . Furthermore , the absence of isoflavones in soy protein may have deleterious consequences on purported cardio-protective effects BACKGROUND New dietary strategies to reduce cardiovascular disease ( CVD ) risk include the addition of fiber to the diet . The effect of soluble-fiber consumption derived from Plantago ovata husk on lipid risk factors in patients with CVD is unknown . OBJECTIVE We compared the effects of soluble fiber ( P. ovata husk ) with those of insoluble fiber ( P. ovata seeds ) on plasma lipid , lipoprotein , and apolipoprotein ( apo ) concentrations within a CVD secondary prevention program . DESIGN In a r and omized , crossover , controlled , single-blind design , 28 men with CVD ( myocardial infa rct ion or stable angina ) and an LDL-cholesterol concentration < /=3.35 mmol/L consumed for 8 wk , under controlled conditions , a low-saturated-fat diet supplemented with 10.5 g P. ovata husk/d or 10.5 g P. ovata seeds/d . Fasting plasma lipid concentrations and polymorphisms of genes involved in lipid metabolism , such as apo A-IV , apo E , and fatty acid-binding protein , were measured . RESULTS Plasma triacylglycerol decreased ( 6.7 % ; P < 0.02 ) , the ratio of apo B 100 to apo A-I decreased ( 4.7 % ; P < 0.02 ) , and apo A-I increased ( 4.3 % ; P < 0.01 ) in the P. ovata husk consumers . Compared with the intake of insoluble fiber , the intake of P. ovata husk increased HDL-cholesterol concentrations by 6.7 % ( P = 0.006 ) and decreased the ratio of total to HDL cholesterol and of LDL to HDL cholesterol by 10.6 % ( P = 0.002 ) and 14.2 % ( P = 0.003 ) , respectively . CONCLUSION In the secondary prevention of CVD , P. ovata husk intake induces a more beneficial effect on the cardiovascular lipid risk-factor profile than does an equivalent intake of insoluble fiber To compare the effects of oat-bran fiber on blood lipids , we studied 84 healthy middle-aged men and women who were placed on metabolic diets , for 2 wk , that were supplemented with either wheat bran ( n = 42 ) or oat bran ( n = 42 ) . Fiber supplementation was 1.6 micrograms dietary fiber/J ( 6.8 g dietary fiber/1000 kcal ) to a maximum of 16.4 g fiber/d . Significantly greater decrease with oat than with wheat were seen in total cholesterol ( 0.56 + /- 0.08 mmol/L and 0.29 + /- 0.08 mmol/L , P = 0.022 ) and low-density-lipoprotein cholesterol ( 0.39 + /- 0.07 mmol/L and 0.15 + /- 0.07 mmol/L , P = 0.024 ) . No significant differences were seen in high-density lipoprotein , apolipoproteins A-1 and B , or triglyceride . We conclude that oat bran has an advantage over wheat bran in lowering serum lipids when tested in metabolic diets on large numbers of individuals with an initial mean serum cholesterol concentration above the desirable range , at 5.61 + /- 0.16 To compare the effects of highly purified ethyl ester concentrates of eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) on serum lipids , apolipoproteins , and serum phospholipid fatty acids in humans , we conducted a double-blind , placebo-controlled , parallel design intervention study . Healthy nonsmoking men ( n = 234 ) aged 36 - 56 y were r and omly assigned to dietary supplementation with 3.8 g EPA/d , 3.6 g DHA/d , or 4.0 g corn oil/d ( placebo ) for 7 wk . Serum triacylglycerols decreased 26 % ( P < 0.0001 ) in the DHA group and 21 % ( P = 0.0001 ) in the EPA group compared with the corn oil group . Although not significant , net decreases in serum triacylglycerols were consistently greater in the DHA group across all quartiles of baseline triacylglycerol concentrations . Serum high-density-lipoprotein cholesterol increased 0.06 mmol/L ( P = 0.0002 ) in the DHA group . In the EPA group , serum total cholesterol decreased 0.15 mmol/L ( P = 0.02 ) and apolipoprotein A-I decreased 0.04 g/L ( P = 0.0003 ) . In the DHA group , serum phospholipid DHA increased by 69 % and EPA increased by 29 % , indicating retroconversion of DHA to EPA . In the EPA group , serum phospholipid EPA increased by 297 % whereas DHA decreased by 15 % , suggesting that EPA is not elongated to DHA in humans . The serum phospholipid ratio of n-3 to n-6 fatty acids increased in both groups , whereas the relative changes in n-6 fatty acids suggested possible alterations in liver desaturation activity in the DHA group . We conclude that both DHA and EPA decrease serum triacylglycerols , but have differential effects on lipoprotein and fatty acid metabolism in humans BACKGROUND Frequent consumption of nuts may lower the risk of cardiovascular disease by favorably altering serum lipid and lipoprotein concentrations . OBJECTIVE We compared the effects of 2 amounts of almond intake with those of a National Cholesterol Education Program Step I diet on serum lipids , lipoproteins , apolipoproteins , and glucose in healthy and mildly hypercholesterolemic adults . DESIGN In a r and omized crossover design , 25 healthy subjects ( 14 men , 11 women ) with a mean ( + /- SD ) age of 41 + /- 13 y were fed 3 isoenergetic diets for 4 wk each after being fed a 2-wk run-in diet ( containing 34 % of energy from fat ) . The experimental diets included a Step I diet , a low-almond diet , and a high-almond diet , in which almonds contributed 0 % , 10 % , and 20 % of total energy , respectively . RESULTS Inverse relations were observed between the percentage of energy in the diet from almonds and the subject 's total cholesterol ( P value for trend < 0.001 ) , LDL-cholesterol ( P < 0.001 ) , and apolipoprotein B ( P < 0.001 ) concentrations and the ratios of LDL to HDL cholesterol ( P < 0.001 ) and of apolipoprotein B to apolipoprotein A ( P < 0.001 ) . Compared with the Step I diet , the high-almond diet reduced total cholesterol ( 0.24 mmol/L or 4.4 % ; P = 0.001 ) , LDL cholesterol ( 0.26 mmol/L or 7.0 % ; P < 0.001 ) , and apolipoprotein B ( 6.6 mg/dL or 6.6 % ; P < 0.001 ) ; increased HDL cholesterol ( 0.02 mmol/L or 1.7 % ; P = 0.08 ) ; and decreased the ratio of LDL to HDL cholesterol ( 8.8 % ; P < 0.001 ) . CONCLUSIONS Isoenergetic incorporation of approximately 68 g of almonds ( 20 % of energy ) into an 8368-kJ ( 2000-kcal ) Step I diet markedly improved the serum lipid profile of healthy and mildly hypercholesterolemic adults . Total and LDL-cholesterol concentrations declined with progressively higher intakes of almonds , which suggests a dose-response relation BACKGROUND The US Food and Drug Administration ( FDA ) approved health cl aims for 2 dietary fibers , beta-glucan ( 0.75 g/serving ) and psyllium ( 1.78 g/serving ) , on the assumption that 4 servings/d would reduce cardiovascular disease risk . OBJECTIVE We assessed the efficacy of this dose of fibers in reducing serum lipid risk factors for cardiovascular disease . DESIGN Sixty-eight hyperlipidemic adults consumed a test ( high-fiber ) and a control low-fat ( 25 % of energy ) , low-cholesterol ( < 150 mg/d ) diet for 1 mo each in a r and omized crossover study . The high-fiber diet included 4 servings/d of foods containing beta-glucan or psyllium that delivered 8 g/d more soluble fiber than did similar , unsupplemented foods in the control diet . Fasting blood sample s and blood pressure readings were obtained at baseline and weeks 2 and 4 , and the subjects ' weight was monitored weekly . RESULTS Compared with the control diet , the high-fiber diet reduced total cholesterol ( 2.1 + /- 0.7 % ; P = 0.003 ) , total : HDL cholesterol ( 2.9 + /- 0.8 % ; P = 0.001 ) , LDL : HDL cholesterol ( 2.4 + /- 1.0 % ; P = 0.015 ) , and apolipoprotein B : A-I ( 1.4 + /- 0.8 % ; P = 0.076 ) . Applying the Framingham cardiovascular disease risk equation to the data confirmed a reduction in risk of 4.2 + /- 1.4 % ( P = 0.003 ) . Small reductions in blood pressure were found after both diets . The subjects reported no significant differences in palatability or gastrointestinal symptoms between the diets . CONCLUSIONS The reduction in serum lipid risk factors for cardiovascular disease supports the FDA 's approval of a health cl aim for a dietary fiber intake of 4 servings/d . Although relatively small in terms of patient treatment , the reduction in cardiovascular disease risk is likely to be significant on a population basis BACKGROUND Previous research supports a role for soy protein in reducing serum lipids ; however , few studies involved healthy male subjects or focused on soy isoflavones ( or did both ) . OBJECTIVE The objective was to ascertain the effects of soy protein varying in isoflavone content on serum lipids in healthy young men . DESIGN Thirty-five males ( x + /- SD age : 27.9 + /- 5.7 y ) consumed milk protein isolate ( MPI ) , low-isoflavone soy protein isolate ( low-iso SPI ; 1.64 + /- 0.19 mg aglycone isoflavones/d ) , and high-isoflavone SPI ( high-iso SPI ; 61.7 + /- 7.4 mg aglycone isoflavones/d ) for 57 d each , separated by 4-wk washout periods , in a r and omized crossover design . Blood sample s were collected at the beginning and end of each treatment period , and total , LDL , and HDL cholesterol ; triacylglycerols ; apolipoprotein ( apo ) B ; apo A-I ; and C-reactive protein ( CRP ) were measured in serum . Twenty-four-hour urine sample s were collected for 3 consecutive days at the end of each treatment period and analyzed for isoflavones . RESULTS Urinary isoflavones were significantly greater with consumption of the high-iso SPI than with that of the low-iso SPI or MPI . The differences between the 3 treatments with respect to individual serum lipids were not significant , but the ratios of total to HDL cholesterol , LDL to HDL cholesterol , and apo B to apo A-I were significantly lower with both SPI treatments than with MPI treatment . CONCLUSION Soy protein , regardless of isoflavone content , modulates serum lipid ratios in a direction beneficial for cardiovascular disease risk in healthy young men BACKGROUND Soy-protein consumption is known to reduce plasma total and LDL cholesterol concentrations . However , the responsible soy component or components and the magnitude of effects in normocholesterolemic and mildly hypercholesterolemic subjects are unclear . OBJECTIVE The present study examined the effects of soy isoflavone consumption on plasma concentrations of triacylglycerol , apolipoprotein ( apo ) A-I , apo B , lipoprotein(a ) , and total , LDL , and HDL cholesterol and on LDL peak particle diameter in normocholesterolemic and mildly hypercholesterolemic postmenopausal women . DESIGN In a r and omized crossover trial , fasting plasma sample s were obtained from 18 postmenopausal women throughout three 93-d periods of daily isolated soy protein ( ISP ) consumption providing an average of 7.1 + /- 1.1 ( control ) , 65 + /- 11 ( low isoflavone ) , or 132 + /- 22 ( high isoflavone ) mg isoflavones/d . RESULTS Compared with values measured during the control diet , the plasma LDL cholesterol concentration was 6.5 % lower ( P < 0.02 ) during the high-isoflavone diet and the ratio of LDL to HDL cholesterol was 8.5 % and 7.7 % lower during the low- and high-isoflavone diets , respectively ( P < 0.02 ) . Isoflavone consumption did not significantly affect plasma concentrations of total or HDL cholesterol , triacylglycerol , apo A-I , apo B , or lipoprotein(a ) or the LDL peak particle diameter . CONCLUSIONS Consumption of isoflavones as a constituent of ISP result ed in small but significant improvements in the lipid profile in normocholesterolemic and mildly hypercholesterolemic postmenopausal women . Although the effects were small , it is possible that isoflavones may contribute to a lower risk of coronary heart disease if consumed over many years in conjunction with other lipid-lowering strategies We investigated the effect of incorporating n-3 polyunsaturated fatty acids ( PUFAs ) into the diet on the lipid-class composition of LDLs , their size , and their susceptibility to oxidation . Forty-seven healthy volunteers incorporated 30 g sunflower-oil ( SO ) margarine/d into their habitual diet during a 3-wk run-in period and then used either SO or a fish-oil-enriched sunflower oil ( FO ) margarine for the following 4 wk . Plasma concentrations of total cholesterol , triacylglycerols , HDL cholesterol , LDL cholesterol , and apolipoproteins A-I and B did not differ significantly between the groups during intervention . The FO margarine increased the concentration of n-3 very-long-chain PUFAs in the LDL particles , showing 93 % ( P < or = 0.0001 ) , 8 % ( P = 0.05 ) , and 35 % ( P = < 0.0001 ) increases in eicosapentaenoic acid , docosapentaenoic acid , and docosahexaenoic acid , respectively , in the FO group compared with 3 % , 7 % , and 7 % , respectively , in the SO group during the intervention . The cholesterol content of the LDL particles increased in the FO group [ total cholesterol : 6 % ( P = 0.008 ) ; cholesterol ester : 12 % ( P = 0.014 ) ] , although it was not significantly different from that in the control group , whereas the other lipid classes and the size of the LDL particles remained unchanged in both groups . A reduction in the alpha-tocopherol content in LDL ( 6 % , P = 0.005 ) was observed in the FO group . Ex vivo oxidation of LDL induced with Cu2 + showed a significantly reduced lag time ( from 91 to 86 min , P = 0.003 ) and lower maximum rate of oxidation ( from 10.5 to 10.2 nmol x mg(-1 ) x min(-1 ) , P = 0.003 ) after intake of the FO margarine . The results indicate that consumption of the FO compared with the SO margarine had no effect on LDL size and lipid composition and led to minor changes in LDL a-tocopherol content and oxidation resistance BACKGROUND Patients treated with hemodialysis frequently experience cardiovascular complications attributed , among other causes , to dyslipidemia , increased oxidative stress , and inflammation . OBJECTIVE The aim of the study was to study the effects of dietary supplementation with concentrated red grape juice ( RGJ ) , a source of polyphenols , on lipoprotein profile , antioxidant capacity , LDL oxidation , and inflammatory biomarkers . DESIGN Twenty-six patients receiving hemodialysis and 15 healthy subjects were instructed to drink 100 mL RGJ/d for 14 d. Blood was drawn at baseline , twice during RGJ supplementation , and twice during the 6-mo follow-up period . As a control , 12 other r and omly recruited hemodialysis patients not receiving RGJ were studied . Lipids , apolipoproteins , oxidized LDL , and antioxidant vitamins were measured in plasma . The bioavailability of RGJ polyphenols was assessed in healthy subjects . RESULTS The maximum plasma concentration of quercetin was achieved 3 h after RGJ ingestion , which indicates that supplement-derived polyphenols are rapidly absorbed . In both healthy subjects and hemodialysis patients , RGJ consumption increased the antioxidant capacity of plasma without affecting concentrations of uric acid or ascorbic acid ; reduced the concentration of oxidized LDL ; and increased the concentration of cholesterol-st and ardized alpha-tocopherol . RGJ supplementation also caused a significant decrease in LDL-cholesterol and apolipoprotein B-100 concentrations , while increasing the concentrations of HDL cholesterol and apolipoprotein A-I. In a further study in hemodialysis patients , RGJ supplementation for 3 wk significantly reduced plasma monocyte chemoattractant protein 1 , an inflammatory biomarker associated with cardiovascular disease risk . CONCLUSION Dietary supplementation with concentrated RGJ improves the lipoprotein profile , reduces plasma concentrations of inflammatory biomarkers and oxidized LDL , and may favor a reduction in cardiovascular disease risk The aim of this study was to evaluate the cholesterol-lowering effects of reducing fat and increasing or not increasing dietary fiber in subjects consuming a mixed Mediterranean-Western diet . Thirty-one free-living , mildly hypercholesterolemic subjects were r and omly allocated to two groups . Subjects in both groups first shifted for 4 wk to a low-fat , low-fiber diet ( LFLFD ) . For an additional 4-wk period , subjects in group 1 continued consuming the LFLFD whereas subjects in group 2 consumed a low-fat , high-fiber diet ( LFHFD ) . Most dietary fatty acids were monounsaturated ( 38 - 41 % ) and fibers , when provided ( up to 35 g/d ) , came from unrefined cereals , legumes , and soluble-fiber-enriched ready-to-eat cereals . After period 1 of the LFLFD , mean serum and low-density-lipoprotein (LDL)-cholesterol concentrations of subjects in groups 1 ( -12.5 % and -15.5 % , respectively ) and 2 ( -10.5 % and -15.5 % , respectively ) decreased significantly from baseline ( P < 0.05 ) . After period 2 , mean serum and LDL-cholesterol concentrations of subjects consuming the LFLFD ( group 1 ) were still lower ( by 8.8 % and 9.2 % , respectively , from baseline ) whereas in subjects consuming the LFHFD ( group 2 ) these values decreased further to significantly lower values ( 14.2 % and 17.6 % from baseline , respectively ) . Fasting high-density-lipoprotein ( HDL ) cholesterol , apolipoprotein A-I , glycemia , and insulinemia did not change significantly . In seven men , postpr and ial lipemia transiently increased more after a breakfast test meal at the completion of the LFHFD period than after the LFLFD period . In conclusion , an LFHFD more comparable with the traditional Mediterranean diet may improve the dietary management of moderate hypercholesterolemia BACKGROUND Naturally occurring plant sterol esters ( SEs ) favorably affect serum cholesterol concentrations in humans and could aid in the treatment of children with familial hypercholesterolemia ( FH ) . OBJECTIVE We studied the effect of SE-enriched spread on serum lipids , lipoproteins , carotenoids , fat-soluble vitamins , and physiologic variables in children with FH aged 7 - 12 y. DESIGN In a r and omized , double-blind crossover study comprising two 8-wk interventions , 38 children with FH consumed 18.2 + /- 1.5 g SE spread/d , corresponding to 1.60 + /- 0.13 g SEs , or a control spread . Blood sample s were analyzed at the start and end of each diet period . RESULTS Plasma LDL-cholesterol concentrations decreased by 10.2 % ( P = 0.003 ) during the SE period compared with the control period . Total cholesterol and apolipoprotein B concentrations were reduced by 7.4 % ( P = 0.007 and P = 0.020 , respectively ) during the SE period . No changes were observed in HDL cholesterol , triacylglycerol , or apolipoprotein A-I. Serum concentration of lipid-adjusted lycopene decreased by 8.1 % ( P = 0.015 ) in the SE period , with no changes in the other carotenoids . Lipid-adjusted retinol and alpha-tocopherol concentrations increased by 15.6 % ( P < 0.001 ) and 7.1 % ( P = 0.027 ) , respectively . There was an increase ( 16.8 % , P = 0.04 ) in alanine transaminase in the SE period , but this was explained by a significantly lower starting concentration in the SE period than in the control period . The children consumed a recommended American Heart Association Step I diet during both intervention periods . CONCLUSION A daily intake of 1.6 g SEs induces an additional reduction in LDL-cholesterol concentrations in children with FH consuming a recommended diet Fish oils , purified eicosapentaenoic acid and docosahexaenoic acid ( DHA ) have been reported to improve blood lipid concentrations , especially those of triglycerides in humans . However , to our knowledge there have been no double-blind studies investigating the effects of DHA-rich fish oil on blood lipid concentrations . Therefore , we conducted a placebo-controlled double-blind study . Twenty-four healthy , normolipidemic young adults took either DHA-rich fish oil capsules containing 1.5 - 1.8 g of DHA or control oil capsules containing 97 % soybean oil and 3 % fish oil for 13 wk . Blood sample s were taken at the start and end of the study , and serum lipids concentrations were compared . There were no significant changes over time in the DHA group in the following serum lipids : total cholesterol , HDL cholesterol , LDL cholesterol , triglycerides , lipoprotein(a ) , and apolipoproteins A1 and B. In contrast , apolipoprotein A1 concentrations slightly ( 10 % ) but significantly increased over time in the control group . Docosahexaenoic acid at a dose of less than 2 g/d did not change serum lipid concentrations of normolipidemic subjects . The effects of DHA in hyperlipidemic patients remain to be investigated in a double-blind study BACKGROUND The magnitude of the effect of soy protein on lipoprotein concentrations is variable . This discordance is likely attributable to the various forms of soy protein used and to unrecognized shifts in dietary fatty acid , cholesterol , and fiber . OBJECTIVE The objective was to evaluate the effect of soybean processing as well as soy consumption relative to animal protein , independent of alterations in major dietary variables , on cardiovascular disease risk factors and vascular endothelial function . DESIGN Twenty-eight hypercholesterolemic subjects ( LDL cholesterol > /=3.36 mmol/L ) aged > 50 y consumed each of 4 diets for 6-wk periods according to a r and omized crossover design . The diets [ 55 % of energy as carbohydrate , 30 % of energy as fat , and 15 % of energy as protein-7.5 % of energy as experimental protein ( 37.5 g/d ) ] were design ed to contain products made from either whole soybeans , soyflour , or soymilk and were compared with a diet containing an equivalent amount of animal protein ( meat , chicken , and dairy products ) . The cholesterol , fiber , and fatty acid profiles of the diets were equalized . All food and drink were provided , and body weight was maintained throughout the study . RESULTS No significant differences in blood pressure , vascular endothelial function , or total cholesterol , VLDL-cholesterol , triacylglycerol , apolipoprotein B , or C-reactive protein concentrations were observed between the diets . Consumption of the soymilk diet result ed in a modest decrease ( 4 % ) in LDL-cholesterol concentrations compared with the animal-protein and soyflour diets ( P < 0.05 ) and higher HDL-cholesterol ( 1 % ) and apolipoprotein A-I ( 2 % ) concentrations compared with the soybean and soyflour diets ( P < 0.05 ) . CONCLUSIONS The results suggest that the consumption of differently processed soy-based products and different types of protein ( animal and soy ) has little clinical effect on cardiovascular disease risk factors , including peripheral endothelial function , when other major dietary variables are held constant In Maastricht and Zeist , The Netherl and s , and Tromsø , Norway , a well-controlled study was performed on the effect of a fish-enriched diet on serum lipids , apolipoproteins A-1 and B , and fatty acid compositions of serum triglycerides and cholesterol esters . For 6 wk healthy male volunteers were given a daily dietary supplement consisting of 135 g mackerel paste ( experimental group , n = 42 ) or meat paste ( control group , n = 42 ) . Dietary adherence was calculated on the basis of urinary excretion of a st and ard amount of lithium added to the supplements . Average compliance was 80 % . Low-density-lipoprotein ( LDL ) and total serum cholesterol concentrations were unaffected . High-density-lipoprotein ( HDL ) cholesterol increased to a comparable degree in both groups . Triglyceride content of serum decreased in the fish group . Apolipoproteins A-1 and B ( both in Maastricht subjects only ) were only slightly affected . In the mackerel group the n-3 fatty acids increased significantly in serum cholesterol esters and triglycerides ; the n-6 fatty acids decreased in cholesterol esters only A crossover study was conducted to examine the effects on plasma lipoprotein concentrations of substituting lean white fish ( LWF ) for beef , port , veal , eggs , and milk products ( BPVEM ) within prudent isoenergetic diets . Fourteen premenopausal women received 8784 kJ--20 % as protein , 50 % as carbohydrates , and 30 % as lipids [ ratio of polyunsaturated to monounsaturated to saturated fatty acids ( P : M : S ) of 1:1:1 compared with 0.4:1:1 in preexperimental diet]-- and 260 mg cholesterol/d . After 4 wk , the BPVEM diet significantly reduced concentrations of plasma cholesterol , low-density-lipoprotein ( LDL ) cholesterol , high-density-lipoprotein ( HDL ) cholesterol , apolipoprotein B , HDL-apolipoprotein A-I , and LDL-apolipoprotein B ( P<0.05 ) as well as plasma postheparin hepatic triacylglycerol lipase activity compared with the preexperimental diet . These effects are probably attributable to elevation of the P : M : S. These responses were not observed with the LWF diet , suggesting that fish protein in LWF maintains unchanged plasma cholesterol concentrations despite a high P : M : S. The LWF diet , compared with the preexperimental diet , reduced very-low-density-lipoprotein triacylglycerol ( P<0.05 ) and also the ratio of LDL cholesterol to apolipoprotein B ( P<0.05 ) , revealing the presence of denser LDL particles . Compared with the BPVEM diet , the LWF diet induced lower concentrations of very-low-density-lipoprotein triacylglycerols ( P<0.05 ) and higher concentrations of LDL triacylglycerol and LDL apolipoprotein B ( P<0.05 ) , which were not associated with any increase in lipoprotein lipase activity . These results suggest that LWF as a substitute for BPVEM in isoenergetic diets with an elevated P : S produces minimal improvement in the lipoprotein profile in premenopausal women The effect of fish consumption on plasma lipoprotein subfraction concentrations was studied in 22 men and women ( age > 40 y ) . Subjects were provided an average American diet ( AAD , 35 % of energy as fat , 14 % as saturated fat , and 35 mg cholesterol/MJ ) for 6 wk before being assigned to a National Cholesterol Education Program ( NCEP ) Step 2 high-fish diet ( n = 11 , 26 % of energy as fat , 4.5 % as saturated fat , and 15 mg cholesterol/MJ ) or a NCEP Step 2 low-fish diet ( n = 11 , 26 % of energy as fat , 4.0 % as saturated fat , and 11 mg cholesterol/MJ ) for 24 wk . All food and drink were provided to study participants . Consumption of the high-fish NCEP Step 2 diet was associated with a significant reduction in medium and small VLDL , compared with the AAD diet , whereas the low-fish diet did not affect VLDL subfractions . Both diets significantly reduced LDL cholesterol concentrations , without modifying LDL subfractions . Both diets also lowered HDL cholesterol concentrations . However , the high-fish diet significantly lowered only the HDL fraction containing both apolipoprotein ( apo ) AI and AII ( LpAI : AII ) and did not change HDL subfractions assessed by NMR , whereas the low-fish diet significantly lowered the HDL fraction containing only apo AI ( LpAI ) and the large NMR HDL fractions , result ing in a significant reduction in HDL particle size . Neither diet affected VLDL and LDL particle size . Our data indicate that within the context of a diet restricted in fat and cholesterol , a higher fish content favorably affects VLDL and HDL subspecies Despite epidemiological evidence that tea consumption is associated with the reduced risk of coronary heart disease , experimental studies design ed to show that tea affects oxidative stress or blood cholesterol concentration have been unsuccessful . We assessed the effects of black tea consumption on lipid and lipoprotein concentrations in mildly hypercholesterolemic adults . Tea and other beverages were included in a carefully controlled weight-maintaining diet . Five servings/d of tea were compared with a placebo beverage in a blinded r and omized crossover study ( 7 men and 8 women , consuming a controlled diet for 3 wk/treatment ) . The caffeine-free placebo was prepared to match the tea in color and taste . In a third period , caffeine was added to the placebo in an amount equal to that in the tea . Five servings/d of tea reduced total cholesterol 6.5 % , LDL cholesterol 11.1 % , apolipoprotein B 5 % and lipoprotein(a ) 16.4 % compared with the placebo with added caffeine . Compared with the placebo without added caffeine , total cholesterol was reduced 3.8 % and LDL cholesterol was reduced 7.5 % whereas apolipoprotein B , Lp(a ) , HDL cholesterol , apolipoprotein A-I and triglycerides were unchanged . Plasma oxidized LDL , F2-isoprostanes , urinary 8-hydroxy-2'-deoxyguanosine , ex vivo ferric ion reducing capacity and thiobarbituric acid reactive substances in LDL were not affected by tea consumption compared with either placebo . Thus , inclusion of tea in a diet moderately low in fat reduces total and LDL cholesterol by significant amounts and may , therefore , reduce the risk of coronary heart disease . Tea consumption did not affect antioxidant status in this study Effects of fish-oil ( FO ) feeding on serum lipids were investigated in a 42-d controlled diet study . Fifteen healthy male college students were assigned to one of three groups : control ( 0 g FO ) ; 5 g FO , supplying 2 g n - 3 ( omega-3 ) fatty acids ( FAs ) ; or 20 g FO , supplying 8 g n - 3 FAs . In an initial 7-d period subjects consumed a basal diet with no FO . Then FO replaced an equivalent amount of margarine for 5 wk . FO feeding significantly ( p less than 0.05 ) decreased the serum n - 6 FAs , linoleic acid , eicosatrienoic acid , and arachidonic acid . A significant increase in the n - 3 FAs , eicosapentaenoic acid and docosahexaenoic acid , was noted in serum , platelet , and neutrophil phospholipids . The 20-g-FO group showed a 30 % decrease ( p less than 0.01 ) in triglycerides after 2 wk FO with no further decrease observed . Thus , 20 g FO produced changes in both FA patterns and triglyceride concentrations whereas 5 g FO produced changes in FA patterns only . Neither FO amount result ed in significant changes in total or HDL cholesterol , apolipoprotein A-I , or apolipoprotein B-100 Six normolipidemic males ingested on separate days a low-fiber test meal [ 2.8 g dietary fiber ( TDF ) ] containing 70 g fat and 756 mg cholesterol , enriched or not with 10 g TDF as oat bran , rice bran , or wheat fiber or 4.2 g TDF as wheat germ . Fasting and postmeal blood sample s were obtained for 7 h and chylomicrons were isolated . Adding fibers to the test meal induced no change in serum glucose or insulin responses . The serum triglyceride response was lower ( P less than or equal to 0.05 ) in the presence of oat bran , wheat fiber , or wheat germ and chylomicron triglycerides were reduced with wheat fiber . All fiber sources reduced chylomicron cholesterol . Cholesterolemia decreased postpr and ially for 6 h and was further lowered in the presence of oat bran . Serum apolipoprotein ( apo ) A-1 and apo B concentrations were not affected . Thus , dietary fibers from cereals may reduce postpr and ial lipemia in humans to a variable extent We found previously that dietary soy protein , compared with casein , reduced plasma LDL cholesterol and increased HDL cholesterol concentrations in healthy women and men . However , there was considerable variation among individuals . The aim of this study was to characterize the lipoprotein responsiveness of individuals to examine whether different response patterns could be identified . Nine normolipemic men consumed 2 liquid-formula diets of identical composition except that the protein component was either soy protein or casein . After 1 mo of consuming each diet , the subjects ' plasma HDL cholesterol ( P < 0.01 ) and apolipoprotein ( apo ) A-I ( P < 0.05 ) concentrations were increased by the soy-protein diet whereas the ratio of LDL cholesterol to HDL cholesterol was decreased ( P < 0.01 ) ; total cholesterol , triacylglycerol , LDL cholesterol , apo B and apo A-II were insignificantly affected . In 5 individuals , however , soy protein reduced mean LDL cholesterol , LDL2 cholesterol , and LDL2 apo B concentrations by 26 % and plasma apo B by 16 % , whereas HDL cholesterol increased by 11 % . In 3 other individuals , soy protein increased mean HDL cholesterol by 17 % and plasma apo A-I by 12 % , but did not lower LDL . In 1 subject , soy protein decreased LDL2 cholesterol by 11 % and increased plasma triacylglycerol by 40 % , but neither HDL cholesterol nor apo A-I increased . We identified 3 types of lipemic responses to dietary soy protein involving a reduction in atherogenic LDL and increase in antiatherogenic HDL . In most subjects , the effects on both LDL and HDL were favorable , although fewer experienced either an increase in HDL or a decrease in LDL2 Eggplant ( Solanum melongena ) is consumed extensively in Brazil . It has been believed that infusion of a powdered preparation of the fruit may reduce serum cholesterol . However , there are few documented reports on its effects on cholesterol metabolism and its possible hypocholesterolemic effect has not been proved by well-controlled studies . The aim of the present study was to observe the effects of S. melongena on the serum cholesterol and triglycerides of 38 hypercholesterolemic human volunteers ingesting S. melongena infusion for five weeks . Thirty-eight hypercholesterolemic subjects receiving either S. melongena infusion ( N = 19 ) or placebo ( N = 19 ) participated in two clinical experiments in which the effect of S. melongena infusion was studied with ( N = 16 ) or without ( N = 38 ) dietary orientation . Total cholesterol and its fractions , triglycerides , and apolipoproteins A and B were measured in blood at the beginning of the experiment and three and five weeks thereafter . No differences were observed compared to control . Intraindividual analysis showed that S. melongena infusion significantly reduced the blood levels of total and LDL cholesterol and of apolipoprotein B. After dietary orientation , no intra- or intergroup differences were seen for any of the parameters analyzed . The results suggest that S. melongena infusion had a modest and transitory effect , which was not different from that obtained with st and ard orientation for dyslipidemia patients ( diet and physical activities ) Plant sterols ( PS ) and MUFA are well-documented cholesterol lowering agents . We aim ed to determine the effect of PS esterified to olive oil fatty acids ( PS-OO ) on blood lipid profile and lipid peroxidation in hypercholesterolaemic subjects . Twenty-one moderately overweight , hypercholesterolaemic subjects consumed three consecutive treatment diets , each lasting 28 d and separated by 4-week washout periods , using a r and omized crossover design . Diets contained 30 % energy as fat , 70 % of which was provided by olive oil ( OO ) , and differed only in the treatment oils : OO , PS esterified to sunflower oil fatty acids ( PS-SO ) , and PS-OO . Both PS-SO and PS-OO treatments provided 1.7 g PS /d . PS-OO and PS-SO consumption result ed in a decrease ( P = 0.0483 ) in LDL-cholesterol ( LDL-C ) concentrations compared with the OO diet . Although total cholesterol and apo B-100 levels were not significantly affected , PS-SO and , to some extent , PS-OO reduced the total : HDL-cholesterol ( HDL-C ) ratio ( P = 0.0142 ) and the apo B-100:apo A-I ratio ( P = 0.0168 ) compared with the OO diet . There were no differences across diets in lipoprotein(a ) ( Lp(a ) ) and lipid peroxidation levels . However , following consumption of OO and PS-SO , Lp(a ) concentrations increased ( P = 0.0050 and 0.0421 , respectively ) , while PS-OO treatment did not affect Lp(a ) levels . Furthermore , there was a decrease ( P = 0.0097 ) in lipid peroxidation levels with PS-OO treatment during the supplementation phase . Our results suggest that supplementing an OO-rich diet with PS-OO favourably alters the plasma lipid profile and may decrease the susceptibility of LDL-C to lipid peroxidation in hypercholesterolaemic subjects Phytosterols ( PS ) are recommended to reduce LDL-cholesterol . However , the influence of cholesterol and fat intake on the lipid-lowering effect of PS in mildly hypercholesterolaemia is unclear . Thus , the aim of the present study was to evaluate whether the efficacy of PS is related to the composition of saturated fat and dietary cholesterol intake . Additionally , serum carotenoid content was analysed to evaluate to what extent it was undermined by PS . This was a 3-month r and omised , parallel trial with a three-arm design . Patients were divided into three groups : healthy diet ( n 24 ) , healthy diet+PS ( n 31 ) and free diet+PS ( n 29 ) , receiving 2 g/d of PS . Healthy and free diets were characterised by a daily ingestion of 6.8 % of saturated fat and 194.4 mg of cholesterol and 12.7 % of saturated fat and 268.1 mg of cholesterol , respectively . After PS therapy , patients receiving the healthy diet+PS or a free diet+PS exhibited a similar reduction in total cholesterol ( 6.7 and 5.5 % ) , LDL-cholesterol ( 9.6 and 7.0 % ) , non-HDL-cholesterol ( 12.2 and 8.9 % ) and apo B-100/apo A-I ratio ( 11.5 and 11.6 % ) , respectively . In patients following the healthy diet , ( β-carotene concentration rose by 26.9 % , whereas the β-carotene and lycopene levels dropped by 21.0 and 22.8 % in the group receiving the free diet+PS , respectively . No change was observed in carotenoid levels in healthy diet+PS group . In conclusion , the efficacy of PS in relation to lipoprotein profile is not influenced by saturated fat or dietary cholesterol intake , which confirms the positive effect of healthy diet therapy in improving the negative effects that PS exert on carotenoid levels Objective : To compare the effects of alpha-linolenic acid ( ALA , C18:3n-3 ) to those of eicosapentaenoic acid ( EPA , C20:5n-3 ) plus docosahexaenoic acid ( DHA , C22:6n-3 ) on cardiovascular risk markers in healthy elderly subjects . Design : A r and omized double-blind nutritional intervention study . Setting : Department of Human Biology , Maastricht University , the Netherl and s . Subjects : Thirty-seven mildly hypercholesterolemic subjects , 14 men and 23 women aged between 60 and 78 years . Interventions : During a run-in period of 3 weeks , subjects consumed an oleic acid-rich diet . The following 6 weeks , 10 subjects remained on the control diet , 13 subjects consumed an ALA-rich diet ( 6.8 g/day ) and 14 subjects an EPA/DHA-rich diet ( 1.05 g EPA/day+0.55 g DHA/day ) . Results : Both n-3 fatty acid diets did not change concentrations of total-cholesterol , LDL-cholesterol , HDL-cholesterol , triacylglycerol and apoA-1 when compared with the oleic acid-rich diet . However , after the EPA/DHA-rich diet , LDL-cholesterol increased by 0.39 mmol/l ( P=0.0323 , 95 % CI ( 0.030 , 0.780 mmol/l ) ) when compared with the ALA-rich diet . Intake of EPA/DHA also increased apoB concentrations by 14 mg/dl ( P=0.0031 , 95 % CI ( 4 , 23 mg/dl ) ) and 12 mg/dl ( P=0.005 , 95 % CI ( 3 , 21 mg/dl ) ) versus the oleic acid and ALA-rich diet , respectively . Except for an EPA/DHA-induced increase in tissue factor pathway inhibitor ( TFPI ) of 14.6 % ( P=0.0184 versus ALA diet , 95 % CI ( 1.5 , 18.3 % ) ) , changes in markers of hemostasis and endothelial integrity did not reach statistical significance following consumption of the two n-3 fatty acid diets . Conclusions : In healthy elderly subjects , ALA might affect concentrations of LDL-cholesterol and apoB more favorably than EPA/DHA , whereas EPA/DHA seems to affect TFPI more beneficially Aim High-density lipoproteins ( HDLs ) have several potentially protective vascular effects . Most clinical studies of therapies targeting HDL have failed to show benefits vs. placebo . Objective To investigate the effects of an HDL-mimetic agent on atherosclerosis by intravascular ultrasonography ( IVUS ) and quantitative coronary angiography ( QCA ) . Design and setting A prospect i ve , double-blinded , r and omized trial was conducted at 51 centres in the USA , the Netherl and s , Canada , and France . Intravascular ultrasonography and QCA were performed to assess coronary atherosclerosis at baseline and 3 ( 2–5 ) weeks after the last study infusion . Patients Five hundred and seven patients were r and omized ; 417 and 461 had paired IVUS and QCA measurements , respectively . Intervention Patients were r and omized to receive 6 weekly infusions of placebo , 3 mg/kg , 6 mg/kg , or 12 mg/kg CER-001 . Main outcome measures The primary efficacy parameter was the nominal change in the total atheroma volume . Nominal changes in per cent atheroma volume on IVUS and coronary scores on QCA were also pre-specified endpoints . Results The nominal change in the total atheroma volume ( adjusted means ) was −2.71 , −3.13 , −1.50 , and −3.05 mm3 with placebo , CER-001 3 mg/kg , 6 mg/kg , and 12 mg/kg , respectively ( primary analysis of 12 mg/kg vs. placebo : P = 0.81 ) . There was also no difference among groups for the nominal change in per cent atheroma volume ( 0.02 , −0.02 , 0.01 , and 0.19 % ; nominal P = 0.53 for 12 mg/kg vs. placebo ) . Change in the coronary artery score was −0.022 , −0.036 , −0.022 , and −0.015 mm ( nominal P = 0.25 , 0.99 , 0.55 ) , and change in the cumulative coronary stenosis score was −0.51 , 2.65 , 0.71 , and −0.77 % ( compared with placebo , nominal P = 0.85 for 12 mg/kg and nominal P = 0.01 for 3 mg/kg ) . The number of patients with major cardiovascular events was 10 ( 8.3 % ) , 16 ( 13.3 % ) , 17 ( 13.7 % ) , and 12 ( 9.8 % ) in the four groups . Conclusion CER-001 infusions did not reduce coronary atherosclerosis on IVUS and QCA when compared with placebo . Whether CER-001 administered in other regimens or to other population s could favourably affect atherosclerosis must await further study . Name of the trial registry : Clinical trials.gov ; Registry 's URL : http:// clinical trials.gov/ct2/show/NCT01201837?term=cer-001&rank=2 ; Trial registration number : NCT01201837 BACKGROUND & AIMS The purpose of this study was to evaluate the effect of low-fat products enriched with plant sterols in addition to a National Cholesterol Education Program step 1 diet on serum lipids and lipoproteins . METHODS This study was a double-blind , r and omised , placebo-controlled cross-over design with a run-in period and 2 intervention periods , each lasting 4 weeks . A total of 46 mildly hypercholesterolemic subjects ( age 50.6+/-9.8 ) completed the trial . The study products consisted of 20 g low-fat margarine ( 35 % fat ) and 250 ml low-fat milk ( 0.7 % fat ) , in total delivering 2.3 g plant sterols/d . RESULTS Serum total and low-density lipoprotein cholesterol were significantly reduced by 5.5 % ( p<0.001 , 95 % CI : 2.5 ; 8.3 ) and 7.7 % ( p=0.001 , 95 % CI : 3.4 ; 11.9 ) , respectively , by plant sterol-enriched products compared to placebo . Serum apolipoprotein B was significantly reduced by 4.6 % ( p<0.05 , 95 % CI : 1.7 ; 7.5 ) , and apolipoprotein B/apolipoprotein A-I by 3.4 % ( p<0.05 , 95 % CI : 0.1 ; 6.6 ) after plant sterol intake compared to the placebo supplement . CONCLUSIONS A combination of low-fat margarine and milk enriched with plant sterols significantly reduced low-density lipoprotein cholesterol , apolipoprotein B and the ratio of apolipoprotein B to apolipoprotein A-I in mildly hypercholesterolemic subjects , but had no effect on C-reactive protein and lipoprotein ( a ) concentrations . SPONSORSHIP Unilever Denmark BACKGROUND The mechanisms of the positive relationship between alcohol intake and plasma concentration of high-density lipoprotein ( HDL ) are still unclear . The present study shows the metabolism modifications of apolipoprotein ( apo ) AI and apoAII in normolipidaemic healthy volunteers after a period of moderate red wine consumption . DESIGN Five non-smoking male subjects were studied at the end of two consecutive 4-week periods , one without alcohol and the other with an intake of 50 g per day of alcohol , in r and om order . The metabolic parameters of apoAI and apoAII in HDL were determined after endogenous labelling using amino acid labelled with stable isotope . Cholesterol , triacylglycerols , HDL-cholesterol , apoAI , apoAII , LpAI , LpAI : AII were determined in plasma at the end of the two study periods . RESULTS Cholesterol and triacylglycerols did not vary significantly during the two periods , whereas HDL-cholesterol increased from 43.8 to 50.0 mg dL-1 ( P < 0.05 ) . ApoAI and apoAII increased significantly ( 20 % and 60 % respectively ) after the diet was supplemented with alcohol . LpAI : AII increased from 73.8 to 101.6 mg dL-1 ( + 32 % ) ( P < 0.05 ) , whereas alcohol had no effect on the concentration of LpAI . The alcohol treatment did not significantly alter the metabolism of apoAI . Conversely , the fractional catabolic rate of apoAII decreased significantly by 21 % ( P < 0.05 ) with alcohol , whereas the production rate of apoAII tended to increase by 18 % ( P = 0.08 ) . CONCLUSION The decrease in the fractional catabolic rate of apoAII could lead to an accumulation of apoAII-containing lipoproteins in plasma and account for the dramatic increase in LpAI : AII observed in the plasma of subjects consuming alcohol Background CSL112 is a new formulation of human apolipoprotein A-I ( apoA-I ) being developed to reduce cardiovascular events following acute coronary syndrome . This phase 2a , r and omized , double-blind , multicenter , dose-ranging trial represents the first clinical investigation to assess the safety and pharmacokinetics/pharmacodynamics of a CSL112 infusion among patients with stable atherosclerotic disease . Methods and Results Patients were r and omized to single ascending doses of CSL112 ( 1.7 , 3.4 , or 6.8 g ) or placebo , administered over a 2-hour period . Primary safety assessment s consisted of alanine aminotransferase or aspartate aminotransferase elevations > 3 × upper limits of normal and study drug – related adverse events . Pharmacokinetic/pharmacodynamic assessment s included apoA-I plasma concentration and measures of the ability of serum to promote cholesterol efflux from cells ex vivo . Of 45 patients r and omized , 7 , 12 , and 14 received 1.7- , 3.4- , and 6.8-g CSL112 , respectively , and 11 received placebo . There were no clinical ly significant elevations ( > 3 × upper limit of normal ) in alanine aminotransferase or aspartate aminotransferase . Adverse events were nonserious and mild and occurred in 5 ( 71 % ) , 5 ( 41 % ) , and 6 ( 43 % ) patients in the CSL112 1.7- , 3.4- , and 6.8-g groups , respectively , compared with 3 ( 27 % ) placebo patients . The imbalance in adverse events was attributable to vessel puncture/infusion-site bruising . CSL112 result ed in rapid ( Tmax≈2 hours ) and dose-dependent increases in apoA-I ( 145 % increase in the 6.8-g group ) and total cholesterol efflux ( up to 3.1-fold higher than placebo ) ( P<0.001 ) . Conclusions CSL112 infusion was well tolerated in patients with stable atherosclerotic disease . CSL112 immediately raised apoA-I levels and caused a rapid and marked increase in the capacity of serum to efflux cholesterol . This potential novel approach for the treatment of atherosclerosis warrants further investigation . Clinical Trial Registration URL : http://www . Clinical Trials.gov . Unique identifier : NCT01499420 The present r and omised parallel study assessed the impact of adding MUFA to a dietary portfolio of cholesterol-lowering foods on the intravascular kinetics of apoAI- and apoB-containing lipoproteins in subjects with dyslipidaemia . A sample of sixteen men and postmenopausal women consumed a run-in stabilisation diet for 4 weeks . Subjects were then r and omly assigned to an experimental dietary portfolio either high or low in MUFA for another 4 weeks . MUFA substituted 13·0 % of total energy from carbohydrate ( CHO ) in the high-MUFA dietary portfolio . Lipoprotein kinetics were assessed after the run-in and portfolio diets using a primed , constant infusion of [2H3]leucine and multicompartmental modelling . The high-MUFA dietary portfolio result ed in higher apoAI pool size ( PS ) compared with the low-MUFA dietary portfolio ( 15·9 % between-diet difference , P¼0·03 ) . This difference appeared to be mainly attributable to a reduction in apoAI fractional catabolic rate ( FCR ) after the high-MUFA diet ( 25·6 % , P¼0·02 v. pre-diet values ) , with no significant change in production rate . The high-MUFA dietary portfolio tended to reduce LDL apoB100 PS compared with the low-MUFA dietary portfolio ( 228·5 % between-diet that adding MUFA to a dietary portfolio of cholesterol-lowering foods provides the added advantage of raising HDL primarily through a reduction in HDL clearance rate . Replacing CHO with MUFA in a dietary portfolio may also lead to reductions in LDL apoB100 concentrations primarily by increasing LDL clearance rate , thus potentiating further the well-known cholesterol-lowering effect of this diet CSL112 is apoA-I purified from human plasma and reconstituted with phosphatidylcholine ( PC ) to form high-density lipoprotein (HDL)-particles suitable for infusion . CSL112 is in development for the potential treatment of acute coronary syndromes ( ACS ) by optimizing cholesterol efflux . This study assesses the pharmacokinetics ( PK ) , safety and tolerability of CSL112 . Repeat doses of CSL112 or placebo were administered intravenously once- ( 3.4 g or 6.8 g ) or twice-weekly ( 3.4 g ) to healthy subjects in a placebo-controlled , r and omized ( 3 CSL112 : 1 placebo ) , ascending-dose study ( NCT01281774 ) . Twenty-seven subjects received CSL112 and nine received placebo . Study endpoints included plasma apoA-I and PC concentrations and specific PK parameters . CSL112 infusions immediately produced robust increases in apoA-I concentration in a dose-proportional manner , reaching levels higher than observed with currently available or investigational HDL products . After infusion of CSL112 , apoA-I levels remained above baseline for approximately 3 days . Multiple infusions of CSL112 were safe and well tolerated with no evidence of major organ toxicity or immunogenicity . CSL112 may provide a novel option to rapidly transport cholesterol from atherosclerotic plaque to the liver and reduce early recurrent events following ACS . The data presented here support continued clinical development of CSL112 in patient population The effect of fish oil rich in eicosapentaenoic ( EPA ) and docosahexaenoic ( DHA ) acids on serum lipoprotein concentrations is not clear , and it is not known whether EPA and DHA are similarly related to serum lipid or lipoprotein levels . We conducted a r and omized , 10-week , dietary supplementation trial in which the effects of 6 g per day of 85 % EPA and DHA were compared with 6 g per day of corn oil in 156 men and women . Multivariate analyses were used to assess independent relations between plasma phospholipid EPA and DHA and serum lipoprotein levels . In the fish oil group triglycerides fell 21 % ( p less than 0.001 ) and high density lipoprotein cholesterol ( HDL-C ) rose 3.8 % ( p less than 0.05 ) . In the corn oil group triglycerides did not change , but HDL-C rose 6.1 % ( p less than 0.01 ) . Compared with fish oil , apolipoprotein A-I ( apo A-I ) rose 5.1 % after corn oil intake ( p less than 0.05 ) . Plasma EPA and DHA levels rose after fish oil intake and fell after corn oil intake ( all p less than 0.001 ) . The change ( delta ) in EPA was inversely correlated with delta triglycerides ( p = 0.035 ) and positively correlated with delta HDL-C and delta apo A-I ( both p less than 0.001 ) in the multivariate analyses . In contrast , delta DHA was not correlated with delta triglycerides but was inversely correlated with delta HDL-C and delta apo A-I ( both p less than 0.001 ) . St and ardizing for DHA removed the difference in apo A-I levels between groups . This study suggests that EPA and DHA are divergently associated with HDL , possibly through different mechanisms Type 2 diabetes is highly prevalent in North America and is associated with increased risk of cardiovascular disease ( CVD ) . Evidence supports a role for soy protein in the reduction of serum lipids related to CVD risk ; however , few studies have focused on adults with type 2 diabetes who are not on lipid-lowering medications and /or do not have diabetic complications . The purpose of this study was to determine the effect of soy protein isolate ( SPI ) consumption on serum lipids in adults with diet-controlled type 2 diabetes . Using a double-blind , r and omized , crossover , placebo-controlled intervention study design , adults with diet-controlled type 2 diabetes ( n = 29 ) consumed SPI ( 80 mg/d aglycone isoflavones ) or milk protein isolate ( MPI ) for 57 d each separated by a 28-d washout period . Twenty-four-hour urine sample s were collected on d 54 - 56 of each treatment for analysis of isoflavones and blood was collected on d 1 and 57 of each treatment and analyzed for serum lipids and apolipoproteins . SPI consumption increased urinary isoflavones compared with MPI . SPI consumption reduced serum LDL cholesterol ( P = 0.04 ) , LDL cholesterol : HDL cholesterol ( P = 0.02 ) , and apolipoprotein B : apolipoprotein A-I ( P = 0.05 ) compared with MPI . SPI did not affect serum total cholesterol , HDL cholesterol , triacylglycerol , apolipoprotein B , or apolipoprotein A-I. These data demonstrate that consumption of soy protein can modulate some serum lipids in a direction beneficial for CVD risk in adults with type 2 diabetes Summary The effects of two moderate doses of long-chain n-3 fatty acids ( 3.0 and 4.5 g EPA + DHA per day for 4 weeks each ) on serum lipids and lipoproteins of patients with familial combined hyperlipidemia ( FCH ) were studied in a double-blind , placebo-controlled clinical trial . In nine patients with FCH n-3 fatty acids led to a statistically significant , dose-dependent fall in very low density lipoprotein ( VLDL ) triglycerides ( 3 g/day : −42 % , 4.5 g/day : −55 % ) VLDL cholesterol ( 3 g/day : −41 % , 4.5 g/day : −47 % ) , and VLDL apolipoprotein ( apo ) B-100 ( 3 g/day : −40 % , 4.5 g/day : −56 % ) . No overall change in low-density lipoprotein ( LDL ) cholesterol was found , as confirmed statistically . However , when analyzing the data of single patients LDL cholesterol and LDL apo B did not change in five patients but increased dose dependently ( from pretreatment 4.80±0.93 mmol/l to 5.70 + 0.93 mmol/l LDL cholesterol after 4.5 g/day ) in four . LDL and VLDL composition as indicated by cholesterol/apo B-100 and triglyceride/apo B-100 ratios did not change significantly . High-density lipoprotein ( HDL ) cholesterol was unchanged ; the HDL cholesterol/apo A-I+apo A-II ratio increased by 19 % ( P<0.05 ) during fish oil treatment . We conclude that in FCH moderate doses of long-chain n-3 fatty acids are highly effective in lowering pathological VLDL triglycerides , VLDL cholesterol , and VLDL apo B. LDL cholesterol must , however , be monitored during treatment as it may rise substantially in some although not in all patients with this disease Alcohol consumption is associated with increased HDL cholesterol levels , which may indicate stimulated reverse cholesterol transport . The mechanism is , however , not known . The aim of this study was to evaluate the effects of alcohol consumption on the first two steps of the reverse cholesterol pathway : cellular cholesterol efflux and plasma cholesterol esterification . Eleven healthy middle-aged men consumed four glasses ( 40 g of alcohol ) of red wine , beer , spirits ( Dutch gin ) , or carbonated mineral water ( control ) daily with evening dinner , for 3 weeks , according to a 4 x 4 Latin square design . After 3 weeks of alcohol consumption the plasma ex vivo cholesterol efflux capacity , measured with Fu5AH cells , was raised by 6.2 % ( P < 0.0001 ) and did not differ between the alcoholic beverages . Plasma cholesterol esterification was increased by 10.8 % after alcohol ( P = 0.008 ) . Changes were statistically significant after beer and spirits , but not after red wine consumption ( P = 0.16 ) . HDL lipids changed after alcohol consumption ; HDL total cholesterol , HDL cholesteryl ester , HDL free cholesterol , HDL phospholipids and plasma apolipoprotein A-I all increased ( P < 0.01 ) . In conclusion , alcohol consumption stimulates cellular cholesterol efflux and its esterification in plasma . These effects were mostly independent of the kind of alcoholic We attempted to ascertain the effects of polyunsaturated fatty acids by conducting two studies in normal young men , in which monounsaturated fats were replaced by polyunsaturated fats within the guidelines of the American Heart Association step 1 diet . Study A employed a r and omized parallel design in which subjects first consumed an average American diet ( AAD ) containing 37 % of calories as fat ( saturated fat , 16 % calories ; monounsaturated fat , 14 % calories ; and polyunsaturated fat , 7 % calories ) . After 3 weeks , one third of the subjects continued with the AAD , one third switched to a step 1 diet in which total fat calories were reduced to 30 % by replacing saturated fat with carbohydrate , and one third switched to a polyunsaturated fat-enriched ( Poly ) diet with the same 30 % fat calories and a reduction of monounsaturated fat from 14 % to 8 % and an increase of polyunsaturated fat from 7 % to 13 % of calories . The r and omized period lasted 6 weeks . Total and low-density lipoprotein ( LDL ) cholesterol levels on the step 1 and Poly diets were reduced compared with levels on the AAD ( P < .001 ) . Total and LDL cholesterol did not differ between the step 1 and Poly diets , although comparison between the two diets is limited by the small study groups . Serum apolipoprotein ( apo ) B levels fell on the Poly diet compared with the AAD . Total high-density lipoprotein ( HDL ) , HDL2 , and HDL3 cholesterol levels were not significantly affected by the diets . Postpr and ial lipid and lipoprotein concentrations did not significantly differ either . In study B , a r and omized crossover design was used in which all subjects ate the step 1 and Poly diets for 5 weeks each with a 4-day break between diets . In the eight subjects studied , the values for fasting plasma total , LDL , and HDL cholesterol ; triglycerides ; apoB ; and apoA-I were essentially identical at the end of each diet period . Postpr and ial triglyceride areas obtained after ingestion of a large , st and ard fat load were also the same . Finally , LDL apoB and HDL apoA-I turnovers were unaffected by replacement of monounsaturates with polyunsaturates . In summary our results indicate that modest exchanges of monounsaturated for polyunsaturated fats do not significantly affect LDL or HDL levels or metabolism , which supports the view that reducing saturated fats is the key to lowering total and LDL cholesterol Previous studies have indicated that consumption of boiled coffee raises total and low density lipoprotein ( LDL ) cholesterol , whereas drip-filtered coffee does not . We have tested the effect on serum lipids of consumed coffee that was first boiled and then filtered through commercial paper coffee filters . Sixty-four healthy volunteers consumed six cups per day of this boiled and filtered coffee for 17 days . Then , they were r and omly divided into three groups , which , for the next 79 days , received either unfiltered boiled coffee ( lipid content , 1.0 g/l ) , boiled and filtered coffee ( 0.02 g lipid/l ) , or no coffee . Serum total cholesterol levels rose by 0.42 mmol/l ( 16 mg/dl ; 95 % confidence interval [ CI ] , 0.14 - 0.71 ) , LDL cholesterol levels by 0.41 mmol/l ( 16 mg/dl ; 95 % CI , 0.16 - 0.66 ) , and apolipoprotein B levels by 8.6 mg/dl ( 95 % CI , 3.8 - 13.4 ) in those who consumed boiled coffee relative to those who consumed boiled and filtered coffee . Responses of triglycerides , high density lipoprotein cholesterol , and apolipoprotein A-I did not differ significantly among these groups . No significant effects on serum lipid levels were found in the boiled and filtered coffee-consuming group compared with those who drank no coffee . In subjects who drank boiled coffee , serum campesterol level , an indicator of cholesterol absorption , remained constant . The serum lathosterol level , an indicator of cholesterol synthesis , increased by 11 % ( p less than 0.05 ) , but the lathosterol to cholesterol ratio did not change . We propose that paper filters of the type used for drip-filtered coffee retain the lipid present in boiled coffee and in that way remove the hypercholesterolemic factor . ( ABSTRACT TRUNCATED AT 250 WORDS Objective : Clinical and epidemiological studies have reported the beneficial effects of tree nuts and peanuts on serum lipid levels . We studied the effects of consuming 15 % of the daily caloric intake in the form of pistachio nuts on the lipid profiles of free-living human subjects with primary , moderate hypercholesterolemia ( serum cholesterol greater than 210 mg/dL ) . Methods : Design : R and omized crossover trial . Setting : Outpatient dietary counseling and blood analysis . Subjects : 15 subjects with moderate hypercholesterolemia . Intervention : Fours weeks of dietary modification with 15 % caloric intake from pistachio nuts . Measures of Outcome : Endpoints were serum lipid levels of total cholesterol , HDL-C , LDL-C , VLDL-C , triglycerides and apolipoproteins A-1 and B-100 . BMI , blood pressure , and nutrient intake ( total energy , fat , protein , and fiber ) were also measured at baseline , during , and after dietary intervention . Results : No statistically significant differences were observed for total energy or percent of energy from protein , carbohydrate or fat . On the pistachio nut diet , a statistically significant decrease was seen for percent energy from saturated fat ( mean difference , −2.7 % ; 95 % CI , −5.4 % to −0.08 % ; p = 0.04 ) . On the pistachio nut diet , statistically significant increases were seen for percent energy from polyunsaturated fat ( mean difference , 6.5 % ; 95 % CI , 4.2 % to 8.9 % ; p<.0001 ) and fiber intake ( mean difference , 15 g ; 95 % CI , 8.4 g to 22 g ; p = 0.0003 ) . On the pistachio diet , statistically significant reductions were seen in TC/HDL-C ( mean difference , −0.38 ; 95 % CI , −0.57 to −0.19 ; p = 0.001 ) , LDL-C/HDL-C ( mean difference , −0.40 ; 95 % CI , −0.66 to −0.15 ; p = 0.004 ) , B-100/A-1 ( mean difference , −0.11 ; 95 % CI , −0.19 to −0.03 ; p = 0.009 ) and a statistically significant increase was seen in HDL-C ( mean difference , 2.3 ; 95 % CI , 0.48 to 4.0 ; p = 0.02 ) . No statistically significant differences were seen for total cholesterol , triglycerides , LDL-C , VLDL-C , apolipoprotein A-1 or apolipoprotein B-100 . No changes were observed in BMI or blood pressure . Conclusion : A diet consisting of 15 % of calories as pistachio nuts ( about 2–3 ounces per day ) over a four week period can favorably improve some lipid profiles in subjects with moderate hypercholesterolemia and may reduce risk of coronary disease In order to test whether hyperlipidaemia and glycaemic control can be improved among diabetes patients by dietary supplementation with purified omega-3 fatty acids , we carried out a double-blind , placebo-controlled trial on 50 type 2 diabetes patients r and omized to 2 g/day purified omega-3 fatty acids or placebo for 10 weeks . Fasting triglycerides decreased significantly with supplementation relative to placebo ( P = 0.01 ) . There was a significant decrease in ApoB-100 and malondialdehyde compared to baseline values and compared to the control group . Omega-3 fatty acids had no significant effect on serum lipid levels , ApoA-I , glucose , insulin and HbA1c CONTEXT Preliminary studies have suggested that both citrus flavonoids and palm tocotrienols reduce cholesterol levels in laboratory animals . OBJECTIVE To examine the effect of these nutrients in combination on blood levels of cholesterol and related cardiovascular disease risk factors . DESIGN Two open-label studies and 1 double-blind study are reported . SETTING Outpatient clinical research setting . PATIENTS Three groups ( n=10 , n=10 , n=120 ) of hypercholesterolemic men and women ( cholesterol levels > 230 mg/dL ) between the ages of 19 and 65 years were recruited . INTERVENTION Subjects were r and omized to consume either 270 mg citrus flavonoids plus 30 mg tocotrienols ( S ) or placebo ( P ) daily for a period of 4 weeks ( group 1 [ G1 ] and group 2 [ G2 ] ) or 12 weeks ( group 3 [ G3 ] ) . MAIN OUTCOME MEASURES Measurements of fasting levels of blood cholesterol , low-density lipoprotein ( LDL ) , high-density lipoprotein ( HDL ) , and triglycerides were made at baseline and 4 weeks ( all groups ) and at 8 weeks and 12 weeks ( G3 ) . RESULTS Daily treatment with S significantly improved cardiovascular parameters compared to P in all groups . Significant reductions were shown in total cholesterol ( 20%-30 % ) , LDL ( 19%-27 % ) , apolipoprotein B ( 21 % ) , and triglycerides ( 24%-34 % ) . HDL levels remained unchanged in G1 and G2 but increased 4 % ( nonsignificant ) in G3 and was accompanied by a significant increase in apolipoprotein A1 ( 5 % ) Non-insulin-dependent diabetes mellitus ( NIDDM ) is associated with elevated very-low-density lipoprotein ( VLDL ) triglyceride concentrations and abnormalities of low-density lipoprotein ( LDL ) composition . Because fish oil supplementation may favorably affect lipid and lipoprotein concentrations in nondiabetic subjects , we determined the effect of fish oil concentrate on plasma lipids and lipoprotein composition in patients with NIDDM . Dietary-supplementation 1-mo periods of 4.0 and 7.5 g of omega-3 fatty acids in fish oil were compared with a placebo of 12 g safflower oil by use of a single-blind crossover design . Medications , including antidiabetic therapy , were continued through the study . Compared with safflower oil treatment , fish oil supplementation result ed in a significant reduction of total plasma triglycerides of 24 % at the 4-g dose and a larger reduction of 39 % at the 7.5-g dose . These decreases were due to similar reductions in VLDL triglycerides . LDL cholesterol levels were mildly elevated , but a larger 20 % increase in LDL apolipoprotein B ( apoB ) concentration was observed . During supplementation with the fish oil concentrate , the LDL cholesterol-to-apoB ratio was significantly reduced when compared with pretreatment values , but not when compared with safflower oil treatment . Highdensity lipoprotein ( HDL ) cholesterol and plasma apoA1 levels were not significantly changed during fish oil treatment . At the 7.5-g dose , fasting glucose and glycohemoglobin levels increased by 20 and 12 % , respectively , but were unchanged at the lower level of supplementation . Thus , in NIDDM patients , dietary supplementation with omega-3 fatty acids induces a reduction in total plasma and VLDL triglyceride levels . However , the observed increase in LDL apoB levels , and the deterioration in glycemic control , indicate thatfurther study will be required to establish whether fish oil has a role in the treatment of NIDDM BACKGROUND Evidence from clinical studies has suggested that cocoa may increase high-density lipoprotein (HDL)-cholesterol concentrations . However , it is unclear whether this effect is attributable to flavonoids or theobromine , both of which are major cocoa components . OBJECTIVES We investigated whether pure theobromine increases serum HDL cholesterol and whether there is an interaction effect between theobromine and cocoa . DESIGN The study had a 2-center , double-blind , r and omized , placebo-controlled , full factorial parallel design . After a 2-wk run-in period , 152 healthy men and women ( aged 40 - 70 y ) were r and omly allocated to consume one 200-mL drink/d for 4 wk that contained 1 ) cocoa , which naturally provided 150 mg theobromine and 325 mg flavonoids [ cocoa intervention ( CC ) ] , 2 ) 850 mg pure theobromine [ theobromine intervention ( TB ) ] , 3 ) cocoa and added theobromine , which provided 1000 mg theobromine and 325 mg flavonoids [ theobromine and cocoa intervention ( TB+CC ) ] , or 4 ) neither cocoa nor theobromine ( placebo ) . Blood lipids and apolipoproteins were measured at the start and end of interventions . RESULTS In a 2-factor analysis , there was a significant main effect of the TB ( P < 0.0001 ) but not CC ( P = 0.1288 ) on HDL cholesterol but no significant interaction ( P = 0.3735 ) . The TB increased HDL-cholesterol concentrations by 0.16 mmol/L ( P < 0.0001 ) . Furthermore , there was a significant main effect of the TB on increasing apolipoprotein A-I ( P < 0.0001 ) and decreasing apolipoprotein B and LDL-cholesterol concentrations ( P < 0.02 ) . CONCLUSIONS Theobromine independently increased serum HDL-cholesterol concentrations by 0.16 mmol/L. The lack of significant cocoa and interaction effects suggested that theobromine may be the main ingredient responsible for the HDL cholesterol-raising effect . This trial was registered at clinical trials.gov as NCT01481389 BACKGROUND & AIMS Blond orange juice is the most consumed fruit juice in the world . It is a source of hesperidin , a bioavailable flavonoid reported to exhibit potential vascular protective actions . However , the specific impact on vascular function of Citrus phytomicronutrients , is unknown . For the first time , we investigated the effects of blond orange juice compared with a control beverage mimicking the composition of orange juice ( including Vitamin C but no phytomicronutrients ) , on antioxidant markers , cardiovascular risk factors and endothelial function . METHODS Twenty five male volunteers with two cardiovascular risk factors ( age over 50 years and LDL-cholesterol between 130 and 190 mg/L ) were enrolled in a r and omized cross-over study . They received 3 times daily 200 mL of either blond orange juice or control beverage for 4 weeks , spaced by a 5-week wash-out . Endothelial function ( flow mediated dilatation and plasma markers ) , oxidative status , lipid profile and inflammatory markers were assessed . RESULTS Daily intakes of orange juice significantly led to a marked antioxidant effect which was correlated to hesperetin plasma levels and related with a decrease in reactive oxygen species . A tendency towards reduction of endothelial dysfunction and modest increase in plasma apoA-I concentration were also observed . This allows further experiments demonstrating the specific effect of phytomicronutrients from orange juice . CONCLUSIONS These findings suggest that daily intake of nutritionally relevant dose of blond orange juice may contribute for a significant antioxidant effect through the phytochemicals contained in . Orange juice may be associated to other healthy foods to achieve a significant effect on the vascular function . This study is recorded in Clinical Trials.com as NCT00539916 OBJECTIVE Dietary guidelines for the prevention of coronary heart disease ( CHD ) have restricted the intake of foods rich in dietary cholesterol , on the grounds that the dietary cholesterol will increase blood cholesterol . In the case of shellfish , this recommendation may limit the intake of a valuable dietary source of long chain n-3 polyunsaturated fatty acids ( LC n-3 PUFA ) . The objective of this study was to undertake a dietary intervention to determine the effects of cold water prawns on plasma lipids and lipoproteins . METHODS 23 healthy male subjects were r and omised to receive either 225 g of cold water prawns or an equivalent weight of fish ( ' crab ' ) sticks as a control for 12 weeks in a cross-over design . Blood sample s were taken at the beginning and end of each intervention for the determination of plasma lipids and lipoproteins by routine enzymatic assays and iodixanol density gradient centrifugation respectively . RESULTS The diets were well matched for the intake of total energy and macronutrients , and body weight remained stable throughout the study . The prawn intervention increased the intake of dietary cholesterol to 750 mg/d against 200 mg/d on the control . The intake of LC n-3 PUFA from prawns was estimated to be between 0.5 - 0.7 g/d . The consumption of prawns produced no significant effects on the concentration of plasma total or LDL cholesterol , triacylglycerol , HDL cholesterol or apolipoproteins A-I and B relative to the control , or within each intervention group over time . There was also no significant effect on LDL density ( particle size ) relative to the control , or any difference between and within treatments in total plasma lipoprotein profiles by density gradient centrifugation . CONCLUSION These findings provide evidence to suggest that the consumption of cold water prawns , at least in healthy , male subjects , should not be restricted on the grounds of this seafood producing an adverse effect on plasma LDL cholesterol Objective : To examine the effects of the inclusion of extruded dry beans in the diet on serum lipoprotein , plasma fibrinogen , plasma viscosity and plasminogen activator inhibitor 1 ( PAI-1 ) levels . Subjects and study design : Twenty-two free living hyperlipidaemic men participated in this r and omised , controlled , cross-over study . The subjects were r and omly assigned to one of two groups . After a run-in period of four weeks , during which subjects followed their normal diet with the exclusion of dry beans , group A had to include 110 g/day of extruded dry beans in the form of baked products for four weeks while group B continued with the run-in diet . A washout period of four weeks followed after which the experimental intervention was crossed-over . Anthropometric measurements , serum lipoproteins and haemostatic variables were measured with st and ard methods and dietary intakes were estimated with five-day dietary records at the beginning and end of each experimental period . Results : Compliance was determined as 83.5 % with a mean intake of 91.9 g/day extruded dry beans . Extruded dry beans did not have significant effects on total serum cholesterol , low density lipoprotein cholesterol , triglycerides , apolipoprotein A or B , plasma fibrinogen and plasma viscosity concentrations . High density lipoprotein cholesterol concentrations decreased in both the dry bean and control periods . Lipoprotein ( a ) concentrations increased with intake of extruded dry beans , but this increase was probably not due to an independent effect of extruded dry beans . Plasminogen activator inhibitor 1 levels were significantly lower after the intake of extruded dry beans compared to the control period . Conclusions : The inclusion of 91.9 g extruded dry beans per day in the diet had no effects on serum lipoproteins , plasma fibrinogen and viscosity levels but decreased PAI-1 levels . Sponsorship : Dry Bean Producers Organisation ( South Africa ) and the Potchefstroom University for Christian Higher Education , Potchefstroom , South Africa . European Journal of Clinical Nutrition ( 2000 ) 54 , Twenty healthy males were divided into two groups : 10 subjects were supplemented for 2 weeks with 400 ml of red wine ( 11 % alcohol ) per day and the other 10 subjects were given 400 ml of white wine ( 11 % alcohol ) per day for a similar period . Blood sample s were drawn prior to wine supplementation , after 1 week and at the end of the study . No significant effects were found on plasma concentrations of urea , creatinine , bilirubin , creatine kinase , amylase , blood cell counts , platelet counts and platelet aggregation . Both red- and white-wine supplementation result ed in a transient minor reduction in plasma glucose concentration and in a minor elevation in blood coagulation properties such as prothrombin time and partial thromboplastin time . Red ( but not white ) wine result ed in an 11 and 26 % increment in plasma triglyceride concentrations after 1 and 2 weeks of supplementation , respectively . Plasma cholesterol , as well as very-low- and low-density-lipoprotein levels did not change during the 2 weeks of red- or white-wine supplementation . The most impressive effect of red-wine intake was a significant ( p < 0.01 ) increase in plasma high-density lipoprotein ( HDL ) cholesterol and in plasma apolipoprotein A-I concentrations by up to 26 and 12 % , respectively . These effects were not observed after the intake of white wine . We conclude that the major effect of red-wine supplementation ( about 40 g of alcohol per day for a period of 2 weeks ) was a significant increase in plasma HDL concentration which may contribute to the reduced risk for cardiovascular diseases observed in red-wine drinkers BACKGROUND Increased consumption of n-3 ( omega-3 ) fatty acids decreases the incidence of coronary heart disease ( CHD ) . OBJECTIVE The objective was to determine whether walnuts ( plant n-3 fatty acid ) and fatty fish ( marine n-3 fatty acid ) have similar effects on serum lipid markers at intakes recommended for primary prevention of CHD . DESIGN In a r and omized crossover feeding trial , 25 normal to mildly hyperlipidemic adults consumed 3 isoenergetic diets ( approximately 30 % total fat and < 10 % saturated fat ) for 4 wk each : a control diet ( no nuts or fish ) , a walnut diet ( 42.5 g walnuts/10.1 mJ ) , or a fish diet ( 113 g salmon , twice/wk ) . Fasting blood was drawn at baseline and at the end of each diet period and analyzed for serum lipids . RESULTS Serum total cholesterol and LDL cholesterol concentrations in adults who followed the walnut diet ( 4.87 + /- 0.18 and 2.77 + /- 0.15 mmol/L , respectively ) were lower than in those who followed the control diet ( 5.14 + /- 0.18 and 3.06 + /- 0.15 mmol/L , respectively ) and those who followed the fish diet ( 5.33 + /- 0.18 and 3.2 + /- 0.15 mmol/L , respectively ; P < 0.0001 ) . The fish diet result ed in decreased serum triglyceride and increased HDL-cholesterol concentrations ( 1.0 + /- 0.11 and 1.23 + /- 0.05 mmol/L , respectively ) compared with the control diet ( 1.12 + /- 0.11 and 1.19 + /- 0.05 mmol/L , respectively ) and the walnut diet ( 1.11 + /- 0.11 mmol/L , P < 0.05 , and 1.18 + /- 0.05 mmol/L , P < 0.001 , respectively ) . The ratios of total cholesterol : HDL cholesterol , LDL cholesterol : HDL cholesterol , and apolipoprotein B : apolipoprotein A-I were lower ( P < 0.05 ) in those who followed the walnut diet compared with those who followed the control and fish diets . CONCLUSION Including walnuts and fatty fish in a healthy diet lowered serum cholesterol and triglyceride concentrations , respectively , which affects CHD risk favorably BACKGROUND Control of hyperlipidemia is vital in patients with cardiovascular disease ( CVD ) . Omega-3 fatty acids ( n-3FAs ) have desirable effects on serum triglyceride ( TG ) levels , thrombosis , and arrhythmia , but lead to increases in serum low-density lipoprotein ( LDL ) and apo-B as well . OBJECTIVE To determine and compare the effects of administration of n-3FAs , vitamin C ( VitC ) and n-3FAs + VitC on the serum levels of LDL , apoB , other serum lipids , and malondialdehyde ( MDA ) . The present study was performed in Tehran University of Medical Sciences from 2000 to 2001 . DESIGN In a double-blind , placebo trial of parallel design , 68 hyperlipidemic patients [ total cholesterol ( TC ) and TG greater than 200 mg/dL ] were r and omly assigned to receive daily 500 mg VitC , 1 g n-3FAs , 500 mg VitC + 1 g n-3FAs , or placebo ( control ) for 10 weeks . Fasting blood sample s were collected at the beginning and at the end of the period . TG , TC , LDL-cholesterol-C ( LDL-C ) , and high-density lipoprotein-cholesterol ( HDL-C ) were measured enzymatically , VitC and MDA colorimetrically , and apo-B and apo-A-I immunoturbidometrically . The pattern of food consumption , socio-economic , and anthropometric indices were determined ; there was no significant change in these indices during the study . RESULTS There was a significant difference in the blood VitC level at the end of the study in comparison to the initial value in the VitC ( p = 0.001 ) and VitC + n-3FAs ( p = 0.027 ) groups . Similarly , the serum TG level at the end of study was significantly different from the initial value in the n-3FAs group ( p = 0.002 ) and also from the final value in the control group ( p = 0.013 ) . In the VitC group , there was a significant decrease in TC ( p = 0.004 ) , apo-B ( p = 0.005 ) , and MDA ( p = 0.015 ) at the end of study as compared to the respective initial values . There was also a significant increase in blood VitC compared to the control value ( p = 0.018 ) and a significant decrease in MDA compared to the n-3FAs group ( p = 0.034 ) . At the end of study , in the n-3FAs group , there was a significant ( p = 0.04 ) and a marginally significant decrease ( p = 0.05 ) , respectively , in TG/HDL and apo-B levels as compared to the initial values , and the TG/HDL ratio showed a significant decrease as compared to the control group ( p = 0.047 ) . CONCLUSION Simultaneous administration of n-3FAs and VitC had no beneficial effects on the lipid profile of hyperlipidemic patients , but 1 g purified n-3FAs daily for 10 weeks is a beneficial supplement for decreasing TG without any increase in LDL-C , apo-B or MDA . Administration of 500 mg VitC for more than 10 weeks might decrease significantly TC and apo-B in hyperlipidemic patients Background Bromodomain and extra-terminal ( BET ) proteins regulate transcription of lipoprotein and inflammatory factors implicated in atherosclerosis . The impact of BET inhibition on atherosclerosis progression is unknown . Methods ASSURE was a double-blind , r and omized , multicenter trial in which 323 patients with angiographic coronary disease and low high-density lipoprotein cholesterol ( HDL-C ) levels were r and omized in a 3:1 fashion to treatment with the BET protein inhibitor RVX-208 200 mg or placebo for 26 weeks . Plaque progression was measured with serial intravascular ultrasound imaging . Lipid levels , safety , and tolerability were also assessed . Results During treatment , apolipoprotein (apo)A-I increased by 10.6 % with placebo ( P < 0.001 compared with baseline ) and 12.8 % with RVX-208 ( P < 0.001 compared with baseline ) , between groups P = 0.18 . HDL-C increased by 9.1 % with placebo ( P < 0.001 compared with baseline ) and 11.1 % with RVX-208 ( P < 0.001 compared with baseline ) , between groups P = 0.24 . Low-density lipoprotein cholesterol ( LDL-C ) decreased by 17.9 % with placebo ( P < 0.001 compared with baseline ) and 15.8 % with RVX-208 ( P < 0.001 compared with baseline ) , between groups P = 0.55 . The primary endpoint , the change in percent atheroma volume , decreased 0.30 % in placebo-treated patients ( P = 0.23 compared with baseline ) and 0.40 % in the RVX-208 group ( P = 0.08 compared with baseline ) , between groups P = 0.81 . Total atheroma volume decreased 3.8 mm3 in the placebo group ( P = 0.01 compared with baseline ) and 4.2 mm3 in the RVX-208 group ( P < 0.001 compared with baseline ) , P = 0.86 between groups . A greater incidence of elevated liver enzymes was observed in RVX-208-treated patients ( 7.1 vs. 0 % , P = 0.009 ) . Conclusion Administration of the BET protein inhibitor RVX-208 showed no greater increase in apoA-I or HDL-C or incremental regression of atherosclerosis than administration of placebo . Trial Registration Clinical Trials.gov identifier — NCT01067820 Almond consumption is associated with ameliorations in obesity , hyperlipidemia , hypertension , and hyperglycemia . The hypothesis of this 12-week r and omized crossover clinical trial was that almond consumption would improve glycemic control and decrease the risk for cardiovascular disease in 20 Chinese patients with type 2 diabetes mellitus ( T2DM ) ( 9 male , 11 female ; 58 years old ; body mass index , 26 kg/m² ) with mild hyperlipidemia . After a 2-week run-in period , patients were assigned to either a control National Cholesterol Education Program step II diet ( control diet ) or an almond diet for 4 weeks , with a 2-week washout period between alternative diets . Almonds were added to the control diet to replace 20 % of total daily calorie intake . Addition of approximately 60 g almonds per day increased dietary intakes of fiber , magnesium , polyunsaturated fatty acid , monounsaturated fatty acid , and vitamin E. Body fat determined with bioelectrical impedance analysis was significantly lower in patients consuming almonds ( almonds vs control : 29.6 % vs 30.4 % ) . The almond diet enhanced plasma α-tocopherol level by a median 26.8 % ( 95 % confidence intervals , 15.1 - 36.6 ) compared with control diet . Furthermore , almond intake decreased total cholesterol , low-density lipoprotein cholesterol , and the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol by 6.0 % ( 1.6 - 9.4 ) , 11.6 % ( 2.8 - 19.1 ) , and 9.7 % ( 0.3 - 20.9 ) , respectively . Plasma apolipoprotein ( apo ) B levels , apo B/apo A-1 ratio , and nonesterified fatty acid also decreased significantly by 15.6 % ( 5.1 - 25.4 ) , 17.4 % ( 2.8 - 19.9 ) , and 5.5 % ( 3.0 - 14.4 ) , respectively . Compared with subjects in the control diet , those in the almond diet had 4.1 % ( 0.9 - 12.5 ) , 0.8 % ( 0.4 - 6.3 ) , and 9.2 % ( 4.4 - 13.2 ) lower levels of fasting insulin , fasting glucose , and homeostasis model assessment of insulin resistance index , respectively . Our results suggested that incorporation of almonds into a healthy diet has beneficial effects on adiposity , glycemic control , and the lipid profile , thereby potentially decreasing the risk for cardiovascular disease in patients with type 2 diabetes mellitus OBJECTIVE Due to its high content of lignans , alpha-linolenic acid and fiber , flaxseed may reduce cardiovascular disease risk in humans . The present study evaluated the effect of flaxseed on markers of cardiovascular disease risk in healthy menopausal women . METHODS One hundred ninety-nine women were r and omly assigned to consume 40 g daily of flaxseed or wheat germ placebo for 12 mo . Fatty acids , apolipoproteins A-1 and B , lipoprotein(a ) , low-density lipoprotein particle size , fibrinogen , C-reactive protein , insulin , and glucose were measured at baseline and at 12 mo . RESULTS In total 179 women were available for the intention-to-treat analysis . Flaxseed increased plasma alpha-linolenic ( P < 0.0001 ) , docosapentaenoic ( P = 0.001 ) , and total omega-3 fatty ( P = 0.0004 ) acids . Differences between flaxseed and wheat germ were observed for apolipoprotein A-1 ( -0.10 + /- 0.26 g/L , P = 0.011 ) and apolipoprotein B ( -0.05 + /- 0.16 g/L , P = 0.047 ) . From baseline , flaxseed raised apolipoproteins A-1 and B by 4.4 % ( P = 0.006 ) and 3 % ( P = 0.054 ) , whereas wheat germ increased these apolipoproteins by 11.6 % ( P < 0.0001 ) and 7 % ( P = 0.0001 ) , respectively . Both treatments increased lipoprotein(a ) ( P < 0.0001 ) and decreased low-density lipoprotein peak particle size ( P < 0.0001 ) . CONCLUSION In this large , long-term , placebo-controlled trial in healthy menopausal women , flaxseed increased some omega-3 fatty acids in plasma and had a limited effect on apolipoprotein metabolism ♦ Background : Lipid abnormalities , particularly high serum concentration of lipoprotein(a ) [ Lp(a ) ] , are one of the major risk factors for cardiovascular disease ( CVD ) in peritoneal dialysis ( PD ) patients . The present study was design ed to investigate the effects of soy consumption on serum lipids and apoproteins , especially Lp(a ) , in PD patients . ♦ Methods : This study was a r and omized clinical trial in which 40 PD patients ( 20 males , 20 females ) were r and omly assigned to either the soy or the control group . Patients in the soy group received 28 g/day textured soy flour ( containing 14 g of soy protein ) for 8 weeks , whereas patients in the control group received their usual diet , without any soy . At baseline and the end of week 8 of the study , 5 mL of blood was collected from each patient after a 12- to 14-hour fast and serum triglyceride , total cholesterol , low density lipoprotein-cholesterol ( LDL-C ) , high density lipoprotein-cholesterol ( HDL-C ) , apoprotein B100 ( apo B100 ) , apoprotein AI ( apo AI ) , and Lp(a ) were measured . ♦ Results : In the present study , serum Lp(a ) concentrations were above the normal range in 86 % of the PD patients . Mean serum Lp(a ) concentration was reduced significantly , by 41 % , in the soy group at the end of week 8 compared to baseline ( p < 0.01 ) ; the reduction was also significant compared to the control group ( p < 0.05 ) . During the study , mean serum Lp(a ) concentration did not change significantly in the control group . There were no significant differences between the two groups in mean changes in serum triglyceride , total cholesterol , HDL-C , LDL-C , apo B100 , or apoAI . ♦ Conclusion : The results of our study indicate that soy consumption reduces serum Lp(a ) concentration , which is a risk factor for cardiovascular disease in peritoneal dialysis patients STUDY OBJECTIVE To determine the effects of fish oil supplementation on plasma cholesterol in middle-aged men with isolated hypercholesterolemia . DESIGN R and omized double-blind placebo-controlled ( safflower oil ) two-period crossover trial with 12-week treatment periods . SETTING Outpatient general medicine clinic at a university-affiliated Veterans Affairs hospital . PATIENTS Thirty-eight men with plasma cholesterol between 5.68 and 7.76 mmol/L ( 220 to 300 mg/dL ) , triglyceride levels less than 3.39 mmol/L ( 300 mg/dL ) , and free of coexisting diseases . INTERVENTIONS Fish oil and placebo ( safflower oil ) supplementation . After basal measurements and a 4-week lead-in period , twenty 1-g capsules of either fish oil or placebo oil were provided for 12 weeks ( period 1 ) . After a 4-week washout phase participants then received the other oil for an additional 12 weeks ( period 2 ) . MEASUREMENTS AND MAIN RESULTS Blood was drawn at the beginning and end of each study period and analyzed for levels of total cholesterol , high-density lipoprotein ( HDL ) cholesterol , triglycerides , apolipoprotein A1 , and apolipoprotein B. Low-density lipoprotein ( LDL ) cholesterol was calculated using the Friedewald equation . Total and LDL cholesterol increased from the before treatment values by 4.8 % and 9.1 % , respectively , after ingestion of fish oil . Compared with placebo , LDL cholesterol was significantly higher ( 4.5 compared with 4.1 mmol/L , P = 0.01 ) and triglycerides lower ( 1.3 compared with 1.8 mmol/L , P = 0.01 ) after fish oil . Total and HDL cholesterol and apolipoprotein A1 and B levels did not differ . CONCLUSIONS Fish oil supplements do not lower plasma cholesterol levels in middle-aged men with hypercholesterolemia without elevated triglycerides . They should not be recommended as a method to lower plasma cholesterol in these patients We examined the effects on blood pressure , plasma lipoproteins , and platelet function when marine oil supplements ( rich in n-3 fatty acids ) or vegetable oil supplements ( rich in n-6 fatty acids ) were added to the usual diets of patients with mild essential hypertension . In a r and omized , double-blind , parallel-group study , patients received 50 g of either marine oil ( n = 8) or vegetable oil ( n = 8) daily for 6 weeks following a baseline observation period . Diastolic blood pressure declined during treatment with fish oil ( mean + /- SEM , 96 + /- 2 v 89 + /- 2 mm Hg , P = .02 ) , but did not change with vegetable oil ( 92 + /- 1 v 94 + /- 1 mm Hg ) . Systolic blood pressure did not change significantly during either treatment . Serum triglycerides declined ( by approximately 30 % ) in patients receiving only marine oil , but total cholesterol , LDL- , HDL- , HDL2- , and HDL3-cholesterol-subfractions and apolipoproteins A-I and B were unchanged in both treatment groups . Bleeding time increased by 33 % during treatment with marine oil but did not change with vegetable oil supplements . Marine oil did not alter in vitro platelet aggregation thresholds . The lack of a significant correlation between blood pressure changes and platelet membrane fluidity , plasma renin activity , aldosterone , norepinephrine , or epinephrine suggests that these variables did not mediate the antihypertensive effect of the marine oil . We conclude that large doses of marine oil reduce diastolic blood pressure , lower triglycerides , and increase bleeding time in patients with mild hypertension Long chain n-3 polyunsaturated fatty acids ( n-3 LCPUFA ) lower risk of coronary heart disease ( CHD ) , but mechanisms are not well understood . We used proteomics to identify human serum proteins that are altered by n-3 LCPUFA . Such proteins could identify pathways whereby they affect CHD . Eighty-one healthy volunteers entered a double blind r and omised trial to receive 3.5 g of fish oil or 3.5 g of high oleic sunflower oil daily . Serum was collected before and after 6 wk of intervention . Serum was analysed by proteomics using 2-DE . Proteins that were differentially regulated were identified by MS . We also analysed serum apolipoprotein A1 ( apo A1 ) , high-density lipoprotein ( HDL ) particle size and haptoglobin . Serum levels of apo A1 , apo L1 , zinc-alpha-2-glycoprotein , haptoglobin precursor , alpha-1-antitrypsin precursor , antithrombin III-like protein , serum amyloid P component and haemopexin were significantly downregulated ( all p<0.05 ) by fish oil compared with high oleic sunflower oil supplementation . Fish oil supplementation caused a significant shift towards the larger , more cholesterol-rich HDL(2 ) particle . The alterations in serum proteins and HDL size imply that fish oil activates anti-inflammatory and lipid modulating mechanisms believed to impede the early onset of CHD . These proteins are potential diagnostic biomarkers to assess the mechanisms whereby fish oil protects against CHD in humans OBJECTIVE The present study was carried out to determine effects of test meals of different fatty acid compositions on postpr and ial lipoprotein and apolipoprotein metabolism . DESIGN The study was a r and omized , single blind design . SETTING The study was carried out in the Clinical Investigation Unit of the Royal Surrey County Hospital . SUBJECTS Twelve male normal subjects with an average age of 22.4 + /- 1.4 years ( mean + /- SD ) were selected from the student population of the University of Surrey ; one subject dropped out of the study because he found the test meal unpalatable . INTERVENTIONS The subjects were given three evening test meals on three separate occasions , in which the oils used were either a mixed oil ( rich in saturated fatty acids and approximated the fatty acid intake of the current UK diet ) , corn oil ( rich in n-6 fatty acids ) , or fish oil ( rich in n-3 fatty acids ) 40 g of the oil under investigation were incorporated into a rice-based test meal . Triacylglycerol-rich lipoproteins-triacylglycerol ( TRL-TAG ) , TRL-cholesterol ( TRL-cholesterol ) , plasma-TAG , plasma cholesterol ( T-C ) , and serum apolipoprotein A-I and B ( apo A-I and B ) responses were measured . Postpr and ial responses were followed for 11 h. RESULTS Postpr and ial plasma-TAG responses , calculated as incremental areas under the response curves ( IAUC ) were significantly reduced following the fish oil meal [ 365.5 + /- 145.4 mmol/l x min ( mean + /- SD ) [ compared with the mixed oil meal ( 552.0 + /- 141.7 mmol/l x min ) ( P < 0.05 ) and there was a strong trend towards the same direction in the TRL-TAG responses . In all instances , plasma- and TRL-TAG showed a biphasic response with increased concentrations occurring at 1h and between 3 and 7h postpr and ially . TRL-cholesterol , T-C , and serum apo A-I and B responses to the three meals were similar . CONCLUSIONS The findings support the view that fish oils decrease postpr and ial lipaemia and this may be an important aspect of their beneficial effects in reducing risk of coronary heart disease ( CHD ) . Further work is required to determine the mechanisms responsible for this effect OBJECTIVES To determine whether , in individuals with hypercholesterolemia , substituting dietary soybean products for cows ' milk products improves the plasma lipid profile and whether any change in the profile is due partially to soy oil . DESIGN R and omized 3-treatment crossover trial . SETTING Family practice clinics and an outpatient clinic in London , Ont . PARTICIPANTS Seventeen healthy men and 17 healthy women with elevated plasma levels of total and low-density-lipoprotein ( LDL ) cholesterol and with normal plasma levels of triglycerides . INTERVENTIONS Participants incorporated into their normal diet either 2 % cows ' milk products , soybean products or a combination of skim milk products and soy oil , each over period of 4 weeks , with 22-week wash-out periods . Plasma lipid profile , blood pressure and body weight were assessed after each dietary and wash-out period . OUTCOME MEASURES Plasma levels of total and lipoprotein cholesterol , plasma levels of triglycerides , apolipoprotein B and A1 levels , blood pressure and plasma lipid peroxidation . RESULTS The change in diet had no effect on body mass index , levels of apolipoproteins B and A1 and most plasma lipids . During the soybean period , the subjects ' mean level of high-density-lipoprotein ( HDL ) cholesterol increased 9 % ( p < 0.04 ) and their mean LDL/HDL cholesterol ratio decreased 14 % ( p < 0.007 ) . These effects were less pronounced during the skim milk/soy oil period . In the 24 subjects with the highest initial LDL cholesterol level and LDL/HDL cholesterol ratio , the mean LDL cholesterol level decreased 11 % after the soybean period . In all subjects , changes in the LDL/HDL cholesterol ratio induced by a soybean diet were negatively correlated with the initial LDL/HDL cholesterol ratio and positively correlated with the initial HDL cholesterol level . CONCLUSIONS In people with hypercholesterolemia , the plasma lipid profile improved after treatment with a soybean-product diet , and this improvement was partially due to soy oil . The degree of responsiveness was associated with initial risk factors for coronary artery disease Objective : The risk of heart disease increases significantly in women after menopause mostly because of estrogen deficiency . Soy protein , a good source of isoflavones that are known to bind estrogen receptors , has also been promoted as a dietary means for reducing the risk of heart disease . The aim of this study was to examine the effects of soy protein consumption on heart disease risk in postmenopausal women . Methods : Moderately hypercholesterolemic postmenopausal women were r and omly assigned to consume soy or control foods daily for 1 year . Serum sample s were analyzed for total cholesterol , low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , triglycerides , apolipoprotein ( Apo ) A , and Apo B. Sixty-two women completed the study . Results : There was a trend for total cholesterol and high-density lipoprotein cholesterol levels to increase after 1 year of soy protein supplementation ( 230.04 ± 6.1 vs 242.57 ± 6.2 mg/dL , P < 0.1 , and 56.87 ± 2.5 vs 60.33 ± 2.5 mg/dL , P < 0.1 , respectively ) . There were no significant differences in low-density lipoprotein cholesterol or triglyceride levels ; however , a significant increase in Apo B levels ( 105.5 ± 5.9 vs 120.21 ± 5.9 mg/dL ; P = 0.002 ) and a significant decrease in Apo A levels ( 189.36 ± 10 vs 173.21 ± 10 mg/dL ; P = 0.009 ) were seen . Conclusions : Our data indicate that 1-year soy protein supplementation did not confer cardiovascular benefits , in terms of favorable alterations in the lipid profile , in this cohort of postmenopausal women . These findings , as well as those from other studies , lend credence to the decision of the Food and Drug Administration to reevaluate the soy protein health cl aim issued a decade ago Moderate alcohol consumption is associated with a reduced risk of coronary heart disease . Part of this inverse association may be explained by its effects on HDL . Paraoxonase , an HDL-associated enzyme , has been suggested to protect against LDL oxidation . We examined the effects of moderate consumption of red wine , beer and spirits in comparison with mineral water on paraoxonase activity in serum . In this diet-controlled , r and omised , cross-over study 11 healthy middle-aged men consumed each of the beverages with evening dinner for 3 weeks . At the end of each 3 week period , blood sample s were collected pre- and postpr and ially and after an overnight fast . Fasting paraoxonase activity was higher after intake of wine ( P<0 . 001 ) , beer ( P<0.001 ) , and spirits ( P<0.001 ) than after water consumption ( 149.4+/-111.1 , 152.6+/-113.1 , 152.8+/-116.5 and 143 . 1+/-107.9 U/l serum ) , but did not differ significantly between the 3 alcoholic beverages . Similar effects were observed pre- and postpr and ially . The increases in paraoxonase activity were strongly correlated with coincident increases in concentrations of HDL-C and apo A-I ( r=0.60 , P<0.05 and r=0.70 , P<0.05 ) . These data suggest that increased serum paraoxonase may be one of the biological mechanisms underlying the reduced coronary heart disease risk in moderate alcohol Objective : To assess the effect of a 4-week herring diet compared to a reference diet on biomarkers for cardiovascular disease in obese subjects . Design : R and omized crossover trial . Setting : Department of Internal Medicine , Sahlgrenska University Hospital . Subjects : Fifteen healthy obese men and women ( age 24–70 years ) included , 13 completed . Intervention : Subjects were r and omly assigned to four weeks of herring diet ( 150 g baked herring fillets/day 5 , days/week ) or reference diet ( pork and chicken fillets ) and switched diets after 2 weeks washout . P-total cholesterol , p-TAG , p-HDL , p-HDL2 , p-HDL3 , p-LDL , p-apolipoprotein A , p-apolipoprotein B , p-Lipoprotein ( a ) , p-fibrinogen , p-C- reactive protein and p-antioxidative capacity were analysed at 0,2,4,6,8 and 10 weeks . Results : P-HDL was significantly higher after the herring diet period compared to after the reference diet period ; 1.22 vs 1.13 mmol/l ( P=0.036 ) . There was a small , but not statistically significant , decrease in TAG but no effect on other biomarkers . TEAC and FRAP , but not ORAC-values , indicated that plasma antioxidants may have been reduced . CRP tended to be lower after the herring diet compared to after the reference diet . Conclusions : Consumption of oven-baked herring ( 150g/day , 5 days/week ) for 4 weeks , compared to consumption of pork and chicken fillets , significantly increased p-HDL . Patients with insulin resistance and obesity , who commonly have low HDL , may therefore benefit from addition of herring to the diet . Sponsorship : Region Västra Götal and , National board of fisheries ( Dr 223 - 2451 - 01 ) , Sweden ( EU structural funds ) , The Swedish Research Council for Environment , Agricultural Sciences and Spatial Planning ( FORMAS ) ( Grant No 2001 - 1246 ) BACKGROUND Inhibition of cholesteryl ester transfer protein ( CETP ) has been shown to have a substantial effect on plasma lipoprotein levels . We investigated whether torcetrapib , a potent CETP inhibitor , might reduce major cardiovascular events . The trial was terminated prematurely because of an increased risk of death and cardiac events in patients receiving torcetrapib . METHODS We conducted a r and omized , double-blind study involving 15,067 patients at high cardiovascular risk . The patients received either torcetrapib plus atorvastatin or atorvastatin alone . The primary outcome was the time to the first major cardiovascular event , which was defined as death from coronary heart disease , nonfatal myocardial infa rct ion , stroke , or hospitalization for unstable angina . RESULTS At 12 months in patients who received torcetrapib , there was an increase of 72.1 % in high-density lipoprotein cholesterol and a decrease of 24.9 % in low-density lipoprotein cholesterol , as compared with baseline ( P<0.001 for both comparisons ) , in addition to an increase of 5.4 mm Hg in systolic blood pressure , a decrease in serum potassium , and increases in serum sodium , bicarbonate , and aldosterone ( P<0.001 for all comparisons ) . There was also an increased risk of cardiovascular events ( hazard ratio , 1.25 ; 95 % confidence interval [ CI ] , 1.09 to 1.44 ; P=0.001 ) and death from any cause ( hazard ratio , 1.58 ; 95 % CI , 1.14 to 2.19 ; P=0.006 ) . Post hoc analyses showed an increased risk of death in patients treated with torcetrapib whose reduction in potassium or increase in bicarbonate was greater than the median change . CONCLUSIONS Torcetrapib therapy result ed in an increased risk of mortality and morbidity of unknown mechanism . Although there was evidence of an off-target effect of torcetrapib , we can not rule out adverse effects related to CETP inhibition . ( Clinical Trials.gov number , NCT00134264 [ Clinical Trials.gov ] . ) In addition to their usual diet , 17 lactovegetarian college students consumed 400 kcal of test foods per day containing one extra-large egg for three weeks and similar isocaloric eggless foods for an additional three weeks in a r and omised double-blind crossover trial . Ingestion of the egg increased dietary cholesterol from 97 to 418 mg per day . Mean plasma low density lipoprotein ( LDL ) cholesterol was 12 % higher ( p = 0.005 ) and mean plasma apolipoprotein B was 9 % higher ( p = 0.007 ) when eggs were being consumed than during the eggless period . Mean plasma high density lipoprotein cholesterol , apolipoproteins A-I and A-II , very low density lipoprotein cholesterol , and total triglycerides did not change significantly . Thus , ingestion of egg seems selectively to raise cholesterol and protein in LDL particles in the plasma of free-living normal people . Plasma LDL may be more sensitive to cholesterol at low intakes than at moderate to high intakes A r and omized controlled trial was conducted to examine the effects of coffee ( as commonly drunk in Britain ) on blood pressure and plasma lipids in healthy subjects . Fifty-four subjects followed three regimens successively , the order being r and omized according to a Latin square design : five or more cups of coffee daily for 4 weeks ; five or more cups of decaffeinated coffee daily for 4 weeks but no ordinary coffee ; no coffee for 4 weeks . Coffee appeared to cause a small rise ( of 3 mm Hg ) in recumbent systolic blood pressure ; this effect was less than , and obscured by , changes induced by posture and mild stress . No consistent changes attributable to coffee were found in diastolic blood pressure or pulse rate . Small changes in the expected directions occurred in plasma high density lipoprotein ( HDL ) cholesterol and apolipoprotein AI ( decrease ) , and in total cholesterol , non-HDL cholesterol and apolipoprotein B ( increase ) , but none of these were statistically significant . The effect of coffee on risk of heart disease in Britain is probably small Objective : Cardiovascular disease ( CVD ) is the major morbidity and cause of death in diabetic subjects . Observational studies have shown the association of low vitamin D status with poor glycemic control , atherogenic lipid profile , and CVD . However , the possible link between circulating 25-hydroxycholecalciferol and apoproteins ( Apo A1 and B ) and the atherogenic lipoprotein ( a ) [ Lp(a ) ] has not been documented to date . Methods : Ninety subjects with type 2 diabetes ( T2D ) aged 30–60 years from both sexes were r and omly allocated to one of the 3 groups to receive 2 bottles a day of either ( 1 ) plain doogh ( PD ; containing 150 mg calcium and no detectable vitamin D/250 mL ) ; ( 2 ) vitamin D – fortified doogh ( DD ; containing 150 mg calcium and 500 IU vitamin D/250 mL ) ; or ( 3 ) calcium- and vitamin D – fortified doogh ( CDD ; containing 250 mg calcium and 500 IU vitamin D/250 mL ) for 12 weeks . Anthropometric , dietary , and laboratory assessment s , including Apo A1 , Apo B , and Lp(a ) , were done . Results : Improvement of vitamin D status in DD and CDD groups , compared to PD , result ed in a significant increase in Apo A1 ( mean changes 0.22 ± 0.38 , 0.20 ± 0.27 and 0.01 ± 0.35 g/L , respectively , p = 0.047 ) and a significant decrease in serum Lp(a ) ( mean changes −0.08 ± 0.30 , −0.08 ± 0.31 , and 0.14 ± 0.25 μmol/L , respectively , p = 0.011 ) . There was no significant difference between DD and CDD groups . Serum Apo B did not change significantly in any of the groups . Conclusions : Significant amelioration of serum Apo A1 and Lp(a ) following improvement of vitamin D status in T2D subjects may have preventive implication s against long-term diabetic complications , notably CVD . This trial was registered at Clinical Trials.gov as NTC01229891 The unique composition of green kiwifruit has the potential to benefit CVD risk . The aim of the present study was to investigate the effect of consuming two green kiwifruits daily in conjunction with a healthy diet on plasma lipids and other metabolic markers and to examine response according to APOE genotype in hypercholesterolaemic men . After undergoing a 4-week healthy diet , eighty-five hypercholesterolaemic men ( LDL-cholesterol ( LDL-C ) > 3.0 mmol/l and TAG < 3 mmol/l ) completed an 8-week r and omised controlled cross-over study of two 4-week intervention sequences of two green kiwifruits per d plus healthy diet ( intervention ) or healthy diet alone ( control ) . Anthropometric measures , blood pressure ( BP ) and fasting blood sample s ( plasma lipids , serum apoA1 and apoB , insulin , glucose , high-sensitivity C-reactive protein ( hs-CRP ) ) were taken at baseline , and at 4 and 8 weeks . After the kiwifruit intervention , plasma HDL-cholesterol ( HDL-C ) concentrations were significantly higher ( mean difference 0.04 ; 95 % CI 0.01 , 0.07 mmol/l ; P = 0.004 ) and the total cholesterol (TC):HDL-C ratio was significantly lower ( mean difference 20.5 ; 95 % CI 20.24 , 20.05 mmol/l ; P = 0.002 ) compared with the control . In carriers of the APOE4 allele , TAG decreased significantly ( mean difference -0.18 ; 95 % CI -0.34 , -0.02 mol/l ; P = 0.03 ) with kiwifruit compared with control . There were no significant differences between the two interventions for plasma TC , LDL-C , insulin , glucose , hs-CRP and BP . The small but significant increase in HDL-C and decrease in TC : HDL-C ratio and TAG ( in APOE4 carriers ) suggest that the regular inclusion of green kiwifruit as part of a healthy diet may be beneficial in improving the lipid profiles of men with high cholesterol The effects of dried garlic on blood lipids , apolipoproteins and blood coagulation parameters in hyperlipemic patients were studies in two controlled , r and omized , double-blind studies . Both studies comprised placebo and therapy periods of 6 weeks each . The doses administered were 3 X 198 mg in Study I ( 34 patients ) and 3 X 450 mg in Study II ( 51 patients ) . In both studies , the following serum parameters were measured every 3 weeks : total cholesterol , HDL ( high density lipoprotein)- and LDL ( low density lipoprotein)-cholesterol , triglycerides and several safety parameters . In addition , apolipoproteins A and B , euglobulin lysis time , fibrin split products , prothrombin time , whole blood coagulation time and fibrinogen levels were determined in the second study only . The results indicated that neither dosage of dried garlic showed any significant effect on any of the parameters measured . It is therefore concluded that , if there is any effect of garlic on the parameters measured , it is not apparent when using a dried preparation in the dosage studied A higher excretion of dry matter , fat , nitrogen , energy , and total bile acids in ileal effluents ; a lower plasma low-density-lipoprotein ( LDL ) and total cholesterols ( 12.1 % and 9.0 % lower respectively ) ; but no change in plasma high-density-lipoprotein ( HDL ) cholesterol or apolipoproteins A-I and B were observed in nine subjects with ileostomies when they consumed an oat-bran , bread-based , high-fiber diet ( HFD ) as compared with a wheat-flour , bread-based , low-fiber diet ( LFD ) for 3 wk with a crossover design . Of the nine subjects only the subjects with a low daily excretion of bile acids had an elevated excretion of total bile acids during the HFD compared with the LFD . Total cholesterol , LDL cholesterol , and apolipoprotein B in plasma also decreased by 11.3 % , 15.3 % , and 10.7 % , respectively , after consumption of the HFD for 3 wk The effects of boiled coffee , filtered coffee , and tea on serum lipoprotein lipids and apoproteins were compared in 42 middle-aged hypercholesterolemic subjects ( 21 men and 21 women ) . The subjects consumed the beverages , eight cups a day , in r and om order during successive 4-week periods with 2-week run-in intervals in a crossover design . The diet was kept unchanged . Statistically significant differences were found between the periods in serum total cholesterol ( P less than .0001 ANOVA ) , LDL cholesterol ( P less than .01 ) , and apoprotein B ( P less than .01 ) levels . All differences were due to significantly higher levels during boiled coffee as compared with filtered coffee and tea . No statistically significant differences were found between the filtered coffee and tea periods . There were no differences in serum VLDL cholesterol or triglyceride , HDL cholesterol , and apoprotein A-I concentrations between the periods . Consumption of boiled coffee thus increased the concentration of low density lipoprotein in the serum without affecting its lipid-protein composition . The effect seemed to be determined by the method of brewing BACKGROUND AND AIMS Plant sterols are naturally occurring cholesterol-lowering compounds which are industrially incorporated in various foods . A novel food carrier is rye bread , the intake of which can be monitored in trials utilizing newly defined plasma biomarkers . Our aim was to determine the effects of plant sterols incorporated into high-fiber rye bread on serum total and LDL cholesterol , apoB/apoA1 and total cholesterol/HDL cholesterol ratios and lipophilic (pro)vitamins in healthy free-living normocholesterolemic individuals . METHODS AND RESULTS In this double-blind , dietary intervention trial the subjects ( n=68 ) were r and omized to receive a rye bread ( 9.3g/d fiber ) with added plant sterols ( 2g/d ) ( active ) or without ( control ) . In the second phase of the study the amount of rye bread was doubled providing 18.6g/d fiber and in the active group 4g/d plant sterols . Compliance was monitored utilizing 3-day food diaries and a novel rye fiber-derived biomarker in plasma . Intake of rye bread enriched with 2g/d of plant sterols during two weeks reduced significantly serum total and LDL cholesterol , apoB/apoA1 and total cholesterol/HDL cholesterol ratios by 5.1 % , 8.1 % , 8.3 % and 7.2 % , respectively , compared to controls . Correspondingly , the following two-week treatment with 4g/d of plant sterols result ed in 6.5 % , 10.4 % , 5.5 % and 3.7 % difference compared to controls , being most pronounced for LDL ( 0.33 mmol/L ) . The treatments did not affect lipophilic (pro)vitamin levels . CONCLUSION Rye bread enriched with 2 - 4g/d of nonesterified plant sterols beneficially modifies cardiovascular lipid risk factors in normocholesterolemic subjects compared to controls Beta-carotene in doses of up to 300 mg daily raises high-density lipoprotein cholesterol levels within 2 to 4 weeks in healthy subjects . The authors , in this study , investigate the short-term effects of high-dose beta-carotene upon serum lipids , lipoproteins , and selected sex steroid hormones in 59 adult patients with Type IIa or IIb hyperlipidemia and 36 healthy subjects . Volunteers took beta-carotene ( 300 mg ) or wheat germ oil capsules daily for 30 days . Lipids were measured on days 1 , 14 , 21 , and 30 . Betacarotene , retinol , free and total testosterone , and estradiol levels were measured on days 1 and 30 . Total high-density lipoprotein cholesterol levels increased 10 % ( p < 0.01 ) over baseline in all groups by day 14 but returned to baseline by day 30 . Total cholesterol , low-density lipoprotein cholesterol , and triglyceride levels transiently increased between days 14 and 21 by up to 9 % , 8 % , and 20 % , respectively , only in the patients with hyperlipidemia treated with beta-carotene , but returned to baseline on day 30 . Apolipoproteins A and B were unchanged . Despite 20-fold increases of plasma beta-carotene levels there , were no reports of carotenodermia and no alteration in sex steroid hormones , retinol levels , hepatic transaminases , or persistent changes in serum lipids that were attributable to beta-carotene In a double-blind , placebo-controlled study , thirty-three subjects were allocated to undergo either a 4-week treatment with oral Mg supplementation ( Mg(OH)2 ; 411 - 548 mg Mg/d ) or a placebo . The urinary excretion of Mg increased significantly in both the first 2 weeks and the following 2 weeks of Mg supplementation , while the urinary Na excretion also increased significantly over the experimental period . The systolic and diastolic blood pressure values decreased significantly in the Mg group , but not in the placebo group . The urinary aldosterone excretion and packed cell volume increased significantly during the last 2 weeks of the experimental period compared with the run-in period and first 2 weeks of supplementation . There was a statistically significant positive correlation between the values for urinary noradrenaline excretion and diastolic blood pressure at the end of the supplementation period ( both expressed as a percentage of the run-in value ) . Statistically significant increases in lecithin-cholesterol acyltransferase ( EC 2.3.1.43 ; LCAT ) , HDL-cholesterol and apolipoprotein AI were also observed after Mg supplementation . A significant positive correlation was observed between the levels of LCAT and urinary Mg excretion for the experimental period ( expressed as a percentage of the run-in value ) . The total cholesterol : HDL-cholesterol ratio decreased significantly during the last 2 weeks of Mg supplementation compared with the first 2 weeks and the run-in periods , but this did not occur in the placebo group . These results suggest that Mg supplementation may lower blood pressure through the suppression of the adrenergic activity and possible natriuresis , while also improving the serum lipids through the activation of LCAT in human subjects AIMS to assess the hypocholesterolaemic effect of adding 50 g of oatbran to the diet of hypercholesterolaemic subjects already prescribed a diet with less than 30 % of energy from fat . METHODS twenty-nine volunteers aged 21 - 67 years with total serum cholesterol levels 5.59 - 8.5 mmol/L prescribed a diet containing less than 30 % of energy intake as fat , and with a body mass index between 19.8 and 29.3 , were enrolled in a crossover study to assess the effect of the addition to the diet of 50 g daily of oatbran . After six weeks of an oat-free control diet , subjects were r and omised to eat 50 g daily of oatbran or to continue on the oat-free diet . Six weeks later the subjects crossed to the alternative diet for a further six week period . Lipid levels were assessed in weeks five and six of each study period . RESULTS twenty-four subjects completed the study consuming 51.7 ( SD 15.5 ) g of oatbran daily during the treatment phase . No significant difference was seen between the oatbran and control diet periods in body mass index , energy or fat intake , or in total cholesterol , LDL and HDL fractions , apolipoprotein A1 and B levels , or triglyceride levels . Considerable variation was observed between the paired lipid results . CONCLUSIONS ingestion of 50 g of oatbran daily by hypercholesterolaemic subjects on a low fat diet showed no influence on serum lipid levels . The importance of using at least duplicate sample s in assessing changes in lipid values is emphasised The influence of dietary supplementation with n-3 versus n-6 fatty acids on plasma lipoprotein(a ) ( Lp[a ] ) levels was studied . Thirty-five male hospitalized patients with coronary artery disease were treated for 4 weeks with 12 g/day of fish oil ( approximately 8.5 g of n-3 fatty acids ) in combination with a 5,000 kilojoule , 30 % fat diet and moderate exercise . Eighteen control patients given the same dietary and training program were treated with 12 g/day of rapeseed oil . Plasma Lp(a ) , in addition to several lipids and lipoproteins , blood clotting factors , and platelet reactivity , were measured before and at the end of therapy . Results can be summarized as follows : total cholesterol , low-density lipoprotein cholesterol , and apolipoprotein B levels decreased significantly in both the rapeseed oil ( -14.4 % , -20.3 % , -15.2 % , respectively ) and fish oil ( -12.2 % , -16.0 % , and -14.2 % , respectively ) groups . Triglycerides decreased ( -20.3 % ) and high-density lipoprotein cholesterol increased ( + 8.3 % ) significantly only in patients treated with fish oil . Plasma Lp(a ) levels were reduced by 14 % in the fish oil group , but unaffected in the rapeseed oil group . Patients treated with fish oil could be categorized into 2 subgroups : " responders , " with a reduction in Lp(a ) by 24 % and " nonresponders , " with a small nonsignificant increase in serum Lp(a ) . Responders and nonresponders exhibited a marked reduction in cholesterol , low-density lipoprotein cholesterol , apolipoprotein B , and triglycerides , and an increase in high-density lipoprotein3 cholesterol . There was a large reduction in tissue plasminogen activator in the fish oil group , which correlated significantly with reduction in Lp(a ) . ( ABSTRACT TRUNCATED AT 250 WORDS The effects of boiled coffee ( BC ) and filtered coffee ( FC ) on serum lipoproteins were compared in 41 healthy subjects whose serum cholesterol concentration was less than 7 mmol/l . The subjects consumed in r and om order BC and FC for 4-week periods in a crossover design . The individual daily consumption ranged from 2 to 14 cups ( mean 5.7 cups per day ) and was similar during both study periods . The serum total and LDL-cholesterol and apoprotein B concentrations were higher ( P less than 0.001 ) and HDL-cholesterol lower ( P less than 0.05 ) after BC than after FC . Bodyweight , apoprotein A-I and triglycerides remained unchanged . In the 16 subjects who consumed coffee less than 5 cups per day the difference in serum total cholesterol between the BC and FC periods was non-significant ( P = 0.16 ) . The differences in serum total cholesterol and LDL-cholesterol between the periods showed significant linear correlations with the amount of coffee consumed daily ( r = 0.52 , P less than 0.001 and r = 0.33 , P less than 0.05 , respectively ) but no association was found between the difference in HDL-cholesterol and the amount of coffee ( r = 0.14 , P = 0.39 ) . The results indicate a dose-dependent increasing effect on serum total and LDL-cholesterol and apoprotein B concentrations of boiled coffee The effects of beta-glucan-rich oat bran on serum lipids and lipoproteins were examined in a r and omized 8-week study . After a 4-week run-in phase , subjects with mild to moderate hypercholesterolemia [ serum total cholesterol ( TC ) 5.5 - 8.5 mmol/l ] on cholesterol-lowering diets were r and omly allocated to an oat bran ( 10.3 g beta-glucan/day ) or wheat bran group . Thirty-six subjects ( 20 in the oat bran group , 16 in the wheat bran group ) completed the study . The diet was identical in both groups during the trial and no significant changes in body weight were found . Serum TC and low-density lipoprotein cholesterol ( LDL-C ) significantly declined in the oat bran group during the first 4 weeks from 7.03 + /- 0.81 to 6.72 + /- 0.97 ( p = 0.028 ) and from 4.90 + /- 0.69 to 4.61 + /- 0.89 mmol/l ( p = 0.038 ) , respectively , but at 8 weeks the values were not significantly different from baseline . Changes in serum TC were mainly confined to those who ate at least two-thirds of the planned daily dose of oat bran . In wheat bran group no changes were observed in serum TC or LDL-C levels . Apolipoprotein A1 and B did not change significantly in either group . Only subjects with apolipoprotein E 3/3 phenotype ( n = 12 ) had hypocholesterolemic response to oat bran at 4 weeks , but no change was found in those with apolipoprotein E 4/4 or 4/3 ( n = 7 ) . ( ABSTRACT TRUNCATED AT 250 WORDS CONTEXT Interest remains high in cholesteryl ester transfer protein ( CETP ) inhibitors as cardioprotective agents . Few studies have documented the efficacy and safety of CETP inhibitors in combination with commonly used statins . OBJECTIVE To examine the biochemical effects , safety , and tolerability of evacetrapib , as monotherapy and in combination with statins , in patients with dyslipidemia . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial conducted among 398 patients with elevated low-density lipoprotein cholesterol ( LDL-C ) or low high-density lipoprotein cholesterol ( HDL-C ) levels from April 2010 to January 2011 at community and academic centers in the United States and Europe . INTERVENTIONS Following dietary lead-in , patients were r and omly assigned to receive placebo ( n = 38 ) ; evacetrapib monotherapy , 30 mg/d ( n = 40 ) , 100 mg/d ( n = 39 ) , or 500 mg/d ( n = 42 ) ; or statin therapy ( n = 239 ) ( simvastatin , 40 mg/d ; atorvastatin , 20 mg/d ; or rosuvastatin , 10 mg/d ) with or without evacetrapib , 100 mg/d , for 12 weeks . MAIN OUTCOME MEASURES The co- primary end points were percentage changes from baseline in HDL-C and LDL-C after 12 weeks of treatment . RESULTS The mean baseline HDL-C level was 55.1 ( SD , 15.3 ) mg/dL and the mean baseline LDL-C level was 144.3 ( SD , 26.6 ) mg/dL. As monotherapy , evacetrapib produced dose-dependent increases in HDL-C of 30.0 to 66.0 mg/dL ( 53.6 % to 128.8 % ) compared with a decrease with placebo of -0.7 mg/dL ( -3.0 % ; P < .001 for all compared with placebo ) and decreases in LDL-C of -20.5 to -51.4 mg/dL ( -13.6 % to -35.9 % ) compared with an increase with placebo of 7.2 mg/dL ( 3.9 % ; P < .001 for all compared with placebo ) . In combination with statin therapy , evacetrapib , 100 mg/d , produced increases in HDL-C of 42.1 to 50.5 mg/dL ( 78.5 % to 88.5 % ; P < .001 for all compared with statin monotherapy ) and decreases in LDL-C of -67.1 to -75.8 mg/dL ( -11.2 % to -13.9 % ; P < .001 for all compared with statin monotherapy ) . Compared with evacetrapib monotherapy , the combination of statins and evacetrapib result ed in greater reductions in LDL-C ( P < .001 ) but no greater increase in HDL-C ( P = .39 ) . Although the study was underpowered , no adverse effects were observed . CONCLUSIONS Compared with placebo or statin monotherapy , evacetrapib as monotherapy or in combination with statins increased HDL-C levels and decreased LDL-C levels . The effects on cardiovascular outcomes require further investigation . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01105975 Twenty-one mildly hypercholesterolemic men consumed a diet that was low in fat ( < 30 % of energy ) and cholesterol ( 300 mg/d ) and were given muffins containing 25 g protein + 20 g dietary fiber daily from either isolated soybean protein + soybean cotyledon fiber , isolated soybean protein + cellulose , casein + soybean cotyledon fiber or casein + cellulose . All subjects progressed through the low fat , low cholesterol baseline period , lasting 2 wk , and then through all four dietary treatments , lasting 4 wk each , according to a Latin square design . Plasma concentrations of total , LDL , HDL and VLDL cholesterol , total and VLDL triacylglycerols , and apolipoprotein A-I and B were measured at the end of each period . When data from all subjects were analyzed , dietary treatments did not influence lipemia ; however , in subjects with initial total cholesterol concentrations > 5.7 mmol/L , both isolated soybean protein treatments result ed in significantly lower total cholesterol compared with the two casein treatments ( P < 0.05 ) . In addition , a negative linear relationship was observed when a subject 's total or LDL cholesterol change after each of the soybean treatments was regressed against the subject 's baseline cholesterol concentration ( P < 0.05 ) . Apolipoprotein A-I varied dependent on baseline cholesterol with no apparent pattern , whereas apolipoprotein B levels were not affected . Results indicate that consumption of 25 g soybean protein/d is associated with lower total cholesterol concentrations in individuals with initial cholesterol concentrations > 5.7 Background Intake of fish and long-chain n-3 fatty acids has been of wide interest due to their beneficial effects on cardiovascular risk factors and lower coronary heart disease ( CHD ) risk . Aim of the study The aim of this pilot study was to examine the effects of fatty fish and lean ( white ) fish on fatty acid composition of serum lipids and cardiovascular risk factors in subjects with CHD using multiple drugs for this condition . Methods The study was an 8-week controlled , parallel intervention . Inclusion criteria were myocardial infa rct ion or unstable ischemic attack , age under 70 years , use of betablockers and presence of sinus rhythm . The subjects were r and omized to one of the following groups : 4 meals/week fatty fish ( n = 11 ) , 4 meals/week lean fish ( n = 12 ) and control diet including lean meat ( n = 10 ) . Results The mean ( ±SD ) of reported fish meals per week was 4.3 ± 0.4 , 4.7 ± 1.1 and 0.6 ± 0.4 in the groups , respectively . The proportions of eicosapentaenoic and docosahexaenoic acids in serum lipids increased in the fatty fish group only ( P < 0.05 ) . Systolic and diastolic blood pressure levels decreased in the lean fish group ( 0 vs. 8 week : 3.5 ± 3.2 and 4.6 ± 3.6 % , respectively , P < 0.05 ) . Serum total triglyceride concentration did not significantly change . HDL cholesterol concentration change differed among groups but without significant post hoc differences . Apolipoprotein A-1 concentration decreased in the control group ( 0 vs. 8 week , P < 0.05 ) . Coagulation factors , 25-hydroxy vitamin D , and heart rate variability ( 24 h Holter ) did not change among the groups . Conclusions Our results suggest that intake of lean fish at least four times per week could reduce blood pressure levels in CHD patients Our aim was to test the hypocholesterolemic effect of a low-dose formulation of soy proteins supplemented with isolated b-sitosterol in a ratio of 4:1 in 20 moderately hypercholesterolemic subjects . The study has been divided in three different periods of forty days each : a stabilization diet period , then a treatment period during which all subjects assumed 10 g one time a day of the tested product and , finally , a wash out period . From the end of the stabilization diet period to the end of the soy protein added in b-sitosterol supplementation we observed a 0.45 + /- 0.30 mmol/L , 0.09 + /- 0.31 mmol/L and 0.17 + /- 0.22 mmol/L mean + /- SE decrease in respectively LDL-C , TG and apoB levels , associated with a 0.12 + /- 0.25 and 0.03 + /- 0.51 mg/dL mean increase respectively in HDL-C and apoA plasma concentrations . According to this recommends , low doses of soy protein added in b-sitosterol seems to be a practical and safe alternative for patients seeking modest reductions in LDL-C ( < 15 % ) Objective — In this r and omized double-blind placebo-controlled cross-over study the effects of spreads enriched with plant sterols were determined on serum lipids , lipoprotein and apolipoprotein concentrations in a Belgian population . Methods — Fourty-two healthy adult volunteers ( 22 men and 20 women ) with an average age of 55 ( SD 9 ) years and with serum total cholesterol concentrations below 300 mg/dl , consumed during two consecutive periods of 4 weeks two different low-fat spreads . Both the plant sterol rich and control spreads contained 35 % of fat and had an almost equal fat composition . The sterol content of the enriched spread was 8.3 % . Intake of the spreads was 25 g/day . Results — Serum total and LDL-cholesterol concentrations lowered by 7 % ( 18 mg/dl ) and 10 % ( 16 mg/dl ) , respectively , with the plant sterol-enriched compared to the control spread . Serum HDLcholesterol concentration did not significantly differ between the two spreads . Apolipoprotein B concentrations lowered by 8 % ( 0.08 g/l ) with the plant sterol-enriched spread , while concentrations of apolipoprotein A-I did not change . Conclusion — These findings indicate that a daily intake of 25 gram low-fat spread containing 2 gram plant sterol per day is effective in lowering blood total and LDL cholesterol , and apolipoprotein B concentrations . This lowering may help to reduce the risk of heart disease in the population Moderate alcohol consumption increases HDL cholesterol , which is involved in reverse cholesterol transport ( RCT ) . The aim of this study was to investigate the effect of moderate alcohol consumption on cholesterol efflux , using J774 mouse macrophages and Fu5AH cells , and on other parameters in the RCT pathway . Twenty-three healthy men ( 45–65 years ) participated in a r and omized , partially diet-controlled , crossover trial . They consumed four glasses of whisky ( 40 g of alcohol ) or water daily for 17 days . After 17 days of whisky consumption , serum capacity to induce ABCA1-dependent cholesterol efflux from J774 mouse macrophages was increased by 17.5 % ( P = 0.027 ) compared with water consumption . Plasma capacity to induce cholesterol efflux from Fu5AH cells increased by 4.6 % ( P = 0.002 ) . Preβ-HDL , apolipoprotein A-I ( apoA-I ) , and lipoprotein A-I : A-II also increased by 31.6 , 6.2 , and 5.7 % ( P < 0.05 ) , respectively , after whisky consumption compared with water consumption . Changes of cAMP-stimulated cholesterol efflux correlated ( r = 0.65 , P < 0.05 ) with changes of apoA-I but not with changes of preβ-HDL ( r = 0.30 , P = 0.18 ) . Cholesterol efflux capacities from serum of lean men were higher than those from overweight men . In conclusion , this study shows that moderate alcohol consumption increases the capacity of serum to induce cholesterol efflux from J774 mouse macrophages , which may be mediated by ABCA1 OBJECTIVES The aim of this study was to determine the relationship between atheroma regression and arterial wall remodeling . BACKGROUND Infusion of reconstituted high-density lipoprotein ( rHDL ) containing recombinant apolipoprotein A-I Milano ( AIM ) has been reported to promote rapid regression of coronary atherosclerosis . The current study analyzed intravascular ultrasound ( IVUS ) to define the changes that take place in the arterial wall that accompanied atheroma regression in this study . METHODS Forty-seven patients , ages 30 to 75 years , after an acute coronary syndrome were r and omized to receive five weekly infusions of placebo or rHDL containing either low- or high-dose AIM . External elastic membrane ( EEM ) and lumen volumes were compared between coronary IVUS studies at baseline and follow-up . RESULTS In comparison with baseline , infusion of rHDL was associated with a 4.6 % reduction in EEM volume . Lumen volume did not change . In 10-mm arterial subsegments with the greatest plaque burden at baseline , atheroma volume regressed by 10.9 % with a similar reduction in EEM volume but with no change in lumen size . In contrast , EEM and atheroma volume did not change in the 10-mm segments containing the least plaque burden . The reduction in EEM in the most diseased segments was only apparent in subjects who underwent plaque regression . Reduction in EEM volume correlated with the decreased atheroma volume ( r = 0.62 ) , but there was no correlation between change in lumen size and change in plaque volume . CONCLUSIONS Remodeling of the arterial wall is a focal and heterogeneous process . After infusion of rHDL containing AIM , regression of coronary atherosclerosis is accompanied by reverse remodeling of the EEM , result ing in no change in luminal dimensions Consumption of soy protein may reduce the risk of cardiovascular disease both through reduction in serum lipids and by the antioxidant properties of protein-associated soy isoflavones . However , the effect that processing required for the manufacture of breakfast cereals may have on the lipid lowering and antioxidant activities of soy has not been studied . We have therefore assessed the health benefits of soy incorporation into breakfast cereals . Twenty-five hyperlipidemic men and women took soy ( providing 36 g/d soy protein and 168 mg/d isoflavones ) and control breakfast cereals , each for 3 weeks in a r and omized crossover study with a 2-week washout period between treatments . Fasting blood sample s were obtained pretreatment and at weeks 2 and 3 of each treatment . No significant difference was seen in serum lipids between treatments at week 3 apart from a 3.8 % + /- 1.5 % higher apolipoprotein A-1 level on control versus soy ( P = .021 ) . However , oxidized low-density lipoprotein ( LDL ) was reduced on the test compared with the control both as total dienes in LDL and as the ratio of conjugated dienes to cholesterol in the LDL fraction by 9.2 % + /- 4.3 % ( P = .042 ) and 8.7 % + /- 4.2 % ( P = .050 ) , respectively . High isoflavone intakes in soy breakfast cereals may decrease the risk of cardiovascular disease by reducing oxidized LDL , while having no significant effect on the absolute concentration of LDL cholesterol Low plasma concentrations of high-density lipoprotein ( HDL ) are associated with increased risk of coronary heart disease . Several drugs that induce the microsomal cytochrome P-450-dependent enzyme system in liver and intestine , the sites of HDL apolipoprotein ( apo ) A-I and A-II synthesis , raise plasma HDL concentrations in humans . To test the hypothesis that phytochemicals with cytochrome P-450-inducing activity may also increase plasma HDL concentrations , two controlled dietary trials were undertaken in healthy nonsmoking males aged 20 - 28 y. One study examined the effect of replacing 300 g glucosinolate-free vegetables with 300 g Brussels sprouts/d for 3 wk . The other study examined the effects of 150 mg eugenol/d in capsule form , using a double-blind , placebo-controlled crossover design . There were no significant increases in plasma apo A-I , apo A-II , HDL cholesterol , or HDL phospholipids . These results suggest that dietary phytochemicals that induce members of the cytochrome P-450 system do not necessarily raise plasma HDL concentrations in humans , but do not exclude the possibility that some phytochemicals may have such an effect Background / Objectives : Diets high in nuts reduce cholesterol , probably due to their favorable lipid profile and other bioactive substances . However , the physical form of the nut may be important as the cell wall of intact nuts may limit the hypocholesterolemic effect of nuts by reducing lipid bioavailability . Therefore , we investigated the effects on blood lipids of incorporating three different forms of hazelnuts ( ground , sliced and whole ) into the usual diet . Subjects/ Methods : In a r and omized crossover study with three phases , 48 mildly hypercholesterolemic participants were asked to consume 30 g of ground , sliced or whole hazelnuts for 4 weeks . Body weight , plasma total cholesterol ( TC ) , low-density lipoprotein cholesterol ( LDL-C ) , high-density lipoprotein cholesterol ( HDL-C ) , triacylglycerol ( TAG ) , apolipoprotein ( apo ) A1 , apo B100 and α-tocopherol were measured at baseline and at the end of each dietary phase . Results : There were no significant differences in any outcome variable between the different forms of nuts ( all P⩾0.159 ) . However , compared with baseline , mean values at the end of each hazelnut intervention were significantly higher for HDL-C ( P=0.023 ) and α-tocopherol ( P=0.005 ) , and significantly lower for TC ( P<0.001 ) , LDL-C ( P<0.001 ) , TC : HDL-C ratio ( P<0.001 ) , apo B100 ( P=0.002 ) and apo B100:apo A1 ratio ( P<0.001 ) , with no significant difference in body weight ( P=0.813 ) . Conclusions : The ingestion of three different forms of hazelnuts equally improved the lipoprotein profile and α-tocopherol concentrations in mildly hypercholesterolemic individuals . Hazelnuts can therefore be incorporated into the usual diet as a means of reducing cardiovascular disease risk BACKGROUND Patients with homozygous familial hypercholesterolemia ( HoFH ) are at extremely elevated risk for early cardiovascular disease because of exposure to elevated low-density lipoprotein cholesterol ( LDL-C ) plasma levels from birth . Lowering LDL-C by statin therapy is the cornerstone for cardiovascular disease prevention , but the residual risk in HoFH remains high , emphasizing the need for additional therapies . In the present study , we evaluated the effect of serial infusions with CER-001 , a recombinant human apolipoprotein A-I (apoA-I)-containing high-density lipoprotein-mimetic particle , on carotid artery wall dimensions in patients with HoFH . METHODS AND RESULTS Twenty-three patients ( mean age 39.4 ± 13.5 years , mean LDL-C 214.2 ± 81.5 mg/dL ) with genetically confirmed homozygosity or compound heterozygosity for LDLR , APOB , PCSK9 , or LDLRAP1 mutations received 12 biweekly infusions with CER-001 ( 8 mg/kg ) . Before and 1 hour after the first infusion , lipid values were measured . Magnetic resonance imaging ( 3-T magnetic resonance imaging ) scans of the carotid arteries were acquired at baseline and after 24 weeks to assess changes in artery wall dimensions . After CER-001 infusion , apoA-I increased from 114.8 ± 20.7 mg/dL to 129.3 ± 23.0 mg/dL. After 24 weeks , mean vessel wall area ( primary end point ) decreased from 17.23 to 16.75 mm(2 ) ( P = .008 ) . A trend toward reduction of mean vessel wall thickness was observed ( 0.75 mm at baseline and 0.74 mm at follow-up , P = .0835 ) . CONCLUSIONS In HoFH , 12 biweekly infusions with an apoA-I-containing high-density lipoprotein-mimetic particle result ed in a significant reduction in carotid mean vessel wall area , implying that CER-001 may reverse atherogenic changes in the arterial wall on top of maximal low-density lipoprotein-lowering therapy . This finding supports further clinical evaluation of apoA-I-containing particles in patients with HoFH OBJECTIVES The aim of this study was to determine whether a novel small molecule RVX-208 affects apolipoprotein (apo)A-I and high-density lipoprotein cholesterol ( HDL-C ) levels in vitro and in vivo . BACKGROUND Increased apoA-I and HDL-C levels are potential therapeutic targets for reducing atherosclerotic disease . METHODS HepG2 cells were treated with 0 to 60 mumol/l RVX-208 followed by assays for apoA-I and HDL-C production . For in vivo studies , African green monkeys ( AGMs ) received 15 to 60 mg/kg/day RVX-208 , and the serum was analyzed for lipoprotein levels , HDL-subparticle distribution , cholesterol efflux , and activity of lipid-modifying enzymes . A phase I clinical trial was conducted in healthy volunteers ( given 1 to 20 mg/kg/day of RVX-208 ) to assess safety , tolerability , and pharmacokinetics . RESULTS The RVX-208 induced apoA-I messenger ribonucleic acid and protein synthesis in HepG2 cells , leading to increased levels of pre-beta-migrating and alpha-lipoprotein particles containing apoA-I ( LpA-I ) in spent media . Similarly , in AGMs , RVX-208 treatment for 63 days increased serum apoA-I and HDL-C levels ( 60 % and 97 % , respectively ) . In addition , the levels of pre-beta(1)-LpA-I and alpha1-LpA-I HDL-subparticles were increased as well as adenosine triphosphate binding cassette AI , adenosine triphosphate binding cassette G1 , and scavenger receptor class B type I-dependent cholesterol efflux . These changes were not mediated by cholesteryl-ester-transfer protein . Treatment of humans for 1 week with oral RVX-208 increased apoA-I , pre-beta-HDL , and HDL functionality . CONCLUSIONS RVX-208 increases apoA-I and HDL-C in vitro and in vivo . In AGMs , RVX-208 raises serum pre-beta(1)-LpA-I and alpha-LpA-I levels and enhances cholesterol efflux . Data in humans point to beneficial features of RVX-208 that might be useful for treating atherosclerosis OBJECTIVES There is increasing evidence that intake of sour tea ( Hibiscus sabdariffa ) has hypoglycemic and hypolipidemic effects and may benefit patients suffering from metabolic disorders such as diabetes . The objective of the present study was to investigate the hypolipidemic effects of sour tea in patients with diabetes and compare them with those of black tea . DESIGN In this sequential r and omized controlled clinical trial , 60 patients with diabetes were recruited and r and omly assigned into two groups : sour tea ( ST ) and black tea ( BT ) . They were instructed to consume sour tea or black tea two times a day for 1 month . OUTCOME MEASURES Fasting blood sample s were taken at the beginning and at the end of the study for evaluation of lipids , lipoproteins , and apoproteins . RESULTS Fifty-three ( 53 ) patients concluded the study . In the ST group , mean of high-density lipoprotein-cholesterol ( HDLc ) increased significantly ( p = 0.002 ) at the end of the study , whereas changes in apolipoprotein-A1 , and lipoprotein ( a ) were not significant . Also , a significant decrease in the mean of total cholesterol , low density lipoprotein-cholesterol , triglycerides , and Apo-B100 were seen in this group . In the BT group , only HDLc showed significant change ( p = 0.002 ) at the end of the study and changes in the other measures were not statistically significant . CONCLUSIONS The results of the present study showed that ST has a significant effect on blood lipid profile in patients with diabetes Animal experiments show that the kidney contributes to apolipoprotein (apo)A-I catabolism . We tested relationships of HDL cholesterol ( HDL-C ) and apo-I with kidney function in subjects without severe chronic kidney disease . Included was a r and om sample of the general population ( part of the PREVEND cohort ) . Kidney function [ estimated glomerular filtration rate ( e-GFR ) by two well-established equations and creatinine clearance ] , HDL-C , triglycerides , apoA-I and insulin resistance ( HOMAir ) were measured in 2,484 fasting subjects ( e-GFR≥45 ml/min/1.73m2 ) without macroalbuminuria , cardiovascular disease , diabetes , or the use of anti-hypertensives and /or lipid-lowering agents . HDL-C ( r = −0.056 to −0.102 , P < 0.01 to < 0.001 ) and apo A-I ( r = −0.096 to −0.126 , P < 0.001 ) were correlated inversely with both GFR estimates and creatinine clearance in univariate analyses . Multiple linear regression analyses also demonstrated inverse relationships of HDL-C and apoA-I with all measures of kidney function even after adjustment for age , sex , waist circumference , HOMAir , triglycerides , and urinary albumin excretion ( P = 0.053 to 0.004 ) . In conclusion , HDL-C and apoA-I are inversely related to e-GFR and creatinine clearance in subjects without severely compromised kidney function , which fits the concept that the kidney contributes to apoA-I regulation in humans . High glomerular filtration rate may be an independent determinant of a pro-atherogenic lipoprotein profile |
1,812 | 23,437,439 | Compared with dual therapy , boceprevir triple therapy increased risk for hematologic adverse events and telaprevir triple therapy increased risk for anemia and rash .
A large well- design ed cohort study and 18 smaller cohort studies found that an SVR after antiviral therapy was associated with lower risk for all-cause mortality than was no SVR .
SVR rates for genotype 1 infection are higher with triple therapy that includes a protease inhibitor than with st and ard dual therapy .
An SVR after antiviral therapy appears associated with improved clinical outcomes . | BACKGROUND Multiple treatments are available for chronic hepatitis C virus ( HCV ) infection .
PURPOSE To compare benefits and harms of antiviral regimens for chronic HCV infection in treatment-naive adults . | AIM The therapy of chronic hepatitis C genotype 4 ( HCV-4 ) has not been optimized yet . This r and omized , prospect i ve , parallel-group clinical trial compared the efficacy and safety of pegylated interferon α-2a ( PEG-IFN α-2a ) plus ribavirin and PEG-IFN α-2b plus ribavirin and assessed the health-related quality of life ( HRQOL ) in patients with chronic HCV-4 . METHODS Eligible patients with proven chronic HCV-4 were r and omized to receive either a weekly dose of PEG-IFN α-2a ( 180 μg ) or PEG-IFN α-2b ( 1.5 μg/kg ) and a daily dose of ribavirin ( 1000 - 1200 mg ) for 48 weeks with 24 weeks post-treatment follow-up . The primary end point was sustained virological response ( SVR ) defined by undetectable HCV RNA 24 weeks after treatment . The Short form-36 Health Survey version 2 ( SF-36v2 ) and the Chronic Liver Disease question naires ( CLDQ ) were assessed before , during and after therapy . RESULTS The overall SVR rate of the entire cohort was 59.9 % . The SVR rates were significantly higher in patients treated with PEG-IFN α-2a and ribavirin ( Group A ; n=109 ) compared with those treated with PEG-IFN α-2b and ribavirin ( Group B ; n=108 , 70.6 vs. 54.6 % , respectively ; P=0.017 ) . The relapse rates were 5.1 % for PEG-IFN α-2a and 15.7 % for PEG-IFN α-2b ( P=0.0019 ) . The SF-36v2 and CLDQ were low during therapy and improved significantly after therapy successful therapy . CONCLUSION Pegylated interferon α-2a plus ribavirin was significantly more effective than PEG-IFN α-2b and ribavirin therapy in the treatment of chronic HCV-4 patients . The tolerability and adverse events were comparable between the two regimens . The HRQOL improved significantly after successful PEG-IFN α-2a plus ribavirin therapy BACKGROUND / AIMS As evidence accumulates relating to mother-to-child ( vertical ) transmission of hepatitis C virus ( HCV ) , it is timely to draw up guidelines for the clinical management of HCV infected pregnant women and their children . METHODS A review of evidence from the European Paediatric HCV Network ( EPHN ) prospect i ve study of HCV infected women and their children and other published studies . Meeting of EPHN clinical experts to reach a consensus on recommendations for management . Each recommendation was grade d according to the level of evidence . RESULTS / CONCLUSIONS Although several risk factors for mother-to-child transmission have been identified , none are modifiable and there are currently no interventions available to prevent vertical transmission of HCV . Data on timing of loss of maternal antibodies and reliability of diagnostic tests inform the optimum follow-up schedule for confirmation or exclusion of infection in children born to HCV infected women . Based on the current evidence , routine antenatal screening for HCV should not be introduced and neither elective caesarean section nor avoidance of breastfeeding should be recommended to HCV infected women to prevent mother-to-child transmission of HCV . HCV/HIV co-infected women should follow existing HIV guidelines Previous trials investigating the efficacy of treatment duration s shorter than the st and ard of 24 weeks for chronic hepatitis C virus ( HCV ) genotype 2/3 infections have yielded discordant results . The aims of this investigator‐initiated phase III study were to compare the efficacy of 12 or 24 weeks of treatment and to identify patients suitable for short‐term therapy . Three hundred eighty‐two genotype 2/3–infected patients [ intention‐to‐treat ( ITT ) population ] at 31 centers in Denmark , Finl and , Norway , and Sweden were r and omized to 12 or 24 weeks of peginterferon α‐2a ( 180 μg/week ) plus ribavirin ( 800 mg/day ) . Twelve weeks of therapy was inferior to 24 weeks in the ITT population ( sustained viral response [ SVR ] rates : 59 % versus 78 % , P < 0.0001 ) and in the subgroups of patients infected with genotype 2 ( 56 % versus 82 % , P = 0.006 ) or 3 ( 58 % versus 78 % , P = 0.0015 ) . These differences were observed regardless of the fibrosis stage . Age and HCV‐RNA levels on days 7 and 29 were independent predictors of SVR . Short‐term treatment was useful in patients < 40 years old , especially if HCV‐RNA was undetectable on day 29 , and also in patients ≥ 40 years old , provided that HCV‐RNA was below 1000 IU/mL on day 7 in addition to being undetectable on day 29 . If neither of these two criteria were met for patients ≥ 40 years old , 24 weeks of therapy was superior ( P < 0.0001 ) . Conclusion : Peginterferon/ribavirin treatment for 12 weeks in HCV genotype 2/3 infection is overall inferior to 24 weeks of treatment but may be useful in some patients with a rapid initial clearance of virus . ( HEPATOLOGY 2008 . BACKGROUND & AIMS Ribavirin ( RBV ) combined with either pegylated interferon ( PegIFN ) alpha2a or PegIFNalpha2b is the st and ard of care for chronic hepatitis C virus ( HCV ) infection . Due to the lack of head-to-head studies , the 2 PegIFNs have not been directly compared . The endpoints of our study were safety and antiviral efficacy of the 2 regimens . METHODS Treatment-naïve patients with chronic hepatitis C were r and omly ( 1:1 ) assigned after stratification for HCV genotype to receive either 1.5 mcg/Kg/week PegIFNalpha2b plus RBV 800 - 1200 mg/day or 180 mcg/week PegIFNalpha2a plus RBV 800 - 1200 mg/day for 24 or 48 weeks according to HCV genotype . The study was powered to detect a difference of at least 10 % in safety and efficacy of the 2 regimens . RESULTS The 212 patients on PegIFNalpha2a and the 219 patients on PegIFNalpha2b had similar baseline characteristics , including cirrhosis ( 20 % vs 18 % , respectively ) . By intention to treat , the 2 groups showed similar rates of treatment-related serious adverse events ( 1 % vs 1 % , respectively ) and drop out rates for adverse effects ( 7 % vs 6 % , respectively ) . Overall , sustained virologic response ( SVR ) rate was higher in PegIFNalpha2a than in PegIFNalpha2b patients ( 66 % vs 54 % , respectively , P = .02 ) , being 48 % vs 32 % in the 222 HCV-1 and -4 patients ( P = .04 ) , and 96 % vs 82 % , respectively , in the 143 HCV-2 patients ( P = .01 ) . PegIFNalpha2a independently predicted SVR in the logistic regression analysis ( odds ratio , 1.88 ; 95 % confidence interval : 1.20 - 2.96 ) . CONCLUSIONS Although the 2 regimens showed a similar safety profile , the PegIFNalpha2a-based treatment yielded significantly more SVR than PegIFNalpha2b BACKGROUND & AIMS There is increasing interest in identifying patients with chronic hepatitis C genotype 2 or 3 infection in whom it is possible to lower the burden of therapy while retaining high levels of efficacy . METHODS Treatment-naive patients with chronic hepatitis C genotype 2/3 infection were r and omized to receive peginterferon alfa-2b ( 1.5μg/kg/wk ) for 24weeks ( group A ) ; peginterferon alfa-2b ( 1.0μg/kg/wk ) for 24weeks ( group B ) ; or peginterferon alfa-2b ( 1.5μg/kg/wk ) for 16weeks ( group C ) , each in combination with weight-based ribavirin ( 800 - 1200mg/d ) . The study population comprised two cohorts : the Hep-Net cohort enrolled in Germany and an International cohort enrolled at study sites throughout Europe and Asia . The primary end point was sustained virological response ( SVR ) . RESULTS The study included 682 patients ; 80.2 % had genotype 3 infection . In the intent-to-treat population , SVR rates were 66.5 % , 64.3 % , and 56.6 % in groups A , B , and C , and were similar in Asian and white patients . Treatment differences ( A vs. B and A vs. C ) failed to reach the predefined margin for noninferiority of -10 % ; and thus groups B and C failed to show noninferiority relative to group A. Among patients with undetectable HCV RNA at week 4 , SVR rates were 75.3 % , 75.9 % , and 72.4 % , respectively . Relapse rates were 17.8 % , 16.3 % , and 29.3 % , respectively . Treatment-emergent serious adverse events were highest in group A and lowest in group C , and adverse events leading to discontinuation were similar across treatment arms . CONCLUSIONS For patients with chronic hepatitis C genotype 2/3 infection , 24weeks of peginterferon alfa-2b ( 1.5μg/kg/wk ) plus weight-based ribavirin remains a st and ard-of-care therapy ; however , treatment for 16weeks may be considered for patients with undetectable HCV RNA at week 4 of the treatment BACKGROUND Patients with chronic hepatitis C virus ( HCV ) infection who have not had a response to therapy with peginterferon and ribavirin may benefit from the addition of multiple direct-acting antiviral agents to their treatment regimen . METHODS This open-label , phase 2a study included an exploratory cohort of 21 patients with chronic HCV genotype 1 infection who had not had a response to previous therapy ( i.e. , had not had ≥2 log(10 ) decline in HCV RNA after ≥12 weeks of treatment with peginterferon and ribavirin ) . We r and omly assigned patients to receive the NS5A replication complex inhibitor daclatasvir ( 60 mg once daily ) and the NS3 protease inhibitor asunaprevir ( 600 mg twice daily ) alone ( group A , 11 patients ) or in combination with peginterferon alfa-2a and ribavirin ( group B , 10 patients ) for 24 weeks . The primary end point was the percentage of patients with a sustained virologic response 12 weeks after the end of the treatment period . RESULTS A total of 4 patients in group A ( 36 % ; 2 of 9 with HCV genotype 1a and 2 of 2 with genotype 1b ) had a sustained virologic response at 12 weeks after treatment and also at 24 weeks after treatment .. Six patients ( all with HCV genotype 1a ) had viral breakthrough while receiving therapy , and resistance mutations to both antiviral agents were found in all cases ; 1 patient had a viral response at the end of treatment but had a relapse after the treatment period . All 10 patients in group B had a sustained virologic response at 12 weeks after treatment , and 9 had a sustained virologic response at 24 weeks after treatment . Diarrhea was the most common adverse event in both groups . Six patients had transient elevations of alanine aminotransferase levels to more than 3 times the upper limit of the normal range . CONCLUSIONS This preliminary study involving patients with HCV genotype 1 infection who had not had a response to prior therapy showed that a sustained virologic response can be achieved with two direct-acting antiviral agents only . In addition , a high rate of sustained virologic response was achieved when the two direct-acting antiviral agents were combined with peginterferon alfa-2a and ribavirin . ( Funded by Bristol-Myers Squibb ; Clinical Trials.gov number , NCT01012895 . ) AIM To evaluate the significance of induction with high doses of pegylated interferon -2b ( Peg-IFNalpha-2b ) and the predictability of sustained virologic response ( SVR ) in naïve patients with chronic hepatitis C. METHODS 188 consecutive naïve patients with chronic hepatitis C were enrolled in a r and omised controlled clinical trial . Patients were r and omised to receive either Peg-IFN -2b 3.0 mcg/kg QW x 12 weeks followed by 1.5 mcg/kg QW x 36 weeks plus 800 - 1200 mg ribavirin ( Arm A ) or Peg-IFNalpha-2b 1.5 mcg/kg QW x 48 weeks plus 800 - 1200 mg ribavirin ( Arm B ) . HCV-RNA was obtained at 0 , 4 , 8 , 12 , 16 , 24 , 48 and 72 weeks . Differences between schemes were evaluated by Kaplan-Meier curves . Predictability of SVR was assessed by two-way contingency table analysis and ROC curve analysis . RESULTS From 176 patients , 75 had genotype 1 , 15 genotype 2 , 75 genotype 3 and 11 genotype 4 . No statistical significance emerged in HCV-RNA positivity , side effects and withdrawals between schemes . Patients with genotype 1 achieved lower SVR ( 46.6 % ) in comparison to patients with genotypes 2/3 ( 94.1 % , p < 0.001 ) and 4 ( 90.9 % , p = 0.002 ) . The most appropriate time for estimation of SVR for genotype 1 is week 8 ( accuracy = 0.84 , AUC = 0.90 ) while predictability increases with time in genotypes 2/3 , reaching maximum accuracy = 0.93 and AUC = 0.76 at week 16 . CONCLUSION Induction with high doses of Peg-IFNalpha-2b does not preclude better outcome and rapid virologic response at 4 weeks of treatment sufficiently predicts SVR . These findings might be useful in an attempt to gain supportive evidence for decision making in difficult-to-treat patients Background In patients with chronic hepatitis C virus ( HCV ) genotype 2 or 3 , 24 weeks ' treatment with pegylated interferon alfa ( PEG-IFN-alpha ) and ribavirin induces a sustained virological response ( SVR ) in almost 80 % of cases . Evidence suggests that a similar response rate may be obtained with shorter treatment periods , especially in patients with a rapid virological response ( RVR ) . The aim of this study was to compare the efficacy of 12 or 24 weeks of treatment in patients with chronic HCV genotype 2 or 3 and to identify patients suitable for 12 weeks treatment . Methods Two hundred and ten patients received PEG-IFN-alpha-2a ( 180 ug/week ) and ribavirin ( 800 - 1200 mg/day ) for 4 weeks . Patients with a RVR ( HCV RNA not detectable ) were r and omized ( 1:1 ) to either 12 ( group A1 ) or 24 ( group A2 ) weeks of combination therapy . Patients without a RVR continued with 24-weeks ' combination therapy ( group B ) . HCV RNA was monitored at weeks 4 , 8 , 12 , and 24 , and at week 24 post-treatment . Results At study end , end of treatment response ( ETR ) was observed in 62 ( 86 % ) patients of group A1 and in 55 ( 77 % ) patients of group A2 ( p < 0.05 ) Relapse rate was 3 % each in groups A1 and A2 , and 6 % in group B. Among patients with a HCVRNA test 24 weeks after the end of treatment , SVR was observed in 60 ( 83 % ) of group A1 patients and in 53 ( 75 % ) of group A2 patients . Rapid virological response , low baseline HCV RNA levels , elevated alanine aminotransferase levels and low fibrosis score , were the strongest covariates associated with SVR , independent of HCV genotype . No baseline characteristic was associated with relapse . Conclusion In HCV patients with genotype 2 or 3 , 12-week combination therapy is as efficacious as 24-week therapy and several independent covariates were predictive of SVR.Trial registration Trial number IS RCT BACKGROUND A sustained virological response ( SVR ) rate of 41 % has been achieved with interferon alfa-2b plus ribavirin therapy of chronic hepatitis C. In this r and omised trial , peginterferon alfa-2b plus ribavirin was compared with interferon alfa-2b plus ribavirin . METHODS 1530 patients with chronic hepatitis C were assigned interferon alfa-2b ( 3 MU subcutaneously three times per week ) plus ribavirin 1000 - 1200 mg/day orally , peginterferon alfa-2b 1.5 microg/kg each week plus 800 mg/day ribavirin , or peginterferon alfa-2b 1.5 microg/kg per week for 4 weeks then 0.5 microg/kg per week plus ribavirin 1000 - 1200 mg/day for 48 weeks . The primary endpoint was the SVR rate ( undetectable hepatitis C virus [ HCV ] RNA in serum at 24-week follow-up ) . Analyses were based on patients who received at least one dose of study medication . FINDINGS The SVR rate was significantly higher ( p=0.01 for both comparisons ) in the higher-dose peginterferon group ( 274/511 [ 54 % ] ) than in the lower-dose peginterferon ( 244/514 [ 47 % ] ) or interferon ( 235/505 [ 47 % ] ) groups . Among patients with HCV genotype 1 infection , the corresponding SVR rates were 42 % ( 145/348 ) , 34 % ( 118/349 ) , and 33 % ( 114/343 ) . The rate for patients with genotype 2 and 3 infections was about 80 % for all treatment groups . Secondary analyses identified bodyweight as an important predictor of SVR , prompting comparison of the interferon regimens after adjusting ribavirin for bodyweight ( mg/kg ) . Side-effect profiles were similar between the treatment groups . INTERPRETATION In patients with chronic hepatitis C , the most effective therapy is the combination of peginterferon alfa-2b 1.5 microg/kg per week plus ribavirin . The benefit is mostly achieved in patients with HCV genotype 1 infections BACKGROUND Patients infected with hepatitis C virus ( HCV ) genotype 2 or 3 have sustained virologic response rates of approximately 80 % after receiving treatment with peginterferon and ribavirin for 24 weeks . We conducted a large , r and omized , multinational , noninferiority trial to determine whether similar efficacy could be achieved with only 16 weeks of treatment with peginterferon alfa-2a and ribavirin . METHODS We r and omly assigned 1469 patients with HCV genotype 2 or 3 to receive 180 mug of peginterferon alfa-2a weekly , plus 800 mg of ribavirin daily , for either 16 or 24 weeks . A sustained virologic response was defined as an undetectable serum HCV RNA level ( < 50 IU per milliliter ) 24 weeks after the end of treatment . RESULTS The study failed to demonstrate that the 16-week regimen was noninferior to the 24-week regimen . The sustained virologic response rate was significantly lower in patients treated for 16 weeks than in patients treated for 24 weeks ( 62 % vs. 70 % ; odds ratio for 16 weeks vs. 24 weeks , 0.67 ; 95 % confidence interval , 0.54 to 0.84 ; P<0.001 ) . In addition , the rate of relapse ( a detectable HCV RNA level during follow-up in patients who had undetectable HCV RNA at the end of treatment ) was significantly greater in the 16-week group ( 31 % , vs. 18 % in the 24-week group ; P<0.001 ) . The sustained virologic response rates in patients with a pretreatment serum HCV RNA level of 400,000 IU per milliliter or less was 82 % with the 16-week regimen and 81 % with the 24-week regimen . Among patients with a rapid virologic response ( an undetectable HCV RNA level by week 4 ) , sustained virologic response rates were 79 % in the 16-week group and 85 % in the 24-week group ( P=0.02 ) . CONCLUSIONS Treatment with peginterferon and ribavirin for 16 weeks in patients infected with HCV genotype 2 or 3 results in a lower overall sustained virologic response rate than treatment with the st and ard 24-week regimen . ( Clinical Trials.gov number , NCT00077636 [ Clinical Trials.gov ] . ) OBJECTIVE : To test the feasibility of creating a valid and reliable checklist with the following features : appropriate for assessing both r and omised and non-r and omised studies ; provision of both an overall score for study quality and a profile of scores not only for the quality of reporting , internal validity ( bias and confounding ) and power , but also for external validity . DESIGN : A pilot version was first developed , based on epidemiological principles , review s , and existing checklists for r and omised studies . Face and content validity were assessed by three experienced review ers and reliability was determined using two raters assessing 10 r and omised and 10 non-r and omised studies . Using different raters , the checklist was revised and tested for internal consistency ( Kuder-Richardson 20 ) , test-retest and inter-rater reliability ( Spearman correlation coefficient and sign rank test ; kappa statistics ) , criterion validity , and respondent burden . MAIN RESULTS : The performance of the checklist improved considerably after revision of a pilot version . The Quality Index had high internal consistency ( KR-20 : 0.89 ) as did the subscales apart from external validity ( KR-20 : 0.54 ) . Test-retest ( r 0.88 ) and inter-rater ( r 0.75 ) reliability of the Quality Index were good . Reliability of the subscales varied from good ( bias ) to poor ( external validity ) . The Quality Index correlated highly with an existing , established instrument for assessing r and omised studies ( r 0.90 ) . There was little difference between its performance with non-r and omised and with r and omised studies . Raters took about 20 minutes to assess each paper ( range 10 to 45 minutes ) . CONCLUSIONS : This study has shown that it is feasible to develop a checklist that can be used to assess the method ological quality not only of r and omised controlled trials but also non-r and omised studies . It has also shown that it is possible to produce a checklist that provides a profile of the paper , alerting review ers to its particular method ological strengths and weaknesses . Further work is required to improve the checklist and the training of raters in the assessment of external validity Context Few studies address long-term outcomes of antiviral therapy for patients with chronic hepatitis C and cirrhosis . Contribution This prospect i ve study of adults with chronic hepatitis C and cirrhosis compares outcomes between 74 patients who declined treatment and 271 patients treated with thrice-weekly interferon injections for 26 to 88 weeks . Median follow-up was 6.8 years . Fewer treated patients developed hepatocellular cancer ( 31 % vs. 47 % of untreated patients ) or died ( 17 % vs. 32 % ) . Caution s Because the study was not a r and omized , controlled trial , prognostic factors other than interferon might have contributed to the differences between groups . The Editors Chronic hepatitis C is a common disease that progresses slowly to cirrhosis and eventually may lead to hepatocellular carcinoma ( 1 - 5 ) . The annual incidence of hepatocellular carcinoma and mortality rate were 1.4 % to 3.3 % and 1.9 % to 5.5 % , respectively , in retrospective series of white patients with hepatitis C virus (HCV)related compensated cirrhosis ( 4 - 9 ) ; in Japan , the annual incidence of hepatocellular carcinoma was 5 % to 7 % ( 10 - 12 ) . Risk factors for hepatocellular carcinoma include age older than 50 to 60 years , male sex , advanced fibrosis stage , high histologic activity score , and high alanine aminotransferase ( ALT ) levels ( 4 - 14 ) . Several retrospective studies have shown inhibition of hepatocellular carcinoma development after interferon therapy ( 11 - 14 ) . This inhibitory effect was seen in patients with moderate fibrosis for whom antiviral therapy was effective ( 11 - 14 ) . However , the inhibitory effect in patients with liver cirrhosis was not statistically significant ( 4 , 7 , 8 , 15 ) , possibly because of the low efficacy of interferon therapy in cirrhotic patients ( 15 - 17 ) . Other retrospective ( 6 , 9 ) and prospect i ve ( 18 ) studies that had small patient sample s indicated that interferon therapy reduced the development of hepatocellular carcinoma . Because cirrhosis is a major risk factor for hepatocellular carcinoma , a prospect i ve study is needed to determine whether interferon therapy benefits cirrhotic patients . We previously performed 2 prospect i ve studies on the efficacy of interferon treatment in cirrhotic patients ( 19 , 20 ) . During enrollment , many cirrhotic patients who fulfilled the inclusion criteria were enrolled as controls to clarify the long-term effect of interferon therapy on development of liver tumors . We conducted a 7-year study on the inhibition of hepatocellular carcinoma development in the previous cohorts of our multicenter , prospect i ve study . Methods Study Sample Enrollment of Patients with Compensated Liver Cirrhosis Design s for the 2 protocol s , Interferon alfa-2a prospect i ve trial for cirrhotic patients modification of treatment duration by monitoring HCV RNA in the serum ( 19 ) and Natural interferon trial for cirrhotic patients modification of interferon treatment duration according to pretreatment viral load ( 20 ) were finalized on 18 December 1992 and 20 April 1993 , respectively . While discussing these 2 protocol s , we decided to extend the prospect i ve studies after the initial trial to examine the effect of antiviral therapy on the inhibition of hepatocellular carcinoma development and patient survival as secondary end points . Inclusion Criteria Our previous reports ( 19 , 20 ) describe in more detail the diagnosis of chronic hepatitis C with cirrhosis and the inclusion criteria for the 2 trials ( 19 , 20 ) . The diagnostic criteria were elevated serum ALT levels for more than 6 months , positivity for anti-HCV antibody by the phytohemagglutinin assay ( Dinabbot , Tokyo , Japan ) or enzyme-linked immunosorbent assay ( Ortho Diagnostic Systems , Tokyo , Japan ) , and abnormal histologic findings on liver biopsy specimens . The presence of HCV RNA was tested by reverse transcriptase polymerase chain reaction ( RT-PCR ) ( detection limit , 102 copies/mL ) , and the serum HCV RNA level was measured by competitive RT-PCR according to the method of Kato and colleagues ( 21 ) . The HCV genotype was established by using the method of Okamoto and colleagues ( 22 ) . Liver biopsy was done in all patients within 12 months before enrollment , and specimens were evaluated according to the criteria of Desmet and colleagues ( 23 ) . Inclusion criteria were based on liver histologic characteristics indicating fibrotic stage F4 , positivity for HCV RNA by RT-PCR , platelet count greater than 50 109 cells/L , leukocyte count greater than 3 109 cells/L , and ChildPugh A classification . We excluded patients who had liver cirrhosis caused by hepatitis B , autoimmune hepatitis , primary biliary cirrhosis , or drug-induced liver disease . Before enrollment , patients had abdominal ultrasonography , dynamic computed tomography ( CT ) , or magnetic resonance imaging ( MRI ) ; we excluded patients who were found to have hepatocellular carcinoma . Antiviral Therapy A total of 157 patients received 9 million units ( MU ) of interferon-2a ( Nippon Roche KK , Tokyo , Japan ) by intramuscular injection 3 times a week for 32 to 88 weeks ; duration of therapy was based on serum HCV RNA status during therapy ( 19 ) . The mean and median duration of therapy were 44 and 48 weeks , respectively , and the mean and median dose of interferon were 1011 and 936 MU ( range , 42 to 2378 MU ) , respectively . A total of 114 patients received 9 or 6 MU of natural interferon- ( Sumitomo Pharmaceutical Co. , Osaka , Japan ) by subcutaneous injection 3 times a week for 6 months ( patients with low viral load ) or 12 months ( patients with high viral load ) ( 20 ) . The mean and median duration of therapy were 33 and 26 weeks , respectively , and the mean and median dose of interferon were 688 MU and 564 MU ( range , 18 to 1404 MU ) , respectively . For the 2 trials combined , the mean duration of treatment was 39 weeks ( range , 1 to 88 weeks ) and the mean dose of interferon was 875 MU ( range , 18 to 2376 MU ) . Eighty-eight percent of the patients took more than 80 % of the drug during 80 % of the scheduled treatment period . Patients negative for HCV RNA more than 24 weeks after the completion of interferon therapy were considered to show a sustained virologic response , while patients positive for HCV RNA more than 24 weeks after the completion of interferon therapy were considered to show a nonsustained response . Study Design This was not a r and omized study . A total of 271 patients received interferon therapy ; 74 patients who fulfilled the inclusion criteria for the trials but declined to receive interferon therapy instead received periodic medical screenings at outpatient clinics in each institute , provided informed consent , and were enrolled in the untreated group ( Figure 1 ) . Thus , the sample size for this study was set at 345 as of April 1996 . We established a 5-year follow-up study to obtain statistical significance with a power of 80 % on the assumption that the efficacy of interferon therapy would be 25 % and the incidence of hepatocellular carcinoma development among responders would be reduced to a risk ratio of 0.3 compared to untreated patients or nonsustained responders based on the preliminary data from the retrospective cohort study ( 11 ) . In April 2001 , we extended the length of the mean follow-up period from 5 years to 7 years because the incidence of hepatocellular carcinoma development in the interferon group was higher than initially anticipated . Figure 1 . Flow diagram of the trial . Approval The ethics committee of each participating institution approved the study . Informed consent was obtained from each patient according to the Helsinki Declaration . Previously participating physicians at 6 institutes had resigned before this follow-up study began , and the new chief physicians did not resu bmi t this protocol to the ethical committee of each institute . Thus , we did not follow the patients enrolled at these institutes ( n= 17 ) . We considered these patients to be censored participants who did not go on to participate in the subsequent follow-up study . Patient Follow-up We followed patients by performing blood tests and measuring biochemical variables every 1 to 2 months . Abdominal ultrasonography was done every 3 to 6 months . Patients did not receive any additional antiviral therapy thereafter because the Japanese National Health Insurance plan did not approve interferon treatment for cirrhotic patients . If a patient relocated during follow-up , data from medical examinations at the nearest outpatient clinic were collected from a private physician or by fax or telephone . Patients without data from a medical consultation were contacted by letter or telephone and advised to receive a medical check-up at the closest outpatient clinic . The median follow-up period from the time of initial enrollment was 6.8 years ( range , 0.04 to 10.4 years ) . Detection of Hepatocellular Carcinoma If a suspicious hepatocellular lesion was detected by ultrasonography , the patient had dynamic CT or MRI , along with arteriography . Board-certificated radiologists at each institute diagnosed hepatocellular carcinoma on the basis of typical patterns , such as early-phase hyperattenuation area and late-phase hypoattenuation on dynamic CT or MRI . At times , board-certified pathologists who were unaware of patients ' clinical data confirmed the diagnosis using ultrasonography-guided tumor biopsy . Treatment of Hepatocellular Carcinoma If the liver tumor consisted of fewer than 3 nodules that were less than 3 cm in diameter , patients received percutaneous ethanol injection therapy , microwave coagulation therapy , radiofrequency ablation therapy , or surgical hepatectomy ( 24 - 28 ) . Patients with stage III and IV hepatocellular carcinomas were treated with transarterial chemoembolization or chemotherapy ( 29 ) . Patient Survival We examined patient survival or the causes of death . Statistical Analysis We used SAS , version 8.2 ( SAS Institute , Inc. , Cary , North Carolina ) , for statistical analysis . A Wilcoxon test or Fisher exact test was used to compare the distribution of variables between the groups . We compared sustained virological response ( SVR ) in chronic hepatitis C patients with severe fibrosis treated with pegylated interferon ( Peg-IFN ) alpha-2b 1.5 microg/kg/week or 0.75 microg/kg/week in combination with ribavirin 800 mg/day for 48 weeks . This was a multicentre r and omized controlled study . SVR was observed in 44.5 % ( 45/101 ) of patients treated with the st and ard dose of Peg-IFN and 37.2 % ( 38/102 ) of patients treated with the low dose ( NS ) . In patients with genotypes 1 , 4 and 5 , SVR was observed in 25.0 % of patients who received the st and ard dose and 16.9 % of patients who received the low dose of Peg-IFN ( P = NS ) . In patients with genotypes 1 , 4 and 5 and low viraemia , SVR was obtained in 27.3 % of patients treated with the st and ard dose and 25.8 % of patients treated with the low dose ( P = NS ) . In the high-viraemia subgroup , SVR was obtained in 24.0 % and 9.1 % of patients , respectively . In patients with genotypes 2 and 3 , SVR was similar in both groups ( 73.2%vs 73.0 % ) . Thus , ( 1 ) patients with genotypes 2 and 3 and severe fibrosis can be treated with low dose of Peg-IFN and ribavirin , ( 2 ) this study suggests that patients with genotypes 1 , 4 and 5 and high viraemia could receive a st and ard dose of Peg-IFN associated with ribavirin for 48 weeks , ( 3 ) side effects limit the efficacy of the treatment with st and ard dose of Peg-IFN in patients with genotypes 1 , 4 and 5 and low viraemia , ( 4 ) more studies are needed for patients with genotype 2 or 3 to define the optimal duration ( 24 or 48 weeks ) in patients with severe fibrosis BACKGROUND Treatment with peginterferon alfa-2a alone produces significantly higher sustained virologic responses than treatment with interferon alfa-2a alone in patients with chronic hepatitis C virus ( HCV ) infection . We compared the efficacy and safety of peginterferon alfa-2a plus ribavirin , interferon alfa-2b plus ribavirin , and peginterferon alfa-2a alone in the initial treatment of chronic hepatitis C. METHODS A total of 1121 patients were r and omly assigned to treatment and received at least one dose of study medication , consisting of 180 microg of peginterferon alfa-2a once weekly plus daily ribavirin ( 1000 or 1200 mg , depending on body weight ) , weekly peginterferon alfa-2a plus daily placebo , or 3 million units of interferon alfa-2b thrice weekly plus daily ribavirin for 48 weeks . RESULTS A significantly higher proportion of patients who received peginterferon alfa-2a plus ribavirin had a sustained virologic response ( defined as the absence of detectable HCV RNA 24 weeks after cessation of therapy ) than of patients who received interferon alfa-2b plus ribavirin ( 56 percent vs. 44 percent , P<0.001 ) or peginterferon alfa-2a alone ( 56 percent vs. 29 percent , P<0.001 ) . The proportions of patients with HCV genotype 1 who had sustained virologic responses were 46 percent , 36 percent , and 21 percent , respectively , for the three regimens . Among patients with HCV genotype 1 and high base-line levels of HCV RNA , the proportions of those with sustained virologic responses were 41 percent , 33 percent , and 13 percent , respectively . The overall safety profiles of the three treatment regimens were similar ; the incidence of influenza-like symptoms and depression was lower in the groups receiving peginterferon alfa-2a than in the group receiving interferon alfa-2b plus ribavirin . CONCLUSIONS In patients with chronic hepatitis C , once-weekly peginterferon alfa-2a plus ribavirin was tolerated as well as interferon alfa-2b plus ribavirin and produced significant improvements in the rate of sustained virologic response , as compared with interferon alfa-2b plus ribavirin or peginterferon alfa-2a alone Current st and ard-of-care antiviral treatment for patients with chronic hepatitis C is combination therapy with pegylated interferon ( PEG-IFN ) alfa plus ribavirin . Two large clinical trials determined that each PEG-IFN alfa compound , when given in combination with ribavirin , results in overall sustained virological response ( SVR ) rates of approximately 50 % ; SVR rates in patients infected with hepatitis C virus ( HCV ) genotype 1 are typically lower ( 42 - 46 % ) . Differences in study design , treatment regimens , and patient population s preclude comparison of the data across trials ; therefore , the most effective use of PEG-IFN alfa in combination with ribavirin is unclear . The Individualized Dosing Efficacy vs Flat Dosing to Assess Optimal Pegylated Interferon Therapy ( IDEAL ) study is a phase 3b , r and omized , parallel-group , US multicentre trial in treatment-naive genotype 1 patients with chronic hepatitis C. Initially , this study was undertaken to evaluate the efficacy and safety of weight-based ribavirin dosing ( 800 - 1400 mg / day ) and PEG-IFN alfa-2b dosing ( arm 1 : PEG-IFN alfa-2b 1.5 microg / kg / week ; arm 2 : PEG-IFN alfa-2b 1.0 microg / kg / week ) . However , because a clinical trial directly comparing the efficacy and safety of PEG-IFN alfa-2a and alfa-2b in combination with weight-based ribavirin dosing has not been performed , an additional arm ( arm 3 : PEG-IFN alfa-2a 180 microg / week plus ribavirin 1000 - 1200 mg / day ) was included to address this important issue . IDEAL is fully enrolled ( > 3000 patients ) and complete study data , including SVR rates , are expected in early 2008 . Herein , we present the scientific rationale and study design , discuss key data from other trials , and summarize our expectations of this study BACKGROUND Conflicting reports exist in the medical literature regarding the association between industry funding and published research findings . In this study , we examine the association between industry funding and the statistical significance of results in recently published medical and surgical trials . METHODS We examined a consecutive series of 332 r and omized trials published between January 1999 and June 2001 in 8 leading surgical journals and 5 medical journals . Each eligible study was independently review ed for method ological quality using a 21-point index with 5 domains : r and omization , outcomes , eligibility criteria , interventions and statistical issues . Our primary analysis included studies that explicitly identified the primary outcome and reported it as statistically significant . For studies that did not explicitly identify a primary outcome , we defined a " positive " study as one with at least 1 statistically significant outcome measure . We used multivariable regression analysis to determine whether there was an association between reported industry funding and trial results , while controlling for study quality and sample size . RESULTS Among the 332 r and omized trials , there were 158 drug trials , 87 surgical trials and 87 trials of other therapies . In 122 ( 37 % ) of the trials , authors declared industry funding . An unadjusted analysis of this sample of trials revealed that industry funding was associated with a statistically significant result in favour of the new industry product ( odds ratio [ OR ] 1.9 , 95 % confidence interval [ CI ] 1.3 - 3.5 ) . The association remained significant after adjustment for study quality and sample size ( adjusted OR 1.8 , 95 % CI 1.1 - 3.0 ) . There was a nonsignificant difference between surgical trials ( OR 8.0 , 95 % CI 1.1 - 53.2 ) and drug trials ( OR 1.6 , 95 % CI 1.1 - 2.8 ) , both of which were likely to have a pro-industry result ( relative OR 5.0 , 95 % CI 0.7 - 37.5 , p = 0.14 ) . INTERPRETATION Industry-funded trials are more likely to be associated with statistically significant pro-industry findings , both in medical trials and surgical interventions BACKGROUND AND AIM To compare the efficacy and safety of pegylated interferon ( PEG-I ) at 1 and 1.5 microg/kg , and in combination with ribavirin ( RBV ) for 24 weeks in naïve Japanese patients infected with hepatitis C virus genotype 2 . METHODS The present study was an open-label , r and omized trial of 55 patients receiving PEG-I ( 1 or 1.5 microg/kg body weight [ BW ] , subcutaneously , once a week ) and RBV for 24 weeks . The patients were followed up for 24 weeks without treatment . RESULTS The intention-to-treat analyses showed that the proportion of patients with a sustained virological response ( SVR ) in the 1-microg/kg PEG-I-RBV group ( 38.5 % , 10/26 ) was lower than that of the 1.5-microg/kg PEG-I-RBV group ( 74.1 % , 20/27 ; P = 0.013 ) . The PEG-I dose was reduced in two of the 26 patients of the 1-microg/kg PEG-I-RBV group ( one because of thrombocytopenia at 2 weeks , and one because of generalized fatigue at 20 weeks ) , and four of the 27 patients of the 1.5-microg/kg PEG-I-RBV group ( one because of neutropenia at 20 weeks , and three because of generalized fatigue at 1 , 5 , and 8 weeks ) . The multivariate analysis identified age ( < 60 years ) and dose of PEG-I ( 1.5 microg/kg ) as significant determinants of SVR . CONCLUSION The dose of PEG-I to be used at the start of therapy should be 1.5-microg/kg BW in naïve Japanese patients infected with hepatitis C virus genotype 2 BACKGROUND We hypothesized that in patients with hepatitis C virus ( HCV ) genotype 2 or 3 in whom HCV RNA is not detectable after 4 weeks of therapy , 12 weeks of treatment is as effective as 24 weeks . METHODS A total of 283 patients were r and omly assigned to a st and ard 24-week regimen of peginterferon alfa-2b at a dose of 1.0 mug per kilogram weekly plus ribavirin at a dose of 1000 mg or 1200 mg daily , on the basis of body weight . Of these , 70 patients were assigned to the 24-week regimen ( st and ard- duration group ) and 213 patients to a variable regimen ( variable- duration group ) of 12 or 24 weeks , depending on whether tests for HCV RNA were negative or positive at week 4 . The primary end point was HCV that was not detectable by polymerase-chain-reaction ( PCR ) assay 24 weeks after the completion of therapy . RESULTS In the st and ard- duration group , 45 ( 64 percent ) patients had HCV that was not detectable by PCR assay at week 4 , as compared with 133 ( 62 percent ) in the variable- duration group ( difference [ the rate in the st and ard- duration group minus that in the variable- duration group ] , 2 percent ; 95 percent confidence interval , -11 to 15 percent ) . Fifty-three patients ( 76 percent ) in the st and ard- duration group and 164 patients ( 77 percent ) in the variable- duration group had a sustained virologic response ( difference , -1 percent ; 95 percent confidence interval , -13 to 10 percent ) . Fewer patients in the variable- duration group receiving the 12-week regimen had adverse events and withdrew than in the group receiving the 24-week regimen ( P=0.045 ) . The rate of relapse ( defined as HCV not detectable at the end of treatment but detectable at the end of follow-up ) was 3.6 percent in the st and ard- duration group and 8.9 percent in the variable- duration group ( P=0.16 ) . Overall , the rate of sustained virologic response was 80 percent among patients with HCV genotype 2 and 66 percent among those with genotype 3 ( P<0.001 ) . CONCLUSIONS A shorter course of therapy over 12 weeks with peginterferon alfa-2b and ribavirin is as effective as a 24-week course for patients with HCV genotype 2 or 3 who have a response to treatment at 4 weeks In patients with hepatitis C virus (HCV)-related advanced fibrosis/cirrhosis , 30 % of sustained HCV clearance has been reported with pegylated interferon alpha-2a ( PEG-IFN ) alone , but the efficacy and tolerability of the PEG-IFN/ribavirin ( RBV ) combination remain poorly defined . A total of 124 treatment-naïve patients with biopsy proved HCV-related advanced fibrosis/cirrhosis ( Ishak score F4-F6 , Child-Pugh score < or = 7 ) were r and omized to 48 weeks of PEG-IFN ( 180 microg sc weekly ) and st and ard dose of RBV ( 1000/1200 mg po daily , STD ) or PEG-IFN ( 180 microg sc weekly ) and low-dose of RBV ( 600/800 mg po daily , LOW ) . Sustained virologic response ( SVR ) rates with PEG-IFN/STD RBV ( 52 % ) were higher -- albeit not significantly -- than that with PEG-IFN/LOW RBV ( 38 % , P = 0.153 ) . In multivariate analysis , genotype 2/3 and a baseline platelet count > or = 150 x 10(9)/L were independently associated with SVR . The likelihood of SVR was < 7 % if viraemia had not declined by > or = 2 log or to undetectable levels after 12 weeks . Nine adverse events in the STD RBV and 15 in the LOW RBV group were classified as severe ( including two deaths ) ; dose reductions for intolerance were required in 78 % and 57 % ( P = 0.013 ) , and treatment was terminated early in 23 % and 27 % of patients ( P = n.s . ) . The benefit/risk ratio of treating compensated HCV-cirrhotics with STD PEG-IFN/RBV is favourable UNLABELLED A recent nonr and omized pilot trial showed that hepatitis C virus ( HCV ) patients with genotype 2/3 and rapid virological response ( RVR ) had a 90 % sustained virological response ( SVR ) rate after 14 weeks of treatment . We aim ed to assess this concept in a r and omized controlled trial . In the trial , 428 treatment-naïve HCV RNA-positive patients with genotype 2 or 3 were enrolled . Patients with RVR were r and omized to 14 ( group A ) or 24 ( group B ) weeks of treatment . Patients were treated with pegylated interferon alpha-2b ( 1.5 microg/kg ) subcutaneously weekly and ribavirin ( 800 - 1400 mg ) orally daily . The noninferiority margin was set to be 10 % between the two groups with a one-sided 2.5 % significance level . RVR was obtained in 302 of 428 ( 71 % ) , and 298 of these were r and omized to group A ( n = 148 ) or group B ( n = 150 ) . In the intention-to-treat analysis , SVR rates were 120 of 148 ( 81.1 % ) in group A and 136 of 150 ( 90.7 % ) in group B ( difference , 9.6 % ; 95 % confidence interval , 1.7 - 17.7 ) . Among patients with an HCV RNA test 24 weeks after the end of treatment , 120 of 139 ( 86.3 % ) patients in group A achieved SVR compared with 136 of 146 ( 93.2 % ) in group B ( difference , 6.9 % ; 95 % confidence interval , -0.1 to + 13.9 ) . CONCLUSION We can not formally cl aim that 14 weeks of treatment is noninferior to 24 weeks of treatment . However , the SVR rate after 14 weeks of treatment is high , and although longer treatment may give slightly better SVR , we believe economical savings and fewer side effects make it rational to treat patients with genotype 2 or 3 and RVR for only 14 weeks Background : The recommended treatment for patients infected with hepatitis C virus genotype 2 ( HCV2 ) is pegylated interferon ( peginterferon ) and ribavirin for 24 weeks . Aim : To assess whether a shorter 16-week treatment is as effective as a st and ard 24-week treatment . Methods : Patients with HCV2 infection were r and omised in a 1:2 ratio to either 16 weeks ( n = 50 ) or 24 weeks ( n = 100 ) of treatment with peginterferon α-2a ( 180 μg/week ) and weight-based ribavirin 1000–1200 mg/day , with a 24-week follow-up period . A rapid virological response ( RVR ) was defined as seronegative for HCV RNA at 4 weeks of treatment , and the primary end point , sustained virological response ( SVR ) , as seronegative for HCV RNA at the 24-week follow-up . Results : The rate of RVR and SVR was 86 % ( 43/50 , 95 % confidence interval ( CI ) 76 % to 96 % ) and 94 % ( 47/50 , CI 87 % to 100 % ) , respectively , in the 16-week group , which was comparable to 87 % ( 87/100 , CI 80 % to 94 % ) and 95 % ( 95/100 , CI 91 % to 99 % ) in the 24-week group . Patients with RVR had a significantly higher SVR rate than patients without RVR in both 16-week ( 100 % vs 57 % , p = 0.015 ) and 24-week groups ( 98 % vs 77 % , p = 0.002 ) . Multivariate analysis showed that RVR and age were independent factors associated with SVR . Both treatment arms were equally well tolerated . The incidence of alopecia was significantly higher in the 24-week group ( 49 % ) than in the 16-week group ( 20 % , p = 0.001 ) . Conclusion : 16 weeks and 24 weeks of peginterferon treatment with weight-based ribavirin at a dose of 1000–1200 mg/day provided equal efficacy in patients with HCV2 who achieved RVR at 4 weeks BACKGROUND The long-term benefit for chronic hepatitis C ( CHC ) patients treated with interferon (IFN)/ribavirin ( RBV ) combination therapy remains unclear . We aim ed to evaluate the long-term effects of IFN monotherapy and IFN/RBV combination therapy on reducing hepatocellular carcinoma ( HCC ) and mortality in patients with chronic hepatitis C virus ( HCV ) infection , adjusting for risk factors . METHODS A total of 1,619 patients with biopsy-proven CHC , including 1,057 receiving IFN-based therapy ( 760 on IFN/RBV combination therapy ) and 562 untreated controls from three medical centres and one regional core hospital in Taiwan were enrolled in this retrospective- prospect i ve cohort study . RESULTS The incidence of HCC and survival during a follow-up period of 1.0 - 15.3 ( mean 5.18 ) and 1 - 16 ( mean 5.15 ) years in treated and untreated patients , respectively , was analysed using Cox proportional hazards regression . The cumulative incidence of HCC was 35.2 % and 12.2 % for untreated and treated groups , respectively ( P=0.0013 ) . The cumulative survival rate was 93.1 % and 96.2 % for untreated and treated groups , respectively ( P=0.3928 ) . Significantly lower incidences of HCC and mortality were observed in sustained virological responders ( both for IFN monotherapy and IFN/RBV combination ) but not in nonresponders when compared with untreated patients . HCV genotype 1 patients had significantly higher incidences of HCC than genotype non-1 patients . In multivariate analysis , pre-existing cirrhosis , non-response , HCV genotype-1 and age were associated with HCC ; pre-existing cirrhosis and non-response correlated to mortality . CONCLUSION A sustained virological response secondary to IFN monotherapy or IFN/RBV combination therapy could reduce the risk for HCC and improve survival of CHC patients Background Pegylated interferon ( PegIFN ) plus ribavirin is the st and ard therapy for patients with chronic hepatitis C genotype 1 . Although several r and omized clinical trials have compared PegIFNα-2a with PegIFNα-2b , these 2 regimens have not been directly compared in Asian patients . We , therefore , compared the safety and antiviral efficacy of these agents in Japanese patients . Methods A total of 201 PegIFN-naïve , chronic hepatitis C patients were r and omly assigned to once-weekly PegIFNα-2a ( 180 μg ) or PegIFNα-2b ( 60–150 μg ) plus ribavirin . We compared the sustained virological response ( SVR ) rates between the 2 regimens and analyzed their effects in relation to baseline characteristics , including single nucleotide polymorphisms ( SNPs ) near the interleukin-28B ( IL28B ) gene ( rs8099917 ) . Results PegIFNα-2a was associated with a higher SVR rate than PegIFNα-2b ( 65.3 vs. 51.0 % , P = 0.039 ) . PegIFNα-2a and SNPs near IL28B independently predicted SVR ( odds ratio 2.36 ; 95 % confidence interval [ CI ] 1.19–15.50 , and odds ratio 7.31 ; 95 % CI 3.45–4.68 , respectively ) in logistic regression analysis . PegIFNα-2a was more effective than PegIFNα-2b ( 81.8 vs. 62.7 % , P = 0.014 ) in IL28B TT genotype patients , despite similarly low SVR rates in patients with TG or GG genotypes ( 36.4 vs. 35.9 % ) . Patients weighing < 60 kg , women , and patients aged > 60 years had significantly higher SVR rates with PegIFNα-2a than with PegIFNα-2b ( 63.9 , 61.3 , and 67.3 % vs. 43.8 , 43.3 , and 39.2 % , respectively ) . Conclusions PegIFNα-2a plus ribavirin result ed in higher SVR rates than PegIFNα-2b plus ribavirin in Japanese patients . PegIFNα-2a-based treatment should therefore be the preferred choice for women , older or low-weight patients , and those with the IL28B TT genotype BACKGROUND AND AIM We assessed whether the two regimens of pegylated alpha-interferon-2b ( PEG-IFN-alpha2b ) plus ribavirin and pegylated alpha-interferon-2a ( PEG-IFN-alpha2a ) plus ribavirin showed differences in terms of sustained virological response , withdrawal due to side-effects and dose adjustment requirements in the treatment of naive chronic hepatitis C virus ( HCV ) patients . METHODS A prospect i ve non-r and omized , open-label comparison was made of naive HCV-infected patients undergoing st and ard 24- or 48-week treatment with two PEG-IFN combined with weight-based dosing regimen of ribavirin ( PEG-IFN-alpha2a/ribavirin , n = 91 ; PEG-IFN-alpha2b/ribavirin , n = 92 ) . RESULTS Sustained virological response was similar in PEG-IFN-alpha2a and PEG-IFN-alpha2b ( 65.9 % vs 62 % , P = 0.64 ) , without differences according to genotype . In 117 patients with HCV genotype 1 , the corresponding rates were 50.8 % versus 46.6 % ( P = 0.713 ) . Rapid virological response at 4 weeks , early virological response at 12 weeks and transient virological response were also similar . In the multivariate analysis , HCV genotype ( odds ratio [ OR ] = 0.076 , 95 % confidence interval [ CI ] 0.029 - 0.198 , P = 0.000 ) and presence of steatosis in the liver biopsy ( OR = 2.799 , 95 % CI 1.362 - 5.755 , P = 0.005 ) were significantly associated with response to antiviral therapy . The rate of withdrawals due to treatment-related adverse events was 13.2 % in the group of PEG-IFN-alpha2a and 10.9 % in the group of PEG-IFN-alpha2b . Dose modification of PEG-IFN was necessary in eight patients given PEG-IFN-alpha2a and in seven given PEG-IFN-alpha2b . CONCLUSION The two PEG-IFN plus ribavirin have comparable anti-HCV activity as shown by similar percentages of patients with sustained virological response BACKGROUND & AIMS St and ard therapy of patients with chronic hepatitis C virus ( HCV ) infected with HCV genotype-2 or -3 is the combination of pegylated interferon-alpha and ribavirin for 24 weeks . Whether shorter treatment duration s are possible for these patients without compromising sustained virologic response rates is unknown . METHODS Patients chronically infected with HCV-2 ( n = 39 ) , HCV-2/3 ( n = 1 ) , or HCV-3 ( n = 113 ) were treated with peginterferon-alpha-2a ( 180 microg/wk ) plus ribavirin 800 - 1200 mg/day . HCV RNA was quantitatively assessed after 4 weeks . Patients with a rapid virologic response ( HCV RNA below 600 IU/mL ) were r and omized for a total treatment duration of 16 ( group A ) or 24 weeks ( group B ) . All patients with HCV RNA > or = 600 IU/mL at week 4 ( group C ) were treated for 24 weeks . End-of-treatment and sustained virologic response were assessed by qualitative RT-PCR ( sensitivity 50 IU/mL ) . RESULTS Only 11 of 153 patients ( 7 % ) were allocated to group C. End-of-treatment and sustained virologic response rates were 94 % and 82 % , ( group A ) , 85 % and 80 % ( group B ) , and 73 % and 36 % ( group C ) , respectively . In patients infected with genotype HCV-3 and high viral load ( > 800,000 IU/mL ) , a significant lower sustained virologic response rate was found than in patients infected with HCV-3 and a viral load lower or equal to 800,000 IU/mL ( 59 % vs 85 % , respectively ; P = .003 ) . CONCLUSIONS In HCV-2 and -3 ( low viral load)-infected patients who have a rapid virologic response , treatment for 16 weeks with peginterferon-alpha-2a and ribavirin is sufficient . In patients infected by HCV-3 ( high viral load ) , longer treatment may be necessary BACKGROUND & AIMS To evaluate the efficacy and safety of telaprevir in combination with peginterferon-α2b ( PEG-IFN ) and ribavirin ( RBV ) in patients with chronic hepatitis C. METHODS In a multi-center r and omized clinical trial in Japan , on patients infected with HCV of genotype 1 , 126 patients were assigned to telaprevir for 12 weeks along with PEG-IFN and RBV for 24 weeks ( Group A ) , while 63 to PEG-IFN and RBV for 48 weeks ( Group B ) . RESULTS HCV RNA disappeared more swiftly in patients in Group A than B , and the frequency of patients without detectable HCV RNA at week 4 ( rapid virological response ( RVR ) ) was higher in Group A than B ( 84.0 % vs. 4.8 % , p < 0.0001 ) . Grade 3 and 4 skin disorders , including Stevens-Johnson syndrome and drug rashes with eosinophilia and systemic symptoms , as well as Grade 3 anemia ( < 8.0 g/dl ) , occurred more frequently in Group A than B ( skin disorders , 11.9 % vs. 4.8 % ; anemia , 11.1 % vs. 0.0 % ) . The total RBV dose was smaller in Group A than B ( 47.0 % vs. 77.7 % of the target , p < 0.0001 ) . Despite these drawbacks , sustained virological response ( SVR ) was achieved more frequently in Group A than B ( 73.0 % vs. 49.2 % , p=0.0020 ) . CONCLUSIONS Although the triple therapy with telaprevir-based regimen for 24 weeks result ed in more adverse events and less total RBV dose than PEG-IFN and RBV for 48 weeks , it was able to achieve higher SVR within shorter duration by carefully monitoring adverse events and modifying the RBV dose as required Guidelines for the treatment of patients infected with hepatitis C virus of genotypes 2 and 3 ( HCV-2 and HCV-3 , respectively ) recommend a 24-week course of Peg-interferon ( Peg-IFN ) alpha-2a combined with ribavirin , despite 50 % of patients in registration trials attaining a sustained virologic response ( SVR ) following Peg-IFN alpha-2a monotherapy . The aim of this study was to delineate patient characteristics that might help to identify individuals likely to benefit from ribavirin discontinuation . One hundred and forty-four HCV-2- and HCV-3-infected patients initiated Peg-IFN alpha-2a ( 180 microg/week ) and ribavirin ( 1000 or 1200 mg/day ) ; those with viral clearance at week 4 were r and omized to either Peg-IFN alpha-2a monotherapy ( n = 59 ) or continuing combination therapy ( n = 61 ) until week 12 . Overall , all but one patient with a rapid virologic response ( RVR ) responded by the end of therapy and the overall SVR rates were lower after discontinuation of ribavirin ( 54%vs 82 % ; P < 0.001 ) . In RVR patients who discontinued ribavirin , low baseline viraemia helped predict SVR ( odds ratio 11.2 , 95 % CI 2.7 - 47.1 ) . SVR rates were similar in patients receiving mono- or combination therapy with low ( < or = 300,000 IU/mL ) and intermediate viraemia ( 86%vs 81 % and 70%vs 71 % , 86 % refers to low viraemic patients receiving monotherapy and 81 % to those receiving combination therapy . Similarly , 70 % refers to patients with intermediate viraemic levels receiving monotherapy and 71 % to those receiving combination therapy ) , but different in those with high ( > 700,000 IU/mL ) viraemia ( 37%vs 88 % ; P = 0.004 ) . Thus in HCV-2- and HCV-3-infected patients , withdrawal of ribavirin and continuation of Peg-IFN alpha-2a monotherapy may be appropriate to attain an SVR , providing viraemia is cleared early during therapy and associated with low baseline viral load . These results warrant future investigations , as discontinuing ribavirin could lead to considerable savings in cost and quality of life related to over-treatment UNLABELLED Retrospective studies suggest that subjects with chronic hepatitis C and advanced fibrosis who achieve a sustained virological response ( SVR ) have a lower risk of hepatic decompensation and hepatocellular carcinoma ( HCC ) . In this prospect i ve analysis , we compared the rate of death from any cause or liver transplantation , and of liver-related morbidity and mortality , after antiviral therapy among patients who achieved SVR , virologic nonresponders ( NR ) , and those with initial viral clearance but subsequent breakthrough or relapse ( BT/R ) in the HALT-C ( Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis ) Trial . Laboratory and /or clinical outcome data were available for 140 of the 180 patients who achieved SVR . Patients with nonresponse ( NR ; n = 309 ) or who experienced breakthrough or relapse ( BT/R ; n = 77 ) were evaluated every 3 months for 3.5 years and then every 6 months thereafter . Outcomes included death , liver-related death , liver transplantation , decompensated liver disease , and HCC . Median follow-up for the SVR , BT/R , and NR groups of patients was 86 , 85 , and 79 months , respectively . At 7.5 years , the adjusted cumulative rate of death/liver transplantation and of liver-related morbidity/mortality in the SVR group ( 2.2 % and 2.7 % , respectively ) was significantly lower than that of the NR group ( 21.3 % and 27.2 % , P < 0.001 for both ) but not the BT/R group ( 4.4 % and 8.7 % ) . The adjusted hazard ratio ( HR ) for time to death/liver transplantation ( HR = 0.17 , 95 % confidence interval [ CI ] = 0.06 - 0.46 ) or development of liver-related morbidity/mortality ( HR = 0.15 , 95 % CI = 0.06 - 0.38 ) or HCC ( HR = 0.19 , 95 % CI = 0.04 - 0.80 ) was significant for SVR compared to NR . Laboratory tests related to liver disease severity improved following SVR . CONCLUSION Patients with advanced chronic hepatitis C who achieved SVR had a marked reduction in death/liver transplantation , and in liver-related morbidity/mortality , although they remain at risk for HCC BACKGROUND AND AIMS In chronic hepatitis C virus ( HCV ) infection with genotype 3 , therapy with pegylated interferon ( peg-IFN ) alfa-2b in a dose of 1.5 mug/kg/week and ribavirin ( 800 - 1000 mg/day ) is recommended for 24 weeks . Reduced doses of peg-IFN may increase compliance and decrease cost and adverse events . This study aim ed to assess the safety and efficacy of two different regimens of peg-IFN alfa-2b , in combination with ribavirin , in genotype 3 patients . METHODS A total of 103 liver biopsy-proven chronic HCV patients with genotype 3 , having alanine aminotransferase levels > 1.2 x ULN and positive HCV-RNA were r and omized into two groups : group I ( n = 76 ; age , 43.1 + /- 11.4 years ; male/female , 67/9 ) received peg-IFN 1.0 mug/kg/week + ribavirin 10.6 mg/kg/day , while group II ( n = 27 ; age , 37.3 + /- 11.6 years ; male/female , 21/6 ) received peg-IFN 1.5 microg/kg/week + ribavirin 10.6 mg/kg/day . Patients in both groups were treated for 24 weeks . End of treatment viral response ( ETVR ) and sustained viral response ( SVR ) after a 6-month follow-up period were assessed . RESULTS In both groups I and II , one patient was lost to follow-up , while one patient in group II withdrew due to side-effects . ETVR was seen in 72/76 ( 94.7 % ) of patients in the low dose group and 24/27 ( 88.9 % ) of patients in the high dose group ( P = 0.375 ) . SVR was seen in 60/76 ( 78.9 % ) of patients in the low dose group and 25/27 ( 92.6 % ) of patients in the high dose group ( P = 0.145 ) . Age ( Pearson correlation coefficient = 0.263 ; P = 0.008 ) and fibrosis ( correlation coefficient , 0.263 ; P = 0.008 ) showed a significant correlation with the SVR . CONCLUSION In patients with genotype 3 , peg-IFN at 1.0 microg/kg/week with ribavirin is as effective as peg-IFN at 1.5 mug/kg/week with ribavirin BACKGROUND Treatment with pegylated interferon ( peginterferon ) and ribavirin for 48 weeks is more effective than conventional interferon and ribavirin in patients with chronic hepatitis C. OBJECTIVE To assess the efficacy and safety of 24 or 48 weeks of treatment with peginterferon-alpha2a plus a low or st and ard dose of ribavirin . DESIGN R and omized , double-blind trial . SETTING 99 international centers . PATIENTS 1311 patients with chronic hepatitis C. INTERVENTION Peginterferon-alpha2a , 180 microg/wk , for 24 or 48 weeks plus a low-dose ( 800 mg/d ) or st and ard weight-based dose ( 1000 or 1200 mg/d ) of ribavirin . MEASUREMENT Sustained virologic response : undetectable HCV RNA concentration at the end of treatment and during 12 to 24 weeks of follow-up . RESULTS Overall and in patients infected with HCV genotype 1 , 48 weeks of treatment was statistically superior to 24 weeks and st and ard-dose ribavirin was statistically superior to low-dose ribavirin . In patients with HCV genotype 1 , absolute differences in sustained virologic response rates between 48 and 24 weeks of treatment were 11.2 % ( 95 % CI , 3.6 % to 18.9 % ) and 11.9 % ( CI , 4.7 % to 18.9 % ) , respectively , between st and ard- and low-dose ribavirin . Sustained virologic response rates for peginterferon-alpha2a and st and ard-dose ribavirin for 48 weeks were 63 % ( CI , 59 % to 68 % ) overall and 52 % ( CI , 46 % to 58 % ) in patients with HCV genotype 1 . In patients with HCV genotypes 2 or 3 , the sustained virologic response rates in the 4 treatment groups were not statistically significantly different . CONCLUSION Treatment with peginterferon-alpha2a and ribavirin may be individualized by genotype . Patients with HCV genotype 1 require treatment for 48 weeks and a st and ard dose of ribavirin ; those with HCV genotypes 2 or 3 seem to be adequately treated with a low dose of ribavirin for 24 weeks BACKGROUND & AIMS Patients with chronic hepatitis C virus ( HCV ) infection are frequently treated with a combination of pegylated interferon ( peginterferon ) and ribavirin . This study compared the efficacy and safety of peginterferon alfa-2a and peginterferon alfa-2b , each in combination with ribavirin . METHODS A total of 320 consecutive , treatment-naive , HCV RNA-positive patients with chronic hepatitis were r and omly assigned to once-weekly peginterferon alfa-2a ( 180 microg , group A ) or peginterferon alfa-2b ( 1.5 microg/kg , group B ) plus ribavirin 1000 mg/day ( body weight < 75 kg ) or 1200 mg/day ( body weight > or=75 kg ) for 48 weeks ( genotype 1 or 4 ) or 24 weeks ( genotype 2 or 3 ) . The primary end point was sustained virological response ( SVR ) by intention-to-treat . RESULTS More patients in group A than group B achieved an SVR ( 110/160 [ 68.8 % ] vs 87/160 [ 54.4 % ] ; P = .008 ) . Higher SVR rates were obtained in group A than group B among patients with genotype 1/4 ( 51/93 [ 54.8 % ] vs 37/93 [ 39.8 % ] ; P = .04 ) , with genotype 2/3 ( 59/67 [ 88.1 % ] vs 50/67 [ 74.6 % ] ; P = .046 ) , without cirrhosis ( 96/127 [ 75.6 % ] vs 75/134 [ 55.9 % ] ; P = .005 ) , and with baseline levels HCV RNA > 500,000 IU/mL ( 58/84 [ 69 % ] vs 43/93 [ 46.2 % ] ; P = .002 ) . SVR rates in groups A and B were not statistically different among patients with baseline HCV RNA < or=500,000 IU/mL ( 52/76 [ 68.4 % ] vs 44/67 [ 65.7 % ] ; P = .727 ) or in patients with cirrhosis ( 14/33 [ 42.4 % ] vs 12/26 [ 46.1 % ] ; P = .774 ) . CONCLUSIONS In patients with chronic HCV infection , peginterferon alfa-2a plus ribavirin produced a significantly higher SVR rate than peginterferon alfa-2b plus ribavirin BACKGROUND & AIMS Recent studies have shown that 12 weeks of treatment with telaprevir , administered every 8 hours ( q8h ) , combined with pegylated interferon ( peginterferon ) alfa-2a plus ribavirin significantly increased the rate of hepatitis C virus ( HCV ) eradication ( sustained virologic response [ SVR ] ) in patients infected with HCV genotype 1 compared with approved therapy . We investigated the efficacy , safety , tolerability , and pharmacokinetics of telaprevir given q8h or every 12 hours ( q12 h ) in combination with peginterferon alfa-2a or alfa-2b . METHODS Treatment-naive patients ( n = 161 ) infected with HCV genotype 1 were r and omly assigned to groups that were given open-label telaprevir ( 750 mg q8 h or 1125 mg q12 h ) in combination with st and ard doses of peginterferon alfa-2a ( 180 μg/wk ) and ribavirin ( 1000 - 1200 mg/day ) or peginterferon alfa-2b ( 1.5 μg·kg(-1)·wk(-1 ) ) and ribavirin ( 800 - 1200 mg/day ) . Patients received triple therapy for 12 weeks , followed by 12 or 36 additional weeks of treatment with peginterferon alfa and ribavirin , based on virologic response . RESULTS Baseline characteristics were similar for all groups . SVR rates were 81.0 % to 85.0 % among groups ; most patients received 24 weeks of therapy ( 68.0 % ) . There were no significant differences in SVR rates ( intent-to-treat analysis ) among groups ( P ≥ .787 ) , between the pooled q8 h and q12 h groups ( P = .997 ) , or between the pooled peginterferon alfa-2a/ribavirin and peginterferon alfa-2b/ribavirin groups ( P = .906 ) . The safety profile was similar among all groups . CONCLUSIONS A high proportion ( > 80 % ) of patients achieved an SVR regardless of the telaprevir dosing frequency ( q8 h or q12 h ) or type of peginterferon alfa used ( alfa-2a or alfa-2b ) BACKGROUND & AIMS Patients with chronic hepatitis C and persistently normal alanine aminotransferase ( ALT ) levels have been routinely excluded from large r and omized treatment trials ; consequently , the efficacy and safety of antiviral therapy in this population are unknown . METHODS Patients with at least 3 normal ALT values over an 18-month period were r and omized ( 3:3:1 ) to treatment with peginterferon alfa-2a 180 mug/wk plus ribavirin 800 mg/day for 24 weeks ( 212 patients ) , the same combination for 48 weeks ( 210 patients ) , or no treatment ( 69 patients ) in a multinational study . All patients were monitored for 72 weeks . The primary measure of efficacy was sustained virologic response ( SVR ) , defined as undetectable serum hepatitis C virus ( HCV ) RNA by qualitative polymerase chain reaction at the end of 24 weeks of untreated follow-up . RESULTS No patient cleared HCV RNA in the untreated control group . SVR rates of 30 % and 52 % were obtained in the 24- and 48-week treatment groups , respectively . In patients infected with HCV genotype 1 , SVR rates of 13 % and 40 % were obtained with 24 and 48 weeks of treatment , respectively ( P < .0001 ) . In patients infected with genotypes 2 or 3 , SVR rates were 72 % and 78 % with 24 and 48 weeks of treatment , respectively ( P = .452 ) . Treatment-related flares in ALT activity were not observed . CONCLUSIONS The efficacy and safety of peginterferon alfa-2a and ribavirin combination therapy in patients with chronic hepatitis C and persistently normal ALT levels are similar to that in patients with elevated ALT levels . The indication for treatment of hepatitis C can be evaluated independently from baseline ALT activity |
1,813 | 11,869,564 | There is no evidence that ' long course therapy ' is superior to ' short course therapy ' .
REVIEW ER 'S CONCLUSIONS Zidovudine , nevirapine and delivery by elective caesarean section appear to be very effective in decreasing the risk of mother-to-child transmission of HIV infection | BACKGROUND At the end of 1998 over 33 million people were infected with the human immunodeficiency virus ( HIV ) and over one million children had been infected from their mothers .
OBJECTIVES The objective of this review was to assess what interventions may be effective in decreasing the risk of mother-to-child transmission of HIV infection as well as their effect on neonatal and maternal mortality and morbidity . | BACKGROUND The AIDS Clinical Trials Group protocol 076 zidovudine prophylaxis regimen for HIV-1-infected pregnant women and their babies has been associated with a significant decrease in vertical HIV-1 transmission in non-breastfeeding women in developed countries . We compared the safety and efficacy of short-course nevirapine or zidovudine during labour and the first week of life . METHODS From November , 1997 , to April , 1999 , we enrolled 626 HIV-1-infected pregnant women at Mulago Hospital in Kampala , Ug and a. We r and omly assigned mothers nevirapine 200 mg orally at onset of labour and 2 mg/kg to babies within 72 h of birth , or zidovudine 600 mg orally to the mother at onset of labour and 300 mg every 3 h until delivery , and 4 mg/kg orally twice daily to babies for 7 days after birth . We tested babies for HIV-1 infection at birth , 6 - 8 weeks , and 14 - 16 weeks by HIV-1 RNA PCR . We assessed HIV-1 transmission and HIV-1-free survival with Kaplan-Meier analysis . FINDINGS Nearly all babies ( 98.8 % ) were breastfed , and 95.6 % were still breastfeeding at age 14 - 16 weeks . The estimated risks of HIV-1 transmission in the zidovudine and nevirapine groups were : 10.4 % and 8.2 % at birth ( p=0.354 ) ; 21.3 % and 11.9 % by age 6 - 8 weeks ( p=0.0027 ) ; and 25.1 % and 13.1 % by age 14 - 16 weeks ( p=0.0006 ) . The efficacy of nevirapine compared with zidovudine was 47 % ( 95 % CI 20 - 64 ) up to age 14 - 16 weeks . The two regimens were well tolerated and adverse events were similar in the two groups . INTERPRETATION Nevirapine lowered the risk of HIV-1 transmission during the first 14 - 16 weeks of life by nearly 50 % in a breastfeeding population . This simple and inexpensive regimen could decrease mother-to-child HIV-1 transmission in less-developed countries The safety , toxicity , and pharmacokinetics of intrapartum and early newborn nevirapine were evaluated in 17 human immunodeficiency virus type 1-infected women in labor and their newborns . No adverse effects of nevirapine were noted in any study mothers or infants . Following maternal dosing with 200 mg during labor , concentrations exceeding 100 ng/mL ( 10 times the in vitro IC50 ) were achieved in the newborns . Nevirapine elimination was prolonged in both mothers and infants , with median half-lives ranging from 36.8 to 65.7 h. Administration of 200 mg orally to the mothers in labor and of a single 2-mg/kg oral dose to the infants at 48 - 72 h after birth maintained serum concentrations in the infants > 100 ng/mL through 7 days of life BACKGROUND Perinatal transmission of human immunodeficiency virus ( HIV ) type 1 contributes significantly to infant mortality . Exposure in the birth canal may account for some transmission . We examined the efficacy of a birth canal washing procedure in reducing perinatal transmission in Malawi . METHODS The infection status of infants of 3327 control women ( conventional delivery procedures ) was compared with that of 3637 infants of intervention-delivered women . The infants ' HIV status was determined by polymerase chain reaction on dried blood spots collected at 6 and 12 weeks of age . The intervention consisted of manual cleansing of the birth canal with a cotton pad soaked in 0.25 % chlorhexidine , which was done on admission in labour and every 4 h until delivery . FINDINGS No adverse reactions to the intervention procedure were seen . 2094 ( 30 % ) of the enrolled women were HIV-infected , and 59 % of their infants were seen in follow-up . Among 982 vaginal vertex singleton deliveries to HIV-infected women , 269 ( 27 % ) infants were infected . The intervention had no significant impact on HIV transmission rates ( 27 % in 505 intervention women compared with 28 % in 477 control women ) , except when membranes were ruptured more than 4 h before delivery ( transmission 25 % in the intervention group vs 39 % in the control group ) . INTERPRETATION If birth canal exposure is an important risk factor , different or additional methods to reduce the risk of perinatal HIV transmission should be tested . Alternatively , perhaps birth canal exposure is not a major contributor to perinatal infection risk BACKGROUND In HIV-1-infected women , poor micronutrient status has been associated with faster progression of HIV-1 disease and adverse birth outcomes . We assessed the effects of vitamin A and multivitamins on birth outcomes in such women . METHODS In Tanzania , 1075 HIV-1-infected pregnant women at between 12 and 27 weeks ' gestation received placebo ( n=267 ) , vitamin A ( n=269 ) , multivitamins excluding vitamin A ( n=269 ) , or multivitamins including vitamin A ( n=270 ) in a r and omised , double-blind , placebo-controlled trial with a 2x2 factorial design . We measured the effects of multivitamins and vitamin A on birth outcomes and counts of T lymphocyte subsets . We did analyses by intention to treat . RESULTS 30 fetal deaths occurred among women assigned multivitamins compared with 49 among those not on multivitamins ( relative risk 0.61 [ 95 % CI 0.39 - 0.94 ] p=0.02 ) . Multivitamin supplementation decreased the risk of low birthweight ( < 2500 g ) by 44 % ( 0.56 [ 0.38 - 0.82 ] p=0.003 ) , severe preterm birth ( < 34 weeks of gestation ) by 39 % ( 0.61 [ 0.38 - 0.96 ] p=0.03 ) , and small size for gestational age at birth by 43 % ( 0.57 [ 0.39 - 0.82 ] p=0.002 ) . Vitamin A supplementation had no significant effect on these variables . Multivitamins , but not vitamin A , result ed in a significant increase in CD4 , CD8 , and CD3 counts . INTERPRETATION Multivitamin supplementation is a low-cost way of substantially decreasing adverse pregnancy outcomes and increasing T-cell counts in HIV-1-infected women . The clinical relevance of our findings for vertical transmission and clinical progression of HIV-1 disease is yet to be ascertained BACKGROUND AND METHODS Maternal-infant transmission is the primary means by which young children become infected with human immunodeficiency virus type 1 ( HIV ) . We conducted a r and omized , double-blind , placebo-controlled trial of the efficacy and safety of zidovudine in reducing the risk of maternal-infant HIV transmission . HIV-infected pregnant women ( 14 to 34 weeks ' gestation ) with CD4 + T-lymphocyte counts above 200 cells per cubic millimeter who had not received antiretroviral therapy during the current pregnancy were enrolled . The zidovudine regimen included antepartum zidovudine ( 100 mg orally five times daily ) , intrapartum zidovudine ( 2 mg per kilogram of body weight given intravenously over one hour , then 1 mg per kilogram per hour until delivery ) , and zidovudine for the newborn ( 2 mg per kilogram orally every six hours for six weeks ) . Infants with at least one positive HIV culture of peripheral-blood mononuclear cells were classified as HIV-infected . RESULTS From April 1991 through December 20 , 1993 , the cutoff date for the first interim analysis of efficacy , 477 pregnant women were enrolled ; during the study period , 409 gave birth to 415 live-born infants . HIV-infection status was known for 363 births ( 180 in the zidovudine group and 183 in the placebo group ) . Thirteen infants in the zidovudine group and 40 in the placebo group were HIV-infected . The proportions infected at 18 months , as estimated by the Kaplan-Meier method , were 8.3 percent ( 95 percent confidence interval , 3.9 to 12.8 percent ) in the zidovudine group and 25.5 percent ( 95 percent confidence interval , 18.4 to 32.5 percent ) in the placebo group . This corresponds to a 67.5 percent ( 95 percent confidence interval , 40.7 to 82.1 percent ) relative reduction in the risk of HIV transmission ( Z = 4.03 , P = 0.00006 ) . Minimal short-term toxic effects were observed . The level of hemoglobin at birth in the infants in the zidovudine group was significantly lower than that in the infants in the placebo group . By 12 weeks of age , hemoglobin values in the two groups were similar . CONCLUSIONS In pregnant women with mildly symptomatic HIV disease and no prior treatment with antiretroviral drugs during the pregnancy , a regimen consisting of zidovudine given ante partum and intra partum to the mother and to the newborn for six weeks reduced the risk of maternal-infant HIV transmission by approximately two thirds We conducted a double-blind , placebo-controlled trial of the efficacy of oral azidothymidine ( AZT ) in 282 patients with the acquired immunodeficiency syndrome ( AIDS ) manifested by Pneumocystis carinii pneumonia alone , or with advanced AIDS-related complex . The subjects were stratified according to numbers of T cells with CD4 surface markers and were r and omly assigned to receive either 250 mg of AZT or placebo by mouth every four hours for a total of 24 weeks . One hundred forty-five subjects received AZT , and 137 received placebo . When the study was terminated , 27 subjects had completed 24 weeks of the study , 152 had completed 16 weeks , and the remainder had completed at least 8 weeks . Nineteen placebo recipients and 1 AZT recipient died during the study ( P less than 0.001 ) . Opportunistic infections developed in 45 subjects receiving placebo , as compared with 24 receiving AZT . The base-line Karnofsky performance score and weight increased significantly among AZT recipients ( P less than 0.001 ) . A statistically significant increase in the number of CD4 cells was noted in subjects receiving AZT ( P less than 0.001 ) . After 12 weeks , the number of CD4 cells declined to pretreatment values among AZT recipients with AIDS but not amonG AZT recipients with AIDS-related complex . Skin-test anergy was partially reversed in 29 percent of subjects receiving AZT , as compared with 9 percent of those receiving placebo ( P less than 0.001 ) . These data demonstrate that AZT administration can decrease mortality and the frequency of opportunistic infections in a selected group of subjects with AIDS or AIDS-related complex , at least over the 8 to 24 weeks of observation in this study The goal of this exercise was to provide estimates of the mother-to-child transmission rate ( TR ) of human immunodeficiency virus type 1 ( HIV-1 ) , calculated according to st and ardized methods . Prospect i ve cohort studies in Africa ( 8) , the Caribbean ( 1 ) , Europe ( 3 ) , and the U.S.A. ( 1 ) observed from birth children born to women known to be HIV infected at the time of delivery . TRs were calculated and compared by investigators during a meeting in Ghent ( Belgium ) in September 1993 according to agreed methodology . TRs were calculated following the direct and the indirect methods developed in 1992 by the Ghent Working Group . The direct method uses a classification of children born to HIV-seropositive mothers according to their probable HIV infection status at 15 months of age or before , if they die or are lost to follow-up . Minimum , intermediate , and maximum estimates of TR are computed depending on how children classified as indeterminate are counted . The indirect method is applied for studies with a comparison cohort of children born to HIV-seronegative mothers . TRs in developed countries ranged from 14 to 25 % with the direct method ( intermediate estimate ) . In the developing world , they ranged from 13 to 42 % with the direct method , from 21 to 43 % with the indirect method , and most of the studies reported a TR in the range of 25 to 30 % . With use of a st and ardized methodology , the overall TR of HIV-1 tends to be higher in Africa than in Europe or the U.S.A. ( ABSTRACT TRUNCATED AT 250 WORDS CONTEXT With the success of zidovudine chemoprophylaxis for prevention of perinatal transmission of the human immunodeficiency virus ( HIV ) , an increasing number of HIV-exposed but uninfected children will have in utero exposure to zidovudine and other antiretroviral drugs . OBJECTIVE To evaluate the long-term effects of in utero exposure to zidovudine vs placebo among a r and omized cohort of uninfected children . DESIGN Prospect i ve cohort study based on data collected during Pediatric AIDS Clinical Trials Group Protocol 076 , a perinatal zidovudine HIV prevention trial , and Protocol 219 , a long-term observational protocol . SETTING Pediatric research clinics in the United States . PATIENTS Two hundred thirty-four uninfected children born to 230 HIV-infected women enrolled in Protocol 076 and followed up through February 28 , 1997 , in Protocol 219 ( 122 in the zidovudine group and 112 in the placebo group ) . MAIN OUTCOME MEASURES Physical growth measurements , immunologic parameters , cognitive/developmental function , occurrence of neoplasms , and mortality data assessed every 6 months for children younger than 24 months and yearly thereafter or as clinical ly indicated . Baseline echocardiogram and funduscopic evaluations were collected before 36 months of age . RESULTS Median age of children at time of last follow-up visit was 4.2 years ( range , 3.2 - 5.6 years ) . There were no significant differences between children exposed to zidovudine and those who received placebo in terms of sequential data on lymphocyte subsets ; weight , height , and head circumference z scores ; and cognitive/developmental function . No deaths or malignancies occurred . Two children ( both exposed to zidovudine ) are being followed up for abnormal , unexplained ophthalmic findings . One child exposed to zidovudine had a mild cardiomyopathy on echocardiogram at the age of 48 months ; the child is clinical ly asymptomatic . CONCLUSIONS No adverse effects were observed in HIV-uninfected children with in utero and neonatal exposure to zidovudine followed up for as long as 5.6 years . Continued prospect i ve evaluations of children born to HIV-infected women who are exposed to antiretroviral or immunotherapeutic agents are critical to assess the long-term safety of interventions that prevent perinatal HIV transmission BACKGROUND The efficacy and safety of adding a protease inhibitor to two nucleoside analogues to treat human immunodeficiency virus type 1 ( HIV-1 ) infection are not clear . We compared treatment with the protease inhibitor indinavir in addition to zidovudine and lamivudine with treatment with the two nucleosides alone in HIV-infected adults previously treated with zidovudine . METHODS A total of 1156 patients not previously treated with lamivudine or protease inhibitors were stratified according to CD4 cell count ( 50 or fewer vs. 51 to 200 cells per cubic millimeter ) and r and omly assigned to one of two daily regimens : 600 mg of zidovudine ( or stavudine ) and 300 mg of lamivudine , or that regimen with 2400 mg of indinavir . The primary end point was the time to the development of the acquired immunodeficiency syndrome ( AIDS ) or death . RESULTS The proportion of patients whose disease progressed to AIDS or death was lower with indinavir , zidovudine , and lamivudine ( 6 percent ) than with zidovudine and lamivudine alone ( 11 percent ; estimated hazard ratio , 0.50 ; 95 percent confidence interval , 0.33 to 0.76 ; P=0.001 ) . Mortality in the two groups was 1.4 percent and 3.1 percent , respectively ( estimated hazard ratio , 0.43 ; 95 percent confidence interval , 0.19 to 0.99 ; P=0.04 ) . The effects of treatment were similar in both CD4 cell strata . The responses of CD4 cells and plasma HIV-1 RNA paralleled the clinical results . CONCLUSIONS Treatment with indinavir , zidovudine , and lamivudine as compared with zidovudine and lamivudine alone significantly slows the progression of HIV-1 disease in patients with 200 CD4 cells or fewer per cubic millimeter and prior exposure to zidovudine BACKGROUND Many developing countries have not implemented the AIDS Clinical Trials Group 076 zidovudine regimen for prevention of perinatal HIV-1 transmission because of its complexity and cost . We investigated the safety and efficacy of short-course oral zidovudine administered during late pregnancy and labour . METHODS In a r and omised , double-blind , placebo-controlled trial , HIV-1-infected pregnant women at two Bangkok hospitals were r and omly assigned placebo or one zidovudine 300 mg tablet twice daily from 36 weeks ' gestation and every 3 h from onset of labour until delivery . Mothers were given infant formula and asked not to breastfeed . The main endpoint was babies ' HIV-1-infection status , tested with HIV-1-DNA PCR at birth , 2 months , and 6 months . We measured maternal plasma viral concentrations by RNA PCR . FINDINGS Between May , 1996 , and December , 1997 , 397 women were r and omised ; 393 gave birth to 395 live-born babies . Median duration of antenatal treatment was 25 days , and median number of doses during labour was three . 99 % of women took at least 90 % of scheduled antenatal doses . Adverse events were similar in the study groups . Of 392 babies with at least one PCR test , 55 tested positive : 18 in the zidovudine group and 37 in the placebo group . The estimated transmission risks were 9.4 % ( 95 % CI 5.2 - 13.5 ) on zidovudine and 18.9 % ( 13.2 - 24.2 ) on placebo ( p=0.006 ; efficacy 50.1 % [ 15.4 - 70.6 ] ) . Between enrolment and delivery , women in the zidovudine group had a mean decrease in viral load of 0.56 log . About 80 % of the treatment effect was explained by lowered maternal viral concentrations at delivery . INTERPRETATION A short course of twice-daily oral zidovudine was safe and well tolerated and , in the absence of breastfeeding , can lessen the risk for mother-to-child HIV-1 transmission by half . This regimen could prevent many HIV-1 infections during late pregnancy and labour in less-developed countries unable to implement the full 076 regimen BACKGROUND In Africa , the risk of mother-to-child transmission of HIV-1 infection is high . Short-course perinatal oral zidovudine might decrease the rate of transmission . We assessed the safety and efficacy of such a regimen among HIV-1-seropositive breastfeeding women in Abidjan , Côte d'Ivoire . METHODS From April , 1996 , to February , 1998 , all consenting , eligible HIV-1-seropositive pregnant women attending a public antenatal clinic in Abidjan were enrolled at 36 weeks ' gestation and r and omly assigned placebo or zidovudine ( 300 mg tablets ) , one tablet twice daily until the onset of labour , one tablet at onset of labour , and one tablet every 3 h until delivery . We used HIV-1-DNA PCR to test the infection status of babies at birth , 4 weeks , and 3 months . We stopped the study on Feb 18 , 1998 , when efficacy results were available from a study in Bangkok , Thail and , in which the same regimen was used in a non-breastfeeding population . FINDINGS 280 women were enrolled ( 140 in each group ) . The median duration of the prenatal drug regimen was 27 days ( range 1 - 80 ) and the median duration of labour was 7.5 h. Treatment was well tolerated with no withdrawals because of adverse events . All babies were breastfed . Among babies with known infection status at age 3 months , 30 ( 26.1 % ) of 115 babies in the placebo group and 19 ( 16.5 % ) of 115 in the zidovudine group were identified as HIV-1 infected . The estimated risk of HIV-1 transmission in the placebo and zidovudine groups were 21.7 % and 12.2 % ( p=0.05 ) at 4 weeks , and 24.9 % and 15.7 % ( p=0.07 ) at 3 months . Efficacy was 44 % ( 95 % CI -1 to 69 ) at age 4 weeks and 37 % ( -5 to 63 ) at 3 months . INTERPRETATION Short-course oral zidovudine was safe , well tolerated , and decreased mother-to-child transmission of HIV-1 at age 3 months . Substantial efforts will be needed to ensure successful widespread implementation of such a regimen BACKGROUND AND METHODS A placebo-controlled trial has shown that treatment with zidovudine reduces the rate at which human immunodeficiency virus type 1 ( HIV-1 ) is transmitted from mother to infant . We present data from that trial showing the number of infected infants at 18 months of age and the relation between the maternal viral load , the risk of HIV-1 transmission , and the efficacy of zidovudine treatment . Viral cultures were obtained , and HIV-1 RNA was measured by two assays in sample s of maternal blood obtained at study entry and at delivery . RESULTS In 402 mother-infant pairs , the rate of transmission of HIV-1 was 7.6 percent ( 95 percent confidence interval , 4.3 to 12.3 percent ) with zidovudine treatment and 22.6 percent ( 95 percent confidence interval , 17.0 to 29.0 percent ) with placebo ( P<0.001 ) . In the placebo group , a large viral burden at entry or delivery or a positive culture was associated with an increased risk of transmission ( the transmission rate was greater than 40 percent in the highest quartile of the RNA level ) . In both groups , transmission occurred at a wide range of maternal plasma HIV-1 RNA levels . Zidovudine reduced plasma RNA levels somewhat ( median reduction , 0.24 log ) . Zidovudine was effective regardless of the HIV-1 RNA level or the CD4 + count at entry . In the zidovudine group , however , after we adjusted for the base-line HIV-1 RNA level and CD4 + count , the reduction in viral RNA from base line to delivery was not significantly associated with the risk of transmission of HIV-1 . CONCLUSIONS A high maternal plasma concentration of virus is a risk factor for the transmission of HIV-1 from an untreated mother to her infant . The reduction in such transmission after zidovudine treatment is only partly explained by the reduction in plasma levels of viral RNA . To prevent HIV-1 transmission , initiating maternal treatment with zidovudine is recommended regardless of the plasma level of HIV-1 RNA or the CD4 + count Objective During the pilot phase of a trial to evaluate the effectiveness of caesarean section delivery compared with vaginal delivery in reducing mother‐to‐child transmission of human immunodeficiency virus ( HIV ) infection , the feasibility of r and omisation to mode of delivery was assessed OBJECTIVE To determine the safety , pharmacokinetics , tolerance , antiretroviral activity , and infant HIV infection status after giving a single dose of nevirapine to HIV-1-infected pregnant women during labor and their newborns during the first week of life . DESIGN An open label phase I/II study . SETTING Tertiary care hospital , Kampala , Ug and a. PATIENTS AND INTERVENTIONS Nevirapine , 200 mg , was given as a single dose during labor to 21 HIV-1-infected pregnant Ug and an women . In cohort 1 , eight infants did not receive nevirapine whereas in cohort 2 , 13 infants received a single dose of nevirapine , 2 mg/kg , at 72 h of age . OUTCOMES The number and type of adverse events ; nevirapine concentrations in the plasma and breast milk ; maternal plasma HIV-1 RNA copy number before and up to 6 weeks after delivery ; and HIV-1 infection status of the infants were monitored . RESULTS Nevirapine was well tolerated by women and infants ; no serious adverse events that were related to nevirapine were observed . Median nevirapine concentration in the women at delivery was 1623 ng/ml ( range 238 - 2356 ng/ml ) ; median cord/maternal blood ratio of 0.75 ( 0.37 - 0.93 ) . The median half-life in women was 61.3 h ( 27 - 90 h ) and the transplacental nevirapine half-life in infants who did not receive a neonatal dose was 54 h. The median half-life after a single dose at 72 h in infants was 46.5 h. During the first week of life , the median colostrum/breast milk to maternal plasma nevirapine concentration was 60.5 % ( 25 - 122 % ) . The median nevirapine concentration in breast milk 1 week after delivery was 103 ng/ml ( 25 - 309 ng/ml ) . Plasma nevirapine concentrations were above 100 ng/ml in all infants from both cohorts tested at age 7 days . Maternal HIV-1 RNA levels decreased by a median of 1.3 logs at 1 week postpartum , and returned to baseline by 6 weeks postpartum . Detectable plasma HIV-1 RNA was observed in one out of 22 ( 4.5 % ) infants at birth ; three out of 21 ( 14 % ) at 6 weeks ; and four out of 21 ( 19 % ) at 6 months of age . CONCLUSION The administration of a single dose of nevirapine to women during labor and to their newborns at 72 h was well tolerated and showed potent antiretroviral activity in the women at 1 week after dosing without rebound above baseline 6 weeks after a single dose . The nevirapine concentration was maintained above the target of 100 ng/ml in infants at age 7 days , even in those infants not receiving a neonatal dose . This regimen has promise as prophylaxis against intrapartum and early breast milk transmission in a breastfeeding population BACKGROUND Zidovudine reduces the rate of vertical transmission of HIV in non-breastfed population s. We assessed the acceptability , tolerance , and 6-month efficacy of a short regimen of oral zidovudine in African population s practising breastfeeding . METHODS A r and omised double-blind placebo-controlled trial was carried out in public clinics of Abidjan , Côte d'Ivoire , and Bobo-Dioulasso , Burkina Faso . Eligible participants were women aged 18 years or older , who had confirmed HIV-1 infection and pregnancy of 36 - 38 weeks duration , and who gave written informed consent . Exclusion criteria were severe anaemia , neutropenia , abnormal liver function , and sickle-cell disease . Women were r and omly assigned zidovudine ( n=214 ; 300 mg twice daily until labour , 600 mg at beginning of labour , and 300 mg twice daily for 7 days post partum ) or matching placebo ( n=217 ) . The primary outcome was the diagnosis of HIV-1 infection in the infant on the basis of sequential DNA PCR tests at days 1 - 8 , 45 , 90 , and 180 . We compared the probability of infection at a given age in the two groups . Analyses were by intention to treat . FINDINGS Women were enrolled between September , 1995 , and February , 1998 , when enrolment to the placebo group was stopped . Analysis was based on 421 women and 400 lifeborn infants . Baseline demographic , clinical , and laboratory characteristics were similar in the two groups . The Kaplan-Meier probability of HIV infection in the infant at 6 months was 18.0 % in the zidovudine group ( n=192 ) and 27.5 % in the placebo group ( n=197 ; relative efficacy 0.38 [ 95 % CI 0.05 - 0.60 ] ; p=0.027 ) . Adjustment for centre , period of recruitment , mode of delivery , maternal CD4-cell count , duration of labour , prolonged rupture of membranes , and duration of breastfeeding did not change the treatment effect . The proportions of women taking more than 80 % of the planned maximum dose were 75 % before delivery , 81 % during labour , and 83 % post partum , without statistical difference between the groups . No major adverse biological or clinical event was reported in excess among women and children of the zidovudine group . INTERPRETATION A short course of oral zidovudine given during the peripartum period is well accepted and well tolerated , and provides a 38 % reduction in early vertical transmission of HIV-1 infection despite breastfeeding Pediatric AIDS Clinical Trials Group protocol 185 evaluated whether zidovudine combined with human immunodeficiency virus ( HIV ) hyperimmune immunoglobulin ( HIVIG ) infusions administered monthly during pregnancy and to the neonate at birth would significantly lower perinatal HIV transmission compared with treatment with zidovudine and intravenous immunoglobulin ( IVIG ) without HIV antibody . Subjects had baseline CD4 cell counts < /=500/microL ( 22 % had counts < 200/microL ) and required zidovudine for maternal health ( 24 % received zidovudine before pregnancy ) . Transmission was associated with lower maternal baseline CD4 cell count ( odds ratio , 1.58 per 100-cell decrement ; P=.005 ; 10.0 % vs. 3.6 % transmission for count < 200 vs. > /=200/microL ) but not with time of zidovudine initiation ( 5.6 % vs. 4.8 % if started before vs. during pregnancy ; P=. 75 ) . The Kaplan-Meier transmission rate for HIVIG recipients was 4 . 1 % ( 95 % confidence interval , 1.5%-6.7 % ) and for IVIG recipients was 6.0 % ( 2.8%-9.1 % ) ( P=.36 ) . The unexpectedly low transmission confirmed that zidovudine prophylaxis is highly effective , even for women with advanced HIV disease and prior zidovudine therapy , although it limited the study 's ability to address whether passive immunization diminishes perinatal transmission |
1,814 | 19,349,632 | Commonly Used LDL Subfraction Tests and Terms If LDL subfractions are predictive of cardiovascular risk and are of incremental value when added to established cardiovascular risk factors , it remains to be determined whether the different characteristics of the LDL subfractions assessed by various methods would result in similar predictive abilities for estimating cardiovascular risk .
Lipid research ers have proposed that small , dense LDL particles confer greater atherogenic risk than larger , less dense LDL particles ( 6 , 7 ) . | A critical component of lowering the cardiovascular disease burden across the population is identification and aggressive treatment of high-risk individuals .
The Adult Treatment Panel III of the Expert Panel of the National Cholesterol Education Program ( 1 ) has identified a group of risk factors associated with cardiovascular disease , including elevated low-density lipoprotein ( LDL ) cholesterol concentrations , cigarette smoking , hypertension , reduced high-density lipoprotein ( HDL ) cholesterol concentrations , family history of premature coronary heart disease , and older age .
Current efforts have focused on determining whether additional diagnostic criteria could improve the accuracy of cardiovascular disease risk estimation ( 25 ) .
Measures of LDL subfractions have been suggested as a potential risk factor .
Many terms are used to describe the characteristics and distribution of LDL particles ; these include LDL subclasses , particles , particle concentration , particle numbers , and various patterns .
In vitro , small , dense LDL particles are more avidly taken up by macrophages than larger , less dense LDL particles ; are more susceptible to oxidative modification , have a greater propensity for transport into the arterial subendothelial space ; and have a greater binding potential to arterial wall proteoglycans ( 8 , 9 ) .
The American Diabetes Association and the American College of Cardiology Foundation convened a panel of experts to develop a consensus position for patients with cardiometabolic risk ( 10 ) .
They noted that limited data from cross-sectional and prospect i ve studies suggest that LDL particle number may be a better discriminator of cardiometabolic risk than LDL cholesterol concentrations .
They pointed out several limitations , including availability and accuracy of the method and consistency of the predictive power across ethnic groups , ages , and conditions that affect lipid metabolism .
They concluded that it is yet to be determined whether treatment decisions would be improved if LDL subfraction measurements were added to the current risk factors used to estimate cardiovascular risk .
We sought to evaluate the association between LDL subfractions and incidence and progression of clinical cardiovascular disease .
We also summarize the potential value of LDL subfraction tests used only in research laboratories . | BACKGROUND The natural history of atherosclerosis progression following revascularization procedures ( PTCA or CABG ) limits the long-term benefits of these procedures and requires continuation of risk management . MATERIAL / METHODS Of 392 patients with multivessel disease r and omized to an initial strategy of PTCA or CABG in the Emory Angioplasty Versus Surgery Trial ( EAST ) , 298 patients ( 152 PTCA and 146 CABG ) completed 3-year angiographic follow-up . Native coronary artery disease progression was defined as lesions with < 50 % diameter stenosis ( % S ) at baseline , measured by QCA , that increased at least 10%S to become > or=50%S during the 3-year follow-up . Major ischemic events ( new Q-wave myocardial infa rct ion , a large reversible thallium defect or additional revascularization procedures ) attributed to these new lesions were determined based on the ECG ischemic changes and /or the details of the coronary anatomy . RESULTS Of 298 patients , 53 ( 18 % ) ( 15 % of PTCA and 21 % of CABG ) developed at least one significant new native coronary artery lesion . Of 136 patients with events , 19 ( 14 % ) had such events due to progression . In multivariate analysis , native coronary disease progression was independently correlated with hypertension ( OR=2.4 , p=0.03 ) , ST segment depression = 1 mm on baseline ETT ( OR=2.7 , p=0.01 ) , and percent of small LDL particles ( LDL IIIa-IVb ) ( OR=1.2 for every 5 % increase , p=0.01 ) . CONCLUSIONS In EAST , the native CAD progression accounted for one in seven major ischemic episodes over a 3-year follow-up . Patients with metabolic atherogenic risk profiles were more likely to have disease progression . These findings indicate the importance of more aggressive risk factor modification following revascularization AIMS To evaluate the association of low-density lipoprotein cholesterol ( LDL-C ) levels in small and large LDL particles with risk of incident coronary heart disease ( CHD ) . METHODS AND RESULTS We performed a prospect i ve case-control study nested in the EPIC-Norfolk cohort . Cases were apparently healthy men and women aged 45 - 79 years who developed fatal or non-fatal CHD ( n = 1035 ) , and who were matched by age , gender , and enrollment time to 1920 controls who remained free of CHD . Electrophoretic characteristics of LDL particles were measured using 2 - 16 % polyacrylamide gradient gel electrophoresis . Concentrations of LDL-C(<255 A ) were higher in cases than controls in men ( 1.34 + /- 0.88 vs. 1.15 + /- 0.80 mmol/L , P < 0.001 ) as well as in women ( 1.12 + /- 0.84 vs. 0.94 + /- 0.74 mmol/L , P < 0.001 ) . The unadjusted odds ratio ( OR ) for future CHD in men of the top tertile of LDL-C(<255 A ) was 1.68 ( 95 % CI , 1.33 - 2.13 ; P < 0.001 ) whereas in women the unadjusted OR was 1.53 ( 95 % CI , 1.13 - 2.07 ; P < 0.001 ) . However , after further adjustments for confounding variables , the association between LDL-C(<255 A ) and CHD was no longer significant in men and in women . CONCLUSION Cholesterol concentrations in different LDL subclasses show different relationships with CHD risk in this European cohort Background — Changes in conventional lipid risk factors with gemfibrozil treatment only partially explain the reductions in coronary heart disease ( CHD ) events experienced by men in the Veterans Affairs High-Density Lipoprotein Intervention Trial ( VA-HIT ) . We examined whether measurement of low-density lipoprotein ( LDL ) and high-density lipoprotein ( HDL ) particle subclasses provides additional information relative to CHD risk reduction . Methods and Results — This is a prospect i ve nested case-control study of 364 men with a new CHD event ( nonfatal myocardial infa rct ion or cardiac death ) during a 5.1-year ( median ) follow-up and 697 age-matched controls . Nuclear magnetic resonance ( NMR ) spectroscopy was used to quantify levels of LDL and HDL particle subclasses and mean particle sizes in plasma obtained at baseline and after 7 months of treatment with gemfibrozil or placebo . Odds ratios for a 1-SD increment of each lipoprotein variable were calculated with adjusted logistic regression models . Gemfibrozil treatment increased LDL size and lowered numbers of LDL particles ( −5 % ) while raising numbers of HDL particles ( 10 % ) and small HDL subclass particles ( 21 % ) . Concentrations of these LDL and HDL particles achieved with gemfibrozil were significant , independent predictors of new CHD events . For total LDL and HDL particles , odds ratios predicting CHD benefit were 1.28 ( 95 % CI , 1.12 to 1.47 ) and 0.71 ( 95 % CI , 0.61 to 0.81 ) , respectively . Mean LDL and HDL particle sizes were not associated with CHD events . Conclusions — The effects of gemfibrozil on NMR-measured LDL and HDL particle subclasses , which are not reflected by conventional lipoprotein cholesterol measures , help to explain the demonstrated benefit of this therapy in patients with low HDL cholesterol Abstract Objective To examine the extent and nature of outcome reporting bias in a broad cohort of published r and omised trials . Design Retrospective review of publications and follow up survey of authors . Cohort All journal articles of r and omised trials indexed in PubMed whose primary publication appeared in December 2000 . Main outcome measures Prevalence of incompletely reported outcomes per trial ; reasons for not reporting outcomes ; association between completeness of reporting and statistical significance . Results 519 trials with 553 publications and 10 557 outcomes were identified . Survey responders ( response rate 69 % ) provided information on unreported outcomes but were often unreliable — for 32 % of those who denied the existence of such outcomes there was evidence to the contrary in their publications . On average , over 20 % of the outcomes measured in a parallel group trial were incompletely reported . Within a trial , such outcomes had a higher odds of being statistically non-significant compared with fully reported outcomes ( odds ratio 2.0 ( 95 % confidence interval 1.6 to 2.7 ) for efficacy outcomes ; 1.9 ( 1.1 to 3.5 ) for harm outcomes ) . The most commonly reported reasons for omitting efficacy outcomes included space constraints , lack of clinical importance , and lack of statistical significance . Conclusions Incomplete reporting of outcomes within published articles of r and omised trials is common and is associated with statistical non- significance . The medical literature therefore represents a selective and biased subset of study outcomes , and trial protocol s should be made publicly available OBJECTIVES To investigate the mechanisms by which bezafibrate retarded the progression of coronary lesions in the Bezafibrate Coronary Atherosclerosis Intervention Trial ( BECAIT ) , we examined the relationships of on-trial lipoproteins and lipoprotein subfractions to the angiographic outcome measurements . BACKGROUND BECAIT , the first double-blind , placebo-controlled , r and omized serial angiographic trial of a fibrate compound , showed that progression of focal coronary atherosclerosis in young survivors of myocardial infa rct ion could be retarded by bezafibrate treatment . METHODS A total of 92 dyslipoproteinemic men who had survived a first myocardial infa rct ion before the age of 45 years were r and omly assigned to treatment for 5 years with bezafibrate ( 200 mg three times daily ) or placebo ; 81 patients underwent baseline and at least one post-treatment coronary angiography . RESULTS In addition to the decrease in very low density lipoprotein ( VLDL ) cholesterol ( -53 % ) and triglyceride ( -46 % ) and plasma apolipoprotein ( apo ) B ( -9 % ) levels , bezafibrate treatment result ed in a significant increase in high density lipoprotein-3 ( HDL3 ) cholesterol ( + 9 % ) level and a shift in the low density lipoprotein ( LDL ) subclass distribution toward larger particle species ( peak particle diameter + 032 nm ) . The on-trial HDL3 cholesterol and plasma apo B concentrations were found to be independent predictors of the changes in mean minimum lumen diameter ( r=-0.23 , p < 0.05 ) , and percent ( % ) stenosis ( r = 0.30 , p < 0.01 ) , respectively . Decreases in small dense LDL and /or VLDL lipid concentrations were unrelated to disease progression . CONCLUSIONS Our results suggest that the effect of bezafibrate on progression of focal coronary atherosclerosis could be at least partly attributed to a rise in HDL3 cholesterol and a decrease in the total number of apo B-containing lipoproteins Background —The Diabetes Atherosclerosis Intervention Study showed that treatment with fenofibrate decreases progression of coronary atherosclerosis in subjects with type 2 diabetes . We determined whether on-treatment plasma lipid concentrations and LDL particle size contribute to the favorable effect of fenofibrate on the progression of coronary artery disease ( CAD ) . Methods and Results —A total of 418 subjects with type 2 diabetes were r and omly assigned to 200 mg micronized fenofibrate daily or placebo . The mean follow-up time was 39.6 months . LDL peak particle diameter ( LDL size ) was determined by polyacrylamide gradient gel electrophoresis from 405 subjects at baseline and at the end of the study . Progression of CAD was measured with quantitative coronary angiography . LDL size increased significantly more in the fenofibrate group than in the placebo group ( 0.98±1.04 versus 0.32±0.92 nm , P < 0.001 ) . In the combined group , small LDL size was significantly associated with progression of CAD measured as the increase of percentage diameter stenosis ( r = −0.16 , P = 0.002 ) and decreases in minimum ( r = −0.11 , P = 0.030 ) and mean ( r = −0.10 , P = 0.045 ) lumen diameter . High on-treatment LDL cholesterol , apolipoprotein B , and triglyceride concentrations were also associated with the progression of CAD . In regression analyses , small LDL size added to the effect of LDL cholesterol and apolipoprotein B on the progression of CAD . Similar associations were observed in the fenofibrate group , whereas in the placebo group , lipoprotein variables were not significantly correlated with the progression of CAD . Conclusions —Changes in LDL size and plasma lipid levels account for part of the antiatherogenic effect of fenofibrate in type 2 diabetes Accumulating evidence suggests that triglyceride-rich lipoproteins contribute to coronary artery disease . Using data from the Monitored Atherosclerosis Regression Study , an angiographic trial of middle-aged men and women r and omized to lovastatin or placebo , we investigated relationships between lipoprotein subclasses and progression of coronary artery atherosclerosis . Coronary artery lesion progression was determined by quantitative coronary angiography in low- grade ( < 50 % diameter stenosis ) , high- grade ( > or = 50 % diameter stenosis ) , and all coronary artery lesions in 220 baseline/2-year angiogram pairs . Analytical ultracentrifugation was used to measure lipoprotein masses that were statistically evaluated for treatment group differences and relationships to progression of coronary artery atherosclerosis . All low density lipoprotein ( LDL ) , intermediate density lipoprotein ( IDL ) , and very low density lipoprotein ( VLDL ) masses were significantly lowered and all high density lipoprotein ( HDL ) masses were significantly raised with lovastatin therapy . The mass of smallest LDL ( Svedberg flotation rate [ Sf ] 0 to 3 ) , IDL ( Sf 12 to 20 ) , all VLDL subclasses ( Sf 20 to 60 , Sf 60 to 100 , and Sf 100 to 400 ) , and peak LDL flotation rate were significantly related to the progression of coronary artery lesions , specifically low- grade lesions . Greater baseline levels of HDL3 , were related to a lower likelihood of coronary artery lesion progression . In multivariate analyses , small VLDL ( Sf 20 to 60 ) and HDL3 mass were the most important correlates of coronary artery lesion progression . These results provide further evidence for the importance of triglyceride-rich lipoproteins in the progression of coronary artery disease . In addition , these results present new evidence for the possible protective role of HDL3 in the progression of coronary artery lesions . More specific information on coronary artery lesion progression may be obtained through the study of specific apolipoprotein B-containing lipoproteins OBJECTIVE To investigate the prospect i ve association of low-density lipoprotein ( LDL ) particle diameter with the incidence of fatal and nonfatal coronary artery disease ( CAD ) . DESIGN A nested case-control study . SETTING Cases and controls were identified from a population -based sample of men and women combining all of the 5 cross-sectional surveys conducted from 1979 to 1990 of the Stanford Five-City Project ( FCP ) . PARTICIPANTS Incident CAD cases were identified through FCP surveillance between 1979 and 1992 . Controls were matched by sex , 5-year age groups , survey time point , ethnicity , and FCP treatment condition . The sample included 124 matched pairs : 90 pairs of men and 34 pairs of women . MAIN OUTCOME MEASURES LDL peak particle diameter ( LDL size ) was determined by gradient gel electrophoresis on plasma sample s collected during the cross-sectional surveys ( stored at 70 degrees C for 5 - 15 years ) . Established CAD risk-factor data were available from FCP baseline measurements . RESULTS LDL size was smaller among CAD cases than controls ( mean + /- SD ) ( 26.17 + /- 1.00 nm vs 26.68 + /- 0.90 nm ; P<.001 ) . The association was grade d across control quintiles of LDL size . The significant case-control difference in LDL size was independent of levels of high-density lipoprotein cholesterol ( HDL-C ) , non-HDL cholesterol ( non-HDL-C ) , triglyceride , smoking , systolic blood pressure , and body mass index , but was not significant after adjusting for the ratio of total cholesterol ( TC ) to HDL-C ( TC : HDL-C ) . Among all the physiological risk factors , LDL size was the best differentiator of CAD status in conditional logistic regression . However , when added to the physiological parameters above , the TC : HDL-C ratio was found to be a stronger independent predictor of CAD status . CONCLUSION LDL size was significantly smaller in CAD cases than in controls in a prospect i ve , population -based study . These findings support other evidence of a role for small , dense LDL particles in the etiology of atherosclerosis Objective —The Women 's Health Initiative r and omized hormone trials unexpectedly demonstrated an increase in early coronary events . In an effort to explain this finding , we examined lipoprotein particle concentrations and their interactions with hormone therapy in a case – control sub study . Methods and Results —We r and omized 16 608 postmenopausal women with intact uterus to conjugated estrogens 0.625 mg with medroxyprogesterone acetate 2.5 mg daily or to placebo , and 10 739 women with prior hysterectomy to conjugated estrogens 0.625 mg daily or placebo , and measured lipoprotein subclasses by nuclear magnetic resonance spectroscopy at baseline and year 1 in 354 women with early coronary events and matched controls . Postmenopausal hormone therapy raised high-density lipoprotein cholesterol and particle concentration and reduced low-density lipoprotein cholesterol ( LDL-C ; all P<0.001 versus placebo ) . In contrast , neither unopposed estrogen nor estrogen with progestin lowered low-density lipoprotein particle concentration ( LDL-P ) . Conclusions —Postmenopausal hormone therapy – induced reductions in LDL-C were not paralleled by favorable effects on LDL-P. This finding may account for the absence of coronary protection conferred by estrogen in the r and omized hormone trials A predominance of small , dense , low density lipoprotein ( LDL ) particles has consistently been associated with coronary heart disease ( CHD ) in young and middle-aged subjects in cross-sectional studies . Recently , 3 prospect i ve , case-control studies showed that decreased LDL size is a predictor of CHD in middle-aged subjects . However , it is not known whether decreased LDL size is mainly associated with premature CHD or whether it continues to play a role in CHD risk at older ages also . We performed a prospect i ve , nested case-control study in 86 subjects ( 58 nondiabetic and 28 type 2 diabetic ) aged 65 to 74 years who were free of myocardial infa rct ion at baseline and who then had a myocardial infa rct ion or CHD death during a 3.5-year follow-up ( cases ) and in 172 controls matched for sex and diabetes status but who remained free of CHD during follow-up . LDL particle size determined by gradient gel electrophoresis ( 268.2+/-0.9 versus 268.5+/-0.7 A , P=0.782 ) and the proportion of subjects with LDL subclass phenotype B ( 20.9 versus 21 . 5 , P=0.914 ) were similar among cases and controls . Furthermore , diastolic blood pressure , total cholesterol , high density lipoprotein cholesterol , triglycerides , apolipoprotein A(1 ) , fasting glucose , fasting insulin , waist-to-hip ratio , and body mass index were not associated with CHD risk . However , smoking and increased systolic blood pressure , apolipoprotein B levels , and the total cholesterol-high density lipoprotein cholesterol ratio were significant predictors of CHD events both in univariate and multivariate analyses . Our findings indicate that LDL size is not a predictor of CHD events in elderly white subjects after controlling for diabetes status CONTEXT Small low-density lipoprotein ( LDL ) particle size has been hypothesized to be a risk factor for coronary heart disease ( CHD ) . Animal models link large LDL to atherosclerosis . However , the strong association between small LDL and other risk factors , particularly triglyceride levels , impedes determining whether LDL size independently predicts CHD in humans . OBJECTIVE To examine whether LDL size is an independent predictor of recurrent coronary events in patients with known CHD , as opposed to a marker for other lipid abnormalities . DESIGN AND SETTING Prospect i ve , nested case-control study in the Cholesterol and Recurrent Events ( CARE ) trial , a r and omized placebo-controlled trial of pravastatin conducted in 1989 - 1996 . PARTICIPANTS Survivors of myocardial infa rct ion with typical LDL concentrations ( 416 cases and 421 controls ) . MAIN OUTCOME MEASURE Subsequent myocardial infa rct ion or coronary death during the 5-year follow-up , analyzed by quintile of LDL particle size and by treatment group . RESULTS Overall , the mean LDL size was identical in cases and controls ( 25.6 nm ) . In patients in the placebo group , large LDL predicted coronary events in models adjusted only for age ( relative risk [ RR ] , 1.79 ; 95 % confidence interval [ CI ] , 1.01 - 3.17 ) and for age and lipid and nonlipid risk factors ( RR , 4.00 ; 95 % CI , 1.81 - 8.82 ) , comparing those in the highest ( mean , 26.6 nm ) and lowest ( mean , 24.5 nm ) quintiles of LDL size . This increased risk was not present in those taking pravastatin ( age-adjusted analysis : RR , 0.98 ; 95 % CI , 0.47 - 2.04 ; P = .046 for interaction for a difference in the effect of LDL size on coronary events between the placebo and treatment groups ; multivariable analysis : RR , 1.33 ; 95 % CI , 0.52 - 3.38 ; P = .11 for interaction ) . CONCLUSIONS Large LDL size was an independent predictor of coronary events in a typical population with myocardial infa rct ion , but the adverse effect was not present among patients who were treated with pravastatin . Identifying patients on the basis of LDL size may not be useful clinical ly , since effective treatment for elevated LDL cholesterol concentrations also effectively treats risk associated with large LDL Background —Nuclear magnetic resonance ( NMR ) offers an alternative , spectroscopic means of quantifying LDL and of measuring LDL particle size . Methods and Results —We conducted a prospect i ve nested case-control study among healthy middle-aged women to assess LDL particle size ( NMR ) and concentration ( NMR ) as risk factors for future myocardial infa rct ion , stroke , or death of coronary heart disease . Median baseline levels of LDL particle concentration ( NMR ) were higher ( 1597 vs 1404 nmol/L;P = 0.0001 ) and LDL particle size ( NMR ) was lower ( 21.5 vs 21.8 nm;P = 0.046 ) among women who subsequently had cardiovascular events ( n=130 ) than among those who did not ( n= 130 ) . Of these 2 factors , LDL particle concentration ( NMR ) was the stronger predictor ( relative risk for the highest compared with the lowest quartile=4.17 , 95 % CI 1.96–8.87 ) . This compared with a relative risk of 3.11 ( 95 % CI 1.55–6.26 ) for the ratio of total cholesterol to HDL cholesterol and a relative risk of 5.91 ( 95 % CI 2.65–13.15 ) for C-reactive protein . The areas under the receiver operating characteristic curves for LDL particle concentration ( NMR ) , total cholesterol to HDL cholesterol ratio , and C-reactive protein were 0.64 , 0.64 , and 0.66 , respectively . LDL particle concentration ( NMR ) correlated with several traditionally assessed lipid and nonlipid risk factors , and thus adjustment for these tended to attenuate the magnitude of association between LDL particle concentration ( NMR ) and risk . Conclusions —In this cohort , LDL particle concentration measured by NMR spectroscopy was a predictor of future cardiovascular risk . However , the magnitude of predictive value of LDL particle concentration ( NMR ) was not substantively different from that of the total cholesterol to HDL cholesterol ratio and was less than that of C-reactive protein CONTEXT Despite improved underst and ing of atherothrombosis , cardiovascular prediction algorithms for women have largely relied on traditional risk factors . OBJECTIVE To develop and vali date cardiovascular risk algorithms for women based on a large panel of traditional and novel risk factors . DESIGN , SETTING , AND PARTICIPANTS Thirty-five factors were assessed among 24 558 initially healthy US women 45 years or older who were followed up for a median of 10.2 years ( through March 2004 ) for incident cardiovascular events ( an adjudicated composite of myocardial infa rct ion , ischemic stroke , coronary revascularization , and cardiovascular death ) . We used data among a r and om two thirds ( derivation cohort , n = 16 400 ) to develop new risk algorithms that were then tested to compare observed and predicted outcomes in the remaining one third of women ( validation cohort , n = 8158 ) . MAIN OUTCOME MEASURE Minimization of the Bayes Information Criterion was used in the derivation cohort to develop the best-fitting parsimonious prediction models . In the validation cohort , we compared predicted vs actual 10-year cardiovascular event rates when the new algorithms were compared with models based on covariates included in the Adult Treatment Panel III risk score . RESULTS In the derivation cohort , a best-fitting model ( model A ) and a clinical ly simplified model ( model B , the Reynolds Risk Score ) had lower Bayes Information Criterion scores than models based on covariates used in Adult Treatment Panel III . In the validation cohort , all measures of fit , discrimination , and calibration were improved when either model A or B was used . For example , among participants without diabetes with estimated 10-year risks according to the Adult Treatment Panel III of 5 % to less than 10 % ( n = 603 ) or 10 % to less than 20 % ( n = 156 ) , model A reclassified 379 ( 50 % ) into higher- or lower-risk categories that in each instance more accurately matched actual event rates . Similar effects were achieved for clinical ly simplified model B limited to age , systolic blood pressure , hemoglobin A(1c ) if diabetic , smoking , total and high-density lipoprotein cholesterol , high-sensitivity C-reactive protein , and parental history of myocardial infa rct ion before age 60 years . Neither new algorithm provided substantive information about women at very low risk based on the published Adult Treatment Panel III score . CONCLUSION We developed , vali date d , and demonstrated highly improved accuracy of 2 clinical algorithms for global cardiovascular risk prediction that reclassified 40 % to 50 % of women at intermediate risk into higher- or lower-risk categories Aim /hypothesisTo examine whether nuclear magnetic resonance lipoprotein spectroscopy improves the prediction of coronary artery disease in patients with Type 1 diabetes , independently of conventional lipid and other risk factors . Methods A prospect i ve nested case-control design of subjects with childhood onset Type 1 diabetes from the Pittsburgh Epidemiology of Diabetes Complications Study was used . 59 controls were age- , sex- and duration -matched to 59 incident cases of coronary artery disease ( fatal or non-fatal myocardial infa rct ion , angina , coronary stenosis > 50 % ) occurring during 10 years of follow-up . Lipid mass and particle concentrations of VLDL , LDL , and HDL subclasses , grouped into three size categories ( large , medium , and small ) , were assessed prior to event with nuclear magnetic resonance spectroscopy . Results Univariate analyses showed that both lipid mass and particle concentrations of all three VLDL subclasses , small LDL , medium LDL , and medium HDL were increased in CAD cases compared to controls , while large HDL was decreased . Mean LDL and HDL particle sizes were lower in cases . In multivariate models using conventional lipid and non-lipid risk factors , triglycerides and overt nephropathy were the strongest predictors of CAD . Nuclear magnetic resonance measures further improved the prediction , i.e. large HDL particle concentration ( OR=0.43 , p=0.030 ) , medium HDL mass ( OR=3.79 , p=0.026 ) and total VLDL particle concentration ( OR=2.33 , p=0.033 ) . Conclusion /interpretationWhile these results underscore the importance of triglycerides and overt nephropathy in CAD risk in Type 1 diabetic patients , they also suggest that nuclear magnetic resonance lipoprotein spectroscopy could further refine its prediction and show novel findings concerning HDL subclasses Lipoprotein subclass measurements may enhance the prediction of coronary artery disease ( CAD ) risk , but clinical application of such information has been hindered by the relatively laborious and time-consuming nature of laboratory measurement methods . In this study , lipoprotein subclass analyses were performed on frozen plasma sample s from 241 participants in the Pravastatin Limitation of Atherosclerosis in the Coronary arteries Trial using an automated nuclear magnetic resonance technique . The objective was to determine if levels of these subclasses provided additional information on the progression of CAD , based on the change in the minimum lumen diameter , over a 3-year period . After adjustment for race , sex , age , treatment group , baseline lumen diameter , and chemically measured levels of triglycerides , low-density lipoprotein ( LDL ) cholesterol , and high-density lipoprotein ( HDL ) cholesterol , on-trial predictors ( p < 0.05 ) of progression included an elevated LDL particle number , and levels of small LDL and small HDL . Within treatment groups , CAD progression was most strongly related to the LDL particle number ( placebo ) and levels of small HDL ( pravastatin ) . In logistic regression models that adjusted for chemically determined lipid levels and other covariates , a small LDL level > or = 30 mg/dl ( median ) was associated with a ninefold increased risk of CAD progression ( p < 0.01 ) in the placebo group . These results indicate that levels of various lipoprotein subclasses may provide useful information on CAD risk even if levels of traditional risk factors are known Background Only limited data are available for risk factors for intracerebral haemorrhage ( ICH ) in subjects with established cerebrovascular disease . Design We performed a nested case-control study of participants of the Perindopril Protection Against Recurrent Stroke Study ( PROGRESS ) . This was a r and omized , placebo-controlled trial that established the beneficial effects of blood pressure lowering in 6105 patients with cerebrovascular disease . Methods Each of 41 subjects who experienced ICH during a mean follow-up of 3.9 years was matched to 1 - 3 control subjects . Lipoprotein particles and other plasma markers were measured in baseline blood sample s from PROGRESS participants . Results In comparison with control subjects , ICH cases had increased mean low-density lipoprotein ( LDL ) diameter ( P=0.04 ) and increased large LDL particle concentration ( P=0.03 ) . The odds ratio ( adjusted for regression dilution bias ) for ICH risk with 10 mmHg increase in systolic blood pressure ( SBP ) was 1.45 ( 95 % confidence interval : 1.01 - 2.09 , P=0.05 ) , with a 1 nm increase in mean LDL diameter it was 2.15 ( 95 % confidence interval : 0.97 - 4.77 , P=0.06 ) , and with 100 nmol/l increase in large LDL particle concentration it was 1.18 ( 95 % confidence interval : 0.98 - 1.43 , P=0.08 ) . Plasma levels of C-reactive protein ( CRP ) , soluble vascular cell adhesion molecule 1 ( sVCAM-1 ) , homocysteine , amino-terminal-pro-B-type natriuretic peptide ( NT-proBNP ) , and renin were not associated with ICH risk . Conclusion SBP predicted ICH risk in subjects with cerebrovascular disease , whereas CRP , sVCAM-1 , homocysteine , NT-proBNP , and renin did not predict ICH risk . The trends for prediction of ICH risk by mean LDL particle diameter and large LDL particle concentration are hypothesis generating and require confirmation in larger studies Associations between plasma lipoprotein subfractions and changes in coronary artery diseases ( CAD ) were examined in 74 men who completed the St. Thomas ' Atherosclerosis Regression Study ( STARS ) . Plasma lipoproteins were isolated by stepwise , preparative ultracentrifugation at repeated intervals during the 38-month trial . Paired coronary angiograms were quantitatively analyzed by a computerized method . In univariate linear regression analysis , changes in mean absolute width ( delta MAWS ) and minimum absolute with ( delta MinAWS ) of coronary segments were significantly correlated with in-trial concentrations of cholesterol in intermediate-density lipoprotein ( [ IDL ] d = 1.006 to 1.019 kg/L ) , low-density lipoprotein ( [ LDL2 ] d = 1.019 to 1.040 kg/L ; LDL3 , d = 1.040 to 1.063 kg/L ) , and high-density lipoprotein ( [ HDL3 ] d = 1.125 to 1.210 kg/L ) subfractions ; no significant associations were found with other lipoproteins . IDL , LDL3 , and HDL3 cholesterol were then selected for multiple linear regression analysis because these variables were not co-correlated and because they attained a significance of P less than or equal to .1 in univariate regression . In this analysis , only LDL3 cholesterol level was a significant negative predictor ( P < .05 ) of both delta MAWS and delta MinAWS ; a positive association between delta MinAWS and HDL3 cholesterol level just failed to reach conventional statistical significance ( P = .066 ) . Correlations between changes in coronary luminal dimensions and LDL3 cholesterol level were independent of age , smoking , weight , and blood pressure . Most patients showing regression of coronary atherosclerosis had an LDL3 cholesterol level of less than 1.8 mmol/L. The findings suggest that LDL3 is the plasma lipoprotein subfraction that exerts the single most powerful effect on the course of CAD in middle-aged men with hypercholesterolemia OBJECTIVES We assessed relations of low-density lipoprotein ( LDL ) particle number ( LDL-P ) and LDL particle size as measured by nuclear magnetic resonance spectroscopy with LDL cholesterol ( LDL-C ) and the risk of future coronary artery disease ( CAD ) . BACKGROUND Whereas LDL-C is an established risk factor for CAD , its discriminative power is limited . Measuring LDL-P and size may have stronger associations with CAD than LDL-C. METHODS A nested case-control study was performed in the prospect i ve EPIC ( European Prospect i ve Investigation into Cancer and Nutrition)-Norfolk study , which comprises 25,663 subjects . Cases ( n = 1,003 ) were individuals who developed CAD during 6 year follow-up . Control subjects ( n = 1,885 ) were matched for age , gender , and enrollment time . Odds ratios ( ORs ) for future CAD were calculated , and we also evaluated whether LDL-P could improve the Framingham risk score ( FRS ) to predict CAD . RESULTS In univariate analyses , LDL-P ( OR 2.00 , 95 % confidence interval [ CI ] 1.58 to 2.59 ) and non-high-density lipoprotein cholesterol ( non-HDL-C ) ( OR 2.14 , 95 % CI 1.69 to 2.69 ) were more closely associated with CAD than LDL-C ( OR 1.73 , 95 % CI 1.37 to 2.18 ) . The additional value of LDL-P was lost after adjustment for HDL-C and triglyceride levels . Whereas LDL size was inversely related to CAD ( OR 0.60 , 95 % CI 0.47 to 0.76 ) , this relation was abolished upon adjustment for LDL-P. In a model adjusted for the FRS , LDL-P retained its association with CAD ( p for trend 0.02 ) . CONCLUSIONS In this large study of individuals with moderately elevated LDL-C , LDL-P was related to CAD on top of FRS as well as after adjusting for LDL-C. The additional value of LDL-P was comparable to non-HDL-C , and it was abolished after adjusting for triglycerides and OBJECTIVE To test whether a predominance of small , dense low-density lipoprotein ( LDL ) particles and elevated triglyceride levels are independent risk factors for myocardial infa rct ion ( MI ) . DESIGN Nested case-control study with prospect ively collected sample s. SETTING Prospect i ve cohort study . PARTICIPANTS Blood sample s were collected at baseline ( 85 % nonfasting sample s ) from 14916 men aged 40 to 84 years in the Physicians ' Health Study . MAIN OUTCOME MEASUREMENTS Myocardial infa rct ion diagnosed during 7 years of follow-up . RESULTS Cases ( n=266 ) had a significantly smaller LDL diameter ( mean [ SD ] , 25.6 [ 0.9 ] nm ) than did controls ( n=308 ) matched on age and smoking ( mean [ SD ] , 25.9 [ 8 ] nm ; P<.001 ) . Cases also had higher median triglyceride levels ( 1.90 vs 1.49 mmol/L [ 168 vs 132 mg/dL ] ; P<.001 ) . The LDL diameter had a high inverse correlation with triglyceride level ( r=-0.71 ) , and a high direct correlation with high-density lipoprotein cholesterol ( HDL-C ) level ( r=0.60 ) . We observed a significant multiplicative interaction between triglyceride and total cholesterol ( TC ) levels ( P=.01 ) . After simultaneous adjustment for lipids and a variety of coronary risk factors , LDL particle diameter was no longer a statistically significant risk indicator , with a relative risk ( RR ) of 1.09 ( 95 % confidence interval [ CI ] , 0.85 - 1.40 ) per 0.8-nm decrease . However , triglyceride level remained significant with an RR of 1.40 ( 95 % CI , 1.10 - 1.77 ) per 1.13 mmol/L ( 100-mg/dL ) increase . The association between triglyceride level and MI risk appeared linear across the distribution ; men in the highest quintile had a risk about 2.5 times that of those in the lowest quintile . The TC level , but not HDL-C level , also remained significant , with an RR of 1.80 ( 95 % CI , 1.44 - 2.26 ) per 1.03-mmol/L ( 40-mg/dL ) increase . CONCLUSIONS These findings indicate that nonfasting triglyceride levels appear to be a strong and independent predictor of future risk of MI , particularly when the total cholesterol level is also elevated . In contrast , LDL particle diameter is associated with risk of MI , but not after adjustment for triglyceride level . Increased triglyceride level , small LDL particle diameter , and decreased HDL-C levels appear to reflect underlying metabolic perturbations with adverse consequences for risk of MI ; elevated triglyceride levels may help identify high-risk individuals Decreased low-density lipoprotein ( LDL ) particle size is associated with coronary heart disease ( CHD ) risk among middle-aged Caucasian population s , and has been consistently correlated with increased plasma levels of triglyceride and decreased levels of high-density lipoprotein ( HDL ) cholesterol . This study examines whether these risk factors predict CHD among older Japanese-American men . With use of the Honolulu Heart Program Lipoprotein Exam 3 ( 1980 to 1982 ) as baseline , and 12-year follow-up for CHD events , a nested , case-control study was design ed . One hundred forty-five incident CHD cases were identified and matched to 2 controls each . LDL particle diameter ( size ) was determined by gradient gel electrophoresis . A 10-angstrom ( A ) decrease in LDL size at baseline was associated with increased risk of incident CHD ( relative risk 1.28 , 95 % confidence interval 1.01 to 1.63 ) . After adjustment for baseline risk factors , the LDL size association was no longer statistically significant ( relative risk 1.13 , 95 % confidence interval 0.86 to 1.49 ) . When principal components analysis was used to define a composite variable for LDL size , triglycerides , and HDL cholesterol , this component predicted CHD independent of smoking , alcohol consumption , physical activity , body mass index , hypertension , diabetes , and beta-blocker use ( p < 0.01 ) . Therefore , this prospect i ve analysis of data from older , Japanese-American men demonstrated that decreased LDL size is a univariate predictor of incident CHD , and that a composite risk factor of LDL size , triglyceride , and HDL cholesterol was a risk factor for CHD independent of other risk factors |
1,815 | 29,975,497 | Strengthened warnings increased attention to warnings , recall of warnings , and thinking about the health risks of smoking .
Strengthened warnings also increased several perceived effectiveness outcomes , including perceptions that warnings reduce smoking and motivate quitting .
Strengthened cigarette pack warnings achieve their goal of attracting attention and enhancing motivation to act . | The current study sought to examine the impact of strengthening cigarette pack warnings on attention , message processing , and perceived effectiveness , through a systematic review of longitudinal observational studies . | Objectives To investigate the links between health warning labels ( WLs ) on cigarette packets and relapse among recently quit smokers . Design Prospect i ve longitudinal cohort survey . Setting Australia , Canada , the UK and the USA . Participants 1936 recent ex-smokers ( 44.4 % male ) from one of the first six waves ( 2002–2007 ) of the International Tobacco Control 4-Country policy evaluation survey , who were followed up in the next wave . Main outcome measures Whether participants had relapsed at follow-up ( approximately 1 year later ) . Results In multivariate analysis , very frequent noticing of WLs among ex-smokers was associated with greater relapse 1 year later ( OR : 1.52 , 95 % CI 1.11 to 2.09 , p<0.01 ) , but this effect disappeared after controlling for urges to smoke and self-efficacy ( OR : 1.29 , 95 % CI 0.92 to 1.80 , p=0.135 ) . In contrast , reporting that WLs make staying quit ‘ a lot ’ more likely ( compared with ‘ not at all ’ likely ) was associated with a lower likelihood of relapse 1 year later ( OR : 0.65 , 95 % CI 0.49 to 0.86 , p<0.01 ) and this effect remained robust across all models tested , increasing in some . Conclusions This study provides the first longitudinal evidence that health warnings can help ex-smokers stay quit . Once the authors control for greater exposure to cigarettes , which is underst and ably predictive of relapse , WL effects are positive . However , it may be that ex-smokers need to actively use the health consequences that WLs highlight to remind them of their reasons for quitting , rather than it being something that happens automatically . Ex-smokers should be encouraged to use pack warnings to counter urges to resume smoking . Novel warnings may be more likely to facilitate this BACKGROUND In June 2012 , Canada implemented new pictorial warnings on cigarette packages , along with package inserts with messages to promote response efficacy ( i.e. , perceived quitting benefits ) and self-efficacy ( i.e. , confidence to quit ) . This study assessed smokers ' attention toward warnings and inserts and its relationship with efficacy beliefs , risk perceptions and cessation at follow-up . METHODS Data were analyzed in 2015 from a prospect i ve online consumer panel of adult Canadian smokers surveyed every four months between September 2012 and September 2014 . Generalized Estimating Equation models were estimated to assess associations between reading inserts , reading warnings and efficacy beliefs ( self-efficacy , response efficacy ) , risk perceptions , quit attempts of any length , and sustained quit attempts ( i.e. , 30days or more ) at follow-up . Models adjusted for socio-demographics , smoking-related variables , and time-in- sample effects . RESULTS Over the study period , reading warnings significantly decreased ( p<0.0001 ) while reading inserts increased ( p=0.004 ) . More frequent reading of warnings was associated independently with stronger response efficacy ( Boften/very often vs never=0.28 , 95 % CI : 0.11 - 0.46 ) and risk perceptions at follow-up ( Boften/very often vs never=0.31 , 95 % CI : 0.06 - 0.56 ) . More frequent reading of inserts was associated independently with stronger self-efficacy to quit at follow-up ( Btwice or more vs none=0.30 , 95 % CI : 0.14 - 0.47 ) , quit attempts ( ORtwice or more vs none=1.68 , 95 % CI : 1.28 - 2.19 ) , and sustained quit attempts ( ORtwice or more vs none=1.48 , 95 % CI : 1.01 - 2.17 ) . CONCLUSIONS More frequent reading of inserts was associated with self-efficacy to quit , quit attempts , and sustained quitting at follow-up , suggesting that inserts complement pictorial HWLs Objectives : To examine the impact of health warnings on smokers by comparing the short-term impact of new graphic ( 2006 ) Australian warnings with : ( i ) earlier ( 2003 ) United Kingdom larger text-based warnings ; ( ii ) and Canadian graphic warnings ( late 2000 ) ; and also to extend our underst and ing of warning wear-out . Methods : The International Tobacco Control Policy Evaluation Survey ( ITC Project ) follows prospect i ve cohorts ( with replenishment ) of adult smokers annually ( five waves : 2002–2006 ) , in Canada , United States , UK and Australia ( around 2000 per country per wave ; total n = 17 773 ) . Measures were of pack warning salience ( reading and noticing ) ; cognitive responses ( thoughts of harm and quitting ) ; and two behavioural responses : forgoing cigarettes and avoiding the warnings . Results : All four indicators of impact increased markedly among Australian smokers following the introduction of graphic warnings . Controlling for date of introduction , they stimulated more cognitive responses than the UK ( text-only ) changes , and were avoided more , did not significantly increase forgoing cigarettes , but were read and noticed less . The findings also extend previous work showing partial wear-out of both graphic and text-only warnings , but the Canadian warnings have more sustained effects than UK ones . Conclusions : Australia ’s new health warnings increased reactions that are prospect ively predictive of cessation activity . Warning size increases warning effectiveness and graphic warnings may be superior to text-based warnings . While there is partial wear-out in the initial impact associated with all warnings , stronger warnings tend to sustain their effects for longer . These findings support arguments for governments to exceed minimum FCTC requirements on warnings Recent research has made significant progress identifying measures of the perceived effectiveness ( PE ) of persuasive messages and providing evidence of a causal link from PE to actual effectiveness ( AE ) . This article provides additional evidence of the utility of PE through unique analysis and consideration of another dimension of PE important to underst and ing the PE – AE association . Current smokers ( N=1,139 ) watched four r and omly selected antismoking Public Service Announcements ( PSAs ) . PE scores aggregated by message were used instead of individual PE scores to create a summed total , minimizing the likelihood that PE perceptions are consequences of an individual 's intention to quit , supporting instead the PE → AE order . Linear regression analyses provide evidence of PE 's positive and significant influence on smoking-cessation-related behavioral intentions The objective of this research was to compare the response of adult smokers in Malaysia to newly proposed pictorial cigarette warnings against the current text-only warnings . The study population included 140 adult male smokers who were enrolled in a r and omized trial to view either the new pictorial warnings ( intervention ) or the old text-only warnings ( control ) . Participants completed pre-exposure and post-exposure question naires that assessed their awareness of the health risks of smoking , response to the package warnings , and interest in quitting smoking . Exposure to the pictorial warnings result ed in increased awareness of the risks of smoking , stronger behavioral response to the warnings and increased interest in quitting smoking . The new warnings in Malaysia will increase smokers ’ knowledge of the adverse health effects of smoking and have a positive effect on interest in quitting Background Cigarette smoking is considered the first preventable cause of death in the world . Social , familial , and personal factors play an important role in prevention or cessation of smoking . Educating the public in order to enhance their knowledge , change their attitude and improve their habits is also effective in this respect . In 2007 , the executive protocol of the Comprehensive Law on Smoking Control was compiled in the Ministry of Health and according to the Article 5 of this law pictorial health warning labels had to be applied on cigarette packaging . This study was design ed and conducted in 2 phases of before and 9 months after the implementation of this law and evaluated the effect of it on smokers ’ knowledge , attitude and pattern of smoking . Material s and Methods This was a cross-sectional descriptive study conducted to evaluate the effect of cigarette packs ’ pictorial health warning labels on the knowledge , attitude and smoking pattern of smokers residing in Tehran . After calculating the size of under study population and estimation of the exclusions , 1731 subjects were r and omly selected using the multiphase cluster method from the 22 districts of Tehran . Data were collected using a question naire design ed according to the st and ard question naire of the World Health Organization ( WHO ) and International Union Against Tuberculosis and Lung Disease ( IUATLD ) . Qualitative and quantitative value and reliability of the variables including cigarette consumption , knowledge about the law , and pattern of smoking were evaluated in 2 phases and the quality of pictures and their effects on the mentioned variables were assessed in the 2nd phase . Results Before adopting the pictorial warning labels in the first phase of the study , 1731 respondents were evaluated out of which 71.8 % were males and 28.2 % were females . These cases had an average of 17.6±12.3 years history of smoking . A total of 38 % ( 675 subjects ) used Iranian cigarette br and s and 39.5 % were aware of the implementation of pictorial health warning labels on cigarette packs . In terms of smokers ’ attitude towards the implementation of this law , they mostly had no opinion about it . A total of 33.3 % stated that they may cut down on smoking as the result of this law . Men had a higher percentage of smoking a cigarette first thing in the morning before breakfast and women had a higher rate of consuming foreign cigarette br and s ( P < 0.001 ) . In the second phase of the study , 1590 cases of the phase 1 subjects participated . Subjects had a significantly higher knowledge about the implementation of pictorial health warning labels on cigarette packs ( P < 0.001 ) . Attitude towards this law did not change significantly compared to the first phase although the mean score improved by 0.07 % . Enforcement of this law result ed in decreased consumption in 7.6 % of the participants . However , the Wilcoxon test did not show any significant difference . In terms of the quality of pictures , 61.6 % had no opinion , and 28.7 % expressed that the pictures had poor quality . No significant difference was observed between the Iranian or foreign br and s in terms of smoking rate after applying the pictorial warning labels . Conclusion We believed that the smoking rate would decrease after applying the pictorial health warning labels on cigarette packs . However , it did not happen . Also , adopting these labels did not have a significant effect on smokers changing their favorite br and from Iranian to foreign br and s or vice versa . Type and quality of pictures require major revision and corrections This study reports consumer reactions to the graphic health warnings selected by the Food and Drug Administration to be placed on cigarette packs in the United States . We recruited three sets of respondents for an experimental study from a national opt-in e-mail list sample : ( i ) current smokers aged 25 or older , ( ii ) young adult smokers aged 18 - 24 and ( iii ) youth aged 13 - 17 who are current smokers or who may be susceptible to initiation of smoking . Participants were r and omly assigned to be exposed to a pack of cigarettes with one of nine graphic health warnings or with a text-only warning statement . All three age groups had overall strong negative emotional ( ß = 4.7 , P < 0.001 for adults ; ß = 4.6 , P < 0.001 for young adults and ß = 4.0 , P < 0.001 for youth ) and cognitive ( ß = 2.4 , P < 0.001 for adults ; ß = 3.0 , P < 0.001 for young adults and ß = 4.6 , P < 0.001 for youth ) reactions to the proposed labels . The strong negative emotional and cognitive reactions following a single exposure to the graphic health warnings suggest that , with repeated exposures over time , graphic health warnings may influence smokers ' beliefs , intentions and behaviors Background It is important to monitor whether anti-smoking messages ( if any ) are noticed by the public in China and whether they have any impact on smokers ’ quitting behaviours over time Purpose This study aim ed to examine Chinese smokers ' exposure to anti-smoking messages in a range of channels and to determine if exposure was associated with subsequent quit attempts . Method A prospect i ve cohort design was employed . Participants were 6,509 adult smokers who completed at least one of the first three waves ( 2006–2009 ) of the International Tobacco Control ( ITC ) China Survey sample d from six Chinese cities . The main measures were reported exposure to anti-smoking messages in a range of channels and smokers ' subsequent quit attempts . Generalized Estimating Equations ( GEE ) modelling was used to combine respondents from all three waves while accounting for inherent within-person correlation . Results The overall exposure levels to anti-smoking messages were low and varied between cities and from one channel to another . Television was the medium with the greatest overall exposure ( over 50 % in almost all the cities across all the waves ) . After controlling for a range of covariates , higher level of combined exposure were positively related to higher subsequent quit attempts ( adjusted odds ratio = 1.03 , 95 % CI 1.02 ~ 1.05 , p < .001 ) ; among the individual channels , exposures in newspapers and on posters were significant in their own right . Conclusion The findings suggest that anti-smoking warning messages have the potential to stimulate Chinese smokers to make quit attempts , but they also indicate that the levels and strength of warning messages in China need to be increased . China should consider adopting proven international practice s , including m and ating pictorial health warnings on cigarette packages , adopting prominent point-of-sale warnings , and carrying out strong and ongoing mass media campaigns INTRODUCTION Article 11 of the World Health Organization 's Framework Convention on Tobacco Control ( FCTC ) requires countries to implement health warnings on tobacco products . The Article 11 guidelines advise countries to periodically rotate warnings to prevent " wearout " of the health warnings . This study investigates potential wearout of cigarette health warnings during a period of 9 years in 2 countries : Canada , where larger pictorial warnings were implemented approximately 1 year prior to the study , and in the United States , where small text-only warnings were in place for 17 years at the beginning of the study . METHODS Data were drawn from national sample s of smokers from the International Tobacco Control ( ITC ) Surveys in Canada ( N = 5,309 ) , and the United States ( N = 6,412 ) who were originally recruited by telephone with r and om digit dialing . Changes in 4 measures of health warning effectiveness and in a composite Labels Impact Index were examined over 8 waves of survey data ( 2002 - 2011 ) . Analyses were conducted in 2012 . RESULTS The health warning effectiveness measures and the Labels Impact Index indicated that the effectiveness of both the Canadian , and the U.S. warnings declined significantly over time . The Canadian warnings showed greater declines in effectiveness than the U.S. warnings , likely due to the initial novelty of the Canadian warnings . Despite the greater decline in Canada , the Canadian pictorial warnings were significantly more effective than the U.S. text-only warnings throughout the study . CONCLUSIONS Health warnings decline in effectiveness over time . Health warnings on tobacco products should be changed periodically to maintain effectiveness IMPORTANCE Pictorial warnings on cigarette packs draw attention and increase quit intentions , but their effect on smoking behavior remains uncertain . OBJECTIVE To assess the effect of adding pictorial warnings to the front and back of cigarette packs . DESIGN , SETTING , AND PARTICIPANTS This 4-week between-participant r and omized clinical trial was carried out in California and North Carolina . We recruited a convenience sample of adult cigarette smokers from the general population beginning September 2014 through August 2015 . Of 2149 smokers who enrolled , 88 % completed the trial . No participants withdrew owing to adverse events . INTERVENTIONS We r and omly assigned participants to receive on their cigarette packs for 4 weeks either text-only warnings ( one of the Surgeon General 's warnings currently in use in the United States on the side of the cigarette packs ) or pictorial warnings ( one of the Family Smoking Prevention and Tobacco Control Act 's required text warnings and pictures that showed harms of smoking on the top half of the front and back of the cigarette packs ) . MAIN OUTCOMES AND MEASURES The primary trial outcome was attempting to quit smoking during the study . We hypothesized that smokers r and omized to receive pictorial warnings would be more likely to report a quit attempt during the study than smokers r and omized to receive a text-only Surgeon General 's warning . RESULTS Of the 2149 participants who began the trial ( 1039 men , 1060 women , and 34 transgender people ; mean [ SD ] age , 39.7 [ 13.4 ] years for text-only warning , 39.8 [ 13.7 ] for pictorial warnings ) , 1901 completed it . In intent-to-treat analyses ( n = 2149 ) , smokers whose packs had pictorial warnings were more likely than those whose packs had text-only warnings to attempt to quit smoking during the 4-week trial ( 40 % vs 34 % ; odds ratio [ OR ] , 1.29 ; 95 % CI , 1.09 - 1.54 ) . The findings did not differ across any demographic groups . Having quit smoking for at least the 7 days prior to the end of the trial was more common among smokers who received pictorial than those who received text-only warnings ( 5.7 % vs 3.8 % ; OR , 1.53 ; 95 % CI , 1.02 - 2.29 ) . Pictorial warnings also increased forgoing a cigarette , intentions to quit smoking , negative emotional reactions , thinking about the harms of smoking , and conversations about quitting . CONCLUSIONS AND RELEVANCE Pictorial warnings effectively increased intentions to quit , forgoing cigarettes , quit attempts , and successfully quitting smoking over 4 weeks . Our trial findings suggest that implementing pictorial warnings on cigarette packs in the United States would discourage smoking . TRIAL REGISTRATION clinical trials.gov Identifier : NCT02247908 BACKGROUND : New health warnings and contents labelling on tobacco products were introduced in Australia in 1995 . OBJECTIVE : To assess awareness of the new warnings at a time when a mix of packs with old and new warnings were being sold and on changes in relevant knowledge and attitudes from shortly before the implementation of the new warnings . DESIGN AND SUBJECTS : Approximately 500 smokers and 500 non-smokers were surveyed in December 1994 , before implementation of the new warnings . Similar numbers were also surveyed in May 1995 , part-way through implementation . Respondents were selected by r and om-digit dialling of telephone numbers in Australia . Smokers were over sample d. In addition , 243 smokers from the initial survey were re-surveyed in May 1995 . MAIN OUTCOME MEASURES : Awareness of change to health warnings , knowledge of health warnings and tobacco smoke constituents , beliefs about the health effects of smoking , and perceived impact of the warnings . RESULTS : There was high awareness of the new warnings , particularly among smokers , with the increased size of the new warnings being the most salient feature . More than a third of smokers reported being affected by the warnings , with reductions in consumption and talking about warnings being the most common effects . Among smokers , there was an increase in knowledge about the main constituents of tobacco smoke . The number of types of health effects mentioned also increased as did the number of warnings correctly recalled . Overall beliefs about the six warning statements became stronger . Few changes were found for non-smokers . The knowledge and recall effects were replicated in the re-contact sub sample , but the belief changes were not . CONCLUSIONS : These results suggest the new health warnings are result ing in better informed smokers and thus suggest that informative health warnings can play an important role in better informing consumers |
1,816 | 23,489,944 | Routine adenosine testing is associated with an improvement in freedom from AF post-PVI .
Paradoxically acute adenosine-induced PV reconnection may portend a greater likelihood of AF recurrence despite additional ablation . | INTRODUCTION Pulmonary vein reconnection is a major limitation of pulmonary vein isolation ( PVI ) for symptomatic atrial fibrillation ( AF ) .
Adenosine may unmask dormant PV conduction and facilitate consolidation of PV isolation .
We performed a systematic review of the literature to determine the impact of routine adenosine administration on clinical outcomes in patients undergoing PVI . | INTRODUCTION Dormant pulmonary vein ( PV ) conduction can be provoked by adenosine triphosphate ( ATP ) after extensive encircling pulmonary vein isolation ( EEPVI ) . However , the clinical implication of reconnection between the left atrium ( LA ) and isolated PVs provoked by ATP ( ATP-reconnection ) remains unknown . METHODS AND RESULTS We studied the clinical consequences of ATP-reconnection during intravenous isoproterenol infusion ( ISP-infusion ) . EEPVI severs conduction between the LA and ipsilateral PVs at their junction . Radiofrequency energy is applied at a distance from the PV ostia guided by double Lasso catheters placed within the ipsilateral superior and inferior PVs . This study comprised 82 patients ( 67 men , 56 + /- 9 years old ) with atrial fibrillation ( AF ) who underwent injection of ATP during ISP infusion after successful EEPVI ( ATP(+ ) group ) . We compared clinical characteristics of 170 patients who underwent earlier EEPVI prior to our use of ATP injection after successful EEPVI ( ATP(N/D ) group ) with those of ATP(+ ) group patients who underwent one session of EEPVI . ATP-reconnection occurred in 34 ( 41 % ) of 82 ATP(+ ) group patients . Additional radiofrequency applications were performed to eliminate ATP-reconnection in all ipsilateral PVs . Continuous ATP-reconnection of more than 20 seconds duration occurred in six ( 7.3 % ) of 82 patients . A total of 102 ( 60 % ) of 170 patients in the ATP(N/D ) group had no recurrence of AF , whereas 60 ( 73 % ) of 82 ATP(+ ) group patients who underwent only one EEPVI session have had no recurrence of AF in a 6.1 + /- 3.3-month follow-up period ( P = 0.04 ) . CONCLUSION Radiofrequency application for provoked ATP-reconnection may reduce clinical AF recurrence BACKGROUND Catheter ablation ( CA ) by wide encirclement of pulmonary veins ( WEPV ) restores sinus rhythm in up to 95 % . Complex PV-left atrial ( LA ) connections make achieving electrical isolation ( EI ) challenging . We examined anatomical and technical features associated with resistance to EI during WEPV in a prospect i ve study . METHODS One hundred one consecutive patients with symptomatic AF underwent first-time CA guided by electroanatomic mapping and CT integration ( Cartomerg ) . Following double-transseptal access , WEPV was performed . After completion of PV encirclement , the line was mapped and where no signal could be obtained , CA was performed inside the WE line at the site of earliest PV breakthrough on the circular mapping catheter . Sites of EI were tagged . Anatomic studies of corresponding regions of the venoatrial junction in 24 adult hearts were performed . RESULTS Sites resistant to EI were located at the inferior quadrant ( P < 0.001 ) for the RSPV , superior quadrant ( P < 0.001 ) for the RIPV , and the inferior and anterior quadrants ( P < 0.001 ) for the LSPV . EI was significantly less frequent at the posterior quadrant ( P < 0.001 ) for the LIPV . To achieve EI , CA was necessary inside the WE on the intervenous ridge on the right in 51 % and on the left in 41 % . The LPV/LAA ridge was investigated by anatomic studies that demonstrated considerable variation in the narrowest width ( 3 - 23.7 mm ) and transmural thickness ( 1 - 5 mm ) . CONCLUSION Sites of EI after WEPV have a preferential distribution determined by anatomic features . CA on the intervenous ridge is required in a significant proportion of patients to achieve EI . Atrial folds and ridges increase myocardial thickness creating technical and anatomic challenges for achieving transmural lesions AIMS Pulmonary vein ( PV ) isolation is a curative treatment for patients with atrial fibrillation . The aim of this study was to evaluate prospect ively the effects of adenosine administration on the PV activity and atrio-venous conduction after PV isolation . METHODS AND RESULTS Twenty-nine patients ( 21 m ; age : 55+/-8 years ) were su bmi tted to ostial PV isolation guided by basket catheter recordings . After successful isolation , the effects of a 12 mg intravenous bolus of adenosine were tested in 62 PVs . In 22/62 PVs ( 35 % ) , left atrium (LA)-to-PV conduction was transiently ( 16.6+/-7.1 s , range : 3.8 - 27.9 s ) or permanently ( 3 PVs ) restored in response to adenosine administration . The prevalence of this phenomenon was 39 % in left superior PVs , 43 % in right superior PVs , and 22 % in left inferior PVs ( p=0.365 ) . It occurred more frequently in the presence of dissociated PV activity ( 11/15 PVs , 73 % vs. 11/47 PVs , 23 % ; p=0.002 ) , whereas it was not influenced by the median duration of the radiofrequency current ( RFC ) delivery for each PV [ 19 ( IQR : 12 - 26 ) min vs. 16 ( IQR : 11 - 24 ) min : p=0.636 ] . A lengthening or shortening of the LA-PV conduction time was observed at LA-PV conduction appearance and disappearance in 36 % and 55 % of the cases , respectively . Further RFC applications ( median : 5.5 min , IQR : 4 - 11 min ) at the residual conduction breakthrough(s ) indicated by the basket catheter recordings definitively eliminated adenosine-induced recovery of LA-PV conduction in all cases . Finally , when present , intrinsic PV discharge was invariably depressed by adenosine administration . CONCLUSIONS Adenosine may transiently or permanently re-establish LA-PV conduction after apparently successful PV isolation . This phenomenon is abolished by additional RFC delivery . However , its possible influence on the clinical results of PV ablation must be evaluated by properly design ed , r and omized studies INTRODUCTION Catheter ablation for paroxysmal AF ( PAF ) is limited by an unacceptable recurrence rate , mainly due to pulmonary vein ( PV ) reconnection . Strategies to minimize reconnection include adenosine infusion and also a waiting period of 30 minutes after PV isolation . The aim of the present study was to assess whether these two strategies revealed the same conduction gap . METHODS AND RESULTS In total , 88 consecutive patients ( 54 males , mean age of 60 years ) with drug refractory PAF underwent circumferential PV isolation ( CPVI ) . After isolation of ipsilateral PVs , with entry and exit block checked using a circular mapping catheter , 20 mg ATP was injected during isoproterenol infusion to reveal dormant conduction gap(s ) . Unless the reconnection revealed by ATP persisted , PVs were further remapped with the circular mapping catheter at 30 minutes postisolation . Totally , PV reconnection was observed in 56 ( 64 % ) patients . 24.3 % veins ( 80/329 ) were found reconnected . Re assessment at 30 minutes postablation was more efficient as compared to ATP induction ( 19.8 % vs 14.6 % for ATP ) . The agreement between these 2 methods is moderate ( kappa value = 0.50 ) . In veins that transiently reconnected after ATP administration and later observed at 30 minutes postablation , 94 % ( 17 of 19 ) of them were found being reconnected with the same gap . CONCLUSION Acute PV reconnection is common , occurring in 64 % of patients , as detected by adenosine infusion and waiting time . Each shows a unique quality as compared to one another . The combined use of these 2 methods may reduce the AF recurrence rate after CPVI BACKGROUND Pulmonary vein ( PV ) isolation ( PVI ) has emerged as an effective therapy for paroxysmal atrial fibrillation ( AF ) . However , AF recurs in up to 50 % of patients , generally because of recovery of PV conduction . Adenosine given during the initial procedure may reveal dormant PV conduction , thereby identifying the need for additional ablation , leading to improved outcomes . The Adenosine Following Pulmonary Vein Isolation to Target Dormant Conduction Elimination ( ADVICE ) study is a prospect i ve multicentre r and omized trial assessing the impact of adenosine-guided PVI in preventing AF recurrences . METHODS Patients undergoing a first PVI procedure for paroxysmal AF will be recruited . After st and ard PVI is completed , all patients will receive intravenous adenosine in an attempt to unmask dormant conduction . If dormant conduction is elicited , patients will be r and omized to no further ablation ( control group ) or additional adenosine-guided ablation until dormant conduction is abolished . If no dormant conduction is revealed , r and omly selected patients will be followed in a registry . The primary outcome is time to first documented symptomatic AF recurrence . Assuming that dormant conduction is present in 50 % of patients post PVI and symptomatic AF recurs in 45 % of controls , 244 patients with dormant conduction will be required to obtain > 90 % power to detect a difference of 20 % . Thus , a total of 488 patients will be enrolled and followed for 12 months . CONCLUSION The ADVICE trial will assess whether a PVI strategy incorporating elimination of dormant conduction unmasked by intravenous adenosine will decrease the rate of recurrent symptomatic AF compared with st and ard PVI BACKGROUND Although it is well recognized that recovery of pulmonary vein ( PV ) conduction is common among patients who fail atrial fibrillation ( AF ) ablation , little is known about the precise time course of recurrence . OBJECTIVE To determine the incidence and time course of early recurrence of conduction after PV isolation during AF ablation . METHODS The patient population was composed of 14 consecutive patients ( 9 men [ 64 % ] ; age 56 + /- 7 years ) with AF who underwent radiofrequency catheter ablation via circumferential ablation with PV isolation , determined by a circular mapping catheter . After successful isolation of the PVs , repeat circular electrode recordings from each PV were obtained at 30 and 60 minutes . RESULTS After complete isolation of all PVs , early PV recurrence was observed in 13 ( 93 % ) patients and 26 veins ( 50 % ) . Seventeen veins ( 33 % ) showed a first recurrence at 30 minutes , while nine veins ( 17 % ) showed a first recurrence at 60 minutes . CONCLUSION The results reveal an extremely high rate of early recurrence of PV conduction following AF ablation . It is particularly notable that about one-fifth of the veins remained isolated at 30 minutes , but subsequently developed recurrence between 30 and 60 minutes . Of the veins that showed early recurrence , one-third developed a first recurrence at 60 minutes . These findings suggest that AF ablation procedures should incorporate a 60-minute waiting period after initial isolation in order to detect early recurrence of conduction |
1,817 | 29,441,476 | An influence of ARC on antimicrobial pharmacokinetics has been observed , with ARC consistently being associated with subtherapeutic antibiotic plasma concentrations .
Conclusion ARC is a prevalent condition in critically ill patients , especially in young people , with urinary CrCl being the best diagnostic method because mathematical estimates tend to underestimate CrCl .
ARC increases renal drug elimination and has a clear influence on certain antimicrobial plasma levels , but is yet to define its impact on clinical outcomes and on pharmacokinetics of other types of drugs . | Background Traditionally , renal function in critically ill patients has been assessed to identify renal dysfunction , and dose adjustment is generally accepted in such a context .
Nevertheless , augmented renal clearance ( ARC ) is a less well-studied phenomenon that could lead to faster elimination of drugs , result ing in subtherapeutic concentrations and poorer clinical outcomes when st and ard dosage guidelines are followed .
Objective The aim of this systematic review was to gather and summarise all the available evidence on ARC in critically ill patients , including its definition , underlying mechanisms , epidemiology , diagnosis and impact on both drug pharmacokinetics and clinical outcomes .
Results Augmented renal clearance , defined as a creatinine clearance ( CrCl ) > 130 mL/min/1.73 m2 , preferably measured in urine , is present in 20–65 % of critically ill patients .
Younger age , polytrauma and lower severity illness have been identified as risk factors . | CONTEXT Although acute renal failure ( ARF ) is believed to be common in the setting of critical illness and is associated with a high risk of death , little is known about its epidemiology and outcome or how these vary in different regions of the world . OBJECTIVES To determine the period prevalence of ARF in intensive care unit ( ICU ) patients in multiple countries ; to characterize differences in etiology , illness severity , and clinical practice ; and to determine the impact of these differences on patient outcomes . DESIGN , SETTING , AND PATIENTS Prospect i ve observational study of ICU patients who either were treated with renal replacement therapy ( RRT ) or fulfilled at least 1 of the predefined criteria for ARF from September 2000 to December 2001 at 54 hospitals in 23 countries . MAIN OUTCOME MEASURES Occurrence of ARF , factors contributing to etiology , illness severity , treatment , need for renal support after hospital discharge , and hospital mortality . RESULTS Of 29 269 critically ill patients admitted during the study period , 1738 ( 5.7 % ; 95 % confidence interval [ CI ] , 5.5%-6.0 % ) had ARF during their ICU stay , including 1260 who were treated with RRT . The most common contributing factor to ARF was septic shock ( 47.5 % ; 95 % CI , 45.2%-49.5 % ) . Approximately 30 % of patients had preadmission renal dysfunction . Overall hospital mortality was 60.3 % ( 95 % CI , 58.0%-62.6 % ) . Dialysis dependence at hospital discharge was 13.8 % ( 95 % CI , 11.2%-16.3 % ) for survivors . Independent risk factors for hospital mortality included use of vasopressors ( odds ratio [ OR ] , 1.95 ; 95 % CI , 1.50 - 2.55 ; P<.001 ) , mechanical ventilation ( OR , 2.11 ; 95 % CI , 1.58 - 2.82 ; P<.001 ) , septic shock ( OR , 1.36 ; 95 % CI , 1.03 - 1.79 ; P = .03 ) , cardiogenic shock ( OR , 1.41 ; 95 % CI , 1.05 - 1.90 ; P = .02 ) , and hepatorenal syndrome ( OR , 1.87 ; 95 % CI , 1.07 - 3.28 ; P = .03 ) . CONCLUSION In this multinational study , the period prevalence of ARF requiring RRT in the ICU was between 5 % and 6 % and was associated with a high hospital mortality rate Background Correct antibiotic dosing remains a challenge for the clinician . The aim of this study was to assess the influence of augmented renal clearance on pharmacokinetic/pharmacodynamic target attainment in critically ill patients receiving meropenem or piperacillin/tazobactam , administered as an extended infusion . Methods This was a prospect i ve , observational , pharmacokinetic study executed at the medical and surgical intensive care unit at a large academic medical center . Elegible patients were adult patients without renal dysfunction receiving meropenem or piperacillin/tazobactam as an extended infusion . Serial blood sample s were collected to describe the antibiotic pharmacokinetics . Urine sample s were taken from a 24-hour collection to measure creatinine clearance . Relevant data were drawn from the electronic patient file and the intensive care information system . Results We obtained data from 61 patients and observed extensive pharmacokinetic variability . Forty-eight percent of the patients did not achieve the desired pharmacokinetic/pharmacodynamic target ( 100 % f T > MIC ) , of which almost 80 % had a measured creatinine clearance > 130 mL/min . Multivariate logistic regression demonstrated that high creatinine clearance was an independent predictor of not achieving the pharmacokinetic/pharmacodynamic target . Seven out of nineteen patients ( 37 % ) displaying a creatinine clearance > 130 mL/min did not achieve the minimum pharmacokinetic/pharmacodynamic target of 50 % f T > MIC . Conclusions In this large patient cohort , we observed significant variability in pharmacokinetic/pharmacodynamic target attainment in critically ill patients . A large proportion of the patients without renal dysfunction , most of whom displayed a creatinine clearance > 130 mL/min , did not achieve the desired pharmacokinetic/pharmacodynamic target , even with the use of alternative administration methods . Consequently , these patients may be at risk for treatment failure without dose up-titration BACKGROUND Higher daptomycin doses are advocated for select methicillin-resistant Staphylococcus aureus (MRSA)-related infections , but the probabilities of target attainment ( PTA ) and toxicity of these doses have not been characterized in critically ill patients . METHODS We evaluated the plasma pharmacokinetics ( PK ) and clinical outcomes of a cohort of critically ill patients treated with daptomycin 6 - 8 mg/kg/day for primarily Staphylococcus species-related infections . Daptomycin concentrations were measured intensively over the initial 96-hour dosing period . Data were modeled by population PK analyses , and Monte Carlo simulation was used to estimate the probabilities of effect and toxicity with st and ard and alternate dosing regimens . RESULTS Fifty patients with a mean ( SD ) age of 69.7 ( 12.2 ) years , weight 74.5 ( 20.3 ) kg , and creatinine clearance 56.8 ( 38.2 ) mL/minute were enrolled with measurements of 12 ( 2.2 ) daptomycin sample s per patient . Significantly lower daptomycin exposures were observed despite comparable doses in a subset of patients ( n = 13 ) with augmented clearance ( CL ) . No covariates of CL were identified , but this subset was significantly more likely to be in severe sepsis or septic shock , have higher Sequential Organ Failure Assessment scores , and MRSA bacteremia . In-hospital mortality was significantly higher ( 30.7 % vs 10.8 % ) in patients with augmented daptomycin CL . Use of an empiric fixed dose of 750 mg of daptomycin is predicted to achieve a comparable PTA with a lower probability of toxicity as compared to the use of 10 mg/kg in critically ill patients . CONCLUSIONS A re appraisal of current daptomycin dosing recommendations is needed to improve the PTA and reduce toxicity among critically ill patients Background In ICU patients with normal serum creatinine ( SCr ) , a state of increased renal drug excretion has been described ( creatinine clearance ≥130 ml/min/1.73 m2 ) , and named augmented renal clearance ( ARC ) . In ICU patients , the accuracy of GFR estimates is insufficient . However , in clinical practice , the physician has not at one ’s disposal patient measured creatinine clearance ( CrCl ) when prescribing . The primary objective of this study was to assess the accuracy of 4 formulas to estimate GFR ( Cockcroft-Gault ( CG ) , Robert , sMDRD , and CKD-EPI formulas ) with other covariates to detect ARC in ICU patients . Methods We enroled 360 consecutive ICU patients with normal SCr in this prospect i ve observational study conducted in a primary teaching hospital . Comparisons between CrCl values and 4 estimated GFR ( eGFR ) formulas were estimated . Results In these 360 patients , ARC was observed in 33 % of patients most of them trauma . Individual predictive values of equations were poor and the phenomenon increased in ARC subgroup . CG and CKD-EPI were more accurate to detect an ARC . Multivariable analysis showed that the best-fitting model included 3 factors independently correlated to ARC : trauma patients , cut-off values of age ≤58 years , and CKD-EPI more than 108 ml/min/1.73 m2 . Conclusions In ICU patients with normal SCr , eGFR formulas are imprecise in assessing CrCl . If measured CrCl must be ideally used to detect modifications of the renal function , in clinical practice , age , reason for admission , and CKD-EPI could be used as screening tool to identify ARC Our objective was to prospect ively determine the factors influencing the probability of a good microbiological or clinical outcome in patients with nosocomial pneumonia treated with a fluoroquinolone . Levofloxacin was administered as an infusion of 500 mg/h for 1.5 h ( total dose , 750 mg ) . For patients with Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus , a second drug was added ( ceftazidime or piperacillin/tazobactam for P. aeruginosa and vancomycin for methicillin-resistant S. aureus ) . Population pharmacokinetic studies of 58 patients demonstrated that this population h and led the drug differently from population s of volunteers . Multivariate logistic regression analysis ( n=47 patients ) demonstrated that only the age of the patient and the achievement of an area under the curve : minimum inhibitory concentration ratio of > or = 87 had a significant effect on eradication of the pathogen ( P<.001 ) . Achieving the breakpoint made the patient 4 times more likely to achieve eradication . The effect was greatest in patients > or = 67 years old Introduction The aim of this study was to explore changes in glomerular filtration ( GFR ) and renal tubular function in critically ill patients at risk of augmented renal clearance ( ARC ) , using exogenous marker compounds . Methods This prospect i ve , observational pharmacokinetic ( PK ) study was performed in a university-affiliated , tertiary-level , adult intensive care unit ( ICU ) . Patients aged less than or equal to 60 years , manifesting a systemic inflammatory response , with an expected ICU length of stay more than 24 hours , no evidence of acute renal impairment ( plasma creatinine concentration < 120 μmol/L ) and no history of chronic kidney disease or renal replacement therapy were eligible for inclusion . The following study markers were administered concurrently : sinistrin 2,500 mg ( Inutest ; Laevosan , Linz , Austria ) , p-aminohippuric acid ( PAH ) 440 mg ( 4 % p-aminohippuric acid sodium salt ; CFM Oskar Tropitzsch , Marktredwitz , Germany ) , rac-pindolol 5 or 15 mg ( Barbloc ; Alphapharm , Millers Point , NSW , Australia ) and fluconazole 100 mg ( Diflucan ; Pfizer Australia Pty Ltd , West Ryde , NSW , Australia ) . Plasma concentrations were then measured at 5 , 10 , 15 , 30 , 60 and 120 minutes and 4 , 6 , 12 and 24 hours post-administration . Non-compartmental PK analysis was used to quantify GFR , tubular secretion and tubular reabsorption . Results Twenty patients were included in the study . Marker administration was well tolerated , with no adverse events reported . Sinistrin clearance as a marker of GFR was significantly elevated ( mean , 180 ( 95 % confidence interval ( CI ) , 141 to 219 ) ml/min ) and correlated well with creatinine clearance ( r = 0.70 , P < 0.01 ) . Net tubular secretion of PAH , a marker of tubular anion secretion , was also elevated ( mean , 428 ( 95 % CI , 306 to 550 ) ml/min ) , as was net tubular reabsorption of fluconazole ( mean , 135 ( 95 % CI , 100 to 169 ) ml/min ) . Net tubular secretion of (S)- and (R)-pinodolol , a marker of tubular cation secretion , was impaired . Conclusions In critically ill patients at risk of ARC , significant alterations in glomerular filtration , renal tubular secretion and tubular reabsorption are apparent . This has implication s for accurate dosing of renally eliminated drugs See related commentary by De Waele and Carlier , http://ccforum.com/content/17/2/130 Introduction Improved methods to optimize drug dosing in the critically ill are urgently needed . Traditional prescribing culture involves recognition of factors that m and ate dose reduction ( such as renal impairment ) , although optimizing drug exposure , through more frequent or augmented dosing , represents an evolving strategy . Elevated creatinine clearance ( CLCR ) has been associated with sub-therapeutic antibacterial concentrations in the critically ill , a concept termed augmented renal clearance ( ARC ) . We aim ed to determine the prevalence of ARC in a cohort of septic and traumatized critically ill patients , while also examining demographic , physiological and illness severity characteristics that may help identify this phenomenon . Methods This prospect i ve observational study was performed in a 30-bed tertiary level , university affiliated , adult intensive care unit . Consecutive traumatized and septic critically ill patients , receiving antibacterial therapy , with a plasma creatinine concentration ≤110 μmol/L , were eligible for enrolment . Pulse contour analysis ( Vigileo / Flo Trac ® system , Edwards Lifesciences , Irvine , CA , USA ) , was used to provide continuous cardiac index ( CI ) assessment over a single six-hour dosing interval . Urinary CLCR measures were obtained concurrently . Results Seventy-one patients contributed data ( sepsis n = 43 , multi-trauma n = 28 ) . Overall , 57.7 % of the cohort manifested ARC , although there was a greater prevalence in trauma ( 85.7 % versus 39.5 % , P < 0.001 ) . In all patients , a weak correlation was noted between CI and CLCR ( r = 0.346 , P = 0.003 ) . This was mostly driven by septic patients ( r = 0.508 , P = 0.001 ) , as no correlation ( r = -0.012 , P = 0.951 ) was identified in trauma . Those manifesting ARC were younger ( P<0.001 ) , male ( P = 0.012 ) , with lower acute physiology and chronic health evaluation ( APACHE ) II ( P= 0.008 ) and modified sequential organ failure assessment ( SOFA ) scores ( P = 0.013 ) , and higher cardiac indices ( P = 0.013 ) . In multivariate analysis , age ≤50 years , trauma , and a modified SOFA score ≤4 , were identified as significant risk factors . These had greater utility in predicting ARC , compared with CI assessment alone . Conclusions Diagnosis , illness severity and age , are likely to significantly influence renal drug elimination in the critically ill , and must be regularly considered in future study design and daily prescribing practice Introduction We conducted a study to evaluate the incidence , risk factors and outcomes associated with early acute kidney injury ( AKI ) in sepsis . Methods The study was a retrospective interrogation of prospect ively collected data from the Australian New Zeal and Intensive Care Society Adult Patient Data base . Data were collected from 57 intensive care units ( ICUs ) across Australia . In total , 120,123 patients admitted to ICU for more than 24 hours from 1 January 2000 to 31 December 2005 were included in the analysis . The main outcome measures were clinical and laboratory data and outcomes . Results Of 120,123 patients admitted , 33,375 had a sepsis-related diagnosis ( 27.8 % ) . Among septic patients , 14,039 ( 42.1 % ) had concomitant AKI ( septic AKI ) . Sepsis accounted for 32.4 % of all patients with AKI . For septic AKI stratified by RIFLE ( risk of renal failure , injury to the kidney , failure of kidney function , loss of kidney function and end-stage kidney disease ) category , 38.5 % of patients belonged to the risk category , 38.8 % to the injury category and 22.7 % to the failure category . Septic AKI patients had greater acuity of illness ( P < 0.0001 ) , lower blood pressure ( P < 0.0001 ) , higher heart rates ( P < 0.0001 ) , worse pulmonary function measures by arterial oxygen tension/fraction of inspired oxygen ratio ( P < 0.0001 ) , greater acidaemia ( P < 0.0001 ) and higher white cell counts ( P < 0.0001 ) compared with patients with nonseptic AKI . Septic AKI was also associated with greater severity of AKI ( RIFLE category injury or failure ) compared with nonseptic AKI . Septic AKI was associated with a significantly higher crude and co-variate adjusted mortality in the ICU ( 19.8 % versus 13.4 % ; odds ratio 1.60 , 95 % confidence interval 1.5 to 1.7 ; P < 0.001 ) and in hospital ( 29.7 % versus 21.6 % ; odds ratio 1.53 , 95 % confidence interval 1.46 to 1.60 ; P < 0.001 ) compared with nonseptic AKI . Septic AKI was associated with higher ICU and hospital mortality across all strata of RIFLE categories . Septic AKI patients had longer duration s of stay in both ICU and hospital across all strata of RIFLE categories . ConclusionS eptic AKI is common during the first 24 hours after ICU admission . Patients with septic AKI are generally sicker , with a higher burden of illness , and have greater abnormalities in acute physiology compared with patients with nonseptic AKI . Moreover , septic AKI is independently associated with higher odds of death and longer duration of hospitalization Augmented renal clearance ( ARC ) is known to influence β-lactam antibiotic pharmacokinetics . This sub study of the BLING-II trial aim ed to explore the association between ARC and patient outcomes in a large r and omised clinical trial . BLING-II enrolled 432 participants with severe sepsis r and omised to receive β-lactam therapy by continuous or intermittent infusion . An 8-h creatinine clearance ( CLCr ) measured on Day 1 was used to identify ARC , defined as CLCr ≥ 130 mL/min . Patients receiving any form of renal replacement therapy were excluded . Primary outcome was alive ICU-free days at Day 28 . Secondary outcomes included 90-day mortality and clinical cure at 14 days following antibiotic cessation . A total of 254 patients were included , among which 45 ( 17.7 % ) manifested ARC [ median ( IQR ) CLCr 165 ( 144 - 198 ) mL/min ] . ARC patients were younger ( P < 0.001 ) , more commonly male ( P = 0.04 ) and had less organ dysfunction ( P < 0.001 ) . There was no difference in ICU-free days at Day 28 [ ARC , 21 ( 12 - 24 ) days ; no ARC , 21 ( 11 - 25 ) days ; P = 0.89 ] , although clinical cure was significantly greater in the unadjusted analysis in those manifesting ARC [ 33/45 ( 73.3 % ) vs. 115/209 ( 55.0 % ) P = 0.02 ] . This was attenuated in the multivariable analysis . No difference was noted in 90-day mortality . There were no statistically significant differences in clinical outcomes in ARC patients according to the dosing strategy employed . In this sub study of a large clinical trial of β-lactam antibiotics in severe sepsis , ARC was not associated with any differences in outcomes , regardless of dosing strategy Altered pharmacokinetics in burn patients may affect antibiotic plasma concentrations . Typical once-daily dosing ( ODD ) of 15 mg/kg amikacin ( AMK ) in burn patients does not always produce peak concentrations ( C(max ) ) reaching the therapeutic objective of six to eight times the minimal inhibitory concentration ( MIC ) . We recorded plasma concentrations following administration of 20 mg/kg AMK in burn patients and studied factors affecting pharmacokinetics . Mean C(max ) was 48.3+/-10.8 mg/L and the C(max)/MIC ratio was 6+/-1.35 . Statistical analysis demonstrated a relationship between C(max ) and the area of the burn and Unit Burn St and ard , and between AMK clearance and creatinine clearance ( Cl(CR ) ) . We conclude that ODD regimens of AMK in patients with burns > 15 % body surface area and /or with Cl(CR ) > 120 mL/min could require doses > 20 mg/kg to reach adequate C(max ) . In all cases , patient therapeutic drug monitoring is essential to ensure the safe usage of these dosing recommendations BACKGROUND Acute renal failure ( ARF ) is associated with a persistent high mortality in critically ill patients in intensive care units ( ICUs ) . Most studies to date have focused on patients with established , intrinsic ARF or relatively severe ARF due to multiple factors . None have examined outcomes of dialysis-dependent chronic renal failure [ end-stage renal disease ( ESRD ) ] patients in the ICU . We examined the incidence and outcomes of ARF in the ICU using a st and ard definition and compared these to outcomes of ICU patients with either ESRD or no renal failure . We sought to determine the impact of renal dysfunction and /or loss of organ function on outcome . METHODS We prospect ively scored 1530 admissions to eight ICUs over a 10-month period for illness severity at ICU admission using the Acute Physiological and Chronic Health Evaluation ( APACHE III ) evaluation tool . Patients were defined as having ARF based on the definition of Hou et al ( Am J Med 74:243 - 248,1983 ) design ed to detect significant measurable declines in renal function based on serum creatinine . ESRD patients were identified as being chronically dialysis-dependent prior to ICU admission and the remainder had no renal failure . Clinical characteristics at ICU admission and ICU and hospital outcomes were compared between the three groups . RESULTS We identified 254 cases of ARF , 57 cases of ESRD and 1219 cases of no renal failure for an incidence of ARF of 17 % . Roughly half the ARF patients had ARF at ICU admission and the remainder developed ARF during their ICU stay . Only 11 % of ARF patients required dialysis support . ARF patients had significantly higher acute illness severity scores than those with no renal failure , whereas patients with ESRD had intermediate severity scores . ICU mortality was 23 % for patients with ARF , 11 % for those with ESRD , and 5 % for those with no renal failure . There was no difference in outcome between patients who had ARF at ICU admission and those who developed ARF in the ICU . Patients with ARF severe enough to require dialysis had a mortality of 57 % . APACHE III predicted outcome very well in patients with no renal failure and patients with ARF at the time of scoring but underpredicted mortality in those who developed ARF after ICU admission and overestimated mortality in patients with ESRD . CONCLUSIONS ARF is common in ICU patients and has a persistent negative impact on outcomes , although the majority of ARF is not severe enough to require dialysis support . The mortality of patients with ARF from all causes is almost exactly similar to that noted using the same criteria two decades ago . More profound ARF requiring dialysis continues to have an even greater mortality . Nevertheless , acute declines in renal function are associated with a mortality that is not well explained simply by loss of organ function . The majority of ARF patients who did not require dialysis still had a considerably higher mortality than the ESRD patients , all of whom required dialysis ; while ARF patients who did require dialysis had a much higher morality than ESRD patients . APACHE III performs well and captures the mortality of patients with ARF at the time of scoring . Development of ARF after scoring has a profound effect on st and ardized mortality . We were unable to identify a unique mortality associated with ARF , but the presence of measurable renal insufficiency continues to be a sensitive marker for poor outcome Augmented renal clearance ( ARC ) is being increasingly described in neurocritical care practice . The mechanisms driving this phenomenon are largely unknown . The aim of this project was therefore to explore changes in renal function , cardiac output ( CO ) , and atrial natriuretic peptide ( ANP ) concentrations in patients with isolated traumatic brain injury ( TBI ) . This prospect i ve observational cohort study was conducted in a tertiary-level , university-affiliated intensive care unit ( ICU ) . Patients with normal plasma creatinine concentrations ( < 120 μmol/L ) at admission and no history of chronic kidney disease , admitted with isolated TBI , were eligible for enrollment . Continuous CO measures were obtained using arterial pulse waveform analysis . Eight-hour urinary creatinine clearances ( CLCR ) were used to quantify renal function . ANP concentrations in plasma were measured on alternate days . Data were collected from study enrollment until ICU discharge , death , or day 15 , which ever came first . Eleven patients , contributing 100 ICU days of physiological data , were enrolled into the study . Most participants were young men , requiring mechanical ventilation . Median ICU length of stay was 9.6 [ 7.8 - 13.0 ] days . Elevated CLCR measures ( > 150 mL/min ) were frequent and appeared to parallel changes in CO . Plasma ANP concentrations were also significantly elevated over the study period ( minimum value = 243 pg/mL ) . These data suggest that ARC is likely to complicate the care of TBI patients with normal plasma creatinine concentrations , and may be driven by associated cardiovascular changes and /or elevated plasma ANP concentrations . However , significant additional research is required to further underst and these findings Background Accuracy of glomerular filtration rate ( GFR ) estimates has been question ed and several authors recommend routine use of measured renal creatinine clearance ( CLCR ) as a surrogate of GFR in the intensive care unit ( ICU ) . Our purpose was to compare estimates of GFR using Cockroft – Gault ( CG ) , Chronic Kidney Disease Epidemiology Collaboration ( CKD-EPI ) and Modification of Diet in Renal Disease Study ( MDRD ) equations with 8h-CLCR , within a population of critically ill patients with a wide range of measured CLCR . Methods Through a prospect i ve , observational study of 54 patients with normal serum creatinine ( sCr ) admitted to ICU , daily 8h-CLCR ( reference method ) and GFR estimates ( 644 paired sample s ) were matched and compared . Augmented renal clearance ( ARC ) was defined as 8h-CLCR > 130 ml/min/1.73 m2 . Results No significant difference was found between mean 8h-CLCR ( 135.5 ml/min/1.73 m2 ) and CG equation ( 135.7 ml/min/1.73 m2 ) , but significant differences ( p < 0.01 ) were found for the MDRD ( 124.4 ml/min/1.73 m2 ) and CKD-EPI ( 107.6 ml/min/1.73 m2 ) equations . Correlation between 8h-CLCR and all estimates was weak ( R = 0.2 , 0.19 and 0.34 , respectively ) . We observed poor agreement in terms of precision ( 40.9 , 39.8 and 33.4 % , respectively ) . Analysing subgroups , we observed that all equations significantly underestimated 8h-CLCR > 120 ml/min/1.73 m2 and overestimated 8h-CLCR < 120 ml/min/1.73 m2 ( p < 0.05 ) . The incidence of ARC patients was 55.6 % . Conclusions Estimates of GFR using CG , CKD-EPI and MDRD formulae are flawed in the critically ill with normal sCr , significantly underestimating renal function in those with ARC and overestimating it in those with normal or decreased 8h-CLCR . Globally , the population exhibited ARC on more than half of the ICU admission days Introduction Achievement of optimal vancomycin exposure is crucial to improve the management of patients with life-threatening infections caused by susceptible Gram-positive bacteria and is of particular concern in patients with augmented renal clearance ( ARC ) . The aim of this study was to develop a dosing nomogram for the administration of vancomycin by continuous infusion for the first 24 hours of therapy based on the measured urinary creatinine clearance ( 8 h CLCR ) . Methods This single-center study included all critically ill patients treated with vancomycin over a 13-month period ( group 1 ) , in which we retrospectively assessed the correlation between vancomycin clearance and 8 h CLCR . This data was used to develop a formula for optimised drug dosing . The efficiency of this formula was prospect ively evaluated in a second cohort of 25 consecutive critically ill patients ( group 2 ) . Vancomycin serum concentrations between 20 to 30 mg/L were considered adequate . ARC was defined as 8 h CLCR more than 130 ml/min/1.73 m2 . Results The incidence of ARC was 36 % ( n = 29/79 ) and 40 % ( 10/25 ) in group 1 ( n = 79 ) and 2 ( n = 25 ) , respectively . The mean serum vancomycin concentration on day 1 was 21.5 ( 6.4 ) and 24.5 ( 5.2 ) mg/L , for both groups respectively . On the treatment day , vancomycin plasma clearance was 5.12 ( 1.9 ) L/h in group 1 and correlated significantly with the 8 h CLCR ( r2 = 0.66 ; P < 0.001 ) . The achievement of adequate vancomycin serum concentrations in group 2 was 84 % ( n = 21/25 ) versus 51 % ( n = 40/79 ) – P < 0.005 . Conclusions This new vancomycin nomogram enabled the achievement of adequate serum concentrations in 84 % of the patients on the first day of treatment Background The Chronic Kidney Disease Epidemiology Collaboration ( CKD-EPI ) estimated glomerular filtration rate ( eGFR ) has been widely integrated into clinical practice . Although useful in screening for CKD , its ’ application in critically ill patients with normal plasma creatinine concentrations remains uncertain . The aim of this study was to assess the performance of CKD-EPI eGFR in comparison to creatinine clearance ( CLCR ) in this setting . Methods This prospect i ve observational study was performed in a tertiary level , university affiliated intensive care unit ( ICU ) . Study participants had to have an expected ICU length of stay > 24 hours , a plasma creatinine concentration < 121 μmol/L , and no history of prior renal replacement therapy or CKD . CKD-EPI eGFR was compared against 8-hour measured urinary CLCR . Data capture occurred within 48 hours of admission . Results One hundred and ten patients ( n = 110 ) were enrolled in the study . 63.6 % were male , the mean age was 50.9 ( 16.9 ) years , 57.3 % received invasive mechanical ventilation , and 30 % required vasopressor support . The mean CLCR was 125 ( 45.1 ) ml/min/1.73 m2 , compared to a CKD-EPI eGFR of 101 ( 23.7 ) ml/min/1.73 m2 ( P < 0.001 ) . Moderate correlation was evident ( r = 0.72 ) , although there was significant bias and imprecision ( 24.4 + /− 32.5 ml/min/1.73 m2 ) . In those patients with a CKD-EPI eGFR between 60–119 ml/min/1.73 m2 ( n = 77 ) , 41.6 % displayed augmented renal clearance ( CLCR ≥ 130 ml/min/1.73 m2 ) , while 7.8 % had a CLCR < 60 ml/min/1.73 m2 . Conclusions These data suggest CKD-EPI eGFR and measured CLCR produce significantly disparate results when estimating renal function in this population . Clinicians should consider carefully which value they employ in clinical practice , particularly drug dose modification Introduction Increasingly , derived estimates of glomerular filtration , such as the modification of diet in renal disease ( MDRD ) equation and Cockcroft-Gault ( CG ) formula are being employed in the intensive care unit ( ICU ) . To date , these estimates have not been rigorously vali date d in those with augmented clearances , result ing in potentially inaccurate drug prescription . Methods Post-hoc analysis of prospect ively collected data in two tertiary level ICU 's in Australia and Portugal . Patients with normal serum creatinine concentrations manifesting augmented renal clearance ( ARC ) ( measured creatinine clearance ( CLCR ) > 130 ml/min/1.73 m2 ) were identified by chart review . Comparison between measured values and MDRD and CG estimates were then undertaken . Spearman correlation coefficients ( rs ) were calculated to determine goodness of fit , and precision and bias were assessed using Bl and -Altman plots . Results Eighty-six patients were included in analysis . The median [ IQR ] measured CLCR was 162 [ 145 - 190 ] ml/min/1.73 m2 , as compared to 135 [ 116 - 171 ] , 93 [ 83 - 110 ] , 124[102 - 154 ] , and 108 [ 87 - 135 ] ml/min/1.73 m2 estimated by CG , modified CG , 4-variable MDRD and 6-variable MDRD formulae . All of the equations significantly under-estimated the measured value , with CG displaying the smallest bias ( 39 ml/min/1.73 m2 ) . Although a moderate correlation was noted between CLCR and CG ( rs = 0.26 , P = 0.017 ) and 4-variable MDRD ( rs = 0.22 , P = 0.047 ) , neither had acceptable precision for clinical application in this setting . CG estimates had the highest sensitivity for correctly identifying patients with ARC ( 62 % ) . Conclusions Derived estimates of GFR are inaccurate in the setting of ARC , and should be interpreted with caution by the physician . A measured CLCR should be performed to accurately guide drug dosing Background Augmented renal clearance ( ARC ) of circulating solutes and drugs has been recently often reported in intensive care unit ( ICU ) patients . However , only few studies on ARC have been reported in Japan . The aims of this pilot study were to determine the prevalence and risk factors for ARC in Japanese ICU patients with normal serum creatinine levels and to evaluate the association between ARC and estimated glomerular filtration rate ( eGFR ) calculated using the Japanese equation . Methods We conducted a prospect i ve observational study from May 2015 to April 2016 at the emergency ICU of a tertiary university hospital ; 111 patients were enrolled ( mean age , 67 years ; interquartile range , 53–77 years ) . We measured 8-h creatinine clearance ( CLCR ) within 24 h after admission , and ARC was defined as body surface area-adjusted CLCR ≥ 130 mL/min/1.73 m2 . Multiple logistic regression analysis was performed to identify the risk factors for ARC . Moreover , a receiver operating curve ( ROC ) analysis , including area under the receiver operating curve ( AUROC ) was performed to examine eGFR accuracy and other significant variables in predicting ARC . Results In total , 43 patients ( 38.7 % ) manifested ARC . Multiple logistic regression analysis was performed for age , body weight , body height , history of diabetes mellitus , Acute Physiology and Chronic Health Evaluation II scores , admission categories of post-operative patients without sepsis and trauma , and serum albumin , and only age was identified as an independent risk factor for ARC ( odds ratio , 0.95 ; 95 % confidence interval [ CI ] , 0.91–0.98 ) . Moreover , the AUROC of ARC for age and eGFR was 0.81 ( 95 % CI , 0.72–0.89 ) and 0.81 ( 95 % CI , 0.73–0.89 ) , respectively . The optimal cutoff values for detecting ARC were age and eGFR of ≤63 years ( sensitivity , 72.1 % ; specificity , 82.4 % ) and ≥76 mL/min/1.73 m2 ( sensitivity , 81.4 % ; specificity , 72.1 % ) , respectively . Conclusions ARC is common in Japanese ICU patients , and age was an independent risk factor for ARC . In addition , age and eGFR calculated using the Japanese equation were suggested to be useful screening tools for identifying Japanese patients with ARC Objective An augmented renal clearance has been described in some groups of critically ill patients , and it might induce sub-optimal concentrations of drugs eliminated by glomerular filtration , mainly antibiotics . Studies on its occurrence and determinants are lacking . Our goals were to determine the incidence and associated factors of augmented renal clearance and the effects on vancomycin concentrations and dosing in a series of intensive care unit patients . Methods We prospect ively studied 363 patients admitted during 1 year to a clinical -surgical intensive care unit . Patients with serum creatinine > 1.3mg/dL were excluded . Creatinine clearance was calculated from a 24-hour urine collection . Patients were grouped according to the presence of augmented renal clearance ( creatinine clearance > 120mL/min/1.73m2 ) , and possible risk factors were analyzed with bivariate and logistic regression analysis . In patients treated with vancomycin , dosage and plasma concentrations were registered . Results Augmented renal clearance was present in 103 patients ( 28 % ) ; they were younger ( 48±15 versus 65±17 years , p<0.0001 ) , had more frequent obstetric ( 16 versus 7 % , p=0.0006 ) and trauma admissions ( 10 versus 3 % , p=0.016 ) and fewer comorbidities . The only independent determinants for the development of augmented renal clearance were age ( OR 0.95 ; p<0.0001 ; 95%CI 0.93 - 0.96 ) and absence of diabetes ( OR 0.34 ; p=0.03 ; 95%CI 0.12 - 0.92 ) . Twelve of the 46 patients who received vancomycin had augmented renal clearance and despite higher doses , had lower concentrations . Conclusions In this cohort of critically ill patients , augmented renal clearance was a common finding . Age and absence of diabetes were the only independent determinants . Therefore , younger and previously healthy patients might require larger vancomycin dosing Objective To determine the incidence and effect on mortality of early acute kidney injury in severely injured trauma patients using the Acute Kidney Injury Network creatinine criteria . Design A retrospective cohort study of severely injured trauma patients admitted to the shock trauma intensive care unit . Setting Texas Trauma Institute , a state design ated level I trauma unit certified by the American College of Surgeons Committee on Trauma . Patients 901 severely injured trauma patients admitted over a 15 month period to the shock trauma intensive care unit . Interventions Retrospective analysis of prospect ively collected data abstract ed from an electronic trauma data base . Measurements and Main Results Of 901 eligible patients admitted to the shock trauma intensive care unit after traumatic injury , 54 patients ( 6 % ) developed acute kidney injury , of whom 10 ( 19 % ) required renal replacement therapy . The 30-day mortality rate for the entire cohort was 83/901 ( 9.2 % ) . Patients with early acute kidney injury had a mortality rate of 16/54 ( 29.6 % ) . When corrected for multiple covariates including injury severity scores , the development of early acute kidney injury was associated with a significantly higher risk of death at 30 days with an OR of 3.4 ( 95 % CI 1.6 - 7.4 ) . Conclusions Applying the Acute Kidney Injury Network creatinine criteria in severely injured trauma patients , the incidence of early acute kidney injury was 6 % . After correction for injury severity , development of early acute kidney injury was independently associated with significantly higher 30-day mortality INTRODUCTION We describe incidence and patient factors associated with augmented renal clearance ( ARC ) in adult intensive care unit ( ICU ) patients . MATERIAL S AND METHODS A prospect i ve observational study in a mixed cohort of surgical and medical ICU patients receiving antimicrobial therapy at the Ghent University Hospital , Belgium . Kidney function was assessed by the 24-hour creatinine clearance ( Ccr ) ; ARC defined as at least one Ccr of > 130 mL/min per 1.73 m2 . Multivariate logistic regression analysis : to assess variables associated with ARC occurrence . Therapeutic failure ( TF ) : an impaired clinical response and need for alternate antimicrobial therapy . RESULTS Of the 128 patients and 599 studied treatment days , ARC was present in 51.6 % of the patients . Twelve percent permanently expressed ARC . ARC patients had a median Ccr of 144 mL/min per 1.73 m2 ( IQR 98 - 196 ) . Median serum creatinine concentration on the first day of ARC was 0.54 mg/dL ( IQR 0.48 - 0.69 ) . Patients with ARC were significantly younger ( P<.001 ) . Age and male gender were independently associated with ARC whereas the APACHE II score was not . ARC patients had more TF ( 18 ( 27.3 % ) vs. 8 ( 12.9 % ) ; P=.04 ) . CONCLUSION ARC was documented in approximately 52 % of a mixed ICU patient population receiving antibiotic treatment with worse clinical outcome . Young age and male gender were independently associated with ARC presence BACKGROUND Morbidity and mortality for critically ill patients with infections remains a global healthcare problem . We aim ed to determine whether β-lactam antibiotic dosing in critically ill patients achieves concentrations associated with maximal activity and whether antibiotic concentrations affect patient outcome . METHODS This was a prospect i ve , multinational pharmacokinetic point-prevalence study including 8 β-lactam antibiotics . Two blood sample s were taken from each patient during a single dosing interval . The primary pharmacokinetic/pharmacodynamic targets were free antibiotic concentrations above the minimum inhibitory concentration ( MIC ) of the pathogen at both 50 % ( 50 % f T > MIC ) and 100 % ( 100 % f T > MIC ) of the dosing interval . We used skewed logistic regression to describe the effect of antibiotic exposure on patient outcome . RESULTS We included 384 patients ( 361 evaluable patients ) across 68 hospitals . The median age was 61 ( interquartile range [ IQR ] , 48 - 73 ) years , the median Acute Physiology and Chronic Health Evaluation II score was 18 ( IQR , 14 - 24 ) , and 65 % of patients were male . Of the 248 patients treated for infection , 16 % did not achieve 50 % f T > MIC and these patients were 32 % less likely to have a positive clinical outcome ( odds ratio [ OR ] , 0.68 ; P = .009 ) . Positive clinical outcome was associated with increasing 50 % f T > MIC and 100 % f T > MIC ratios ( OR , 1.02 and 1.56 , respectively ; P < .03 ) , with significant interaction with sickness severity status . CONCLUSIONS Infected critically ill patients may have adverse outcomes as a result of inadeqaute antibiotic exposure ; a paradigm change to more personalized antibiotic dosing may be necessary to improve outcomes for these most seriously ill patients Objective : To describe the prevalence and natural history of augmented renal clearance in a cohort of recently admitted critically ill patients with normal plasma creatinine concentrations . Design : Multicenter , prospect i ve , observational study . Setting : Four , tertiary-level , university-affiliated , ICUs in Australia , Singapore , Hong Kong , and Portugal . Patients : Study participants had to have an expected ICU length of stay more than 24 hours , no evidence of absolute renal impairment ( admission plasma creatinine < 120 µmol/L ) , and no history of prior renal replacement therapy or chronic kidney disease . Convenience sampling was used at each participating site . Interventions : Eight-hour urinary creatinine clearances were collected daily , as the primary method of measuring renal function . Augmented renal clearance was defined by a creatinine clearance more than or equal to 130 mL/min/1.73 m2 . Additional demographic , physiological , therapeutic , and outcome data were recorded prospect ively . Measurements and Main Results : Nine hundred thirty-two patients were admitted to the participating ICUs over the study period , and 281 of which were recruited into the study , contributing 1,660 individual creatinine clearance measures . The mean age ( 95 % CI ) was 54.4 years ( 52.5–56.4 yr ) , Acute Physiology and Chronic Health Evaluation II score was 16 ( 15.2–16.7 ) , and ICU mortality was 8.5 % . Overall , 65.1 % manifested augmented renal clearance on at least one occasion during the first seven study days ; the majority ( 74 % ) of whom did so on more than or equal to 50 % of their creatinine clearance measures . Using a mixed-effects model , the presence of augmented renal clearance on study day 1 strongly predicted ( p = 0.019 ) sustained elevation of creatinine clearance in these patients over the first week in ICU . Conclusions : Augmented renal clearance appears to be a common finding in this patient group , with sustained elevation of creatinine clearance throughout the first week in ICU . Future studies should focus on the implication s for accurate dosing of renally eliminated pharmaceuticals in patients with augmented renal clearance , in addition to the potential impact on individual clinical outcomes Glomerular hyperfiltration and albuminuria are two pathological conditions that could alter renal drug elimination , but they have been rarely studied in a critical care setting . The aims of this descriptive , prospect i ve study performed on 89 critically ill patients are to determine rates of glomerular hyperfiltration ( main objective ) and albuminuria ( secondary objective ) . On admission , 17.9 % of patients presented with glomerular hyperfiltration , climbing to rates as high as 30 % during the first week of admission . Seventy-five percent showed albuminuria on admission , with rates remaining high throughout the week of the study . Since glomerular hyperfiltration as well as albuminuria are frequent pathophysiological conditions in critical care patients , the implication s that these phenomena may have regarding drug elimination need further evaluation Objectives Acute renal failure is a complication in critically ill patients that has been associated with an excess risk of hospital mortality . Whether this reflects the severity of the disease or whether acute renal failure is an independent risk factor is unknown . The aim of this study was to analyze severity of illness and mortality in a group of critically ill patients with acute renal failure requiring renal replacement therapy in a number of Austrian intensive care units . Design Prospect i ve , multicenter cohort study . Patients and Setting A total of 17,126 patients admitted consecutively to 30 medical , surgical , and mixed intensive care units in Austria over a period of 2 yrs . Measurements and Main Results Analyzed data included admission data , Simplified Acute Physiology Score , Logistic Organ Dysfunction system , Simplified Therapeutic Intervention Scoring System , length of intensive care unit stay , intensive care unit mortality , and hospital mortality . Of the admitted patients , 4.9 % ( n = 839 ) underwent renal replacement therapy because of acute renal failure ( renal replacement therapy patients ) . These patients had a significantly higher hospital mortality ( 62.8 % vs. 15.6 % , p < .001 ) , which remained significantly higher even when renal replacement therapy patients were matched with control subjects for age , severity of illness , and treatment center . Since univariate analysis demonstrated further intensity of treatment to be an additional predictor for outcome , a multivariate model including therapeutic interventions was developed . Five interventions were associated with nonsurvival ( mechanical ventilation , single vasoactive medication , multiple vasoactive medication , cardiopulmonary resuscitation , and treatment of complicated metabolic acidosis/alkalosis ) . In contrast , the use of enteral nutrition predicted a favorable outcome . Conclusions The results of our study suggest that acute renal failure in patients undergoing renal replacement therapy presents an excess risk of in-hospital death . This increased risk can not be explained solely by a more pronounced severity of illness . Our results provide strong evidence that acute renal failure presents a specific and independent risk factor for poor prognosis Background Patients with subarachnoid hemorrhage ( SAH ) typically exhibit hyperdynamic cardiovascular hemodynamics , which may lead to increased medication clearance . The aims of this study were to evaluate the actual creatinine clearance ( CrClA ) in an aneurysmal SAH population and the effect of the development of cerebral vasospasm ( CV ) along with its treatment to better underst and if this population exhibits augmented renal clearance ( ARC ) . Methods This was a prospect i ve , single-center study in a neurosciences ICU at a university hospital . A total of 20 patients were consented and provided a 24-h urine sample to measure the CrClA. If patients experienced CV , a 24-h urine collection was repeated during vasospasm treatment . CrClA was measured using a modified Jaffe assay . Results Among the 20 patients enrolled , the mean SAH CrClA was 325.93 ± 135.20 ml/min 1.73 m2 and this differed significantly from the SAH estimated creatinine clearance ( CrClE ) 144.93 ± 42.82 ml/min 1.73 m2 ( p < 0.001 ) . Four patients developed CV ; the mean CV CrClA was 558.43 ± 356.12 ml/min 1.73 m2 and there was no significant difference when compared to those patients ’ mean SAH CrClA ( 246.91 ± 84.14 ml/min 1.73 m2 , p = 0.16 ) . Conclusions ARC was present in 100 % of the patients with recent SAH enrolled . Although ARC remained present in the patients who experienced CV , their creatinine clearance was not significantly further augmented . Further work is needed to clarify the impact of such clearances on renally excreted medications and how the development and treatment of CV further augment these findings The aim of this study was to evaluate the effect of augmented renal clearance ( ARC ) on vancomycin serum concentrations in critically ill patients . This prospect i ve , single-centre , observational , cohort study included 93 consecutive , critically ill septic patients who started treatment that included vancomycin by continuous infusion , admitted over a 2-year period ( March 2006 to February 2008 ) . ARC was defined as 24-h creatinine clearance ( CL(Cr))>130 mL/min/1.73 m(2 ) . Two groups were analysed : Group A , 56 patients with a CL(Cr)≤130 mL/min/1.73 m(2 ) ; and Group B , 37 patients with a CL(Cr)>130 mL/min/1.73 m(2 ) . Vancomycin therapeutic levels were assessed on the first 3 days of treatment ( D(1 ) , D(2 ) and D(3 ) ) . Serum vancomycin levels on D(1 ) , D(2 ) and D(3 ) , respectively , were 13.1 , 16.6 and 18.6 μmol/L for Group A and 9.7 , 11.7 and 13.8 μmol/L for Group B ( P<0.05 per day ) . The correlation between CL(Cr ) and serum vancomycin on D(1 ) was -0.57 ( P<0.001 ) . ARC was strongly associated with subtherapeutic vancomycin serum concentrations on the first 3 days of treatment Whilst augmented renal clearance ( ARC ) is associated with reduced β-lactam plasma concentrations , its impact on clinical outcomes is unclear . This single-centre prospect i ve , observational , cohort study included non-pregnant , critically ill patients aged 18 - 60 years with presumed severe infection treated with imipenem , meropenem , piperacillin/tazobactam or cefepime and with creatinine clearance ( CL(Cr ) ) ≥60 mL/min . Peak , intermediate and trough levels of β-lactams were drawn on Days 1 - 3 and 5 . Concentrations were deemed ' subthreshold ' if they did not meet EUCAST-defined non-species-related breakpoints . Primary and secondary endpoints were clinical response 28 days after inclusion , and ARC prevalence ( CL(Cr)≥130 mL/min ) and subthreshold and undetectable concentrations , respectively . Logistic regression was used to evaluate associations between ARC , antibiotic concentrations and clinical failure . From 2010 to 2013 , 100 patients were enrolled ( mean age , 45 years ; median CL(Cr ) at inclusion , 144.1 mL/min ) . ARC was present in 64 ( 64 % ) of the patients . Most patients received imipenem/cilastatin ( 54 % ) . Moreover , 86 % and 27 % of patients had at least one subthreshold or undetectable trough level , respectively . Among imipenem and piperacillin trough levels , 77 % and 61 % were subthreshold , respectively , but intermediate levels of both antibiotics were largely above threshold . ARC strongly predicted undetectable trough concentrations ( OR=3.3 , 95 % CI 1.11 - 9.94 ) . A link between ARC and clinical failure ( 18/98 ; 18 % ) was not observed . ARC and subthreshold β-lactam antibiotic concentrations were widespread but were not associated with clinical failure . Larger studies are necessary to determine whether st and ard dosing regimens in the presence of ARC impact negatively on clinical outcome and antibiotic resistance BACKGROUND Recent evidence suggests that current antimicrobial dosing may be inadequate for some critically ill patients . A major contributor in patients with unimpaired renal function may be Augmented Renal Clearance ( ARC ) , wherein urinary creatinine clearance exceeds that predicted by serum creatinine concentration . We used pharmacokinetic data to evaluate the diagnostic accuracy of a recently proposed ARC score . METHODS Pharmacokinetic data from trauma/surgical intensive care unit patients receiving piperacillin/tazobactam were evaluated . We combined intermediate scores ( 4–6 points ) into a single low score ( ⩽6 ) group and compared pharmacokinetic parameters against the high ( ≥7 ) ARC score group . Diagnostic performance was evaluated using median clearance and volume of distribution , area under the antibiotic time-concentration curve ( AUC ) , and achievement of free concentrations greater than a minimum inhibitory concentration ( MIC ) of 16 & mgr;g/mL for at least 50 % of the dose interval ( fT > MIC ≥ 50 % ) . Alternative dosing strategies were explored in silico . RESULTS The ARC score was 100 % sensitive and 71.4 % specific for detecting increased clearance , increased volume of distribution , decreased AUC , and fT > MIC < 50 % at an MIC of 16 & mgr;g/mL. The area under the receiver operating characteristic curve was 0.86 for each , reflecting a high degree of diagnostic accuracy for the ARC score . Serum creatinine less than 0.6 mg/dL had comparable specificity ( 71.4 % ) but was less sensitive ( 66.7 % ) and accurate ( area under the receiver operating characteristic curve , 0.69 ) for detecting higher clearance rates . Monte Carlo pharmacokinetic simulations demonstrated increased time at therapeutic drug levels with extended infusion dosing at a drug cost savings of up to 66.7 % over multiple intermittent dosing regimens . CONCLUSION Given its ability to predict antimicrobial clearance above population medians , which could compromise therapy , the ARC score should be considered as a means to identify patients at risk for subtherapeutic antibiotic levels . Adequately powered studies should prospect ively confirm the utility of the ARC score and the role of antimicrobial therapeutic drug monitoring in such patients . LEVEL OF EVIDENCE Diagnostic tests , level III Objective : Doripenem is a valuable broad-spectrum antibiotic for empirical therapy in critically ill patients , although little data exist to guide effective dosing . We sought to describe the population pharmacokinetics of doripenem in critically ill patients with nosocomial pneumonia and then to use Monte Carlo dosing simulations to procure clinical ly relevant dosing recommendations for that population . Design : Pharmacokinetic analysis of Phase III Trial data . Setting : Critical care units at multiple centers . Patients : Thirty-one critically ill adult patients with nosocomial pneumonia . Interventions : Serial blood sample s were taken on day 2 or 3 of treatment and used for population pharmacokinetic analysis with nonlinear mixed effects modelling and Monte Carlo simulation . Measurements and Main Results : A two-compartment linear model was most appropriate . The mean values for doripenem clearance ( 20.4 ± 14.2 L/hr ) and volume of distribution ( 45.9 ± 36.3 L ) were larger than that observed in previous studies in noncritically ill patients . Doripenem clearance was correlated with creatinine clearance and peripheral volume of distribution with patient body weight . Administration by extended infusion negated much of the pharmacokinetic variability caused by different patient body weight and renal function and enabled achievement of concentrations associated with maximal bacterial killing . Conclusions : This is the first article describing the pharmacokinetics/pharmacodynamics of doripenem solely in critically ill patients and emphasizes the effect of patient weight and creatinine clearance on pharmacokinetics . Use of extended infusions with this antibiotic should be encouraged as it maximizes the likelihood of achieving target blood concentrations |
1,818 | 32,103,455 | The use of chewing gum after colorectal surgery is a safe and effective intervention in reducing the incidence of POI and merits routine use alongside other ERAS pathways in the postoperative setting | Chewing gum as a form of sham feeding is an inexpensive and well-tolerated means of promoting gastrointestinal motility following major abdominal surgery .
Although recognised by the Enhanced Recovery After Surgery ( ERAS ) Society as one of the multimodal approaches to expedite recovery after surgery , strong evidence to support its use in routine postoperative practice is lacking . | Background A number of studies with conflicting results have evaluated the effect of chewing gum on post-operative gastrointestinal recovery in patients after major colorectal surgery . Objective The objective of the study was to study the efficacy of chewing gum in patients with rectal cancer after elective open proctectomy only . Methods A r and omized controlled clinical trial was performed . We recruited patients who would undergo elective open proctectomy for rectal cancer in Sichuan Academy of Medical Sciences and Sichuan Provincial People 's Hospital . Patients in the intervention arm received chewing gum 3 times a day postoperatively . All patients in the trial were placed on the same perioperative management and st and ardized post-operative care plans . The primary outcome was time to the first peristalsis sounds , time to first flatus and the first defecation . Results A total of 89 patients were recruited . The time to the first flatus was 42.33 ± 3.46 h in the gum group and 49.20 ± 1.42 h in the control group ( p < 0.05 ) . The time to the first defecation was significantly shorter in the gum-chewing group than in the control group ( 66.07 ± 2.36 vs. 78.37 ± 1.62 h ; p < 0.05 ) . Post-operative ileus ( POI ) was confirmed in 2 patients in the gum-chewing group and in 7 in the control group ( 7.0 % vs. 23.9 % ; p = 0.028 ) . Discussion The present study suggests that chewing gum is a method to reduce the time to first flatus , time to first defecation and POI in patients undergoing elective open proctectomy for rectal cancer BACKGROUND : Prolonged intestinal paralysis can be a problem after gastrointestinal surgery . Several systematic review s and meta-analyses have suggested the efficacy of gum chewing for the prevention of postoperative ileus . OBJECTIVE : The purpose of this study was to examine the efficacy of gum chewing for the recovery of bowel function after surgery for left-sided colorectal cancer and to determine the physiological mechanism underlying the effect of gum chewing on bowel function . DESIGN : This was a single-center , placebo-controlled , parallel-group , prospect i ve r and omized trial . SETTING S : The study was conducted at a general hospital in Japan . PATIENTS : Forty-eight patients with left-sided colorectal cancer were included . INTERVENTIONS : The patients were r and omly assigned to a gum group ( N = 25 ) and a control group ( N = 23 ) . Four patients in the gum group and 1 in the control group were subsequently excluded because of difficulties in continuing the trial , result ing in the analysis of 21 and 22 patients in the respective groups . Patients in the gum group chewed commercial gum 3 times a day for ≥5 minutes each time from postoperative day 1 to the first day of food intake . MAIN OUTCOME MEASURES : The time to first flatus and first bowel movement after the operation were recorded , and the colonic transit time was measured . Gut hormones ( gastrin , des-acyl ghrelin , motilin , and serotonin ) were measured preoperatively , perioperatively , and on postoperative days 1 , 3 , 5 , 7 , and 10 . RESULTS : Gum chewing did not significantly shorten the time to the first flatus ( 53 ± 2 vs 49 ± 26 hours ; p = 0.481 ; gum vs control group ) , time to first bowel movement ( 94 ± 44 vs 109 ± 34 hours ; p = 0.234 ) , or the colonic transit time ( 88 ± 28 vs 88 ± 21 hours ; p = 0.968 ) . However , gum chewing significantly increased the serum levels of des-acyl ghrelin and gastrin . LIMITATIONS : The main limitation was a greater rate of complications than anticipated , which limited the significance of the findings . CONCLUSIONS : Gum chewing changed the serum levels of des-acyl ghrelin and gastrin , but we were unable to demonstrate an effect on the recovery of bowel function HYPOTHESIS Gum chewing after elective open colon resection may stimulate bowel motility and decrease duration of postoperative ileus . DESIGN AND SETTING Prospect i ve , r and omized study in a community-based teaching hospital . PATIENTS Thirty-four patients undergoing elective open sigmoid resections for recurrent diverticulitis or cancer . MAIN OUTCOME MEASURES First feelings of hunger , time to first flatus , time to first bowel movement , length of hospital stay , and complications . RESULTS A total of 34 patients were r and omized into 2 groups : a gum-chewing group ( n = 17 ) or a control group ( n = 17 ) . The patients in the gum-chewing group chewed sugarless gum 3 times daily for 1 hour each time until discharge . Patient demographics , intraoperative , and postoperative care were equivalent between the 2 groups . All gum-chewing patients tolerated the gum . The first passage of flatus occurred on postoperative hour 65.4 in the gum-chewing group and on hour 80.2 in the control group ( P = .05 ) . The first bowel movement occurred on postoperative hour 63.2 in the gum-chewing group and on hour 89.4 in the control group ( P = .04 ) . The first feelings of hunger were felt on postoperative hour 63.5 in the gum-chewing group and on hour 72.8 in the control group ( P = .27 ) . There were no major complications in either group . The total length of hospital stay was shorter in the gum-chewing group ( day 4.3 ) than in the control group ( day 6.8 ) , ( P = .01 ) . CONCLUSIONS Gum chewing speeds recovery after elective open sigmoid resection by stimulating bowel motility . Gum chewing is an inexpensive and helpful adjunct to postoperative care after colectomy BACKGROUND Postoperative ileus generates a high impact on morbidity , hospital stay , and costs . OBJECTIVE To study the efficiency and safety of chewing gum to decrease postoperative ileus in colorectal surgery . METHOD A r and omized controlled trial was performed including 64 patients who underwent elective colorectal surgery with primary anastomosis in a tertiary referral center . Patients were divided in two groups : ( i ) A : gum chewing group ( n = 32 ) , and ( ii ) B : patients who had st and ard postoperative recovery ( n = 32 ) . RESULTS Postoperative ileus was observed in 6 % ( 2/32 ) of the gum-chewing group and in 21.8 % ( 7/32 ) in the st and ard postoperative recovery group , with an odds ratio of 0.167 ( 95 % CI : 0.37 - 0.75 ; p = 0.006 ) . Vomiting was present in two patients from group A and in eight from group B ( 6.25 vs. 25.0 % ; p = 0.03 ) . Passage of flatus within the first 48 hours was present in 30 patients from group A and in 20 from group B ( 94 vs. 63 % ; p = 0.002 ) . There was earlier oral feeding ( 96 ± 53 vs. 117 ± 65 hours ; p= 0.164 ) and a shorter length of hospital stay ( 7 ± 5 vs. 9 ± 5 days ; p= 0.26 ) in the gum-chewing group ( p N.S. ) . CONCLUSIONS The use of chewing gum after colorectal surgery was associated with less postoperative ileus and vomiting , and with an increased passage of flatus within the first 48 hours after surgery . Since gum chewing is an inexpensive procedure and is not associated with higher morbidity , it can be safely used for a faster postoperative recovery in elective colorectal surgery BACKGROUND Postoperative ileus limits early hospital discharge for patients who have undergone laparoscopic procedures . Sham feeding has been reported to enhance bowel motility . Here , the effect of gum chewing is evaluated as a convenient method to enhance postoperative recovery from ileus after laparoscopic colectomy . STUDY DESIGN A total of 19 patients who underwent elective laparoscopic colectomy for colorectal cancer participated in the study . Each patient was r and omly assigned to one of two groups : a gum-chewing group ( n = 10 , mean age 58.6 years , range 50 to 71 years ) or a control group ( n = 9 , mean age 60.6 years , range 45 to 80 years ) . The patients in the gum-chewing group chewed gum three times a day from the first postoperative AM until oral intake . The times of the first passage of flatus and defecation were recorded precisely . RESULTS The first passage of flatus was seen , on average , on postoperative day 2.1 in the gum-chewing group and on day 3.2 in the control group ( p < 0.01 ) . The first defecation was 2.7 days sooner in the gum-chewing group ( postoperative day 3.1 ) than in the control group ( 5.8 days ; p < 0.01 ) . All patients tolerated gum chewing on the first operative AM . The postoperative hospital stays for the gum-chewing and control groups were 13.5+/-3.0 days and 14.5+/-6.1 days , respectively . CONCLUSIONS Gum chewing aids early recovery from postoperative ileus and is an inexpensive and physiologic method for stimulating bowel motility . Gum chewing should be added as an adjunct treatment in postoperative care because it might contribute to shorter hospital stays Objective : Prolonged ileus — the failure of postoperative ileus to resolve within a few days after major abdominal surgery — leads to significant medical consequences for the patient and costs to the hospital system . The aim of this retrospective analysis of prospect ively collected data was to identify independent preoperative and intraoperative risk factors for prolonged ileus in a large consecutive series of patients who had undergone resection for colorectal cancer . Methods : Patients were drawn from a hospital registry of 2400 consecutive resections over the period 1995–2009 . Thirty-four potential predictors of prolonged ileus were analyzed by logistic regression . Results : Prolonged ileus occurred in 14.0 % of patients . Statistically significant independent predictors of prolonged ileus were male sex ( OR : 1.7 , P < 0.001 ) , peripheral vascular disease ( OR : 1.8 , P < 0.001 ) , respiratory comorbidity ( OR : 1.6 , P < 0.001 ) , resection at urgent operation ( OR : 2.2 , P < 0.001 ) , perioperative transfusion ( OR : 1.6 , P < 0.010 ) , stoma constructed ( OR : 1.4 , P < 0.001 ) , and operation lasting ≥3 hours ( OR : 1.6 , P < 0.001 ) . Conclusions : These features can be used to alert medical and nursing staff to patients likely to experience prolonged ileus after bowel resection so that they can be monitored closely in the postoperative period and available treatments targeted toward them . These features may also be useful in the research context to facilitate the more efficient selection of high-risk patients as subjects in clinical trials of prevention or treatment Objective : The aim of this trial was to investigate whether a routine of allowing normal food at will increases morbidity after major upper gastrointestinal ( GI ) surgery . Summary Background Data : Nil-by-mouth with enteral tube feeding is widely practice d for several days after major upper GI surgery . After other abdominal operations , normal food at will has been shown to be safe and to improve gut function . Methods : Patients were r and omly assigned to a routine of nil-by-mouth and enteral tube feeding by needle-catheter jejunostomy ( ETF group ) or normal food at will from the first day after major upper GI surgery . Primary end point was rate of major complications and death . Secondary outcomes were minor complications and adverse events , bowel function , and length of stay . All patients were invited to a follow-up at 8 weeks after discharge from the hospital . Results : Four hundred fifty-three patients who underwent major open upper GI surgery in 5 centers were enrolled between 2001 and 2006 . Four hundred forty-seven patients were correctly r and omized . Of 227 patients 76 ( 33.5 % ) had major complications in the ETF group compared with 62 ( 28.2 % ) of 220 patients allowed normal food at will ( P = 0.26 , 95 % CI for the difference in rate from −3.3 to 13.9 ) . In the ETF group , 36 ( 15.9 % ) patients were reoperated compared with 29 ( 13.2 % ) in the group allowed normal food at will ( P = 0.50 ) and 30-day mortality was 10 ( 4.4 % ) of 227 and 11 ( 5.0 % ) of 220 patients , respectively ( P = 0.83 ) . Time to resumed bowel function was significantly in favor of allowing normal food at will ( P = 0.01 ) , as were the total number of major complications , length of stay , and rate of postdischarge complications . Conclusions : Allowing patients to eat normal food at will from the first day after major upper GI surgery does not increase morbidity compared with traditional care with nil-by-mouth and enteral feeding AIM This study aim ed to determine the effect of gum chewing on the reduction of postoperative ileus and recovery after surgery . METHODS This study was conducted a r and omized controlled trial in 60 patients who underwent colorectal surgery between November 2011 and December 2012 . Patients in the experimental group chewed gum three times a day . The time of flatus and defecation , the time to start feeding , pain levels and time of discharge were monitored . RESULTS Post-surgery results for gum-chewing were first flatus and defecation times and the time to start feeding was shorter ; pain levels were lower on the 3rd - 5th days ; patients were discharged in a shorter time post-surgery . CONCLUSIONS Chewing gum is a simple intervention for reducing postoperative ileus after colorectal surgery . Further studies that examine the effectiveness of gum chewing on other surgical interventions in which the development risk of postoperative ileus should be performed Objective : To determine whether sham feeding with chewing gum improved gastrointestinal recovery after colorectal resection surgery , in the presence of routine postoperative feeding . Background : Sham feeding with chewing gum has been shown to accelerate the return of gut function after colorectal surgery . This study sought to determine whether sham feeding with gum , after colorectal resection , accelerates return of gastrointestinal function in patients on a rapid feeding enhanced recovery program . Methods : A r and omized “ two armed ” controlled clinical trial was performed . Equal groups of open and laparoscopic colorectal resection surgical patients were recruited . Patients in the intervention arm received chewing gum 4 times a day postoperatively . All patients in the trial were placed on an established , st and ardized Enhanced Recovery After Surgery program . The primary outcome was time to return of gut function , assessed by time to flatus and first bowel motion . Secondary outcomes were time to tolerate diet , symptoms of ileus in the form of nausea , vomiting and distension , pain as assessed by analgesic consumption and visual analogue scales , complications , and length of hospital stay . Results : A total of 161 patients were recruited . Postoperative morbidity was equivalent between groups , with no complications related to gum chewing . There was no difference between groups with respect to the primary outcomes of time to flatus and bowel motion . There was less perception of pain in the intervention group on days 2 to 5 , and no difference with respect to all other secondary outcomes . Conclusions : Sham feeding with gum , after open and laparoscopic colorectal resectional surgery is safe , but does not hasten the return of gastrointestinal function in patients who receive accelerated postoperative feeding . ( ACTRN12607000538448 PURPOSE : The purpose of this prospect i ve , attention-controlled , r and omized study was to determine whether postoperative gum chewing reduces the duration of postoperative ileus symptoms following elective open or laparoscopic sigmoid colectomy when compared with st and ard care or an attention-control intervention . SUBJECTS AND SETTING S : Forty-seven subjects scheduled for either an open or laparoscopic colon resection participated in the study . Subjects were recruited preoperatively at the preadmission learning centers of the 2 acute care medical centers that comprised the study setting s. METHODS : Subjects were r and omized to 3 groups : ( 1 ) st and ard postoperative care ( n = 18 ) ; ( 2 ) st and ard care and a silicone-adhesive patch applied to the deltoid region of the upper arm as an attention control ( n = 16 ) ; and ( 3 ) st and ard care and gum chewing ( n = 13 ) . St and ard postoperative care included removal of the nasogastric tube , early ambulation , nothing by mouth with ice chips only until the first passage of flatus , and then advancement of diet until tolerance of solid food . RESULTS : No statistically significant differences were found among the 3 study groups for the 4 postoperative outcome variables measured : ( 1 ) first passage of flatus ; ( 2 ) first bowel movement ; ( 3 ) return of hunger ; and ( 4 ) ability to tolerate solid food for one meal . CONCLUSION : Postoperative gum chewing was not found to be more effective than st and ard postoperative care or our attention-control intervention in reducing the duration of postoperative ileus symptoms , length of stay , or complications among patients following open/laparoscopic sigmoid colectomy |
1,819 | 25,871,671 | FINDINGS Intravenous thrombolysis is the mainstay of acute ischemic stroke management for any patient with disabling deficits presenting within 4.5 hours from symptom onset .
R and omized trials have demonstrated that more patients return to having good function ( defined by being independent and having slight disability or less ) when treated within 4.5 hours after symptom onset with intravenous recombinant tissue plasminogen activator ( IV rtPA ) therapy .
Regardless of mode of reperfusion , earlier reperfusion is associated with better clinical outcomes .
AND RELEVANCE Intravenous rtPA remains the st and ard of care for patients with moderate to severe neurological deficits who present within 4.5 hours of symptom onset .
Outcomes for some patients with acute ischemic stroke and moderate to severe neurological deficits due to proximal artery occlusion are improved with endovascular reperfusion therapy . | IMPORTANCE Acute ischemic stroke is a major cause of mortality and morbidity in the United States .
We review the latest data and evidence supporting catheter-directed treatment for proximal artery occlusion as an adjunct to intravenous thrombolysis in patients with acute stroke .
OBJECTIVE To review the pathophysiology of acute brain ischemia and infa rct ion and the evidence supporting various stroke reperfusion treatments . | See related article , p 2509 Intra-arterial therapy ( IAT ) for acute ischemic stroke ( AIS ) has dramatically evolved during the past decade to include aspiration and stent-retriever devices . Recent r and omized controlled trials have demonstrated the superior revascularization efficacy of stent-retrievers compared with the first-generation Merci device.1,2 Additionally , the Diffusion and Perfusion Imaging Evaluation for Underst and ing Stroke Evolution ( DEFUSE ) 2 , the Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy ( MR RESCUE ) , and the Interventional Management of Stroke ( IMS ) III trials have confirmed the importance of early revascularization for achieving better clinical outcome .3–5 Despite these data , the current heterogeneity in cerebral angiographic revascularization grading ( CARG ) poses a major obstacle to further advances in stroke therapy . To date , several CARG scales have been used to measure the success of IAT.6–14 Even when the same scale is used in different studies , it is applied using varying operational criteria , which further confounds the interpretation of this key metric.10 The lack of a uniform grading approach limits comparison of revascularization rates across clinical trials and hinders the translation of promising , early phase angiographic results into proven , clinical ly effective treatments.6–14 For these reasons , it is critical that CARG scales be st and ardized and end points for successful revascularization be refined.6 This will lead to a greater underst and ing of the aspects of revascularization that are strongly predictive of clinical response . The optimal grading scale must demonstrate ( 1 ) a strong correlation with clinical outcome , ( 2 ) simplicity and feasibility of scale interpretation while ensuring characterization of relevant angiographic findings , and ( 3 ) high inter-rater reproducibility . To address these issues , a multidisciplinary panel of neurointerventionalists , neuroradiologists , and stroke neurologists with extensive experience in neuroimaging and IAT , convened at the “ Consensus Meeting on Revascularization Grading Following Endovascular Therapy ” with the goal Background and Purpose — The only Food and Drug Administration ( FDA ) -approved treatment for acute ischemic stroke is tissue plasminogen activator ( tPA ) given intravenously within 3 hours of symptom onset . An alternative strategy for opening intracranial vessels during stroke is mechanical embolectomy , especially for patients ineligible for intravenous tPA . Methods — We investigated the safety and efficacy of a novel embolectomy device ( Merci Retriever ) to open occluded intracranial large vessels within 8 hours of the onset of stroke symptoms in a prospect i ve , nonr and omized , multicenter trial . All patients were ineligible for intravenous tPA . Primary outcomes were recanalization and safety , and secondary outcomes were neurological outcome at 90 days in recanalized versus nonrecanalized patients . Results — Recanalization was achieved in 46 % ( 69/151 ) of patients on intention to treat analysis , and in 48 % ( 68/141 ) of patients in whom the device was deployed . This rate is significantly higher than that expected using an historical control of 18 % ( P<0.0001 ) . Clinical ly significant procedural complications occurred in 10 of 141 ( 7.1 % ) patients . Symptomatic intracranial hemorrhages was observed in 11 of 141 ( 7.8 % ) patients . Good neurological outcomes ( modified Rankin score ≤2 ) were more frequent at 90 days in patients with successful recanalization compared with patients with unsuccessful recanalization ( 46 % versus 10 % ; relative risk [ RR ] , 4.4 ; 95 % CI , 2.1 to 9.3 ; P<0.0001 ) , and mortality was less ( 32 % versus 54 % ; RR , 0.59 ; 95 % CI , 0.39 to 0.89 ; P=0.01 ) . Conclusions — A novel endovascular embolectomy device can significantly restore vascular patency during acute ischemic stroke within 8 hours of stroke symptom onset and provides an alternative intervention for patients who are otherwise ineligible for thrombolytics Background and Purpose — Desmoteplase is a novel plasminogen activator with favorable features in vitro compared with available agents . This study evaluated safety and efficacy of intravenous ( IV ) desmoteplase in patients with perfusion/diffusion mismatch on MRI 3 to 9 hours after onset of acute ischemic stroke . Methods — DEDAS was a placebo-controlled , double-blind , r and omized , dose-escalation study investigating doses of 90 & mgr;g/kg and 125 & mgr;g/kg desmoteplase . Eligibility criteria included baseline National Institute of Health Stroke Scale ( NIHSS ) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch . The safety end point was the rate of symptomatic intracranial hemorrhage . Primary efficacy co-end points were MRI reperfusion 4 to 8 hours after treatment and good clinical outcome at 90 days . The primary analyses were intent-to-treat . Before unblinding , a target population , excluding patients violating specific MRI criteria , was defined . Results — Thirty-seven patients were r and omized and received treatment ( intent-to-treat ; placebo : n=8 ; 90 & mgr;g/kg : n=14 ; 125 & mgr;g/kg : n=15 ) . No symptomatic intracranial hemorrhage occurred . Reperfusion was achieved in 37.5 % ( 95 % CI [ 8.5 ; 75.5 ] ) of placebo patients , 18.2 % ( 2.3 ; 51.8 ) of patients treated with 90 & mgr;g/kg desmoteplase , and 53.3 % ( 26.6 ; 78.7 ) of patients treated with 125 & mgr;g/kg desmoteplase . Good clinical outcome at 90 days occurred in 25.0 % ( 3.2 ; 65.1 ) treated with placebo , 28.6 % ( 8.4 ; 58.1 ) treated with 90 & mgr;g/kg desmoteplase and 60.0 % ( 32.3 ; 83.7 ) treated with 125 & mgr;g/kg desmoteplase . In the target population ( n=25 ) , the difference compared with placebo increased and was statistically significant for good clinical outcome with 125 & mgr;g/kg desmoteplase ( P=0.022 ) . Conclusions — Treatment with IV desmoteplase 3 to 9 hours after ischemic stroke onset appears safe . At a dose of 125 & mgr;g/kg desmoteplase appeared to improve clinical outcome , especially in patients fulfilling all MRI criteria . The results of DEDAS generally support the results of its predecessor study , Desmoteplase in Acute Ischemic Stroke ( DIAS ) Background and Purpose — The Penumbra Pivotal Stroke Trial reported a 25 % good outcome ( modified Rankin scale score ≤2 ) despite an 81 % recanalization rate . We evaluated the association of a favorable initial noncontrast CT and a short time to recanalization in predicting good outcome . Methods — Data were from the Penumbra Pivotal Stroke Trial . Baseline scans were evaluated by 2 experienced readers blinded to outcomes using ASPECTS . ASPECTS scores were dichotomized into > 7 and ≤7 for primary analysis . Data on degree of recanalization based on thrombolysis in myocardial infa rct ion scores , stroke onset to recanalization , and CT to recanalization times were obtained . Primary outcome was modified Rankin scale score ≤2 at 3 months . Results — Median baseline NIHSS was 18 ( range , 8–34 ) and median baseline ASPECTS score was 6 ( range , 0–10 ) ; 81.2 % achieved recanalization ( thrombolysis in myocardial infa rct ion , 2–3 ) and ( 27.7 % ) achieved good outcome . Good outcome was significantly higher in the ASPECTS score > 7 group when compared to the ASPECTS score ≤7 group ( 50 % vs 15 % ; RR , 3.3 ; 95 % CI , 1.6–6.8 ; P=0.0001 ) . No patient with an ASPECTS score ≤4 ( n=28 ) or without recanalization ( n=16 ) had a good outcome . There was an interaction between baseline ASPECTS score ( > 7 and ≤7 ) and onset to recanalization time ( ≤300 minutes and > 300 minutes ) in predicting good outcome ( P=0.06 ) . Conclusion — Patients with baseline CT ASPECTS score ≤4 do not benefit from recanalization . Fast recanalization may benefit patients with evident damage on the CT scan ( ASPECTS score > 4 ) . Overall , patients benefit the most with early recanalization and a favorable baseline CT scan ( ASPECTS score > 7 ) Background and Purpose — The Middle Cerebral Artery Embolism Local Fibrinolytic Intervention Trial ( MELT ) Japan was organized to determine the safety and clinical efficacy of intraarterial infusion of urokinase ( UK ) in patients with stroke within 6 hours of onset . Methods — Patients with ischemic stroke presenting within 6 hours of onset and displaying occlusions of the M1 or M2 portion of the middle cerebral artery on carotid angiography were r and omized to the UK or control groups . Clinical outcome was assessed by the modified Rankin Scale , National Institutes of Health Stroke Scale , and Barthel Index . Results — The Independent Monitoring Committee recommended stopping the trial after approval of intravenous infusion of recombinant tissue plasminogen activator in Japan . A total of 114 patients underwent r and omization , 57 patients in each group . Background characteristics were comparable between the 2 groups . The primary end point of favorable outcome ( modified Rankin Scale 0 to 2 ) at 90 days was somewhat more frequent in the UK group than in the control group ( 49.1 % and 38.6 % , OR : 1.54 , 95 % CI : 0.73 to 3.23 ) but did not reach a significant level ( P=0.345 ) . However , excellent functional outcome ( modified Rankin Scale 0 to 1 ) at 90 days , a preplanned secondary end point , was more frequent in the UK group than in the control group ( 42.1 % and 22.8 % , P=0.045 , OR : 2.46 , 95 % CI : 1.09 to 5.54 ) . There were significantly more patients with National Institutes of Health Stroke Scale 0 or 1 at 90 days in the UK group than the control group ( P=0.017 ) . The 90-day cumulative mortality was 5.3 % in the UK group and 3.5 % in the control group ( P=1.000 ) , and intracerebral hemorrhage within 24 hours of treatment occurred in 9 % and 2 % , respectively ( P=0.206 ) . Conclusions — The trial was aborted prematurely and the primary end point did not reach statistical significance . Nevertheless , the secondary analyses suggested that intraarterial fibrinolysis has the potential to increase the likelihood of excellent functional outcome BACKGROUND Trials of endovascular therapy for ischemic stroke have produced variable results . We conducted this study to test whether more advanced imaging selection , recently developed devices , and earlier intervention improve outcomes . METHODS We r and omly assigned patients with ischemic stroke who were receiving 0.9 mg of alteplase per kilogram of body weight less than 4.5 hours after the onset of ischemic stroke either to undergo endovascular thrombectomy with the Solitaire FR ( Flow Restoration ) stent retriever or to continue receiving alteplase alone . All the patients had occlusion of the internal carotid or middle cerebral artery and evidence of salvageable brain tissue and ischemic core of less than 70 ml on computed tomographic ( CT ) perfusion imaging . The co primary outcomes were reperfusion at 24 hours and early neurologic improvement ( ≥8-point reduction on the National Institutes of Health Stroke Scale or a score of 0 or 1 at day 3 ) . Secondary outcomes included the functional score on the modified Rankin scale at 90 days . RESULTS The trial was stopped early because of efficacy after 70 patients had undergone r and omization ( 35 patients in each group ) . The percentage of ischemic territory that had undergone reperfusion at 24 hours was greater in the endovascular-therapy group than in the alteplase-only group ( median , 100 % vs. 37 % ; P<0.001 ) . Endovascular therapy , initiated at a median of 210 minutes after the onset of stroke , increased early neurologic improvement at 3 days ( 80 % vs. 37 % , P=0.002 ) and improved the functional outcome at 90 days , with more patients achieving functional independence ( score of 0 to 2 on the modified Rankin scale , 71 % vs. 40 % ; P=0.01 ) . There were no significant differences in rates of death or symptomatic intracerebral hemorrhage . CONCLUSIONS In patients with ischemic stroke with a proximal cerebral arterial occlusion and salvageable tissue on CT perfusion imaging , early thrombectomy with the Solitaire FR stent retriever , as compared with alteplase alone , improved reperfusion , early neurologic recovery , and functional outcome . ( Funded by the Australian National Health and Medical Research Council and others ; EXTEND-IA Clinical Trials.gov number , NCT01492725 , and Australian New Zeal and Clinical Trials Registry number , ACTRN12611000969965 . ) Objective : To test the transferability of the Helsinki stroke thrombolysis model that achieved a median 20-minute door-to-needle time ( DNT ) to an Australian health care setting . Methods : The existing “ code stroke ” model at the Royal Melbourne Hospital was evaluated and restructured to include key components of the Helsinki model : 1 ) ambulance prenotification with patient details alerting the stroke team to meet the patient on arrival ; 2 ) patients transferred directly from triage onto the CT table on the ambulance stretcher ; and 3 ) tissue plasminogen activator ( tPA ) delivered in CT immediately after imaging . We analyzed our prospect i ve , consecutive tPA registry for effects of these protocol changes on our DNT after implementation during business hours ( 8 am to 5 pm Monday – Friday ) from May 2012 . Results : There were 48 patients treated with tPA in the 8 months after the protocol change . Compared with 85 patients treated in 2011 , the median ( interquartile range ) DNT was reduced from 61 ( 43–75 ) minutes to 46 ( 24–79 ) minutes ( p = 0.040 ) . All of the effect came from the change in the in-hours DNT , down from 43 ( 33–59 ) to 25 ( 19–48 ) minutes ( p = 0.009 ) , whereas the out-of-hours delays remain unchanged , from 67 ( 55–82 ) to 62 ( 44–95 ) minutes ( p = 0.835 ) . Conclusion : We demonstrated rapid transferability of an optimized tPA protocol to a different health care setting . With the cooperation of ambulance , emergency , and stroke teams , we succeeded in the absence of a dedicated neurologic emergency department or electronic patient records , which are features of the Finnish system . The next challenge is providing the same service out-of-hours Background and Purpose — We report on workflow and process-based performance measures and their effect on clinical outcome in Solitaire FR Thrombectomy for Acute Revascularization ( STAR ) , a multicenter , prospect i ve , single-arm study of Solitaire FR thrombectomy in large vessel anterior circulation stroke patients . Methods — Two hundred two patients were enrolled across 14 centers in Europe , Canada , and Australia . The following time intervals were measured : stroke onset to hospital arrival , hospital arrival to baseline imaging , baseline imaging to groin puncture , groin puncture to first stent deployment , and first stent deployment to reperfusion . Effects of time of day , general anesthesia use , and multimodal imaging on workflow were evaluated . Patient characteristics and workflow processes associated with prolonged interval times and good clinical outcome ( 90-day modified Rankin score , 0–2 ) were analyzed . Results — Median times were onset of stroke to hospital arrival , 123 minutes ( interquartile range , 163 minutes ) ; hospital arrival to thrombolysis in cerebral infa rct ion ( TICI ) 2b/3 or final digital subtraction angiography , 133 minutes ( interquartile range , 99 minutes ) ; and baseline imaging to groin puncture , 86 minutes ( interquartile range , 24 minutes ) . Time from baseline imaging to puncture was prolonged in patients receiving intravenous tissue-type plasminogen activator ( 32-minute mean delay ) and when magnetic resonance – based imaging at baseline was used ( 18-minute mean delay ) . Extracranial carotid disease delayed puncture to first stent deployment time on average by 25 minutes . For each 1-hour increase in stroke onset to final digital subtraction angiography ( or TICI 2b/3 ) time , odds of good clinical outcome decreased by 38 % . Conclusions — Interval times in the STAR study reflect current intra-arterial therapy for patients with acute ischemic stroke . Improving workflow metrics can further improve clinical outcome . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT01327989 Background and Purpose — The purpose of this clinical evaluation was to assess the safety and effectiveness of the Penumbra System in the revascularization of patients presenting with acute ischemic stroke secondary to intracranial large vessel occlusive disease . Methods — In this prospect i ve , multicenter , single-arm study , 125 patients with neurological deficits as defined by a National Institutes of Health Stroke Scale score ≥8 , presented within 8 hours of symptom onset , and an angiographic occlusion ( Thrombolysis In Myocardial Infa rct ion [ TIMI ] Grade 0 or 1 ) of a treatable large intracranial vessel were enrolled . Patients who presented within 3 hours from symptom onset had to be ineligible or refractory to recombinant tissue plasminogen activator therapy . All patients were followed clinical ly for 90 days postprocedure . Results — A total of 125 target vessels in 125 patients were treated by the Penumbra System . Postprocedure , 81.6 % of the treated vessels were successfully revascularized to TIMI 2 to 3 . There were 18 procedural events reported in 16 patients ( 12.8 % ) , 3 patients ( 2.4 % ) had events that were considered serious . A total of 35 patients ( 28 % ) were found to have intracranial hemorrhage on 24-hour CT of which 14 ( 11.2 % ) were symptomatic . All cause mortality was 32.8 % at 90 days with 25 % of the patients achieving a modified Rankin Scale score of ≤2 . Conclusions — These results suggest the Penumbra System allows safe and effective revascularization in patients experiencing ischemic stroke secondary to large vessel occlusive disease who present within 8 hours from symptom onset Background and Purpose — Most acute ischemic stroke patients arrive after the 3-hour time window for recombinant tissue plasminogen activator ( rtPA ) administration . The Desmoteplase In Acute Ischemic Stroke trial ( DIAS ) was a dose-finding r and omized trial design ed to evaluate the safety and efficacy of intravenous desmoteplase , a highly fibrin-specific and nonneurotoxic thrombolytic agent , administered within 3 to 9 hours of ischemic stroke onset in patients with perfusion/diffusion mismatch on MRI . Methods — DIAS was a placebo-controlled , double-blind , r and omized , dose-finding phase II trial . Patients with National Institute of Health Stroke Scale ( NIHSS ) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch were eligible . Of 104 patients , the first 47 ( referred to as Part 1 ) were r and omized to fixed doses of desmoteplase ( 25 mg , 37.5 mg , or 50 mg ) or placebo . Because of an excessive rate of symptomatic intracranial hemorrhage ( sICH ) , lower weight-adjusted doses escalating through 62.5 & mgr;g/kg , 90 & mgr;g/kg , and 125 & mgr;g/kg were subsequently investigated in 57 patients ( referred to as Part 2 ) . The safety endpoint was the rate of sICH . Efficacy endpoints were the rate of reperfusion on MRI after 4 to 8 hours and clinical outcome as assessed by NIHSS , modified Rankin scale , and Barthel Index at 90 days . Results — Part 1 was terminated prematurely because of high rates of sICH with desmoteplase ( 26.7 % ) . In Part 2 , the sICH rate was 2.2 % . No sICH occurred with placebo in either part . Reperfusion rates up to 71.4 % ( P=0.0012 ) were observed with desmoteplase ( 125 & mgr;g/kg ) compared with 19.2 % with placebo . Favorable 90-day clinical outcome was found in 22.2 % of placebo-treated patients and between 13.3 % ( 62.5 & mgr;g/kg ; P=0.757 ) and 60.0 % ( 125 & mgr;g/kg ; P=0.0090 ) of desmoteplase-treated patients . Early reperfusion correlated favorably with clinical outcome ( P=0.0028 ) . Favorable outcome occurred in 52.5 % of patients experiencing reperfusion versus 24.6 % of patients without reperfusion . Conclusions — Intravenous desmoteplase administered 3 to 9 hours after acute ischemic stroke in patients selected with perfusion/diffusion mismatch is associated with a higher rate of reperfusion and better clinical outcome compared with placebo . The sICH rate with desmoteplase was low , using doses up to 125 & mgr;g/kg BACKGROUND In patients with acute ischemic stroke caused by a proximal intracranial arterial occlusion , intraarterial treatment is highly effective for emergency revascularization . However , proof of a beneficial effect on functional outcome is lacking . METHODS We r and omly assigned eligible patients to either intraarterial treatment plus usual care or usual care alone . Eligible patients had a proximal arterial occlusion in the anterior cerebral circulation that was confirmed on vessel imaging and that could be treated intraarterially within 6 hours after symptom onset . The primary outcome was the modified Rankin scale score at 90 days ; this categorical scale measures functional outcome , with scores ranging from 0 ( no symptoms ) to 6 ( death ) . The treatment effect was estimated with ordinal logistic regression as a common odds ratio , adjusted for prespecified prognostic factors . The adjusted common odds ratio measured the likelihood that intraarterial treatment would lead to lower modified Rankin scores , as compared with usual care alone ( shift analysis ) . RESULTS We enrolled 500 patients at 16 medical centers in The Netherl and s ( 233 assigned to intraarterial treatment and 267 to usual care alone ) . The mean age was 65 years ( range , 23 to 96 ) , and 445 patients ( 89.0 % ) were treated with intravenous alteplase before r and omization . Retrievable stents were used in 190 of the 233 patients ( 81.5 % ) assigned to intraarterial treatment . The adjusted common odds ratio was 1.67 ( 95 % confidence interval [ CI ] , 1.21 to 2.30 ) . There was an absolute difference of 13.5 percentage points ( 95 % CI , 5.9 to 21.2 ) in the rate of functional independence ( modified Rankin score , 0 to 2 ) in favor of the intervention ( 32.6 % vs. 19.1 % ) . There were no significant differences in mortality or the occurrence of symptomatic intracerebral hemorrhage . CONCLUSIONS In patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation , intraarterial treatment administered within 6 hours after stroke onset was effective and safe . ( Funded by the Dutch Heart Foundation and others ; MR CLEAN Netherl and s Trial Registry number , NTR1804 , and Current Controlled Trials number , IS RCT N10888758 . ) BACKGROUND Whether endovascular stroke treatment improves clinical outcomes is unclear because of the paucity of data from r and omised placebo-controlled trials . We aim ed to establish whether MRI can be used to identify patients who are most likely to benefit from endovascular reperfusion . METHODS In this prospect i ve cohort study we consecutively enrolled patients scheduled to have endovascular treatment within 12 h of onset of stroke at eight centres in the USA and one in Austria . Aided by an automated image analysis computer program , investigators interpreted a baseline MRI scan taken before treatment to establish whether the patient had an MRI profile ( target mismatch ) that suggested salvageable tissue was present . Reperfusion was assessed on an early follow-up MRI scan ( within 12 h of the revascularisation procedure ) and defined as a more than 50 % reduction in the volume of the lesion from baseline on perfusion-weighted MRI . The primary outcome was favourable clinical response , defined as an improvement of 8 or more on the National Institutes of Health Stroke Scale between baseline and day 30 or a score of 0 - 1 at day 30 . The secondary clinical endpoint was good functional outcome , defined as a modified Rankin scale score of 2 or less at day 90 . Analyses were adjusted for imbalances in baseline predictors of outcome . Investigators assessing outcomes were masked to baseline data . FINDINGS 138 patients were enrolled . 110 patients had catheter angiography and of these 104 had an MRI profile and 99 could be assessed for reperfusion . 46 of 78 ( 59 % ) patients with target mismatch and 12 of 21 ( 57 % ) patients without target mismatch had reperfusion after endovascular treatment . The adjusted odds ratio ( OR ) for favourable clinical response associated with reperfusion was 8·8 ( 95 % CI 2·7 - 29·0 ) in the target mismatch group and 0·2 ( 0·0 - 1·6 ) in the no target mismatch group ( p=0·003 for difference between ORs ) . Reperfusion was associated with increased good functional outcome at 90 days ( OR 4·0 , 95 % CI 1·3 - 12·2 ) in the target mismatch group , but not in the no target mismatch group ( 1·9 , 0·2 - 18·7 ) . INTERPRETATION Target mismatch patients who had early reperfusion after endovascular stroke treatment had more favourable clinical outcomes . No association between reperfusion and favourable outcomes was present in patients without target mismatch . Our data suggest that a r and omised controlled trial of endovascular treatment for patients with the target mismatch profile is warranted . FUNDING National Institute for Neurological Disorders and Stroke BACKGROUND The aim of the Safe Implementation of Thrombolysis in Stroke-Monitoring Study ( SITS-MOST ) was to assess the safety and efficacy of intravenous alteplase as thrombolytic therapy within the first 3 h of onset of acute ischaemic stroke . Under European Union regulations , SITS-MOST was required to assess the safety profile of alteplase in clinical practice by comparison with results in r and omised controlled trials . METHODS 6483 patients were recruited from 285 centres ( 50 % with little previous experience in stroke thrombolysis ) in 14 countries between 2002 and 2006 for this prospect i ve , open , monitored , observational study . Primary outcomes were symptomatic ( a deterioration in National Institutes of Health stroke scale score of > or=4 ) intracerebral haemorrhage type 2 within 24 h and mortality at 3 months . We compared mortality , the proportion of patients with symptomatic intracerebral haemorrhage as per the Cochrane definition , and functional outcome at 3 months with relevant pooled results from r and omised controlled trials . FINDINGS Baseline characteristics of patients in SITS-MOST were much the same as those in the pooled r and omised controlled trials . At 24 h , the proportion of patients with symptomatic intracerebral haemorrhage ( per the SITS-MOST protocol ) was 1.7 % ( 107/6444 ; 95 % CI 1.4 - 2.0 ) ; at 7 days , the proportion with the same condition as per the Cochrane definition was 7.3 % ( 468/6438 ; 6.7 - 7.9 ) compared with 8.6 % ( 40/465 ; 6.3 - 11.6 ) in the pooled r and omised controlled trials . The mortality rate at 3 months in SITS-MOST was 11.3 % ( 701/6218 ; 10.5 - 12.1 ) compared with 17.3 % ( 83/479 ; 14.1 - 21.1 ) in the pooled r and omised controlled trials . INTERPRETATION These data confirm that intravenous alteplase is safe and effective in routine clinical use when used within 3 h of stroke onset , even by centres with little previous experience of thrombolytic therapy for acute stroke . The findings should encourage wider use of thrombolytic therapy for suitable patients treated in stroke centres BACKGROUND Whether brain imaging can identify patients who are most likely to benefit from therapies for acute ischemic stroke and whether endovascular thrombectomy improves clinical outcomes in such patients remains unclear . METHODS In this study , we r and omly assigned patients within 8 hours after the onset of large-vessel , anterior-circulation strokes to undergo mechanical embolectomy ( Merci Retriever or Penumbra System ) or receive st and ard care . All patients underwent pretreatment computed tomography or magnetic resonance imaging of the brain . R and omization was stratified according to whether the patient had a favorable penumbral pattern ( substantial salvageable tissue and small infa rct core ) or a nonpenumbral pattern ( large core or small or absent penumbra ) . We assessed outcomes using the 90-day modified Rankin scale , ranging from 0 ( no symptoms ) to 6 ( dead ) . RESULTS Among 118 eligible patients , the mean age was 65.5 years , the mean time to enrollment was 5.5 hours , and 58 % had a favorable penumbral pattern . Revascularization in the embolectomy group was achieved in 67 % of the patients . Ninety-day mortality was 21 % , and the rate of symptomatic intracranial hemorrhage was 4 % ; neither rate differed across groups . Among all patients , mean scores on the modified Rankin scale did not differ between embolectomy and st and ard care ( 3.9 vs. 3.9 , P=0.99 ) . Embolectomy was not superior to st and ard care in patients with either a favorable penumbral pattern ( mean score , 3.9 vs. 3.4 ; P=0.23 ) or a nonpenumbral pattern ( mean score , 4.0 vs. 4.4 ; P=0.32 ) . In the primary analysis of scores on the 90-day modified Rankin scale , there was no interaction between the pretreatment imaging pattern and treatment assignment ( P=0.14 ) . CONCLUSIONS A favorable penumbral pattern on neuroimaging did not identify patients who would differentially benefit from endovascular therapy for acute ischemic stroke , nor was embolectomy shown to be superior to st and ard care . ( Funded by the National Institute of Neurological Disorders and Stroke ; MR RESCUE Clinical Trials.gov number , NCT00389467 . ) Rationale Early reperfusion in patients experiencing acute ischemic stroke is critical , especially for patients with large vessel occlusion who have poor prognosis without revascularization . Solitaire ™ stent retriever devices have been shown to immediately restore vascular perfusion safely , rapidly , and effectively in acute ischemic stroke patients with large vessel occlusions . Aim The aim of the study was to demonstrate that , among patients with large vessel , anterior circulation occlusion who have received intravenous tissue plasminogen activator , treatment with Solitaire revascularization devices reduces degree of disability 3 months post stroke . Design The study is a global multicenter , two-arm , prospect i ve , r and omized , open , blinded end-point trial comparing functional outcomes in acute ischemic stroke patients who are treated with either intravenous tissue plasminogen activator alone or intravenous tissue plasminogen activator in combination with the Solitaire device . Up to 833 patients will be enrolled . Procedures Patients who have received intravenous tissue plasminogen activator are r and omized to either continue with intravenous tissue plasminogen activator alone or additionally proceed to neurothrombectomy using the Solitaire device within six-hours of symptom onset . Study Outcomes The primary end-point is 90-day global disability , assessed with the modified Rankin Scale ( mRS ) . Secondary outcomes include mortality at 90 days , functional independence ( mRS ≤ 2 ) at 90 days , change in National Institutes of Health Stroke Scale at 27 h , reperfusion at 27 h , and thrombolysis in cerebral infa rct ion 2b/3 flow at the end of the procedure . Analysis Statistical analysis will be conducted using simultaneous success criteria on the overall distribution of modified Rankin Scale ( Rankin shift ) and proportions of subjects achieving functional independence ( mRS 0–2 ) Background and Purpose — Measures of a therapy ’s effect size are important guides to clinicians , patients , and policy-makers on treatment decisions in clinical practice . The ECASS 3 trial demonstrated a statistically significant benefit of intravenous tissue plasminogen activator for acute cerebral ischemia in the 3- to 4.5-hour window , but an effect size estimate incorporating benefit and harm across all levels of poststroke disability has not previously been derived . Methods — Joint outcome table specification was used to derive number needed to treat to benefit ( NNTB ) and number needed to treat to harm ( NNTH ) values summarizing treatment impact over the entire outcome range on the modified Rankin scale of global disability , including both expert-dependent and expert-independent ( algorithmic and repeated r and om sampling ) array generation . Results — For the full 7-category modified Rankin scale , algorithmic analysis demonstrated that the NNTB for 1 additional patient to have a better outcome by ≥1 grade s than with placebo must lie between 4.0 and 13.0 . In bootstrap simulations , the mean NNTB was 7.1 . Expert joint outcome table analyses indicated that the NNTB for improved final outcome was 6.1 ( 95 % CI , 5.6–6.7 ) and the NNTH 37.5 ( 95 % CI , 34.6–40.5 ) . Benefit per 100 patients treated was 16.3 and harm per 100 was 2.7 . The likelihood of help to harm ratio was 6.0 . Conclusions — Treatment with tissue plasminogen activator in the 3- to 4.5-hour window confers benefit on approximately half as many patients as treatment <3 hours , with no increase in the conferral of harm . Approximately 1 in 6 patients has a better and 1 in 35 has a worse outcome as a result of therapy BACKGROUND In September , 2008 , the European Acute Stroke Study III ( ECASS III ) r and omised trial and the Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Registry ( SITS-ISTR ) observational study reported the efficacy and safety of the extension of the time window for intravenous alteplase treatment from within 3 h to within 4.5 h after stroke onset . We aim ed to assess the implementation of the wider time window , its effect on the admission-to-treatment time , and safety and functional outcome in patients recorded in SITS-ISTR . METHODS Patients treated according to the criteria of the European Summary of Product Characteristics , except for the time window , were included . Patients were grouped according to whether they were registered into SITS-ISTR before or after October , 2008 . We measured admission-to-treatment time and rates of symptomatic intracerebral haemorrhage , mortality , and functional independence at 3 months . FINDINGS 23 942 patients were included in SITS-ISTR between December , 2002 , and February , 2010 , of whom 2376 were treated 3 - 4.5 h after symptom onset . The proportion of patients treated within 3 - 4.5 h by the end of 2009 was three times higher than in the first three quarters of 2008 ( 282 of 1293 [ 22 % ] vs 67 of 1023 [ 7 % ] ) . The median admission-to-treatment time was 65 min both for patients registered before and after October , 2008 ( p=0.94 ) . 352 ( 2 % ) of 21 204 patients treated within 3 h and 52 ( 2 % ) of 2317 treated within 3 - 4.5 h of stroke had symptomatic intracerebral haemorrhage at 3 months ( adjusted odds ratio [ OR ] 1.44 , 95 % CI 1.05 - 1.97 ; p=0.02 ) . 2287 ( 12 % ) of 18 583 patients who were treated within 3 h and 218 ( 12 % ) of 1817 who were treated within 3 - 4.5 h had died by the 3-month follow-up ( adjusted OR 1.26 , 95 % CI 1.07 - 1.49 ; p=0.005 ) ; 10 531 ( 57 % ) of 18 317 patients treated within 3 h of stroke and 1075 ( 60 % ) of 1784 who were treated within 3 - 4.5 h were functionally independent at 3 months ( adjusted OR 0.84 , 95 % CI 0.75 - 0.95 ; p=0.005 ) . INTERPRETATION Since October , 2008 , thrombolysis within 3 - 4.5 h after stroke has been implemented rapidly , with a simultaneous increase in the number of patients treated within 3 h ; admission-to-treatment time has not increased . Safety and functional outcomes are less favourable after 3 h , but the wider time window now offers an opportunity for treatment of those patients who can not be treated earlier . Thrombolysis should be initiated within 4.5 h after onset of ischaemic stroke , although every effort should be made to treat patients as early as possible after symptom onset . FUNDING Boehringer Ingelheim , Ferrer , the European Union Public Health Executive Authority , and Medical Training and Research ( ALF ) from Stockholm County Council and Karolinska Institutet Background and Purpose — To determine the effect of intravenous tissue plasminogen activator ( IV-tPA ) on outcomes in patients with severe major anterior circulation ischemic stroke . Methods — Prospect ively , 649 patients with acute stroke had admission National Institutes of Health stroke scale ( NIHSS ) scores , noncontrast computed tomography ( CT ) , CT angiography ( CTA ) , and 6-month outcome assessed using modified Rankin scale . IV-tPA treatment decisions were made before CTA , at the time of noncontrast CT scanning , as per routine clinical protocol . Severe symptoms were defined as NIHSS>10 . Poor outcome was defined as modified Rankin scale > 2 . Major occlusions were identified on CTA . Univariate and multivariate stepwise-forward logistic regression analyses of the full cohort were performed . Results — Of 649 patients , 188 ( 29 % ) patients presented with NIHSS>10 , and 64 out of 188 ( 34 % ) patients received IV-tPA . Admission NIHSS , large artery occlusion , and IV-tPA all independently predicted good outcomes ; however , a significant interaction existed between IV-tPA and occlusion ( P<0.001 ) . Of the patients who presented with NIHSS>10 with anterior circulation occlusion , twice the percentage had good outcomes if they received IV-tPA ( 17 out of 49 patients , 35 % ) than if they did not ( 13 out of 77 patients , 17 % ; P=0.031 ) . The number needed to treat was 7 ( 95 % confidence interval , 3–60 ) . Conclusions — IV-tPA treatment result ed in significantly better outcomes in patients with severely symptomatic stroke with major anterior circulation occlusions . The 35 % good outcome rate was similar to rates found in endovascular therapy trials . Vascular imaging may help in patient selection and stratification for trials of IV-thrombolytic and endovascular therapies BACKGROUND The Solitaire Flow Restoration Device is a novel , self-exp and ing stent retriever design ed to yield rapid flow restoration in acute cerebral ischaemia . We compared the efficacy and safety of Solitaire with the st and ard , predicate mechanical thrombectomy device , the Merci Retrieval System . METHODS In this r and omised , parallel-group , non-inferiority trial , we enrolled patients from 18 sites ( 17 in the USA and one in France ) . Patients were eligible for inclusion if they had acute ischaemic stroke with moderate to severe neurological deficits and were treatable by thrombectomy within 8 h of stroke symptom onset . We used a computer-generated r and omisation sequence to r and omly allocate patients to receive thrombectomy treatment with either Solitaire or Merci ( 1:1 ; block sizes of four and stratified by centre and stroke severity ) . The primary endpoint was Thrombolysis In Myocardial Ischemia ( TIMI ) scale 2 or 3 flow in all treatable vessels without symptomatic intracranial haemorrhage , after up to three passes of the assigned device , as assessed by an independent core laboratory , which was masked to study assignment . Primary analysis was done by intention to treat . A prespecified efficacy stopping rule triggered an early halt to the trial . The study is registered with Clinical Trials.gov , number NCT 01054560 . RESULTS Between February , 2010 , and February , 2011 , we r and omly allocated 58 patients to the Solitaire group and 55 patients to the Merci group . The primary efficacy outcome was achieved more often in the Solitaire group than it was in the Merci group ( 61%vs 24 % ; difference 37 % [ 95 % CI 19 - 53 ] , odds ratio [ OR ] 4·87 [ 95 % CI 2·14 - 11·10 ] ; p(non-inferiority)<0·0001 , p(superiority)=0·0001 ) . More patients had good 3-month neurological outcome with Solitaire than with Merci ( 58%vs 33 % ; difference 25 % [ 6 - 43 ] , OR 2·78 [ 1·25 - 6·22 ] ; p(non-inferiority)=0·0001 , p(superiority)=0·02 ) . 90-day mortality was lower in the Solitaire group than it was in the Merci group ( 17 vs 38 ; difference -21 % [ -39 to -3 ] , OR 0·34 [ 0·14 - 0·81 ] ; p(non-inferiority)=0·0001 , p(superiority)=0·02 ) . INTERPRETATION The Solitaire Flow Restoration Device achieved substantially better angiographic , safety , and clinical outcomes than did the Merci Retrieval System . The Solitaire device might be a future treatment of choice for endovascular recanalisation in acute ischaemic stroke . FUNDING Covidien/ev3 BACKGROUND Thrombolytic therapy for acute ischemic stroke has been approached cautiously because there were high rates of intracerebral hemorrhage in early clinical trials . We performed a r and omized , double-blind trial of intravenous recombinant tissue plasminogen activator ( t-PA ) for ischemic stroke after recent pilot studies suggested that t-PA was beneficial when treatment was begun within three hours of the onset of stroke . METHODS The trial had two parts . Part 1 ( in which 291 patients were enrolled ) tested whether t-PA had clinical activity , as indicated by an improvement of 4 points over base-line values in the score of the National Institutes of Health stroke scale ( NIHSS ) or the resolution of the neurologic deficit within 24 hours of the onset of stroke . Part 2 ( in which 333 patients were enrolled ) used a global test statistic to assess clinical outcome at three months , according to scores on the Barthel index , modified Rankin scale , Glasgow outcome scale , and NIHSS : RESULTS In part 1 , there was no significant difference between the group given t-PA and that given placebo in the percentages of patients with neurologic improvement at 24 hours , although a benefit was observed for the t-PA group at three months for all four outcome measures . In part 2 , the long-term clinical benefit of t-PA predicted by the results of part 1 was confirmed ( global odds ratio for a favorable outcome , 1.7 ; 95 percent confidence interval , 1.2 to 2.6 ) . As compared with patients given placebo , patients treated with t-PA were at least 30 percent more likely to have minimal or no disability at three months on the assessment scales . Symptomatic intracerebral hemorrhage within 36 hours after the onset of stroke occurred in 6.4 percent of patients given t-PA but only 0.6 percent of patients given placebo ( P < 0.001 ) . Mortality at three months was 17 percent in the t-PA group and 21 percent in the placebo group ( P = 0.30 ) . CONCLUSIONS Despite an increased incidence of symptomatic intracerebral hemorrhage , treatment with intravenous t-PA within three hours of the onset of ischemic stroke improved clinical outcome at three months Objectives : Efficacy of thrombolytic therapy for ischemic stroke decreases with time elapsed from symptom onset . We analyzed the effect of interventions aim ed to reduce treatment delays in our single-center observational series . Methods : All consecutive ischemic stroke patients treated with IV alteplase ( tissue plasminogen activator [ tPA ] ) were prospect ively registered in the Helsinki Stroke Thrombolysis Registry . A series of interventions to reduce treatment delays were implemented over the years 1998 to 2011 . In-hospital delays were analyzed as annual median door-to-needle time ( DNT ) in minutes , with interquartile range . Results : A total of 1,860 patients were treated between June 1995 and June 2011 , which included 174 patients with basilar artery occlusion ( BAO ) treated mostly beyond 4.5 hours from symptom onset . In the non-BAO patients , the DNT was reduced annually , from median 105 minutes ( 65–120 ) in 1998 , to 60 minutes ( 48–80 ) in 2003 , further on to 20 minutes ( 14–32 ) in 2011 . In 2011 , we treated with tPA 31 % of ischemic stroke patients admitted to our hospital . Of these , 94 % were treated within 60 minutes from arrival . Performing angiography or perfusion imaging doubled the in-hospital delays . Patients with in-hospital stroke or arriving very soon from symptom onset had longer delays because there was no time to prepare for their arrival . Conclusions : With multiple concurrent strategies it is possible to cut the median in-hospital delay to 20 minutes . The key is to do as little as possible after the patient has arrived at the emergency room and as much as possible before that , while the patient is being transported BACKGROUND Endovascular therapy is increasingly used after the administration of intravenous tissue plasminogen activator ( t-PA ) for patients with moderate-to-severe acute ischemic stroke , but whether a combined approach is more effective than intravenous t-PA alone is uncertain . METHODS We r and omly assigned eligible patients who had received intravenous t-PA within 3 hours after symptom onset to receive additional endovascular therapy or intravenous t-PA alone , in a 2:1 ratio . The primary outcome measure was a modified Rankin scale score of 2 or less ( indicating functional independence ) at 90 days ( scores range from 0 to 6 , with higher scores indicating greater disability ) . RESULTS The study was stopped early because of futility after 656 participants had undergone r and omization ( 434 patients to endovascular therapy and 222 to intravenous t-PA alone ) . The proportion of participants with a modified Rankin score of 2 or less at 90 days did not differ significantly according to treatment ( 40.8 % with endovascular therapy and 38.7 % with intravenous t-PA ; absolute adjusted difference , 1.5 percentage points ; 95 % confidence interval [ CI ] , -6.1 to 9.1 , with adjustment for the National Institutes of Health Stroke Scale [ NIHSS ] score [ 8 - 19 , indicating moderately severe stroke , or ≥20 , indicating severe stroke ] ) , nor were there significant differences for the predefined subgroups of patients with an NIHSS score of 20 or higher ( 6.8 percentage points ; 95 % CI , -4.4 to 18.1 ) and those with a score of 19 or lower ( -1.0 percentage point ; 95 % CI , -10.8 to 8.8 ) . Findings in the endovascular-therapy and intravenous t-PA groups were similar for mortality at 90 days ( 19.1 % and 21.6 % , respectively ; P=0.52 ) and the proportion of patients with symptomatic intracerebral hemorrhage within 30 hours after initiation of t-PA ( 6.2 % and 5.9 % , respectively ; P=0.83 ) . CONCLUSIONS The trial showed similar safety outcomes and no significant difference in functional independence with endovascular therapy after intravenous t-PA , as compared with intravenous t-PA alone . ( Funded by the National Institutes of Health and others ; Clinical Trials.gov number , NCT00359424 . ) OBJECTIVE To determine whether prespecified baseline magnetic resonance imaging ( MRI ) profiles can identify stroke patients who have a robust clinical response after early reperfusion when treated 3 to 6 hours after symptom onset . METHODS We conducted a prospect i ve , multicenter study of 74 consecutive stroke patients admitted to academic stroke centers in North America and Europe . An MRI scan was obtained immediately before and 3 to 6 hours after treatment with intravenous tissue plasminogen activator 3 to 6 hours after symptom onset . Baseline MRI profiles were used to categorize patients into subgroups , and clinical responses were compared based on whether early reperfusion was achieved . RESULTS Early reperfusion was associated with significantly increased odds of achieving a favorable clinical response in patients with a perfusion/diffusion mismatch ( odds ratio , 5.4 ; p = 0.039 ) and an even more favorable response in patients with the Target Mismatch profile ( odds ratio , 8.7 ; p = 0.011 ) . Patients with the No Mismatch profile did not appear to benefit from early reperfusion . Early reperfusion was associated with fatal intracranial hemorrhage in patients with the Malignant profile . INTERPRETATION For stroke patients treated 3 to 6 hours after onset , baseline MRI findings can identify subgroups that are likely to benefit from reperfusion therapies and can potentially identify subgroups that are unlikely to benefit or may be harmed IMPORTANCE Time to thrombolysis is crucial for outcome in acute ischemic stroke . OBJECTIVE To determine if starting thrombolysis in a specialized ambulance reduces delays . DESIGN , SETTING , AND PARTICIPANTS In the Prehospital Acute Neurological Treatment and Optimization of Medical care in Stroke Study ( PHANTOM-S ) , conducted in Berlin , Germany , we r and omly assigned weeks with and without availability of the Stroke Emergency Mobile ( STEMO ) from May 1 , 2011 , to January 31 , 2013 . Berlin has an established stroke care infrastructure with 14 stroke units . We included 6182 adult patients ( STEMO weeks : 44.3 % male , mean [ SD ] age , 73.9 [ 15.0 ] y ; control weeks : 45.2 % male , mean [ SD ] age , 74.3 [ 14.9 ] y ) for whom a stroke dispatch was activated . INTERVENTIONS The intervention comprised an ambulance ( STEMO ) equipped with a CT scanner , point-of-care laboratory , and telemedicine connection ; a stroke identification algorithm at dispatcher level ; and a prehospital stroke team . Thrombolysis was started before transport to hospital if ischemic stroke was confirmed and contraindications excluded . MAIN OUTCOMES AND MEASURES Primary outcome was alarm-to-thrombolysis time . Secondary outcomes included thrombolysis rate , secondary intracerebral hemorrhage after thrombolysis , and 7-day mortality . RESULTS Time reduction was assessed in all patients with a stroke dispatch from the entire catchment area in STEMO weeks ( 3213 patients ) vs control weeks ( 2969 patients ) and in patients in whom STEMO was available and deployed ( 1804 patients ) vs control weeks ( 2969 patients ) . Compared with thrombolysis during control weeks , there was a reduction of 15 minutes ( 95 % CI , 11 - 19 ) in alarm-to-treatment times in the catchment area during STEMO weeks ( 76.3 min ; 95 % CI , 73.2 - 79.3 vs 61.4 min ; 95 % CI , 58.7 - 64.0 ; P < .001 ) . Among patients for whom STEMO was deployed , mean alarm-to-treatment time ( 51.8 min ; 95 % CI , 49.0 - 54.6 ) was shorter by 25 minutes ( 95 % CI , 20 - 29 ; P < .001 ) than during control weeks . Thrombolysis rates in ischemic stroke were 29 % ( 310/1070 ) during STEMO weeks and 33 % ( 200/614 ) after STEMO deployment vs 21 % ( 220/1041 ) during control weeks ( differences , 8 % ; 95 % CI , 4%-12 % ; P < .001 , and 12 % , 95 % CI , 7%-16 % ; P < .001 , respectively ) . STEMO deployment incurred no increased risk for intracerebral hemorrhage ( STEMO deployment : 7/200 ; conventional care : 22/323 ; adjusted odds ratio [ OR ] , 0.42 , 95 % CI , 0.18 - 1.03 ; P = .06 ) or 7-day mortality ( 9/199 vs 15/323 ; adjusted OR , 0.76 ; 95 % CI , 0.31 - 1.82 ; P = .53 ) . CONCLUSIONS AND RELEVANCE Compared with usual care , the use of ambulance-based thrombolysis result ed in decreased time to treatment without an increase in adverse events . Further studies are needed to assess the effects on clinical outcomes . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01382862 BACKGROUND The IMS III trial did not show a clinical benefit of endovascular treatment compared with intravenous alteplase ( recombinant tissue plasminogen activator ) alone for moderate or severe ischaemic strokes . Late reperfusion of tissue that was no longer salvageable could be one explanation , as suggested by previous exploratory studies that showed an association between time to reperfusion and good clinical outcome . We sought to vali date this association in a preplanned analysis of data from the IMS III trial . METHODS We used data for patients with complete proximal arterial occlusions in the anterior circulation who received endovascular treatment and achieved angiographic reperfusion ( score on Thrombolysis in Cerebral Infa rct ion scale of grade 2 - 3 ) during the endovascular procedure ( within 7 h of symptom onset ) . We used logistic regression to model good clinical outcome ( defined as a modified Rankin Scale score of 0 - 2 at 3 months ) as a function of the time to reperfusion . We prespecified variables to be considered for adjustment , including age , baseline National Institutes of Health Stroke Scale score , sex , and baseline blood glucose concentration . FINDINGS Of 240 patients who were otherwise eligible for inclusion in our analysis , 182 ( 76 % ) achieved angiographic reperfusion . Mean time from symptom onset to reperfusion ( ie , procedure end ) was 325 min ( SD 52 ) . Increased time to reperfusion was associated with a decreased likelihood of good clinical outcome ( unadjusted relative risk for every 30-min delay 0·85 [ 95 % CI 0·77 - 0·94 ] ; adjusted relative risk 0·88 [ 0·80 - 0·98 ] ) . INTERPRETATION Delays in time to angiographic reperfusion lead to a decreased likelihood of good clinical outcome in patients after moderate to severe stroke . Rapid reperfusion could be crucial for the success of future acute endovascular trials . FUNDING US National Institutes of Health and National Institute of Neurological Disorders and Stroke Background Early management improves outcome in acute stroke . This study was design ed to assess the prehospital path from symptom onset to arrival in hospital and to identify factors associated with prehospital delay . Methods A prospect i ve study was conducted including patients with acute ischaemic stroke , intracerebral haemorrhage and transient ischaemic attack admitted to hospital . Time intervals for prehospital delay , background data , severity , type of first medical contact and mode of transport were recorded . Univariate and multivariate analyses were performed to identify factors influencing prehospital delay . Results A total of 440 patients were included , with a mean age of 71.4±13.0 years ( 44.3 % female subjects ) , consisting of 65.9 % patients with ischaemic stroke , 11.4 % with intracerebral haemorrhage and 22.7 % with transient ischaemic attack . The median time from symptom onset to admission was 3.0 h ( 179 min ; IQR 77–542 ) . The median decision delay was 1.5 h ( 92 min , IQR 25–405 ) and accounted for 55.1 % ( median value ) of the prehospital delay . 310 ( 70.5 % ) patients arrived by ambulance . In the multivariate linear regression analysis , high National Institute of Health Stroke Scale score ( p<0.001 ) , transport by ambulance ( p<0.001 ) and lower age ( p=0.048 ) were significantly associated with early admission . Conclusions Severe strokes , use of ambulance and lower age are associated with reduced prehospital delay . The present study shows that more than half of the delay is caused by the hesitation to contact medical services . Public information campaigns should focus on fast symptom recognition and the importance of immediately contacting the Emergency Medical Services upon symptom onset Objective To assess the feasibility , safety and preliminary efficacy of intra-arterial thrombolysis ( IAT ) compared with st and ard intravenous thrombolysis ( IVT ) for acute ischemic stroke . Methods Eligible patients with ischemic stroke , who were devoid of contraindications , started IVT within 3 h or IAT as soon as possible within 6 h. Patients were r and omized within 3 h of onset to receive either intravenous alteplase , in accordance with the current European labeling , or up to 0.9 mg/kg intra-arterial alteplase ( maximum 90 mg ) , over 60 min into the thrombus , if necessary with mechanical clot disruption and /or retrieval . The purpose of the study was to determine the proportion of favorable outcome at 90 days . Safety endpoints included symptomatic intracranial hemorrhage ( SICH ) , death and other serious adverse events . Results 54 patients ( 25 IAT ) were enrolled . Median time from stroke onset to start to treatment was 3 h 15 min for IAT and 2 h 35 min for IVT ( p<0.001 ) . Almost twice as many patients on IAT as those on IVT survived without residual disability ( 12/25 vs 8/29 ; OR 3.2 ; 95 % CI 0.9 to 11.4 ; p=0.067 ) . SICH occurred in 2/25 patients on IAT and in 4/29 on IVT ( OR 0.5 ; CI 0.1 to 3.3 ; p=0.675 ) . Mortality at day 7 was 5/25 ( IAT ) compared with 4/29 ( IVT ) ( OR 1.6 ; CI 0.4 to 6.7 ; p=0.718 ) . There was no significant difference in the rate of other serious adverse events . Conclusions Rapid initiation of IAT is a safe and feasible alternative to IVT in acute ischemic stroke . Trial registration number NCT00540527 Background — Meaningful delays occurred in the Interventional Management of Stroke ( IMS ) III trial . Analysis of the work flow will identify factors contributing to the in-hospital delays . Methods and Results — In the endovascular arm of the IMS III trial , the following time intervals were calculated : stroke onset to emergency department arrival ; emergency department to computed tomography ( CT ) ; CT to intravenous tissue plasminogen activator start ; intravenous tissue plasminogen activator start to r and omization ; r and omization to groin puncture ; groin puncture to thrombus identification ; thrombus identification to start of endovascular therapy ; and start of endovascular therapy to reperfusion . The effects of enrollment time , CT angiography use , interhospital transfers , and intubation on work flow were evaluated . Delays occurred notably in the time intervals from intravenous tissue plasminogen activator initiation to groin puncture ( median 84 minutes ) and start of endovascular therapy to reperfusion ( median 85 minutes ) . The CT to groin puncture time was significantly shorter during working hours than after . Times from emergency department to reperfusion and groin puncture to reperfusion decreased over the trial period . Patients with CT angiography had shorter emergency department to reperfusion and onset to reperfusion times . Transfer of patients result ed in a longer onset to reperfusion time compared with those treated in the same center . Age , sex , National Institutes of Health Stroke Scale score , and intubation did not affect delays . Conclusions — Important delays were identified before reperfusion in the IMS III trial . Delays decreased as the trial progressed . Use of CT angiography and endovascular treatment in the same center were associated with time savings . These data may help in optimizing work flow in current and future endovascular trials . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00359424 |
1,820 | 20,422,436 | Conclusions J-pouch or STEA are acceptable and safe options after AR for rectal cancer . | Background A meta- analysis of published literature comparing J-pouch with side to end anastomosis after anterior resection ( AR ) for rectal cancer . | Functional variables after coloanal anastomosis or anastomosis with J pouch were investigated in 40 patients in a prospect i ve r and omized study . Continence for liquids and gas control were superior after J pouch anastomosis compared with coloanal reconstruction . The neorectal capacity was higher after J pouch anastomosis . The perception threshold for stool filling was higher in patients with J pouch resembling those values observed preoperatively . Quality of life was improved in subjects with with J pouch , although differences did not reach a significant level Objective To assess the efficacy of a novel coloplasty colonic pouch design in optimizing bowel function after ultralow anterior resection . Summary Background Data A colonic J-pouch may reduce excessive stool frequency and incontinence after anterior resection , but at the risk of evacuation problems . Experimental surgery on pigs has suggested that a coloplasty pouch ( CP ) may be a useful alternative . Although CP has recently been shown to be feasible in patients , there is no r and omized controlled trial comparing bowel function with the J-pouch . Methods After anterior resection for cancer , patients were allocated to either J-pouch or CP-anal anastomoses . Continence scoring , anorectal manometry , and endoanal ultrasound assessment s were made before surgery . All complications were recorded , and these preoperative assessment s were repeated at 4 months . The assessment s were repeated again at 1 year , and a quality of life question naire was added . Results Eighty-eight patients were recruited from October 1998 to April 2000 . Both groups were well matched for age , gender , staging , adjuvant therapy , and mean follow-up . There were no differences in the intraoperative time and hospital stay . CP result ed in more anastomotic leaks . At 4 months , J-pouch patients had 10.3 % less stool fragmentation but poorer stool deferment and more nocturnal leakage . However , there were no differences in the bowel function , continence score , and quality of life at 1 year . There were no differences in the anorectal manometry and endoanal ultrasound findings . Conclusions Coloplasty pouches result ed in more anastomotic leaks and minimal differences in bowel function . At present , the J-pouch remains the benchmark for routine clinical practice , and due care ( including defunctioning stoma ) should be exercised in situations requiring CP Objectives To compare a colonic J-pouch or a side-to-end anastomosis after low-anterior resection for rectal cancer with regard to functional and surgical outcome . Summary Background Data A complication after restorative rectal surgery with a straight anastomosis is low-anterior resection syndrome with a postoperatively deteriorated anorectal function . The colonic J-reservoir is sometimes used with the purpose of reducing these symptoms . An alternative method is to use a simple side-to-end anastomosis . Methods One-hundred patients with rectal cancer undergoing total mesorectal excision and colo-anal anastomosis were r and omized to receive either a colonic pouch or a side-to-end anastomosis using the descending colon . Surgical results and complications were recorded . Patients were followed with a functional evaluation at 6 and 12 months postoperatively . Results Fifty patients were r and omized to each group . Patient characteristics in both groups were very similar regarding age , gender , tumor level , and Dukes ’ stages . A large proportion of the patients received short-term preoperative radiotherapy ( 78 % ) . There was no significant difference in surgical outcome between the 2 techniques with respect to anastomotic height ( 4 cm ) , perioperative blood loss ( 500 ml ) , hospital stay ( 11 days ) , postoperative complications , reoperations or pelvic sepsis rates . Comparing functional results in the 2 study groups , only the ability to evacuate the bowel in < 15 minutes at 6 months reached a significant difference in favor of the pouch procedure . Conclusions The data from this study show that either a colonic J-pouch or a side-to-end anastomosis performed on the descending colon in low-anterior resection with total mesorectal excision are methods that can be used with similar expected functional and surgical results A system has been constructed to evaluate the design , implementation , and analysis of r and omized control trials ( RCT ) . The degree of quadruple blinding ( the r and omization process , the physicians and patients as to therapy , and the physicians as to ongoing results ) is considered to be the most important aspect of any trial . The analytic techniques are scored with the same emphasis as is placed on the control of bias in the planning and implementation of the studies . Description of the patient and treatment material s and the measurement of various controls of quality have less weight . An index of quality of a RCT is proposed with its pros and cons . If published papers were to approximate these principles , there would be a marked improvement in the quality of r and omized control trials . Finally , a reasonable st and ard design and conduct of trials will facilitate the interpretation of those with conflicting results and help in making valid combinations of undersized trials Background : Total mesorectal excision ( TME ) and colonic J pouch reconstruction has been widely practice d for mid- or low-rectal cancer . However , the laparoscopic version of TME has never been described . Methods : Five patients suffering from newly diagnosed mid- to low-rectal cancer were seen between March and July 1999 . These five patients were selected for laparoscopic TME and colonic J pouch reconstruction because preoperative investigations revealed resectable tumor without extrarectal disease . Results : There were three men and two women with a mean age of 61 years . The average body weight was 69 kg ( range , 57 - 80 ) . None of the patients had had previous abdominal operations . In all five patients , the tumor was located within 9 cm from anal verge . The average size of the main incision was 5 cm . All patients had a covering ileostomy at the end of the procedure . The mean operating time was 208 min ; average blood loss was 158 ml ; and mean hospital stay was 10.6 days . Three patients had Dukes ' B disease and two had Dukes ' C disease . The resection margins ( proximal , circumferential , and distal ) were all clear . There were no deaths or major complications . Two patients suffered from transient urinary retention . After ileostomy closure , the median frequency of bowel motion was twice per day at 6-month follow-up . Neither incontinence nor nocturnal soiling was reported . Conclusion : To the best of our knowledge , this is the first published series of such an operation . With good patient selection , laparoscopic-assisted TME and colonic J pouch-anal anastomosis is safe and feasible The efficacy of colon-J-pouch anal anastomosis ( CPAA ) in reducing defecatory frequency and urgency and the incidence of anastomotic fistulas has been proved by several studies but only as compared to straight colo-anal anastomosis ( CAA ) of the end-to-end type . We investigated the role played by the colon pouch in the strict sense , without the influence of a different CAA model , in a r and omised prospect i ve study comparing CPAA and straight side-to-end CAA . Over the period from 1994 to 1998 we selected 66 of 118 patients operated on for rectal cancer : a CPAA was constructed in 35 ( group P ) and a direct side-to-end CAA in 31 ( group D ) . The two groups were well matched for surgeon , type of patient , stage of disease and incidence of radiotherapy and presented no differences in operative mortality , general and anastomotic morbidity , or need for reoperation . Functional results : after 3 , 12 and 36 months , defecatory frequency > or = 4 movements/day was observed in 93.4 , 67.7 and 41.6 % of cases , respectively , in group D as against 25.7 , 14.2 and 13 % , respectively , in group P ( P < 0.05 ) , while defecatory urgency was recorded in 77.4 , 35.4 and 27.9 % of cases , respectively , in group D as against 34.2 , 17.1 and 9 % , respectively , in group P ( p < 0.05 ) . In the long term , incontinence was also significantly lower in group P. The colon pouch improves sphincter rehabilitation after anal recanalization compared to straight side-to-end CAA . It does not affect anastomotic morbidity but affords a protective effect on function in irradiated patients . CPAA proves to be the optimal reconstruction option after excision of the rectum Introduction : Colonic pouches have been used for 20 years to provide reservoir function after reconstructive proctectomy for rectal cancer . More recently coloplasty has been advocated as an alternative to a colonic pouch . However there have been no long-term r and omized , controlled trials to compare functional outcomes of coloplasty , colonic J-Pouch ( JP ) , or a straight anastomosis ( SA ) after the treatment of low rectal cancer . Aim : To compare the complications , long-term functional outcome , and quality of life ( QOL ) of patients undergoing a coloplasty , JP , or an SA in reconstruction of the lower gastrointestinal tract after proctectomy for low rectal cancer . Methods : A multicenter study enrolled patients with low rectal cancer , who were r and omized intraoperatively to coloplasty ( CP-1 ) or SA if JP was not feasible , or JP or coloplasty ( CP-2 ) if a JP was feasible . Patients were followed for 24 months with SF-36 surveys to evaluate the QOL . Bowel function was measured quantitatively and using Fecal Incontinence Severity Index ( FISI ) . Urinary function and sexual function were also assessed . Results : Three hundred sixty-four patients were r and omized . All patients were evaluated for complications and recurrence . Mean age was 60 ±12 years , 71 % were male . Twenty-three ( 7.4 % ) died within 24 months of surgery . No significant difference was observed in the complications among the 4 groups . Two hundred ninety-seven of 364 were evaluated for functional outcome at 24 months . There was no difference in bowel function between the CP-1 and SA groups . JP patients had fewer bowel movements , less clustering , used fewer pads and had a lower FISI than the CP-2 group . Other parameters were not statistically different . QOL scores at 24 months were similar for each of the 4 groups . Conclusions : In patients undergoing a restorative resection for low rectal cancer , a colonic JP offers significant advantages in function over an SA or a coloplasty . In patients who can not have a pouch , coloplasty seems not to improve the bowel function of patients over that with an SA PURPOSE : The colonic J-pouch anastomosis has been advocated to obviate urgent and frequent defecations following a sphincter-saving rectal excision . Physiologic characteristics of the colonic J-pouch were compared with those of the traditional straight anastomosis and related to clinical function . METHOD : Patients with total mesorectal excision for carcinoma were r and omized to either a straight ( n=23 ) or a colonic pouch anastomosis ( n=23 ) . The patients were examined before and at one year after surgery ( n=42 ) , which included laboratory studies , and a question naire regarding anorectal function was completed . RESULTS : Preoperative compliance of the rectum was restored after surgery in the pouch group , 2.9 ( 2.2–3.4 ) ml/cm H2O , but there was a significant decrease after surgery in the straight anastomosis group , 1.9 (1.1–2.3)P<0.001 ( median ( interquartile range ) ) . Sphincter pressures in both groups were similar . In a multiple regression analysis , high compliance was associated with favorable clinical function , and hypermotility of the anal canal was associated with adverse clinical function . CONCLUSIONS : Colonic pouch-anal anastomosis restores neorectal compliance , which is important for good function after low anterior resection . Presence of an unstable internal sphincter is a negative factor for clinical function in both straight and pouch anastomoses PURPOSE : Colonic pouches have gained increasing popularity in reconstruction after low anterior resection . In this prospect i ve , r and omized trial colonic pouch reconstruction is compared with side-to-end anastomosis for functional outcome . METHODS : From October 1995 to October 1996 , 29 patients had colonic pouch and 30 patients had side-to-end anastomosis reconstruction after low anterior resection . Patients were matched for age , gender , and tumor stage and localization . All patients underwent functional evaluation preoperatively and at three and six months post-operatively . RESULTS : There was no difference in preoperative anorectal function . The operating time was higher in the colonic pouch group ( 167vs . 149 minutes ) . Twenty-three patients ( 79.3 percent ) with colonic pouch had a protective stoma compared with 21 patients ( 70 percent ) with side-to-end anastomosis . Postoperative complications were 10.3 and 13.3 percent , respectively . There was no difference in manometric pressure of the anus , in anorectal angle , and in continence status after three and six months . Stool frequency was higher in the side-to-end anastomosis group , with 2.2vs . 5.4 per day at three months and 2.3vs . 3.1 per day at six months . Constipation was noted in two patients with colonic pouch ( 7 percent ) and none in the side-to-end anastomosis group at three months and twovs . none at six months . Maximum tolerated volume and threshold volume was higher in the colonic pouch group at three and at six months . CONCLUSION : Both forms of reconstruction have similar satisfactory long-term functional results . The major advantage of colonic pouch was seen in the immediate postoperative phase Abstract Several studies have shown a lower rate of anastomotic leakages in patients with coloanal J-pouch reconstruction than in those with straight coloanal anastomosis following anterior resection of the rectum . This study investigated whether this difference is due to a better anastomotic microcirculation . Thirty-two healthy , adult Göttinger mini-pigs underwent anterior rectal resection . They were subsequently r and omized to following four groups ( eight pigs per group ) : straight end-to-end , side-to-end , small pouch ( 4 cm ) , and large pouch ( 8 cm ) coloanal anastomosis . Bowel perfusion was measured before and after vessel ligature at predefined locations using laser Doppler flowmetry . After completion of the anastomosis microcirculation was investigated 1 cm above , below , and directly at the anastomotic site . Following vessel ligature there was a 25 % drop in blood flow . After completion of the anastomosis there was a further decrease of 25 % in the distal segment , while no changes were observed above the anastomosis . There were no statistical differences either before or after completion of the anastomosis between the various groups . It is concluded that anastomotic blood flow does not depend on the type of coloanal reconstruction in healthy pigs PURPOSE : Different studies have shown that low colorectal and coloanal anastomosis often yield poor functional results . The aim of the present study was to investigate whether a colonic reservoir is able to improve functional results . METHODS : Thirty-eight consecutive patients subjected to low anterior resection were r and omized following rectal excision in two groups . One ( n=19 ) had a stapled straight coloanal anastomosis , and the other ( n=19 ) had a 10-cm stapled colonic pouch low rectal anastomosis . Median anastomotic distance above the anal verge was 3.38±0.56 cm and 2.14±0.36 cm in both groups , respectively . Continence alterations , urgency , tenesmus , defecatory frequency , anal resting and maximum voluntary squeezing pressures , and maximum tolerable volume were evaluated one year later . RESULTS : One patient died of pulmonary embolism , and seven presented with a recurrence and were excluded from the study . Stool frequency was greater than three movements per day in 33.3 percent of cases with a reservoir and in 73.3 percent of those with a straight coloanal anastomosis ( P<0.05 ) . Maximum tolerable volume was significantly greater in patients with a reservoir ( 335 ± 195 ) than in those without ( 148 ± 38 ) ( P<0.05 ) . There were no significant differences in other variables studied . CONCLUSIONS : This study shows that some aspects of defecatory function after rectal excision could improve with a colonic reservoir PURPOSE Functional disturbances are common after anterior resection for rectal cancer . This study was design ed to compare functional and physiologic outcome after low anterior resection and total mesorectal excision with a colonic J-pouch or a side-to-end anastomosis . METHODS Functional and physiologic variables were analyzed in patients r and omized to a J-pouch ( n = 36 ) or side-to-end anastomosis ( n = 35 ) . Postoperative functional outcome was investigated with question naires . Anorectal manometry was performed preoperatively and at six months , one year , and two years postoperatively . RESULTS There was no statistical difference in functional outcome between groups at two years . Maximum neorectal volume increased in both groups but was approximately 40 percent greater at two years in pouches compared with the side-to-end anastomosis . Anal sphincter pressures volumes were halved postoperatively and did not recover during follow-up of two years . Male gender , low anastomotic level , pelvic sepsis , and the postoperative decrease of sphincter pressures were independent factors for more incontinence symptoms . CONCLUSIONS Colonic J-pouch and side-to-end anastomosis gives comparable functional results two years after low anterior resection . Neorectal volume had no detectable influence on function . There was a pronounced and sustained postoperative decrease in sphincter pressures PURPOSE : Functional results after low anterior resection with straight coloanal anastomosis are poor . Although certain functional aspects are improved with coloanal J-pouch anastomosis , evacuation difficulties are encountered in some of these patients . The aim of the study was to investigate the functional results of different reconstruction methods after low anterior resection in a st and ardized pig model . METHODS : Thirty-two adult Göttinger mini pigs were r and omly assigned either to straight end-to-end ( Group 1 ) , side-to-end ( Group 2 ) , small ( 4-cm limb length ) J-pouch ( Group 3 ) , or large ( 8-cm limb length ) J-pouch ( Group 4 ) coloanal anastomosis after low rectal excision . The animals were investigated 12 weeks after the operation by measuring neorectal compliance and ceruletide-induced defecation . Eight pigs without operation were used as controls ( Group 5 ) . RESULTS : Compliance was lowest in Groups 1 and 2 , which were significantly different compared with both pouch design s and controls . Neorectal compliance of pigs with either small or large pouches did not differ significantly compared with one another or controls . Defecation was significantly impaired in pigs with a large pouch compared with all other groups . Pigs with side-to-end anastomoses had as rapid an evacuation as animals with straight coloanal reconstruction . CONCLUSION : Coloanal J-pouch reconstruction adequately restores reservoir capacity after low anterior resection of the rectum . From a functional point of view , side-to-end is not superior to straight coloanal anastomosis . Compared with small pouches , a large pouch design does not lead to better neorectal compliance in the pig model , whereas pouch evacuation seems to be considerably compromised PURPOSE Colonic J-pouch has been constructed to overcome reservoir dysfunction after restorative rectal surgery , whereas no effort has been made for sphincter dysfunction . We conducted a prospect i ve , r and omized study comparing surgical and functional outcomes between side-to-end anastomosis and colonic J-pouch after low anterior resection in which the anastomosis was constructed from the abdomen . METHODS Fifty-six consecutive patients with middle-to-low rectal cancer undergoing low anterior resection were r and omly assigned to side-to-end or colonic J-pouch group preoperatively . Surgical outcomes of all the patients were recorded . Patients underwent functional evaluation , including anorectal manometry and functional assessment , preoperatively and then 3 months , 6 months , 1 year , and 2 years postoperatively . RESULTS Twenty-four patients in each group completed the study . The demographic data and preoperative functional assessment did not differ between the two groups . There was no significant difference in surgical outcomes with regard to anastomotic height ( 5 cm ) , blood loss , protective colostomy , operative time , complications , and adjuvant therapy . Anal pressures showed no significant change postoperatively and during the follow-up period ; there were no differences between the two groups . Temporal minor fecal incontinence was noted in the early postoperative period in both groups . With regard to bowel function , a significant reduction of volume of urgency and maximal tolerable volume was found postoperatively in both groups ; however , a faster recovery was noted in the colonic J-pouch group . Stool frequency increased significantly after surgery in both groups ; however , in contrast to rectal volume , a faster recovery was noted in the side-to-end group . CONCLUSIONS Anastomosis after low anterior resection for middle to low rectal cancer could be performed safely from the abdomen . It minimized sphincter injury and showed good continence preservation . On the other h and , the surgical outcomes and long-term functional results of side-to-end anastomosis were comparable with colonic J-pouch . Side-to-end anastomosis provides an easier , alternative way for reconstruction after restorative rectal surgery |
1,821 | 27,096,438 | Overall , the combination was better than placebo for the primary outcomes of pain-free and headache relief at two hours .
Using 50 mg of sumatriptan , rather than 85 mg , in the combination did not significantly change the result .
Treating early , when pain was still mild , was significantly better than treating once pain was moderate or severe for pain-free responses at two hours and during the 24 hours post dose .
Adverse events were mostly mild or moderate in severity and rarely led to withdrawal ; they were more common with the combination than with placebo ( moderate quality evidence ) .Where the data allowed direct comparison , combination treatment was superior to either monotherapy , but adverse events were less frequent with naproxen than with sumatriptan ( moderate quality evidence ) .
Combination treatment was effective in the acute treatment of migraine headaches .
The effect was greater than for the same dose of either sumatriptan or naproxen alone , but additional benefits over sumatriptan alone were not large .
More participants achieved good relief when medication was taken early in the attack , when pain was still mild .
Adverse events were more common with the combination and sumatriptan alone than with placebo or naproxen alone | BACKGROUND This is an up date d version of the original Cochrane review published in October 2013 on ' Sumatriptan plus naproxen for acute migraine attacks in adults'.Migraine is a common disabling condition and a burden for the individual , health services , and society .
It affects two to three times more women than men , and is most common in the age range 30 to 50 years .
Effective abortive treatments include the triptan and non-steroidal anti-inflammatory classes of drugs .
These drugs have different mechanisms of action and combining them may provide better relief .
Sumatriptan plus naproxen is now available in combination form for the acute treatment of migraine .
OBJECTIVES To determine the efficacy and tolerability of sumatriptan plus naproxen , administered together as separate tablets or taken as a fixed-dose combination tablet , compared with placebo and other active interventions in the treatment of acute migraine attacks in adults . | Abstract Variability in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size Forty to 78 % of the patients using sumatriptan for the acute treatment of migraine may present recurrence at least occasionally . The concomitant use of a NSAID ( nonsteroidal anti-inflammatory drug ) has been recommended to decrease the recurrence rate . Sixty seven patients that treated successfully 8 migraine attacks with 100 mg of sumatritpan PO and presented recurrence in at least 5 attacks were studied prospect ively . The patients received 100 mg of sumatriptan and 550 mg of naproxen sodium PO to treat 4 consecutive moderate or severe migraine attacks . The recurrence rate , once at least 62.5 % ( 5 out of 8 attacks ) , decreased to 14.2 % ( 38 out of 268 attacks ) with the combination of compounds ( p<0.0001 ) . We then studied two groups of 13 patients made r and omicaly from the 67 initially evaluated , that were given sumatriptan 100 mg plus naproxen sodium 550 mg or placebo , in a double-blind design , to treat 3 other consecutive migraine attacks . Each group of patients treated 39 attacks . The recurrence among the patients taking sumatriptan plus placebo was 59 % ( 23 out of 39 attacks ) and the recurrence presented by the group taking sumatriptan plus naproxen was 25.5 % ( 10 out of 39 attacks ) ( p<0.0003 ) . We concluded that the combination of sumatriptan plus naproxen sodium decreases significantly migraine recurrence presented by patients taking sumatriptan alone Objective Probable migraine is a common , disabling migraine subtype fulfilling all but one of the diagnostic criteria for migraine . This study was conducted to evaluate the efficacy and tolerability of sumatriptan/naproxen sodium for the acute treatment of probable migraine without aura . Methods Patients treated a headache of probable migraine without aura when pain was moderate or severe with sumatriptan/naproxen sodium ( n = 222 intent-to-treat ( ITT ) ) or placebo ( n = 221 ITT/complete case analysis a ) in this r and omized , double-blind , parallel-group study . Results Sumatriptan/naproxen sodium was more effective than placebo with respect to the co- primary efficacy endpoints two-hour pain-free response ( 29 % sumatriptan/naproxen sodium vs 11 % placebo , p < 0.001 ) and two- to 24-hour sustained pain-free response ( 24 % sumatriptan/naproxen sodium vs 9 % placebo , p < 0.001 ) . Sumatriptan/naproxen sodium was significantly more effective than placebo with respect to the secondary efficacy endpoints of pain-free response four hours postdose ( p < 0.001 ) , pain-free response maintained one to two hours postdose ( p = 0.034 ) and two to four hours postdose ( p < 0.001 ) , headache relief four hours postdose ( p < 0.001 ) , headache relief maintained two to four hours postdose ( p = 0.015 ) , sustained headache relief two through 24 hours postdose ( p = 0.002 ) , and rescue medication use ( p < 0.001 ) ; but not productivity scores . The most common adverse events were dizziness ( 4 % sumatriptan/naproxen sodium,<1 % placebo ) , dry mouth ( 2 % sumatriptan/naproxen sodium , < 1 % placebo ) , and nausea ( 2 % sumatriptan/naproxen sodium , < 1 % placebo ) . Conclusion Sumatriptan/naproxen sodium is effective in the acute treatment of probable migraine as demonstrated by higher rates of freedom from pain and restoration of function Objective : To estimate the 1-year prevalences of primary headache disorders and identify their principal risk factors in the general population of Russia . Methods : A countrywide population -based r and om sample of 2725 biologically unrelated adults in 35 cities and nine rural areas were interviewed in a door-to-door survey using a previously vali date d diagnostic question naire . Results : Of the 2725 eligible adults contacted , 2025 ( 74.3 % ) responded ( females 52.6 % , mean age 39.5 ± 13.4 years ) . Of these , 1273 ( 62.9 % ) reported headache ‘ not related to flu , hangover , cold , head injury ’ occurring at least once in the previous year . The gender- and age-st and ardized 1-year prevalence of migraine was 20.8 % . Female gender ( odds ratio ( OR ) = 3.8 ; 95 % confidence interval ( CI ) 2.8–5.1 ) and obesity ( OR = 1.5 ; 1.1–2.1 ) were positively associated with this type of headache . The gender- and age-st and ardized 1-year prevalence of tension-type headache ( TTH ) was 30.8 % . TTH was more prevalent in urban than in rural areas ( OR = 1.6 ; 1.3–2.0 ) . Headache on ≥15 days/month was reported by 213 ( 10.5 % ) respondents ( gender- and age-st and ardized prevalence 10.4 % ) , and associated with low socioeconomic status ( OR = 3.4 ; 2.4–4.9 ) , obesity ( OR = 3.0 ; 2.1–4.3 ) , female gender ( OR = 2.9 ; 2.1–4.1 ) and age over 40 years ( OR = 2.6 ; 1.9–3.6 ) . The majority of these respondents ( 68.1 % ) overused acute headache medications . Conclusion : The study demonstrated a high prevalence of migraine and a very high prevalence of headache on ≥15 days/month , and revealed unmet health-care needs of people with headache in Russia OBJECTIVES To evaluate the long-term safety and tolerability of sumatriptan-naproxen sodium for the treatment of moderate to severe acute migraines and to assess the safety of administration of an optional second dose . PATIENTS AND METHODS A 12-month , multicenter , open-label safety study was conducted in adults treated for migraine attacks of moderate to severe intensity from April 14 , 2004 , to August 18 , 2005 . Safety evaluations included adverse events and laboratory tests . RESULTS Of 600 patients enrolled , 565 ( 94 % ) were treated for at least 1 migraine . Of treated patients , 414 ( 73 % ) and 362 ( 64 % ) completed 6 and 12 months of treatment , respectively . Of the 24,485 attacks treated , 17,144 ( 70 % ) were treated with only 1 dose . On average , patients treated 5 migraine attacks per month , with a median of 6 days between attacks . The most common treatment-related adverse events were nausea , muscle tightness , and dizziness . Fourteen patients reported 1 or more serious adverse event with only 1 judged probably related to treatment . No deaths occurred . Eight percent of patients discontinued participation in the study because of adverse events or pregnancy . The rates of adverse events reported were no higher after treatment with 2 tablets ( at least 2 hours apart ) compared with 1 tablet . CONCLUSIONS In this 12-month data set of more than 24,000 migraine attacks in 565 patients , sumatriptan-naproxen sodium formulated in a single tablet was well tolerated when used episodically for the treatment of acute migraine . The adverse events did not differ from those expected for the individual components alone , and no new or unexpected findings occurred OBJECTIVE To describe return to normal function , productivity , and satisfaction of patients with moderate or severe migraine attacks treated with combined sumatriptan/naproxen sodium , sumatriptan alone , naproxen sodium alone , or placebo . PATIENTS , DESIGN , AND SETTING Patients in 2 identical , US , phase 3 , r and omized , double-blind , parallel-group , placebo-controlled , single-dose , multicenter studies treated a single moderate or severe migraine attack with sumatriptan/naproxen sodium ( 85 mg sumatriptan formulated with RT Technology and 500 mg naproxen sodium in a single-tablet formulation ) , sumatriptan , naproxen sodium , or placebo . MAIN OUTCOME MEASURES Ability to function ( not impaired , mildly impaired , severely impaired , or required bed rest ) was collected in diary cards completed immediately prior to treatment , every 30 minutes for the first 2 hours , and hourly from 2 to 24 hours while awake . Patients completed the Productivity Assessment Question naire ( PAQ ) 24 hours after study drug administration . The Patient Perception of Migraine Question naire ( PPMQ ) was administered at screening and 24 hours post treatment to capture patient satisfaction . RESULTS Compared with the other groups , the sumatriptan/naproxen sodium group reported significantly higher levels of normal or mildly impaired functioning as early as 2 and 4 hours after dosing . They also demonstrated greater reductions in workplace productivity loss compared with placebo in both studies , and were consistently more satisfied with their treatment compared with patients in other treatment groups and compared with their usual medications . CONCLUSIONS Treatment with sumatriptan/naproxen sodium allowed significantly more subjects to return to normal or mildly impaired functioning more quickly , and sumatriptan/naproxen sodium patients were significantly more satisfied with their treatment compared with other treatment groups . Overall productivity loss was significantly reduced following use of sumatriptan/naproxen sodium CONTEXT Multiple pathogenic mechanisms may be involved in generating the migraine symptom complex , and multimechanism-targeted therapy may confer advantages over monotherapy . OBJECTIVE To evaluate the efficacy and safety of a fixed-dose tablet containing sumatriptan succinate and naproxen sodium relative to efficacy and safety of each monotherapy and placebo for the acute treatment of migraine . DESIGN , SETTING , AND PARTICIPANTS Two replicate , r and omized , double-blind , single-attack , parallel-group studies conducted among 1461 ( study 1 ) and 1495 ( study 2 ) patients at 118 US clinical centers who were diagnosed as having migraine and received study treatment for a moderate or severe migraine attack . INTERVENTIONS Patients were r and omized in a 1:1:1:1 ratio to receive a single tablet containing sumatriptan , 85 mg , and naproxen sodium , 500 mg ; sumatriptan , 85 mg ( monotherapy ) ; naproxen sodium , 500 mg ( monotherapy ) ; or placebo , to be used after onset of a migraine with moderate to severe pain . MAIN OUTCOME MEASURES Primary outcome measures included the percentages of patients with headache relief 2 hours after dosing , absence of photophobia , absence of phonophobia , and absence of nausea for the comparison between sumatriptan-naproxen sodium and placebo , and the percentages of patients with sustained pain-free response for the comparison between sumatriptan-naproxen sodium and each monotherapy . RESULTS Sumatriptan-naproxen sodium was more effective than placebo for headache relief at 2 hours after dosing ( study 1 , 65 % vs 28 % ; P<.001 and study 2 , 57 % vs 29 % ; P<.001 ) , absence of photophobia at 2 hours ( 58 % vs 26 % ; P<.001 and 50 % vs 32 % ; P<.001 ) , and absence of phonophobia at 2 hours ( 61 % vs 38 % ; P<.001 and 56 % vs 34 % ; P<.001 ) . The absence of nausea 2 hours after dosing was higher with sumatriptan-naproxen sodium than placebo in study 1 ( 71 % vs 65 % ; P = .007 ) , but in study 2 rates of absence of nausea did not differ between sumatriptan-naproxen sodium and placebo ( 65 % vs 64 % ; P = .71 ) . For 2- to 24-hour sustained pain-free response , sumatriptan-naproxen sodium was superior at P<.01 ( 25 % and 23 % in studies 1 and 2 , respectively ) to sumatriptan monotherapy ( 16 % and 14 % in studies 1 and 2 ) , naproxen sodium monotherapy ( 10 % and 10 % in studies 1 and 2 ) , and placebo ( 8 % and 7 % in studies 1 and 2 ) . The incidence of adverse events was similar between sumatriptan-naproxen sodium and sumatriptan monotherapy . CONCLUSION Sumatriptan , 85 mg , plus naproxen sodium , 500 mg , as a single tablet for acute treatment of migraine result ed in more favorable clinical benefits compared with either monotherapy , with an acceptable and well-tolerated adverse effect profile . TRIAL REGISTRATION clinical trials.gov Identifiers : NCT00434083 ( study 1 ) ; NCT00433732 ( study 2 ) OBJECTIVE To evaluate efficacy and tolerability of a single , fixed-dose tablet of sumatriptan 85 mg/naproxen sodium 500 mg ( sumatriptan/naproxen sodium ) vs placebo in migraineurs who had discontinued treatment with a short-acting triptan because of poor response or intolerance . BACKGROUND Triptan monotherapy is ineffective or poorly tolerated in 1 of 3 migraineurs and in 2 of 5 migraine attacks . In April , 2008 , the Food and Drug Administration approved the combination therapy sumatriptan/naproxen sodium , developed specifically to target multiple migraine mechanisms . This combination product offers an alternative migraine therapy for patients who have reported poor response or intolerance to short-acting triptans . METHODS Two replicate , r and omized , multicenter , double-blind , placebo-controlled , 2-attack crossover trials evaluated migraineurs who had discontinued a short-acting triptan in the past year because of poor response or intolerance . Patients were instructed to treat within 1 hour and while pain was mild . RESULTS Patients ( n = 144 study 1 ; n = 139 study 2 ) had discontinued an average of 3.3 triptans before study entry . Sumatriptan/naproxen sodium was superior ( P < .001 ) to placebo for 2- through 24-hour sustained pain-free response ( primary end point ) ( study 1 , 26 % vs 8 % ; study 2 , 31 % vs 8 % ) and pain-free response 2 hours post dose ( key secondary end point ) ( study 1 , 40 % vs 17 % ; study 2 , 44 % vs 14 % ) . A similar pattern of results was observed for other end points that evaluated acute ( 2- or 4-hour ) , intermediate ( 8-hour ) , or 2- through 24-hour sustained response for migraine ( ie , pain and associated symptoms ) , photophobia , phonophobia , or nausea ( with the exception of nausea 2 and 4 hours post dose ) . The percentage of patients with at least 1 adverse event ( regardless of causality ) was 11 % with sumatriptan/naproxen sodium compared with 4 % with placebo in study 1 and 9 % with sumatriptan/naproxen sodium compared with 5 % with placebo in study 2 . Only 1 adverse event in 1 study was reported in > or = 2 % of patients after treatment with sumatriptan/naproxen sodium and reported more frequently with sumatriptan/naproxen than placebo : chest discomfort was reported in 2 % of subjects in study 1 , and no events met this threshold in study 2 . No serious adverse events attributed to study medication were reported in either study . CONCLUSION In migraineurs who reported poor response to a short-acting triptan , sumatriptan/naproxen sodium was generally well tolerated and significantly more effective than placebo in conferring initial , intermediate , and sustained efficacy for pain and migraine-associated symptoms of photophobia and phonophobia OBJECTIVE To evaluate the impact of a sumatriptan/naproxen sodium combination tablet on patient satisfaction , productivity , and functional disability in menstrual migraine treated during the mild pain phase of a single menstrual migraine attack associated with dysmenorrhea . BACKGROUND Menstrual migraineurs with dysmenorrhea represent a unique patient population not previously studied . When health outcomes end points are analyzed alongside traditional efficacy end points in migraine studies , a more comprehensive and robust underst and ing of the many factors that may influence patients ' choice of and adherence to pharmacological treatments for migraine is observed . METHODS In 2 replicate , multicenter , r and omized , double-blind , placebo-controlled trials , participants with menstrual migraine and dysmenorrhea treated a single menstrual migraine attack with a single fixed-dose tablet of sumatriptan 85 mg formulated with RT Technology ™ and naproxen sodium 500 mg ( sumatriptan-naproxen sodium ) or placebo . RESULTS Participants r and omized to sumatriptan-naproxen sodium were significantly more satisfied than those r and omized to placebo at 24 hours post dose , as demonstrated by higher satisfaction subscale scores for efficacy ( P < .001 for both studies ) , functionality ( P = .003 for study 1 ; P < .001 for study 2 ) , and ease of use ( P = .027 for study 1 ; P = .011 for study 2 ) . There was little bothersomeness of side effects associated with either treatment . Use of sumatriptan-naproxen sodium was also associated with lower reported " lost-time equivalents " in work and leisure time ( pooled analysis , P = .003 ) and lower rates of functional disability ( P = .05 , study 1 ; P < .001 , study 2 ) compared with placebo . CONCLUSION A fixed-dose combination tablet containing sumatriptan and naproxen sodium significantly improved patient satisfaction , productivity , and restoration of normal functioning in menstrual migraineurs with dysmenorrhea OBJECTIVE This pilot study explored the potential for 2 recognized acute migraine medications , 85 mg of sumatriptan plus 500 mg of naproxen sodium in a combination tablet ( SumaRT/Nap ) and 500 mg of naproxen sodium , to treat and modify the disease progression of migraine . In other words , can these medications both abort an acute attack of migraine and reduce the number of future migraine attacks ? BACKGROUND Patients suffering with moderate to severe attacks of migraine desire acute treatment . As migraine frequency increases , so does the need for more frequent relief of acute attacks . This may lead to medication overuse and potentially medication overuse headache ( MOH ) . Ideally , acute medication would have the ability to abort an attack of migraine and reduce the likelihood of future attacks . STUDY DESIGN The primary endpoint of this study was a reduction in migraine headache days from baseline through month 3 of the study . Subjects were r and omized 1:1 to treat 14 or fewer migraines per month with SumaRT/Nap ( Group A ) or naproxen sodium ( Group B ) for 3 months . Subjects in group A utilized SumaRT/Nap were encouraged , but not required , to treat migraine headache within 1 hour of onset of headache when the pain was mild . They could re-treat if needed after 2 hours . Subjects in group B utilized the same treatment strategy with 500 mg of naproxen sodium . Tablets of study medication were identical for both groups . Subjects recorded headache days , migraine attacks , duration of attacks , treatment , and treatment results daily on paper diaries . Subjects took the Migraine Disability Assessment Test ( MIDAS ) at r and omization and 3 months later at the end of study . RESULTS Naproxen sodium was associated with a statistically significant reduction in migraine headache days at month 3 compared to baseline ( P = .0002 ) . SumaRT/Nap was also associated with a reduction of migraine headache days , but this decrease did not reach statistical significance ( P = .2 ) . In addition , subjects in the naproxen sodium group had a statistically significant reduction of migraine attacks in all 3 months of the study compared to baseline . A greater than 50 % reduction in the number of migraine headache days at month 3 occurred in 43 % ( 6/14 ) of subjects in group B compared to 17 % ( 3/18 ) of subjects in group A. Consistent with large regulatory studies comparing the efficacy of SumaRT/Nap with naproxen sodium , SumaRT/Nap in this study was statistically superior to naproxen sodium at 2 hours in reducing headache severity during months 2 and 3 . There was a reduction of acute medication used from baseline to month 3 and improvement in MIDAS scores for both groups . CONCLUSION Naproxen sodium , when used as a sole acute treatment early in attacks , appears to reduce the frequency of headache days and migraine attacks for a select number of subjects over a 3-month period . SumaRT/Nap is more effective at 2-hour headache reduction than naproxen sodium alone , but has less impact on reducing attack frequency or the number of headache days . Both treatments were well tolerated , and there was no convincing evidence that either medication led to MOH OBJECTIVES The primary objective was to compare the efficacy of a sumatriptan and naproxen combination medication ( SumaRT/Nap-85 mg sumatriptan and 500 mg naproxen sodium ) , a butalbital-containing combination medication ( BCM-50 mg butalbital , 325 mg acetaminophen , 40 mg caffeine ) , and placebo when used to treat moderate to severe migraine headache pain in subjects who used BCMs in the past . BACKGROUND Despite the lack of Food and Drug Administration approval and the absence of placebo-controlled trials to demonstrate efficacy , butalbital-containing medications are among the most commonly prescribed acute migraine treatments in the United States . Butalbital-containing medications are associated with serious and undesirable side effects , and have been linked to the chronification of migraine and development of medication-overuse headaches . This study compares the relative efficacy , safety , and tolerability of a fixed dose SumaRT/Nap versus a BCM and placebo . METHODS Enrolled subjects were required to have treated at least 1 migraine with a butalbital medication in the past . Enrolled subjects treated 3 moderate to severe migraines using each of the 3 study treatments once in a r and omized sequence . The primary endpoint compared SumaRT/Nap versus BCM for sustained pain freedom at 2 - 24 hours without the use of any rescue medication . This study combines data from 2 identical outpatient , r and omized , multicenter , double-blind , double-dummy , 3 attack crossover studies in adult migraineurs ( International Classification of Headache Disorders , 2nd edition ) . RESULTS A total of 442 subjects treated at least 1 attack with study medication . The majority of the treated subjects were female ( 88 % ) with a mean age 43 years , who reported that their migraines had a severe impact on their lives ( 78 % with Headache Impact Test-6 of > 59 ) . At screening , 88 % of subjects reported current butalbital use ; 68 % had used butalbital for more than 6 weeks ; and 82 % reported satisfaction with butalbital . Across treatment groups , 28 - 29 % of subjects took study medication within 15 minutes of migraine onset , 34 - 37 % of subjects took study medication > 15 minutes to 2 hours after onset , and 32 - 36 % of subjects took study medication more than 2 hours after onset . This study did not detect a difference at the nominal 0.05 level in percent sustained pain-free between SumaRT/Nap ( 8 % ) , BCM ( 6 % ) , and placebo ( 3 % ) . SumaRT/Nap was superior to BCM for pain free at 2 , 4 , 6 , 8 , 24 , 48 hours ( P≤.044 ) ; pain relief ( mild or no pain ) at 2 , 4 , 6 , 8 , 24 , 48 hours ( P≤.01 ) ; sustained pain relief 2 - 24 hours ( P<.001 ) ; migraine free ( pain free with no nausea , photophobia , or phonophobia ) at 4 , 6 , 8 , 24 , 48 hours ( P≤.046 ) ; and complete symptom free ( migraine free with no neck/sinus pain ) at 4 , 6 , 8 , 48 hours ( P≤.031 ) . Adverse event incidence was similar for all treatments ( 10 % , 12 % , and 9 % for placebo , SumaRT/Nap , and BCM , respectively ) . Nausea was the most frequent adverse event ( 2 % , 2 % , and < 1 % for placebo , SumaRT/Nap , and BCM , respectively ) . Five serious adverse events were reported by 3 subjects : viral meningitis and colon neoplasm ( placebo ) ; chest pain and hypertension 17 days postdose ( SumaRT/Nap ) ; and breast cancer ( BCM ) . Investigators judged no serious adverse events related to study medication . CONCLUSIONS This study primarily included subjects whose migraines significantly impacted their lives . Before the study , these subjects used butalbital-containing medications as part of their current migraine treatment regimen and were satisfied with it , suggesting they were butalbital responders who had found a workable treatment strategy for themselves . When treated with SumaRT/Nap versus BCM in this study , however , a significant proportion of subjects reported better treatment outcomes for themselves for both migraine pain and associated symptoms . Use of SumaRT/Nap was also associated with less rescue medication use and a longer time before use of rescue medication compared with both BCM and placebo BACKGROUND Dysmenorrhea and menstrual migraine may share a common pathogenic pathway . Both appear to be mediated , in part , by an excess of prostagl and in production that occurs during menstruation . METHODS Data were pooled from two replicate r and omized controlled trials of 621 adult menstrual migraineurs with dysmenorrhea who treated migraine with sumatriptan-naproxen or placebo . Along with headache symptoms , nonpain menstrual symptoms ( bloating , fatigue , and irritability ) and menstrual pain symptoms ( abdominal and back pain ) were recorded at the time periods of 30 minutes and 1 , 2 , 4 , and 4 - 24 hours . Relief of menstrual symptoms was compared using a Cochran-Mantel-Haenszel test . Logistic regression was used to determine the odds of a headache response with increasing numbers of moderate to severe dymenorrheic symptoms . RESULTS Sumatriptan-naproxen was superior to placebo for relief of tiredness , irritability , and abdominal pain at the time periods of 2 , 4 , and 4 - 24 hours ( p≤0.023 ) ; back pain at the time periods of 4 and 4 - 24 hours ( p≤0.023 ) ; and bloating at 4 - 24 hours endpoint ( p=0.01 ) . The odds ratios ( ORs ) of attaining migraine pain freedom for 2 hours and for sustained 2 - 24 hours decreased as moderate to severe dysmenorrhea symptoms increased with sumatriptan-naproxen versus placebo . CONCLUSIONS Treatment with sumatriptan-naproxen may provide relief of menstrual symptoms and migraine in female migraineurs with dysmenorrhea . The presence of moderate to severe dysmenorrhea symptoms is associated with decreased response rates for menstrual migraine , suggesting that the co-occurrence of these disorders may negatively impact the results of migraine-abortive therapy OBJECTIVE : To evaluate the efficacy and tolerability of sumatriptan – naproxen during the mild pain phase of a single menstrual migraine attack associated with dysmenorrhea . METHODS : Two replicate r and omized , multicenter , double-blind , placebo-controlled , trials of adults with menstrual migraine and dysmenorrhea were conducted . Participants treated their menstrual migraine attack during the mild pain phase ( within 1 hour of onset ) with sumatriptan 85 mg and naproxen sodium 500 mg in a single fixed-dose formulation ( sumatriptan – naproxen ) or placebo . The primary endpoint was 2-hour pain-free response . RESULTS : Sumatriptan – naproxen was statistically superior to placebo in both studies ( n=311 , Study 1 ; n=310 , Study 2 ) for 2-hour and , 2- to 24-hour sustained pain-free response , use of headache and menstrual rescue medications , and several nonpain menstrual symptom categories . Two-hour pain-free rates were Study 1 , 42 % compared with 23 % , and Study 2 , 52 % compared with 22 % , P<.001 . Two- to 24-hour sustained pain-free rates were Study 1 , 29 % compared with 18 % , P=.022 ; Study 2 , 38 % compared with 10 % , P<.001 . Headache and menstrual medication rates were Study 1 , 37 % compared with 53 % , P=.005 ; Study 2 , 31 % compared with 69 % , P<.001 . Women treated with sumatriptan – naproxen continued to be pain free through 48 hours compared with placebo : Study 1 , 26 % compared with 17 % , P=.040 ; Study 2 , 28 % compared with 8 % , P<.001 . No serious adverse events were reported in either study ; nausea and dizziness were the most frequently reported adverse events . CONCLUSION : Sumatriptan – naproxen provided an effective pain-free response at 2 hours , which was maintained up to 48 hours in menstrual migraineurs with dysmenorrhea . Sumatriptan – naproxen was well-tolerated and result ed in decreased rescue medication use and relief of nonpainful menstrual symptoms . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00329459 and NCT00329355 LEVEL OF EVIDENCE : A novel composite endpoint , sustained pain-free/no adverse events , was recently proposed as a more rigorous means of capturing in a single measure the attributes of migraine pharmacotherapy that patients consider most important : rapid and sustained pain-free response with no side-effects . Using pooled data from two replicate r and omized , double-blind , parallel-group , placebo-controlled studies , this post hoc analysis compared the fixed-dose combination tablet sumatriptan/naproxen sodium ( n = 726 ) with sumatriptan monotherapy ( n = 723 ) , naproxen sodium monotherapy ( n = 720 ) , and placebo ( n = 742 ) with respect to sustained pain-free/no adverse events and closely related composite measures . Sustained pain-free/no adverse events was defined as having both a sustained pain-free response from 2 through 24 hours post-dose with no use of rescue medication and having no adverse events within up to 5 days after dosing with study medication . The percentage of patients with sustained pain-free/no adverse events was 16 % with sumatriptan/naproxen sodium compared with 11 % , 9 % and 7 % for sumatriptan , naproxen sodium and placebo , respectively ( p50.01 sumatriptan/naproxen sodium versus each other treatment ) . Sumatriptan/naproxen sodium was also significantly more effective than sumatriptan , naproxen sodium , and placebo for other composite endpoints including the percentages of patients with ( 1 ) sustained pain-free/no adverse events within 1 day ; ( 2 ) sustained pain-free/no drug-related adverse events within up to 5 days ; ( 3 ) sustained pain-free/no drug-related adverse events within 1 day ; ( 4 ) sustained pain relief/no adverse events within up to 5 days ; and ( 5 ) sustained pain relief/no adverse events within 1 day . The results demonstrate the superiority of sumatriptan/naproxen sodium to sumatriptan monotherapy , naproxen sodium monotherapy and placebo with respect to the rigorous and clinical ly relevant endpoint of sustained pain-free/no adverse events and reinforce the usefulness of utilizing this new composite endpoint Two identical r and omized , placebo-controlled , crossover studies were conducted to evaluate consistency of response to sumatriptan/naproxen sodium 85/500 mg ( S/NS ) over four attacks in adults with migraine . Patients were instructed to treat within 1 h of pain onset while pain was mild . Co- primary end-points were pain-free response at 2 h ( 2hPF ) and 24-h sustained pain-free response ( 24hSPF ) calculated as percentages of all attacks . In Study 1 , 570 patients treated 1693 attacks with S/NS and 424 with placebo . In Study 2 , 565 patients treated 1678 attacks with S/NS and 422 with placebo . Compared with placebo , S/NS conferred higher 2hPF rates ( Study 1 : S/NS 52 % , placebo 25 % ; Study 2 : S/NS 50 % , placebo 20 % ; both P < 0.001 ) and higher 24hSPF rates ( Study 1 : S/NS 37 % , placebo 17 % ; Study 2 : S/NS 34 % , placebo 12 % ; both P < 0.001 ) . 2hPF was reported in at least two of the first three S/NS-treated attacks in 55.0 % of patients in Study 1 and 52.1 % of patients in Study 2 . 24hSPF was reported in at least two of the first three S/NS-treated attacks in 35.7 % of patients in Study 1 and 32.6 % of patients in Study 2 . The incidences of any adverse event and of specific adverse events were low and generally similar between S/NS and placebo Abstract One way to ensure adequate sensitivity for analgesic trials is to test the intervention on patients who have established pain of moderate to severe intensity . The usual criterion is at least moderate pain on a categorical pain intensity scale . When visual analogue scales ( VAS ) are the only pain measure in trials we need to know what point on a VAS represents moderate pain , so that these trials can be included in meta‐ analysis when baseline pain of at least moderate intensity is an inclusion criterion . To investigate this we used individual patient data from 1080 patients from r and omised controlled trials of various analgesics . Baseline pain was measured using a 4‐point categorical pain intensity scale and a pain intensity VAS under identical conditions . The distribution of the VAS scores was examined for 736 patients reporting moderate pain and for 344 reporting severe pain . The VAS scores corresponding to moderate or severe pain were also examined by gender . Baseline VAS scores recorded by patients reporting moderate pain were significantly different from those of patients reporting severe pain . Of the patients reporting moderate pain 85 % scored over 30 mm on the corresponding VAS , with a mean score of 49 mm . For those reporting severe pain 85 % scored over 54 mm with a mean score of 75 mm . There was no difference between the corresponding VAS scores of men and women . Our results indicate that if a patient records a baseline VAS score in excess of 30 mm they would probably have recorded at least moderate pain on a 4‐point categorical scale OBJECTIVE To describe the pain relief , satisfaction , and health-related quality of life results of moderate or severe migraines treated with a sumatriptan/naproxen sodium combination tablet . METHODS Sumatriptan and naproxen sodium as a single-dose formulation tablet was used to treat moderate to severe migraines over a 12-month period in a phase 3 , open-label , multicenter study ( n = 565 ) in patients with at least 6 months ' history of migraine headaches . RESULTS Seventy percent of all attacks were treated with 1 dose of sumatriptan/naproxen sodium . Overall subjects treated 24,485 attacks ; of these , 81 % attacks achieved pain relief and 60 % pain-free by 2 hours . At 3 months , the percentage of patients satisfied or very satisfied increased from baseline on all 8 Patient Perception of Migraine Question naire ( PPMQ ) items and remained high throughout the study . Mean Migraine-Specific Quality of Life Question naire ( MSQ ) domain scores also increased by 13 - 15 points from baseline during this time and remained high . CONCLUSIONS Sumatriptan/naproxen sodium provides consistent relief of migraine attacks over 12 months , result ing in improved patient satisfaction and migraine specific quality of life OBJECTIVE To evaluate the efficacy and tolerability of treatment with a combination of sumatriptan 50 mg ( encapsulated ) and naproxen sodium 500 mg administered concurrently in the acute treatment of migraine . BACKGROUND The pathogenesis of migraine involves multiple peripheral and central neural mechanisms that individually have been successful targets for acute ( abortive ) and preventive treatment . This suggests that multi-mechanism therapy , which acts on multiple target sites , may confer improved efficacy and symptom relief for patients with migraine . DESIGN AND METHODS This was a multicenter , r and omized , double-blind , double-dummy , placebo-controlled , four-arm study . Participants ( n = 972 ) treated a single moderate or severe migraine attack with placebo , naproxen sodium 500 mg , sumatriptan 50 mg , or a combination of sumatriptan 50 mg and naproxen sodium 500 mg . In the latter two treatment arms , the sumatriptan tablets were encapsulated in order to achieve blinding of the study . RESULTS In the sumatriptan plus naproxen sodium group , 46 % of subjects achieved 24-hour pain relief response ( primary endpoint ) , which was significantly more effective than sumatriptan alone ( 29 % ) , naproxen sodium alone ( 25 % ) , or placebo ( 17 % ) ( P < .001 ) . Two-hour headache response also significantly favored the sumatriptan 50 mg plus naproxen sodium 500 mg therapy ( 65 % ) versus sumatriptan ( 49 % ) , naproxen sodium ( 46 % ) , or placebo ( 27 % ) ( P < .001 ) . A similar pattern of between-group differences was observed for 2-hour pain-free response and sustained pain-free response ( P < .001 ) . The incidence of headache recurrence up to 24 hours after treatment was lowest in the sumatriptan plus naproxen sodium group ( 29 % ) versus sumatriptan alone ( 41 % ; P = .048 ) , versus naproxen sodium alone ( 47 % ; P= .0035 ) , and versus placebo ( 38 % ; P= .08 ) . The incidences of the associated symptoms of migraine were significantly lower at 2 hours following sumatriptan 50 mg plus naproxen sodium 500 mg treatment versus placebo ( P < .001 ) . The frequencies and types of adverse events reported did not differ between treatment groups , with dizziness and somnolence being the most common . CONCLUSIONS This is among the first prospect i ve studies to demonstrate that multi-mechanism acute therapy for migraine , combining a triptan and an analgesic , is well tolerated and offers improved clinical benefits over monotherapy with these selected st and ard antimigraine treatments . Specifically , sumatriptan 50 mg ( encapsulated ) and naproxen sodium 500 mg result ed in significantly superior pain relief as compared to monotherapy with either sumatriptan 50 mg ( encapsulated ) or naproxen sodium 500 mg for the acute treatment of migraine . Because encapsulation of the sumatriptan for blinding purpose s may have altered its pharmacokinetic profile and thereby decreased the efficacy responses , additional studies are warranted that do not involve encapsulation of the active treatments and assess the true onset of action of multi-mechanism therapy in migraine . This study did show that the combination of sumatriptan and naproxen sodium was well tolerated and that there was no significant increase in the incidence of adverse events compared to monotherapy Background : Research suggests treating a migraine at the first sign of pain increases the likelihood of the best clinical outcome . Objective : To investigate the efficacy and tolerability of a fixed-dose , single-tablet formulation of sumatriptan 85 mg , formulated with RT Technology , and naproxen sodium 500 mg ( sumatriptan/naproxen ) as early intervention acute therapy for migraine . Methods : Patients ( aged 18 to 65 years ) with International Headache Society – defined migraine with or without aura were enrolled in one of two identically design ed , r and omized , double-blind , parallel group , placebo-controlled studies . Patients treated a single migraine within 1 hour of onset of migraine head pain and while the pain was mild with either sumatriptan/naproxen or placebo . The primary efficacy measure was the percentage of patients who became pain-free 2 hours postdose . Results : Intent-to-treat analyses consisted of 576 and 535 migraineurs . At 2 hours , 52 % and 51 % of sumatriptan/naproxen-treated patients were pain free , as compared to 17 % and 15 % of placebo-treated patients ( p < 0.001 ) . Significant pain-free responses in favor of sumatriptan/naproxen were demonstrated as early as 30 minutes , maintained at 1 hour , and sustained from 2 to 24 hours . At 2 and 4 hours , sumatriptan/naproxen provided significantly lower rates of traditional migraine-associated symptoms ( nausea , photophobia , and phonophobia ) and nontraditional migraine-associated symptoms ( neck pain/discomfort and sinus pain/pressure ) . The most commonly reported adverse events were nausea ( ≤4 % ) and dizziness ( ≤2 % ) . Conclusion : The fixed-dose single-tablet formulation of sumatriptan/naproxen was effective and well tolerated in an early intervention paradigm for the acute treatment of migraine , including traditional and nontraditional symptoms Anti-inflammatory and pain therapies have been associated with blood pressure ( BP ) destabilization . Hence , the effects on BP of sumatriptan/naproxen sodium in fixed-dose combination , sumatriptan 85 mg , and naproxen sodium 500 mg administered intermittently for the acute treatment of migraine attacks were assessed . Patients with migraine with or without aura and no history of hypertension were r and omized to sumatriptan/naproxen sodium ( n=135 ) , sumatriptan ( n=136 ) , or naproxen sodium ( n=136 ) to treat migraine attacks for 6 months in a double-blind , parallel-group trial . Following a treated migraine attack , patients performed 2 consecutive days of self-measured BPs beginning ≥24 hours after the last dose of study medication and transmitted them by a transtelephonic modem . The primary end point was the change from baseline in self-measured BP at 6 months . Changes in self-measured BP from baseline to 6 months for sumatriptan/naproxen sodium were -2.1/-1.5 mm Hg ( 95 % confidence intervals , -3.4 to -0.8 for systolic and -2.6 to -0.3 for diastolic ) . Mean changes from baseline in self-measured BP did not differ among the 3 treatment groups . Additional categorical analyses did not show increases from baseline with sumatriptan/naproxen sodium relative to either of the monotherapy groups . Intermittent acute migraine treatment with sumatriptan/naproxen sodium for up to 6 months was associated with clinical ly insignificant decreases in self-measured BP that were similar to those with sumatriptan or naproxen alone in normotensive patients with migraine |
1,822 | 25,408,702 | Our result revealed that there was no evidence of a significant difference in rates of clinical pregnancy and miscarriage in women with clomiphene citrate-resistant PCOS undergoing LOD compared to the gonadotropin arm .
The decrease in multiple pregnancies rate in women undergoing LOD makes this option attractive .
The increase in live birth rate in the gonadotropin group may be because of the higher rate of multiple pregnancies in these women . | BACKGROUND Some trials have compared laparoscopic ovarian drilling ( LOD ) with gonadotropins but , because of variations in study design and small sample size , the results are inconsistent and definitive conclusions about the relative efficacy of LOD and gonadotropins can not be extracted from the individual studies .
OBJECTIVE To evaluate the relative efficacy of LOD and gonadotropins for infertile women with clomiphene citrate- resistant poly cystic ovary syndrome ( PCOS ) . | BACKGROUND Recombinant FSH ( rFSH ) is the current st and ard treatment for ovulation induction in women with polycystic ovary syndrome ( PCOS ) that do not respond to clomiphene citrate . Ovulation induction with rFSH is known to be costly due to the necessity of daily injections and intensive monitoring . An alternative strategy , starting with electrocautery of the ovaries , may be a less costly option . METHODS An economic evaluation was set up alongside a multicentre r and omized clinical trial comparing laparoscopic electrocautery of the ovaries , followed by clomiphene citrate and rFSH when anovulation persisted , and treatment with rFSH in 168 women with clomiphene citrate-resistant PCOS . Data on re sources used for treatment and productivity loss were collected prospect ively up to an eventual ongoing pregnancy with a time horizon of 12 months . RESULTS At 12 months the ongoing pregnancy rates were 67 % for both the electrocautery strategy and rFSH treatment . Mean total costs per woman were 5308 euros for the electrocautery strategy and 5925 euros for treatment with rFSH , result ing in a mean difference of 617 ( 95 % CI : -382 euros to 1614 euros ) . CONCLUSIONS The total treatment costs up to an ongoing pregnancy are comparable for rFSH treatment and an alternative strategy starting with electrocautery . Due to a lower number of multiple pregnancies , the electrocautery strategy can be expected to result in lower total costs when costs of the delivery are included STUDY OBJECTIVE To analyze the efficacy of laparoscopic ovarian drilling using monopolar diathermy in women with anovulatory infertility with clomiphene-resistant polycystic ovary syndrome ( PCOS ) , and to determine factors influencing pregnancy rate and pregnancy outcomes . DESIGN Prospect i ve study ( Canadian Task Force classification II-2 ) . SETTING Infertility clinic in a tertiary referral teaching hospital . PATIENTS Seventy women with clomiphene-resistant PCOS . INTERVENTION Laparoscopic ovarian drilling , with follow-up for 4.5 years . MEASUREMENTS AND MAIN RESULTS Follow-up data , which were available for 66 patients , showed a spontaneous ovulation rate of 81.8 % , cumulative ovulation rate of 93.9 % , and pregnancy rate of 54.5 % . Successful pregnancies were commonly complicated by gestational diabetes mellitus and pregnancy-induced hypertension . Pregnancy rates ( 23.5 % ) were low in women with tuboperitoneal disease and those whose partners had subfertile male factors . Statistical evaluation using a proportion test ( Z test ) and multivariable logistical regression analysis showed that elevated luteinizing hormone levels ( > 10 IU/L ) , short duration of infertility ( <3 yrs ) , and absence of preexisting tubal disease were associated with better outcomes . CONCLUSION Laparoscopic ovarian drilling is an effective surgical procedure in women with clomiphene-resistant PCOS OBJECTIVE This study aim ed to compare two methods of treatment of infertility with gonadotropin with laparoscopic ovarian electrocauterization in patients with clomiphene citrate-resistant polycystic ovary syndrome ( PCOS ) . METHODS A number of 104 nulipara patients with polycystic ovary syndrome , who were resistant to clomiphene citrate were r and omly assigned to two groups . One group received gonadotropin ; after the bleeding withdrawal and from the third day of the cycle , the injection of human menopausal gonadotropin ( HMG ) was started with 10 mg medroxy progesterone . The patients were followed with serial trans-vaginal sonographies . When the diameter of follicles reached to 18 mm , human chorionic gonadotropin ( HCG ) was prescribed . The other group was treated with laparoscopic ovarian electrocauterization under general anesthesia . If after 3 cycles , the anovulation was established with progesterone measurement , the clomiphene citrate was prescribed . Gonadotropin was administered , if the lack of ovulation persisted . RESULTS No significant difference was documented between the two groups in terms of the obesity indexes , duration of infertility , age , sonographic and laboratory findings . In the gonadotropin group , 37 cases ( 71 % ) of pregnancy occurred . The rate of pregnancy was the same in the other group consisting of 18 cases treated by electrocautery , 9 cases with cautery + clomiphene , and 10 cases with clomiphene + cautery + gonadotropin . In the group treated with gonadotropin , there were 1 triple and 4 twins pregnancies . In the group treated with ovarian electrocautery , one twin pregnancy was observed . In the group treated with gonadotropin , 2 cases of ovarian hyperstimulation syndrome , 1 case of ectopic pregnancy and 6 cases of miscarriage occurred ; the corresponding figure in the ovarian electrocautery group consisted of 5 cases of miscarriage . CONCLUSION Our findings suggest that ovarian electrocauterization is an appropriate method with good efficacy and low complication rate for infertility treatment of women with clomiphene citrate-resistant polycystic ovary syndrome BACKGROUND Long-term effects of laparoscopic electrocautery of the ovaries are unknown . To study the long-term effects of laparoscopic electrocautery of the ovaries and gonadotrophins , we followed women with clomiphene-resistant polycystic ovary syndrome ( PCOS ) r and omly allocated to one of these treatments until 8 - 12 years after their initial treatment . METHODS Between February 1998 and October 2001 168 women with clomiphene citrate-resistant PCOS were included in a r and omized controlled trial comparing an electrocautery strategy to a strategy starting with rFSH . In 2009 these women were contacted about their reproductive outcome and menstrual cycle regularity . Analysis was by intention-to-treat . We compared time to conception result ing in live birth , subsequent pregnancies , ectopic and multiple pregnancies , menopause , as well as minimal and maximal menstrual cycle length . RESULTS After 8 - 12 years , the cumulative proportion of women with a first child was 86 % in women who had been allocated to electrocautery versus 81 % in women who had been allocated to immediate rFSH [ relative ratio ( RR ) : 1.1 ; 95 % confidence interval ( CI ) : 0.92 - 1.2 ] . Treatment with electrocautery result ed in a significantly lower need for stimulated cycles to reach a live birth ; 53 % after electrocautery versus 76 % after rFSH ( RR : 0.69 ; 95 % CI : 0.55 - 0.88).The cumulative proportion of women with a second child was 61 % after electrocautery versus 46 % after immediate rFSH ( RR : 1.4 ; 95 % CI : 1.00 - 1.9 ) . Overall , there were 7 twins out of 134 deliveries ( 5 % ) after electrocautery versus 10 twins out of 124 deliveries ( 8 % ) in the rFSH group ( RR : 0.65 ; 95 % CI : 0.25 - 1.6 ) . Fifty-four per cent of the women allocated to electrocautery had a regular menstrual cycle 8 - 12 years after r and omization versus 36 % in those allocated to rFSH ( RR : 1.5 ; 95 % CI : 0.87 - 2.6 ) . CONCLUSION In women with clomiphene-resistant PCOS , laparoscopic electrocautery of the ovaries is as effective as ovulation induction with FSH treatment in terms of live births , but reduces the need for ovulation induction or ART in a significantly higher proportion of women and increases the chance for a second child . Clinicians may use these data when informing clomiphene-resistant anovulatory women about treatment options Abstract Objective To compare the effectiveness of an electrocautery strategy with ovulation induction using recombinant follicle stimulating hormone in patients with polycystic ovary syndrome . Design R and omised controlled trial . Setting Secondary and tertiary hospitals in the Netherl and s. Participants 168 patients with clomiphene citrate resistant polycystic ovary syndrome : 83 were allocated electrocautery and 85 were allocated recombinant follicle stimulating hormone . Intervention Laparoscopic electrocautery of the ovaries followed by clomiphene citrate and recombinant follicle stimulating hormone if anovulation persisted , or induction of ovulation with recombinant follicle stimulating hormone . Main outcome measure Ongoing pregnancy within 12 months . Results . The cumulative rate of ongoing pregnancy after recombinant follicle stimulating hormone was 67 % . With only electrocautery it was 34 % , which increased to 49 % after clomiphene citrate was given . Subsequent recombinant follicle stimulating hormone increased the rate to 67 % at 12 months ( rate ratio 1.01 , 95 % confidence interval 0.81 to 1.24 ) . No complications occurred from electrocautery with or without clomiphene citrate . Patients allocated to electrocautery had a significantly lower risk of multiple pregnancy ( 0.11 , 0.01 to 0.86 ) . Conclusion The ongoing pregnancy rate from ovulation induction with laparoscopic electrocautery followed by clomiphene citrate and recombinant follicle stimulating hormone if anovulation persisted , or recombinant follicle stimulating hormone , seems equivalent to ovulation induction with recombinant follicle stimulating hormone , but the former procedure carries a lower risk of multiple pregnancy BACKGROUND Ovulation induction with gonadotrophins is the st and ard treatment strategy for women with clomiphene citrate (CC)-resistant polycystic ovary syndrome ( PCOS ) . Laparoscopic electrocautery of the ovaries is an alternative treatment modality , leading to a comparable cumulative pregnancy rate . In deciding which treatment to opt for , women 's health-related quality of life ( HRQoL ) should be taken into account . METHODS A total of 168 CC-resistant women with PCOS were r and omly assigned to receive either the electrocautery strategy , entailing laparoscopic electrocautery of the ovaries followed by CC and recombinant FSH ( rFSH ) if anovulation persisted , or ovulation induction with rFSH . We assessed women 's HRQoL with the st and ard question naires Short Form-36 , Rotterdam Symptom Checklist and Center for Epidemiological Studies Depression Scale , administered before r and omization and 2 , 12 and 24 weeks thereafter . RESULTS The intention to treat analysis revealed no significant differences between the treatment groups on any of the scales at any point during follow-up . In women without an ongoing pregnancy , those treated with rFSH showed significantly more depressive symptoms than women allocated to the electrocautery strategy , with or without CC , although differences were small . CONCLUSIONS Overall , HRQoL was not affected in both groups . In women still under treatment , rFSH was slightly more burdensome for women 's HRQoL than electrocautery with or without CC This prospect i ve , r and omized study included 18 polycystic ovarian syndrome ( PCOS ) patients with severe ovarian dysfunction , who were evaluated by st and ard clomiphene and FSH stimulation . In this group of patients , a 6 month down-regulation with gonadotrophin-releasing hormone ( GnRH ) analogues gave outcomes similar to laparoscopic ovarian laser diathermy with respect to stimulatory outcome and pregnancy rate . Clomiphene stimulation with 50 mg of clomiphene/day and FSH stimulation in a low-dose , step-up protocol with purified FSH did not result in oligofollicular development ; thus patients were divided into two subgroups : one subgroup received laparoscopic laser drilling and the other received 6 months of therapy with GnRH analogues plus add-back therapy after diagnostic laparoscopy . Subsequently , three cycles of low-dose , step-up stimulation with recombinant FSH were started . In both groups , approximately 30 % of cycles still remained anovulatory . In the down-regulated subgroup , this mainly happened in the first cycle . In each group , ovulation was achieved in 14 cycles , intrauterine insemination was performed , and five pregnancies were obtained . This result ed in a pregnancy rate of 36 % per ovulatory cycle in both groups . Overall , 50 % of the formerly unreactive patients in both groups overcame childlessness . In achieving this , long-term treatment with GnRH analogues was as successful as laparoscopic laser diathermy OBJECTIVE To compare the effectiveness of laparoscopic ovarian diathermy with gonadotropin ovulation induction for women with clomiphene citrate-resistant polycystic ovary syndrome . DESIGN R and omized controlled trial . SETTING A tertiary referral fertility clinic . PATIENT(S ) Women with anovulatory infertility secondary to clomiphene-resistant polycystic ovary syndrome . Inclusion criteria were age of < 39 years , body mass index of < 35 kg/m(2 ) , failure to ovulate with 150 mg of clomiphene citrate for 5 days in the early follicular phase , > 12 months of infertility , and no other causes of infertility . INTERVENTION(S ) Laparoscopic ovarian diathermy versus three cycles of urinary or recombinant gonadotropins . MAIN OUTCOME MEASURE(S ) Cumulative pregnancy and miscarriage rates . RESULT ( S ) Cumulative pregnancy rates were 28 % at 6 months for laparoscopic ovarian diathermy and 33 % for three cycles of ovulation induction with gonadotropins . There were three miscarriages in each group . Women in the laparoscopic ovarian diathermy arm of the study had four additional spontaneous pregnancies 6 to 12 months after surgery . CONCLUSION ( S ) There was no statistically significant difference in pregnancy or miscarriage rates during the 6-month follow-up period or the three cycles . Laparoscopic ovarian diathermy is a safe and effective alternative to ovulation induction with gonadotropins This prospect i ve observational study aim ed to assess ovarian reserve after three different methods for induction of ovulation in 60 women between 30 and 40 years old with polycystic ovary syndrome . Women were equally divided into three groups . Group I included women who responded to clomiphene citrate . Women enrolled in groups II and III were subjected to either unilateral or bilateral ovarian drilling , respectively . Ovarian reserve testing was performed once before and three months after treatment . Basal serum inhibin B level showed a significant decrease after bilateral drilling compared with predrilling level ( 53.8 ± 13.5 vs 46.3 ± 6.2 pg/mL ; P= 0.031 ) . The antral follicle counts and summed ovarian volume showed a significant decrease after bilateral drilling ( 16.5 ± 1.3 vs 14.9 ± 2.1 ; P= 0.007 and 11.5 ± 1.0 vs 10.3 ± 1.1/mm3 ; P= 0.001 ) . We concluded that diminished ovarian reserve may occur after bilateral ovarian drilling but not after clomiphene citrate induction of ovulation or unilateral drilling Therapeutic approaches to chronic anovulation from polycystic ovaries in clomiphene-resistant infertile patients are under debate . This study discusses evidence that supports the possible predictive value of serum basal level of and rostenedione in the choice of the better therapy between laparoscopic ovarian electrocautery and ovulation induction . Lower and rostenedione levels seem to be correlated with a better ovarian response after ovulation induction with gonadotropins , while high and rostenedione levels are associated with a higher incidence of conception after laparoscopic ovarian electrocautery . Obesity does not seem to represent a hindrance to laparoscopic treatment BACKGROUND Laparoscopic ovarian diathermy and gonadotrophin ovulation induction for women with clomiphene citrate resistant polycystic ovary syndrome have been shown to result in similar pregnancy rates , but their relative cost-effectiveness has not been evaluated . METHODS A cost-minimization study was undertaken alongside a r and omized controlled trial in women with anovulatory infertility secondary to clomiphene resistant polycystic ovary syndrome . Inclusion criteria were age less than 39 years , body mass index less than 35 kg/m(2 ) , failure to ovulate with 150 mg of clomiphene citrate for 5 days in the early follicular phase , more than 12 months of infertility and no other causes of infertility . Laparoscopic ovarian diathermy was compared with three cycles of urinary or recombinant gonadotrophins . Direct and indirect costs were based on the results of a r and omized trial . RESULTS The cost of a live birth was one third lower in the group that underwent laparoscopic ovarian diathermy compared to those women who received gonadotrophins ( 19 640 New Zeal and dollars and 29 836 New Zeal and dollars , respectively ) . CONCLUSIONS This economic evaluation shows that treating women with clomiphene-resistant polycystic ovarian syndrome with laparoscopic ovarian diathermy results in a significant reduction in both direct and indirect costs Laparoscopic ovarian drilling ( LOD ) is the accepted second-line treatment for clomiphene citrate-resistant anovulatory infertility in polycystic ovary syndrome ( PCOS ) . Although multiple pregnancy rates are reduced with ovarian drilling procedures , postoperative adhesion formation is a potential complication in up to 85 % of the women subjected to laparoscopic destructive ovarian procedures . Our objective was to determine the effectiveness of a new , specially design ed laparoscopic device and technique that might enable treatment for patients with anovulatory PCOS with less trauma and fewer postoperative adhesions . Thirty-five infertile clomiphene citrate-resistant women with PCOS were included . Seventeen women underwent laparoscopic ovarian multi-needle intervention ( LOMNI ) , and 18 women received step-up ovulation induction treatment with recombinant follicle-stimulating hormone followed by intrauterine insemination for three cycles . Patients were followed for a period of 6 months after either laparoscopic surgery or the initiation of ovulation induction therapy . Outcome measures were cycle regularity , pregnancy rate , safety , postoperative adhesion formation , and cost effectiveness . There were no significant differences between the two groups in terms of age , body-mass index , duration of infertility , and basal cycle-day 2 hormone levels . Significant improvement in cycle regularity ( p < .01 ) was found after LOMNI . Cumulative pregnancy rates ( 35.3 % in the LOMNI group vs 33.3 % in the ovulation induction group ) did not differ between the groups . No adverse events following surgery were noted . Moderate ovarian hyperstimulation syndrome and multiple pregnancies occurred in four and two patients , respectively , in the ovulation induction group . Eight nonpregnant women in the LOMNI group underwent repeat laparoscopy at the end of the follow-up period . No adhesion formation attributable to LOMNI was observed in any of those eight women . The cost of LOMNI was significantly ( p < .001 ) lower than the ovulation induction treatment . In conclusion , LOMNI may be a safe , inexpensive , and effective procedure for the treatment of CC-resistant infertility in patients with PCOS . It seems to preserve the beneficial effects and probably omits unwanted effects ( such as adhesion formation ) of LOD Transvaginal hydrolaparoscopic ovarian drilling ( THLOD ) appears to be an effective minimally invasive procedure to induce ovulation in women with polycystic ovary syndrome ( PCOS ) . Postoperative endocrinological alterations following THLOD show significant decrease of serum LH and testosterone concentrations |
1,823 | 25,956,217 | The findings differ but , overall , do not provide evidence that patients with OPMDs have a poorer QoL compared with healthy patients . | There is a paucity of literature on quality of life ( QoL ) in patients with oral potentially malignant disorders ( OPMDs ) despite these conditions being relatively common , chronic , and potentially debilitating .
The aim of this paper is to systematic ally review the literature on QoL in patients with OPMDs . | BACKGROUND Symptomatic oral lichen planus ( OLP ) has been palliated with a wide spectrum of topical and systemic therapies . Although the majority of management strategies include corticosteroids , few have been evaluated in r and omized controlled trials . OBJECTIVE We investigated the acceptability and efficacy of topical fluticasone propionate spray ( FP ) and betamethasone sodium phosphate mouthrinse ( BSP ) upon the signs and symptoms of OLP , assessing patient quality of life changes as a consequence of these therapies . METHODS We implemented a r and omized , crossover study in which each drug was administered for a period of 6 weeks with an intervening washout period of 2 weeks at an outpatient oral medicine unit in London , United Kingdom . We treated 48 patients with biopsy-proven symptomatic OLP , and 44 patients ( 92 % ) completed the study . The dosage was 50 microg two dose unit sprays and BSP 500 microg , each 4 times daily . Symptomatic improvement was evaluated by means of a visual analogue scale ( VAS ) , the McGill pain score , the Oral Health Impact Profile ( OHIP ) , and Oral Health Quality of Life ( OHQoL ) question naires . The total surface area of the lesions , including all white , erythematous , and ulcerative lesions was measured at each visit . The efficacy , ease of application , and adverse effects associated with each medication were recorded . RESULTS Both FP and BSP mouthwash caused both a statistically significant reduction in painful symptoms as measured by the VAS and improvement in quality of life as measured by the OHIP and OHoQL indices . There was no significant difference between the two corticosteroids in their efficacy in reducing painful symptoms ( measured by the VAS ) or in their effect on patient quality of life . Both FP and BSP significantly reduced the surface area of oral lesions . However , FP was statistically significantly better than BSP in reducing lesion surface area . There was no statistically significant difference between the patient-assessed effects of the 2 therapies . CONCLUSIONS FP and BSP are both effective in the short-term clinical management of symptomatic OLP . FP is more acceptable to patients than BSP because of the convenience of the spray form OBJECTIVE Our purpose was to investigate the efficacy and safety of 0.1 % topical tacrolimus in erosive or ulcerative oral lichen planus . METHODS This was an open-label , noncomparative study conducted in an outpatient oral medicine unit in London , United Kingdom . The study covered an 8-week period with a 22-week follow-up after cessation of therapy . Nineteen patients , aged 28 to 87 years with biopsy-proven oral lichen planus refractory to , or dependent on , systemic immunosuppressive agents , were enrolled . Seventeen patients ( 89 % ) completed the study . Application of 0.1 % tacrolimus was administered to all symptomatic oral mucosal lesions . Clinical review took place 1 , 3 , 5 , 7 , and 8 weeks after commencing therapy . Alleviation of symptoms was evaluated by using a visual analogue scale as well as the McGill Pain and Oral Health Impact profile question naires . The extent of the oral mucosal erosion or ulceration was directly measured by the same clinician at all visits . Safety assessment s included monitoring of adverse events , complete blood cell count , renal and hepatic clinical chemistry , and tacrolimus blood concentrations . RESULTS Tacrolimus caused a statistically significant improvement in symptoms within 1 week of commencement of therapy . A mean decrease of 73.3 % occurred in the area of ulceration over the 8-week study period . Local irritation ( in 6 subjects , 35 % ) was the most commonly reported adverse effect . Laboratory values showed no significant changes with time . Therapeutic levels of tacrolimus were demonstrated in 8 subjects but were unrelated to the extent of oral mucosal involvement . Thirteen of 17 patients suffered a relapse of oral lichen planus within 2 to 15 weeks of cessation of tacrolimus therapy . CONCLUSION Topical tacrolimus is effective therapy for erosive or ulcerative oral lichen planus Background Economic evaluations to inform decisions about allocation of health re sources are scarce in Low and Middle Income Countries , including in Sri Lanka . This is in part due to a lack of country-specific utility weights , which are necessary to derive appropriate Quality Adjusted Life Years . The EQ-5D-3L , a generic multi-attribute instrument ( MAUI ) , is most widely used to measure and value health states in high income countries ; nevertheless , the sensitivity of generic MAUIs has been criticised in some conditions such as cancer . This article describes a protocol to produce both a generic EQ-5D-3L and cancer specific EORTC-8D utility index in Sri Lanka . Method EQ-5D-3L and EORTC-8D health states will be valued using the Time Trade-Off technique , by a representative population sample ( n = 780 invited ) identified using stratified multi-stage cluster sampling with probability proportionate to size method . Households will be r and omly selected within 30 clusters across four districts ; one adult ( ≥18 years ) within each household will be selected using the Kish grid method . Data will be collected via face-to-face interview , with a Time Trade-Off board employed as a visual aid . Of the 243 EQ-5D-3L and 81,290 EORTC-8D health states , 196 and 84 respectively will be directly valued . In EQ-5D-3L , all health states that combine level 3 on mobility with either level 1 on usual activities or self-care were excluded . Each participant will first complete the EQ-5D-3L , rank and value 14 EQ-5D-3L states ( plus the worst health state and “ immediate death ” ) , and then rank and value seven EORTC-8D states ( plus “ immediate death ” ) . Participant demographic and health characteristics will be also collected . Regression models will be fitted to estimate utility indices for EQ-5D-3L and EORTC-8D health states for Sri Lanka . The dependent variable will be the utility value . Different specifications of independent variables will be derived from the ordinal EQ-5D-3L to test for the best-fitting model . Discussion In Sri Lanka , a LMIC health state valuation will have to be carried out using face to face interview instead of online methods . The proposed study will provide the first country-specific health state valuations for Sri Lanka , and one of the first valuations to be completed in a South Asian Country UNLABELLED Implant overdentures and conventional prostheses have been compared in several trials using a variety of functional and oral health-related quality of life ( OHQOL ) outcomes . In this paper , we describe the impact of implant overdentures on general and OHQOL in seniors . OBJECTIVES To compare the oral health-related and general quality of life of seniors ( aged 65 - 75 years ) who received either m and ibular implant overdentures or conventional dentures . METHODS Sixty edentulous patients were recruited . Thirty received m and ibular overdentures retained by two implants ( IOD ) and a conventional maxillary denture , the other 30 subjects received new maxillary and m and ibular conventional complete dentures ( CD ) . All completed the 20-item version of the Oral Health Impact Profile ( OHIP-20 ) before treatment , then at two and 6 months after delivery of the dentures . The SF-36 general health question naire was completed at baseline and 6 months only . RESULTS Pretreatment and 6-month data from 55 subjects were analyzed . Those who received the IODs had significantly better OHIP-20 total scores at 6 months . Results for IOD subjects were also superior in the functional limitation , physical pain , physical disability and psychological disability subscales . While no significant between group difference was found on the SF-36 health survey , significant pre-post-treatment differences within the IOD group were detected for the role emotional , vitality and the social function scales . CONCLUSIONS M and ibular overdentures retained by two implants provide elderly patients with better OHQOL . General health-related quality of life improved in the implant group BACKGROUND Lichen planus is a common chronic inflammatory mucocutaneous disease , affecting 0.1 % to 4 % of the general population . There is no published r and omized active control clinical trial on pimecrolimus for the treatment of oral lichen planus ( OLP ) . OBJECTIVE The purpose of this study was to compare the efficacy and safety of pimecrolimus 1 % cream with triamcinolone acetonide 0.1 % paste in treating OLP . METHODS In this investigator-blinded parallel-group r and omized clinical trial , 40 patients were r and omly assigned in two equal groups to receive either pimecrolimus 1 % cream or triamcinolone acetonide 0.1 % paste 4 times daily for a total of 2 months and followed up for another 2 months . The patients were assessed for painful symptoms measured by visual analog scale , the Oral Health Impact Profile score , and objective clinical score . Nonparametric tests were used to assess the main outcomes . Intention-to-treat analysis was used . RESULTS Eighteen patients in pimecrolimus group and 17 patients in triamcinolone group finished the 4-month trial course . Both pimecrolimus and triamcinolone groups showed significant improvement in all measured efficacy end points throughout the visits . There was no significant difference between changes from baseline median values of pimecrolimus and triamcinolone groups after treatment termination in terms of visual analog scale score ( -9.8 + /- 11.3 vs -8.4 + /- 18.3 , P = .70 ) , Oral Health Impact Profile score ( -1.5 + /- 2.6 vs -1.6 + /- 2.1 , P = .38 ) , and clinical score ( -0.7 + /- 0.6 vs -0.8 + /- 0.7 , P = .86 ) , respectively . Two patients in pimecrolimus group experienced prominent but transient burning sensation whereas none of the patients in triamcinolone group had any prominent adverse event ( P = .24 ) . LIMITATIONS Blood levels in pimecrolimus group were not measured and carcinogenicity of pimecrolimus , especially in its long-term use for OLP , is yet to be determined . CONCLUSION This study showed that patients with OLP may benefit from both topical pimecrolimus and triamcinolone acetonide therapy with minimal side effects . Further studies should be conducted to assess the maintenance effects and long-term safety of both drugs ( Cochrane skin group identifier : CSG TrialNo . 22 ) Background : Dermatologists see patients with oral mucosal conditions . Objectives : To evaluate oral health-related quality of life ( OHRQoL ) and the burden of disease of dermatological patients with oral mucosal diseases . Methods : All consecutive patients ( April 2005 to November 2006 ) coming to the oral health care unit of the IDI-IRCCS in Rome were asked to complete oral health-specific ( 14-item Oral Health Impact Profile , OHIP-14 ) , generic health status ( 12-item Short Form of Medical Outcome Study , SF-12 ) and general psychological ( 12-item General Health Question naire , GHQ-12 ) question naires . Physicians and patients gave a global assessment of severity of disease on a 5-point scale . Results : 206 patients participated . Recurrent aphthous stomatitis ( RAS ) had the highest impact on OHRQoL. Women had poorer OHRQoL both on physical and mental scales of the SF-12 . 33.7 % of patients were GHQ-positive with women showing a much higher prevalence than men ( 39.7 vs. 20.3 % ) . OHIP-14 high scores were observed in RAS , followed by oral lichen planus and burning mouth syndrome . Patients whose condition was ‘ underestimated ’ by the physicians had the worst OHRQoL and psychological status . Conclusions : Administration of specific and generic question naires provides a detailed picture of the impact of oral diseases on patients , which adds information that may be useful in clinical practice . The possible contribution of such tools should be assessed in a r and omized controlled trial The aim of this study was to describe prospect ively quality of life and mood in patients with oral or oropharyngeal cancer treated with surgery + /- radiotherapy . Seventy-five patients completed the EORTC Core Question naire , the EORTC Head and Neck Cancer module and the Center for Epidemiologic Studies ' Depression Scale before treatment and 6 and 12 months later . There was a significant deterioration of physical functioning , fatigue and almost all head and neck symptoms except pain , which improved . Patients with stage III/IV and patients receiving combined treatment had significantly worse physical symptoms compared to patients with stage I/II and patients treated with surgery only , respectively . Before and after treatment there was a high level of depressive symptomatology . However , after treatment a gradual improvement in emotional functioning occurred . Surgical treatment for oral or oropharyngeal cancer results in significant deterioration of physical functioning and symptoms during the first year , especially when combined with radiotherapy . Despite this , there is an improvement of emotional functioning after treatment , probably as a result of adaptation and coping processes OBJECTIVE To test the reliability and responsiveness of the Chronic Oral Mucosal Diseases Question naire ( COMDQ ) , in measuring the quality of life ( QofL ) in patients with chronic oral mucosal conditions . METHODS A r and om sample of 160 patients with the following chronic oral mucosal conditions , recurrent aphthous stomatitis , oral lichen planus , the more common vesiculobullous conditions ( mucous membrane pemphigoid and pemphigus vulgaris ) and orofacial granulomatosis received a copy of the COMDQ . A subset of 100 patients received the question naire on two further occasions , 2 weeks and 3 months later . Statistical tests were carried out to evaluate the test-retest reliability and responsiveness of this instrument . RESULTS This study has demonstrated that the COMDQ has good test-retest reliability with an intraclass correlation coefficient of 0.81 and is responsive to changes in the patients ' overall conditions . CONCLUSION In conclusion , this study has further demonstrated the reliability and responsiveness of the COMDQ in assessing QofL in patients with chronic oral mucosal diseases The aim of this study was to evaluate the sensitivity of two patient-centred outcome measures to the topical application of a corticosteroid ( betamethasone ) in the treatment of oral lichen planus ( OLP ) . Forty-eight patients with clinical and histological features of OLP were recruited to take part in a 6-week study of the effectiveness of topical betamethasone for the treatment of symptomatic OLP . Participants completed a question naire incorporating the 16-item UK Oral Health Related Quality Of Life measure ( OHQOL ) and the 14-item Oral Health Impact Profile ( OHIP-14 ) , rated their pain on ' global ' and visual analogue scales ( VAS ) and underwent an oral examination , at the start and end of the trial . Four ( 8\% ) patients failed to complete the study . The clinical signs of OLP had improved for half ( 22 ) of the patients following treatment . Twenty-nine ( 66 % ) reported that their oral pain had reduced ( ' global ' scale ) . More objective ly , there were significant differences in VAS ratings of pain ( P = 0.005 ) , OHIP-14 scores ( P = 0.036 ) and OHQOL scores ( P = 0.003 ) between the start and end of the trial . In conclusion , both OHQOL and OHIP-14 , patient-centred outcome measures are sensitive to the clinical effects of topical betamethasone in the treatment of oral lichen planus INTRODUCTION The aims of this study were to test the validity and reliability of a newly developed discipline-specific question naire , the Chronic Oral Mucosal Diseases Question naire ( COMDQ ) , to measure quality of life in patients with chronic oral mucosal conditions . MATERIAL S AND METHODS Two patient sample s were recruited for the purpose s of this study . First , a r and om sample of 160 patients attending the Oral Medicine Unit of Cork University Dental School and Hospital with the following chronic oral mucosal conditions , recurrent aphthous stomatitis , oral lichen planus , the more common vesiculobullous conditions ( mucous membrane pemphigoid and pemphigus vulgaris ) and orofacial granulomatosis . Second , the COMDQ was r and omly distributed to a sample of 100 patients without a chronic oral mucosal condition . Convergent and discriminative validity and internal consistency of the newly developed question naire were assessed . RESULTS This study has demonstrated that the newly developed question naire has good convergent validity with Pearson correlation coefficient of 0.819 with Oral Health Impact Profile-14 and 0.883 with Visual Analogue Scale for pain scores . The discriminative validity was also good with statistically significant differences between patients with chronic oral mucosal conditions and without chronic oral mucosal conditions . The new instrument has also demonstrated excellent reliability with Cronbach 's alpha of 0.929 . CONCLUSIONS In conclusion , this study has demonstrated that the COMDQ is a valid and reliable measure to assess quality of life in patients with chronic oral mucosal diseases and therefore will be a valuable instrument in the management of these conditions |
1,824 | 24,694,015 | There is a positive association between MI primary stability and CtTh of the receptor site . | OBJECTIVE To investigate whether there is evidence to support the association between cortical thickness ( CtTh ) and the primary stability of mini-implants ( MI ) . | PURPOSE The aim of this prospect i ve clinical study was to assess the risk factors associated with failure of mini-implants used for orthodontic anchorage . MATERIAL S AND METHODS A total of 140 mini-implants in 44 patients , including 48 miniplates and 92 freest and ing miniscrews , were examined in the study . A variety of orthodontic loads were applied . The majority of implants were placed in the posterior maxilla ( 104/140 ) , and the next most common location was the posterior m and ible ( 34/140 ) . RESULTS A cumulative survival rate of 89 % ( 125/140 ) was found by Kaplan-Meier analysis . There was no significant difference in the survival rate between miniplates and freest and ing miniscrews , but miniplates were used in more hazardous situations . The Cox proportional-hazards regression model identified anatomic location and peri-implant soft tissue character as 2 independent prognostic indicators . The estimated relative risk of implant failure in the posterior m and ible was 1.101 ( 95 % confidence interval , 0.942 to 1.301 ; P = .046 ) . The risk ratio of failure for implants surrounded by nonkeratinized mucosa was 1.117 ( 95 % confidence interval , 0.899 to 1.405 ; P = .026 ) . DISCUSSION AND CONCLUSION The results confirmed the effectiveness of orthodontic mini-implants , but in certain situations adjustment of the treatment plan or modifications in the technique of implant placement may lead to improved success rates INTRODUCTION The purpose of this study was to determine the success rate , positional stability , and patient evaluation of orthodontic mini-implants ( OMIs ) . METHODS Thirteen patients ( 8 girls , 5 boys ; average age , 14 years 10 months ) were treated with 82 OMIs measuring 1.6 mm in diameter and 6 mm in length placed in the buccal alveoli ( 1 unloaded OMI and 1 loaded OMI per quadrant ) . The right or left side of each arch was r and omly selected for immediate loading with up to 250 g of direct force ; the contralateral side was loaded 3 to 5 weeks later . Serial impressions , clinical observations , and orthodontic maintenance were performed until adequate space closure was achieved . RESULTS The overall OMI success rate was 70.73 % . As calculated with a mixed-model analysis , there was no statistically significant difference between the success rates of immediately loaded OMIs ( 80.0 % ) and delayed loaded OMIs ( 80.95 % ) . The combined success rate for loaded OMIs ( 80.49 % ) was significantly higher than that of unloaded OMIs ( 60.98 % ) . Patients ' motivation for OMI treatment was primarily the desire to avoid headgear . Using a 100-mm visual analog scale , the patients indicated average scores of 54.77 for the amount of pain during OMI placement and 27.10 for the amount of pain during OMI removal . CONCLUSIONS OMIs are a predictable , effective , and well-tolerated anchorage source for adolescents . Neither the timing of force application nor the force itself precipitated failure of the OMIs . Orthodontic forces can be applied immediately to OMIs . Various anatomic and behavioral conditions unique to adolescents and a clinical learning curve can affect the success rate of OMIs AIM The purpose of this investigation was to determine and compare the accuracy of four available mechanical torque-limiting gauges ( MTLGs ) for mini-screw placement . MATERIAL S AND METHODS The torque outputs of six r and omly obtained MTLGs , either of the screwdriver or torque ratchet type of four mini-screw manufacturers were obtained . Mounted on a joint , a universal testing machine applied perpendicular force to a lever arm with a crosshead speed of 1 mm/min . For each device , 10 repetitions of the corresponding target torque level were recorded after initial sterilisation ( 1 ) and after 5 , 10 , 20 , 50 and 100 times to evaluate its potential influence on MTLGs . The breakpoints ( N cm ) were calculated for comparison of the groups . Descriptive statistics and mean breakpoints values for each MTLG computed and compared with the reference values indicated on the respective torque gauges provided by the producer . RESULTS The mean torque values for the AbsoAnchor MTLG devices were significantly below torque levels , but provide consistent torque values . All but one obtained values for the Spider Screw , MTLG of the screw driver type , were within the indicated moment range during the first 50-times of sterilization process . But after 100-times of steam sterilization all mean breakpoint values were relevantly higher than the indicated torque range values . Each individual MTLG produced independently constant breakpoint torque values , but differed significantly from each other . For all but the Spider Screw MTLG , the sterilisation process had a statistically significant different influence at the various breakpoint torque levels . CONCLUSION After application of the manufacturers ' preset torque levels , significant variations were observed between individual devices . The torque output of each individual device deviated in varying degrees from target torque values and was influenced by various degrees by the sterilisation process over time |
1,825 | 25,601,394 | Results Results indicate that hypertrophic outcomes are similar when training with repetition duration s ranging from 0.5 to 8 s. Conclusions From a practical st and point it would seem that a fairly wide range of repetition duration s can be employed if the primary goal is to maximize muscle growth . | Background Maximizing the hypertrophic response to resistance training ( RT ) is thought to be best achieved by proper manipulation of exercise program variables including exercise selection , exercise order , length of rest intervals , intensity of maximal load , and training volume .
An often overlooked variable that also may impact muscle growth is repetition duration .
Duration amounts to the sum total of the concentric , eccentric , and isometric components of a repetition , and is predicated on the tempo at which the repetition is performed .
Objective We conducted a systematic review and meta- analysis to determine whether alterations in repetition duration can amplify the hypertrophic response to RT . | The purpose of this study was to examine the effect of isokinetic eccentric ( ECC ) and concentric ( CON ) training at two velocities [ fast , 180 ° s−1 ( 3.14 rad s−1 ) and slow,30 ° s−1(0.52 rad s−1 ) ] on muscle hypertrophy . Twenty-four untrained volunteers ( age 18–36 years ) participated in fast- ( n=13 ) or slow- ( n=11 ) velocity training , where they trained one arm eccentrically for 8 weeks followed by CON training of the opposite arm for 8 weeks . Ten subjects served as controls ( CNT ) . Subjects were tested before and after training for elbow flexor muscle thickness by sonography and isokinetic strength ( Biodex ) . Overall , ECC training result ed in greater hypertrophy than CON training ( P<0.01 ) . No significant strength or hypertrophy changes occurred in the CNT group . ECC ( 180 ° s−1 ) training result ed in greater hypertrophy than CON ( 180 ° s−1 ) training and CON ( 30 ° s−1 ) training ( P<0.01 ) . ECC ( 30 ° s−1 ) training result ed in greater hypertrophy than CON ( 180 ° s−1 ) training ( P<0.05 ) , but not CON ( 30 ° s−1 ) training . ECC ( 180 ° s−1 ) training result ed in the greatest increases in strength ( P<0.01 ) . We conclude that ECC fast training is the most effective for muscle hypertrophy and strength gain 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 Ten healthy young men ( 21.0 + /- 1.5 yr , 1.79 + /- 0.1 m , 82.7 + /- 14.7 kg , means + /- SD ) participated in 8 wk of intense unilateral resistance training ( knee extension exercise ) such that one leg was trained ( T ) and the other acted as an untrained ( UT ) control . After the 8 wk of unilateral training , infusions of L-[ring-d(5)]phenylalanine , L-[ring-(13)C(6)]phenylalanine , and d(3)-alpha-ketoisocaproic acid were used to measure mixed muscle protein synthesis in the T and UT legs by the direct incorporation method [ fractional synthetic rate ( FSR ) ] . Protein synthesis was determined at rest as well as 4 h and 28 h after an acute bout of resistance exercise performed at the same intensity relative to the gain in single repetition maximum before and after training . Training increased mean muscle fiber cross-sectional area only in the T leg ( type I : 16 + /- 10 % ; type II : 20 + /- 19 % , P < 0.05 ) . Acute resistance exercise increased muscle protein FSR in both legs at 4 h ( T : 162 + /- 76 % ; UT : 108 + /- 62 % , P < 0.01 vs. rest ) with the increase in the T leg being significantly higher than in the UT leg at this time ( P < 0.01 ) . At 28 h postexercise , FSR in the T leg had returned to resting levels ; however , the rate of protein synthesis in the UT leg remained elevated above resting ( 70 + /- 49 % , P < 0.01 ) . We conclude that resistance training attenuates the protein synthetic response to acute resistance exercise , despite higher initial increases in FSR , by shortening the duration for which protein synthesis is elevated The authors investigated the effects of low-intensity resistance training on muscle size and strength in older men and women . Thirty-five participants ( age 59 - 76 yr ) were r and omly assigned to 2 groups and performed low-intensity ( 50 % of 1-repetition maximum ) knee-extension and -flexion exercises with either slow movement and tonic force generation ( LST ; 3-s eccentric , 3-s concentric , and 1-s isometric actions with no rest between repetitions ) or normal speed ( LN ; 1-s concentric and 1-s eccentric actions with 1-s rests between repetitions ) twice a week for 12 wk ( 2-wk preparation and 10-wk intervention ) . The LST significantly increased thigh-muscle thickness , as well as isometric knee-extension and -flexion strength . The LN significantly improved strength , but its hypertrophic effect was limited . These results indicate that even for older individuals , the LST can be an effective method for gaining muscle mass and strength 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 A two-arm , prospect i ve , r and omized , controlled trial study was conducted to investigate the effects of movement velocity during progressive resistance training ( PRT ) on the size and contractile properties of individual fibers from human vastus lateralis muscles . The effects of age and sex were examined by a design that included 63 subjects organized into four groups : young ( 20 - 30 yr ) men and women , and older ( 65 - 80 yr ) men and women . In each group , one-half of the subjects underwent a traditional PRT protocol that involved shortening contractions at low velocities against high loads , while the other half performed a modified PRT protocol that involved contractions at 3.5 times higher velocity against reduced loads . Muscles were sample d by needle biopsy before and after the 14-wk PRT program , and functional tests were performed on permeabilized individual fiber segments isolated from the biopsies . We tested the hypothesis that , compared with low-velocity PRT , high-velocity PRT results in a greater increase in the cross-sectional area , force , and power of type 2 fibers . Both types of PRT increased the cross-sectional area , force , and power of type 2 fibers by 8 - 12 % , independent of the sex or age of the subject . Contrary to our hypothesis , the velocity at which the PRT was performed did not affect the fiber-level outcomes substantially . We conclude that , compared with low-velocity PRT , resistance training performed at velocities up to 3.5 times higher against reduced loads is equally effective for eliciting an adaptive response in type 2 fibers from human skeletal muscle PURPOSE To compare effects on strength in the early phase of resistance training with one or three sets and fast or slow speeds . METHODS A total of 115 healthy , untrained subjects were r and omized to a control group or one of four training groups : one set fast ( approximately 140 degrees.s(-1 ) ) , three sets fast , one set slow ( approximately 50 degrees.s(-1 ) ) , or three sets slow . All subjects attended training 3 x wk(-1 ) for 6 wk . Subjects in the training groups performed unilateral elbow flexion contractions with a target six- to eight-repetition maximum load . Control subjects sat at the training bench but did not train . One repetition maximum strength , arm circumference , and biceps skinfold thickness were measured before and after training . RESULTS One slow set increased strength by 25 % ( 95 % CI 13 - 36 % , P < 0.001 ) . Three sets of training produced greater increases in strength than one set ( difference = 23 % of initial strength , 95 % CI 12 - 34 % , P < 0.001 ) and fast training result ed in a greater increase in strength than slow training ( difference = 11 % , 95 % CI 0.2 - 23 % , P = 0.046 ) . The interaction between sets and speed was negative ( -15 % ) and of borderline significance ( P = 0.052 ) , suggesting there is a benefit of training with three sets or fast speeds , but there is not an additive benefit of training with both . CONCLUSIONS Three sets of exercise produce twice the strength increase of one set in the early phase of resistance training . Training fast produces greater strength increases than training slow ; however , there does not appear to be any additional benefit of training with both three sets and fast contractions We previously reported that low‐intensity [ 50 % of one repetition maximum ( 1RM ) ] resistance training with slow movement and tonic force generation ( LST ) causes muscle hypertrophy and strength gain in older participants . The aim of this study was to determine whether resistance training with slow movement and much more reduced intensity ( 30%1RM ) increases muscle size and strength in older adults . Eighteen participants ( 60–77 years ) were r and omly assigned to two groups . One group performed very low‐intensity ( 30 % 1RM ) knee extension exercise with continuous muscle contraction ( LST : 3‐s eccentric , 3‐s concentric , and 1‐s isometric actions with no rest between each repetition ) twice a week for 12 weeks . The other group underwent intermitted muscle contraction ( CON : 1‐s concentric and 1‐s eccentric actions with 1‐s rest between each repetition ) for the same time period . The 1RM , isometric and isokinetic strengths , and cross‐sectional image of the mid‐thigh obtained by magnetic resonance imaging were examined before and after the intervention . LST significantly increased the cross‐sectional area of the quadriceps muscle ( 5·0 % , P<0·001 ) and isometric and isokinetic knee extension strengths ( P<0·05 ) . CON failed to increase muscle size ( 1·1 % , P = 0·12 ) , but significantly improved its strength ( P<0·05 ) . These results indicate that even if the intensity is as low as 30 % 1RM , LST can increase muscle size and strength in healthy older adults . The large total contraction time may be related to muscle hypertrophy and strength gain . LST would be useful for preventing sarcopenia in older individuals The purpose of this study was to investigate the effects of a six-week ( 16 - 17 training sessions ) low velocity resistance training program ( LV ) on various performance measures as compared to a traditional strength ( TS ) and a traditional muscular endurance ( TE ) resistance training program . Thirty-four healthy adult females ( 21.1 ± 2.7 y ) were r and omly divided into 4 groups : control ( C ) , TS , TE , and LV . Workouts consisted of 3 exercises : leg press ( LP ) , back squat ( SQ ) , and knee extension ( KE ) . Each subject was pre- and posttested for 1 repetition maximum ( 1RM ) , muscular endurance , maximal oxygen consumption ( VO2max ) , muscular power , and body composition . After the pretesting , TS , TE , and LV groups attended a minimum of 16 out of 17 training sessions in which the LP , SQ , and KE were performed to fatigue for each of 3 sets . For each training session , TS trained at 6 - 10 RM and TE trained at 20 - 30 RM both with 1 - 2 second concentric/1 - 2 second eccentric ; and LV trained at 6 - 10 RM , with 10 second concentric/4 s eccentric . Statistical significance was determined at an alpha level of 0.05 . LV increased relative LP and KE 1 RM , but the percent increase was smaller than TS , and not different from C in the SQ . For muscular endurance , LV improved similarly to TE for LP and less than TS and TE for KE . Body composition improved for all groups including C ( significant main effect ) . In conclusion , muscular strength improved with LV training however , TS showed a larger improvement . Muscular endurance improved with LV training , but not above what TE or TS demonstrated . For all other variables , there were no significant improvements for LV beyond what C demonstrated We performed a r and omized exercise training study to assess the effects of traditional Nautilus-style ( TR ) or superslow ( SS ) strength training on muscular strength , body composition , aerobic capacity , and cardiovascular endurance . Subjects were 14 healthy , sedentary women , 19–45 years of age ( mean ± SD age , 32.7 ± 8.9 years ) , r and omized to either the SS or TR training protocol s and trained 3 times per week for 10 weeks . Measurements were taken both before and after training , which included a maximal incremental exercise test on a cycle ergometer , body composition , and 1 repetition maximum ( 1RM ) tests on 8 Nautilus machines . Both groups increased their strength significantly on all 8 exercises , whereas the TR group increased significantly more than the SS group on bench press ( 34 % vs. 11 % ) , torso arm ( anterior lateral pull-down ) ( 27 % vs. 12 % ) , leg press ( 33 % vs. 7 % ) , leg extension ( 56 % vs. 24 % ) , and leg curl ( 40 % vs. 15 % ) . Thus , the TR group 's improvement in total exercise weight lifted was significantly greater than that of the SS group after testing ( 39 % vs. 15 % ) . Exercise duration on the cycle ergometer and work rate significantly improved for both groups , but there was no group-by-training interaction . No significant differences were found for body composition or additional aerobic variables measured . Both strength training protocol s produced a significant improvement in strength during a 10-week training period , but the TR protocol produced better gains in the absence of changes in percentage of body fat , body mass index , lean body mass , and body weight . In addition , strength training alone did not improve Vo2max , yet short-term endurance increased |
1,826 | 29,195,594 | Mean follow-up time : 43 ( 8 - 104 ) weeks with a mean of 6 ( 2 - 18 ) research assessment s. Neither planned weeks , duration of sessions , frequency of sessions per week , nor actual attended sessions were associated with long-term alcohol use outcomes .
However , frequency of research assessment s was positively associated with PDA and PHD .
CONCLUSION No associations between long-term alcohol use outcomes and planned or actual attended duration of psychosocial treatment in outpatient care .
Research assessment s and , accordingly , the research project in itself may influence outcome in studies of psychosocial treatment for alcohol use disorder | BACKGROUND The recommendations in clinical guidelines for duration of therapy for alcohol use disorder ( AUD ) are based on consensus decisions .
In reality , we do not know the optimal duration of an alcohol treatment course . | Although negative affect is a common precipitant of alcohol relapse , there are few interventions for alcohol dependence that specifically target negative affect . In this stage 1a/1b treatment development study , several affect regulation strategies ( e.g. , mindfulness , prolonged exposure , distress tolerance ) were combined to create a new treatment supplement called affect regulation training ( ART ) , which could be added to enhance cognitive-behavioral therapy ( CBT ) for alcohol dependence . A draft therapy manual was given to therapists and treatment experts before being administered to several patients who also provided input . After two rounds of manual development ( stage 1a ) , a pilot r and omized clinical trial ( N=77 ) of alcohol-dependent out patients who reported drinking often in negative affect situations was conducted ( stage 1b ) . Participants received 12-weekly , 90-minute sessions of either CBT for alcohol dependence plus ART ( CBT+ART ) or CBT plus a healthy lifestyles control condition ( CBT+HLS ) . Baseline , end-of-treatment , and 3- and 6-month posttreatment interviews were conducted . For both treatment conditions , participant ratings of treatment satisfaction were high , with CBT+ART rated significantly higher . Drinking outcome results indicated greater reductions in alcohol use for CBT+ART when compared to CBT+HLS , with moderate effect sizes for percent days abstinent , drinks per day , drinks per drinking day , and percent heavy drinking days . Overall , findings support further research on affect regulation interventions for negative affect drinkers AIMS Acamprosate in combination with psychosocial treatment has been shown to be effective for the treatment of alcohol dependence . The goal of the present study was to determine whether the addition of psychosocial intervention to the medical prescription of acamprosate contributes to treatment outcome . METHODS Patients ( n = 248 ) meeting DSM-IV criteria for alcohol dependence or abuse were recruited in 14 outpatient treatment centres and r and omized into one of three treatment conditions : acamprosate ; acamprosate plus minimal intervention aim ed at motivational enhancement ( 3-weekly sessions of 20 min ) ; and acamprosate plus brief cognitive behavioural therapy ( 7-weekly sessions of 60 min ) . Acamprosate was prescribed for 28 weeks , medically monitored by a physician on six occasions lasting 10 min . Drinking behaviour , medication compliance and psychological distress were assessed throughout the treatment period . Follow-up assessment was undertaken 6 months after termination of pharmacological treatment . RESULTS Of 241 patients with intention to treat ( ITT ) , 114 ( 47.3 % ) remained in treatment for the full 28 weeks ; 169 of the ITT population ( 70.1 % ) were seen for follow-up . No statistically significant differences were found between treatment groups for any of the drinking outcomes either at the end of the 28 weeks of treatment or at 6-month follow-up . There were no statistically significant differences in medication compliance , drop-out rates , or psychological distress . However , a significant interaction effect was observed between treatment centre and treatment group , indicating that brief interventions were differentially effective in different treatment centres . CONCLUSIONS A clear supplemental value of minimal and brief psychosocial interventions to the prescription of acamprosate was not demonstrated . The widely held belief that pharmacotherapy for alcohol dependence should always be combined with psychosocial intervention is debatable and merits further research BACKGROUND This study evaluated the serotonergic antidepressant nefazodone versus placebo and specific cognitive-behavioral therapy ( CBT ) versus nondirective group counseling ( GC ) for relapse prevention in alcohol dependence in a large prospect i ve , r and omized , and placebo-controlled double-blind study at 3 German university centers . METHOD 242 male patients fulfilling at least 5 criteria for alcohol dependence according to DSM-IV and ICD-10 were eligible , after detoxification , for one of the following treatment combinations : nefazodone + CBT , nefazodone + GC , placebo + CBT , and placebo + GC . Either nefazodone or placebo was administered throughout the evaluation period of 15 months . Either CBT or GC was applied during the first 12 weeks as group therapy according to operationalized manuals . The main outcome measures ( assessed at 3 and 12 months of treatment ) were the cumulative number of abstinent days , the amount of ethanol consumed during specified evaluation periods of 3 and 12 months , the number of relapses , and the duration of time until first relapse . RESULTS After 12 weeks of treatment , no statistically significant differences were observed between the 4 treatment combinations in any outcome measure . After 52 weeks , the only significant difference was observed in the amount of ethanol consumed , with the nefazodone + GC group showing higher alcohol intake than the other 3 groups . CONCLUSIONS The results from this carefully design ed clinical trial suggest that the 4 treatment combinations do not differ substantially in their efficacy for relapse prevention in nondepressed , severely alcohol-dependent patients . Nefazodone might even increase the risk of consuming a larger amount of ethanol per relapse in a subset of patients . CBT as performed in this study was associated with little additional benefit compared with structured GC Summary The comparative effects of alcoholism treatment programmes were examined by r and omly assigning 113 male and female detoxified alcoholics to either : a 6-week inpatient programme , a 6-week outpatient programme or a single confrontational interview . On a variety of outcome measures , that included both levels of drinking and general functioning taken 6 and 18 months after intake , no treatment appeared to be consistently more effective than another . Furthermore , those who stayed in treatment did not show significantly more long-term improvement than those who refused or dropped out of treatment . Abstinent subjects felt more often than drinkers that they had achieved the goals they had set themselves and by the final follow-up there were many positive differences in apparent lifestyle . Although individual drinking patterns were unstable , on average , almost half the subjects located had either abstained or were drinking moderately . Patient and treatment variables combined explained up to 57 % of the variance in amount drunk after treatment , with patient variables providing the strongest associations OBJECTIVE This study was design ed to conduct a r and omized controlled trial of motivational enhancement therapy ( MET ) with two control conditions : nondirective reflective listening ( NDRL ) and no further counseling ( NFC ) ; and to conduct this study in a sample of patients with a primary diagnosis of mild to moderate alcohol dependence , in a " real-life " clinical setting . METHOD Patients with mild to moderate alcohol dependence were recruited , assessed and treated at the Community Alcohol and Drug Service of Christchurch , New Zeal and . All patients received a feedback/education session before r and omization to either four sessions of MET , four sessions of NDRL , or NFC . Outcome data on 122 subjects ( 57.4 % men ) were obtained 6 months following the end of treatment , by an interviewer who was blind to the treatment condition . The primary drinking outcome was unequivocal heavy drinking , defined as drinking 10 or more st and ard drinks six or more times in the follow-up period . Global assessment scale ( GAS ) measured general personal/social functioning . RESULTS Of patients treated with MET , 42.9 % showed unequivocal heavy drinking compared with 62.5 % of the NDRL and 65.0 % of the NFC groups ( p = .04 ) . No significant differences were found for GAS score according to treatment condition . CONCLUSIONS In patients with mild to moderate alcohol dependence , MET is more effective for reducing unequivocal heavy drinking than either a feedback/education session alone or four sessions of NDRL . MET can be considered an effective " value added " counseling intervention in a real-life clinical setting . In patients with mild to moderate alcohol dependence , nondirective reflective listening provides no additional advantage over a feedback/education session alone CONTEXT Alcohol dependence treatment may include medications , behavioral therapies , or both . It is unknown how combining these treatments may impact their effectiveness , especially in the context of primary care and other nonspecialty setting s. OBJECTIVES To evaluate the efficacy of medication , behavioral therapies , and their combinations for treatment of alcohol dependence and to evaluate placebo effect on overall outcome . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial conducted January 2001-January 2004 among 1383 recently alcohol-abstinent volunteers ( median age , 44 years ) from 11 US academic sites with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , diagnoses of primary alcohol dependence . INTERVENTIONS Eight groups of patients received medical management with 16 weeks of naltrexone ( 100 mg/d ) or acamprosate ( 3 g/d ) , both , and /or both placebos , with or without a combined behavioral intervention ( CBI ) . A ninth group received CBI only ( no pills ) . Patients were also evaluated for up to 1 year after treatment . MAIN OUTCOME MEASURES Percent days abstinent from alcohol and time to first heavy drinking day . RESULTS All groups showed substantial reduction in drinking . During treatment , patients receiving naltrexone plus medical management ( n = 302 ) , CBI plus medical management and placebos ( n = 305 ) , or both naltrexone and CBI plus medical management ( n = 309 ) had higher percent days abstinent ( 80.6 , 79.2 , and 77.1 , respectively ) than the 75.1 in those receiving placebos and medical management only ( n = 305 ) , a significant naltrexone x behavioral intervention interaction ( P = .009 ) . Naltrexone also reduced risk of a heavy drinking day ( hazard ratio , 0.72 ; 97.5 % CI , 0.53 - 0.98 ; P = .02 ) over time , most evident in those receiving medical management but not CBI . Acamprosate showed no significant effect on drinking vs placebo , either by itself or with any combination of naltrexone , CBI , or both . During treatment , those receiving CBI without pills or medical management ( n = 157 ) had lower percent days abstinent ( 66.6 ) than those receiving placebo plus medical management alone ( n = 153 ) or placebo plus medical management and CBI ( n = 156 ) ( 73.8 and 79.8 , respectively ; P<.001 ) . One year after treatment , these between-group effects were similar but no longer significant . CONCLUSIONS Patients receiving medical management with naltrexone , CBI , or both fared better on drinking outcomes , whereas acamprosate showed no evidence of efficacy , with or without CBI . No combination produced better efficacy than naltrexone or CBI alone in the presence of medical management . Placebo pills and meeting with a health care professional had a positive effect above that of CBI during treatment . Naltrexone with medical management could be delivered in health care setting s , thus serving alcohol-dependent patients who might otherwise not receive treatment . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00006206 OBJECTIVE To assess the benefits of matching alcohol dependent clients to three different treatments with reference to a variety of client attributes . METHODS Two parallel but independent r and omized clinical trials were conducted , one with alcohol dependent clients receiving outpatient therapy ( N = 952 ; 72 % male ) and one with clients receiving aftercare therapy following inpatient or day hospital treatment ( N = 774 ; 80 % male ) . Clients were r and omly assigned to one of three 12-week , manual-guided , individually delivered treatments : Cognitive Behavioral Coping Skills Therapy , Motivational Enhancement Therapy or Twelve-Step Facilitation Therapy . Clients were then monitored over a 1-year posttreatment period . Individual differences in response to treatment were modeled as a latent growth process and evaluated for 10 primary matching variables and 16 contrasts specified a priori . The primary outcome measures were percent days abstinent and drinks per drinking day during the 1-year posttreatment period . RESULTS Clients attended on average two-thirds of treatment sessions offered , indicating that substantial amounts of treatment were delivered , and research follow-up rates exceeded 90 % of living subjects interviewed at the 1-year posttreatment assessment . Significant and sustained improvements in drinking outcomes were achieved from baseline to 1-year posttreatment by the clients assigned to each of these well-defined and individually delivered psychosocial treatments . There was little difference in outcomes by type of treatment . Only one attribute , psychiatric severity , demonstrated a significant attribute by treatment interaction : In the outpatient study , clients low in psychiatric severity had more abstinent days after 12-step facilitation treatment than after cognitive behavioral therapy . Neither treatment was clearly superior for clients with higher levels of psychiatric severity . Two other attributes showed time-dependent matching effects : motivation among out patients and meaning-seeking among aftercare clients . Client attributes of motivational readiness , network support for drinking , alcohol involvement , gender , psychiatric severity and sociopathy were prognostic of drinking outcomes over time . CONCLUSIONS The findings suggest that psychiatric severity should be considered when assigning clients to outpatient therapies . The lack of other robust matching effects suggests that , aside from psychiatric severity , providers need not take these client characteristics into account when triaging clients to one or the other of these three individually delivered treatment approaches , despite their different treatment philosophies AIMS To determine the efficacy of motivational enhancement therapy ( MET ) on alcohol use in patients with the hepatitis C virus ( HCV ) and an alcohol use disorder ( AUD ) . DESIGN R and omized , single-blind , controlled trial comparing MET to a control education condition with 6-month follow-up . SETTING Patients were recruited from hepatitis clinics at the Minneapolis , Minnesota and Portl and , Oregon Veterans Affairs Health Care Systems , USA . PARTICIPANTS AND INTERVENTION Patients with HCV , an AUD and continued alcohol use ( n = 139 ) were r and omized to receive either MET ( n = 70 ) or a control education condition ( n = 69 ) over 3 months . MEASUREMENTS Data were self-reported percentage of days abstinent from alcohol and number of st and ard alcohol drinks per week 6 months after r and omization . FINDINGS At baseline , subjects in MET had 34.98 % days abstinent , which increased to 73.15 % at 6 months compared to 34.63 and 59.49 % for the control condition . Multi-level models examined changes in alcohol consumption between MET and control groups . Results showed a significant increase in percentage of days abstinent overall ( F(1120.4 ) = 28.04 , P < 0.001 ) and a significant group × time effect ( F(1119.9 ) = 5.23 , P = 0.024 ) with the MET group showing a greater increase in percentage of days abstinent at 6 months compared with the education control condition . There were no significant differences between groups for drinks per week . The effect size of the MET intervention was moderate ( 0.45 ) for percentage of days abstinent . CONCLUSION Motivational enhancement therapy ( MET ) appears to increase the percentage of days abstinent in patients with chronic hepatitis C , alcohol use disorders and ongoing alcohol use IMPORTANCE People with substance dependence have health consequences , high health care utilization , and frequent comorbidity but often receive poor- quality care . Chronic care management ( CCM ) has been proposed as an approach to improve care and outcomes . OBJECTIVE To determine whether CCM for alcohol and other drug dependence improves substance use outcomes compared with usual primary care . DESIGN , SETTING , AND PARTICIPANTS The AHEAD study , a r and omized trial conducted among 563 people with alcohol and other drug dependence at a Boston , Massachusetts , hospital-based primary care practice . Participants were recruited from September 2006 to September 2008 from a freest and ing residential detoxification unit and referrals from an urban teaching hospital and advertisements ; 95 % completed 12-month follow-up . INTERVENTIONS Participants were r and omized to receive CCM ( n=282 ) or no CCM ( n=281 ) . Chronic care management included longitudinal care coordinated with a primary care clinician ; motivational enhancement therapy ; relapse prevention counseling ; and on-site medical , addiction , and psychiatric treatment , social work assistance , and referrals ( including mutual help ) . The no CCM ( control ) group received a primary care appointment and a list of treatment re sources including a telephone number to arrange counseling . MAIN OUTCOMES AND MEASURES The primary outcome was self-reported abstinence from opioids , stimulants , or heavy drinking . Biomarkers were secondary outcomes . RESULTS There was no significant difference in abstinence from opioids , stimulants , or heavy drinking between the CCM ( 44 % ) and control ( 42 % ) groups ( adjusted odds ratio , 0.84 ; 95 % CI , 0.65 - 1.10 ; P=.21 ) . No significant differences were found for secondary outcomes of addiction severity , health-related quality of life , or drug problems . No subgroup effects were found except among those with alcohol dependence , in whom CCM was associated with fewer alcohol problems ( mean score , 10 vs 13 ; incidence rate ratio , 0.85 ; 95 % CI , 0.72 - 1.00 ; P=.048 ) . CONCLUSIONS AND RELEVANCE Among persons with alcohol and other drug dependence , CCM compared with a primary care appointment but no CCM did not increase self-reported abstinence over 12 months . Whether more intensive or longer- duration CCM is effective requires further investigation . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00278447 ABSTRACT BACKGROUND Alcohol use disorder is one of the leading causes of disability worldwide . Despite the availability of efficacious treatments , few individuals with an alcohol use disorder are actively engaged in treatment . Available evidence suggests that primary care may play a crucial role in the identification of patients with an alcohol use disorder , delivery of interventions , and the success of treatment . OBJECTIVE The principal aims of this study were to test the effectiveness of a primary care-based Alcohol Care Management ( ACM ) program for alcohol use disorder and treatment engagement in veterans . DESIGN The design of the study was a 26-week single-blind r and omized clinical trial . The study was conducted in the primary care practice s at three VA medical centers . Participants were r and omly assigned to treatment in ACM or st and ard treatment in a specialty outpatient addiction treatment program . PARTICIPANTS One hundred and sixty-three alcohol-dependent veterans were r and omized . INTERVENTIONACM focused on the use of pharmacotherapy and psychosocial support . ACM was delivered in-person or by telephone within the primary care clinic . MAIN MEASUREMENTS Engagement in treatment and heavy alcohol consumption . KEY RESULTS The ACM condition had a significantly higher proportion of participants engaged in treatment over the 26 weeks [ OR = 5.36 , 95 % CI = ( 2.99 , 9.59 ) ] . The percentage of heavy drinking days were significantly lower in the ACM condition [ OR = 2.16 , 95 % CI = ( 1.27 , 3.66 ) ] , while overall abstinence did not differ between groups . CONCLUSIONS Results demonstrate that treatment for an alcohol use disorder can be delivered effectively within primary care , leading to greater rates of engagement in treatment and greater reductions in heavy drinking CONTEXT Telephone-based disease management protocol s have shown promise in improving outcomes in a number of medical and psychiatric disorders , but this approach to continuing care has received little study in alcohol- and drug-dependent individuals . OBJECTIVE To compare telephone-based continuing care with 2 more intensive face-to-face continuing care interventions . DESIGN A r and omized 3-group clinical trial with a 2-year follow-up . SETTING Two outpatient substance abuse treatment programs , one community-based and the other at a Veterans Affairs medical center facility . PATIENTS Alcohol- and /or cocaine-dependent patients ( N = 359 ) who had completed 4-week intensive outpatient programs . INTERVENTIONS Three 12-week continuing care treatments : weekly telephone-based monitoring and brief counseling contacts combined with weekly supportive group sessions in the first 4 weeks ( TEL ) , twice-weekly cognitive-behavioral relapse prevention ( RP ) , and twice-weekly st and ard group counseling ( STND ) . MAIN OUTCOME MEASURES Percentage of days abstinent from alcohol and cocaine , total abstinence from alcohol and cocaine , negative consequences of substance use , cocaine urine toxicological results , and gamma-glutamyltransferase . RESULTS Participants in TEL had higher rates of total abstinence over the follow-up than those in STND ( P<.05 ) . In alcohol-dependent participants , 24-month gamma-glutamyltransferase levels were lower in TEL than in RP ( P = .005 ) . In cocaine-dependent participants , there was a significant group x time interaction ( P = .03 ) in which the rate of cocaine-positive urine sample s increased more rapidly in RP as compared with TEL . On percentage of days abstinent or negative consequences of substance use , TEL did not differ from RP or STND . Participants with high scores on a composite risk indicator , based on co-occurring alcohol and cocaine dependence and poor progress toward achieving intensive outpatient program goals , had better total abstinence outcomes up to 21 months if they received STND rather than TEL , whereas those with lower scores had higher abstinence rates in TEL than in STND ( P = .04 ) . CONCLUSIONS Telephone-based continuing care appears to be an effective form of step-down treatment for most patients with alcohol and cocaine dependence who complete an initial stabilization treatment , compared with more intensive face-to-face interventions . However , high-risk patients may have better outcomes if they first receive group counseling continuing care after completing intensive outpatient programs The purpose of this study was to examine the clinical efficacy and cost effectiveness of brief relationship therapy ( BRT ) , a shortened version of st and ard behavioral couples therapy ( S-BCT ) , with alcoholic male patients ( N = 100 ) and their nonsubstance-abusing female partners . Participants were r and omly assigned to 1 of 4 treatment conditions : ( a ) BRT , ( b ) S-BCT , ( c ) individual-based treatment ( IBT ) , or ( d ) psychoeducational attention control treatment ( PACT ) . Equivalency testing revealed that , compared with those assigned to S-BCT , participants who were r and omly assigned to BRT had equivalent posttreatment and 12-month follow-up heavy drinking outcomes . Moreover , at 12-month follow-up , heavy drinking and dyadic adjustment outcomes for patients who received BRT were superior to those of patients who received IBT or PACT . BRT was significantly more cost effective than the S-BCT , IBT , or PACT A r and omized controlled trial for an innovative alcohol-adapted anger management treatment ( AM ) for outpatient alcohol dependent individuals scoring moderate or above on anger is described . AM treatment outcomes were compared to those of an empirically-supported intervention , Alcoholics Anonymous Facilitation treatment ( AAF ) . Clients in AM , relative to clients in AAF , were hypothesized to have greater improvement in anger and anger-related cognitions and lesser AA involvement during the 6-month follow-up . Anger-related variables were hypothesized to be stronger predictors of improved alcohol outcomes in the AM treatment condition and AA involvement was hypothesized to be a stronger predictor of alcohol outcomes in the AAF treatment group . Seventy-six alcohol dependent men and women were r and omly assigned to treatment condition and followed for 6 months after treatment end . Both AM and AAF treatments were followed by significant reductions in heavy drinking days , alcohol consequences , anger , and maladaptive anger-related thoughts and increases in abstinence and self-confidence regarding not drinking to anger-related triggers . Treatment with AAF was associated with greater AA involvement relative to treatment with AM . Changes in anger and AA involvement were predictive of posttreatment alcohol outcomes for both treatments . Change in trait anger was a stronger predictor of posttreatment alcohol consequences for AM than for AAF clients ; during-treatment AA meeting attendance was a stronger predictor of posttreatment heavy drinking and alcohol consequences for AAF than for AM clients . Anger-related constructs and drinking triggers should be foci in treatment of alcohol dependence for anger-involved clients BACKGROUND Alcohol screening , brief intervention , and referral to specialized treatment ( ASBIR ) reduce drinking and related harms . Unanswered questions are how to manage nondependent patients with poor response to brief interventions , how to manage dependent patients who do not obtain treatment , and how to ensure population -wide delivery of ASBIR . Telephone-administered counseling may provide answers . METHODS We conducted a 12-month r and omized controlled trial of a telephone and mail intervention for non-treatment-seeking primary care patients with alcohol use disorders . We enrolled 897 subjects after systematic screening in 18 primary care clinic waiting rooms in and around Madison and Milwaukee , Wisconsin , and subsequent telephone-administered diagnostic interviews . Experimental subjects received up to six sessions of protocol -driven telephone counseling based on principles of motivational interviewing and stages of readiness to change . Control subjects received a pamphlet on healthy lifestyles . The paper reports on 3-month drinking outcomes for men and women with alcohol abuse and dependence . RESULTS Male experimental subjects ( N=199 ) manifested a 30.6 % decline in risky drinking days , compared with a 8.3 % decline in controls ( N=201 , p<0.001 ) . The total consumption declined by 17.3 % compared with 12.9 % by controls ( p=0.001 ) . Female experimental subjects ( N=246 ) manifested a 17.2 % decrease in risky drinking days compared with an 11.5 % decrease by controls ( N=251 ; p = NS ) and a 13.9 % decline in total consumption compared with 11.0 % by controls ( p = NS ) . Greater numbers of telephone counseling sessions were associated with greater declines in drinking . CONCLUSION Following systematic screening , a six-session telephone and mail intervention is more effective than a pamphlet in reducing drinking at 3 months for non-treatment-seeking men with alcohol abuse and dependence . An intervention effect of the enrollment procedures may have obscured further intervention effectiveness . Telephone counseling shows promise for non-treatment-seeking primary care patients with alcohol use disorders BACKGROUND Naltrexone is approved for the treatment of alcohol dependence when used in conjunction with a psychosocial intervention . This study was undertaken to examine the impact of 3 types of psychosocial treatment combined with either naltrexone or placebo treatment on alcohol dependency over 24 weeks of treatment : ( 1 ) Cognitive-Behavioral Therapy ( CBT ) + medication clinic , ( 2 ) BRENDA ( an intervention promoting pharmacotherapy ) + medication clinic , and ( 3 ) a medication clinic model with limited therapeutic content . METHODS Two hundred and forty alcohol-dependent subjects were enrolled in a 24-week double-blind placebo-controlled study of naltrexone ( 100 mg/d ) . Subjects were also r and omly assigned to 1 of 3 psychosocial interventions . All patients were assessed for alcohol use , medication adherence , and adverse events at regularly scheduled research visits . RESULTS There was a modest main treatment effect for the psychosocial condition favoring those subjects r and omized to CBT . Intent-to-treat analyses suggested that there was no overall efficacy of naltrexone and no medication by psychosocial intervention interaction . There was a relatively low level of medication adherence ( 50 % adhered ) across conditions , and this was associated with poor outcome . CONCLUSIONS Results from this 24-week treatment study demonstrate the importance of the psychosocial component in the treatment of alcohol dependence . Moreover , results demonstrate a substantial association between medication adherence and treatment outcomes . The findings suggest that further research is needed to determine the appropriate use of pharmacotherapy in maximizing treatment response AIM This study evaluated two strategies to facilitate involvement in Alcoholics Anonymous (AA)--a 12-Step-based directive approach and a motivational enhancement approach -- during skills-focused individual treatment . DESIGN R and omized controlled trial with assessment s at baseline , end of treatment and 3 , 6 , 9 and 12 months after treatment . PARTICIPANTS , SETTING AND INTERVENTION : A total of 169 alcoholic out- patients ( 57 women ) assigned r and omly to one of three conditions : a directive approach to facilitating AA , a motivational enhancement approach to facilitating AA or treatment as usual , with no special emphasis on AA . MEASUREMENTS Self-report of AA meeting attendance and involvement , alcohol consumption ( percentage of days abstinent , percentage of days heavy drinking ) and negative alcohol consequences . FINDINGS Participants exposed to the 12-Step directive condition for facilitating AA involvement reported more AA meeting attendance , more evidence of active involvement in AA and a higher percentage of days abstinent relative to participants in the treatment-as-usual comparison group . Evidence also suggested that the effect of the directive strategy on abstinent days was mediated partially through AA involvement . The motivational enhancement approach to facilitating AA had no effect on outcome measures . CONCLUSIONS These results suggest that treatment providers can use a 12-Step-based directive approach to effectively facilitate involvement in AA and thereby improve client outcome The aim of this study was to determine whether a socially focused treatment can effect change in the patient 's social network from one that reinforces drinking to one that reinforces sobriety . Alcohol dependent men and women ( N = 210 ) recruited from the community were r and omly assigned to 1 of 3 outpatient treatment conditions : network support ( NS ) , network support + contingency management ( NS + CM ) , or case management ( CaseM ; a control condition ) . Analysis of drinking rates for 186 participants at 15 months indicated a significant interaction effect of Treatment x Time , with both NS conditions yielding better outcomes than the CaseM condition . Analyses of social network variables at posttreatment indicated that the NS conditions did not reduce social support for drinking relative to the CaseM condition but did increase behavioral and attitudinal support for abstinence as well as Alcoholics Anonymous ( AA ) involvement . Both the NS variables and AA involvement variables were significantly correlated with drinking outcomes . These findings indicate that drinkers ' social networks can be changed by a treatment that is specifically design ed to do so , and that these changes contribute to improved drinking outcomes AIMS Two r and omized controlled trials of residential drug abuse treatment programs found the programs to be equally effective , based on outcomes among those assigned to the treatments . This study aim ed to compare the relative efficacy of the programs , based on outcomes among those who received the specific treatment program as planned . DESIGN Secondary analyses of data from two concurrent r and omized controlled trials , with stratification by actual length of stay . SETTING Two residential drug abuse treatment facilities in the United States . PARTICIPANTS Six hundred and twenty-eight clients were enrolled over a 2-year period , representing 85 % of all clients admitted , 91 % of all eligible clients , and 95 % of those asked to participate . INTERVENTIONS At one facility , clients were r and omized to 3-month or 6-month versions of a traditional therapeutic community program . At the second facility , clients were r and omized to 3-month or 6-month versions of a modified therapeutic community program that emphasized relapse prevention and health education . MEASUREMENTS Time from admission to first drug use ( except alcohol ) ; and Addiction Severity Index ( ASI ) composite scores for severity of drug , alcohol , legal , and employment problems . FINDINGS Five hundred and thirty-nine clients ( 86 % ) completed a follow-up interview at least 16.5 months after admission . In the relapse prevention trial , benefits of the 6-month program were generally limited to those who stayed at least 40 days . In the therapeutic community trial , among those who stayed at least 171 days , the 12-month program had a beneficial effect on employment . Otherwise , there were inconsistent differences between the 6- and 12-month programs . CONCLUSIONS On average , clients who stayed in treatment at least 80 days benefited from continuing in treatment for up to 6 months , but not beyond . Conversely , those admitted to programs of longer planned duration who dropped out of treatment early had worse outcomes than those who dropped out of shorter programs . Thus , although longer planned duration of treatment may be efficacious , it is not effective AIMS AND DESIGN A r and omized clinical trial was performed to evaluate the influence of two formats of cognitive-behavioral psychotherapy ( individual vs. group ) in the treatment of alcohol and /or drug dependent patients . SETTING Public outpatient drug dependence service . PARTICIPANTS One hundred and fifty-five alcohol and /or drug-dependent patients . INTERVENTION The patients were r and omly assigned to individual ( n = 77 ) or group ( n = 78 ) treatment formats . The treatment was developed into two phases : acquisition ( eight sessions ) and maintenance ( nine sessions ) , distributed over an 8-month period . MEASUREMENTS Alcohol and drug use , severity of dependence , and alcohol- and drug-related problems were evaluated at pre-treatment and 15 months after admission to treatment . FINDINGS At follow-up evaluation both groups of patients presented similar levels of drug consumption , dependence and associated problems . Although group-treated patients reported slightly higher levels of alcohol consumption ( both at baseline and follow-up ) differences between the formats disappear if baseline levels are included as covariates . Compliance with treatment and a measure of drug severity were predictors of success for the drug dependents . The number of sessions attended and high GGT levels at admission were positively correlated with success for the alcohol dependents . CONCLUSIONS The two modalities presented similar outcomes and , as the group format could present a better cost-benefit ratio , it may be used without decreasing compliance with treatment or treatment effectiveness OBJECTIVE There has been increasing recognition among alcohol treatment research ers that research assessment exposure subject reactivity effects can contribute to clinical outcomes , decrease study design sensitivity , and confound research findings . The present study is an experimental investigation of two of the more salient components of the research assessment interview ( i.e. , frequency and comprehensiveness ) and their effects on clinical outcomes ( Part I : Alcohol Use and Related Consequences ) and treatment participation ( Part II : Treatment Engagement and Involvement ) . METHOD The study design was a 2 ( Frequency of Assessment ) x 2 ( Comprehensiveness of Assessment ) completely r and omized factorial , and study participants were r and omly assigned , using an urn r and omization procedure , to one of the result ing four experimental research assessment exposure conditions : ( 1 ) frequent-comprehensive , ( 2 ) frequent-brief , ( 3 ) infrequent-comprehensive , and ( 4 ) infrequent-brief . Study participants were recruited from one of two hospital-based outpatient alcohol- and other substance-abuse clinics . Two hundred thirty-five subjects were r and omly assigned to one of the four research assessment exposure conditions . RESULTS Research assessment exposure subject reactivity effects were related significantly to alcohol use and related negative consequences , such that subjects assigned to the infrequent-brief research assessment exposure condition reported the poorest outcomes . CONCLUSIONS The research protocol s used to study alcohol treatments have clinical efficacy and can alter the outcomes ( e.g. , alcohol use ) under investigation . It is important for research ers to control/account for subject reactivity effects when conducting alcohol treatment outcome trials . Accurate interpretation of data derived from clinical trials of alcohol treatments necessitates taking research assessment exposure subject reactivity effects into consideration AIM To compare the effectiveness of st and ard behavioral couples therapy for alcohol problems to two maintenance enhanced therapies . DESIGN R and omized clinical trial . SETTING Outpatient substance abuse treatment clinic . PARTICIPANTS Ninety males with alcohol abuse or dependence and their female partners . INTERVENTIONS Weekly , outpatient therapy in one of three r and omly assigned conditions : Alcohol Behavioral Couples Therapy ( ABCT ) , Alcoholics Anonymous plus ABCT ( AA/ABCT ) or Relapse Prevention plus ABCT ( RP/ABCT ) . FINDINGS The men significantly reduced the frequency of drinking and heavy drinking during treatment . During the first 6 months post-treatment , 65.7 % of male subjects were classified as improved on a composite measure of drinking and drinking-related consequences . Compared to baseline levels , the percentage of abstinent days increased and heavy drinking days decreased , but the three conditions did not differ . Two outcome variables favored the purely behavioral treatment conditions ( ABCT and RP/ABCT ) over the AA/ABCT condition : time to the first heavy drinking day was longer for subjects in the ABCT condition than subjects in the AA/ABCT condition , and subjects in the RP/ABCT condition tended to have shorter drinking episodes than subjects in the AA/ABCT condition . Subjects who complied with post-treatment maintenance plans were more likely to be abstinent than subjects who did not . CONCLUSIONS Results favored the two behavioral conditions and did not suggest additional benefit from combining AA with behavioral couples therapy , but those who did attend AA showed a positive impact This pilot study examined effects of Parent Skills with Behavioral Couples Therapy ( PSBCT ) on substance use , parenting , and relationship conflict among fathers with alcohol use disorders . Male participants ( N = 30 ) entering outpatient alcohol treatment , their female partners , and a custodial child ( 8 to 12 years ) were r and omly assigned to ( a ) PSBCT ; ( b ) Behavioral Couples Therapy ( BCT ) ; or ( c ) Individual-Based Treatment ( IBT ) . Children were not actively involved in treatment . Parents completed measures of substance use , couples ' dyadic adjustment , partner violence , parenting , and Child Protection Services ( CPS ) involvement at pretreatment , posttreatment , 6- and 12-month follow-up . PSBCT was comparable to BCT on substance use , dyadic adjustment , and partner violence ; both groups showed clinical ly meaningful effects over IBT . Compared to BCT , PSBCT result ed in larger effect sizes on parenting and CPS involvement throughout follow-up . PSBCT for fathers may enhance parenting couple- or individual-based treatment , and warrant examination in a larger , r and omized efficacy trial This study was design ed to investigate the effects of treatment length restriction and follow-up interview style on the outcomes of male alcohol abusers in out-patient treatment . Subjects ( N = 48 ) were r and omly assigned to one of four independent groups based on the factorial combination of the two independent variables . Extensive pretreatment data were collected about subjects ' drinking and related behaviors , and subjects were then scheduled for monthly interviews . Subjects were interviewed for 18 months postadmission concerning these same factors . Subjects ' self-reports were compared with collateral reports , official records , and breath tests . Outcome results showed no effects of follow-up interview style or treatment length restriction on drinking behavior and employment outcomes . However , subjects ' drinking behavior postadmission was considerably improved compared to their pretreatment ethanol consumption . Temporal analyses of the drinking behavior data showed that it was possible to predict drinking behavior , especially of the same type , within pretreatment and postadmission intervals . However , it was not possible to predict postadmission drinking from pretreatment drinking . Treatment implication s of the findings are discussed BACKGROUND Cognitive behavioral therapy ( CBT ) is an evidence -based treatment for alcohol use disorders ( AUDs ) , yet is rarely implemented with high fidelity in clinical practice . Computer-based delivery of CBT offers the potential to address dissemination challenges , but to date there have been no evaluations of a web-based CBT program for alcohol use within a clinical sample . METHODS This study r and omized treatment-seeking individuals with a current AUD to 1 of 3 treatments at a community outpatient facility : ( i ) st and ard treatment as usual ( TAU ) ; ( ii ) TAU plus on-site access to a computerized CBT targeting alcohol use ( TAU + CBT4CBT ) ; or ( iii ) CBT4CBT plus brief weekly clinical monitoring ( CBT4CBT + monitoring ) . Participant alcohol use was assessed weekly during an 8-week treatment period , as well as 1 , 3 , and 6 months after treatment . RESULTS Sixty-eight individuals ( 65 % male ; 54 % African American ) were r and omized ( TAU = 22 ; TAU + CBT4CBT = 22 ; CBT4CBT + monitoring = 24 ) . There were significantly higher rates of treatment completion among participants assigned to 1 of the CBT4CBT conditions compared to TAU ( Wald = 6.86 , p < 0.01 ) . Significant reductions in alcohol use were found across all conditions within treatment , with participants assigned to TAU + CBT4CBT demonstrating greater increases in percentage of days abstinent ( PDA ) compared to TAU , t(536.4 ) = 2.68 , p < 0.01 , d = 0.71 , 95 % CI ( 0.60 , 3.91 ) , for the full sample . Preliminary findings suggest the estimated costs of all self-reported AUD-related services utilized by participants were considerably lower for those assigned to CBT4CBT conditions compared to TAU , both within treatment and during follow-up . CONCLUSIONS This trial demonstrated the safety , feasibility , and preliminary efficacy of web-based CBT4CBT targeting alcohol use . CBT4CBT was superior to TAU at increasing PDA when delivered as an add-on , and it was not significantly different from TAU or TAU + CBT4CBT when delivered with clinical monitoring only AIMS Cognitive-behavioral treatments ( CBT ) are among the most popular interventions offered for alcohol and other substance use disorders , but it is not clear how they achieve their effects . CBT is purported to exert its beneficial effects by altering coping skills , but data supporting coping changes as the mechanism of action are mixed . The purpose of this pilot study was to test a treatment in which coping skills were trained in a highly individualized way , allowing us to determine if such training would result in an effective treatment . DESIGN Participants were assigned r and omly to a comprehensive packaged CBT program ( PCBT ) , or to an individualized assessment and treatment program ( IATP ) . The IATP program employed experience sampling via cellphone to assess coping skills prior to treatment , and provided therapists with a detailed underst and ing of patients ' coping strengths and deficits . SETTING Out-patient treatment . PARTICIPANTS A total of 110 alcohol-dependent men and women . MEASUREMENTS Participants in both conditions completed experience sampling of situations , drinking and coping efforts prior to , and following , 12 weeks of treatment . Time-line follow-back procedures were also used to record drinking at baseline and post-treatment . FINDINGS IATP yielded higher proportion of days abstinent ( PDA ) at post-treatment ( P < 0.05 ) than did PCBT , and equivalent heavy drinking days . IATP also elicited more momentary coping responses and less drinking in high-risk situations , as recorded by experience sampling at post-treatment . Post-treatment coping response rates were associated with decreases in drinking . CONCLUSIONS The IATP approach was more successful than PCBT at training adaptive coping responses for use in situations presenting a high risk for drinking . The highly individualized IATP approach may prove to be an effective treatment strategy for alcohol-dependent patients BACKGROUND In several studies , patients with alcohol dependence treated with the opioid antagonist naltrexone have shown fewer relapses to heavy drinking than those receiving placebo . An interaction between the naltrexone effect and the type of psychological therapy has been observed . METHODS A 6-month , double-blind , placebo-controlled , parallel-group study was performed at 10 different investigation sites . After a placebo run-in period of 1 week , 118 patients were r and omized into 4 treatment groups-50 mg of naltrexone daily or placebo in combination with either cognitive behavioral therapy ( CBT ) or supportive therapy . The CBT was performed over nine sessions according to the manual of Project MATCH ( Matching Alcoholism Treatments to Client Heterogeneity ) . The supportive therapy was defined as " the treatment as usual . " Alcohol consumption , craving , carbohydrate-deficient transferrin , medication compliance by tablet count , and adverse clinical events were assessed at all visits . Other liver enzymes and psychiatric symptoms were also determined . RESULTS Ninety-one ( 77 % ) patients completed the study , and 92 ( 78 % ) were 80 % compliant with the medication regimen . A lower percentage of heavy-drinking days was shown in the naltrexone group ( p = 0.045 ) compared with the placebo group , as was a lower craving score ( p = 0.029 ) . These results are supported by the lower levels of liver enzyme activities ( p < 0.010 for aspartate aminotransferase , alanine aminotransferase , and gamma-glutamyltransferase ) , but not by the carbohydrate-deficient transferrin levels , in the naltrexone group . The mean time period before the first day of heavy drinking was longer for the group treated with CBT ( p = 0.010 ) , especially in combination with naltrexone ( p = 0.007 ) . Naltrexone was well tolerated , and no patients discontinued the study due to side effects . CONCLUSIONS This study supports the effect of naltrexone in outpatient treatment of alcohol dependence and suggests that a beneficial interaction effect with CBT can be expected UNLABELLED Problem drinkers ( 52 males , 38 females ) recruited through advertisements were r and omly assigned to one of three treatments : GUIDELINES three sessions of advice using a pamphlet outlining basic steps for achieving abstinence or moderate drinking . Manual : three sessions of instruction in the use of a ' self-help ' manual presenting a step-by-step approach for attaining abstinence or moderate drinking . Therapist : six or more sessions of instruction in the methods outlined in the ' self-help ' manual . At 3 , 6 and 12 months follow-up , no significant differences were found among the groups in reduction of heavy drinking days ( i.e. days when consumption exceeded four drinks , each containing 13.6 g/ethanol ) . Overall , the number of heavy days were reduced from an average of 43 at intake , to 20 over the 1-year follow-up period . Females , however , had significantly greater reductions than males ( 75 % versus 35 % ) . Three months after treatment the rate of successful moderate drinkers was significantly higher for females than males in the GUIDELINES ( 60 % versus 33 % ) and the Manual condition ( 63 % versus 18 % ) , but not in the Therapist condition ( 25 % versus 35 % ) . At 1-year follow-up , females were more successful than males in all conditions . Mean changes in GGT and MCV levels lended support to the change in drinking status ( from heavy drinker at intake to moderate drinker at follow-up ) , based on clients ' self-reports OBJECTIVE A r and omized controlled trial was conducted to examine the effectiveness of Moderation-Oriented Cue Exposure ( MOCE ) in comparison to Behavioral Self-Control Training ( BSCT ) . The main hypothesis was that MOCE would be more effective than BSCT among a sample of problem drinkers aim ing at moderate drinking . A subsidiary hypothesis was that MOCE would be relatively more effective than BSCT among problem drinkers with higher levels of alcohol dependence . METHOD Clients ( N = 91 ; 75 % men ) were r and omly allocated to either MOCE or BSCT . Treatment was delivered in weekly sessions by two trained therapists , in a nested design in which therapists switched to the alternative treatment modality approximately halfway through the trial . Follow-up was carried out 6 months following posttreatment assessment , with 85 % successful contact . RESULTS There was no evidence for the general superiority of MOCE over BSCT . The subsidiary hypothesis was not confirmed . A sub sample of clients ( n = 14 ) showing levels of dependence at baseline above the commonly accepted cut-point for a moderation goal ( Severity of Alcohol Dependence Question naire [ SADQ ] > 29 ) showed outcomes at least as favorable as those below the cut-point . The validity of self-reports of alcohol consumption and problems was supported by significant relationships with liver function tests ( gamma-glutamyl transferase and alanine transferase ) . CONCLUSIONS These results provide no grounds for the replacement of BSCT by MOCE in routine , moderation-oriented treatment practice . Assuming they prefer it to abstinence and that it is not contra-indicated on other grounds , there seems no reason why clients showing a higher level of dependence ( SADQ = 30 - 45 ) should not be offered a moderation goal The effect of combining relapse prevention counselling with use of an alcohol-sensitizing drug was examined . Fifty-six alcoholic subjects who participated in a clinical trial of the short-acting alcohol sensitizing drug , citrated calcium carbimide , were r and omly assigned to : ( i ) a Physician Advice condition in which subjects took the drug within a context design ed to reinforce the medical management of their drinking problem ; and ( ii ) a Relapse Prevention condition in which subjects were instructed to pair use of the drug with planned entry into high risk drinking situations and to gradually reduce reliance on the drug by developing alternative coping behaviour patterns . As predicted , subjects receiving carbimide in conjunction with relapse prevention counselling showed significant growth in internal attribution for change ; whereas those receiving carbimide under more traditional medical management showed no movement toward internality . On measurement of alcohol consumption at 6 , 12 and 18 months follow-up , there was some indication of superior maintenance of treatment gains at 18 months post-treatment for subjects who had received relapse prevention counselling , although the effect did not reach a conventional level of significance ( F = 2.82 ; P less than 0.06 ) . The findings are interpreted as consistent with a cognitive social-learning analysis of the maintenance of behaviour change Summary The Marital Systems Study ( MSS ) compared the effectiveness of a short-term systems-based outpatient treatment consisting of eight sessions of Conjoint Therapy with a single session of Advice Counselling which also involved the spouse . Eligible couples were r and omly assigned to either Conjoint Therapy or Advice Counselling . In all , 218 couples were recruited for the Study . From this initial sample , 102 couples dropped out of treatment or follow-up leaving the remaining 116 couples as the Study sample . Couples in both Advice Counselling and Conjoint Therapy showed significant improvement on all marital adjustment and drinking-related outcome measures . Although significant treatment-by-time interactions were found on three of the nine variables , there were no significant differences in the change pattern between the groups on the principal drinking outcome measure , the percentage of heavy drinking days . There were also no significant between-group differences on any of the outcome measures . In essence , a single session of Advice Counselling was as effective as eight sessions of Conjoint Therapy . Couples completing the Study represented a socially stable group , with a moderate degree of alcohol-related difficulties and relatively non-distressed marital relationships . Thus , the findings pertaining to the relative effectiveness of the two treatments may be limited to this specific client population BACKGROUND Naltrexone may improve success in primary care treatment of alcohol dependence ( AD ) . This study tests naltrexone and primary care management ( PCM ) vs naltrexone and cognitive behavior therapy ( CBT ) and tests naltrexone maintenance among patients who respond to an initial course of naltrexone combined with PCM vs CBT . METHODS A nested sequence of 3 r and omized trials was conducted . In study 1 , 197 subjects with AD participated in a 10-week comparison of PCM and naltrexone ( 50 mg/d ) vs CBT and naltrexone ( 50 mg/d ) . In study 2 , 53 PCM responders from study 1 continued in a 24-week placebo-controlled study of maintenance naltrexone . In study 3 , 60 CBT responders from study 1 continued in a 24-week placebo-controlled study of maintenance naltrexone and CBT . RESULTS Study 1 : No difference in the response to treatment ; 84.1 % ( 74/88 ) of the PCM patients and 86.5 % ( 77/89 ) of the CBT patients avoided persistent heavy drinking . Percentage of days abstinent ( PDA ) declined over time for PCM vs CBT ( P = .03 ) . Study 2 : Higher response maintenance for PCM and naltrexone ( 21/26 , 80.8 % ) vs PCM and placebo ( 14/27 , 51.9 % ; P = .03 ) and PDA declined more for the placebo group ( P = .02 ) . Study 3 : The differences between naltrexone vs placebo on maintenance of response ( 25/30 , 83.3 % vs 21/30 , 70.0 % ) or PDA did not reach statistical significance . CONCLUSIONS Naltrexone yielded comparable results during the initial 10 weeks of treatment when combined with PCM or CBT . Maintenance of improvement was enhanced by continued naltrexone treatment in the PCM but not in the CBT arm OBJECTIVE The study tested whether adding up to 18 months of telephone continuing care , either as monitoring and feedback ( TM ) or longer contacts that included counseling ( TMC ) , to intensive outpatient programs ( IOPs ) improved outcomes for alcohol-dependent patients . METHOD Participants ( N = 252 ) who completed 3 weeks of IOP were r and omized to up to 36 sessions of TM ( M = 11.5 sessions ) , TMC ( M = 9.1 sessions ) , or IOP only ( treatment as usual [ TAU ] ) . Quarterly assessment of alcohol use ( 79.9 % assessed at 18 months ) was corroborated with available collateral reports ( N = 63 at 12 months ) . Participants with cocaine dependence ( N = 199 ) also provided urine sample s. RESULTS Main effects favored TMC over TAU on any alcohol use ( odds ratio [ OR ] = 1.88 , CI [ 1.13 , 3.14 ] ) and any heavy alcohol use ( OR = 1.74 , CI [ 1.03 , 2.94 ] ) . TMC produced fewer days of alcohol use during Months 10 - 18 and heavy alcohol use during Months 13 - 18 than TAU ( ds = 0.46 - 0.65 ) . TMC also produced fewer days of any alcohol use and heavy alcohol use than TM during Months 4 - 6 ( ds = 0.39 and 0.43 ) . TM produced lower percent days alcohol use than TAU during Months 10 - 12 and 13 - 15 ( ds = 0.41 and 0.39 ) . There were no treatment effects on rates of cocaine-positive urines . CONCLUSIONS Adding telephone continuing care to IOP improved alcohol use outcomes relative to IOP alone . Conversely , shorter calls that provided monitoring and feedback but no counseling generally did not improve outcomes over IOP Married or cohabiting female alcoholic patients ( n = 138 ) and their non-substance-abusing male partners were r and omly assigned to 1 of 3 equally intensive interventions : ( a ) behavioral couples therapy plus individual-based treatment ( BCT ; n = 46 ) , ( b ) individual-based treatment only ( IBT ; n = 46 ) , or ( c ) psychoeducational attention control treatment ( PACT ; n = 46 ) . During treatment , participants in BCT showed significantly greater improvement in dyadic adjustment than those in IBT or PACT ; drinking frequency was not significantly different among participants in the different conditions . During the 1-year posttreatment follow-up , compared with participants who received IBT or PACT , participants who received BCT reported ( a ) fewer days of drinking , ( b ) fewer drinking-related negative consequences , ( c ) higher dyadic adjustment , and ( d ) reduced partner violence In this study , 126 clients ( 87 men , 39 women ) entering outpatient alcoholism treatment were assigned r and omly to 1 of 3 preparatory conditions : a role induction ( RI ) session , a motivational interview ( MI ) session , or a no-preparatory session control group ( CG ) . Clients assigned to the MI preparatory condition attended more treatment sessions and had fewer heavy drinking days during and 12 months after treatment relative to CG clients . Clients assigned to MI , relative to CG clients , also had more abstinent days during treatment and during the first 3 months posttreatment , although this difference was not maintained through the remainder of the 12-month follow-up period . Clients assigned to the RI condition showed no significant advantage over those in the CG condition Ninety-seven alcohol-dependent patients were treated for 12 weeks in a double-blind , placebo-controlled study evaluating naltrexone and two manual guided psychotherapies in the treatment of alcohol dependence . Patients were r and omized to receive either naltrexone or placebo and either coping skills/relapse prevention therapy or a supportive therapy design ed to support the patient 's own efforts at abstinence without teaching specific coping skills . Naltrexone proved superior to placebo in measures of drinking and alcohol-related problems , including abstention rates , number of drinking days , relapse , and severity of alcohol-related problems . Medication interacted with the type of psychotherapy received . The cumulative rate of abstinence was highest for patients treated with naltrexone and supportive therapy . For those patients who initiated drinking , however , patients who received naltrexone and coping skills therapy were the least likely to relapse Patients were r and omly assigned to 1 of 3 treatments : brief broad-spectrum ( BBS ) , extended relationship enhancement ( ERE ) , or extended cognitive-behavioral ( ECB ) . A hierarchical latent growth model was used to analyze the data of 188 patients ( 82 % ) followed for 18 months . ERE treatment was significantly more effective in increasing abstinence of patients entering treatment with a network unsupportive of abstinence or with a low level of investment in their network , whereas BBS treatment was more effective for patients with either ( a ) both a social network unsupportive of abstinence and a low level of network investment or ( b ) high investment in a network supportive of abstinence . ECB outcomes were neither as good as those matched nor as bad as those mismatched to the different exposures of relationship enhancement . This suggests that dose of relationship enhancement should be determined after assessing patient relationships Burtscheidt W , Wölwer W , Schwarz R , Strauss W , Gaebel W. Out‐patient behaviour therapy in alcoholism : treatment outcome after 2 years . Acta Psychiatr Sc and 2002 : 106 : 227–232 . © Blackwell Munksgaard 2002 Alcohol and drug patients were r and omized into two groups , one receiving three months and the other six months of outpatient treatment to determine differences in treatment outcomes . Most clients had received prior 30 days of inpatient treatment . Patients were contacted after the first 70 days of outpatient treatment and 12 refused participation . Consenters were r and omized and assigned into control ( n = 103 ) and experimental ( n = 127 ) groups , and interviewed at discharge , and three and six months later . A gratuity of $ 10.00 was offered after a completed phone interview . Data were analyzed using chi-square , t-test , and multivariate logistic regression techniques . Controls had lower treatment drop-out and higher follow-up attrition rates than experimentals . There were no major differences in reported subsequent alcohol/drug use , or attendance to aftercare , Alcohol Anonymous ( AA ) and support groups during the 3 and 6 months follow-up surveys . More controls re-entered treatment than experimentals at 3 months post-treatment , but there was no such difference at 6 months post-treatment . In terms of ancillary effects , experimentals had slightly more desirable outcomes with respect to abstinence at time of discharge , and use of cocaine at 3 months follow-up . Controls were more likely to use cocaine and less likely to re-enter inpatient treatment or attend aftercare than experimentals . At six months the few who reported using painkillers were controls . Relapse was predictably influenced both at 3 and 6 months by pretreatment use of cocaine as primary drug , and by duration of abstinence from all chemicals . The predictive influence of cocaine was greater at 3 than at 6 months post-discharge This study evaluated the efficacy of a contingency management ( CM ) procedure that provided opportunities to win prizes as reinforcers . At intake to outpatient treatment , 42 alcohol-dependent veterans were r and omly assigned to receive st and ard treatment or st and ard treatment plus CM , in which they earned the chance to win prizes for su bmi tting negative Breathalyzer sample s and completing steps toward treatment goals . Eighty-four percent of the CM participants were retained in treatment for an 8-week period compared with 22 % of the st and ard treatment participants ( p < .001 ) . By the end of the treatment period , 69 % of those receiving CM were still abstinent , but 61 % of those receiving st and ard treatment had used alcohol ( p < .05 ) . These results support the efficacy of this CM procedure . Participants earned an average of $ 200 in prizes . This CM procedure may be suitable for use in st and ard treatment setting s because prizes can be solicited from the community This study sought to examine the effectiveness of a " st and ard " outpatient alcoholism treatment ( ST ) program . An outpatient alcoholism treatment as it is commonly practice d in the US ( with group and individual therapy , and an emphasis on Alcoholics Anonymous [ AA ] ) , was compared with a minimal treatment ( MT ) approach ( weekly alcohol education movies ) . At 6 months , ST patients surpassed those in MT in terms of complete abstinence , reduction in amount of alcohol consumed , length of sobriety at follow-up , improvement in employment status , number of AA meetings attended , and lower initial drop-out . It is concluded that a ST approach is more helpful than MT in treating severely alcohol-dependent individuals who have not been able to cut down drinking on their own . Those already drinking less appeared to be helped by MT Abstract : Although naltrexone has been shown to be effective in the treatment of alcohol dependence , less is known about its efficacy when combined with different behavioral therapies . Previous work has suggested that naltrexone works best when combined with weekly cognitive behavioral therapy ( CBT ) . This study examined the efficacy of naltrexone when combined with CBT or a motivational enhancement therapy involving less patient contact . Outpatient alcoholics ( N = 160 ) were r and omly assigned to either naltrexone ( 50 mg/d ) or placebo and either CBT ( 12 sessions ) or motivational enhancement therapy ( 4 sessions ) , in a 4-cell design , and treated over a 12-week period . Subjects were evaluated periodically for alcohol consumption , craving , and biologic markers of drinking ( carbohydrate-deficient transferrin and γ-glutamyltransferase ) . There was high retention and adherence to therapy and medication in the trial with no significant difference across the treatment groups . Naltrexone , independent of therapy assignment , increased the time to first relapse . However , the CBT-naltrexone group did better than the other groups on a variety of outcome measures . Fewer CBT-naltrexone-treated subjects relapsed , and those that did had both fewer , and more time between , subsequent relapses . This r and omized controlled trial is consistent with previous reports about the utility of combining naltrexone with CBT . Despite being more efficient to administer , the combination of motivational enhancement therapy and naltrexone is less effective than CBT and naltrexone . Because CBT and naltrexone share common mechanisms of action , such as craving reduction and relapse prevention , these therapies are likely to be well suited to use in combination Men inpatient alcoholics ( N = 174 ) from a Veterans Administration medical center who were preselected by employment status were r and omly assigned to one of three outpatient treatment interventions : ( 1 ) medication only , ( 2 ) active support or ( 3 ) untreated medical monitoring . Subjects were followed monthly for 1 year , with an 85 % 12-month follow-up rate . Although the sample as a whole showed reduced alcohol misuse and improved social functioning after 12 months , the specific form of treatment was unrelated to outcome . These findings suggest that the intensity of the outpatient treatment experience is not related to outcome and that time-consuming interventions are not differentially cost-effective |
1,827 | 22,895,914 | There was no apparent effect on other adverse maternal or neonatal outcomes .
Care by the same or separate staff had no apparent effects .
Hospital birth centres are associated with lower rates of medical interventions during labour and birth and higher levels of satisfaction , without increasing risk to mothers or babies | BACKGROUND Alternative institutional setting s have been established for the care of pregnant women who prefer little or no medical intervention .
The setting s may offer care throughout pregnancy and birth , or only during labour ; they may be part of hospitals or freest and ing entities .
Specially design ed labour rooms include bedroom-like rooms , ambient rooms , and Snoezelen rooms .
OBJECTIVES Primary : to assess the effects of care in an alternative institutional birth environment compared to care in a conventional setting .
Secondary : to determine if the effects of birth setting s are influenced by staffing , architectural features , organizational models or geographical location . | OBJECTIVE to study the effect of birth centre care on the duration of breast feeding , breast feeding complications , and women 's experiences of breast feeding . DESIGN r and omised controlled trial . SETTING in-hospital birth centre at South Hospital , Stockholm , and st and ard obstetric care in the Greater Stockholm area . SUBJECTS 1230 women with expected date of birth between October 1989 and February 1992 , interested in participating in a birth centre trial , and meeting medical low-risk criteria . 617 women were allocated to the experimental group offered birth centre care ( EG ) , and 613 to the control group offered st and ard obstetric care ( CG ) . MAIN OUTCOME MEASURES duration of breast feeding , breast feeding complications such as sore nipples , engorgement , milk stasis , and mastitis , and women 's experiences of breast feeding . FINDINGS no difference was found between EG and CG in the duration of breast feeding . Ninety-three per cent in both groups were breast feeding exclusively two months post partum . The average number of months of breast feeding , exclusively or partly , when investigated one year after the birth was 8.6 in EG and 8.5 in CG . No difference was observed in women 's experiences of breast feeding , but rather more women in EG than in CG reported sore nipples , 36 % and 30 % respectively ( p = 0.03 ) , and milk stasis , 26 % and 19 % respectively ( p = 0.002 ) . CONCLUSIONS birth centre care had no effect on the duration of breast feeding , or on women 's experiences of breast feeding . Prenatal attitudes were probably more significant predictors of these outcomes than differences in the two modes of maternity care in this population of highly breast feeding-motivated women . The larger proportion of sore nipples and milk stasis in the EG might have been due to earlier discharge , or to midwives less skilled in assisting with breast feeding at the birth centre than in the postpartum wards Objectives To compare the outcome of two methods of maternity care during the antenatal period and at delivery . One was to be midwife‐led for both antenatal care and delivery , the latter taking place in rooms similar to those in one 's own home to simulate home confinement . The other would be consultant‐led with the mothers labouring in the delivery suite rooms with resuscitation equipment for both mother and baby in evidence , monitors present and a delivery bed on which both anaesthetic and obstetric procedures could be easily and safely carried out Abstract Objective : To examine whether intrapartum care and delivery of low risk women in a midwife managed delivery unit differs from that in a consultant led labour ward . Design : Pragmatic r and omised controlled trial . Subjects were r and omised in a 2:1 ratio between the midwives unit and the labour ward . Setting : Aberdeen Maternity Hospital , Grampian . Subjects—2844 low risk women , as defined by existing booking criteria for general practitioner units in Grampian . 1900 women were r and omised to the midwives unit and 944 to the labour ward . Main outcome measures : Maternal and perinatal morbidity . Results : Of the women r and omised to the midwives unit , 647 ( 34 % ) were transferred to the labour ward antepartum , 303 ( 16 % ) were transferred intrapartum , and 80 ( 4 % ) were lost to follow up . 870 women ( 46 % ) were delivered in the midwives unit . Primigravid women ( 255/596 , 43 % ) were significantly more likely to be transferred intrapartum than multigravid women ( 48/577 , 8 % ) . Significant differences between the midwives unit and labour ward were found in monitoring , fetal distress , analgesia , mobility , and use of episiotomy . There were no significant differences in mode of delivery or fetal outcome . Conclusions : Midwife managed intrapartum care for low risk women results in more mobility and less intervention with no increase in neonatal morbidity . However , the high rate of transfer shows that antenatal criteria are unable to determine who will remain at low risk throughout pregnancy and labour Objective To compare perinatal outcomes , maternal outcomes , and interventions in labour by planned place of birth at the start of care in labour for women with low risk pregnancies . Design Prospect i ve cohort study . Setting Engl and : all NHS trusts providing intrapartum care at home , all freest and ing midwifery units , all alongside midwifery units ( midwife led units on a hospital site with an obstetric unit ) , and a stratified r and om sample of obstetric units . Participants 64 538 eligible women with a singleton , term ( ≥37 weeks gestation ) , and “ booked ” pregnancy who gave birth between April 2008 and April 2010 . Planned caesarean sections and caesarean sections before the onset of labour and unplanned home births were excluded . Main outcome measure A composite primary outcome of perinatal mortality and intrapartum related neonatal morbidities ( stillbirth after start of care in labour , early neonatal death , neonatal encephalopathy , meconium aspiration syndrome , brachial plexus injury , fractured humerus , or fractured clavicle ) was used to compare outcomes by planned place of birth at the start of care in labour ( at home , freest and ing midwifery units , alongside midwifery units , and obstetric units ) . Results There were 250 primary outcome events and an overall weighted incidence of 4.3 per 1000 births ( 95 % CI 3.3 to 5.5 ) . Overall , there were no significant differences in the adjusted odds of the primary outcome for any of the non-obstetric unit setting s compared with obstetric units . For nulliparous women , the odds of the primary outcome were higher for planned home births ( adjusted odds ratio 1.75 , 95 % CI 1.07 to 2.86 ) but not for either midwifery unit setting . For multiparous women , there were no significant differences in the incidence of the primary outcome by planned place of birth . Interventions during labour were substantially lower in all non-obstetric unit setting s. Transfers from non-obstetric unit setting s were more frequent for nulliparous women ( 36 % to 45 % ) than for multiparous women ( 9 % to 13 % ) . Conclusions The results support a policy of offering healthy women with low risk pregnancies a choice of birth setting . Women planning birth in a midwifery unit and multiparous women planning birth at home experience fewer interventions than those planning birth in an obstetric unit with no impact on perinatal outcomes . For nulliparous women , planned home births also have fewer interventions but have poorer perinatal outcomes Please cite this paper as : Bernitz S , Roll and R , Blix E , Jacobsen M , Sjøborg K , Øian P. Is the operative delivery rate in low‐risk women dependent on the level of birth care ? A r and omised controlled trial . BJOG 2011;118:1357–1364 This r and omized , controlled trial compared women 's satisfaction with care at an in-hospital birth center with st and ard obstetric care in Stockholm . Subjects were 1230 women with an expected date of birth between October 1989 and February 1992 , who expressed interest in birth center care , and who were medically low risk . The intervention was the r and om allocation of maternity care at the birth center or st and ard obstetric care . Birth center women expressed greater satisfaction with antenatal , intrapartum , and postpartum care , especially psychological aspects of care . Of these women , 63 percent thought that the antenatal care had raised their self-esteem , versus 18 percent of the control group . Eighty-nine percent of the experimental group would prefer birth center care for any future birth , and 46 percent of the control group would prefer st and ard care . Birth center care successfully meets the needs of women who are interested in natural childbirth and active involvement in their own care , and are concerned about the psychological aspects of birth Objective : The midwifery service at our hospital has been observed to have a 2 % cesarean birth rate consistently over a 10-year period . There are substantial differences in labor management style between the midwives and physicians . We sought to test the hypothesis that the low cesarean birth rate on the midwifery service was the result of patient selection bias . Methods : A r and omized blinded clinical trial was conducted in which 492 low-risk patients were assigned to either physician or midwifery management . The provider responsible for labor management was unable to determine group assignment . Patients in the midwifery group were managed by previously established protocol s , and outcome was attributed to the midwives even if the patients subsequently required transfer to physician management . Route of delivery was the primary outcome measurement . Continuous variables were analyzed using Student t test and discrete variables using x2 . Results : There were no demographic differences between the groups , and the admission pelvic examinations were the same . The patients assigned to the midwifery group had a 2.1 % cesarean birth rate , whereas those assigned to physician management had a 0.4 % rate . The higher rate of operative vaginal deliveries in the physician group was statistically significant . There were no differences in neonatal outcomes . The physician-managed group had significantly more episiotomies and third- and fourth-degree extensions . Conclusions : The 2 % cesarean birth rate observed on the midwifery service appeared to be the result of patient selection bias . A low cesarean birth rate can be achieved by either physician or midwifery management in a selected low-risk population OBJECTIVE to investigate whether there are differences between the cost of intrapartum care for women at low obstetric risk in a midwife-managed labour and delivery unit and that in a consultant-led labour and delivery ward . DESIGN cost analysis based on the findings of a r and omised controlled trial comparing two alternative types of intrapartum care . SETTING Aberdeen Maternity Hospital , Grampian . SUBJECTS the number of women ' booked ' for care in the Midwives ' Unit in a st and ard year and a comparable group of women cared for in the consultant-led labour ward . PRIMARY OUTCOME MEASURE the cost ' outcome ' is the extra ( or reduced ) cost per woman result ing from the introduction of a midwife-managed delivery unit . FINDINGS the baseline extra cost of the introduction of the Midwives ' Unit was found to be 40.71 pounds per woman . Depending on the scenario used , this ranged from a cost saving of 9.74 pounds per woman to an additional cost of 44.23 pounds per woman . CONCLUSIONS this study has shown that , in terms of costs incurred during the intrapartum period , the marginal cost of caring for women at low obstetric risk alongside women at high obstetric risk in a st and ard labour ward is small . However , the impact of establishing a separate midwife-managed delivery unit , requiring an increase in midwifery staffing levels , can be significant BACKGROUND Nearly all hospitalized laboring women spend most of the time in bed . We made simple but radical modifications to a hospital labor room , which included the removal of the st and ard hospital bed and the addition of equipment to promote relaxation , mobility , and calm . We design ed a pilot study , the objectives of which were to test the feasibility of a r and omized trial and the acceptability of the modified labor room to women and their care providers . METHODS Women were assessed and invited to participate just before their admission to the labor and delivery suite . Sixty-two women at two Toronto teaching hospitals were r and omly allocated to either the st and ard labor room or the " ambient room . " Data about labor and birth events were abstract ed from the medical records . Participants and their nurses and physicians completed question naires to elicit their views of their experiences with the labor rooms . RESULTS Women 's and practitioners ' evaluations of the ambient room were generally very positive . Nineteen women ( 65.5 % ) in the ambient group , compared with 4 ( 13.3 % ) in the st and ard group , reported spending 50 percent or less of their hospital labor in the st and ard labor bed . Twelve women allocated to the ambient room had artificial oxytocin infusions , compared with 21 allocated to the st and ard room ( X ( 2 ) = 4.73 , p = 0.03 ) . CONCLUSION We conclude that the ambient labor room should be evaluated in an adequately powered r and omized controlled trial A controlled clinical trial was carried out to assess whether a birth room setting would influence the care of mothers and newborns . Of the 163 low-risk women enrolled , 49 ( 30 % ) manifested some prenatal risk and were excluded . The remaining 114 were allocated by strict alternation to a birth room or a conventional setting . Of the 56 women allocated to the birth room , 63 % of the primiparas and 19 % of the multiparas were later transferred . The numbers in the two setting s who had oxytocin stimulation , epidural anesthesia , forceps delivery or cesarean section did not show statistically significant differences . The episiotomy rates were slightly lower in the birth room than in the conventional setting , and the rates of an intact perineum were higher in the birth room . Neither the Apgar scores nor the morbidity rates of the infants showed statistically significant differences related to the setting to which the mother had been allocated , although more infants from the conventional setting were admitted to a special care unit . Both " experimental " groups of women less often received routine perineal shaving , enemas or intravenous infusions than did an obstetrically similar nonexperimental comparison group . Despite the apparent inability in this setting for the birth room to influence the rate of major obstetric procedures ( except for episiotomy ) and outcomes , the authors believe that a birth room is desirable in tertiary care centres as well as in community hospitals Objective 1 . To explore whether there are differences in women 's satisfaction with care in a midwife‐managed delivery unit compared with that in a consultant‐led labour ward . 2 . To compare factors relating to continuity , choice and control between the two r and omised groups As part of a controlled , clinical trial conducted to compare medical and psychological outcomes of a birth room and a conventional hospital setting , we examined the behavior of fathers toward their partners and infants . One hundred fourteen couples were systematic ally assigned to either locale by strict alternation . They learned about this allocation on arrival at the hospital in labor . Observations of fathers ' behavior were made at midlabor and during home visits at three months and one year . During labor , fathers assigned to the conventional setting were more involved in helping and encouraging their partners . Parenting behavior was not influenced by the birth setting . Unexpectedly , fathers were more involved with their infants when the mothers had expressed less satisfaction with childbirth . Compensation behavior may explain these results , which can be seen as appropriately adaptive in the face of perceived environmental deficiencies affecting the laboring woman and the infant Summary . A r and omized controlled trial of two environments for delivery was conducted at Queen Charlotte 's Maternity Hospital . A total of 253 parous women expecting to have a labour ward delivery were invited to participate in the trial but only 148 agreed . These women were r and omly allocated to be delivered either with st and ard labour ward management ( n= 72 ) or in the birthroom — a small bedroom decorated in a homely manner , without facilities for epidural analgesia or electronic fetal monitoring ( n= 76 ) . Eleven women in the birthroom group and 10 in the labour ward group withdrew from the trial before labour and four were transferred from the birthroom to the labour ward when in labour . A question naire sent in the postnatal period to the women who completed the trial was returned by 80 % . In the birthroom group there was significantly ( i ) decreased admission‐to‐delivery interval ( ii ) less analgesia ( iii ) more freedom of movement ( iv ) less suturing ( v ) increased rooming‐in . No difference was found in the assessment of difficulty of labour nor in the method of subsequent infant feeding Background . The objective of the study was to compare women 's use of obstetric analgesia , experience of pain in labor , and other aspects of the childbirth experience at an in‐hospital birth center and with st and ard maternity care . The birth center care was characterized by comprehensive antenatal , intrapartum and post partum care , on the same premises with a home‐like environment and the same team of midwives , restricted use of medical technology and pharmacological pain relief , and discharge within 24 h after birth OBJECTIVE to examine whether there are differences in the midwife 's role in , and satisfaction with , intrapartum care and delivery of women at low obstetric risk in a midwife-managed delivery unit compared to a consultant-led labour ward . DESIGN a pragmatic r and omised controlled trial . Subjects were r and omised in a 2:1 ratio between the midwives ' unit and the labour ward . SETTING Aberdeen Maternity Hospital , Grampian , UK . SUBJECTS midwives within the delivery suite who cared for the 2844 women at low obstetric risk receiving care in a pragmatic r and omised controlled trial of the two delivery areas . PRIMARY OUTCOME MEASURES continuity of carer and midwife satisfaction . FINDINGS midwives looking after women in the midwives ' unit group were significantly more likely to be of a higher grade , more qualified and have a longer length of experience than those in the labour ward group . There was greater continuity of carer both during labour and after delivery in the midwives ' unit group . Despite a small but statistically significant difference in overall satisfaction between the groups , area of ' booking ' or area of delivery were not important in predicting midwife satisfaction . Autonomy and continuity of carer were the best predictors of midwife satisfaction . CONCLUSIONS midwife-managed intrapartum care increases continuity of carer and , therefore , midwife satisfaction . Extending this outside the delivery suite requires a system of care that is acceptable to midwives as well as women . Such systems will depend to a large extent on geography , consumer dem and and availability of re sources . However , midwife satisfaction should also be considered . In order to do this further research is required to fully evaluate the effect these systems have on the midwives working in them BACKGROUND The safety of birth center care for low-risk women is an important issue , but it has not yet been studied in r and omized controlled trials . Our purpose was to evaluate the effect of birth center care on women 's health during pregnancy , birth , and 2 months postpartum by comparing the outcomes with those of women experiencing st and ard maternity care in the greater Stockholm area . METHODS Of 1860 women , 928 were r and omly allocated to birth center care and 932 to st and ard antenatal , intrapartum , and postpartum care . Information about medical procedures and health outcomes was collected from clinical records , and a question naire was mailed to women 2 months after the birth . Analysis was by " intention to treat ; " that is , all antenatal , intrapartum , and postpartum transfers were included in the birth center group . RESULTS During pregnancy , birth center women made fewer visits to midwives and doctors , experienced fewer tests , and reported fewer health problems . No statistical difference occurred in hospital admissions ( 4.8 % ) compared with the control group ( 4.7 % ) . During labor , birth center women used more alternative birth positions , had longer labors , and did not differ in perineal lacerations . In both groups 1.7 percent of women developed complications , requiring more than 7 days of hospital care after the birth . During the first 2 postpartum months , about 20 percent of women in both groups saw a doctor for similar types of health problems , and no statistical difference occurred in hospital readmissions , 1.4 and 0.8 percent in the birth center and control groups , respectively . CONCLUSION The results suggest that birth center care is effective in identifying significant maternal complications and as safe for women as st and ard maternity care A material of 292 normal pregnant women was subdivided at r and om for delivery either in the traditional delivery room or a newly established environmental room . The alterations in the physical environment of delivery did not result in more numerous spontaneous deliveries . A high frequency of episiotomies , stimulation of contractions and artificial deliveries in primiparae occurred particularly when it is considered that two thoroughly investigated groups of low-risk pregnant women were concerned . However , qualitative differences in the experience of the course of delivery were found in favour of the environmental room . The quality of the experience of delivery did not depend so much on the physical environment but more on contact with the staff members responsible for conduct of the delivery OBJECTIVE To compare the efficacy of midwife-managed care and obstetrician-managed care for women assessed to be at low risk in the initial intrapartum period . METHODS 1,050 women assessed to be at low risk on admission to labour ward in the Prince of Wales Hospital participated in this study . By computer-generated r and om allocation , 563 ( 54 % ) women were assigned to Group A ( experimental ) under midwifery care , and 487 ( 46 % ) women to Group B ( control ) under obstetrician care . The outcomes and complications between the 2 groups were compared . Data were analyzed by 2 x 2 contingency tables and Chi-square . RESULTS 150 ( 26.6 % ) women in the experimental group were taken over by the obstetricians . 46 ( 30.7 % ) women were transferred to obstetrician-management for the preference of epidural analgesia . The other reasons for taken over the remaining 104 ( 69.3 % ) women were fetal distress , poor progress of labour , complications in first or second stage of labour . The experimental group had less oxytocic augmentation ( Chi-square = 7.49 , p = 0.006 ) and the insertion of intravenous infusion ( Chi-square = 5.34 , p = 0.02 ) . Both groups had similar outcomes on normal delivery , operative vaginal delivery , caesarean section and complications . CONCLUSIONS Midwife-managed care is as safe as obstetrician-managed care for women who were assessed to be at low risk in the intrapartum period . Routine visit by obstetrician is not necessary and the midwives are able to detect complications in the course of labour and alert the obstetrician for taking the necessary action BACKGROUND Women 's experiences of childbirth may affect their future reproduction , and the model of care affects their experiences , suggesting that a causal link may exist between model of care and future reproduction . The study objective was to examine whether the birth center model of care during a woman 's first pregnancy affects whether or not she has a second baby , and on the spacing to the next birth . METHODS Between October 1989 and July 1993 , a total of 1860 women at low medical risk in early pregnancy , who participated in a r and omized controlled trial of in-hospital birth center care versus st and ard care , gave birth . The 1063 primiparas in the trial , 543 in the birth center group and 520 in the st and ard care group , were included in a secondary analysis in which women 's personal identification codes were linked to the Swedish National Birth Register , which included information about their subsequent birth during the following 7 to 10 years . Time to an event curves were constructed by means of the Kaplan Meier method . RESULTS The observation period after the first birth was on average 8.8 years in the birth center group and 8.7 years in the st and ard care group . No statistical difference was found between the groups in time to second birth , which was 2.85 and 2.82 years , respectively ( median ; log-rank 1.26 ; p=0.26 ) . CONCLUSION A woman 's model of care , such as birth center care , during her first pregnancy does not seem to be a sufficiently important factor to affect subsequent reproduction in Sweden Birthing centre care offers women with a low risk of complication in pregnancy an alternative to conventional care for the birthing of their baby It is important these two forms of care are appropriately assessed |
1,828 | 20,675,345 | Interventions ranged from a leaflet encouraging patients to ask more questions , to more intensive face-to-face coaching before office visits . | Disparities in provider — patient communication have been shown to exist among Asian Americans , especially those who are low-income and have limited English proficiency .
These disparities have result ed in unmet health care needs and poor quality care .
Health information technology ( health IT ) has not been widely used to improve communication , especially among patients with limited English proficiency . | Vietnamese Americans are a rapidly growing minority group in the United States , yet little is known about their health status . Chronic medical conditions and self-rated health of older Vietnamese Americans were compared with those of non-Hispanic white adults living in California using the 2001 and 2003 California Health Interview Surveys ( CHISs ) . The CHIS employed a r and om-digit-dial telephone survey , and its sample is representative of California 's noninstitutionalized population . The sample included 359 Vietnamese and 25,177 non-Hispanic white adults aged 55 and older . Vietnamese and non-Hispanic white adults were compared in terms of limitations in activities of daily living , chronic medical conditions ( diabetes mellitus , hypertension , heart disease , asthma ) , mental health care , and self-reported health , adjusting for age , sex , and education . Vietnamese were more likely than white participants to report needing help for mental health problems ( adjusted odds ratio (aOR)=2.1 , 95 % confidence interval (CI)=1.4 - 3.1 ) but less likely to have had their medical providers discuss their mental health problems with them ( aOR=0.3 , 95 % CI=0.1 - 0.5 ) . In addition , Vietnamese participants reported significantly worse health than white adults on five of eight domains of the Medical Outcomes Survery 12-item Short Form survey ( P<.006 ) . Clinicians caring for older Vietnamese individuals should be aware of the high risk for mental health needs in this population and should initiate discussion s about mental health with their patients . Further research is needed to better underst and why older Vietnamese Americans are at higher risk for worse self-reported health than older white adults OBJECTIVE Despite the importance of self-management support ( SMS ) , few studies have compared SMS interventions , involved diverse population s , or entailed implementation in safety net setting s. We examined the effects of two SMS strategies across outcomes corresponding to the Chronic Care Model . RESEARCH DESIGN AND METHODS A total of 339 out patients with poorly controlled diabetes from county-run clinics were enrolled in a three-arm trial . Participants , more than half of whom spoke limited English , were uninsured , and /or had less than a high school education , were r and omly assigned to usual care , interactive weekly automated telephone self-management support with nurse follow-up ( ATSM ) , or monthly group medical visits with physician and health educator facilitation ( GMV ) . We measured 1-year changes in structure ( Patient Assessment of Chronic Illness Care [ PACIC ] ) , communication processes ( Interpersonal Processes of Care [ IPC ] ) , and outcomes ( behavioral , functional , and metabolic ) . RESULTS Compared with the usual care group , the ATSM and GMV groups showed improvements in PACIC , with effect sizes of 0.48 and 0.50 , respectively ( P < 0.01 ) . Only the ATSM group showed improvements in IPC ( effect sizes 0.40 vs. usual care and 0.25 vs. GMV , P < 0.05 ) . Both SMS arms showed improvements in self-management behavior versus the usual care arm ( P < 0.05 ) , with gains being greater for the ATSM group than for the GMV group ( effect size 0.27 , P = 0.02 ) . The ATSM group had fewer bed days per month than the usual care group ( −1.7 days , P = 0.05 ) and the GMV group ( −2.3 days , P < 0.01 ) and less interference with daily activities than the usual care group ( odds ratio 0.37 , P = 0.02 ) . We observed no differences in A1C change . CONCLUSIONS Patient-centered SMS improves certain aspects of diabetes care and positively influences self-management behavior . ATSM seems to be a more effective communication vehicle than GMV in improving behavior and quality of life OBJECTIVE To examine the relationship between communication skills training for patients and their compliance with recommended treatment . DESIGN A r and omized control design was used , with patients nested within physicians . Each physician was audiotaped with 6 patients , 2 patients in each of the 3 intervention conditions : ( 1 ) a trained group ( n = 50 ) received a training booklet in the mail 2 to 3 days prior to the scheduled appointment , ( 2 ) an informed group ( n = 49 ) received a brief written summary of the major points contained in the training booklet while in the waiting room prior to the scheduled appointment , and ( 3 ) an untrained group ( n = 51 ) did not receive any form of communication skills intervention . SETTING Participants included physicians and patients from 9 different primary care , family practice locations . Two locations were clinics associated with a large , university-based medical school and hospital , while 7 were private practice offices in the community . PARTICIPANTS The sample included 25 family physicians ( averaging 11 years postresidency ) and 150 patients . Patients were r and omly selected from appointment records and r and omly assigned to 1 of 3 intervention conditions . INTERVENTION A training booklet design ed to instruct patients in information seeking , provision , and verification . MAIN OUTCOME MEASURE Patients ' compliance with medications , behavioral treatment ( e.g. , diet , exercise , smoking cessation ) , and /or follow-up appointments and referrals . RESULTS Trained patients were more compliant overall than untrained or informed patients . Training positively influenced compliance with behavioral treatments and follow-up appointments and referrals . CONCLUSION Training patients in communication skills may be a cost-effective way of increasing compliance and improving the overall health of patients Abstract OBJECTIVE : To examine how Asian race/ethnicity affects patients ’ health care experiences and satisfaction with care . DESIGN : Telephone interview using r and om-digit dialing , stratified to over- sample adults living in areas with disproportionately large numbers of minorities . PARTICIPANTS AND SETTING : White ( N=3,205 ) and Asian-American ( N=521 ) respondents , weighted to represent all such adults living in the continental U.S. in telephone households . MEASUREMENTS : Reports of health care experiences and trust in the doctor at the last visit , and overall satisfaction with care and desire to change doctors in the last 2 years . MAIN RESULTS : Asian Americans were less likely than whites to report that their doctors ever talked to them about lifestyle or mental health issues ( P≤.01 ) . They were more likely to report that their regular doctors did not underst and their background and values ( P≤.01 ) . When asked about the last visit , they were more likely to report that their doctors did not listen , spend as much time , or involve them in decisions about care as much as they wanted ( all P≤.0001 ) . In multivariable analyses , Asian Americans were less likely than whites to report that they were very satisfied with care ( odds ratio [ OR ] , 0.64 , 95 % confidence interval [ CI ] , 0.42 to 0.99 ) . However , they were not significantly less likely than whites to trust their doctors ( OR , 0.79 , 95 % CI , 0.52 to 1.20 ) , or to change doctors ( OR , 0.93 , 95 % CI , 0.56 to 1.56 ) . CONCLUSIONS : In a national survey , Asian Americans were less likely to receive counseling and less likely to report positive interactions with their doctors than white respondents . More research is needed to determine the reasons for these differences Research on physician-patient communication has focused on the effect of physician communication training on health care outcomes . Much less is known about patient communication training , and even less about the impact of patient race on the effectiveness of patient communication interventions . One hundred and fifty patients of 25 family physicians were r and omly assigned to one of three groups : 14-page patient communication workbook received 2 - 3 days pre-visit , 2-page patient communication h and out received in the waiting room , or control group . Racial differences in the impact of patient communication training communication variables , immediate and delayed recall of information , and adherence to treatment were analyzed by t-test and ANOVA techniques . Across analyses , workbook communication skills training had a strong and significant effect on white patients but minimal or no effect on African-American patients . Minimal differences in dependent variables between racial groups existed for the patient h and out and control groups . A partial correlation analysis was conducted to factor out the variance due to education . Results suggested that patient race accounted for the results over and above differences in education between racial groups . Our results suggested that the benefits of communication training can be enhanced by taking into account patient characteristics such as race and culture CONTEXT Pneumococcal immunization rates for elderly and high-risk patients are only one third to one half the target rate of 60 % established by the US Public Health Service . Limited or marginal literacy , which affects nearly 100 million Americans , especially the elderly , may contribute to these low rates of immunization . OBJECTIVE To determine whether the use of a simple , low-literacy educational tool enhances patient-physician dialogue about pneumococcal vaccination and increases rates of immunization . DESIGN A r and omized controlled trial conducted between May and June of 1998 . SETTING Ambulatory care clinic of a 900-bed public teaching hospital serving a predominantly indigent , low-literate , African American , inner-city population . PARTICIPANTS Of 433 patients who presented for routine primary care , had vaccine indications ( age > or = 65 years or chronic disease ) , and had not been previously vaccinated , 221 were r and omly assigned to the intervention group and 212 to the control group . Of the total patient population ( mean age , 63 years ) , 280 ( 64.7 % ) had less than a high school education , 401 ( 92.6 % ) were African American , and 300 ( 69.3 % ) were female . INTERVENTION One-page , low-literacy ( below fifth- grade level ) educational h and out encouraging patients to " ask your doctor about the pneumonia shot " vs a control group ( 1 -page , low-literacy educational h and out conveying information about nutrition ) . MAIN OUTCOME MEASURES Vaccination rates ( documented by chart audit ) of patients who received pneumococcal vaccination and rates of patients who self-reported having discussed vaccination with their physicians . RESULTS Patients in the intervention group were 4 times more likely to have discussed the pneumococcal vaccine with their physicians than patients in the control group ( 87/221 [ 39.4 % ] vs 21/212 [ 9.9 % ] ; relative risk [ RR ] , 3.97 [ 95 % confidence interval [ CI ] , 2.71 - 5.83 ] ) , and were more than 5 times as likely to have received the pneumococcal vaccine than the control group ( 44/221 [ 19.9 % ] vs 8/212 [ 3.8 % ] ; RR , 5.28 [ 95 % CI , 2.80 - 9.93 ] ) . In a multivariate analysis controlling for race , sex , education , insurance status , age , level of physician training , health status , and vaccine indication , only assignment to the intervention group was statistically significantly related to the probability of being immunized or discussing the issue with their physicians ( P<.001 for both trends ) . CONCLUSIONS A simple , low-literacy educational tool increased pneumococcal vaccination rates and patient-physician discussion s about the vaccine in an elderly , low-literate , indigent , minority population It is important for patients to provide relevant information to the doctor in consultation and to make their own information requirements known . This requires patients to actively participate in the process , something they appear to be reluctant to do . Earlier patient intervention studies have successfully manipulated patient involvement and question asking , although , the latter has tended to be accompanied by increased tension and negative impact . The present study uses a patient education leaflet which uses a wide definition of patient activation . It emphasizes the role of the ' good ' patient as a provider of information extending beyond the recitation of symptoms to include insights to interpretation and meaning . Results showed that patients responded positively to the leaflet and a comparison of doctor ratings of communication quality showed the experimental group performed better than the controls . The findings are considered in terms of improved information exchange and the impact of making the ' rules ' of consultation explicit is also discussed BACKGROUND Active participation and asking questions are important ways in which patients can ensure they underst and what the doctor has said . This study evaluated a question prompt sheet design ed to encourage patients to ask questions in the cancer consultation . PATIENTS AND METHODS Patients ( n = 142 ) were r and omised to receive ( i ) a question prompt sheet or ( ii ) a general sheet informing patients of services available through the regional Cancer Council . Recall of information was assessed in a structured interview 4 - 20 days after the consultation . Question naires to assess patient satisfaction and adjustment to cancer were sent by mail . RESULTS The question prompt sheet had a significant effect in one content area : prognosis . Thirty-five percent of patients who received the question h and out asked questions about prognosis compared to 16 % of those receiving the information h and out . The prompt sheet did not increase the mean number of questions asked overall . Age , in/out-patient status , gender and involvement preference were predictive of both number and duration of patient questions . CONCLUSIONS A question prompt sheet has a limited but important effect on patient question asking behaviour in the cancer consultation This study examined the efficacy of a brief written intervention for primary care patients , design ed to increase their level of participation in the consultation . Patients given the intervention leaflet ( N = 59 ) were compared with those given a control leaflet ( N = 61 ) on various consultation process and outcome measures . Psychological and sociodemographic data were also obtained to determine whether these influenced the effects of the intervention . The results showed that the intervention group had significantly longer consultations and asked more questions than the controls . Younger patients and those from social classes 1 and 2 were more likely to benefit from the intervention , but locus of control and self-efficacy scores were not particularly helpful in predicting outcomes . No differences in patient satisfaction were found nor were any negative effects on the doctor observed . A number of explanations are explored and some directions for future research are discussed CONTEXT Treating hypertension decreases mortality and disability from cardiovascular disease , but most hypertension remains inadequately controlled . OBJECTIVE To determine if a new model of care that uses patient Web services , home blood pressure ( BP ) monitoring , and pharmacist-assisted care improves BP control . DESIGN , SETTING , AND PARTICIPANTS A 3-group r and omized controlled trial , the Electronic Communications and Home Blood Pressure Monitoring study was based on the Chronic Care Model . The trial was conducted at an integrated group practice in Washington state , enrolling 778 participants aged 25 to 75 years with uncontrolled essential hypertension and Internet access . Care was delivered over a secure patient Web site from June 2005 to December 2007 . INTERVENTIONS Participants were r and omly assigned to usual care , home BP monitoring and secure patient Web site training only , or home BP monitoring and secure patient Web site training plus pharmacist care management delivered through Web communications . MAIN OUTCOME MEASURES Percentage of patients with controlled BP ( < 140/90 mm Hg ) and changes in systolic and diastolic BP at 12 months . RESULTS Of 778 patients , 730 ( 94 % ) completed the 1-year follow-up visit . Patients assigned to the home BP monitoring and Web training only group had a nonsignificant increase in the percentage of patients with controlled BP ( < 140/90 mm Hg ) compared with usual care ( 36 % [ 95 % confidence interval { CI } , 30%-42 % ] vs 31 % [ 95 % CI , 25%-37 % ] ; P = .21 ) . Adding Web-based pharmacist care to home BP monitoring and Web training significantly increased the percentage of patients with controlled BP ( 56 % ; 95 % CI , 49%-62 % ) compared with usual care ( P < .001 ) and home BP monitoring and Web training only ( P < .001 ) . Systolic BP was decreased stepwise from usual care to home BP monitoring and Web training only to home BP monitoring and Web training plus pharmacist care . Diastolic BP was decreased only in the pharmacist care group compared with both the usual care and home BP monitoring and Web training only groups . Compared with usual care , the patients who had baseline systolic BP of 160 mm Hg or higher and received home BP monitoring and Web training plus pharmacist care had a greater net reduction in systolic BP ( -13.2 mm Hg [ 95 % CI , -19.2 to -7.1 ] ; P < .001 ) and diastolic BP ( -4.6 mm Hg [ 95 % CI , -8.0 to -1.2 ] ; P < .001 ) , and improved BP control ( relative risk , 3.32 [ 95 % CI , 1.86 to 5.94 ] ; P<.001 ) . CONCLUSION Pharmacist care management delivered through secure patient Web communications improved BP control in patients with hypertension . Trial Registration clinical trials.gov Identifier : NCT00158639 |
1,829 | 28,782,675 | The OR for dyspepsia in individuals with weekly GERS was significantly higher in all geographical regions studied and for all diagnostic criteria .
: The odds of dyspepsia in individuals with weekly GERS is almost 7‐fold that of individuals without GERS ; dyspepsia and GERS overlap in more than 25 % of individuals . | BACKGROUND & AIMS : Dyspepsia and gastroesophageal reflux are highly prevalent in the general population , but they are believed to be separate entities .
We conducted a systematic review and meta‐ analysis to estimate the prevalence of dyspepsia in individuals with gastroesophageal reflux symptoms ( GERS ) , and to quantify overlap between the disorders . | Background and aims : Patients with functional dyspepsia who have hypersensitivity to gastric distension have more prevalent pain , suggesting the presence of hyperalgesia . It is unclear whether this reflects activation of pain specific afferent pathways or multimodal afferent pathways that also mediate non-painful sensations . In the former case , hyperalgesia should occur when intensity of non-painful sensations is still low . The aim of the study was to analyse whether the symptom profile during gastric dissentions in functional dyspepsia patients with hyperalgesia reflects sensitisation of pain specific or multimodal pathways . Methods : Forty eight consecutive dyspeptic patients ( 35 female ) underwent gastric sensitivity testing with a barostat balloon using a double r and om staircase protocol . At the end of every distending step , patients scored perception of upper abdominal sensations on a graphic 0–6 rating scale and completed visual analogue scales ( VAS 0–100 mm ) for pain , nausea , satiety , and fullness . The end point was a rating scale of 5 or more . Results : Hypersensitivity was present in 20 patients ( 40 % ) ; gastric compliance did not differ between normo- and hypersensitive patients . At maximal distension ( score 5 or more ) , hypersensitive patients had significantly lower distending pressures and intra-balloon volumes , but similar VAS scores for pain , nausea , satiety , and fullness compared with normosensitive patients . In both normosensitive and hypersensitive patients , elevation of pain VAS scores with increasing distending pressures paralleled the elevation in VAS scores for nausea , satiety , and fullness . Conclusions : Hypersensitive dyspeptic patients reach the same intensity of painful and non-painful sensations as normosensitive patients but at lower distending pressures . Hyperalgesia occurs in hypersensitive dyspeptic patients at distending pressures that also induce intense non-painful sensations . These findings argue against isolated upregulation of pain specific afferents in functional dyspepsia patients with visceral hypersensitivity OBJECTIVE To evaluate the association between functional gastrointestinal ( GI ) symptoms and a family history of abdominal pain or bowel problems . SUBJECTS AND METHODS A valid self-report question naire that records GI symptoms and spouse 's and first-degree relatives ' history of abdominal pain or bowel troubles and includes the psychosomatic symptom checklist ( a measure of somatization ) was mailed to an age- and sex-stratified r and om sample of Olmsted County , Minnesota , residents aged 30 to 64 years . A logistic regression model that adjusted for age , sex , and somatic symptom score was used to estimate the odds ratio ( OR ) and 95 % confidence interval ( CI ) of a positive family history for each functional GI disorder . RESULTS Six hundred forty-three ( 72 % ) of 892 eligible subjects returned the survey . Reporting a first-degree relative with abdominal pain or bowel problems was significantly associated with reporting of irritable bowel syndrome ( OR , 2.3 ; 95 % CI , 1.3 - 3.9 ) and dyspepsia ( OR , 1.8 ; 95 % CI , 1.05 - 3.0 ) but not constipation , diarrhea , or gastroesophageal reflux . The reporting of a spouse with abdominal pain or bowel problems was not associated with any of these disorders . CONCLUSIONS A history of abdominal pain or bowel troubles in first-degree relatives was significantly associated with irritable bowel syndrome and dyspepsia . Whether the familial associations represent similar exposures in a shared environment , heightened familial awareness of GI symptoms ( reporting bias ) , or genetic factors remains to be determined BACKGROUND / AIMS Dyspepsia and gastroesophageal reflux disease are common chronic diseases . In the clinical setting , some patients express both problems together ; however , little is known about the real prevalence of the presence of the two symptoms . Turkey is particularly interesting because of differences observed from developed countries . We aim ed to derive data from our previous prevalence of gastroesophageal reflux disease study and evaluate the overlap of the two symptoms . METHODS We used a previously vali date d and culturally adapted reflux question naire , which was translated into Turkish . The question naire was applied to 630 r and omly selected subjects older than 20 years living in a population of 8857 adults . RESULTS 28.6 % ( 180/630 ) of all responders defined dyspepsia within the last 12-month period . When symptom prevalence was considered at least weekly , the prevalence was 10 % for heartburn , 15.6 % for acid regurgitation , and 20 % for either symptom . While the prevalence of gastroesophageal reflux disease was 29.4 % in patients with dyspepsia , dyspepsia was found in 43.1 % of patients with gastroesophageal reflux disease . Only 21 % of symptomatic subjects or 8.4 % of the entire study population had both symptoms . Dyspepsia was defined as the most bothersome symptom . 54.3 % of all dyspeptic patients and 67.3 % with both gastroesophageal reflux disease and dyspepsia used a gastric medication ( p>0.05 ) . 29.9 % of subjects with dyspeptic symptoms defined antacid consumption and 28.3 % acid inhibitor therapy . CONCLUSION Dyspepsia was defined as the most bothersome symptom compared to gastroesophageal reflux disease symptoms . The prevalence of dyspepsia in patients with gastroesophageal reflux disease is more common than vice versa . However , the overlap of the two symptom groups was lower than expected in this low-income , Caucasian population BACKGROUND AND STUDY AIMS Gastro-oesophageal reflux disease ( GERD ) and dyspepsia are common digestive disorders that inflict serious harm , burden and economic consequences on individuals worldwide . The aim of this study was to estimate the direct and indirect economic burden of GERD and dyspepsia in the whole population of Tehran , the capital of Iran . PATIENTS AND METHODS The study was performed on a total of 18,180 adult subjects ( age>18 years ) taken as a r and om sample in Tehran province , Iran ( 2006 - 2007 ) . A valid and reliable question naire was used to enquire about the symptoms of GERD , dyspepsia and the frequency of the utilization of health services including physician visits , hospitalisations and productivity loss due to GERD/dyspepsia symptoms in the preceding 6 months . RESULTS GERD was found in 518 ( 41.9 % males ) patients and dyspepsia in 404 patients ( 38.9 % males ) . Further 1007 subjects had both GERD and dyspepsia . The total direct costs of disease per patient for GERD , dyspepsia and their overlap were PPP$97.70 , PPP$108.10 and PPP$101.30 , respectively ( PPP , purchasing power parity dollars ) . The total indirect cost of disease per patient was PPP$13.7 , PPP$12.1 and PPP$32.7 , for GERD , dyspepsia and their overlap , respectively . CONCLUSION According to our results , hospitalisation and physician visits were the main cost of disease that could be minimised by revision of the insurance business in Iran BACKGROUND & AIMS Hypersensitivity to proximal gastric distention as a result of abnormal central nervous system processing of visceral stimuli is a possible pathophysiologic mechanism in functional dyspepsia ( FD ) . Increasing evidence suggests involvement of both lateral and medial pain systems in normal visceral sensitivity and aberrant brain activation patterns in visceral hypersensitivity . We hypothesized that there is involvement of aberrant brain activation in FD with hypersensitivity to gastric distention . Our aim was to investigate regional cerebral blood flow during painful proximal gastric distention in hypersensitive FD . METHODS Brain (15)O-water positron emission tomography was performed in 13 FD patients with symptoms of gastric hypersensitivity during 3 conditions : no distention , sham distention , and isobaric distention to unpleasant or painful sensation . Pain , discomfort , nausea , and bloating during maximal distention were rated on visual analogue scales . Data were analyzed using statistical parametric mapping . RESULTS The threshold for painful distention was 6.6 + /- 3.8 mm Hg greater than the minimal distending pressure . At the corrected P level of less than .05 , subtraction analysis ( painful distention - no distention ) showed activations in bilateral gyrus pre central is , bilateral gyrus frontalis inferior , bilateral gyrus frontalis medialis , bilateral gyrus temporalis superior , bilateral cerebellar hemisphere , and left gyrus temporalis inferior . Sham distention minus no distention showed no activations . CONCLUSIONS Similar to healthy volunteers , proximal stomach distention in FD activates components of the lateral pain system and bilateral frontal inferior gyri , putatively involved in regulation of hunger and satiety . In hypersensitive FD , these activations occur at significantly lower distention pressures . In contrast to findings in normosensitivity , none of the components of the medial pain system were significantly activated BACKGROUND : The heterogeneity of the dyspepsia symptom complex is well known . Several attempts to classify dyspepsia into subgroups have been proposed as a basis for diagnosis and therapy , but data are conflicting . We postulated that dyspepsia comprises three distinct subsets , characterized by pain , early satiety , or nausea/vomiting . We aim ed to identify these subsets of dyspepsia : “ frequent upper abdominal pain ( UAP ) , ” “ early satiety ( ES ) , ” and “ nausea/vomiting ( NV ) . ” METHODS : A population -based , cross-sectional survey study was conducted by mailing a valid question naire to an age- and gender-stratified r and om sample of residents of Olmsted County , MN , aged 20–94 yr ( response rate 55 % ) . Dyspepsia and irritable bowel syndrome ( IBS ) prevalence were estimated by Rome II criteria ; gastroesophageal reflux ( GERD ) by weekly or more frequent heartburn or acid regurgitation . Dyspepsia subgroups were categorized based on a priori defined symptoms . RESULTS : The prevalence ( 95 % CI ) of dyspepsia was 15 % ( 14 , 17 ) . Of 351 dyspeptic subjects , 51 % ( 46 , 56 ) reported UAP , 21 % ( 16 , 25 ) NV , and 47 % ( 42 , 52 ) ES . The overlap of the subgroups was significantly less than expected by chance . Among the three groups , the subjects were similar in age , educational level , IBS status , and overall symptom severity . A high somatic symptom checklist score and those with GERD were associated with greater odds for reporting combination symptoms compared with the upper abdominal pain subgroup of dyspepsia or the early satiety subgroup of dyspepsia , respectively . CONCLUSION : Distinct subgroups of uninvestigated dyspepsia do exist in the general population , suggesting that separate evaluation and treatment strategies are needed OBJECTIVE : Upper gastrointestinal disorders are common in the community , yet the determinants of these symptoms are poorly characterized . The association between upper gastrointestinal symptoms and Helicobacter pylori ( H. pylori ) , socioeconomic status , nonsteroidal antiinflammatory drug ( NSAID ) use , smoking , alcohol , and coffee intake was assessed in a cross-sectional survey . METHODS : Subjects between the ages of 40–49 yr were r and omly selected from the lists of 36 primary care centers . Participants attended their local primary care center and were interviewed by a research er using a vali date d dyspepsia question naire . H. pylori status was determined by a nonfasting 13C-urea breath test . RESULTS : A total of 32,929 subjects were invited , and 8,407 ( 25 % ) attended and were eligible . Of these , 2,329 ( 28 % ) were H. pylori positive and 3,177 ( 38 % ) had dyspepsia . Also , 44 % of H. pylori-infected participants reported dyspepsia compared with 36 % of uninfected subjects [ odds ratio = 1.39 ; 95 % confidence interval ( CI ) 1.26–1.53 ] . H. pylori infection remained a significant risk factor for dyspepsia in a multiple logistic regression model ( odds ratio = 1.21 ; 95 % CI 1.09–1.34 ) , suggesting that 5 % of dyspepsia in the population is attributable to H. pylori . NSAIDs , low educational attainment , renting accommodation , absence of central heating , sharing a bed with siblings , and being married were also significantly associated with dyspepsia in this model . Smoking , but not drinking alcohol or coffee , was marginally associated with dyspepsia , but this finding was not robust . These factors were not associated with any dyspepsia subtype . CONCLUSIONS : H. pylori is significantly associated with dyspepsia and may be responsible for 5 % of upper gastrointestinal symptoms in the community The factors that drive subjects with dyspepsiain the community to seek medical care are uncertain . We aim ed to identify whether psychological factors explainhealth care utilization among subjects with dyspepsia . A sample of residents of westernSydney selected r and omly from the electoral rolls wasmailed a vali date d self-report question naire . Dyspepsiawas defined as pain or discomfort centered in the upper abdomen . Potential predictors ofphysician visits tested included gastrointestinalsymptoms , neuroticism ( by the Eysenck Personality Question naire ) , psychological morbidity ( General Health Question naire ) , and sexual , physical , and emotional abuse(based on st and ardized criteria ) . Among 730 subjects,13 % ( 95 % CI 10.3 - 15.2 % ) had dyspepsia and 70 % ( 95 % CI59.8 - 79.5 % ) had sought medical care . Subjects with dyspepsia had significantly higher neuroticism and psychological morbidity scores and reportedchildhood emotional abuse more often than those withoutdyspepsia ( all P < 0.05 ) , but none of these wereindependent predictors . Male gender ( OR = 0.58 , 95 % CI0.37- 0.91 ) , greater pain severity ( OR = 2.49 , 95 % CI2.12 - 2.91 , P < 0.01 ) , and meeting the Rome criteria for irritable bowel ( OR = 2.0 , 95 % CI 1.06 - 3.78 ) wereassociated with dyspepsia subjects seeing a physician oralternative therapist for abdominal pain or discomfort , explaining 32 % of the deviance . Pain severity ( OR = 1.39 , 95 % CI 1.22 - 1.58 ) and symptoms of five or more years duration ( OR = 5.73 , 95 % CI 3.71 - 8.87)were predictive of dyspepsia subjects ever seeking carefor abdominal pain or discomfort , explaining 15 % of thedeviance . Psychological factors were not significant predictors of seeking medical attention indyspepsia . Health care seeking among community subjectswith dyspepsia is explained in part by symptom severity and duration but not by neuroticism , psychological morbidity , or a history of abuse Background : The majority of patients with gastro‐oesophageal reflux disease do not present with erosive oesophagitis and make up a heterogeneous group . Patients with non‐erosive gastro‐oesophageal reflux disease are less responsive than patients with oesophagitis to acid‐suppressive therapy BACKGROUND / AIMS A link between abuse and irritable bowel syndrome ( IBS ) has been reported in out patients but remains controversial . No population -based studies have investigated this issue . The aim of this study was to determine the prevalence of abuse and its association with symptoms in a representative community sample . METHODS An age- and sex-stratified r and om sample of residents of Olmsted County , Minnesota ranging in age from 30 to 49 years was mailed a valid self-report symptom question naire . Abuse was assessed by st and ard published criteria . RESULTS Of the 919 responders ( 74 % ) , the age-adjusted prevalence of any abuse was 41 % in women and 11 % in men , result ing in an age- and sex-adjusted prevalence of 26 % . Symptoms of IBS , dyspepsia , and frequent heartburn were reported by 14 % , 23 % , and 12 % , respectively . There was a significant association between IBS and sexual abuse , emotional or verbal abuse , and abuse in childhood and adulthood . Similarly , dyspepsia and heartburn were both significantly associated with abuse . In the population , 31 % had visited a physician for gastrointestinal symptoms ; the odds of visiting a physician were highest in those reporting abuse in adulthood and childhood . CONCLUSIONS Self-reported abuse is common in middle-aged subjects ; those who report abuse are more likely to have symptoms consistent with IBS , dyspepsia , or heartburn and to visit a physician for bowel symptoms Abstract Introduction . Gastroesophageal reflux disease ( GERD ) , functional dyspepsia ( FD ) and irritable bowel syndrome ( IBS ) are common functional gastrointestinal conditions with significant impact on the daily lives of individuals . The objective was to investigate the prevalence and overlap of the three conditions in a Western general population . Material and methods . A nationwide study of 100,000 individuals 20 years and above , r and omly selected in the general population . A web-based question naire survey formed the basis of this study . Questions regarding FD and IBS were extracted from the ROME III adult question naire . Questions regarding GERD were developed based on the Montreal definition . Prevalence estimates for GERD , FD IBS were calculated in total and for each sex separately and for four age groups . A Venn diagram was constructed , illustrating the overlap between the three conditions . Results . The overall response rate was 52.2 % . The prevalence of GERD , FD and IBS was 11.2 % , 7.7 % and 10.5 % , respectively , and overlap between two or three of these conditions was seen among 6.5 % of the respondents . Among individuals meeting the criteria of one or more of the conditions GERD , FD and IBS , 30.7 % had overlap between two or all three conditions . Conclusion . GERD , FD and IBS are common conditions in the general population and the overlap between these conditions is also quite common . When diagnosing patients with GERD , FD and IBS , physicians should keep in mind that these patients could be suffering from more than one of these conditions Limited data exist to determine the prevalence and clinical spectrum of gastroesophageal reflux disease ( GERD ) in the Russian population , which might be different from those in Western countries . This study was performed in Moscow on r and omized 1065 adults aged ≥15 years . A vali date d reflux question naire comprising 72 questions and an additional 29 sub- questions were used . The questions assessed ( heartburn and regurgitation ) and related ( dyspepsia , dysphagia , odynophagia and chest pain ) symptoms , the triggering factors of these symptoms , family history and data on demographic and socioeconomic features . GERD was defined as heartburn and /or regurgitation once a week or common . Of the 1065 participants , 42.1 % were male and 57.9 % were female . The prevalences of frequent and occasional symptoms were 17.6 and 22.1 % for heartburn and 17.5 and 21.8 % for regurgitation , respectively , over the last 12 months . The prevalence of GERD was found to be 23.6 % . The rate of GERD was significantly higher in females than in males ( 15.4 vs. 29.5 % , P < 0.001 ) and significantly increased as the age of the participants increased ( P = 0.011 ) . GERD was present in 20.4 % of smokers , 24.2 % of coffee drinkers , 21.5 % of alcohol consumers and 45.9 % of stressed participants . Although the rate of alcohol consumers was lower in those with GERD compared with those without GERD , the rate of coffee drinkers and stressed participants was higher among those with GERD . The rate of additional symptoms was higher even in participants complaining of regurgitation/heartburn rarely , compared with those without complaints . Using the same question naire , which makes it possible to compare the present results with those from different countries , we found the prevalence of GERD in Moscow to be 23.6 % , one of highest in the Western population s. The rates of heartburn and regurgitation were found to be similar , which constitutes a different result than has been found in similar studies . Additional symptoms should be assessed , in all GERD patients even in the presence of rare complaints of regurgitation/heartburn |
1,830 | 28,714,797 | No differences between home-based training with telemonitoring control guidance and centre-based training on physical fitness , physical activity level or health-related quality of life have been observed .
Instead , home-based training was associated with greater patient satisfaction and appears to be more cost-effective than centre-based training .
In the above group , heart rate was monitored by a chest strap and data were uploaded to a web application , allowing the patient , therapist and exercise specialist to review the data .
Thus home-based training with telemonitoring guidance can be used as an alternative to centre-based training for low-to-moderate cardiac risk patients .
Electrical myostimulation ( EMS ) on top of exercise training has no significant additional improvement in exercise capacity in heart failure patients .
EMS has shown potential beneficial effects such as improvement of muscle function , exercise capacities , endothelial function and quality of life , in those patients who are unable or unwilling to adhere to conventional exercise .
However , in a r and omised prospect i ve French trial , the combination of physical exercise with EMS was not associated with greater improvement in oxygen uptake or quality of life .
The study population included only moderately severe and stable heart failure patients with baseline peak oxygen uptake around 16–17ml/kg/min ; thus the results may not be extrapolated to more severe patients .
In a systematic review of the existing literature , progressive resistance training result ed in an increase in lower and upper body strength , and improved aerobic fitness to a similar degree as aerobic training in coronary heart disease cohorts .
Importantly , when progressive resistance training was added to aerobic training , effects on both fitness and strength were enhanced compared to aerobic training alone .
The two contact photoplethysmography-based apps had higher feasibility and better accuracy for heart rate measurement than the two non-contact photoplethysmography-based apps | Cardiac rehabilitation is the main topic of the 12th issue of the Journal .
In cardiac rehabilitation , heart rate monitoring is an essential component of almost all clinical situations : the accuracy of four different heart rate measuring apps was compared to electrocardiogram and pulse oximeter-derived heart rate using medically approved professional devices . | Background The purpose of this study was to evaluate the effect of a physical activity telemonitoring program on daily physical activity level , oxygen uptake capacity ( VO2peak ) , and cardiovascular risk profile in coronary artery disease ( CAD ) patients who completed phase II cardiac rehabilitation ( CR ) . Methods Eighty CAD patients who completed phase II CR were r and omly assigned to an additional telemonitoring intervention or st and ard CR . The patients in the intervention group ( n = 40 ) wore a motion sensor continuously for 18 weeks . Each week these patients received a step count goal , with the aim to gradually increase the patients ’ physical activity level . In the control group ( n = 40 ) , the patients wore an unreadable motion sensor for seven days for measurement purpose s only ( at start of follow-up , and after six and 18 weeks ) . At start of follow-up and after 18 weeks blood lipid profile , glycemic control , waist circumference and body mass index was assessed . VO2peak was assessed at start of follow-up , and after six and 18 weeks . Re-hospitalisation rate was followed during this timeframe . Results In the intervention group , VO2peak increased significantly during follow-up ( P = 0.001 ) , in the control group it did not ( P = 0.273 ) . A significant correlation was found between daily aerobic step count and improvement in VO2peak ( P = 0.030 , r = 0.47 ) . Kaplan-Meier curve analysis showed a trend towards fewer re-hospitalisations for patients in the telemonitoring group ( P = 0.09 ) . Conclusions The study showed that , to maintain exercise tolerance and lower re-hospitalisation rate after hospital-based CR in CAD patients , a physical activity telemonitoring program might be an effective intervention Background Smartphone manufacturers offer mobile health monitoring technology to their customers , including apps using the built-in camera for heart rate assessment . This study aim ed to test the diagnostic accuracy of such heart rate measuring apps in clinical practice . Methods The feasibility and accuracy of measuring heart rate was tested on four commercially available apps using both iPhone 4 and iPhone 5 . ‘ Instant Heart Rate ’ ( IHR ) and ‘ Heart Fitness ’ ( HF ) work with contact photoplethysmography ( contact of fingertip to built-in camera ) , while ‘ What s My Heart Rate ’ ( WMH ) and ‘ Cardiio Version ’ ( CAR ) work with non-contact photoplethysmography . The measurements were compared to electrocardiogram and pulse oximetry-derived heart rate . Results Heart rate measurement using app-based photoplethysmography was performed on 108 r and omly selected patients . The electrocardiogram-derived heart rate correlated well with pulse oximetry ( r = 0.92 ) , IHR ( r = 0.83 ) and HF ( r = 0.96 ) , but somewhat less with WMH ( r = 0.62 ) and CAR ( r = 0.60 ) . The accuracy of app-measured heart rate as compared to electrocardiogram , reported as mean absolute error ( in bpm ± st and ard error ) was 2 ± 0.35 ( pulse oximetry ) , 4.5 ± 1.1 ( IHR ) , 2 ± 0.5 ( HF ) , 7.1 ± 1.4 ( WMH ) and 8.1 ± 1.4 ( CAR ) . Conclusions We found substantial performance differences between the four studied heart rate measuring apps . The two contact photoplethysmography-based apps had higher feasibility and better accuracy for heart rate measurement than the two non-contact photoplethysmography-based apps Background In contrast to the well-accepted benefits of moderate exercise , recent research has suggested potential deleterious effects of repeated marathon running on the cardiovascular system . We thus performed a comprehensive analysis of markers of sub clinical vascular damage in a cohort of runners having finished multiple marathon races successfully . Design This was a prospect i ve , observational study . Methods A total of 97 healthy male Munich marathon participants ( mean age 44 ± 10 years ) underwent detailed training history , cardiopulmonary exercise testing for assessment of peak oxygen uptake , ultrasound for assessment of intima-media-thickness as well as non-invasive assessment s of ankle-brachial index , augmentation index , pulse wave velocity and reactive hyperaemia index . Results Runners had previously completed a median of eight ( range 1–500 ) half marathons , six ( 1–100 ) full marathons and three ( 1–40 ) ultramarathons ; mean weekly and annual training volumes were 59 ± 23 and 1639 ± 979 km . Mean peak oxygen uptake was 50 ± 8 ml/min/kg , and the Munich marathon was finished in 3:45 ± 0:32 h. Runners showed normal mean values for intima-media-thickness ( 0.60 ± 0.14 mm ) , ankle-brachial index ( 1.2 ± 0.1 ) , augmentation index ( 17 ± 13 % ) , pulse wave velocity ( 8.7 ± 1.4 cm/s ) and reactive hyperaemia index ( 1.96 ± 0.50 ) . Age was significantly and independently associated with intima-media-thickness ( r = 0.531 ; p < 0.001 ) , augmentation index ( r = 0.593 ; p < 0.001 ) and pulse wave velocity ( r = 0.357 ; p < 0.001 ) . However , no independent associations of peak oxygen uptake , marathon finishing time , number of completed races or weekly and annual training km with any of the vascular parameters were observed . Conclusions In this cohort of healthy male runners , running multiple marathon races did not pose an additional risk factor for premature sub clinical vascular impairment beyond age Aim Although cardiac rehabilitation improves physical fitness after a cardiac event , many eligible patients do not participate in cardiac rehabilitation and the beneficial effects of cardiac rehabilitation are often not maintained over time . Home-based training with telemonitoring guidance could improve participation rates and enhance long-term effectiveness . Methods and results We r and omised 90 low-to-moderate cardiac risk patients entering cardiac rehabilitation to three months of either home-based training with telemonitoring guidance or centre-based training . Although training adherence was similar between groups , satisfaction was higher in the home-based group ( p = 0.02 ) . Physical fitness improved at discharge ( p < 0.01 ) and at one-year follow-up ( p < 0.01 ) in both groups , without differences between groups ( home-based p = 0.31 and centre-based p = 0.87 ) . Physical activity levels did not change during the one-year study period ( centre-based p = 0.38 , home-based p = 0.80 ) . Healthcare costs were statistically non-significantly lower in the home-based group ( € 437 per patient , 95 % confidence interval –562 to 1436 , p = 0.39 ) . From a societal perspective , a statistically non-significant difference of € 3160 per patient in favour of the home-based group was found ( 95 % confidence interval –460 to 6780 , p = 0.09 ) and the probability that it was more cost-effective varied between 97 % and 75 % ( willingness-to-pay of € 0 and € 100,000 per quality -adjusted life-years , respectively ) . Conclusion We found no differences between home-based training with telemonitoring guidance and centre-based training on physical fitness , physical activity level or health-related quality of life . However , home-based training was associated with a higher patient satisfaction and appears to be more cost-effective than centre-based training . We conclude that home-based training with telemonitoring guidance can be used as an alternative to centre-based training for low-to-moderate cardiac risk patients entering cardiac rehabilitation Background Exercise training as part of a comprehensive cardiac rehabilitation is recommended for patients with cardiac heart failure . It is a valuable method for the improvement of exercise tolerance . Some studies reported a similar improvement with quadricipital electrical myostimulation , but the effect of combined exercise training and electrical myostimulation in cardiac heart failure has not been yet evaluated in a large prospect i ve multicentre study . Purpose The aim of this study was to determine whether the addition of low frequency electrical myostimulation to exercise training may improve exercise capacity and /or muscular strength in cardiac heart failure patients . Methods Ninety-one patients were included ( mean age : 58 ± 9 years ; New York Heart Association II/III : 52/48 % , left ventricular ejection fraction : 30 ± 7 % ) in a prospect i ve French study . The patients were r and omised into two groups : 41 patients in exercise training and 50 in exercise training + electrical myostimulation . All patients underwent 20 exercise training sessions . In addition , in the exercise training + electrical myostimulation group , patients underwent 20 low frequency ( 10 Hz ) quadricipital electrical myostimulation sessions . Each patient underwent a cardiopulmonary exercise test , a six-minute walk test , a muscular function evaluation and a quality of life question naire , before and at the end of the study . Results A significant improvement of exercise capacity ( Δ peak oxygen uptake+15 % in exercise training group and + 14 % in exercise training + electrical myostimulation group ) and of quality of life was observed in both groups without statistically significant differences between the two groups . Mean creatine kinase level increased in the exercise training group whereas it remained stable in the combined group . Conclusions This prospect i ve multicentre study shows that electrical myostimulation on top of exercise training does not demonstrate any significant additional improvement in exercise capacity in cardiac heart failure patients Background Exercise training is an established modality in chronic heart failure . Functional electrical stimulation ( FES ) is an effective alternative mode of training in patients unwilling or unable to exercise ; however , it has not been investigated in elderly patients . We sought to investigate the effects of FES on functional status , quality of life , emotional status and endothelial function in chronic heart failure patients aged 70 years or higher . Methods Thirty patients with stable systolic chronic heart failure ( mean age 75 ± 3 years , New York Heart Association ( NYHA ) class II/III , 37%/63 % ) r and omly underwent a six-week FES training programme or placebo . Question naires addressing quality of life ( Kansas City Cardiomyopathy Question naire ( KCCQ ) , functional and overall ) and emotional stress ( Zung self-rating depression scale ( SDS ) , Beck Depression Inventory ( BDI ) ) , as well as endothelial function ( flow-mediated dilatation ) were assessed at baseline and upon protocol completion . Results A significant improvement in NYHA class ( p = 0.005 ) , KCCQ-functional ( F = 68.6 , p for interaction < 0.001 ) , KCCQ-overall ( F = 66.9 , p < 0.001 ) , BDI ( F = 66.3 , p < 0.001 ) and Zung SDS ( F = 95.1 , p < 0.001 ) was observed in the FES group compared to placebo . Patients in the FES group also had a significant increase in flow-mediated dilatation compared with placebo ( F = 59.1 , p < 0.01 ) . FES-induced per cent change in flow-mediated dilatation was significantly correlated with respective per cent change in KCCQ functional ( r = 0.386 , p = 0.039 ) . Conclusion In this pilot study , FES effectively improved functional status , quality of life , motional stress and endothelial function in elderly chronic heart failure patients and warrants further investigation in this particular group of patients |
1,831 | 21,735,439 | Our estimates of benefits from dietary salt restriction are consistent with the predicted small effects on clinical events attributable to the small blood pressure reduction achieved | BACKGROUND An earlier Cochrane review of dietary advice identified insufficient evidence to assess effects of reduced salt intake on mortality or cardiovascular events .
To assess the long term effects of interventions aim ed at reducing dietary salt on mortality and cardiovascular morbidity.2 .
To investigate whether blood pressure reduction is an explanatory factor in any effect of such dietary interventions on mortality and cardiovascular outcomes . | Sodium restriction can reduce blood pressure in hypertensive patients . The present study indicates that if hypertension is well controlled then the reemergence of hypertension can be decreased by the use of a reduced sodium intake . The present paper demonstrates that in such patients on a normal salt diet , 90 % become hypertensive within 6 months while only 40 % of people on a reduced sodium diet become hypertensive . It is proposed that a high sodium intake activates a number of amplifiers that causes a shift of the dose-response curve to sodium to the left and if not prevented or interrupted leads to the development of hypertension The aim of the present study was to evaluate the effects of a normal-sodium ( 120 mmol sodium ) diet compared with a low-sodium diet ( 80 mmol sodium ) on readmissions for CHF ( congestive heart failure ) during 180 days of follow-up in compensated patients with CHF . A total of 232 compensated CHF patients ( 88 female and 144 male ; New York Heart Association class II-IV ; 55 - 83 years of age , ejection fraction < 35 % and serum creatinine < 2 mg/dl ) were r and omized into two groups : group 1 contained 118 patients ( 45 females and 73 males ) receiving a normal-sodium diet plus oral furosemide [ 250 - 500 mg , b.i.d . ( twice a day ) ] ; and group 2 contained 114 patients ( 43 females and 71 males ) receiving a low-sodium diet plus oral furosemide ( 250 - 500 mg , b.i.d . ) . The treatment was given at 30 days after discharge and for 180 days , in association with a fluid intake of 1000 ml per day . Signs of CHF , body weight , blood pressure , heart rate , laboratory parameters , ECG , echocardiogram , levels of BNP ( brain natriuretic peptide ) and aldosterone levels , and PRA ( plasma renin activity ) were examined at baseline ( 30 days after discharge ) and after 180 days . The normal-sodium group had a significant reduction ( P<0.05 ) in readmissions . BNP values were lower in the normal-sodium group compared with the low sodium group ( 685+/-255 compared with 425+/-125 pg/ml respectively ; P<0.0001 ) . Significant ( P<0.0001 ) increases in aldosterone and PRA were observed in the low-sodium group during follow-up , whereas the normal-sodium group had a small significant reduction ( P=0.039 ) in aldosterone levels and no significant difference in PRA . After 180 days of follow-up , aldosterone levels and PRA were significantly ( P<0.0001 ) higher in the low-sodium group . The normal-sodium group had a lower incidence of rehospitalization during follow-up and a significant decrease in plasma BNP and aldosterone levels , and PRA . The results of the present study show that a normal-sodium diet improves outcome , and sodium depletion has detrimental renal and neurohormonal effects with worse clinical outcome in compensated CHF patients . Further studies are required to determine if this is due to a high dose of diuretic or the low-sodium diet 28 patients who had a sustained diastolic blood pressure of 95 to 104 mm Hg and who had no treatment for it for at least 13 months before the trial , but who were otherwise unselected , took part in a r and omised controlled trial in which the effect of a restricted sodium diet was compared with that of a general health package . The general health package did not include any specific hypotensive procedures . Changes in blood pressure were measured at predetermined intervals over the course of a year . Within each group both systolic and diastolic blood pressure fell to a highly significant extent after a year , but there was no significant difference between the groups . It would thus seem that the antihypertensive effect of a restricted sodium diet may be related to the increased consultation and monitoring activity of such intervention rather than to the dietary manipulation itself Universal reduction in sodium intake has long been recommended , largely because of its proven ability to lower blood pressure for some . However , multiple r and omized trials have also demonstrated that similar reductions in sodium increase plasma renin activity and aldosterone secretion , insulin resistance , sympathetic nerve activity , serum cholesterol , and triglyceride levels . Thus , the health consequences of reducing sodium can not be predicted by its impact on any single physiologic characteristic but will reflect the net of conflicting effects . Some 23 observational studies ( > 360,000 subjects and > 26,000 end points ) linking sodium intake to cardiovascular outcomes have yielded conflicting results . In subjects with average sodium intakes of less than 4.5 g/day , most have found an inverse association of intake with outcome ; in subjects with average intakes greater than 4.5 g/day , most reported direct associations . Finally , in two , a " J-shaped " relation was detected . In addition , three r and omized trials have found that heart failure subjects allocated to 1.8 g of sodium have significantly increased morbidity and mortality compared with those at 2.8 g. At the same time , a r and omized study in retired Taiwanese men found that allocation to an average intake of 3.8 g improved survival compared with 5.3 g. Taken together , these data provide strong support for a " J-shaped " relation of sodium to cardiovascular outcomes . Sodium intakes above and below the range of 2.5 - 6.0 g/day are associated with increased cardiovascular risk . This robust body of evidence does not support universal reduction of sodium intake The present study set out to assess the feasibility of long-term moderate dietary sodium restriction in patients with mild hypertension in general practice . After screening and a run-in phase of 6 - 8 weeks , a total of 77 previously undiagnosed mildly hypertensive patients were identified . Half of them were r and omized to receive a few simple dietary instructions from their general practitioners in order to reduce salt usage ; the others were r and omized to receive no advice . The patients were followed up for 12 months with quarterly visits . A total of 56 patients ( 72.7 % ) completed the study , 26 on a low-sodium diet ( LD ) and 30 on their usual diet ( UD ) . At each visit in the diet phase , patients provided 24h urine , which was analysed for volume and sodium concentration in order to assess their sodium intake . Blood pressure , heart the rate and body weight were recorded . The mean urinary sodium excretion for all diet phase visits overlapped in the two groups ( 177.0 + /- 32.9 vs. 169.3 + /- 49.4 mEq/24h respectively in the LD and UD groups ) . Nevertheless the mean systolic and diastolic blood pressures for all diet phase visits were significantly lower in the LD than in UD group ( 144.2 + /- 11.1/91.6 + /- 6.4 and 148.0 + /- 13.7/95.6 + /- 4.7 mmHg respectively , P less than 0.01 ) . Our data suggest that it is not feasible at present to reduce sodium intake in mild hypertensives with simple and inexpensive dietary instructions , the only ones suitable for widespread application in general practice 1 . Three groups of young patients with borderline hypertension were studied for a 12 months period . The first was on a free sodium diet while the second was on a low-salt diet . The third group of patients underwent acute salt loading . 2 . After 12 months the group on free diet showed a significant increase of intralymphocytic sodium but no change in blood pressure was noted . Five patients who were re-checked after 24 months also had a significant increase in blood pressure . 3 . Patients treated with a low-salt diet showed a significant decrease of both intralymphocytic sodium concentration and blood pressure . 4 . After acute salt loading , borderline subjects with high intralymphocytic sodium showed a significant greater natriuresis whereas intralymphocytic sodium increased only in those subjects in whom it was initially normal |
1,832 | 23,528,548 | ESAs offer an alternative blood conservation method to avoid ABT in patients undergoing hip or knee surgery | Erythropoiesis-stimulating agents ( ESAs ) have been used in orthopedic patients to reduce allogeneic blood transfusion ( ABT ) .
The purpose of this systematic review of r and omized clinical trials is to evaluate the efficacy of preoperative administration of ESAs on hemoglobin level at discharge and frequency of ABT in patients undergoing hip or knee surgery . | Forty patients who were scheduled for a total hip arthroplasty were enrolled in a prospect i ve study and were r and omly divided into two groups . Group 1 received recombinant human erythropoietin ( 300 U/kg twice a week ) , and group 2 received placebo . The medication was started 2 weeks before the operation , and only one dose of medication was given after the operation . Autologous blood was administered at the same time as the medication until the hemoglobin level sank to 10 g/dl . Forty-eight and 49 units of autologous blood were collected in group 1 and group 2 , respectively . Intraoperative homologous blood was transfused only to patients in group 2 . Seven and 13 units of allogenic blood were transfused into group 1 and group 2 patients during the postoperative period , respectively . There were no any significant differences between the groups in terms of early postoperative hemoglobin level and amount of autologous blood collected . However , the increase of the reticulocyte count in patients who received erythropoietin was significantly higher than in the group 2 patients . The study showed that short-term and low-dose erythropoietin usage strongly stimulates the bone marrow . Erythropoietin administration and preoperative autologous blood donation diminished the total units of allogenic blood required during the intraoperative or postoperative pe-riod . Autologous blood administration without concurrent erythropoietin did not stimulate the bone marrow adequately This prospect i ve r and omized trial compared preoperative autologous blood donation ( PAD ) with epoetin alfa in patients undergoing primary total knee reconstruction . Fifty adult patients with pretreatment hemoglobin level of 100 to 130 g/L were r and omized to either epoetin alfa 40,000 U at preoperative days 14 and 7 or to a st and ard PAD protocol . Patient characteristics and operative blood loss were similar between groups . Baseline hematological parameters for epoetin alfa vs PAD were not significantly different ; however , by the day of surgery the epoetin alfa group had significantly higher hemoglobin ( 130 vs 114 g/L ; P < .001 ) , hematocrit ( 0.408 vs 0.352 ; P < .001 ) , and reticulocyte count ( 3.4 vs 2.1 x 10(9 ) cells per liter ; P < .001 ) . These differences remained significant for 1 to 2 days postoperatively . There was no significant difference in the incidence of allogeneic transfusions between groups ( 28 % for epoetin alfa vs 8 % for PAD ; P = .1383 ) . Both treatments were generally well tolerated . Epoetin alfa appears to be a safe alternative to PAD in patients who are at risk for transfusion in the perioperative period following total knee arthroplasty In a prospect i ve r and omized study we investigated the potential of subcutaneous recombinant human erythropoietin ( rhEpo ) as adjuvant treatment for autologous blood transfusions ( 3 units ) in elective surgery . Four and 2 weeks before surgery , 49 patients received 6 x 10,000 U of rhEpo . delta Hb values ( days -28 and 0 ) of the rhEpo group were compared to delta Hb values of 52 controls ( no rhEpo ) . Reticulocytes were measured at days -21 , -14 , -7 and 0 . Peri- and postoperative supplementary homologous blood requirements were compared in the two r and omized groups . delta Hb of rhEpo group was 0.96 g/dl ( mean value ) and 2.38 for controls . Reticulocyte count increased earlier and to higher levels in rhEpo-treated patients . Except in 1 case , Epo was well tolerated . These results indicate that autologous predonation ( 3 x 400 ml ) does not create anemia if adjuvant Epo treatment is given . However , homologous blood requirements were not significantly different , which is probably due to the fact that 96 of the 101 treated patients underwent elective orthopedic surgery requiring limited blood replacement . Significant benefit of the Epo regimen can be expected in elective cardiovascular and hepatic surgery where larger amounts of blood ( 5 - 6 units ) are needed Total hip joint arthroplasty is frequently associated with transfusion of allogeneic blood ( 1 , 2 ) . Although serologic screening has reduced the risk for viral infection to a low level ( 3 , 4 ) , the public is highly concerned about this potential complication of transfusion ( 5 ) . Therefore , further refinement of strategies to avoid exposure to allogeneic blood is needed . The most commonly used preventive strategy is autologous blood donation ( 6 ) . Blood is collected from the patient before surgery and is reinfused if transfusion is necessary . In the past decade , this maneuver , which reduces exposure to pathogens and red cell alloimmunization , has become a st and ard of care in orthopedic surgery ( 7 , 8) . However , autologous blood donation has several disadvantages . First , donation and banking of autologous blood are inconvenient to patients ( 9 , 10 ) . Second , phlebotomy increases the prevalence of postoperative anemia and transfusion ( either autologous or allogeneic ) ( 11 ) . Third , use of autologous blood is not without risk ( 12 , 13 ) . Bacterial contamination of predonated blood ( 14 ) and major transfusion reactions ( due to administrative error ) ( 15 ) are rare but may be life-threatening . Finally and most important , many patients are not eligible for predonation because of concomitant medical conditions ( 16 ) . Erythropoietin , a glycoprotein produced by the kidney , stimulates production of red blood cells from the bone marrow ( 17 ) . Administration of recombinant human erythropoietin ( epoetin alfa ) reduces the risk for allogeneic blood transfusion in patients undergoing total hip joint arthroplasty ( 18 , 19 ) . Factors that influence the response to epoetin alfa include the dose and timing of treatment ( 20 ) , coadministration of iron ( 21 , 22 ) , and baseline hemoglobin concentration ( 23 ) . Although several different preoperative regimens have been described , the regimen approved by the U.S. Food and Drug Administration consists of four subcutaneous injections of epoetin alfa , 600 U/kg of body weight , administered before surgery ( weeks 3 , 2 , and 1 and the day of surgery ) ( 24 ) . Thus , a person weighing 70 kg would require a total dose of 168 000 U. On the basis of subgroup analysis from a previous study ( 18 ) , we hypothesized that a high dose of oral iron used in conjunction with a more prolonged epoetin alfa dosing schedule might produce a better hematologic response than that obtained with the st and ard regimen . We therefore evaluated the efficacy of two different epoetin alfa dose regimens . Methods Patients The study was a double-blind , r and omized , parallel-group , multicenter clinical trial comparing the efficacy of epoetin alfa ( Eprex , Janssen-Ortho Inc. , Toronto , Ontario , Canada ) with placebo in adult patients undergoing total hip joint arthroplasty . The trial was conducted at 13 teaching and 4 community hospitals in Canada from May 1996 to April 1999 . The protocol was approved by the institutional review board of each participating center . Eligible patients had a hemoglobin concentration of 98 to 137 g/L and did not predonate blood . At centers where an autologous blood donation program was available , blood predonation was discussed with patients ; those who participated in the study were either ineligible for predonation because of medical contraindication or declined this option . Persons with rheumatoid arthritis , recent gastrointestinal or intracranial bleeding , iron deficiency , seizures , blood dyscrasias , or uncontrolled hypertension ( diastolic blood pressure>100 mm Hg ) were excluded from the study . Patients who required revision arthroplasty or those in whom red cell salvage devices were considered essential were not enrolled . All patients gave written informed consent . Baseline and R and omization Procedures Participants were screened for eligibility 7 weeks before surgery . A history and physical examination were performed , and a complete blood count , iron studies , and blood chemistry were obtained ; patients then began oral iron therapy . Six weeks before surgery , eligible patients were r and omly assigned to one of three treatment groups . R and omization was performed according to a computer-generated schedule using a block size of 13 and an allocation ratio of 3:5:5 to the high-dose epoetin group , low-dose epoetin group , or placebo group , respectively . Treatment Regimens Patients began daily oral iron therapy at least 42 days before surgery and continued therapy until the day of hospital discharge . Three capsules per day were recommended . In patients who were intolerant of iron , the number of capsules was reduced to the point of tolerability . The iron preparation prescribed was Niferex-150 ( Schwarz Pharma , Mequon , Wisconsin ) . This polysaccharideiron complex was selected because of its good tolerability and high bioavailability of elemental iron ( 150 mg per capsule ) ( 25 ) . Patients received four weekly subcutaneous injections of placebo , high-dose epoetin alfa ( 40 000 U ) , or low-dose epoetin alfa ( 20 000 U ) starting 4 weeks before surgery . The total possible dose was 160 000 U in the high-dose group and 80 000 U in the low-dose group . The study drug was withheld if the hemoglobin concentration was 150 g/L or more , systolic blood pressure was 200 mm Hg or more , or the diastolic blood pressure was 105 mm Hg or more . During the trial , the study coordinator at the data coordinating center , who was aware of the patient 's hemoglobin concentration , authorized administration of study drug before each visit . This person had no contact with patients and did not assess outcomes . Follow-up Schedule Patients were evaluated 28 , 21 , 14 , and 7 days before surgery . At these visits , vital signs and adverse events were recorded by the visiting nurse . Patients , surgeons , and nurses were unaware of treatment assignments and laboratory results . Hemoglobin concentration on the day of surgery was available to the surgeon and other health care personnel , but the reticulocyte count and the previous hemoglobin concentration were not . Blood loss was quantified by weighing sponges and measuring suction volume intraoperatively and subtracting the volume of the irrigation fluid . Patients were seen 1 , 3 , and 5 days after surgery ; blood work was performed at these times . On the fifth day after surgery , patients underwent duplex ultrasonography ( 26 , 27 ) to evaluate both legs for the presence of deep venous thrombosis . Transfusion Policy Transfusion of allogeneic blood was performed according to the usual practice of attending surgeons and anesthesiologists . We did not establish criteria for transfusion ; however , the usual policy in Canada is not to perform transfusion in asymptomatic patients on the basis of a specific hemoglobin threshold . No patient donated or received autologous blood . Outcome Measures The primary outcome measure was occurrence of allogeneic blood transfusion . Secondary outcomes were changes in reticulocyte count and hemoglobin concentration . Adverse events were determined according to World Health Organization criteria ( 28 ) . The proportion of patients who experienced thromboembolic disease ( proximal or distal deep venous thrombosis and pulmonary embolus ) and serious adverse events was compared among the treatment groups . Statistical Analysis Before the start of the study , retrospective chart review was performed to estimate the transfusion rate in patients undergoing hip arthroplasty ( n = 471 ) who had characteristics similar to those of our patients . In those patients , the rate of allogeneic transfusion was 39 % ( 95 % CI , 34 % to 43 % ) . The reduction in the transfusion rate considered clinical ly important was 20 % . On the basis of pharmacokinetic data , the higher dose of epoetin alfa was judged likely to be more efficacious ( 29 ) than the lower dose . Therefore , we estimated that the transfusion rate would decrease from 40 % to 15 % in the high-dose group and from 40 % to 20 % in the low-dose group . In accordance with these assumptions , we used an asymmetric r and omization schedule that allocated a greater number of patients to the low-dose epoetin alfa and placebo groups ( 5 patients for every 3 that were allocated to the high-dose epoetin alfa group ) . This maneuver ensured adequate statistical power ( 80 % ) to compare the transfusion rate in the high-dose and low-dose groups with that in the placebo group . Since an allowance of 5 % was made for unevaluable patients , 83 patients per group were required in the low-dose and placebo groups and 50 patients were needed in the high-dose group . Accordingly , the total sample size requirement was 216 patients . All statistical analyses of efficacy measures were performed on an intention-to-treat basis , which was prospect ively defined to include patients who had received at least one dose of study medication and subsequently underwent surgery within 1 week of the scheduled date . Separate chi-square tests were done to compare the proportion of patients who required transfusion in the placebo group with that among patients assigned to the low-dose epoetin alfa group or the high-dose epoetin alfa group . Bonferroni correction was used as a conservative method of adjusting for multiple comparisons ( 30 ) . Accordingly , an error of 0.025 was considered to indicate statistical significance . Continuous outcome measures were compared by using analysis of variance . Logistic regression analyses were performed to explore the relationship between occurrence of transfusion and age , sex , weight , body mass index , predicted blood volume , baseline reticulocyte count , preoperative reticulocyte count , change in reticulocyte count , baseline hemoglobin concentration , preoperative hemoglobin concentration , change in hemoglobin concentration , baseline serum ferritin level , preoperative serum ferritin level , baseline serum iron level , preoperative serum iron level , number of days receiving iron therapy before surgery , baseline erythropoietin level , and treatment with epoetin alfa . Variables significant at the 0.10 level were examined further in a To study whether the administration of recombinant human erythropoietin increases the amount of autologous blood that can be collected before surgery , we conducted a r and omized , controlled trial of erythropoietin in 47 adults scheduled for elective orthopedic procedures . The patients received either erythropoietin ( 600 units per kilogram of body weight ) or placebo intravenously twice a week for 21 days , during which time up to 6 units of blood was collected . Patients were excluded from donation when their hematocrit values were less than 34 percent . All patients received iron sulfate ( 325 mg orally three times daily ) . The mean number of units collected per patient ( + /- SE ) was 5.4 + /- 0.2 for the erythropoietin group and 4.1 + /- 0.2 for the placebo group . The mean red-cell volume donated by the patients who received erythropoietin was 41 percent greater than that donated by the patients who received placebo ( 961 vs. 683 ml , P less than 0.05 ) . Only 1 of the 23 patients treated with erythropoietin was unable to donate greater than or equal to 4 units ( 4 percent ) as compared with 7 of the 24 patients who received placebo ( 29 percent ) . No adverse effects were attributed to erythropoietin . We conclude that recombinant human erythropoietin increases the ability of patients about to undergo elective surgery to donate autologous blood A multicenter , r and omized , open-label , parallel-group study was conducted to compare the safety and efficacy of perioperative recombinant human erythropoietin ( Epoetin alfa ) with the safety and efficacy of preoperative autologous donation ( PAD ) in total joint arthroplasty . A total of 490 patients scheduled for total joint ( i.e. , hip or knee ) surgery and having hemoglobin ( Hb ) levels > or = 11 to < or = 13 g/dL were r and omized to receive weekly doses of subcutaneous Epoetin alfa on preoperative Days -21 , -14 , and -7 , and on the day of surgery , or to participate in a PAD program . The mean baseline Hb level in both groups was 12.3+/-0.6 g/dL , increasing to 13.8 g/dL in the Epoetin alfa-treated group and decreasing to 11.1 g/dL in the PAD group before or on the day of surgery . In the PAD group , 156/219 ( 71.2 % ) patients were transfused with autologous blood , and 42/219 ( 19.2 % ) patients were transfused with allogeneic blood . A smaller proportion , 27/209 ( 12.9 % ) patients , in the Epoetin alfa-treated group were transfused with allogeneic blood ( P = .078 compared with the PAD group ) . Moreover , patients in the PAD group received a total of 325 units of blood ( 79 allogeneic units and 246 autologous units ) compared with patients in the Epoetin alfa group who received a total of 54 units of blood . The mean postoperative Hb level was 11.0 g/dL in the Epoetin alfa-treated group and 9.2 g/dL in the PAD group . Compared with the PAD arm , mean Hb levels measured preoperatively , postoperatively on Day 1 , and at discharge visits were significantly greater in the Epoetin alfa-treated arm ( P < .0001 ) Background The primary objective of this study was to assess the number of erythropoietin ( EPO ) injections required to reach a hematocrit ( Ht ) of 40 % in moderately anemic patients . The secondary objective was to compare this strategy with autologous blood donation ( ABD ) in elective orthopedic surgery in terms of red blood cell ( RBC ) production . Study design and methods 93 patients with a baseline Ht between 30 and 39 % were r and omized into two groups the day of the preoperative assessment . In the EPO group , patients received 40,000 UI/week sc until they reached a maximal Ht of 40 % . In the ABD group , a RBC pack was collected every week as long as the Ht was above 33 % . Results Two EPO injections were necessary to reach a 40 % Ht in 63 % of the patients . It was possible to collect two RBC packs in 45 % of the patients in the ABD group . Volume of RBC production was significantly higher in the EPO group : 268 ± 142 mL vs 141 ± 129 ( P = 0.0001 ) . In the EPO group , Ht was significantly higher on days one and three after surgery and at discharge . The energy score was better in the EPO group . In the ABD group , 12.6 % patients vs 6.5 % in the EPO group received allogeneic transfusion ( ns ) . Conclusion Only two EPO injections were sufficient to reach a Ht of 40 % in the majority of patients . Therefore , to improve cost/effectiveness , the number of EPO injections should be related to baseline Ht instead of the four injections recommended in the product monograph . RésuméObjectifÉvaluer le nombre d’injections d’érythropoïétine ( EPO ) nécessaires pour atteindre un hématocrite ( Ht ) de 40 % chez des patients modérément anémiques . Aussi , comparer cette stratégie avec le don de sang autologue ( DSA ) en chirurgie orthopédique réglée en termes de production de globules rouges (GR).MéthodeDes patients ( n = 93 ) présentant un Ht de base de 30 à 39 % ont été répartis en deux groupes le jour de l’évaluation préopératoire . Ceux du groupe EPO ont reçu 40,000 UI/semaine sc jusqu’à ce qu’ils présentent un Ht maximal de 40 % . Dans le groupe DSA , un culot globulaire a été prélevé chaque semaine tant que l’Ht était au-dessus de 33%.RésultatsIl a fallu deux injections d’EPO pour atteindre un Ht de 40 % chez 63 % des patients . Il a été possible de prélever deux culots chez 45 % des patients du groupe DSA . Le volume de production de GR a été significativement plus élevé chez ceux du groupe EPO : 268 ± 142mL vs 141 ± 129 ( P = 0,0001 ) . Dans le groupe EPO , l’Ht a été significativement plus élevé aux jours un et trois après l’opération et au moment du congé . Le score d’asthénie était moins prononcé dans le groupe EPO . Une transfusion allogénique a été faite chez 12,6 % des patients du groupe DSA vs 6,5 % du groupe EPO ( ns ) . Conclusion Il a suffi de deux injections d’EPO seulement pour atteindre un Ht de 40 % chez la majorité des patients . Donc , pour améliorer l’efficacité des coûts , il faudrait relier le nombre d’injection d’EPO à l’Ht de base plutôt que de faire les quatre injections recomm and ées dans la monographie du produit Background and objective : Preoperative epoetin alfa administration decreases transfusion requirements and may reduce transfusion complications , such as postoperative infection due to immune suppression and thus hospitalization time . This study examined the impact of preoperative epoetin alfa administration on postoperative recovery and infection rate . Methods : In an open r and omized controlled multicentre trial in patients undergoing orthopaedic surgery , the effects of preoperative administration of epoetin alfa vs. routine care were compared in six countries . Haemoglobin ( Hb ) values , transfusions , time to ambulation , time to discharge , infections and safety were evaluated in patients with preoperative Hb concentrations 10‐13 g dL−1 ( on‐treatment population : epoetin n = 460 ; control n = 235 ) , from study entry until 4‐6 weeks after surgery . Outcome was also compared in patients with and without transfusion . Results : Epoetin‐treated patients had higher Hb values from the day of surgery until discharge ( P < 0.001 ) and lower transfusion rates ( 12 % vs. 46 % ; P < 0.001 ) . Epoetin treatment delivered no significant effect on postoperative recovery ( time to ambulation , time to discharge and infection rate ) . However , the time to ambulation ( 3.8 ± 4.0 vs. 3.1 ± 2.2 days ; P < 0.001 ) and the time to discharge ( 12.9 ± 6.4 vs. 10.2 ± 5.0 days ; P < 0.001 ) was longer in the transfused than in the non‐transfused patients . Side‐effects in both groups were comparable . Conclusions : Epoetin alfa increases perioperative Hb concentration in mild‐to‐moderately anaemic patients and thus reduces transfusion requirements . Patients receiving blood transfusions require a longer hospitalization than non‐transfused patients The aim was to assess the cost-effectiveness of erythropoietin ( EPO ) to reduce patients ' exposure to perioperative allogenic blood products in orthopaedic surgery . The use of EPO was assessed for EPO used alone and for EPO , to augment preoperative autologous donation ( PAD ) . A decision analytical model was design ed incorporating ( i ) the risk of receiving allogeneic blood , ( ii ) the costs of blood products , ( iii ) the likelihood of developing transfusion-related diseases , ( iv ) the costs of transfusion-related diseases , ( v ) the impact of transfusion-related diseases on patient morbidity and mortality and ( vi ) the effect of EPO upon the probability of transfusion . The efficacy of EPO was derived from data from a meta- analysis of published r and omized trials . Estimates for the other parameters were obtained by a systematic review of the literature . EPO alone led to only modest incremental benefit compared to no intervention for orthopaedic surgery ( 0.000024 life-years gained per patient ) . As an augmentation to PAD , EPO also led to modest benefits ( 0.000006 life-years gained per patient ) . For EPO compared to no intervention , the incremental cost per life-year gained was $ 66 million ( Canadian ) . For EPO to augment PAD , the incremental cost per life-year gained was $ 329 million ( Canadian ) . Detailed sensitivity analysis did not reveal any circumstances in which the cost-effectiveness ratios reached a level generally considered attractive . On the basis of cost-effectiveness , the use of EPO to reduce perioperative allogeneic transfusions in orthopaedic surgery did not meet criteria conventionally considered acceptable BACKGROUND People search medline for trials of healthcare interventions for clinical decisions , or to produce systematic review s , practice guidelines , or technology assessment s. Finding all relevant r and omized controlled trials ( RCTs ) with little extraneous material is challenging . OBJECTIVE To provide comparative data on the operating characteristics of search filters design ed to retrieve RCTs from medline . METHODS We identified 38 filters . The testing data base comprises h and search ing data from 161 clinical journals indexed in medline . Sensitivity , specificity and precision were calculated . RESULTS The number of terms and operating characteristics varied considerably . Comparing the retrieval against the single term ' r and omized controlled trials.pt . ' ( sensitivity for retrieving RCTs , 93.7 % ) , 24 of 38 filters had statistically higher sensitivity ; 6 had a sensitivity of at least 99.0 % . Four other filters had specificities ( non retrieval of non- RCTs ) that were statistically not different or better than the single term ( 97.6 % ) . Precision was poor : only two filters had precision ( proportion of retrieved articles that were RCTs ) statistically similar to that of the single term (56.4%)-all others were lower . Filters with more search terms often had lower specificity , especially at high sensitivities . CONCLUSION Many RCT filters exist ( n = 38 ) . These comparative data can direct the choice of an RCT filter Purpose Our aim was to evaluate the effectiveness of two different dosing regimens of human recombinant erythropoietin ( rHu-EPO ) for preoperative autologous blood collection in patients undergoing total hip arthroplasty ( THA ) . Methods Prospect i ve r and omised trials in which erythropoietin 15,000 IU was administered intravenously twice a week or 30,000 IU once a week ( total 90,000 IU ) combined with ferrous II sulphate ( Ferro-Gradumet 2 ) orally and compared with Ferro-Gradumet 2 alone . Results Although different dosing regimens of rHu-EPO administration during preoperative autologous blood donation have similar effects on the collection of two units of autologous blood , preoperative haemoglobin level and perioperative allogenic blood transfusion , a once weekly dose regimen of rHu-EPO was more convenient ( although not statistically significantly ) for patients . Conclusion We recommend the more practical and comfortable but yet highly effective therapeutic regimen with a single weekly intravenous administration of rHu-EPO for patients scheduled for THA BACKGROUND Previous reports have suggested that the use of recombinant human erythropoietin is effective for decreasing the need for perioperative allogeneic blood transfusion . The purpose of this study was to evaluate the efficacy of erythropoietin in combination with , and compared with , preoperative autologous donation for reducing allogeneic blood requirements for total joint arthroplasty . METHODS Two hundred and forty patients undergoing primary and revision total hip or knee arthroplasty were enrolled into three groups with different treatment regimens : ( 1 ) erythropoietin and preoperative autologous donation ( Group 1 ) , ( 2 ) erythropoietin alone ( Group 2 ) , and ( 3 ) preoperative autologous donation alone ( Group 3 ) . Patients were evaluated with regard to requirements for allogeneic transfusion , change from the baseline to the lowest postoperative hemoglobin value , postoperative complications , and adverse reactions . RESULTS The rate of allogeneic transfusion was 11 % in Group 1 ( erythropoietin and preoperative autologous donation ) compared with 28 % in Group 2 ( erythropoietin alone ) and 33 % in Group 3 ( preoperative autologous donation alone ) . Within Group 1 , patients who had a unilateral primary arthroplasty had an allogeneic transfusion rate of 4 % and those who had a bilateral or revision arthroplasty had an allogeneic transfusion rate of 17 % . In Groups 2 and 3 , the allogeneic transfusion rates were 14 % and 15 % , respectively , for the patients who had a unilateral primary arthroplasty and 35 % and 47 % , respectively , for those who had a bilateral or revision arthroplasty . CONCLUSIONS Preoperative use of erythropoietin in conjunction with preoperative autologous donation reduces the need for allogeneic blood transfusion associated with total joint arthroplasty more effectively than does either erythropoietin or preoperative autologous donation alone OBJECTIVES Due to the discovery in the 1980s that blood transfusion can transmit HIV , there has been increased interest in technologies that reduce the amount of allogeneic blood used during and after surgery . These technologies include drugs ( aprotinin , tranexamic acid , epsilon-aminocaproic acid , erythropoietin ) , devices ( cell salvage ) , and techniques ( acute hemodilution , predeposited autologous donation ) . The purpose of this study was to ascertain the degree of practice variation , if any , that exists for eight technologies in nine countries in orthopedic and cardiac surgery . METHODS In each country , either all hospitals or a r and om sample of hospitals with medical/surgical beds were surveyed between 1995 and 1997 . Two instruments were used . The first instrument was a postcard that asked recipients whether the technologies were currently being used in their hospital for orthopedic and /or cardiac surgery to reduce perioperative allogeneic transfusion . The second question naire elicited information regarding the degree of use both in qualitative and quantitative terms . Data were collected , entered , and analyzed in each country , with summary results su bmi tted to the Canadian coordinating center on a st and ardized data collection form . RESULTS Pharmaceuticals were generally used in a much smaller proportion of hospitals in orthopedic than in cardiac surgery . Aprotinin and tranexamic acid were the drugs most frequently used in cardiac surgery . Nonpharmacological technologies were used to a greater degree than drugs in orthopedic surgery , although there was wide variation among technologies and countries . Acute hemodilution and cell salvage were used in a greater proportion of hospitals for cardiac surgery than orthopedic surgery . CONCLUSIONS The results of this survey indicate that there is considerable practice variation in the use of technologies to minimize exposure to perioperative allogeneic transfusion within and between countries BACKGROUND Preoperative treatment with rHuEPO ( epoetin alfa : EPREX , Janssen-Cilag ; or PROCRIT , Ortho Biotech ) in conjunction with iron supplementation increases the erythropoietic response in elective orthopedic surgery patients , but it is not known whether the magnitude of this response is dependent on the route of iron administration . STUDY DESIGN AND METHODS Non-iron-deficient patients undergoing elective orthopedic surgery ( N = 110 ) with baseline Hb > or = 10 to < or = 13 g per dL were r and omly assigned to receive either epoetin alfa ( 600 IU/kg ) plus IV iron ( n = 29 ) or oral iron ( n = 29 ) or placebo plus IV iron ( n = 25 ) or oral iron ( n = 27 ) in this 14-day study . RBC production , Hb , Hct , reticulocytes , iron status , and adverse events were monitored throughout the study . RESULTS Epoetin alfa treatment plus either oral or IV iron supplementation significantly increased total RBC production , Hb , Hct , and reticulocytes over the values seen with the respective placebo treatments ( p = 0.0001 ) . There were no differences between the epoetin alfa treatment groups . Placebo treatment plus oral or IV iron supplementation was not associated with increases in hematologic values . There were no differences in the incidence of adverse events among the treatment groups . CONCLUSION There was a comparable erythropoietic response to epoetin alfa , irrespective of the route of iron administration . The route of iron administration , therefore , does not modulate the erythropoietic response to epoetin alfa in patients who are not iron deficient . Safety and convenience benefits may be gained by adopting oral iron supplementation in this patient subset Background : Controversy exists about the advantages of predeposit of autologous blood ( PDAB ) , and whether more comfortable blood conservation regimens may yield comparable results . To test the hypothesis that preoperative treatment with recombinant human erythropoietin ( rHuEPO ) with or without acute concomitant normovolaemic haemodilution ( ANHD ) is as effective as PDAB in reducing allogeneic blood transfusions , we conducted a prospect i ve r and omised study in women undergoing primary hip replacement BACKGROUND Autologous blood transfusion presents no infectious or immunologic side effects . The aim of this r and omized study was to determine the impact of recombinant human erythropoietin ( rHuEPO ) on the donation of 5 units of autologous blood by nonanemic patients who were c and i date s for elective surgery with transfusion requirements of > or = 5 units . STUDY DESIGN AND METHODS Starting on Day -35 , 420 mL of blood was taken weekly . All patients received 200 mg of iron saccharose complex intravenously at each visit and six subcutaneous injections of rHuEPO ( 141 U/kg ) or placebo between Days -21 and -7 . RESULTS Of 50 patients , 45 completed the study ( placebo , 21 ; rHuEPO , 24 ) . Total red cell production was higher in the rHuEPO group ( p = 0.001 ) . Donation of 5 units was possible for 67 percent ( placebo group ) and 79 percent ( rHuEPO group ) of patients ( p = 0.5 ) . The mean number of blood units donated was 4.6 ( placebo group ) and 4.7 ( rHuEPO group ) . More patients in the placebo group received allogeneic blood ( 9/21 [ 43 % ] vs. 6/23 [ 26 % ] ) , although the difference did not reach significance ( p = 0.34 ) . CONCLUSION In nonanemic patients donating 5 units of blood , rHuEPO associated with intravenous iron increased total red cell production . However , no difference was found between the rHuEPO and placebo groups with regard to the number of units of autologous blood donated of the number of patients receiving allogeneic blood transfusion BACKGROUND AND OBJECTIVES Intravenous ( i.v . ) Recombinant erythropoietin ( Epoetin alfa ) is effective in allowing autologous blood donation in patients unable to donate because of anemia . We undertook this open pilot study in order to asses whether a low subcutaneous ( s.c . ) dose of Epoetin alfa would prove as effective and well tolerated as the higher i.v . dose . Such a move would also decrease costs . MATERIAL S AND METHODS A total Epoetin alfa s.c . dose of 800 IU/kg was compared with a total i.v . dose of 1,800 IU/kg . Twenty-two rheumatoid arthritis patients , unable to donate because of hemoglobin ( Hb ) < 11 g/dl , received 300 IU/kg of IV Epoetin alfa twice weekly for 3 weeks ( 11 patients ) , or 100 IU/kg of s.c . Epoetin alfa twice weekly for 3 weeks plus an i.v . bolus of 200 IU/kg of Epoetin alfa at the first visit ( 11 patients ) . At each visit , all patients received 100 mg of i.v . iron saccharate and when the hematocrit ( hct ) > or = 34 % , 350 ml of autologous blood ( AB ) were collected . RESULTS No significant differences were observed between the 2 groups of treated patients in terms of units of AB collected ( 2.6 + /- 0.6 vs. 2.5 + /- 0.5 units for i.v . and s.c . groups , respectively ) , ml of RBC produced during the study period ( 291 + /- 99 vs. 337 + /- 65 ml for the i.v . and s.c . groups , respectively ) , or in the degree of reduced exposure to allogeneic blood in comparison with the control group . CONCLUSIONS Lower dose of Epoetin alfa ( reduced by 56 % ) , supplemented by i.v . iron , is as effective and well tolerated as higher doses administered i.v . , supplemented by i.v . iron Two hundred patients who were scheduled for a major elective orthopaedic operation were enrolled in a prospect i ve study and were r and omly assigned to one of three treatment groups . Group 1 consisted of sixty patients who received recombinant human erythropoietin , 300 international units per kilogram of body weight per day ; Group 2 , seventy-one patients who received recombinant human erythropoietin , 100 international units per kilogram of body weight per day ; and Group 3 , sixty-nine patients who received a placebo . A total of fifteen doses was given subcutaneously , beginning ten days before the operation and extending through the fourth postoperative day . Patients who declined or were unable to donate autologous blood preoperatively were included in the study and were maintained on iron supplementation orally . The decision to transfuse red blood cells depended on the physician , however , physicians were encouraged not to do so if the hematocrit was more than 0.27 ( 27 per cent ) , unless the clinical symptoms warranted it . Of the 185 patients who were evaluable with regard to efficacy , significantly fewer patients received homologous red-blood-cell transfusions in Groups 1 and 2 ( 17 per cent [ nine ] and 25 per cent [ sixteen ] , respectively ) than in Group 3 ( 54 per cent [ thirty-six ] ) ( p < 0.001 ) . When the patients were stratified into two groups on the basis of the pre-treatment hemoglobin level ( more than 100 to 130 grams per liter or more than 130 grams per liter ) , we found that patients who had received a placebo and had a baseline hemoglobin level of more than 100 to 130 grams per liter were at significantly higher risk for transfusion ( 78 per cent [ twenty-one ] ) than those who had received a placebo and had a baseline level of more than 130 grams per liter ( 36 per cent [ fourteen ] ) . For patients who had a baseline hemoglobin level of more than 100 to 130 grams per liter , the higher dose of recombinant human erythropoietin appeared somewhat more effective than the lower dose , with 14 per cent ( three ) of the patients in Group 1 and 39 per cent ( nine ) in Group 2 needing a transfusion ; however , the difference was not significant ( p = 0.09 ) . For patients who had a baseline hemoglobin level of more than 130 grams per liter , the two doses of recombinant human erythropoietin produced similar results , with 14 per cent ( four ) of the patients in Group 1 and 11 per cent ( four ) in Group 2 needing a transfusion ; this was in contrast to a rate of transfusion of 36 per cent ( fourteen ) in Group 3 ( the patients who received the placebo ) ( p = 0.03 ) . The recombinant human erythropoietin was generally well tolerated , although one patient , who did not have a history of hypertension , had an increase in blood pressure , from a baseline level of 142/78 millimeters of mercury ( 18.93/10.40 kilopascals ) to a level of 220/100 millimeters of mercury ( 29.33/13.33 kilopascals ) , after ten days of treatment with the higher dose . These data suggest that recombinant human erythropoietin , administered before and after major orthopaedic operations , can minimize the need for homologous red-blood-cell transfusion The effect of recombinant human erythropoietin on autologous blood donation was investigated in 73 rheumatoid arthritis patients who underwent hip or knee arthroplasty . Autologous blood donation of 400 mL was successful with recombinant human erythropoietin ( 12,000 U per week ) , and no homologous blood was required . The mean period of blood collection was 33.8 days . Mean hemoglobin levels were 9.7 g/dL before treatment , 10.7 g/dL before surgery , and 10.2 g/dL after surgery . This study confirmed recombinant human erythropoietin is effective for enabling preoperative blood donation in rheumatoid arthritis patients BACKGROUND Previous clinical trials have shown that the use of recombinant human erythropoietin ( EPO ) can facilitate autologous blood donation and reduce allogeneic blood transfusions in autologous blood donors who are anemic at first donation . However , the role of EPO therapy in nonanemic patients remains undefined . To identify this role , a r and omized , controlled , multicenter dose-escalation trial was conducted in patients whose initial hematocrit was > 39 percent ( 0.39 ) . STUDY DESIGN AND METHODS EPO ( 150 , 300 , or 600 units/kg ) or placebo was administered intravenously at each of six phlebotomy visits over a 3-week study period . Sixteen ( 14 % ) of 116 patients were unable to complete the treatment protocol because of adverse events ( n = 11 ) or for personal reasons ( n = 5 ) ; 2 patients ( 1 EPO and 1 placebo ) experienced serious adverse events . RESULTS In 91 evaluable patients , additional red cell production during the study period was 440 + /- 176 , 621 + /- 215 , 644 + /- 196 , and 856 + /- 206 mL ( mean + /- SD ) , respectively , for patients receiving placebo and EPO at 150 , 300 , and 600 units/kg ( p < 0.05 for all EPO groups compared to placebo ) . However , the percentages of patients in each group who received allogeneic blood did not differ : 2 ( 9 % ) of 23 placebo patients and 6 ( 9 % ) of 68 EPO patients . CONCLUSION It is concluded that , while EPO therapy increased preoperative red cell production , no clinical benefit could be demonstrated in autologous blood donors who were not anemic at first blood donation Background : Recombinant human erythropoietin in combination with preoperative autologous blood donation is an established regime for avoiding allogenic blood transfusions . The aim of the study was to determine endogenous erythropoietin production and haemoglobin recovery after preoperative autologous blood donation and surgery , with or without recombinant human erythropoietin treatment This r and omized trial assessed the effect of recombinant human erythropoietin ( EPO ) vs preoperative autologous donation ( PAD ) on postoperative vigor and h and grip strength in patients undergoing primary total joint arthroplasty . Adults with baseline hemoglobin level of 11 to 14 g/dL received EPO ( 600 IU/kg once weekly for 4 doses , n = 130 ) or PAD ( n = 121 ) before primary , unilateral hip or knee arthroplasty . Mean changes in vigor score and h and grip strength from baseline were not significantly different between treatment groups . Multivariate analyses found a significant treatment effect favoring EPO over PAD for vigor , but not for h and grip strength . Patients in the EPO group had higher hemoglobin levels and required fewer transfusions . Both treatments were well tolerated . Additional study is needed to eluci date the influence of blood management strategies on postoperative vigor BACKGROUND This r and omized controlled study was undertaken to determine the effect of recombinant human erythropoietin ( rHuEPO ) on erythropoiesis , autologous blood collection , and allogeneic transfusion risk in elective surgery patients with low baseline hematocrits . STUDY DESIGN AND METHODS Patients ( n = 204 ) with low baseline hematocrits ( < or = 39 % ) , scheduled for orthopedic surgery within 25 to 35 days , were seen every 3 to 4 days for 21 days . At each visit , 450 mL of blood was collected if the hematocrit was > or = 33 percent , and rHuEPO ( 600 U/kg ) or placebo was administered intravenously . RESULTS One hundred seventy-three patients were evaluable . The number of autologous units collected from the rHuEPO and control groups , respectively , was 4.5 + /- 1.0 and 3.0 + /- 1.1 ( p < 0.001 ) , and marrow production of red cells increased by 668 + /- 222 and 353 + /- 155 mL over and above baseline production ( p < 0.05 ) . Allogeneic blood transfusion was required by 31 percent of control and 20 percent of rHuEPO patients ( p = 0.09 ) . Excluding 8 patients who received > 6 units , 29 percent of control and 14 percent of rHuEPO patients required allogeneic blood ( p = 0.015 ) . Logistic regression modeling determined that the risk of allogeneic transfusion was reduced by rHuEPO ( p = 0.025 ) . CONCLUSION The use of rHuEPO stimulates erythropoiesis , permits the storage of more autologous blood , and reduces allogeneic transfusion risk in patients with low hematocrits who are undergoing elective orthopedic surgery . Additional studies are necessary to determine the optimal schedules of rHuEPO administration and autologous blood collection as well as the cost-effectiveness of this strategy BACKGROUND The authors examined the impact of parenteral iron and recombinant human erythropoietin-β ( rHuEPO-β ) administered in the bilateral total knee replacement arthroplasty ( TKRA ) , on postoperative anemia and transfusion requirements in iron-deficient patients . STUDY DESIGN AND METHODS A total of 108 iron-deficient patients were r and omly assigned to two groups : Group C ( control ) or Group IE ( 200 mg of iron sucrose intravenously over 1 hr and 3000 IU of rHuEPO-β subcutaneously during the operation and during the postoperative period if the hemoglobin [ Hb ] level was 70 - 80 g/L ) . One or 2 units of blood were transfused to patients in both groups according to postoperative Hb level ( between 60 and 70 g/L or betweeen 50 and 60 g/L , respectively ) . Perioperative laboratory and clinical outcomes ( Hb , iron variables , postoperative bleeding amount , and number of units of RBCs transfused and incidences ) were documented . RESULTS Although preoperative Hb and the amount of postoperative bleeding were comparable in the two groups , Hb levels at 1 , 2 , and 3 days and at 2 and 6 weeks postoperation were significantly higher in Group IE . Furthermore , the transfusion rate was significantly lower in Group IE ( 20.4 % vs. 53.7 % , p=0.011 ) and the mean number of red blood cell units transfused was markedly lower in Group IE ( 0.2±0.5 vs. 0.8±0.8 , p=0.005 ) . Postoperative iron , ferritin , and transferrin saturation levels were significantly higher in Group IE . CONCLUSIONS Treatment with parenteral iron and low-dose rHuEPO-β in bilateral TKRA effectively attenuated anemia and decreased transfusion requirements in iron-deficient patients For patients who donate blood for autologous use and undergo major orthopedic surgery , low basal hematocrit ( Hct ) is the major cause of allogeneic blood exposure . To determine whether recombinant human erythropoietin ( rHuEPO ) could increase autologous blood procurement and reduce allogeneic blood exposure , a prospect i ve r and omized study was conducted in 50 women undergoing total hip replacement who had basal Hct < 40 percent ( 0.40 ) . Patients were r and omly placed in three groups : those receiving placebo , those receiving 300 U of rHuEPO per kg , and those receiving 600 U of rHuEPO per kg every 3 to 4 days for 21 days . Oral iron ( 125 - 270 mg/day ) was given ; in the last 24 patients , 100 mg of iron saccharate was administered intravenously at each donation . At each visit , 350 mL of blood was collected if Hct was > or = 34 percent ( 0.34 ) . Patients receiving rHuEPO donated a greater amount of blood for autologous use than did patients in the placebo group ( 4.5 + /- 1.1 vs. 2.8 + /- 0.6 units ; p < 0.05 ) and received a significantly lower amount of allogeneic blood ( 1.2 + /- 1.4 vs. 0.4 + /- 0.8 units ; p < 0.05 ) . No difference between the effects of the two doses of rHuEPO was observed . Iron support was a critical factor in the efficacy of treatment . No untoward effects were observed . The rHuEPO emerged as a safe and effective treatment , with adequate iron support , by which to increase preoperative deposit of autologous blood and to reduce exposure to allogeneic blood for patients with low basal Hct |
1,833 | 31,695,506 | For gFOBT , we found no site-specific difference ( proximally vs distally located ) of pooled sensitivities observed in the colorectal cancer ( CRC ) , advanced adenomas , and advanced neoplasms groups .
Summary receiver operating characteristic curve analyses showed similar patterns for both types of FOBT regarding the diagnostic accuracy for detecting colorectal neoplasms according to the anatomical sites of the colorectum .
Conclusion iFOBT had higher sensitivity for detecting advanced adenomas and advanced neoplasia located in the distal colon/rectum than that for those in the proximal colon | Objective We conducted a systematic review and meta- analysis aim ed at evaluating the differences of diagnostic performance of fecal occult blood tests ( FOBTs ) in detecting advanced colorectal neoplasms located in the proximal versus distal colorectum . | BACKGROUND & AIMS Few data have been published on the performance of colorectal cancer ( CRC ) screens that use multiple rounds of the fecal immunochemical test ( FIT ) . We evaluated outcomes of 4 screening rounds in over 7 years in an Italian population -based program . METHODS We conducted a prospect i ve cohort study of 2959 average-risk subjects , aged 50 - 74 years , who were invited for the first screening round in 2001 . We assessed the participation rate , the yield of advanced adenomas and CRC detected in the screening examinations , and we collected information about interval CRCs , with a follow-up period of 8.5 years . RESULTS Participation in each round varied from 56 % to 63 % ; 48.1 % of eligible subjects attended all 4 invitations . The positive predictive value of the FIT for advanced neoplasia ( CRC or advanced adenoma ) was 40 % at the first round , and approximately 33 % in the subsequent rounds . This decrease was attributable mainly to a decrease in the detection of CRC , although a high rate of advanced adenomas ( range , 0.8%-1.7 % ) was observed over all rounds . To find one advanced neoplasia in the study period the number of people that needed to be screened was 28 , and the number of tests needed was 74 . CONCLUSIONS About 60 % of invited individuals participated in every single round of FIT screening for CRC , but less than 50 % attended all 4 tests . A high detection rate of advanced adenomas in all rounds indicates that FIT screening could have a higher impact on incidence of CRC than the guaiac fecal occult blood test Purpose Fecal immunochemical tests ( FITs ) have been developed to address analytical problems inherent in the older guaiac-based fecal occult blood tests ( g-FOBTs ) . Our aim was to compare the performance characteristics of one g-FOBT ( Hemoccult II ) and two FITs ( the Hemoccult ICT and MagStream HemSp ) relative to colonoscopy for the detection of colorectal cancer and significant precursor lesions . We also examined whether a 1-day collection strategy would negatively impact test diagnostic performance . Methods We used a prospect i ve observational cohort design in a Canadian population eligible for screening . All participants received colonoscopy after performing the occult blood tests . Results One thous and seventy-five individuals were enrolled ( mean age 56.3 years , 53.8 % females ) . Using colonoscopy as the gold st and ard , the sensitivity for screen-relevant neoplasm was determined for Hemoccult II ( 7.2 , 95 % CI : 1.1–13.4 ) , Hemoccult ICT ( 23.2 % : 13.2–33.1 ) , and MagStream HemSp using 67 μg/gram stool as the cut-off ( 23.2 % : 13.2–33.1 ) . The Magstream HemSp , using a cut-off threshold of 30 μg/gram stool , had the lowest specificity at 87.6 % ( 85.4–89.6 ) , while the Hemoccult II had the highest at 98.8 % ( 98.1–99.5 ) . Single-day stool testing reduced the false-positive rates of all tests without significantly reducing the sensitivity . Conclusion We found that FITs have a significantly increased sensitivity but reduced specificity for screen-relevant neoplasm compared to g-FOBT using colonoscopy as the gold st and ard . Optimal threshold levels for hemoglobin detection depend on the desired trade off between sensitivity and false-positive rate . Single-day testing with an FIT may be an option to enhance population compliance with screening BACKGROUND In r and omized trials , fecal occult-blood testing reduces mortality from colorectal cancer . However , the duration of the benefit is unknown , as are the effects specific to age and sex . METHODS In the Minnesota Colon Cancer Control Study , 46,551 participants , 50 to 80 years of age , were r and omly assigned to usual care ( control ) or to annual or biennial screening with fecal occult-blood testing . Screening was performed from 1976 through 1982 and from 1986 through 1992 . We used the National Death Index to obtain up date d information on the vital status of participants and to determine causes of death through 2008 . RESULTS Through 30 years of follow-up , 33,020 participants ( 70.9 % ) died . A total of 732 deaths were attributed to colorectal cancer : 200 of the 11,072 deaths ( 1.8 % ) in the annual-screening group , 237 of the 11,004 deaths ( 2.2 % ) in the biennial-screening group , and 295 of the 10,944 deaths ( 2.7 % ) in the control group . Screening reduced colorectal-cancer mortality ( relative risk with annual screening , 0.68 ; 95 % confidence interval [ CI ] , 0.56 to 0.82 ; relative risk with biennial screening , 0.78 ; 95 % CI , 0.65 to 0.93 ) through 30 years of follow-up . No reduction was observed in all-cause mortality ( relative risk with annual screening , 1.00 ; 95 % CI , 0.99 to 1.01 ; relative risk with biennial screening , 0.99 ; 95 % CI , 0.98 to 1.01 ) . The reduction in colorectal-cancer mortality was larger for men than for women in the biennial-screening group ( P=0.04 for interaction ) . CONCLUSIONS The effect of screening with fecal occult-blood testing on colorectal-cancer mortality persists after 30 years but does not influence all-cause mortality . The sustained reduction in colorectal-cancer mortality supports the effect of polypectomy . ( Funded by the Veterans Affairs Merit Review Award Program and others . ) Context Several immunochemical fecal occult blood tests ( FOBTs ) that use different antibodies against human blood components are available . Contribution This study compared characteristics of 6 qualitative immunochemical FOBTs and 1 guaiac-based FOBT to identify adenomas among adults who attended screening colonoscopy . The FOBTs had widely varying performance characteristics . Sensitivity and specificity for detecting advanced adenomas ranged from 25 % to 72 % and 70 % to 97 % , respectively , for the immunochemical tests and were 9 % and 96 % , respectively , for the guaiac test . Caution One-day stool sample s were used , and stool was frozen before testing . Implication Qualitative immunochemical FOBTs have varying performance characteristics for detecting precancerous colorectal lesions . The Editors Colorectal cancer ( CRC ) is the third most common cancer in the world ( 1 ) , with about 1 million new cases and more than 500000 deaths per year . Because most cases of CRC are sporadic and develop from removable precancerous lesions ( adenomas ) and curable early- stage cancer ( 2 ) , screening for CRC has high potential for reducing morbidity and mortality . R and omized , controlled trials have demonstrated reduced mortality with guaiac-based fecal occult blood testing ( FOBT ) followed by colonoscopy or sigmoidoscopy if the FOBT result is positive ( 3 ) . However , guaiac-based FOBT , which detects the pseudoperoxidase activity of heme or hemoglobin , has important limitations . It is not specific for human hemoglobin , and false-positive and false-negative results can result from certain compounds or medications in foods ( for example , red meat or vitamin C ) ( 4 ) that should be avoided during the days before testing . Another important limitation is the low diagnostic performance for precursors to CRC . An advantage of guaiac-based FOBT is the simple analysis , which can easily be done at the physician 's office , even though reliable interpretation of test results requires training ( 5 , 6 ) . Immunochemical FOBTs that use specific antibodies against human blood components overcome the problem of diet or medication restriction . Unlike quantitative immunochemical FOBTs , qualitative immunochemical FOBTs that mostly use immunochromatographic technology also allow simple , office-based analysis . However , there are differences among qualitative immunochemical FOBTs . For example , the antibodies used and the different detection limits may influence the diagnostic performance , especially with respect to detection of precursor lesions . We aim ed to determine and compare performance characteristics of different qualitative immunochemical FOBTs for the detection of colorectal adenomas in a large sample of women and men undergoing screening colonoscopy . Methods Study Design and Sample The analyses were part of the BliTz study ( Begleitende Evaluierung innovativer Testverfahren zur Darmkrebsfrherkennung ) , an ongoing screening study conducted in cooperation with 20 gastroenterology practice s in southwestern Germany since January 2006 that aims to comparatively evaluate new tests for early detection of CRC . The study includes participants undergoing screening colonoscopya procedure that the German health care system has offered since October 2002 to average-risk persons 55 years or older . In Germany , preliminary consultation for any type of cancer screening is mostly done by general practitioners . For screening colonoscopy , patients are referred to the gastroenterologist only when the decision to have colonoscopy is made . All participants had a preliminary consultation with a gastroenterologist to receive detailed information and advice about screening colonoscopy . They were informed about and invited to participate in the study at that time . After we received written informed consent , we asked patients scheduled for screening colonoscopy to provide a stool sample before bowel preparation . Physicians who did colonoscopy and histologic examination were blinded to FOBT results . After colonoscopy , we collected reports on colonoscopic and histologic findings and extracted information in a st and ardized manner while blinded to the results of stool testing . We did not query patients about adverse events of testing ( such as psychological distress ) . The ethics committee of the University of Heidelberg , Heidelberg , Germany , approved the study . We included patients who provided stool sample s for qualitative immunochemical FOBTs until 13 December 2007 . The Figure shows the numbers of all potentially eligible patients . Figure . Study flow diagram . FOBadv = FOB advanced ( ulti med , Ahrensburg , Germany ) ; FOBplus = Bionexia FOBplus ( DIMA , Gttingen , Germany ) ; Hb/Hp C = Bionexia Hb/Hp Complex ( DIMA ) ; HO = HemOccult ( Beckman Coulter , Krefeld , Germany ) ; immoCare = immoCARE-C ( CAREdiagnostica , Voerde , Germany ) ; PreventID CC = PreventID CC ( Preventis , Bensheim , Germany ) ; QuickVue = QuickVue iFOB ( Quidel , San Diego , California ) . * The exclusion of 44 patients overall was due to missing or noninterpretable test cards . Of 1785 patients undergoing screening colonoscopy who agreed to participate , 111 were excluded because of visible rectal bleeding or preceding positive FOBT result . We excluded 13 patients because of inflammatory bowel disease . These patients usually receive close colonoscopic surveillance and would not be regarded as the target population for primary FOBT screening . We excluded 117 patients because they had undergone colonoscopy in the past 5 years and thus would not be eligible for primary FOBT screening ( if the previous colonoscopy result was positive , they are recommended for colonoscopic surveillance ; if the result was negative , they are at very low risk for colorectal neoplasia ) . We further excluded participants whose stool sample s were collected after colonoscopy only ( and thus violated the study protocol [ n= 65 ] ) , those with inadequate bowel preparation before colonoscopy ( n= 79 ) , and those with incomplete colonoscopy ( that is , the cecum was not reached , [ n= 22 ] ) . We excluded patients who received a histologically confirmed diagnosis of CRC ( this subgroup comprised only 11 participants by the end of 2007 and would not allow meaningfully precise performance estimates for this end point ) . Sensitivity with respect to CRC will be analyzed separately after continued recruitment of a much larger number of screening participants . We excluded 10 participants with nondefined polyps ( no histologic reports were available ) because we could not definitively determine the presence or absence of advanced adenomas in this group . Finally , we excluded participants with pseudopolyps ( n= 38 ) because these patients probably have had ulcerative colitis or undocumented inflammatory bowel disease . Stool Sample Collection Participants undergoing screening colonoscopy typically present at the gastroenterology practice for preliminary consultation about 1 week before colonoscopy . At that time , eligible patients received a study package that contained 1 test card for guaiac-based FOBT ( HemOccult , Beckman Coulter , Krefeld , Germany ) , a small container ( 60 mL ) for stool collection , a collection tissue for avoiding contact of the stool with toilet water , and detailed instructions for stool collection . Stool sample s were collected at home with no specific recommendations for diet or medicine restrictions . Patients received detailed instructions for sampling : Collect 1 bowel movement by using the collection tissue ; apply stool with a spatula ( provided in the study package ) on 2 windows of 1 HemOccult test card and store the test card at room temperature ; and fill at least half of the small container with stool by using plastic spoons ( provided in the study package ) , and store a plastic bag with the container in the freezer or , if not possible , in the refrigerator . Although the amount of stool provided varied widely , sufficient stool was available to adequately perform the different tests in all cases . On the day of colonoscopy , patients provided the HemOccult test card and the stool-filled container at the gastroenterology practice . The latter was stored at 20C , then shipped on dry ice to a central laboratory and stored at 20C until analysis . We documented the date s of stool sampling , arrival at the central laboratory , and performance of the immunochemical FOBTs . Laboratory Analyses Physician assistants who were blinded to the results of immunochemical testing analyzed HemOccult test cards at the gastroenterology practice on receipt according to the manufacturer 's instructions . They did analyses of HemOccult without rehydration , and test results were classified as positive , negative , or not interpretable ( for example , owing to incorrect sampling ) . We thawed the stool-filled containers at a median interval of 4 days on arrival at the central laboratory to do qualitative immunochemical FOBTs . Overall , we did 5 tests to determine fecal hemoglobin levels ( Bionexia FOBplus , DIMA , Gttingen , Germany ; PreventID CC , Preventis , Bensheim , Germany ; immoCARE-C , CAREdiagnostica , Voerde , Germany ; FOB advanced , ulti med , Ahrensburg , Germany ; and QuickVue iFOB , Quidel , San Diego , California ) and 1 test to determine both fecal hemoglobin and hemoglobinhaptoglobin levels ( Bionexia Hb/Hp Complex , DIMA ) . All tests are based on immunochromatographic technology . The lower detection limits indicated by the manufacturers were 10 ng/mL ( PreventID CC ) , 25 ng/mL ( Bionexia Hb/Hp Complex ) , 40 ng/mL ( Bionexia FOBplus and FOB advanced ) , and 50 ng/mL ( immoCARE-C and QuickVue iFOB ) . We did all analyses according to the manufacturers ' instructions and under st and ardized conditions . One trained investigator who was blinded to colonoscopy and HemOccult results classified all test results as positive or negative . Although classification was sometimes difficult for borderline results , we did not use an additional category for such results because the distinction between these and positive or negative results would be similarly difficult and BACKGROUND Fecal occult-blood testing and sigmoidoscopy have been recommended for screening for colorectal cancer , but the sensitivity of such combined testing for detecting neoplasia is uncertain . At 13 Veterans Affairs medical centers , we performed colonoscopy to determine the prevalence of neoplasia and the sensitivity of one-time screening with a fecal occult-blood test plus sigmoidoscopy . METHODS Asymptomatic subjects ( age range , 50 to 75 years ) provided stool specimens on cards from three consecutive days for fecal occult-blood testing , which were rehydrated for interpretation . They then underwent colonoscopy . Sigmoidoscopy was defined in this study as examination of the rectum and sigmoid colon during colonoscopy , and sensitivity was estimated by determining how many patients with advanced neoplasia had an adenoma in the rectum or sigmoid colon . Advanced colonic neoplasia was defined as an adenoma 10 mm or more in diameter , a villous adenoma , an adenoma with high- grade dysplasia , or invasive cancer . Classification of subjects according to the findings was based on the most advanced lesion . RESULTS A total of 2885 subjects returned the three specimen cards for fecal occult-blood testing and underwent a complete colonoscopic examination . A total of 23.9 percent of subjects with advanced neoplasia had a positive test for fecal occult blood . As compared with subjects who had a negative test for fecal occult blood , the relative risk of advanced neoplasia in subjects who had a positive test was 3.47 ( 95 percent confidence interval , 2.76 to 4.35 ) . Sigmoidoscopy identified 70.3 percent of all subjects with advanced neoplasia . Combined one-time screening with a fecal occult-blood test and sigmoidoscopy identified 75.8 percent of subjects with advanced neoplasia . CONCLUSIONS One-time screening with both a fecal occult-blood test with rehydration and sigmoidoscopy fails to detect advanced colonic neoplasia in 24 percent of subjects with the condition OBJECTIVES : Quantitative and qualitative immunochemical fecal occult blood tests ( FOBTs ) have been proposed for noninvasive colorectal cancer screening , but comparative evaluation is lacking . The aim of this study was to determine the diagnostic accuracy of two ( quantitative ) enzyme-linked immunosorbent assay (ELISA)-based immunochemical FOBTs for identifying colorectal adenomas in the target population of screening and to compare the results with six ( qualitative ) immunochromatographic FOBTs , previously evaluated in the same study participants using the same stool sample s. METHODS : A total of 1,319 participants of screening colonoscopy at average risk for colorectal neoplasia ( mean age 63 years ; age range 31–86 years ; 50 % men ) were recruited prospect ively from January 2006 to December 2007 in collaboration with 20 gastroenterological practice s in Germany . Fecal hemoglobin and hemoglobin – haptoglobin levels were measured using an automated ELISA ( RIDASCREEN ) . Test performance characteristics at different cutoff values were derived by comparing the results of stool testing with the results of colonoscopy in a blinded manner . RESULTS : A total of 130 participants ( 10 % ) had an advanced adenoma . The area under the receiver-operating characteristic curve with regard to advanced adenomas was 0.68 ( 0.65–0.71 ) for hemoglobin and 0.64 ( 0.61–0.67 ) for hemoglobin – haptoglobin ( P=0.034 ) . At a specificity of ∼95 % , the sensitivity ( 95 % confidence interval ) for advanced adenomas was 33 % ( 25–42 % ) for hemoglobin and 24 % ( 17–32 % ) for hemoglobin – haptoglobin , respectively . The sensitivity for hemoglobin was very close to sensitivities of the six qualitative FOBTs at ( strongly divergent ) levels of specificity observed for the latter . CONCLUSIONS : ELISA-based measurement of hemoglobin was superior to hemoglobin – haptoglobin , but showed a similar sensitivity for advanced adenomas compared with ( qualitative ) immunochromatographic FOBTs at defined levels of specificity . Compared with the latter , its quantitative nature offers advantages in terms of transparency and flexibility regarding the positivity threshold ( e.g. , specificity can be oriented toward available colonoscopy re sources or personal risk profiles ) and in terms of a higher level of st and ardization regarding test analysis and interpretation INTRODUCTION Current investigation for patients with colorectal symptoms without overt rectal bleeding is undertaken by colonoscopy or by flexible sigmoidoscopy and barium enema . A large majority of patients do not have colorectal cancer . There exists no instant , objective measure to discriminate patients who are likely to have colorectal cancer and therefore require expedient investigation . AIM To evaluate the sensitivity and specificity of immunological faecal occult blood testing ( FOBT ) in patients with colorectal symptoms without overt rectal bleeding . METHODS Consecutive patients referred for urgent colonic investigation , were prospect ively studied . A faecal sample was obtained from each one and subjected to immunological FOB which tested either negative or positive . All patients then underwent complete colonic imaging . The correlation between FOBT status and results from colonic imaging was studied . RESULTS Of 126 tested , thirty patients ( 26.8 % ) were FOBT positive . One hundred and twelve patients underwent complete colonic imaging . In the FOBT positive group colonic imaging identified 17 cases of histologically proven adenocarcinoma , 1 recurrent squamous cell carcinoma of anus , 1 adenomatous polyp , 6 cases of diverticulosis , and no pathology in 5 cases . In the 82 FOBT negative patients , no cancers were found . Overall the Immunological Faecal Occult Blood Test was found to have 100 % sensitivity and 86.3 % specificity . CONCLUSION Immunological faecal occult blood testing is a sensitive and specific test in identifying colorectal cancer and may be useful in identifying those patients who warrant urgent investigation . Routine clinical application may be useful in the allocation of re sources Background : Faecal occult blood tests ( FOBTs ) are used for colorectal cancer ( CRC ) screening . We aim ed to assess the sensitivity of an immunochemical FOBT for detecting advanced colorectal neoplasia in the left vs the right colon and to explore reasons for potential differences in site-specific test performance . Methods : We prospect ively measured faecal occult blood levels by a quantitative immunochemical FOBT ( RIDASCREEN ) in 2310 average-risk subjects undergoing screening colonoscopy . We compared diagnostic performance for subjects with left- vs right-sided advanced neoplasia , as well as patient characteristics and adenoma characteristics that have been suggested to impact faecal haemoglobin levels . Results : Sensitivities for subjects with left- vs right-sided advanced neoplasia were 33 % ( 95 % confidence interval ( CI ) , 26–41 % ) and 20 % ( CI , 11–31 % ) ( P=0.04 ) at a specificity of 95 % ( overall sensitivity : 29 % ) and the areas under the receiver-operating characteristics curve were 0.71 ( CI , 0.69–0.72 ) and 0.60 ( CI , 0.58–0.63 ) , respectively . Pedunculated shape was strikingly more common in participants with left- vs right-sided advanced neoplasia ( 47 % vs 14 % ) . In logistic regression analyses adjusted for site , pedunculated shape was statistically significantly associated with test sensitivity ( P=0.04 ) . Conclusions : The immunochemical FOBT in our study was more sensitive for detecting subjects with left- vs right-sided advanced colorectal neoplasia . Our findings may stimulate further diagnostic research in the field as well as modelling analyses to estimate the potential effect of site-specific test performance on the effectiveness of annual or biennial FOBT-based screening programmes , in particular with respect to protection from right-sided CRC Introduction The Bowel Cancer Screening Programme in Engl and began operating in 2006 with the aim of full roll out across Engl and by December 2009 . Subjects aged 60–69 are being invited to complete three guaiac faecal occult blood tests ( 6 windows ) every 2 years . The programme aims to reduce mortality from colorectal cancer by 16 % in those invited for screening . Methods All subjects eligible for screening in the National Health Service in Engl and are included on one data base , which is populated from National Health Service registration data covering about 98 % of the population of Engl and . This analysis is only of subjects invited to participate in the first ( prevalent ) round of screening . Results By October 2008 almost 2.1 million had been invited to participate , with tests being returned by 49.6 % of men and 54.4 % of women invited . Uptake ranged between 55–60 % across the four provincial hubs which administer the programme but was lower in the London hub ( 40 % ) . Of the 1.08 million returning tests 2.5 % of men and 1.5 % of women had an abnormal test . 17 518 ( 10 608 M , 6910 F ) underwent investigation , with 98 % having a colonoscopy as their first investigation . Cancer ( n=1772 ) and higher risk adenomas ( n=6543 ) were found in 11.6 % and 43 % of men and 7.8 % and 29 % of women investigated , respectively . 71 % of cancers were ‘ early ’ ( 10 % polyp cancer , 32 % Dukes A , 30 % Dukes B ) and 77 % were left-sided ( 29 % rectal , 45 % sigmoid ) with only 14 % being right-sided compared with expected figures of 67 % and 24 % for left and right side from UK cancer registration . Conclusion In this first round of screening in Engl and uptake and fecal occult blood test positivity was in line with that from the pilot and the original European trials . Although there was the expected improvement in cancer stage at diagnosis , the proportion with left-sided cancers was higher than expected BACKGROUND & AIMS Several r and omized population -based studies have shown that screening for colorectal cancer ( CRC ) by fecal occult blood tests ( FOBTs ) can reduce CRC mortality . The aim of this French population -based study was to assess whether a similar benefit could be obtained in countries characterized by high performances in the diagnosis and management of CRC . METHODS Small-sized geographic areas , including 91,199 individuals aged 45 - 74 years , were allocated to either FOBT screening or no screening . Six screening rounds were performed . The FOBT was performed without diet restriction and was sent to a central analysis center and processed without rehydration . Screening group participants who had a positive test result were offered a full colonoscopy . The entire population was followed up for 11 years after study entry . RESULTS Acceptability of the test was 52.8 % at the first screening round and varied between 53.8 % and 58.3 % in the successive rounds . Positivity rates were 2.1 % initially and 1.4 % on average in the successive rounds . CRC mortality was significantly lower in the screening population compared with the control population ( mortality ratio , 0.84 ; 95 % confidence interval , 0.71 - 0.99 ) . The reduction in CRC mortality was more pronounced in those who participated at least once ( mortality ratio , 0.67 ; 95 % confidence interval , 0.56 - 0.81 ) . CONCLUSIONS Our findings , together with the results of other trials , suggest that biennial screening by FOBTs can reduce CRC mortality regardless of the quality of the health system and support attempts to introduce large-scale screening programs into the general population OBJECTIVES : The immunological fecal occult blood test ( IFOBT ) has established itself as a more precise marker for colorectal cancer ( CRC ) screening than traditional guaiac-based FOBT . The simpler , cheaper , and more convenient newer office-based IFOBTs have been vali date d for diagnosing CRC . Dimeric isoenzyme of pyruvate kinase , M2-PK , expressed by tumor cells , has as well been proposed as a screening tool for CRC . This is the first study comparing fecal M2-PK as a screening biomarker for CRC against previously evaluated office-based IFOBT and colonoscopy . METHODS : Six hundred forty consecutive subjects ( symptomatic , as well as for CRC screening ) referred for colonoscopy for various indications across five centers in Germany provided the stool sample s for performing M2-PK and an immunochemical FOB strip test . The IFOBT used was a rapid immunochromatographic assay for detection of fecal hemoglobin . For M2-PK , a commercially available s and wich enzyme-linked immunosorbent assay ( ELISA ) was used . The M2-PK test needs 6 h , while the office-based test can be read in just 10 min and is five times cheaper . RESULTS : Office-based IFOBT had sensitivity , specificity , positive predictive value ( PPV ) , negative predictive value ( NPV ) , and positive and negative likelihood ratios ( LR ) of 64.5 , 96.3 , 72.0 , 94.9 , 17.5 , and 0.4 for diagnosing colorectal neoplasia ( CRN ) , while the above performance characteristics for M2-PK at a cutoff value of 4U/mL were 72.4 , 73.8 , 29.0 , 94.8 , 2.8 , and 0.8 respectively . CONCLUSIONS : This office-based IFOBT was found to have significantly higher specificity , PPV , and positive LR as compared with M2-PK . IFOBT proved to be a convenient , noncumbersome , quick , and cheap tool in patients with above-average risk for detection of CRN BACKGROUND An accurate , noninvasive test could improve the effectiveness of colorectal-cancer screening . METHODS We compared a noninvasive , multitarget stool DNA test with a fecal immunochemical test ( FIT ) in persons at average risk for colorectal cancer . The DNA test includes quantitative molecular assays for KRAS mutations , aberrant NDRG4 and BMP3 methylation , and β-actin , plus a hemoglobin immunoassay . Results were generated with the use of a logistic-regression algorithm , with values of 183 or more considered to be positive . FIT values of more than 100 ng of hemoglobin per milliliter of buffer were considered to be positive . Tests were processed independently of colonoscopic findings . RESULTS Of the 9989 participants who could be evaluated , 65 ( 0.7 % ) had colorectal cancer and 757 ( 7.6 % ) had advanced precancerous lesions ( advanced adenomas or sessile serrated polyps measuring ≥1 cm in the greatest dimension ) on colonoscopy . The sensitivity for detecting colorectal cancer was 92.3 % with DNA testing and 73.8 % with FIT ( P=0.002 ) . The sensitivity for detecting advanced precancerous lesions was 42.4 % with DNA testing and 23.8 % with FIT ( P<0.001 ) . The rate of detection of polyps with high- grade dysplasia was 69.2 % with DNA testing and 46.2 % with FIT ( P=0.004 ) ; the rates of detection of serrated sessile polyps measuring 1 cm or more were 42.4 % and 5.1 % , respectively ( P<0.001 ) . Specificities with DNA testing and FIT were 86.6 % and 94.9 % , respectively , among participants with nonadvanced or negative findings ( P<0.001 ) and 89.8 % and 96.4 % , respectively , among those with negative results on colonoscopy ( P<0.001 ) . The numbers of persons who would need to be screened to detect one cancer were 154 with colonoscopy , 166 with DNA testing , and 208 with FIT . CONCLUSIONS In asymptomatic persons at average risk for colorectal cancer , multitarget stool DNA testing detected significantly more cancers than did FIT but had more false positive results . ( Funded by Exact Sciences ; Clinical Trials.gov number , NCT01397747 . ) BACKGROUND & AIMS The fecal immunochemical test ( FIT ) is superior to the guaiac-based fecal occult blood test in detecting neoplasia . There are not much data on the optimal number of FITs to perform . We conducted a population -based trial to determine attendance and diagnostic yield of 1- and 2- sample FIT screening . METHODS The study included 2 r and omly selected groups of subjects aged 50 - 74 years ( 1- sample FIT , n=5007 ; 2- sample FIT , n=3197 ) . The 2- sample group was instructed to collect fecal sample s on 2 consecutive days . Subjects were referred for colonoscopy when at least 1 sample tested positive ( ≥50 ng hemoglobin/mL ) . RESULTS Attendance was 61.5 % in the 1- sample group ( 2979 of 4845 ; 95 % confidence interval , 60.1%-62.9 % ) and 61.3 % in the 2- sample group ( 1875 of 3061 ; 95 % confidence interval , 59.6%-63.0 % ; P=.84 ) . In the 1- sample group 8.1 % tested positive , and in the 2- sample group 12.8 % had at least 1 positive test outcome and 5.0 % had 2 positive test outcomes ( P<.05 ) . When the mean from both test results in the 2- sample group was used , 10.1 % had a positive test outcome ( P<.05 ) . The detection rates for advanced neoplasia were 3.1 % in the 1- sample group , 4.1 % in the 2- sample group with at least 1 positive test outcome , 2.5 % when both test results were positive , and 3.7 % among subjects with the mean from both test results being positive . CONCLUSIONS There is no difference in attendance for subjects offered 1- or 2- sample FIT screening . The results allow for the development of efficient FIT screening strategies that can be adapted for local colonoscopy capacities , rather than varying the cut-off value in a 1- sample strategy OBJECTIVE : Fecal immunochemical testing ( FIT ) is increasingly used for colorectal cancer ( CRC ) screening . We aim ed to estimate its diagnostic accuracy in invitational population screening measured against colonoscopy . METHODS : Participants ( 50–75 years ) in an invitational primary colonoscopy screening program were asked to complete one sample FIT before colonoscopy . We estimated FIT sensitivity , specificity , and predictive values in detecting CRC and advanced neoplasia ( carcinomas and advanced adenomas ) for cutoff levels of 50 ( FIT50 ) , 75 ( FIT75 ) , and 100 ( FIT100 ) ng hemoglobin (Hb)/ml , corresponding with , respectively , 10 , 15 and 20 μg Hb/g feces . RESULTS : A total of 1,256 participants underwent a FIT and screening colonoscopy . Advanced neoplasia was detected by colonoscopy in 119 ( 9 % ) , 8 ( 0.6 % ) of them had CRC . At FIT50 , 121 ( 10 % ) had a positive test result ; 45 ( 37 % ) had advanced neoplasia and 7 ( 6 % ) had CRC . A total of 74 of 1,135 FIT50 negatives ( 7 % ) had advanced neoplasia including 1 ( 0.1 % ) CRC . FIT50 had a sensitivity of 38 % ( 95 % confidence interval ( CI ) : 29–47 ) for advanced neoplasia and 88 % ( 95 % CI : 37–99 ) for CRC at a specificity of 93 % ( 95 % CI : 92–95 ) and 91 % ( 95 % CI : 89–92 ) , respectively . The positive and negative predictive values for FIT50 were 6 % ( 95 % CI : 3–12 ) and almost 100 % ( 95 % CI : 99–100 ) for CRC , and 37 % ( 95 % CI : 29–46 ) and 93 % ( 95 % CI : 92–95 ) for advanced neoplasia . The sensitivity and specificity of FIT75 for advanced neoplasia were 33 % ( 95 % CI : 25–42 ) and 96 % ( 95 % CI : 94–97 ) . At FIT100 , 71 screenees ( 6 % ) had a positive test result . The sensitivity and specificity of FIT100 were for advanced neoplasia 31 % ( 95 % CI : 23–40 ) and 97 % ( 95 % CI : 96–98 ) , and for CRC 75 % ( 95 % CI : 36–96 ) and 95 % ( 95 % CI : 93–96 ) . The area under curve for detecting advanced neoplasia was 0.70 ( 95 % CI : 0.64–0.76 ) . FIT had a similar sensitivity for proximal and distal advanced neoplasia at cutoffs of 50 ( 38 % vs. 37 % ; P=0.99 ) , 75 ( 33 % vs. 31 % ; P=0.85 ) and 100 ( 33 % vs. 29 % ; P=0.68 ) ng Hb/ml . DISCUSSION : Nine out of ten screening participants with CRC and four out of ten with advanced neoplasia will be detected using one single FIT at low cutoff . Sensitivity in detecting proximal and distal advanced neoplasia is comparable BACKGROUND In the National Polyp Study ( NPS ) , colorectal cancer was prevented by colonoscopic removal of adenomatous polyps . We evaluated the long-term effect of colonoscopic polypectomy in a study on mortality from colorectal cancer . METHODS We included in this analysis all patients prospect ively referred for initial colonoscopy ( between 1980 and 1990 ) at NPS clinical centers who had polyps ( adenomas and nonadenomas ) . The National Death Index was used to identify deaths and to determine the cause of death ; follow-up time was as long as 23 years . Mortality from colorectal cancer among patients with adenomas removed was compared with the expected incidence-based mortality from colorectal cancer in the general population , as estimated from the Surveillance Epidemiology and End Results ( SEER ) Program , and with the observed mortality from colorectal cancer among patients with nonadenomatous polyps ( internal control group ) . RESULTS Among 2602 patients who had adenomas removed during participation in the study , after a median of 15.8 years , 1246 patients had died from any cause and 12 had died from colorectal cancer . Given an estimated 25.4 expected deaths from colorectal cancer in the general population , the st and ardized incidence-based mortality ratio was 0.47 ( 95 % confidence interval [ CI ] , 0.26 to 0.80 ) with colonoscopic polypectomy , suggesting a 53 % reduction in mortality . Mortality from colorectal cancer was similar among patients with adenomas and those with nonadenomatous polyps during the first 10 years after polypectomy ( relative risk , 1.2 ; 95 % CI , 0.1 to 10.6 ) . CONCLUSIONS These findings support the hypothesis that colonoscopic removal of adenomatous polyps prevents death from colorectal cancer . ( Funded by the National Cancer Institute and others . ) Background and aims : This prospect i ve trial was design ed to compare the performance characteristics of five different screening tests in parallel for the detection of advanced colonic neoplasia : CT colonography ( CTC ) , colonoscopy ( OC ) , flexible sigmoidoscopy ( FS ) , faecal immunochemical stool testing ( FIT ) and faecal occult blood testing ( FOBT ) . Methods : Average risk adults provided stool specimens for FOBT and FIT , and underwent same-day low-dose 64-multidetector row CTC and OC using segmentally unblinded OC as the st and ard of reference . Sensitivities and specificities were calculated for each single test , and for combinations of FS and stool tests . CTC radiation exposure was measured , and patient comfort levels and preferences were assessed by question naire . Results : 221 adenomas were detected in 307 subjects who completed CTC ( mean radiation dose , 4.5 mSv ) and OC ; 269 patients provided stool sample s for both FOBT and FIT . Sensitivities of OC , CTC , FS , FIT and FOBT for advanced colonic neoplasia were 100 % ( 95 % CI 88.4 % to 100 % ) , 96.7 % ( 82.8 % to 99.9 % ) , 83.3 % ( 95 % CI 65.3 % to 94.4 % ) , 32 % ( 95 % CI 14.9 % to 53.5 ) and 20 % ( 95 % CI 6.8 % to 40.7 % ) , respectively . Combination of FS with FOBT or FIT led to no relevant increase in sensitivity . 12 of 45 advanced adenomas were smaller than 10 mm . 46 % of patients preferred CTC and 37 % preferred OC ( p<0.001 ) . Conclusions : High-resolution and low-dose CTC is feasible for colorectal cancer screening and reaches sensitivities comparable with OC for polyps > 5 mm . For patients who refuse full bowel preparation and OC or CTC , FS should be preferred over stool tests . However , in cases where stool tests are performed , FIT should be recommended rather than FOBT OBJECTIVES To undertake a prescreening evaluation of a new brush-based faecal immunochemical test for haemoglobin , relative to a traditional spatula-sampling immunochemical test . METHODS SETTING Patients aged between 24 and 90 years , scheduled to undergo diagnostic colonoscopy in two major urban hospitals , for a range of clinical indications . DESIGN Patients sample d three stools using a spatula for the reference FlexSure OBT test and two stools using a brush for the InSure test ; order of sampling was r and omised . Faecal haemoglobin was quantified by a modified InSure in a subset of patients to determine whether brush-sampling allowed discrimination between groups . MAIN OUTCOME MEASURES Sensitivity for cancer or adenoma ; false-positive rate in normals . Faecal haemoglobin levels . Preference for sampling method . RESULTS InSure and FlexSure OBT did not differ in their sensitivities for cancer ( 27/36 , 75 % vs 29/36 , 80.5 % , respectively ) , adenomas > or= 10 mm ( 12/29 , 41.4 % vs 13/29 , 44.8 % ) or adenomas < 10 mm ( each 8/56 , 14.3 % ) . Likewise , false-positive rates in normals were similar : 4/179 ( 2.2 % ) and 5/179 ( 2.8 % ) respectively ( specificities of 97.8 % and 97.2 % , respectively ) . Levels of faecal haemoglobin were highest in those with cancers ; those with adenomas had intermediate levels which were also significantly higher than those in normals . The brush sampling method was preferred by 38/46 ( 82.6 % ) , while 4/46 ( 8.7 % ) preferred the spatula ( p<0.00001 ) . CONCLUSIONS InSure is as sensitive and specific as FlexSure OBT for faecal haemoglobin . The novel stool-sampling method of InSure allows discrimination between normals and classes of neoplasia , and is highly preferred . The brush-sampling faecal immunochemical test InSure should now be evaluated in a screening population Importance Individuals with adenomatous polyps are advised to undergo repeated colonoscopy surveillance to prevent subsequent colorectal cancer ( CRC ) , but the relationship between adenomas at colonoscopy and long-term CRC incidence is unclear . Objective To compare long-term CRC incidence by colonoscopy adenoma findings . Design , Setting , and Participants Multicenter , prospect i ve cohort study of participants in the Prostate , Lung , Colorectal , and Ovarian ( PLCO ) Cancer r and omized clinical trial of flexible sigmoidoscopy ( FSG ) beginning in 1993 with follow-up for CRC incidence to 2013 across the United States . Participants included 154 900 men and women aged 55 to 74 years enrolled in PLCO of whom 15 935 underwent colonoscopy following their first positive FSG screening result . The final day of follow-up was December 31 , 2013 . Exposures Enrolled participants had been r and omized to FSG or usual care . Participants who underwent FSG and had abnormal findings were referred for follow-up . Subsequent colonoscopy findings were categorized as advanced adenoma ( ≥1 cm , high- grade dysplasia , or tubulovillous or villous histology ) , nonadvanced adenoma ( < 1 cm without advanced histology ) , or no adenoma . Main Outcomes and Measures The primary outcome was CRC incidence within 15 years of the baseline colonoscopy . The secondary outcome was CRC mortality . Results There were 15 935 participants who underwent colonoscopy ( men , 59.7 % ; white , 90.7 % ; median age , 64 y [ IQR , 61 - 68 ] ) . On initial colonoscopy , 2882 participants ( 18.1 % ) had an advanced adenoma , 5068 participants ( 31.8 % ) had a nonadvanced adenoma , and 7985 participants ( 50.1 % ) had no adenoma ; median follow-up for CRC incidence was 12.9 years . CRC incidence rates per 10 000 person-years of observation were 20.0 ( 95 % CI , 15.3 - 24.7 ; n = 70 ) for advanced adenoma , 9.1 ( 95 % CI , 6.7 - 11.5 ; n = 55 ) for nonadvanced adenoma , and 7.5 ( 95 % CI , 5.8 - 9.7 ; n = 71 ) for no adenoma . Participants with advanced adenoma were significantly more likely to develop CRC compared with participants with no adenoma ( rate ratio [ RR ] , 2.7 [ 95 % CI , 1.9 - 3.7 ] ; P < .001 ) . There was no significant difference in CRC risk between participants with nonadvanced adenoma compared with no adenoma ( RR , 1.2 [ 95 % CI , 0.8 - 1.7 ] ; P = .30 ) . Compared with participants with no adenoma , those with advanced adenoma were at significantly increased risk of CRC death ( RR , 2.6 [ 95 % CI , 1.2 - 5.7 ] , P = .01 ) , but mortality risk in participants with nonadvanced adenoma was not significantly different ( RR , 1.2 [ 95 % CI , 0.5 - 2.7 ] , P = .68 ) . Conclusions and Relevance Over a median of 13 years of follow-up , participants with an advanced adenoma at diagnostic colonoscopy prompted by a positive flexible sigmoidoscopy result were at significantly increased risk of developing colorectal cancer compared with those with no adenoma . Identification of nonadvanced adenoma may not be associated with increased colorectal cancer risk . Trial Registration clinical trials.gov Identifier : Context Because the colonic mucosa constantly sheds cells , testing stool for cancer-related genes could be better for colorectal cancer screening than testing for occult bleeding , which is intermittent . Content A total of 3764 healthy adults had screening colonoscopy , fecal occult blood testing with Hemoccult and HemoccultSensa , and both a first- and a second-generation stool DNA test ( SDT-1 and SDT-2 , respectively ) for a battery of cancer genes . The sensitivity of SDT-1 and HemoccultSensa was very similar for screen-relevant neoplasms ( 20 % and 21 % , respectively ) , whereas the sensitivity of SDT-2 was 40 % . Caution The authors could not measure the specificity of SDT-2 . Implication A second-generation stool test for cancer genes is substantially more sensitive than fecal occult blood testing . The Editors Colorectal cancer remains the second most common cause of death among the types of cancer ( 1 ) . Although screening reduces colorectal cancer mortality ( 26 ) , observed reductions have been modest ( 6 , 7 ) and more than one half of adults in the United States have not received screening ( 8) . More accurate , user-friendly , and widely distributable tools have the potential to improve screening effectiveness , acceptability , and access . Several molecular approaches to screening stool for colorectal cancer have been studied and review ed ( 9 , 10 ) , and stool DNA testing has been jointly endorsed by the American Cancer Society , the U.S. Multi-Society Task Force on Colorectal Cancer , and the American College of Radiology ( 11 ) . The advantages of stool DNA testing include noninvasiveness , absence of bowel preparation or dietary restrictions , and ease of access via mail courier . However , the reported accuracy of stool DNA tests for the detection of colorectal neoplasia varies . In clinical studies that used different assays and selected groups ( 1220 ) , sensitivities ranged from 62 % to 100 % for colorectal cancer and 27 % to 82 % for advanced adenomas , with specificities ranging from 82 % to 100 % . In the only reported multicenter study on asymptomatic average-risk patients ( 21 ) , a precommercial multitarget DNA assay ( SDT-1 , a prototype of PreGenPlus , EXACT Sciences , Marlborough , Massachusetts ) detected 52 % of cases of colorectal cancer , compared with 13 % by Hemoccult ( P = 0.003 ) , at specificities of 94.4 % and 95.2 % , respectively . The accuracy of stool DNA testing is influenced by both biological and technical factors . A panel of markers must be used to accommo date the molecular heterogeneity of colorectal neoplasia , and marker selection critically affects discrimination ( 9 ) . Unlike occult bleeding , which is intermittent ( 22 ) , DNA markers seem to be shed continuously by exfoliation ( 23 ) . Thus , the multiple stool sampling practice d with fecal occult blood tests may not be necessary with stool DNA tests . However , recovery of the minute quantities of human DNA and assay of tumor-specific DNA alterations from stool present technical challenges and require exquisite laboratory sensitivity to achieve optimal detection rates . Our primary aim was to compare the precommercial stool DNA test ( SDT-1 ) , which was studied by Imperiale and colleagues ( 21 ) , with widely used fecal occult blood tests for the detection of screen-relevant neoplasia , defined as curable-stage colorectal cancer ( no distant metastases ) , high- grade dysplasia , or adenomas larger than 1 cm . A secondary aim was to explore neoplasm detection by another stool DNA test 2 ( SDT-2 ) , which uses a more broadly informative marker panel . Methods Table 1 lists the genes used in our test panels and defines several key terms . Table 1 . Definitions Design We conducted this multicenter , prospect i ve , triple-blinded trial , targeting average-risk persons , from 2001 to 2007 . A group of national experts on colorectal cancer screening advised on study design , and institutional review boards at each site approved the study . Because we did not know the effect of diet and medications on DNA assays , patients were r and omly assigned at entry to group A ( restriction of red meat and therapeutic doses of nonsteroidal anti-inflammatory drugs for 3 days before and during stool collection s ) or group B ( no such restrictions ) . All patients were asked not to ingest vitamin C for the 3 days before and during stool collection s. For the companion test , we chose Hemoccult ( Beckman Coulter , Fullerton , California ) , the most widely used fecal occult blood test , which was used in the trials that established the benefit of screening for fecal occult blood ( 24 ) . As a second companion test , we chose the next-generation guaiac test HemoccultSensa ( Beckman Coulter ) . We compared fecal blood results from 3 stools per patient with stool DNA on 1 stool . Experienced technicians performed stool DNA and occult blood testing in separate central laboratories without knowledge of clinical findings or the results of other tests . All patients who completed stool collection s also had colonoscopy , which served as the criterion st and ard . We did not have access to data until after they had been analyzed by statisticians and released by a data monitoring board . Participants We recruited asymptomatic persons age 50 to 80 years who were at average risk for colorectal cancer from communities surrounding 22 participating academic and regional health care systems through direct mail and multimedia advertisements . The exclusion criteria were structural colorectal evaluation ( endoscopic or radiographic ) within 10 years ; fecal blood testing within 1 year ; overt rectal bleeding within 1 month ; previous colorectal resection ; aerodigestive cancer within 5 years ; inability to stop therapeutic doses of nonsteroidal anti-inflammatory drugs or anticoagulants ; coagulopathy ; contraindications to colonoscopy ; chemotherapy within 3 months ; high-risk conditions for colorectal cancer , such as familial adenomatous polyposis , the Lynch syndrome , or other cancer syndromes ; previous colorectal cancer or adenoma ; inflammatory bowel disease ; or more than 2 first-degree relatives with colorectal neoplasia . Study assistants at each site registered participants and r and omly assigned them by using a Web-based management system ; distributed fecal blood test cards , stool collection containers , and colonoscopy preparation material s ; and provided instructions . Stool Collection and Processing Patients collected 3 stools by using plastic buckets mounted to the toilet seat . Promptly after each individual collection , patients smeared stool onto both windows of their Hemoccult and HemoccultSensa cards and then express-shipped smeared cards and the whole stool ( sealed in a bucket in an insulated container cooled with ice packs ) to the Mayo Clinic in Rochester , Minnesota . We froze the first stool from each participant whole at 80 C on receipt and sent it in batches on dry ice to EXACT Sciences ( Marlborough , Massachusetts ) for DNA assay ; each of the subsequent 2 stools were archived in aliquots at 80 C. If the first stool weighed less than 30 g or was received more than 48 hours after defecation , it was rejected for DNA analysis and the second or third stool ( if it met inclusion criteria ) was sent for DNA assay . Stool Assays DNA Testing All assays were polymerase chain reactionbased and were run at EXACT Sciences . Stool DNA test 1 was performed as described in Imperiale and colleagues ' study ( 21 ) . The marker panel for SDT-1 included 21 tumor-specific point mutations ( 3 on the K-ras gene , 10 on the APC gene , and 8 on the p53 gene ) ; the microsatellite-instability marker BAT-26 ; and long DNA , a marker for delayed apoptosis , which is characteristic of exfoliated neoplastic colonocytes ( 12 ) . For SDT-2 , sequence-specific DNA markers were detected by acrylamide gel electrophoresis , as described by Whitney and colleagues ( 24 ) ; the panel consisted of 3 tumor-specific markers broadly informative for both colorectal cancer and adenomas ( 25 ) : K-ras mutations , scanning of APC mutator cluster regions , and methylation of the vimentin gene . We used methods described elsewhere to detect mutant K-ras ( 12 ) , APC scanning ( 25 ) , and vimentin gene methylation ( 20 ) assays . We defined any positive component marker result according to the manufacturer 's preestablished criteria as a positive test result . Occult Blood Testing The manufacturer that developed the Hemoccult and HemoccultSensa cards , without rehydration , trained technicians on-site at the Mayo Clinic . As recommended by the manufacturer , the technicians added the catalyst solution to cards stored at ambient temperature within 48 to 72 hours of collection . We defined a spreading ( enlarging ) blue color in 60 seconds in any window of the cards as a positive result and any other result as negative . Colonoscopy After cathartic preparation , experienced endoscopists performed colonoscopy in all patients . If the examination did not reach the cecum or inspected less than 90 % of the mucosa , the patient was disqualified . Endophotographs documented cecal intubation , and the size and location of all lesions were recorded . Costs not covered by third parties were reimbursed by study funding . Pathologic Examination Local pathologists examined all endoscopically or surgically sample d lesions . A gastrointestinal pathologist at the coordinating site reexamined all lesions to confirm diagnosis . Classification discrepancies of screen-relevant neoplasms were adjudicated by a second expert pathologist . We categorized patients with multiple neoplasms according to the most advanced lesion . For assay of markers in screen-relevant neoplasms , DNA was extracted from microdissected tissue . Statistical Analysis We calculated sample size to ensure adequate power to detect differences in sensitivity comparisons . We powered the study to ensure an adequate number of cases of curable-stage colorectal cancer and high- grade dysplasia and assumed their combined prevalence to be at least 1.5 % . A sample size of 2900 would yield an expected 43 curable-stage cancer or high- grade dysplasia cases , |
1,834 | 31,984,479 | Quantitative analysis suggests that dexamethasone and gabapentin reduced postoperative pain .
The use of paravertebral blocks also reduced postoperative pain scores , analgesia consumption and the incidence of postoperative nausea and vomiting .
Intra-operative opioid requirements were documented to be lower when a pectoral nerves block was performed , which also reduced postoperative pain scores and opioid consumption . | Analgesic protocol s used to treat pain after breast surgery vary significantly .
The aim of this systematic review was to evaluate the available literature on this topic and develop recommendations for optimal pain management after oncological breast surgery . | Background Persistent pain is a challenging clinical problem after breast cancer treatment . After surgery , inflammatory pain and nociceptive input from nerve injury induce central sensitization which may play a role in the genesis of persistent pain . Using quantitative sensory testing , we tested the hypothesis that adding COX-2 inhibition to st and ard treatment reduces hyperalgesia after breast cancer surgery . A secondary hypothesis was that patients developing persistent pain would exhibit more postoperative hyperalgesia . Methods 138 women scheduled for lumpectomy/mastectomy under general anesthesia with paravertebral block were r and omized to COX-2 inhibition ( 2x40 mg parecoxib on day of surgery , thereafter 2x200 mg celecoxib/day until day five ) or placebo . Preoperatively and 1 , 5 , 15 days and 1 , 3 , 6 , 12 months postoperatively , we determined electric and pressure pain tolerance thresholds in dermatomes C6/T4/L1 and a 100 mm VAS score for pain . We calculated the sum of pain tolerance thresholds and analyzed change in these versus preoperatively using mixed models analysis with factor medication . To assess hyperalgesia in persistent pain patients we performed an additional analysis on patients reporting VAS>30 at 12 months . Results 48 COX-2 inhibition and 46 placebo patients were analyzed in a modified intention to treat analysis . Contrary to our primary hypothesis , change in the sum of tolerance thresholds in the COX-2 inhibition group was not different versus placebo . COX-2 inhibition had an effect on pain on movement at postoperative day 5 ( p<0.01 ) . Consistent with our secondary hypothesis , change in sum of pressure pain tolerance thresholds in 11 patients that developed persistent pain was negative versus patients without pain ( p<0.01 ) from day 5 to 1 year postoperatively . Conclusions Perioperative COX-2 inhibition has limited value in preventing sensitization and persistent pain after breast cancer surgery . Central sensitization may play a role in the genesis of persistent postsurgical pain Background : Regional anesthesia improves postoperative analgesia and enhances quality of recovery ( QoR ) after ambulatory surgery . This r and omized , double-blinded , parallel-group , placebo-controlled trial examines the effects of multilevel ultrasound-guided paravertebral blocks ( PVBs ) and total intravenous anesthesia on QoR after ambulatory breast tumor resection . Methods : Sixty-six women were r and omized to st and ardized general anesthesia ( control group ) or PVBs and propofol-based total intravenous anesthesia ( PVB group ) . The PVB group received T1–T5 PVBs with 5 ml of 0.5 % ropivacaine per level , whereas the control group received sham subcutaneous injections . Postoperative QoR was design ated as the primary outcome . The 29-item ambulatory QoR tool was administered in the preadmission clinic , before discharge , and on postoperative days 2 , 4 , and 7 . Secondary outcomes included block success , pain scores , intra- and postoperative morphine consumption , time to rescue analgesia , incidence of nausea and vomiting , and hospital discharge time . Results : Data from sixty-four patients were analyzed . The PVB group had higher QoR scores than control group upon discharge ( 146 vs. 131 ; P < 0.0001 ) and on postoperative day 2 ( 145 vs. 135 ; P = 0.013 ) ; improvements beyond postoperative day 2 lacked statistical significance . None of the PVB group patients required conversion to inhalation gas – based general anesthesia or experienced block-related complications . PVB group patients had improved pain scores on postanesthesia care unit admission and discharge , hospital discharge , and postoperative day 2 ; their intraoperative morphine consumption , incidence of nausea and vomiting , and discharge time were also reduced . Conclusion : Combining multilevel PVBs with total intravenous anesthesia provides reliable anesthesia , improves postoperative analgesia , enhances QoR , and expedites discharge compared with inhalational gas- and opioid-based general anesthesia for ambulatory breast tumor resection BACKGROUND : The efficacy of continuous wound infiltration with local anesthetic has not been compared with that of thoracic paravertebral block ( PVB ) after breast surgery . In this study , we evaluated the analgesic efficacy and morphine consumption of the two techniques after mastectomy . METHODS : Forty-eight patients undergoing modified radical mastectomy with axillary dissection were r and omly assigned to either a preoperative PVB with 20 mL of ropivacaine 0.5 % ( group PVB ) or a continuous ropivacaine 0.5 % infusion ( CRI ) at a 2 mL/h rate for each of two multilumen catheters placed subcutaneously at the end of the procedure ( group CRI ) . The catheters were left in place for 24 h postoperatively . A st and ardized general anesthetic was administered to all patients . Postoperative morphine consumption , pain scores and painful restricted movement of the shoulder for 24 h postoperatively as well as incidence of adverse events , including postoperative nausea and vomiting , were recorded . RESULTS : Morphine consumption was similar between groups ( PVB : 42.6 ± 11 vs CRI : 38.7 ± 11 mg in 24 h , P = 0.225 ) . Absolute pain scores were low in both groups . Four hours after surgery , group PVB showed a significant reduction in postoperative pain ( PVB : 0 [ 0–10 ] vs CRI : 0 [ 0–30 ] , P = 0.002 ) and reduced painful restricted movement ( P = 0.004 ) , whereas the CRI group had lower pain scores ( PVB : 10 [ 0–30 ] vs CRI : 0 [ 0–20 ] , P = 0.034 ) and painful restricted movement ( P = 0.043 ) 16 and 24 h ( PVB : 10 [ 0–30 ] vs CRI : 0 [ 0–30 ] , P = 0.012 ) after surgery . Postoperative nausea and vomiting was significantly more frequent in the CRI group ( P = 0.017 ) . CONCLUSIONS : Continuous wound infiltration of local anesthetics is an effective alternative to paravertebral analgesia after mastectomy with axillary dissection Background The pectoral nerves ( PECS ) block can not block the most internal mammary region , whereas a transversus thoracic muscle plane ( TTP ) block can . The combination of PECS and TTP blocks may be suitable for anterior chest surgery . We studied patients undergoing mastectomy to assess whether the combination of PECS and TTP blocks provides better analgesia than PECS block alone . Methods Seventy adult female patients undergoing unilateral mastectomy under general anaesthesia were r and omly allocated to receive either the combination of PECS and TTP blocks ( PT group , n=35 ) or the PECS block only ( C group , n=35 ) . The primary outcome measure was visual analog scale pain score . Secondary outcomes were the sensory level loss confirmed by cold tests and additional analgesic drugs within 24 h after the operation . Results The visual analog scale pain scores were lower in the PT group than the C group . The use of postoperative additional analgesic drugs was also lower lower in the PT group than that in the C group . In the majority of patients in the PT group , sensory loss was confirmed in both the anterior and the lateral branches of thoracic nerves ( Th2–6 ) . Conclusion Compared with PECS block , the combination of PECS and TTP blocks provides effective perioperative pain relief for breast cancer surgery . Clinical trial registration University Hospital Medical Information Network ( UMIN ) ID number 000018299 Avoidance of general anaesthesia for breast surgery may be because of clinical reasons or patient choice . There is emerging evidence that the use of regional anaesthesia and the avoidance of volatile anaesthetics and opioid analgesia may have beneficial effects on oncological outcomes . We conducted a prospect i ve observational case series of 16 breast cancer surgeries performed under thoracic paravertebral plus pectoral nerve block with propofol sedation to demonstrate feasibility of technique , patient acceptability and surgeon satisfaction . Fifteen out of 16 cases were successfully completed under sedation and regional anaesthesia , with one conversion to general anaesthesia . Eleven out of 16 cases required low‐dose intra‐operative opioid analgesia . Out of the 15 surgical procedures completed under regional anaesthesia with sedation , all patients experienced either no or minimal intra‐operative pain , and all would choose this anaesthetic technique again . Surgeon‐reported operating conditions were ‘ indistinguishable from general anaesthesia ’ in most cases , and surgeons were ‘ extremely satisfied ’ or ‘ satisfied ’ with the technique after every procedure . Combined thoracic paravertebral plus pectoral nerve block with intra‐operative sedation is a feasible technique for breast surgery Background and Objectives Serratus plane block is performed for analgesia of the anterior chest wall . However , there has been no study concerning the appropriate volume for this block . This prospect i ve r and omized controlled study assesses the dermatomal spread and analgesic effects of serratus plane block . Methods Ultrasound-guided serratus plane block was performed for breast cancer surgery . The patients were r and omly assigned to receive 20 or 40 mL of 0.375 % ropivacaine . The primary end point was the number of affected dermatomes as assessed by cold test and pinprick test 20 minutes after the block procedure . Secondary end points were the time until the first postoperative analgesic rescue , adverse effects , and complications . Results The number of affected dermatomes assessed by the cold test for patients receiving 40 mL of 0.375 % ropivacaine was significantly larger than that for patients receiving 20 mL ( P = 0.002 ; 6 [ 5–7 ] vs 4 [ 3–4 ] dermatomes ) . Similarly , with the pinprick test , the affected area was larger for the 40 mL group than for the 20 mL group ( P = 0.009 ; 4 [ 2–6 ] vs 2 [ 1–3 ] dermatomes ) . There were no differences between the 2 groups in secondary end points . Conclusions Ultrasound-guided serratus plane block spread in the craniocaudal direction is more widespread with 40 mL than with 20 mL of 0.375 % ropivacaine . The time until the first postoperative analgesic rescue dose was not extended by a larger volume of injection . Clinical Trials Registration UMIN Clinical Trials Registry ( identifier UMIN000016549 ) BACKGROUND Breast surgery is an exceedingly common procedure with an increased incidence of acute and chronic pain . Pectoral nerve block is a novel peripheral nerve block alternative to neuro-axial and paravertebral blocks for ambulatory breast surgeries . OBJECTIVES This study aims to compare the analgesic efficacy and safety of modified Pecs block with ketamine plus bupivacaine versus bupivacaine in patients undergoing breast cancer surgery . STUDY DESIGN A r and omized , double-blind , prospect i ve study . SETTING Academic medical center . METHODS This study is registered at www . clinical trials.gov under number : ( NCT02620371 ) after approval by the ethics committee of South Egypt Cancer Institute , Assuit University , Assuit , Egypt . Sixty patients aged 18 - 60 years scheduled for modified radical mastectomy were enrolled and r and omly assigned into 2 groups ( 30 patients each ) : Control group patients were given ultrasound-guided , Pecs block with 30 mL of 0.25 % bupivacaine only . Ketamine group patients were given ultrasound-guided , Pecs block with 30 mL of 0.25 % bupivacaine plus ketamine hydrochloride ( 1 mg/kg ) . Patients were followed up for 48 hours postoperatively for vital signs , VAS score , first request of rescue analgesia and total morphine consumption , sedation score , and side effects . RESULTS Ketamine plus bupivacaine in Pecs block compared to bupivacaine alone prolonged the mean time of first request of analgesia ( 18.25 ± 1.98 ) , ( 12.56 ± 2.64 ) , respectively ( P < 0.001 ) , reduced total morphine consumption ( 12.50 ± 4.63 ) , ( 18.86 ± 6.28 ) , respectively ( P = 0.016 ) . With no significant difference in hemodynamics , respiratory rate , oxygen saturation , VAS and sedation scores , and side effects observed between the 2 groups ( P > 0.05 ) . LIMITATIONS This study is limited by its sample size . CONCLUSION The addition of ketamine to modified Pecs block prolonged the time to first request of analgesia and reduced total opioid consumption without serious side effects in patients who underwent a modified radical mastectomy . KEY WORDS Ketamine , bupivacaine , pecs block , postoperative , pain , breast cancer Background and Objectives General anesthesia for breast surgery may be supplemented by using a regional anesthetic technique . We evaluated the efficacy of the first pectoral nerve block ( Pecs I ) in treating postoperative pain after breast cancer surgery . Methods A r and omized , double-blind , dual-centered , placebo-controlled trial was performed . One hundred twenty-eight patients scheduled for unilateral breast cancer surgery were recruited . A multimodal analgesic regimen and surgeon-administered local anesthetic infiltration were used for all patients . Ultrasound-guided Pecs I was performed using bupivacaine or saline . The primary outcome was the patient pain score ( numerical rating scale [ NRS ] ) in the recovery unit 30 minutes after admission or just before the morphine administration ( NRS ≥4/10 ) . The secondary outcomes were postoperative opioid consumption ( ie , in the recovery unit and after 24 hours ) . Results During recovery , no significant difference in NRS was observed between the bupivacaine ( n = 62 , 3.0 [ 1.0–4.0 ] ) and placebo ( n = 65 , 3.0 [ 1.0–5.0 ] ) groups ( P = 0.55 ) . However , the NRS was statistically significantly different , although not clinical ly significant , for patients undergoing major surgeries ( mastectomies or tumorectomies with axillary clearance ) ( n = 29 , 3.0 [ 0.0–4.0 ] vs 4.0 [ 2.0–5.0 ] , P = 0.04 ) . Morphine consumption during recovery did not differ ( 1.5 mg [ 0.0–6.0 mg ] vs 3.0 mg [ 0.0–6.0 mg ] , P = 0.20 ) , except in the major surgery subgroup ( 1.5 mg [ 0.0–6.0 mg ] vs 6.0 mg [ 0.0–12.0 mg ] , P = 0.016 ) . Intraoperative sufentanil and cumulative morphine consumption up to 24 hours did not differ between the 2 groups . Three patients experienced complications related to the Pecs I. Conclusions Pecs I is not better than a saline placebo in the presence of multimodal analgesia for breast cancer surgery . However , its role in extended ( major ) breast surgery may warrant further investigation . Clinical Trial Registration This study was registered at Clinical Trials.gov , identifier NCT01670448 Background : General anaesthesia is currently the conventional technique used for surgical treatment of breast lump . Paravertebral block ( PVB ) has been used for unilateral procedures such as thoracotomy , breast surgery , chest wall trauma , hernia repair or renal surgery . Methods : We compared unilateral thoracic PVB with general anaesthesia ( GA ) in 60 consenting ASA physical status I and II female patients of 18–65 years age , scheduled for unilateral breast surgery . Patients were r and omly assigned into two groups , P ( n=30 ) or G ( n=30 ) , to receive either PVB or GA , respectively . Results : The average time to first post-operative analgesic requirement at visual analogue scale score≥4 ( primary endpoint ) was significantly longer in group P ( 303.97±76.08 min ) than in group G ( 131.33±21.36 min ) , P<0.001 . Total rescue analgesic ( Inj . Tramadol ) requirements in the first 24 h were 105.17±20.46 mg in group P as compared with 176.67±52.08 mg in group G ( P<0.001 ) . Significant post-operative nausea and vomiting requiring treatment occurred in three ( 10.34 % ) patients of the PVB group and eight ( 26.67 % ) patients in the GA group . Conclusion : The present study concludes that unilateral PVB is more efficacious in terms of prolonging post-operative analgesia and reducing morbidities in patients undergoing elective unilateral breast surgery BACKGROUND There is little systematic research on the efficacy and tolerability of the addition of adjunctive analgesic agents in paravertebral analgesia . The addition of adjunctive analgesics , such as fentanyl and clonidine , to local anesthetics has been shown to enhance the quality and duration of sensory neural blockades , and decrease the dose of local anesthetic and supplemental analgesia . OBJECTIVES Investigation of the safety and the analgesic efficacy of adding 1 μg/kg dexmedetomidine to bupivacaine 0.25 % in thoracic paravertebral blocks ( PVB ) in patients undergoing modified radical mastectomy . STUDY DESIGN A r and omized , double-blind trial . SETTING Academic medical center . METHODS Sixty American Society of Anesthesiologists physical status -I - III patients were r and omly assigned to receive thoracicPVB with either 20 mL of bupivacaine 0.25 % ( Group B , n = 30 ) , or 20 mL of bupivacaine 0.25 % + 1 μg/kg dexmedetomidine ( Group BD , n= 30 ) . Assessment parameters included hemodynamics , sedation score , pain severity , time of first analgesics request , total analgesic consumption , and side effects in the first 48 hours . RESULTS There was a significant reduction in pulse rate and diastolic blood pressure starting at 30 minutes in both groups , but more evidence d in group BD ( P < 0.001 ) . Intraoperative Systolic blood pressure showed a significant reduction at 30 minutes in both groups ( P < 0.001 ) then returned to baseline level at 120 minutes in both groups . There was a significant increase in pulse rate starting 2 hours postoperative until 48 hours postoperatively in group B but only after 12 hours until 48 hours in group BD ( P < 0.001 ) . The time of the first rescue analgesic requirement was significantly prolonged in the group BD ( 8.16 ± 42 hours ) in comparison to group B ( 6.48 ± 5.24 hours ) ( P = 0.04 ) . The mean total consumption of intravenous tramadol rescue analgesia in the postanesthesia care unit in the firtst 48 hours postoperatively was significantly decreased in group BD ( 150.19 ± 76.98 mg ) compared to group B ( 194.44 ± 63.91 mg ) ( P = 0.03 ) . No significant serious adverse effects were recorded during the study . LIMITATIONS This study is limited by its sample size . CONCLUSION The addition of dexmedetomidine 1 μg/kg to bupivacaine 0.25 % in thoracic PVB in patients undergoing modified radical mastectomy improves the quality and the duration of analgesia and also provides an analgesic sparing effect with no serious side effects Introduction Paravertebral block ( PVB ) is an alternative to general anaesthesia ( GA ) for breast surgery . However , for extensive surgery multiple punctures are needed increasing the immanent risk of the method . The purpose of this study was to evaluate PVB via catheter and injections at three different levels . Primary outcome was the quality of postoperative analgesia , in particular , the number of patients requiring additional morphine . Methods In a r and omised single blinded clinical study patients scheduled for breast surgery including axillary approach , were r and omly allocated to different anaesthetic techniques , n = 35 each . Patients received either GA with sevoflurane or PVB with catheter at level Th 4 . In PVB- patients a 1:2 mixture of bupivacaine 0.5 % and lidocaine 2 % with adrenaline was injected sequentially 10 ml each at three different levels . Results Complication-free catheter insertion was possible in all 35 scheduled patients . The need for postoperative analgesics was higher after GA compared to PVB ( 22 vs.14 patients ) ; p = 0.056 . Postoperative morphine consumption was 1.55 ( GA ) and 0.26 mg ( PVB ) respectively ( p < 0.001 ) . Visual rating score ( VRS ) for pain at rest and at movement was higher in GA patients on post anaesthesia care unit ( PACU ) as well as on the ward at 1 - 6h and 6 - 12h . Readiness for discharge was earlier after PVB ( 4.96 and 6.52 hours respectively ) . After GA the incidence and severity of postoperative nausea and vomiting ( PONV ) was higher , though not significantly . Patients ’ satisfaction was comparable in both groups . Conclusions Three-level injection PVB via catheter for extensive mastectomy was efficient and well accepted . Using a catheter may enhance safety by avoiding multiple paravertebral punctures when extended spread of analgesia is required . Trial Registration www . Clinical Trial.gov Purpose Retrolaminar block ( RLB ) is a thoracic truncal block that can produce analgesia for the thoracic and abdominal wall . However , the characteristics of RLB are not well known . The aim of this study was to determine analgesic efficacy by measuring postoperative consume of patient-controlled analgesia ( PCA ) , additional nonsteroidal antiinflammatory drug ( NSAID ) rescue , and opioid rescue . Our secondary analysis included assessment of the chronological change in arterial levobupivacaine concentrations after the block . Methods This prospect i ve , r and omized , double-blinded study included 30 patients scheduled for modified radical mastectomy under general anesthesia . The patients were r and omized to receive either a l and mark-guided RLB or paravertebral block ( PVB ) catheter placement on T4 . Continuous infusion with 4 ml/h of 0.25 % levobupivacaine was started for 72 h , after initial injection of 20 ml 0.375 % levobupivacaine before surgery . Postoperative pain was compared using the amount of block PCA ( 3 ml 0.25 % levobupivacaine with 30-min lockout ) , NSAID , and opioid rescue . Arterial blood was sample d for 120 min after the initial injection . Results The frequency of postoperative block PCA use was significantly high after RLB in 24 h [ p = 0.01 ; 6 ( 3–12 ) vs. 2.5 ( 0.3–3 ) times , respectively ] . There was no PCA use after 24 h in either group . There was no postoperative opioid rescue use throughout the study . After RLB and PVB , there was no significant difference in Tmax ( p = 0.14 ; 15 ± 8 vs. 15 ± 8 min , respectively ) and Cmax ( p = 0.2 ; 0.9 ± 0.2 vs. 0.9 ± 0.3 µg/ml , respectively ) , and all the concentrations were below the threshold of local anesthetic systemic toxicity . Conclusion Continuous RLB was not inferior to PVB except for the first 24 h , and was satisfactory after mastectomy . RLB showed safe , low peak arterial levobupivacaine concentrations Background and Objectives Patients undergoing breast cancer surgery frequently experience chronic postoperative pain . The primary objective of this r and omized study was to determine if thoracic paravertebral block ( TPVB ) reduced the incidence of chronic pain after a modified radical mastectomy ( MRM ) when compared with general anesthesia ( GA ) . Methods One hundred eighty women undergoing MRM were r and omized to 1 of 3 study groups : group 1 : st and ardized GA , group 2 : GA with a single-injection TPVB and placebo paravertebral infusion , and group 3 : GA with a continuous TPVB . Outcomes assessed postoperatively included acute postoperative pain and analgesic consumption and , at 3 and 6 months , the incidence and severity of chronic pain and physical and mental health-related quality of life ( HRQOL ) . Results There was no significant difference in the incidence of chronic pain at 3 months ( P = 0.13 ) and 6 months ( P = 0.79 ) after the MRM between the study groups . The relative risk of developing chronic pain ( P = 0.25 ) was also similar between the groups . There was no difference in acute pain ( P = 0.22 ) or postoperative analgesic consumption ( P = 0.67 ) between the groups . Nevertheless , differences were observed in chronic pain – related secondary outcome variables . The TPVB groups reported lower chronic pain scores ( P < 0.05 ) , exhibited fewer symptoms and signs of chronic pain ( P ⩽ 0.01 ) , and also experienced better physical and mental HRQOL than did the GA group . Chronic pain scores also decreased with time in all study groups ( P < 0.05 ) . Conclusions There is no significant difference in the incidence or relative risk of chronic pain at 3 and 6 months after an MRM when TPVB is used in conjunction with GA . Nevertheless , patients who receive a TPVB report less severe chronic pain , exhibit fewer symptoms and signs of chronic pain , and also experience better physical and mental HRQOL Background Dexamethasone has been reported to reduce postoperative symptoms after different surgical procedures . We evaluated the efficacy of preoperative dexamethasone in ameliorating postoperative nausea and vomiting ( PONV ) , and pain after mastectomy . Methods In this prospect i ve , double-blind , placebo-controlled study , 70 patients scheduled for mastectomy with axillary lymph node dissection were analyzed after r and omization to treatment with 8 mg intravenous dexamethasone ( n = 35 ) or placebo ( n = 35 ) . All patients underwent st and ardized procedures for general anesthesia and surgery . Episodes of PONV and pain score were recorded on a visual analogue scale . Analgesic and antiemetic requirements were also recorded . Results Demographic and medical variables were similar between groups . The incidence of PONV was lower in the dexamethasone group at the early postoperative evaluation ( 28.6 % vs. 60 % ; p = 0.02 ) and at 6 h ( 17.2 % vs. 45.8 % ; p = 0.03 ) . More patients in the placebo group required additional antiemetic medication ( 21 vs. 8 ; p = 0.01 ) . Dexamethasone treatment significantly reduced postoperative pain just after surgery ( VAS score , 4.54 ± 1.55 vs. 5.83 ± 2.00 ; p = 0.004 ) , at 6 h ( 3.03 ± 1.20 vs. 4.17 ± 1.24 ; p < 0.0005 ) and at 12 h ( 2.09 ± 0.85 vs. 2.54 ± 0.98 ; p = 0.04 ) . Analgesics were required in more patients of the control group ( 21 vs. 10 ; p = 0.008 ) . There were no adverse events , morbidity or mortality . Conclusions Preoperative intravenous dexamethasone ( 8 mg ) can significantly reduce the incidence of PONV and pain in patients undergoing mastectomy with axillary dissection for breast cancer . Trial registration We hypothesized that improved acute postoperative pain relief will be achieved using general anaesthesia ( GA ) either in combination with continuous thoracic paravertebral block ( GA-cPVB ) or single shot ( GA-sPVB ) as compared to GA supplemented by local wound infiltration ( GA-LWI ) after unilateral major breast cancer surgery . A r and omised controlled trial was conducted in 46 adult women in a day-care or short-stay hospital setting after major breast cancer surgery . Pain-intensity was measured using an 11-point visual analogue scale ( VAS ) until postoperative day 2 . GA-sPVB was stopped due to slow inclusion .No significant difference in VAS score was noted between GA-LWI ( VAS median 0.5 ( interquartile range 0.18–2.00 ) ) and GA-cPVB , ( VAS 0.3 ( 0.00–1.55 , p = 0.195 ) ) 24 hours after surgery or at any point postoperatively until postoperative day 2.We conclude that both GA-LWI and GA-cPVB anaesthetic techniques are equally effective in treatment of acute postoperative pain after major oncological breast surgery . As GA-LWI is easily to perform with fewer complications and it is more cost-effective it should be preferred over GA-cPVB Aim To test for differences in hemodynamic and analgesic properties in patients with breast cancer undergoing quadrantectomy with paravertebral block ( PVB ) induced with a solution of either one or two local anesthetics . Method A prospect i ve , single-center , r and omized , double-blinded , controlled trial was conducted from June 2014 until September 2015 . A total of 85 women with breast cancer were assigned to receive PVB with either 0.5 % levobupivacaine ( n = 42 ) or 0.5 % levobupivacaine with 2 % lidocaine ( n = 43 ) . Hemodynamic variables of interest included intraoperative stroke volume variation ( SVV ) , mean arterial pressure , heart rate , cardiac output , episodes of hypotension , use of crystalloids , and use of inotropes . Analgesic variables of interest were time to block onset , duration of analgesia , and postoperative serial pain assessment using a visual analogue scale . Results Although the use of 0.5 % levobupivacaine with 2 % lidocaine solution for PVB decreased the mean time-to-block onset ( 14 minutes ; P < 0.001 ) , it also caused significantly higher SVV values over the 60 minutes of monitoring ( mean difference : 4.33 ; P < 0.001 ) . Furthermore , the patients who received 0.5 % levobupivacaine with 2 % lidocaine experienced shorter mean duration of analgesia ( 105 minutes ; P = 0.006 ) and more episodes of hypotension ( 17.5 % ; P = 0.048 ) and received more intraoperative crystalloids ( mean volume : 550 mL ; P < 0.001 ) . Conclusion The use of 0.5 % levobupivacaine in comparison with 0.5 % levobupivacaine with 2 % lidocaine solution for PVB had a longer time-to-block onset , but it also reduced hemodynamic disturbances and prolonged the analgesic effect . Registration No. : Background and Aims : Modified radical mastectomy ( MRM ) may be associated with severe post-operative pain , leading to chronic pain syndrome . We compared the post-operative analgesic profile of two ultrasound-guided nerve blocks : Paravertebral block ( PVB ) and serratus plane block ( SPB ) . Methods : This double-blind , r and omised study was conducted on fifty adult females , scheduled for MRM with axillary dissection . After inducing general anaesthesia with intravenous midazolam 1 mg , fentanyl 1.5 mcg/kg , propofol 1–2 mg/kg and vecuronium 0.1 mg/kg , patients were administered either ultrasound-guided thoracic PVB at T4 ( n = 25 ) or SPB at 5th rib ( n = 25 ) with 20 ml of 0.5 % bupivacaine , both as a single level injection . Time to first rescue analgesia and morphine consumption in 4 , 6 , 24 , 48 and 72 h by PCA pump , visual analogue scale score and any adverse effects were recorded . Quantitative variables were compared using the unpaired t-test or the Mann – Whitney U test between the two groups . Qualitative variables were compared using the Chi-square test or Fisher 's exact test . Results : The duration of analgesia ( mean ± St and ard deviation [ SD ] ) was significantly longer in the PVB group compared to SPB group ( 346 ± 57 min vs. 245.6 ± 58 min , P < 0.001 ) . The post-operative 24 h morphine consumption ( mean ± SD ) was significantly higher in the SPB group ( 9.7 ± 2.1 mg ) compared to PVB group ( 6.5 ± 1.5 mg ) ( P < 0.001 ) . Conclusion : Ultrasound-guided SPB is an alternative analgesic technique to thoracic PVB for MRM although PVB provides a longer duration of analgesia AIM To determine whether intravenous ketoprofen is effective as pre-emptive analgesia for breast surgery . DESIGN R and omised , controlled , double blind study . PATIENTS AND METHODS 50 patients undergoing breast surgery under general anaesthesia r and omised to receive either 100 mg intravenous ketoprofen 30 minutes before ( Group I ) , or immediately after surgical incision ( Group II ) . Postoperatively , pain scores ( Visual Analogue Scale , VAS ) and time to rescue analgesic were recorded by an independent , blinded observer . The study was terminated when rescue analgesic was required ( VAS > or = 4 or dem and for analgesic ) . STATISTICAL ANALYSIS Continuous variables were analysed by the unpaired ' t ' test , discrete variables with the chi square test , and survival curves by the log-rank test . RESULTS Pain scores were significantly lower in Group I till 10 hours after surgery . The number of patients requiring analgesia at 4 , 6 , 8 and 10 hours was significantly lower in group I ( 0 % vs. 47 % [ P < 0.0001 ] , 0 % vs. 44 % [ P < 0.003 ] , 0 % vs. 80 % [ P < 0.0001 ] , 0 % vs. 100 % [ P < 0.0001 ] respectively ) . The mean time for rescue analgesic was 15.47 -/+ 2.87 hours in group I versus 4.22 -/+ 2.55 hours in group II ( P < 0.0001 ) . CONCLUSION Pre-emptive analgesia with Intravenous ketoprofen ( 100 mg ) produces better postoperative pain-relief in patients undergoing breast surgery BACKGROUND : Paravertebral blocks ( PVBs ) have been introduced as an alternative to general anesthesia for breast cancer surgeries . The addition of clonidine as an adjuvant in PVBs may enhance quality and duration of analgesia and significantly reduce the consumption of analgesics after breast surgery . In this prospect i ve r and omized double-blind study , we assessed the significance of adding clonidine to the anesthetic mixture for women undergoing mastectomy . METHODS : Sixty patients were r and omized equally into 2 groups , both of which received PVB block , either with or without clonidine . Analgesic consumption was noted up to 2 weeks after the operation . A visual analog scale was used to assess pain postoperatively during the hospital stay , and a numeric rating scale was used when patients were discharged . RESULTS : Analgesic consumption was significantly lower in the clonidine group 48 hours postoperatively with 95 % confidence interval ( CI ) for the difference ( −69.5 % to −6.6 % ) . Pain scores at rest showed significant reduction in the clonidine group during the period from 24 to 72 hours postoperatively with 95 % CI for the ratios of 2 means ( 1.09–3.61 ) , ( 2.04–9.04 ) , and ( 2.54–16.55 ) , respectively , with shoulder movement at 24 , 48 , and 72 hours postoperatively 95 % CI for the ratio of 2 means ( 1.10–3.15 ) , ( 1.32–6.38 ) , and ( 1.33–8.42 ) , respectively . The time needed to resume daily activity was shorter in the clonidine group compared with the control group with 95 % CI for the ratio of 2 means ( 1.14–1.62 ) . CONCLUSION : The addition of clonidine enhanced the analgesic efficacy of PVB up to 3 days postoperatively for patients undergoing breast surgery Abstract Purpose This study evaluated the analgesic efficacy of dexmedetomidine in combination with bupivacaine for single-shot paravertebral block ( PVB ) in patients undergoing major breast cancer surgery . Methods This prospect i ve , r and omized double blind study was conducted in 45 ASA I/II/III females , aged ≥18 years , undergoing modified radical mastectomy or breast conservation surgery with axillary lymph node dissection . Patients in group PB ( paravertebral – bupivacaine ) received PVB with 0.5 % bupivacaine 0.3 ml/kg with 1 ml normal saline ; group PBD ( paravertebral – bupivacaine – dexmedetomidine ) received PVB with 0.5 % bupivacaine 0.3 ml/kg and dexmedetomidine 1 μg/kg in a volume of 1 ml ; and group C ( control ) patients were given a sham block ( a subcutaneous injection with 2 ml normal saline ) before receiving general anesthesia ( GA ) . All patients received analgesia by fentanyl intraoperatively and morphine patient-controlled analgesia postoperatively . Results The control group patients required more intraoperative fentanyl than the other two groups . Patients receiving dexmedetomidine had lower morphine consumption ( p < 0.001 ) , pain scores and incidence of postoperative nausea/vomiting ( p = 0.011 ) ; longer time to first analgesic request ; earlier time to mobilize ; and better satisfaction scores . Heart rate and blood pressure values during the intraoperative period were also lower at many time points in this group . However , the incidence of hypotension and bradycardia were statistically similar in all groups . Conclusions PVB using dexmedetomidine 1 µg/kg added to 0.5 % bupivacaine in patients undergoing major breast cancer surgery under GA provides analgesia of longer duration with decreased postoperative opioid consumption and lower incidence of nausea/vomiting compared to PVB with bupivacaine alone or no PVB Background : Paravertebral block ( PVB ) is useful for post-operative analgesia after breast surgery . Bupivacaine is used for PVB at higher concentrations ( 0.5 % ) , which may lead to systemic toxicity after absorption . Therefore , we proposed to evaluate the efficacy of lower concentrations of bupivacaine with and without fentanyl for thoracic PVB in patients undergoing surgery for carcinoma breast . Methods : Forty-eight patients scheduled for surgery for breast cancer were enrolled in this prospect i ve , r and omized , double-blinded , placebo-controlled trial and were allocated to one of four groups : 0.25 % bupivacaine with epinephrine 5 mcg/ ml , 0.25 % bupivacaine + epinephrine 5 mcg/ ml with 2 mcg/ml fentanyl , 0.5 % bupivacaine + epinephrine 5 mcg/ml or isotonic saline . PVB was performed and 0.3 ml/kg of the test drug was administered before induction of general anaesthesia . The primary outcome assessed was post-operative analgesic requirement for a period of 24 h. Secondary outcome measures were post-operative pain scores at rest and on movement of the arm , latency to first opioid , post-operative nausea and vomiting , quality of sleep , ability to move arm and patient satisfaction . Results : The patient characteristics and anaesthetic technique were comparable among the groups . The rescue analgesic consumption as well as cumulative pain scores at rest and on movement were significantly less in 0.25 % bupivacaine+epinephrine with fentanyl and 0.5 % bupivacaine+epinephrine groups ( P<0.05 ) . The average duration of analgesia was found to be 18 h after either 0.25 % bupivacaine with epinephrine+fentanyl or 0.5 % bupivacaine with epinephrine . Conclusions : Lower concentrations of bupivacaine can be combined with fentanyl to achieve analgesic efficacy similar to bupivacaine at higher concentrations , decreasing the risk of toxicity in PVB Background We aim ed to determine with this r and omized , triple-masked , placebo-controlled study if benefits are afforded by adding a multiple-day , ambulatory , continuous ropivacaine paravertebral nerve block to a single-injection ropivacaine paravertebral block after mastectomy . Methods Preoperatively , 60 subjects undergoing unilateral ( n = 24 ) or bilateral ( n = 36 ) mastectomy received either unilateral or bilateral paravertebral perineural catheter(s ) , respectively , inserted between the third and fourth thoracic transverse process(es ) . All subjects received an initial bolus of ropivacaine 0.5 % ( 15 mL ) via the catheter(s ) . Subjects were r and omized to receive either perineural ropivacaine 0.4 % or normal saline using portable infusion pump(s ) [ 5 mL/h basal ; 300 mL reservoir(s ) ] . Subjects remained hospitalized for at least 1 night and were subsequently discharged home where the catheter(s ) were removed on postoperative day ( POD ) 3 . Subjects were contacted by telephone on PODs 1 , 4 , 8 , and 28 . The primary end point was average pain ( scale , 0–10 ) queried on POD 1 . Results Average pain queried on POD 1 for subjects receiving perineural ropivacaine ( n = 30 ) was a median ( interquartile ) of 2 ( 0–3 ) , compared with 4 ( 1–5 ) for subjects receiving saline ( n = 30 ; 95 % confidence interval difference in medians , −4.0 to −0.3 ; P = 0.021 ] . During this same period , subjects receiving ropivacaine experienced a lower severity of breakthrough pain ( 5 [ 3–6 ] vs 7 [ 5–8 ] ; P = 0.046 ) as well . As a result , subjects receiving perineural ropivacaine experienced less pain-induced physical and emotional dysfunction , as measured with the Brief Pain Inventory ( lower score = less dysfunction ) : 14 ( 4–37 ) versus 57 ( 8–67 ) for subjects receiving perineural saline ( P = 0.012 ) . For the subscale that measures the degree of interference of pain on 7 domains , such as general activity and relationships , subjects receiving perineural saline reported a median score 10 times higher ( more dysfunction ) than those receiving ropivacaine ( 3 [ 0–24 ] vs 33 [ 0–44 ] ; P = 0.035 ) . In contrast , after infusion discontinuation , there were no statistically significant differences detected between treatment groups . Conclusions After mastectomy , adding a multiple-day , ambulatory , continuous ropivacaine infusion to a single-injection ropivacaine paravertebral nerve block results in improved analgesia and less functional deficit during the infusion . However , no benefits were identified after infusion discontinuation BACKGROUND Paravertebral block ( PVB ) is an effective alternative to general anesthesia for breast cancer surgery . Continuous paravertebral block ( CPVB ) anesthesia may extend postoperative analgesia at home and improve quality of early postoperative recovery of breast cancer patients . PURPOSE This double-blinded r and omized trial was conducted to compare degree of pain , nausea , mood , level of symptom distress , and time to return to normal daily activity between PVB and PVB + CPVB in patients undergoing outpatient breast cancer surgery . PATIENTS AND METHODS Between July 2003 and April 2008 we r and omly assigned 94 ( 73 evaluable ) patients in a 1:1:1 ratio with early breast cancer to single injection PVB followed by CPVB infusion of 0.1 % or 0.2 % ropivacaine vs placebo ( saline ) for 48 hours postoperatively for unilateral breast cancer surgery without reconstruction . The primary study endpoint was the degree of pain , nausea , mood state , level of symptom distress , and recovery time . RESULTS Of the 468 patients assessed for eligibility , 94 consented and 21 with incomplete data or follow-up were excluded , leaving 73 subjects for analysis . There was no clinical ly significant difference in degree of postoperative pain , nausea , mood state , level of symptom distress , or return to normal activity among the three study groups . CONCLUSION The current study does not support the routine use of continuous paravertebral catheter anesthesia in patients undergoing operative treatment for breast cancer OBJECTIVES Thoracic paravertebral block ( TPVB ) for breast surgery reduces acute and chronic postoperative pain . Using ultrasound for administering the block makes it easier , with its administration at multiple levels decreasing the number of unblocked segments . We conducted this study to evaluate the efficacy and safety of single- vs double-level ultrasound-guided TPVB in patients undergoing total mastectomy with axillary clearance under general anesthesia . DESIGN This is a prospect i ve , r and omized study . SETTING Recovery room and operation theater . PATIENTS Sixty ASA I and II patients , aged 18 to 60 years , who were scheduled to undergo total mastectomy with axillary clearance under general anesthesia were enrolled in the study . INTERVENTIONS Patients received either single- ( group S ) or double-level ( group D ) ultrasound-guided TPVB at T4 or at T2 and T5 levels , respectively , using 0.3 mL/kg of 0.5 % ropivacaine . MEASUREMENTS Primary outcome measure was 24-hour analgesic consumption , and secondary outcomes included number of segments blocked , postoperative pain scores , time to first request for rescue analgesic , and any side effects . RESULTS The mean total amount of rescue analgesic given in group S was 175.3 ± 70 mg and in group D was 115.7 ± 48 mg ( P = .002 ) . Median number of segments showing less sensation to pinprick was 3 in group S and 4 in group D ( P < .001 ) . The mean time to first request for rescue analgesic was 533 ± 124 minutes in group S and was 611 ± 214 minutes in group D ( P = .118 ) . CONCLUSION Patients receiving double-level TPVB had significantly less 24-hour analgesic consumption in the postoperative period than those in the single-level TPVB group . This could be due to decreased pain sensation to pinprick in significantly greater number of segments in the double-level TPVB group Background The pectoral nerves ( Pecs ) block types I and II are novel techniques to block the pectoral , intercostobrachial , third to sixth intercostals , and the long thoracic nerves . They may provide good analgesia during and after breast surgery . Our study aim ed to compare prospect ively the quality of analgesia after modified radical mastectomy surgery using general anesthesia and Pecs blocks versus general anesthesia alone . Methods One hundred twenty adult female patients scheduled for elective unilateral modified radical mastectomy under general anesthesia were r and omly allocated to receive either general anesthesia plus Pecs block ( Pecs group , n = 60 ) or general anesthesia alone ( control group , n = 60 ) . Results Statistically significant lower visual analog scale pain scores were observed in the Pecs group than in the control group patients . Moreover , postoperative morphine consumption in the Pecs group was lower in the first 12 hours after surgery than in the control group . In addition , statistically significant lower intraoperative fentanyl consumption was observed in the Pecs group than in the control group . In the postanesthesia care unit , nausea and vomiting as well as sedation scores were lower in the Pecs group compared with the control group . Overall , postanesthesia care unit and hospital stays were shorter in the Pecs group than in the control group . Conclusions The combined Pecs I and II block is a simple , easy-to-learn technique that produces good analgesia for radical breast surgery STUDY OBJECTIVE The aim of this study was to evaluate the analgesic efficacy and safety of pectoralis-serratus interfascial plane block in comparison with thoracic paravertebral block for postmastectomy pain . DESIGN A prospect i ve r and omized controlled study . SETTING Tertiary center , university hospital . PATIENTS Sixty-four adult women , American Society of Anesthesiologists physical status classes I , II , and III , scheduled for unilateral modified radical mastectomy with axillary evacuation . INTERVENTIONS Patients were r and omized to receive either pectoralis-serratus interfascial plane block , PS group ( n=32 ) , or thoracic paravertebral block , PV group ( n=32 ) . MEASUREMENTS Twenty-four-hour morphine consumption and the time to rescue analgesic were recorded . The pain intensity evaluated by visual analog scale ( VAS ) score at 0 , 2 , 4 , 8 , 16 , and 24hours postoperatively was also recorded . MAIN RESULTS The median ( interquartile range ) postoperative 24-hour morphine consumption was significantly increased in PS group in comparison to PV group ( PS vs PV ) , 20 mg ( 16 - 23 mg ) vs 12 mg ( 10 - 14 mg ) ( P<.001 ) . The median postoperative time to first analgesic request was significantly shorter in PS group compared to PV group ( PS , 6 hours [ 5 - 7 hours ] , vs PV , 11 hours [ 9 - 13 hours ] ) ( P<.001 ) . The intensity of pain was low in both groups in VAS 0 , 2 , and 4hours postoperatively . However , there was significant reduction in VAS in PV group compared to PS group at 8 , 16 , and 24hours postoperatively . CONCLUSIONS Pectoralis-serratus interfascial plane block was safe and easy to perform and decreased intensity of postmastectomy pain , but it was inferior to thoracic paravertebral block In this study , we compared the effects of two analgesic regimens on perioperative nitric oxide index ( NOx ) and the likelihood of subsequent development of chronic postsurgical pain ( CPSP ) after breast surgery and sought to determine the association among early postoperative pain , NOx , and the likelihood of subsequent development of CPSP . Twenty-nine consecutive ASA I or II patients undergoing breast surgery with axillary clearance were r and omly allocated to one of two groups . Patients in group S ( n = 15 ) received a st and ard intraoperative and postoperative analgesic regimen ( morphine sulfate , diclofenac , dextropropoxyphene hydrochloride + acetaminophen prn ) . Patients in group N ( n = 14 ) received a continuous paravertebral block ( for 48 h ) and acetaminophen and parecoxib ( followed by celecoxib up to 5 days ) . Visual analog scale pain scores at rest and on arm movement were recorded regularly until the fifth postoperative day . A telephone interview was conducted 10 wk postoperatively . The McGill Pain Question naire was used to characterize pain . NOx was estimated preoperatively , at the end of surgery , 30 min and 2 , 4 , 12 , 24 , 48 h postoperatively . Twelve ( 80 % ) patients in group S and no patient in group N developed CPSP ( P = 0.009 ) . Compared with patients with a pain rating index ≥1 ( n = 18 ) 10 wk postoperatively , patients with a pain rating index = 0 ( n = 11 ) had lesser visual analog scale pain scores on movement at each postoperative time point from 30 min until 96 h postoperatively ( P < 0.005 ) and at rest 30 min ( 0.6 ± 1.5 versus 30.2 ± 26.8 ; P = 0.004 ) , 4 h ( 2.3 ± 7.5 versus 19.0 ± 25.8 ; P = 0.013 ) , 8 h ( 4.4 ± 10.2 versus 21.4 ± 27.0 ; P = 0.03 ) and 12 h ( 0.7 ± 1.2 versus 15.4 ± 27.0 ; P = 0.035 ) postoperatively . NOx values were greater in group N compared with group S 48 h postoperatively ( 40.6 ± 20.1 versus 26.4 ± 13.5 ; P = 0.04 ) Few systemic drug interventions are efficacious to improve patient reported quality of recovery after ambulatory surgery . We aim ed to evaluate whether a single dose systemic acetaminophen improve quality of recovery in female patients undergoing ambulatory breast surgery . We hypothesized that patients receiving a single dose systemic acetaminophen at the end of the surgical procedure would have a better global quality of postsurgical recovery compared to the ones receiving saline . The study was a prospect i ve r and omized double blinded , placebo controlled , clinical trial . Healthy female subjects were r and omized to receive 1 g single dose systemic acetaminophen at the end of the surgery or the same volume of saline . The primary outcome was the Quality of Recovery 40 ( QOR-40 ) question naire at 24 hours after surgery . Other data collected included opioid consumption and pain scores . Data were analyzed using group t tests and the Wilcoxon exact test . The association between opioid consumption and quality of recovery was evaluated using Spearman rho . P < .05 was used to reject the null hypothesis for the primary outcome . Seventy subjects were r and omized and sixty-five completed the study . Patients ' baseline characteristics and surgical factors were similar between the study groups . There was a clinical ly significant difference in the global QoR-40 scores between the acetaminophen and the saline groups , median ( IQR ) of 189 ( 183 to 194 ) and 183 ( 175 to 190 ) , respectively , P = .01 . In addition , there was an inverse relationship ( Spearman 's rho= -0.33 ) between oral opioid consumption at home ( oral morphine equivalents ) and 24 hour postoperative quality of recovery , P = .007 . A single dose of systemic acetaminophen improves patient reported quality of recovery after ambulatory breast surgery . The use of systemic acetaminophen is an efficacious strategy to improve patient perceived quality of postsurgical recovery and analgesic outcomes after hospital discharge for ambulatory breast surgery The addition of fentanyl or clonidine to levobupivacaine was evaluated in patients undergoing breast surgery under general anaesthesia with intra‐ and postoperative paravertebral analgesia . Patients were r and omly allocated to four groups : Group L received 19 ml bolus levobupivacaine 0.25 % plus 1 ml saline followed by an infusion of levobupivacaine 0.1 % ; Group LF received 19 ml bolus levobupivacaine 0.25 % plus fentanyl 50 μg followed by an infusion of levobupivacaine 0.05 % with fentanyl 4 μg.ml−1 ; Group LC received 19 ml bolus levobupivacaine 0.25 % plus clonidine 150 μg followed by an infusion of levobupivacaine 0.05 % with clonidine 3 μg.ml−1 ; Group C ( control ) received general anaesthesia without paravertebral analgesia . All groups received postoperative i.v . morphine patient controlled analgesia ( PCA ) . Although mean ( SD ) postoperative PCA morphine consumption was decreased in LF [ 7.9 ( 4.1 ) mg ] and LC [ 5.9 ( 3.5 ) mg]vs L [ 27.7 ( 8.6 ) mg ] or C patients [ 21.7 ( 5.5 ) mg ] , p < 0.01 , paravertebral fentanyl and clonidine were associated with significantly increased vomiting and hypotension , respectively Background The contribution of regional anesthesia with thoracic paravertebral blockade to postoperative analgesia remains unclear . We compared the effect of a combination of paravertebral blockade and propofol general anesthesia ( GA ) with sevoflurane GA and opioid analgesia on postoperative pain and opioid use for patients undergoing breast cancer surgery . Methods Patients having breast cancer surgery were r and omly assigned to paravertebral analgesia with propofol GA ( PPA , n = 187 ) or sevoflurane GA with perioperative opioid analgesia ( SOA , n = 199 ) . The PPA and SOA groups were compared for opioid consumption and pain outcomes ( on a 0 - 10 visual analogue scale [ VAS ] ) at two hours postoperatively using superiority and inferiority statistics . We compared our results with previous publications in a meta- analysis . Results Compared with the SOA group , the PPA group experienced reduced median [ interquartile range ] pain VAS scores ( 1 [ 1,3 ] vs 2.5 [ 1,4 ] , respectively ; median difference −1.0 ; 99 % confidence intervals [ CI ] : −1.5 to −0.5 ) and required less intraoperative fentanyl ( 50 [ 0 , 125 ] µg vs 200 [ 100 , 300 ] µg , respectively ; median difference −100 ; 99 % CI : −150 to −100 ) and less long-acting opioid ( 0 [ 0 , 0 ] mg vs 3.0 [ 0 , 12 ] mg , respectively , morphine equivalents ; median difference −3 ; 99 % CI : −4 to −2 ) . Thus , non-inferiority was detected for all the above outcomes , and superiority tests for each outcome were highly significant in the expected directions ( P < 0.001 ) . Meta- analysis , including the current study , estimated a reduction in worst pain of 2.3 points ( 95 % CI : 1.8 to 2.8 ) on a 0 - 10 scale and a 72 % reduction ( 95 % CI : 42 to 87 ) in mean opioid consumption in the immediate two postoperative hours for PPA vs SOA . Conclusion Our results were largely consistent with previous much smaller studies . Compared with sevoflurane GA with opioid analgesia , the combination of paravertebral analgesia with propofol GA provides an early clinical analgesic benefit in females having breast cancer surgery . This analysis is a sub study of an ongoing multicentre double-blinded r and omized trial ( www . clinical trials.gov , NCT00418457 ) of cancer recurrence . Résumé Context eLa contribution de l’anesthésie régionale avec bloc paravertébral thoracique à l’analgésie postopératoire reste mal connue . Nous avons comparé l’effet de la combinaison bloc paravertébral et anesthésie générale ( AG ) au propofol à l’effet de l’AG au sévoflurane et analgésie par opioïdes sur le niveau de douleur postopératoire et l’utilisation des opioïdes chez des patientes subissant une chirurgie pour cancer du sein . MéthodesDes patientes devant subir une chirurgie pour cancer du sein ont été r and omisées dans deux groupes pour recevoir une AG par propofol et analgésie paravertébrale ( PPA , n = 187 ) ou une AG par sévoflurane avec analgésie périopératoire par opioïdes ( SOA , n = 199 ) . Les groupes PPA et SOA ont été comparés sur le plan de la consommation des opioïdes et des niveaux de douleur ( sur une échelle visuelle analogique [ EVA ] de 0 à 10 ) à deux heures postopératoires utilisant des calculs statistiques de supériorité et d’infériorité . Nous avons comparé nos résultats avec les publications précédentes dans une méta-analyse . RésultatsComparé au groupe SOA , le groupe PPA a présenté des scores médians ( intervalle interquartile ) de douleur réduits sur l’EVA ( respectivement , 1 [ 1,3 ] contre 2,5 [ 1,4 ] ; différence des médianes −1,0 ; intervalle de confiance [ IC ] à 99 % : −1,5 à −0,5 ) et a nécessité moins de fentanyl peropératoire ( respectivement , 50 [ 0 à 125 ] µg contre 200 [ 100 à 300 ] µg ; différence des médianes −100 ; IC à 99 % : −150 à −100 ) et moins d’opioïdes à longue durée d’action ( respectivement , 0 [ 0 , 0 ] mg contre 3,0 [ 0 à 12 ] mg d’équivalent-morphine ; différence des médianes −3 ; IC à 99 % : −4 à −2 ) . Ainsi , une non-infériorité a été détectée pour tous les critères d’évaluation ci-dessus et les tests de supériorité pour chaque critère ont été hautement significatifs dans le sens attendu ( P < 0,001 ) . La méta-analyse incluant l’étude actuelle a estimé une réduction de la pire douleur de 2,3 points ( IC à 95 % : 1,8 à 2,8 ) sur une échelle de 0 à 10 et une diminution de 72 % ( IC à 95 % : 42 à 87 ) de la consommation moyenne d’opioïdes dans les deux heures postopératoires immédiates pour le groupe PPA par rapport au groupe SOA . Conclusion Nos résultats ont été largement concordants avec des études antérieures beaucoup plus petites . Comparativement à l’AG au sévoflurane avec analgésie par opioïdes , l’association d’une analgésie paravertébrale et d’une AG au propofol a fourni des avantages cliniques précoces pour les femmes subissant une chirurgie pour cancer du sein . Cette analyse est une sous-étude d’un essai r and omisé multicentrique à double insu sur la récidive cancéreuse ( www . Clinical Trials.gov : nº NCT00418457 ) Background : Postoperative pain after breast cancer surgery is not uncommon . Narcotic based analgesia is commonly used for postoperative pain management . However , the side-effects and complications of systemic narcotics is a significant disadvantage . Different locoregional anesthetic techniques have been tried including , single and multiple levels paravertebral block ( PVB ) , which seems to have a significant reduction in immediate postoperative pain with fewer side-effects . The aim of this study was to compare unilateral multiple level PVB versus morphine patient-controlled analgesia ( PCA ) for pain relief after breast cancer surgery with unilateral lumpectomy and axillary lymph nodes dissection . Material s and Methods : Forty patients scheduled for breast cancer surgery were r and omized to receive either preoperative unilateral multiple injections PVB at five thoracic dermatomes ( group P , 20 patients ) or postoperative intravenous PCA with morphine ( group M , 20 patients ) for postoperative pain control . Numerical pain scale , mean arterial pressure , heart rate , Time to first analgesic dem and , 24-h morphine consumption side-effects and length of hospital stay were recorded . Results : PVB result ed in a significantly more postoperative analgesia , maintained hemodynamic , more significant reduction in nausea and vomiting , and shorter hospital stay compared with PCA patients . Conclusion : Multiple levels PVB is an effective regional anesthetic technique for postoperative pain management , it provides superior analgesia with less narcotics consumption , and fewer side-effects compared with PCA morphine for patients with breast cancer who undergo unilateral lumpectomy , with axillary lymph nodes dissection Background : Paravertebral block ( PVB ) has the potential to offer long-lasting pain relief because it can uniquely eliminate cortical responses to thoracic dermatomal stimulation . Benefits include a reduction in postoperative nausea and vomiting ( PONV ) , prolonged postoperative pain relief , and potential for ambulatory discharge . Aims : To compare PVB with local infiltration for postoperative analgesia following modified radical mastectomy ( MRM ) . Methods : Forty patients undergoing MRM with axillary dissection were r and omly allocated into two groups . Following induction of general anesthesia in group P , a catheter was inserted in the paravertebral space and 0.3 ml/kg of 0.25 % of bupivacaine was administered followed by continuous infusion , while in group L , the surgical incision was infiltrated with 0.3 ml/kg of 0.25 % bupivacaine . Statistical Analysis : The statistical tests were applied as unpaired student ‘ t ’ test/nonparametric test Wilcoxon Mann Whitney test for comparing different parameters such as VAS score and consumption of drugs . The categorical variables such as nausea and vomiting scores , sedation score , and patient satisfaction score were computed by Chi square test/Fisher exact test . Results : VAS score was significantly lower in group P than in group L throughout the postoperative period . The mean alertness score ( i.e. , less sedation ) was higher in group P in the postoperative period than group L. The incidence of PONV was less in PVB group . Conclusion : PVB at the end of the surgery results in better postoperative analgesia , lesser incidence of PONV , and better alertness score Background The combination of acetaminophen , codeine , and caffeine ( Tylenol 3 , T3 ) is a st and ard postoperative analgesia after breast surgery despite the adverse effects and variable efficacy of narcotics . This study compared the efficacy of a nonnarcotic approach ( acetaminophen and ibuprofen ; AcIBU ) to T3 after outpatient breast surgery . Methods This double-blind r and omized equivalence trial involved patients undergoing outpatient breast surgery . Patients were r and omized ( stratified by procedure type ) to receive AcIBU or T3 four times daily for 7 days , or until free of pain . Pain intensity , measured four times daily by the visual analog scale , was the primary outcome ; secondary outcomes were pain relief with analgesic , days until freedom from pain , adverse effects , discontinuation of drug as a result of adverse effects , and patient satisfaction . Results There were 71 patients r and omized to AcIBU and 70 patients to T3 . Repeated measures analysis showed no significant difference in average pain intensity over 7 days ( AcIBU 19.9 mm vs. T3 20.6 mm ; P = 0.78 ) . Similarly , there was no significant difference in pain relief with analgesic ( P = 0.46 ) . Although no difference in the incidence of adverse effects was observed ( P = 0.94 ) , discontinuation of the study drug as a result of adverse effects was more common with T3 ( 19 % vs. 6 % ; P = 0.018 ) . No significant differences were identified in days until freedom from pain or patient satisfaction ; 92 % of AcIBU and 89 % of T3 patients were satisfied with their pain control ( P = 0.55 ) . Conclusions AcIBU is a safe , effective method of pain control after outpatient breast surgery . Compared to T3 , it provides at least equivalent analgesia and has a more tolerable adverse effect profile BACKGROUND In recent years , thoracic wall nerve blocks , such as the pectoral nerve ( PECS ) block and the serratus plane block have become popular for peri-operative pain control in patients undergoing breast cancer surgery . The effect of PECS block on quality of recovery ( QoR ) after breast cancer surgery has not been evaluated . OBJECTIVES To evaluate the ability of PECS block to decrease postoperative pain and anaesthesia and analgesia requirements and to improve postoperative QoR in patients undergoing breast cancer surgery . DESIGN R and omised controlled study . SETTING A tertiary hospital . PATIENTS Sixty women undergoing breast cancer surgery between April 2014 and February 2015 . INTERVENTIONS The patients were r and omised to receive a PECS block consisting of 30 ml of levobupivacaine 0.25 % after induction of anaesthesia ( PECS group ) or a saline mock block ( control group ) . The patients answered a 40-item QoR question naire ( QoR-40 ) before and 1 day after breast cancer surgery . MAIN OUTCOME MEASURES Numeric Rating Scale score for postoperative pain , requirement for intra-operative propofol and remifentanil , and QoR-40 score on postoperative day 1 . RESULTS PECS block combined with propofol – remifentanil anaesthesia significantly improved the median [ interquartile range ] pain score at 6 h postoperatively ( PECS group 1 [ 0 to 2 ] vs. Control group 1 [ 0.25 to 2.75 ] ; P = 0.018 ] . PECS block also reduced propofol mean ( ± SD ) estimated target blood concentration to maintain bispectral index ( BIS ) between 40 and 50 ( PECS group 2.65 ( ± 0.52 ) vs. Control group 3.08 ( ± 0.41 ) & mgr;g ml−1 ; P < 0.001 ) but not remifentanil consumption ( PECS group 10.5 ( ± 4.28 ) vs. Control group 10.4 ( ± 4.68 ) & mgr;g kg−1 h−1 ; P = 0.95 ) . PECS block did not improve the QoR-40 score on postoperative day 1 ( PECS group 182 [ 176 to 189 ] vs. Control group 174.5 [ 157.75 to 175 ] ) . CONCLUSION In patients undergoing breast cancer surgery , PECS block combined with general anaesthesia reduced the requirement for propofol but not that for remifentanil , due to the inability of the PECS block to reach the internal mammary area . Further , PECS block improved postoperative pain but not the postoperative QoR-40 score due to the factors that can not be measured by analgesia immediately after surgery , such as rebound pain . TRIAL REGISTRATION This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry ( UMIN000013435 ) BACKGROUND Pectoral nerve ( PecS ) block is a recently introduced technique for providing surgical anaesthesia and postoperative analgesia during breast surgery . The present study was planned to compare the efficacy and safety of ultrasound-guided PecS II block with thoracic paravertebral block ( TPVB ) for postoperative analgesia after modified radical mastectomy . METHODS Forty adult female patients undergoing radical mastectomy were r and omly allocated into two groups . Group 1 patients received a TPVB with ropivacaine 0.5 % , 25 ml , whereas Group 2 patents received a PecS II block using same volume of ropivacaine 0.5 % before induction of anaesthesia . Patient-controlled morphine analgesia was used for postoperative pain relief . RESULTS The duration of analgesia was significantly prolonged in patients receiving the PecS II block compared with TPVB [ mean ( sd ) , 294.5 ( 52.76 ) vs 197.5 ( 31.35 ) min in the PecS II and TPVB group , respectively ; P<0.0001 ] . The 24 h morphine consumption was also less in the PecS II block group [ mean ( sd ) , 3.90 ( 0.79 ) vs 5.30 ( 0.98 ) mg in PecS II and TPVB group , respectively ; P<0.0001 ] . Postoperative pain scores were lower in the PecS II group compared with the TVPB group in the initial 2 h after surgery [ median ( IQR ) , 2 ( 2 - 2.5 ) vs 4 ( 3 - 4 ) in the Pecs II and TPVB group , respectively ; P<0.0001 ] . Seventeen patients in the PecS II block group had T2 dermatomal spread compared with four patients in the TPVB group ( P<0.001 ) . No block-related complication was recorded . CONCLUSIONS We found that the PecS II block provided superior postoperative analgesia than the TPVB in patients undergoing modified radical mastectomy without causing any adverse effect . CLINICAL TRIAL REGISTRATION CTRI/2014/06/004692 STUDY OBJECTIVE The aim of this clinical trial was to test the hypothesis whether adding the pectoral nerves ( Pecs ) block type II to the anesthetic procedure reduces opioid consumption during and after breast surgery . DESIGN A prospect i ve r and omized double blind placebo-controlled study . SETTING A secondary hospital . PATIENTS 140 breast cancer stage 1 - 3 patients undergoing mastectomy or tumorectomy with sentinel node or axillary node dissection . INTERVENTIONS Patients were r and omized to receive either a Pecs block with levobupivacaine 0.25 % ( n=70 ) or placebo block with saline ( n=70 ) . MEASUREMENTS The pain levels were evaluated by Numeric Rating Scale ( NRS ) pain scores at 15-minute intervals during the post anesthesia care unit stay time ( PACU ) , at 2-hour intervals for the first 24h on the ward and at 4-hour intervals for the next 24h . Intraoperative and postoperative opioid consumption were recorded during the full stay . Patient satisfaction was evaluated upon discharge using a 10-point scale . MAIN RESULTS Intraoperative sufentanil requirements were comparable for the Pecs and placebo group ( 8.0±3.5μg and 7.8±3.0μg , P=0.730 ) . Patients in the Pecs group experienced significantly less pain than patients in the control group ( P=0.048 ) during their PACU stay . Furthermore , patients in the Pecs group required significant less postoperative opioids ( 9.16±10.15 mg and 14.97±14.38 mg morphine equivalent , P=0.037 ) and required significant fewer postsurgical opioid administration interventions than patients in the control group ( P=0.045 ) . Both patient-groups were very satisfied about their management ( 9.6±0.6 and 9.1±1.8 on a 10-point scale , P=0.211 ) . CONCLUSIONS The Pecs block reduces postsurgical opioid consumption during the PACU stay time for patients undergoing breast surgery ABSTRACT Objective : To assess clinical efficacy of IV paracetamol 1 g and IV dipyrone 1 g on a 24.h dosing schedule in this r and omised , double-blinded study of 40 ASA I – III ( American Society of Anesthesiologists classification of physical status ) patients undergoing surgery for breast cancer . Research design and methods : General anaesthesia using remifentanil and propofol was performed for surgery . The patients were r and omly allocated to two groups , receiving infusions of paracetamol 1 g/100 mL ( Para Group ) or of dipyrone 1 g/100 mL ( Dipy Group ) 30 min before arrival in the recovery area and every 6 h up to 24 h postoperatively . All patients had unrestricted access to opioid rescue medication via an IV patient-controlled analgesia ( PCA ) device . Main outcome measures : The primary variables for clinical equivalence were the differences between the mean values for pain scores at rest and pain scores on coughing over 30 h postoperatively . The equivalence margin was determined as ±10 mm on the visual analogue scale ( VAS ) . Results : Regarding pain scores at rest , the 90 % CI of the mean differences between the treatment groups over 30 h postoperatively was found to be within the predefined equivalence margin [ + 7.5/–6.2 ] , and the CI values for pain scores on coughing [ + 7.3/–9.0 ] were similar . The two groups did not differ in cumulative opioid rescue consumption ( Dipy-Group 14.8 ± 17.7 mg vs. Para Group 12.1 ± 8.8 mg , p = 0.54 ) nor in piritramide loading dose ( Dipy Group 0.95 ± 2.8 mg vs. Para Group 1.3 ± 2.8 mg , p = 0.545 ) . Five patients in the Dipy Group experienced hypotension in contrast to none in the Para Group ( p = 0.047 ) . There were no significant between-treatment differences for other adverse events , patient satisfaction scores ( p = 0.4 ) or quality of recovery scores ( p = 0.3 ) . Conclusion : IV paracetamol 1 g is clinical ly equivalent to IV dipyrone 1 g for postoperative analgesia after surgery for breast cancer Background : Paravertebral and inter pleural blocks ( IPB ) reduce post-operative pain and decrease the effect of post-operative pain on lung functions after breast surgery . This study was design ed to determine their effect on lung functions and post-operative pain in patients undergoing modified radical mastectomy . Material s and Methods : A total of 120 American Society of Anesthesiologists physical status 1 and 2 patients scheduled to undergo breast surgery were r and omly allocated to receive IPB ( Group IPB , n = 60 ) or paravertebral block ( PVB ) ( Group PVB , n = 60 ) with 20 ml of 0.5 % bupivacaine pre-operatively . A st and ard protocol was used to provide general anesthesia . Lung function tests , visual analog scale ( VAS ) for pain at rest and movement , analgesic consumption were recorded everyday post-operatively until discharge . Results : Lung functions decreased on 1st post-operative day and returned to baseline value by 4th post-operative day in both groups . VAS was similar in both groups . There was no significant difference in the consumption of opioids and diclofenac in both groups . Complete block was achieved in 48 patients ( 80 % ) in paravertebral group and 42 patients ( 70 % ) in inter pleural group . Conclusion : To conclude , lung functions are well-preserved in patients undergoing modified radical mastectomy under general anesthesia supplemented with paravertebral or IPB . IPB is as effective as PVB for post-operative pain relief . PVB has the added advantage of achieving a more complete block Breast reconstruction with submuscular tissue implants is associated with substantial postoperative pain . High pain scores despite large doses of opioids were described in earlier studies , which indicated that opioids alone or together with paracetamol are insufficient . In the present placebo-controlled study we aim ed to evaluate the analgesic efficacy of local anaesthesia as a supplement . Forty-three women who had previously been operated on for breast cancer and were listed for unilateral secondary breast reconstruction were assigned at r and om to one of two groups . The patients received 2.5 mg/ml levobupivacaine ( Chirocaine ® ) 15 ml or placebo in a double-blind manner through an indwelling catheter in the operation site every three hours for 45 hours . All patients were given oral paracetamol 1 g x 4 orally and morphine intravenously as patient-controlled analgesia . A visual analogue scale ( VAS ) was used to assess the intensity of the postoperative pain . Amount of morphine used was recorded . The women in the levobupivacaine group ( n=21 ) reported significantly less pain at rest during the first 15 hours postoperatively ( p<0.05 ) . During mobilisation the intensity of pain was lower for the first six hours ( p=0.01 ) and for the interval 18 - 24 hours ( p=0.045 ) in the same group . Total mean ( SD ) consumption of opioids in the levobupivacaine and placebo groups was 24.6 mg ( 22.88 ) and 33.8 mg ( 30.82 ) , respectively ( p=0.28 ) . After reconstruction , levobupivacaine injected locally every third hour as a supplement to paracetamol orally and morphine given by PCA result ed in improved pain relief at rest and during mobilisation . Morphine consumption was reduced , but this was not significant ( p=0.28 ) Background : Regional anesthesia using paravertebral block has been suggested as an ideal adjunct to general anesthesia for modified radical mastectomy . Paravertebral block is an effective management of peri-operative pain for Modified radical mastectomy , however , there are no established guidelines regarding what is the most suitable strategy when varying drugs and dosages between different groups . Aim : To evaluate the effectiveness of paravertebral block comparing the most frequently employed drugs in this procedure ( bupivacaine vs ropivacaine ) . Study Design : Prospect i ve r and omized double blind study . Methods : A total 70 ASA I and II adult female patients undergoing Modified radical mastectomy under paravertebral block followed by general anesthesia were r and omly divided into two groups . The first group was administered 0.375 % Ropivacaine in a dose 0.25 ml /kg in paravertebral block . The second group was administered bupivacaine 0.375 % in dose 0.25 ml /kg in paravertebral block . St and ard induction technique followed . Heart rate ( HR ) , systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , were recorded pre block , post block 5 min , post block 10 min , at skin incision , post skin incision initially at 5 interval for first 15 min till one hour , and every 30 min till end of surgery . Post-operative visual analogue score for pain was recorded at 1 hr , 6 hr and 24 hr . Statistical Analysis : Chi-square test ( Fisher 's exact test ) for qualitative variables . Independent sample t-test for quantitative data . Results : Ropivacaine and Bupivacaine had no difference in intraoperative analgesia as shown by intraoperative hemodynamic parameters . Bupivacaine got better post-operative VAS scores ( P < 0.05 ) in mean and after first , 6 h and 24 BACKGROUND : We examined in this r and omized , double-blind study whether a multilevel paravertebral block performed before general anesthesia with propofol and a laryngeal mask enhances postoperative analgesia after breast cancer surgery . METHODS : Eighty-eight patients were r and omized to receive paravertebral injections with either ropivacaine 0.5 % ( 30 mL ) or an equivalent amount of isotonic saline . Nine patients were excluded after r and omization , thus 79 patients remained for evaluation ( ropivacaine , n = 38 ; placebo , n = 41 ) . Variables of efficacy were the amount of fentanyl delivered by the patient-controlled analgesia device in the postanesthesia care unit ( PACU ) , postoperative pain measured on a numeric rating scale at regular intervals from the day of surgery and until the second postoperative day . RESULTS : The median consumption of fentanyl in the PACU was less in the ropivacaine group compared with the placebo group ( 0 & mgr;g [ range : 0–250 & mgr;g ] versus 100 & mgr;g [ range : 0–800 & mgr;g ] , P = 0.001 ) . Also , fewer patients in the ropivacaine group reported pain ≥3 on the numbers rating scale in the PACU ( 13 vs 31 , P < 0.0001 ) . No statistical difference in pain scores or consumption of analgesics could be demonstrated after discharge from the PACU . CONCLUSIONS : A multilevel paravertebral block provides good analgesia for breast surgery , but the duration of analgesia is briefer than described in previous studies One hundred patients undergoing breast lump excision using a st and ard anaesthetic technique in the Day Care Unit were r and omly divided into five groups . Groups A and B received either saline or diclofenac in a double blinded , fashion before and at the end of the procedure , with both groups receiving 10 ml of 0.5 % bupivacaine infiltration at the end . Groups C and D also received saline or diclofenac before and after surgery but had no bupivacaine infiltration at the end . Group E did not receive any injections but had bupivacaine infiltration at the end of surgery . In the postoperative period , pain was assessed by a visual analogue scale at 30 min intervals until discharge . All patients were requested to complete a pain relief question naire over the 48 h following surgery . There were highly significant differences between those who received bupivcaine and those who did not in the visual analogue scale scores at 30min ( p < 0.001 ) , 60 min ( p < 0.001 ) , 120 min postoperatively ( p = 0.02 ) and at discharge ( p = 0.03 ) . Pain scores were lower in those who received bupivacaine and they were less likely to request rescue medication , although this did not reach significance ( p = 0.07 ) . There were significant differences between the groups who received bupivacaine and diclofenac injection and those who received bupivacaine alone , for visual analogue scale scores at 60 min following surgery ( p = 0.05 ) and at 48 h ( p = 0.002 ) . Pain relief was better in those patients who received both bupivacaine and diclofenac injection . Although not significant ( p = 0.22 ) . fewer patients required rescue medication when diclofenac was given before surgery ( 10 % ) rather than after surgery ( 22.5 % ) . Fewer patients had a fair amount or a great deal of pain in the 48 h following surgery when diclofenac was injected before ( 7.5 % ) rather than after surgery ( 12.5 % ) . The mean number of oral analgesics taken in the 48 h after surgery was also lower in those patients who had the diclofenac before the surgery rather than after STUDY OBJECTIVE To evaluate the analgesic effect of ultrasound-guided erector spinae plane ( ESP ) block in breast cancer surgery . DESIGN R and omized controlled , single-blinded trial . SETTING Operating room . PATIENTS Fifty ASA I-II patients aged 25 - 65 and scheduled for elective breast cancer surgery were included in the study . INTERVENTIONS Patients were r and omized into two groups , ESP and control . Single-shot ultrasound (US)-guided ESP block with 20 ml 0.25 % bupivacaine at the T4 vertebral level was performed preoperatively to all patients in the ESP group . The control group received no intervention . Patients in both groups were provided with intravenous patient-controlled analgesia device containing morphine for postoperative analgesia . MEASUREMENTS Morphine consumption and numeric rating scale ( NRS ) pain scores were recorded at 1 , 6 , 12 and 24 h postoperatively . MAIN RESULTS Morphine consumption at postoperative hours 1 , 6 , 12 and 24 decreased significantly in the ESP group ( p < 0.05 for each time interval ) . Total morphine consumption decreased by 65 % at 24 h compared to the control group ( 5.76 ± 3.8 mg vs 16.6 ± 6.92 mg ) . There was no statistically significant difference between the groups in terms of NRS scores . CONCLUSIONS Our study findings show that US-guided ESP block exhibits a significant analgesic effect in patients undergoing breast cancer surgery . Further studies comparing different regional anesthesia techniques are needed to identify the optimal analgesia technique for this group of patients STUDY OBJECTIVE Breast cancer is the most common malignancy of women all over the world . In this study , we compared the effects of ultrasound-guided modified pectoral nerve ( PECS ) block and erector spinae plane ( ESP ) block on postoperative opioid consumption , pain scores , and intraoperative fentanyl need of patients undergoing unilateral modified radical mastectomy surgery . DESIGN Single-blinded , prospect i ve , r and omized , efficacy study . SETTING Tertiary university hospital , postoperative recovery room and surgical ward . PATIENTS Forty patients ( ASA I-II ) were allocated to two groups . After exclusion , 38 patients were included in the final analysis ( 18 patients in the PECS groups and 20 in the ESP group ) . INTERVENTIONS Modified pectoral nerve block was performed in the PECS group and erector spinae plane block was performed in the ESP group . MEASUREMENTS Postoperative tramadol consumption and pain scores were compared between the groups . Also , intraoperative fentanyl need was measured . MAIN RESULTS Postoperative tramadol consumption was 132.78 ± 22.44 mg in PECS group and 196 ± 27.03 mg in ESP group ( p = 0.001 ) . NRS scores at the 15th and 30th min were similar between the groups . However , median NRS scores were significantly lower in PECS group at the postoperative 60th min , 120th min , 12th hour and 24th hour ( p = 0.024 , p = 0.018 , p = 0.021 and p = 0.011 respectively ) . Intraoperative fentanyl need was 75 mg in PECS group and 87.5 mg in ESP group . The difference was not statistically significant ( p = 0.263 ) . CONCLUSION Modified PECS block reduced postoperative tramadol consumption and pain scores more effectively than ESP block after radical mastectomy surgery Background and Aims : Several locoregional techniques have been described for providing postoperative analgesia after breast surgery . The optimal technique should be easy to perform , reproducible and provide good analgesia . This r and omised control study was design ed to evaluate the postoperative analgesic effect of ultrasound-guided erector spinae plane ( US-guided ESP ) block for modified radical mastectomy ( MRM ) surgery . Methods : A total of 40 females belonging to American Society of Anesthesiologists ' 1 or 2 posted for MRM were r and omly allocated into Group 1 ( control group ) and group 2 ( ESP group ) . Patients in Group 1 received only general anaesthesia ( GA ) and were managed for pain postoperatively according to routine protocol , while group 2 ( ESP group ) patients received unilateral US-guided ESP block preoperatively ( 20 mL 0.5 % bupivacaine to the operating side ) followed by GA . The primary objective of study was to record postoperative 24 h cumulative morphine requirement . Differences between the two groups were analyzed using the Mann – Whitney U-test or a two-tailed Student 's t-test . Results : Postoperative morphine consumption was found to be significantly less in patients receiving US-guided ESP block compared to control group ( 1.95 ± 2.01 mg required in ESP group vs 9.3 ± 2 . 36 mg required in control group , P value = 0.01 ) ) . All the patients in control group required supplemental morphine postoperatively compared to only two patients requiring that in US-guided ESP block group ( P < 0.01 ) . Conclusion : US-guided ESP block when given prior to MRM surgery provided effective postoperative analgesia . CTRI registration no. - CTRI/2018/03/012712 registered in the clinical trial registry , India BACKGROUND Multimodal analgesia can improve postoperative pain and possibly accelerate functional recovery after surgery . Serratus plane block ( SPB ) is a novel , ultrasound-guided regional anaesthetic technique for complete analgesia of the anterolateral chest wall . But , the effect of SPB on the quality of recovery after breast cancer surgery has not been established . OBJECTIVE To test the hypothesis that pre-operative SPB would enhance the quality of recovery following breast cancer surgery . DESIGN A r and omised , double-blind , parallel-group , placebo-controlled trial . SETTING Single university teaching hospital , from March 2016 to June 2017 . PATIENTS Seventy-two women scheduled for breast cancer surgery . INTERVENTION Participants were r and omised in a 1 : 1 ratio to receive SPB with 25 ml of ropivacaine 0.5 % or physiological saline . MAIN OUTCOME MEASURES The primary endpoint was the 40-item Quality of Recovery question naire score 24 hours postoperatively hours . Secondary endpoints were postoperative pain intensity , cumulative opioid consumption , postoperative nausea and vomiting , dizziness , post anaesthesia care unit discharge time and patient satisfaction . RESULTS The global median [ IQR ] 40-item Quality of Recovery question naire score at 24 postoperative hours was significantly higher in the SPB group ( 158 [ 153.8 to 159.3 ] ) than the control group ( 141 [ 139 to 145.3 ] ) with a median difference of 15 ( 95 % confidence interval : 13 to 17 , P < 0.001 ) . Compared with the control group , postoperative pain scores at rest were significantly lower up to 24 h in the SPB group . Pre-operative SPB reduced postoperative cumulative opioid consumption , the incidence of postoperative nausea and vomiting and the post anaesthesia care unit discharge time . In addition , patient satisfaction scores were higher in the SPB group . CONCLUSION Pre-operative administration of SPB with ropivacaine improved the quality of recovery , postoperative analgesia and patient satisfaction following breast cancer surgery . TRIAL REGISTRATION Clinical Trials.gov ( identifier : NCT02691195 ) Purpose : Combined regional and general anesthesia are often used for the management of breast cancer surgery . Thoracic spinal block , thoracic epidural block , thoracic paravertebral block , and multiple intercostal nerve blocks are the regional anesthesia techniques which have been used in breast surgery , but some anesthesiologists are not comfortable because of the complication and side effects . In 2012 , Blanco et al introduced pectoralis nerve ( Pecs ) II block or modified Pecs block as a novel approach to breast surgery . This study aims to determine the effectiveness of combined ultrasound-guided Pecs II block and general anesthesia for reducing intra- and postoperative pain from modified radical mastectomy . Patients and methods : Fifty patients undergoing modified radical mastectomy with general anesthesia were divided into two groups r and omly ( n=25 ) , to either Pecs ( P ) group or control ( C ) group . Ultrasound-guided Pecs II block was done with 0.25 % bupivacaine ( P group ) or 0.9 % NaCl ( C group ) . Patient-controlled analgesia was used to control postoperative pain . Intraoperative opioid consumption , postoperative visual analog scale ( VAS ) score , and postoperative opioid consumption were measured . Results : Intraoperative opioid consumption was significantly lower in P group ( P≤0.05 ) . VAS score at 3 , 6 , 12 , and 24 hrs postoperative were significantly lower in P group ( P≤0.05 ) . Twenty-four hours postoperative opioid consumption was significantly lower in P group ( P≤0.05 ) . There are no complications following Pecs block in both groups , including pneumothorax , vascular puncture , and hematoma . Conclusion : Combined ultrasound-guided Pecs II block and general anesthesia are effective in reducing pain both intra- and postoperatively in patients undergoing modified radical mastectomy . Ultrasound-guided Pecs II block is a relatively safe peripheral nerve block We r and omly allocated 50 women scheduled for radical mastectomy to pectoral nerves‐2 ( PECS‐2 ) block ( n = 25 ) or no block ( n = 25 ) , 20 and 22 of whom we analysed for the primary outcome of a cumulative 24‐h postoperative morphine dose . We gave intra‐operative sufentanil , magnesium , dexamethasone and droperidol . Participants received regular postoperative paracetamol , ibuprofen and patient‐controlled intravenous morphine . Pectoral nerves‐2 block reduced mean ( SD ) cumulative 24 h postoperative morphine dose from 9.7 ( 8.9 ) mg to 5.0 ( 5.4 ) mg and 48 h morphine dose from 12.8 ( 12.5 ) mg to 6.0 ( 6.5 ) mg , p = 0.04 for both . The mean ( SD ) pain scores 24 h and 48 h after surgery were similar with or without block : 0.8 ( 1.4 ) vs. 1.2 ( 1.9 ) , p = 0.39 ; and 0.2 ( 0.4 ) vs. 0.9 ( 1.8 ) , p = 0.09 , respectively . Rates of postoperative nausea , vomiting and pruritus were unaffected . Rates of chronic pain at six postoperative months were 2/19 and 2/18 after block and no block , respectively , p = 0.95 Background and Objectives The objective of this study was to investigate the extent of dermatomal spread following an ultrasound-guided thoracic paravertebral block ( PVB ) when equal volumes of local anesthetic are injected at 1 versus 5 vertebral levels . Methods Seventy patients undergoing a unilateral mastectomy were r and omized to receive either single or multiple injections of a PVB under real-time ultrasound guidance using a parasagittal approach . The patients in the single-injection group received a PVB at T3–T4 level with 25 mL of 0.5 % ropivacaine and 4 subcutaneous sham injections . Patients in the multiple-injection group received 5 injections of a PVB from T1 to T5 level . Five milliliters of 0.5 % ropivacaine was injected at each level . Evaluation of the sensory block was carried out 20 minutes following the completion of the PVB . Results The median ( interquartile range ) dermatomal spread was not significantly different for the single-injection group ( 5 [ 4 - 6 ] ) compared with the multiple-injection group ( 5 [ 5 - 6 ] ) , with a median difference of 0 segments ( 95 % confidence interval , −1 to 0 segments ; P = 0.22 ) . The median time to performance of the single-injection PVB was shorter compared with the multiple-injection group ( 10 minutes ) , with a mean difference of −4 minutes ( 95 % confidence interval , −6 to −3 minutes ; P < 0.001 ) . Conclusions An ultrasound-guided single-injection PVB provides equivalent dermatomal spread and duration of analgesia compared with a multiple-injection PVB . The single-injection technique takes less time to perform and hence may be preferred over a multiple-injection technique . The trial was registered prospect ively at Clinical Trials.gov ( NCT02852421 ) on July 15 , 2016 |
1,835 | 32,103,400 | Peripheral neuropathy is associated with an increase of reactive oxygen species and a decrease in endogenous antioxidants .
Genetic predisposition to oxidative damage may be a factor .
Antioxidant treatment is promising regarding treatment .
Though further research is necessary to better underst and the underlying mechanism , it is evident that oxidative stress is implicated in the pathogenesis of – or is at least systematic ally present in – PN | Peripheral neuropathy ( PN ) is a common disease affecting about 5 % of the general population after the age of 50 .
Causes of PN are numerous and include genetic , diabetes , alcohol , vitamin deficiencies , and gluten sensitivity among others .
This systematic review aim ed to study the association between oxidative stress and PN in an attempt to better underst and PN pathogenesis . | OBJECTIVE To evaluate the efficacy and safety of alpha-lipoic acid given intravenously , followed by oral treatment in type 2 diabetic patients with symptomatic polyneuropathy . RESEARCH DESIGN AND METHODS In a multicenter r and omized double-blind placebo-controlled trial ( Alpha-Lipoic Acid in Diabetic Neuropathy [ ALADIN ] III Study ) , 509 out patients were r and omly assigned to sequential treatment with 600 mg alpha-lipoic acid once daily intravenously for 3 weeks , followed by 600 mg alpha-lipoic acid three times a day orally for 6 months ( A-A ; n = 167 ) ; 600 mg alpha-lipoic acid once daily intravenously for 3 weeks , followed by placebo three times a day orally for 6 months ( A-P ; n = 174 ) ; and placebo once daily intravenously for 3 weeks , followed by placebo three times a day orally for 6 months ( P-P ; n = 168 ) . Outcome measures included the Total Symptom Score ( TSS ) for neuropathic symptoms ( pain , burning , paresthesias , and numbness ) in the feet , and the Neuropathy Impairment Score ( NIS ) . Data analysis was based on the intention to treat . RESULTS No significant differences between the groups were noted for the demographic variables and the nerve function parameters at baseline . The TSS in the feet decreased from baseline to day 19 ( median [ range ] ) by -3.7 ( -12.6 to 5.0 ) points in the group given alpha-lipoic acid intravenously and by -3.0 ( -12.3 to 8.0 ) points in the placebo group ( P = 0.447 ) , but the area under curve on a daily basis was significantly smaller in the active as compared with the placebo group ( 85.6 [ 0 - 219 ] vs. 95.9 [ 5.5 - 220 ] ) ; P = 0.033 ) . After 7 months , the changes in the TSS from baseline were not significantly different between the three groups studied , which could be due to increasing intercenter variability in the TSS during the trial . The NIS decreased after 19 days by -4.34+/-0.35 points ( mean + /- SEM ) in A-A and A-P and -3.49+/-0.58 points in P-P ( P = 0.02 for alpha-lipoic acid versus placebo ) and after 7 months by -5.82+/-0.73 points in A-A , -5.76+/-0.69 points in A-P , and -4.37+/-0.83 points in P-P ( P = 0.09 for A-A vs. P-P ) . The rates of adverse events were not different between the groups throughout the study . CONCLUSIONS These findings indicate that a 3-week intravenous treatment with alpha-lipoic acid , followed by a 6-month oral treatment , had no effect on neuropathic symptoms distinguishable from placebo to a clinical ly meaningful degree , possibly due to increasing intercenter variability in symptom scoring during the study . However , this treatment was associated with a favorable effect on neuropathic deficits without causing significant adverse reactions . Long-term trials that focus on neuropathic deficits rather than symptoms as the primary criterion of efficacy are needed to see whether oral treatment with alpha-lipoic acid over several years may slow or reverse the progression of diabetic neuropathy BACKGROUND QR-333 , a topical compound that contains quercetin , a flavonoid with aldose reductase inhibitor effects , ascorbyl palmitate , and vitamin D(3 ) , was formulated to decrease the oxidative stress that contributes to peripheral diabetic neuropathy and thus alleviate its symptoms . This proof-of-principle study assessed the efficacy and safety of QR-333 against placebo in a small cohort of patients with diabetic neuropathy . METHODS This r and omized , placebo-controlled , double-blind trial included 34 men and women ( 21 - 71 years of age ) with Type 1 or 2 diabetes and diabetic neuropathy who applied QR-333 or placebo ( 2:1 ratio ) , three times daily for 4 weeks , to each foot where symptoms were experienced . Five-point scales were used to determine changes from baseline to endpoint in symptoms and quality of life ( efficacy ) . Safety was assessed through concomitant medications , adverse events , laboratory evaluations , and physical examinations . RESULTS QR-333 reduced the severity of numbness , jolting pain , and irritation from baseline values . Improvements were also seen in overall and specific quality -of-life measures . QR-333 was well tolerated . Eleven patients in the QR-333 group reported 23 adverse events ( all mild or moderate ) ; 4 in the placebo group reported 5 events ( all moderate ) . One patient who applied QR-333 noted a pricking sensation twice , the only adverse event considered possibly related to study treatment . CONCLUSIONS From this preliminary safety study , it appears that QR-333 may safely offer relief of symptoms of diabetic neuropathy and improve quality of life . These findings warrant further investigation of this topical compound Objective . To evaluate the effects of ezetimibe/simvastatin ( EZE/SIMV ) and rosuvastatin ( ROSUV ) on oxidative stress ( OS ) markers in patients with diabetic polyneuropathy ( DPN ) . Methods . We performed a r and omized , double-blind , placebo-controlled phase III clinical trial in adult patients with Type 2 Diabetes Mellitus ( T2DM ) and DPN , as evaluated by composite scores and nerve conduction studies ( NCS ) . Seventy-four subjects with T2DM were allocated 1 : 1 : 1 to placebo , EZE/SIMV 10/20 mg , or ROSUV 20 mg for 16 weeks . All patients were assessed before and after treatment : primary outcomes were lipid peroxidation ( LPO ) , and nitric oxide ( NO ) surrogate levels in plasma ; secondary outcomes included NCS , neuropathic symptom scores , and metabolic parameters . Data were expressed as mean ± SD or SEM , frequencies , and percentages ; we used nonparametric analysis . Results . LPO levels were reduced in both statin arms after 16 weeks of treatment ( p < 0.05 versus baseline ) , without changes in the placebo group . NO levels were not significantly affected by statin treatment , although a trend towards significance concerning increased NO levels was noted in both statin arms . No significant changes were observed for the NCS or composite scores . Discussion . EZE/SIMV and ROSUV are superior to placebo in reducing LPO in subjects with T2DM suffering from polyneuropathy . This trial is registered with NCT02129231 Antiretroviral toxic neuropathy causes morbidity in human immunodeficiency virus ( HIV ) patients under dideoxynucleoside therapy , benefits only partially from medical therapy , and often leads to drug discontinuation . Proposed pathogeneses include a disorder of mitochondrial oxidative metabolism , eventually related to a reduction of mitochondrial DNA content , and interference with nerve growth factor activity . Carnitine is a substrate of energy production reactions in mitochondria and is involved in many anabolic reactions . Acetyl carnitine treatment promotes peripheral nerve regeneration and has neuroprotective properties and a direct analgesic role related to glutamatergic and cholinergic modulation . The aim of this study was to evaluate acetyl-l-carnitine in the treatment of painful antiretroviral toxic neuropathy in HIV patients . Twenty subjects affected by painful antiretroviral toxic neuropathy were treated with oral acetyl-l-carnitine at a dose of 2,000 mg/day for a 4-week period . Efficacy was evaluated by means of the modified Short Form McGill Pain Question naire with each item rated on an 11-point intensity scale at weekly intervals and by electromyography at baseline and final visit . Mean pain intensity score was significantly reduced during the study , changing from 7.35 + /- 1.98 ( mean + /- SD ) at baseline to 5.80 + /- 2.63 at week 4 ( p = 0.0001 ) . Electrophysiological parameters did not significantly change between baseline and week 4 . In this study , acetyl-l-carnitine was effective and well tolerated in symptomatic treatment of painful neuropathy associated with antiretroviral toxicity . On the contrary , no effect was noted on neurophysiological parameters BACKGROUND The majority of patients receiving the platinum-based chemotherapy drug oxaliplatin develop peripheral neurotoxicity . Because this neurotoxicity involves ROS production , we investigated the efficacy of mangafodipir , a molecule that has antioxidant properties and is approved for use as an MRI contrast enhancer . METHODS The effects of mangafodipir were examined in mice following treatment with oxaliplatin . Neurotoxicity , axon myelination , and advanced oxidized protein products ( AOPPs ) were monitored . In addition , we enrolled 23 cancer patients with grade ≥ 2 oxaliplatin-induced neuropathy in a phase II study , with 22 patients receiving i.v . mangafodipir following oxaliplatin . Neuropathic effects were monitored for up to 8 cycles of oxaliplatin and mangafodipir . RESULTS Mangafodipir prevented motor and sensory dysfunction and demyelinating lesion formation . In mice , serum AOPPs decreased after 4 weeks of mangafodipir treatment . In 77 % of patients treated with oxaliplatin and mangafodipir , neuropathy improved or stabilized after 4 cycles . After 8 cycles , neurotoxicity was down grade d to grade ≥ 2 in 6 of 7 patients . Prior to enrollment , patients received an average of 880 ± 239 mg/m2 oxaliplatin . Patients treated with mangafodipir tolerated an additional dose of 458 ± 207 mg/m2 oxaliplatin despite preexisting neuropathy . Mangafodipir responders managed a cumulative dose of 1,426 ± 204 mg/m2 oxaliplatin . Serum AOPPs were lower in responders compared with those in nonresponders . CONCLUSION Our study suggests that mangafodipir can prevent and /or relieve oxaliplatin-induced neuropathy in cancer patients . Trial registration . Clinical trials.gov NCT00727922 . Funding . Université Paris Descartes , Ministère de la Recherche et de l'Enseignement Supérieur , and Assistance Publique-Hôpitaux de Paris Abstract Background and Objective : The management of diabetic neuropathy is still a challenge for physicians . The aim of this study was to assess the efficacy of a new combination of alpha lipoic acid and superoxide dismutase for the treatment of diabetic neuropathy . p ] Methods : The setting of this study was ambulatory ( outpatient ) care . A prospect i ve , non-r and omized , open-label study was conducted in 50 patients with diabetes mellitus and with a deficit in both motor and sensory nerve conduction . Treatment was with a new combination of alpha lipoic acid and superoxide dismutase ( ALA600SOD ® ) for 4 months . Electroneurographic parameters and perceived pain were assessed at baseline and after treatment . Results : After 4 months of treatment , patients significantly ( p < 0.001 ) improved their electroneurographic parameters and their perception of pain . Best improvements were observed in sensory nerve conduction . Conclusion : The combination of two powerful antioxidant agents leads to improvement in both subjective and objective parameters in patients with diabetic neuropathy . New profitable directions for investigations are opened for a non-invasive treatment of diabetic neuropathy in the future Vascular dysfunction , including impaired perfusion has a pivotal role in the pathogenesis of microvascular complications in diabetes mellitus . Both pentoxifylline ( PF ) and pentosan polysulphate ( PPS ) are known to improve microcirculation . Antioxidant and antiproteinuric effects of PF are also known . In a placebo-controlled study , we determined the possible efficacy of PF-PPS combination therapy on diabetic neuropathy and nephropathy in type 2 diabetic patients . Patients in Verum group ( n = 77 ) received PF-PPS infusions ( 100–100 mg/day ) for 5 days . Control diabetics ( Placebo group ; n = 12 ) were given only saline infusions . Specialized cardiovascular autonomic reflex tests , vibration threshold values and urinary albumin excretion were assessed before and after therapy . In Verum group , autonomic score , indicating the severity of cardiac autonomic dysfunction , decreased after therapy ( p ≤ 0.001 ) . Of the reflexes , deep breath and h and grip tests also improved after therapy ( p ≤ 0.001 ) . Vibration threshold values , an indicator of the loss of sensory nerve function , were increased after therapy ( p ≤ 0.001 ) . Results of cardiac autonomic tests and vibration threshold values remained unaltered in Placebo group . Majority of patients had normalbuminuria , which was not affected by PF-PPS . In conclusion , short-term PF-PPS therapy was effective on cardiovascular autonomic function and vibration perception , whereas it failed to reduce albuminuria within normal range in type 2 diabetic patients Background : Lifestyle factors may be associated with chemotherapy‐induced peripheral neuropathy ( CIPN ) . We examined associations between body mass index ( BMI ) and lifestyle factors with CIPN in the Pathways Study , a prospect i ve cohort of women with invasive breast cancer . Methods : Analyses included 1237 women who received taxane treatment and provided data on neurotoxicity symptoms . Baseline interviews assessed BMI ( normal : < 25 kg/m2 ; overweight : 25‐29.9 kg/m2 ; obese : ≥30 kg/m2 ) , moderate‐to‐vigorous physical activity ( MVPA ) ( low : < 2.5 ; medium : 2.5‐5 ; high : > 5 hours/week ) and fruit/vegetable intake ( low : < 35 servings/week ; high : ≥35 servings/week ) . Baseline and six‐month interviews assessed antioxidant supplement use ( nonuser , discontinued , continued user , initiator ) . CIPN was assessed at baseline , six months , and 24 months using the Functional Assessment of Cancer Therapy‐Taxane Neurotoxicity ( FACT‐NTX ) ; a 10 % decrease was considered clinical ly meaningful . Results : At baseline , 65.6 % of patients in the sample were overweight or obese , 29.9 % had low MVPA , 57.5 % had low fruit/vegetable intake , and 9.5 % reported antioxidant supplement use during treatment . In multivariable analyses , increased CIPN was more likely to occur in overweight ( odds ratio [ OR ] = 2.37 , 95 % confidence interval [ CI ] = 1.19 to 4.88 ) and obese patients ( OR = 3.21 , 95 % CI = 1.52 to 7.02 ) compared with normal weight patients at 24 months and less likely to occur in patients with high MVPA compared with those with low MVPA at six ( OR = 0.56 , 95 % CI = 0.34 to 0.94 ) and 24 months ( OR = 0.43 , 95 % CI = 0.21 to 0.87 ) . Compared with nonusers , patients who initiated antioxidant use during treatment were more likely to report increased CIPN at six months ( OR = 3.81 , 95 % CI = 1.82 to 8.04 ) . Conclusions : Obesity and low MVPA were associated with CIPN in breast cancer patients who received taxane treatment OBJECTIVE This open-label study was performed to evaluate the efficacy and safety of oral treatment with the antioxidant alpha-lipoic acid ( ALA , thioctic acid ) in Korean diabetic patients with distal symmetric polyneuropathy ( DSP ) . SUBJECTS AND METHODS Thioctic acid was administered orally using 600 mg once daily for 8 weeks in 61 diabetic patients with symptomatic polyneuropathy . Neuropathic symptoms ( pain , burning sensation , paresthesia , and numbness ) were scored at baseline as well as at 4 and 8 weeks following treatment . In addition , neurological assessment was carried out before and after 8 weeks of treatment , and an overall evaluation was performed at the end of treatment . The primary endpoint was the response rate after 8 weeks of treatment , defined as an improvement in the Total Symptom Score ( TSS ) of > or = 30 % . RESULTS Efficacy was evaluated in 38 patients who had completed the study according to the protocol . Safety was evaluated in all 61 patients who had taken the study medication . Fasting blood glucose and HbA(1)c did not change during the study . The response rate after 8 weeks was 71.4 % . At 4 weeks , the response rate was 47.4 % . The TSS significantly decreased at 4 weeks , which decreased further at 8 weeks ( P<.05 ) . All the individual scores for neuropathic symptoms ( pain , burning sensation , paresthesia , and numbness ) were also significantly reduced at 4 weeks and further decreased at 8 weeks ( P<.05 ) . The duration of diabetes , severity and duration of diabetic polyneuropathy , and all the other demographic and metabolic parameters did not demonstrate an effect on the response rate . The parameters of neurological assessment ( ankle reflexes , pin-prick test , 10-g monofilament test ) and quantitative sensory tests ( vibration , warm and cold sensation ) were not influenced by 8 weeks of treatment with 600 mg of oral thioctic acid per day . Overall efficacy rated as " good/fair " was 86.8 % by the physician and 76.3 % by the patients at the end of an 8-week treatment period . Eleven episodes ( 18.0 % ) of adverse events ( possibly , probably , definitely related ) were reported in seven patients ( 11.5 % ) . CONCLUSION These findings indicate that oral treatment with thioctic acid at a dose of 600 mg/day for 8 weeks improved symptoms of polyneuropathy in Korean diabetic patients without causing serious adverse events Previous studies have suggested that prolidase and nitric oxide ( NO ) regulate many processes , such as collagen synthesis and matrix remodeling . Oxidative stress plays an important role in the development of microvascular complications in diabetic patients . Data on serum prolidase activity in patients with diabetes mellitus or diabetic neuropathy ( DN ) are limited and conflicting . The aim of this study was to measure serum prolidase activity , NO , total antioxidant status ( TAS ) , and malondialdehyde ( MDA ) levels in patients with DN . Forty-five patients with DN and 40 healthy controls were enrolled . Serum prolidase activity , TAS , MDA , and NO levels were determined . Serum MDA and NO levels were significantly higher in DN patients than controls ( p = 0.002 , p = 0.001 , respectively ) , while prolidase activity and TAS levels were lower ( p = 0.003 , p = 0.001 , respectively ) . Prolidase activity was negatively correlated with NO and MDA ( r = −0.911 , p < 0.001 ; r = −0.905 , p < 0.001 , respectively ) , while positively correlated with TAS ( r = 0.981 , p < 0.001 ) in DN patients . The current study is the first showing the decreased serum prolidase enzyme activity . Our results suggest that decreased collagen turnover may occur in DN patients , who have increased oxidative stress and increased NO levels . Decreased prolidase activity seems to be associated with increased NO levels and oxidative stress along with decreased antioxidant levels in DN . Therefore , decreased prolidase activity may play a role in pathogenesis of DN . Prospect i ve clinical studies are necessary to confirm these findings RATIONALE Diabetic peripheral neuropathy is common and causes significant morbidity . Obstructive sleep apnea ( OSA ) is also common in patients with type 2 diabetes . Because OSA is associated with inflammation and oxidative stress , we hypothesized that OSA is associated with peripheral neuropathy in type 2 diabetes . OBJECTIVES To assess the relationship between OSA and peripheral neuropathy in patients with type 2 diabetes . METHODS A cross-sectional study of adults with type 2 diabetes recruited r and omly from the diabetes clinic of two UK hospitals . MEASUREMENTS AND MAIN RESULTS Peripheral neuropathy was diagnosed using the Michigan Neuropathy Screening Instrument . OSA ( apnea-hypopnea index ≥ 5 events/h ) was assessed using home-based , multichannel respiratory monitoring . Serum nitrotyrosine was measured by ELISA , lipid peroxide by spectrophotometer , and microvascular function by laser speckle contrast imaging . Two hundred thirty-four patients ( mean [ SD ] age , 57 [ 12 ] yr ) were analyzed . OSA prevalence was 65 % ( median apnea-hypopnea index , 7.2 ; range , 0 - 93 ) , 40 % of which were moderate to severe . Neuropathy prevalence was higher in patients with OSA than those without ( 60 % vs. 27 % , P < 0.001 ) . After adjustment for possible confounders , OSA remained independently associated with diabetic neuropathy ( odds ratio , 2.82 ; 95 % confidence interval , 1.44 - 5.52 ; P = 0.0034 ) . Nitrotyrosine and lipid peroxide levels ( n = 102 , 74 with OSA ) were higher in OSA and correlated with hypoxemia severity . Cutaneous microvascular function ( n = 71 , 47 with OSA ) was impaired in OSA . CONCLUSIONS We describe a novel independent association between diabetic peripheral neuropathy and OSA . We identified increased nitrosative/oxidative stress and impaired microvascular regulation as potential mechanisms . Prospect i ve and interventional studies are needed to assess the impact of OSA and its treatment on peripheral neuropathy development and progression in patients with type 2 diabetes INTRODUCTION Diabetic polyneuropathy aetiology is based on oxidative stress generation due to production of reactive oxygen species . Ubiquinone is reduced to ubiquinol and redistributed into lipoproteins , possibly to protect them from oxidation . AIMS To evaluate the impact of oral ubiquinone in diabetic polyneuropathy , and the role of lipid peroxidation ( LPO ) and nerve growth factor ( NGF-β ) . METHODS We conducted a double-blind , placebo-controlled clinical trial , patients were r and omized to ubiquinone ( 400 mg ) or placebo daily for 12 weeks . Main outcomes were clinical scores , nerve conduction studies , LPO , NGF-β and safety . RESULTS Twenty four patients on experimental group and twenty five on control group met the inclusion criteria ( mean age 56 years , 22 % male and 78 % female , mean evolution of type 2 diabetes mellitus 10.7 years ) . Significant improvement on experimental vs control group was found in neuropathy symptoms score ( from 2.5 ± 0.7 to 1 ± 0.8 , p<0.001 ) , neuropathy impairment score ( 5.5 ± 4 to 3.1 ± 2.6 , p<0.001 ) , sural sensory nerve amplitude ( 13.0 ± 6.1 to 15.8 ± 5.1 μV , p=0.049 ) , peroneal motor nerve conduction velocity ( 39.7 ± 5.0 to 47.8 ± 4.9 m/s , p=0.047 ) , and ulnar motor nerve conduction velocity ( 48.8 ± 6.8 to 54.5 ± 6.1 m/s , p=0.046 ) . There was a significant reduction of LPO in subjects treated with ubiquinone vs placebo ( 16.7 ± 8.6 and 23.2 ± 15.8 nmol/mL , respectively ) with p<0.05 , and NGF-β did not change ( control 66.5 ± 26.7 vs. experimental 66.8 ± 28.4 pg/mL , p=0.856 ) . No drug-related adverse reactions were reported . CONCLUSIONS Twelve weeks treatment with ubiquinone improves clinical outcomes and nerve conduction parameters of diabetic polyneuropathy ; furthermore , it reduces oxidative stress without significant adverse events OBJECTIVE Because alpha-lipoic acid ( ALA ) , a potent antioxidant , prevents or improves nerve conduction attributes , endoneurial blood flow , and nerve ( Na(+ ) K(+ ) ATPase activity in experimental diabetes and in humans and may improve positive neuropathic sensory symptoms , in this report we further assess the safety and efficacy of ALA on the Total Symptom Score ( TSS ) , a measure of positive neuropathic sensory symptoms . RESEARCH DESIGN AND METHODS Metabolically stable diabetic patients with symptomatic ( stage 2 ) diabetic sensorimotor polyneuropathy ( DSPN ) were r and omized to a parallel , double-blind study of ALA ( 600 mg ) ( n = 60 ) or placebo ( n = 60 ) infused daily intravenously for 5 days/week for 14 treatments . The primary end point was change of the sum score of daily assessment s of severity and duration of TSS . Secondary end points were sum scores of neuropathy signs ( NIS ) , symptoms ( NSC ) , attributes of nerve conduction , quantitative sensation tests ( QSTs ) , and an autonomic test . RESULTS At r and omization , the groups were not significantly different by the criteria of metabolic control or neuropathic end points . After 14 treatments , the TSS of the ALA group had improved from baseline by an average of 5.7 points and the placebo group by an average of 1.8 points ( P < 0.001 ) . Statistically significant improvement from baseline of the ALA , as compared with the placebo group , was also found for each item of the TSS ( lancinating and burning pain , asleep numbness and prickling ) , NIS , one attribute of nerve conduction , and global assessment of efficacy . CONCLUSIONS Intravenous racemic ALA , a potent antioxidant , rapidly and to a significant and meaningful degree , improved such positive neuropathic sensory symptoms as pain and several other neuropathic end points . This improvement of symptoms was attributed to improved nerve pathophysiology , not to increased nerve fiber degeneration . Because of its safety profile and its effect on positive neuropathic sensory symptoms and other neuropathic end points , this drug appears to be a useful ancillary treatment for the symptoms of diabetic polyneuropathy The oxidative modification of low-density lipoprotein ( LDL ) plays a central role in the initiation and acceleration of atherosclerosis . Human serum paraoxonase ( PON1 ) is associated with high-density lipoprotein ( HDL ) and has been shown to reduce the susceptibility of LDL to lipid peroxidation . We investigated whether circulating oxidized LDL ( Ox-LDL ) levels were associated with diabetic vascular complications , and whether the enzymatic activity and gene polymorphisms of PON1 influenced Ox-LDL concentrations in vivo . There was no difference in the plasma Ox-LDL concentrations between diabetic patients with and without macrovascular diseases . However , Ox-LDL concentrations corrected by LDL-cholesterol ( OxLDL/LDL-C ) or apolipoprotein B ( apoB ) concentrations ( Ox-LDL/apoB ) , which probably reflect the proportion of oxidatively modified LDL to total LDL particles , were significantly higher in patients with macrovascular diseases than in those without . In addition , patients with peripheral neuropathy had a significantly higher Ox-LDL/apoB ratio than patients without this complication . The genotype TT of -108C/T polymorphism in the promoter region of the PON1 gene , which is associated with decreased PON1 expression , showed a significantly higher Ox-LDL/apoB ratio than genotypes TC or CC ( TT : 0.60 + /- 0.15 , CT + CC : 0.55 + /- 0.11 , P = .02 ) . Stepwise multiple regression analysis for Ox-LDL concentration revealed that the -108C/T polymorphism , subsequently to apoB concentration , was identified as a significant contributor . In summary , the Ox-LDL/apoB ratio was associated with macrovascular disease and peripheral neuropathy in Japanese patients with type 2 diabetes . Increased Ox-LDL/apoB may result , at least partly , from reduced serum antioxidant capacity in the diabetic state , including the attenuation of PON1 action . Increased Ox-LDL/apoB could be a significant marker for susceptibility to vascular complications in diabetic patients Oxidative stress is implicated in the pathogenesis of experimental diabetic neuropathy , but prospect i ve studies in diabetic patients are lacking . We aim ed to evaluate whether the plasma levels of various biomarkers of oxidative stress predict the progression of diabetic neuropathy and mortality over 6 years . We followed 89 diabetic patients aged 54 ± 14 years ( 59 % with polyneuropathy ) , 72 of whom underwent nerve function re assessment after 6.2 ± 0.8 years , whereas 17 died after 4.2 ± 1.0 years . Plasma markers of oxidative stress at baseline included superoxide anion , hypochlorous acid , peroxynitrite , 8-iso-prostagl and in F2α , vitamin E/lipid ratio , and vitamin C. Neuropathy was assessed by symptoms and deficits , motor and sensory nerve conduction velocity ( MNCV , SNCV ) , vibration perception thresholds ( VPT ) , thermal detection thresholds , and heart rate variability ( HRV ) . Despite a reduction in HbA1c by 1.4 ± 1.6 % ( p < 0.001 ) , median SNCV , sural SNCV , peroneal MNCV , malleolar VPT , and warm TDT deteriorated after 6 years ( all p < 0.05 ) . In multivariate models , increased superoxide generation was associated with a decline in median SNCV ( β = −0.997 ; p = 0.036 ) and deterioration in HRV at rest ( OR 1.63 [ 95 % CI 1.09–2.44 ] ; p = 0.017 ) over 6 years . Low vitamin E/lipid ratio tended to predict a decrease in peroneal MNCV ( β = 0.781 ; p = 0.057 ) and an increase in malleolar VPT ( β = −0.725 ; p = 0.077 ) . Plasma superoxide generation was associated with an increased risk of mortality ( HR 23.2 [ 95 % CI 1.05–513 ] ; p = 0.047 ) . In conclusion , increased plasma superoxide generation predicted the decline in sensory and cardiac autonomic nerve function and mortality over 6 years in diabetic patients , but larger studies are required for confirmation BACKGROUND Mitochondrial toxicity can be induced by reverse-transcriptase inhibitors , and an association between levels of mitochondrial DNA ( mtDNA ) per cell and lipodystrophy , peripheral neuropathy , and HIV infection per se has been suggested . Studies aim ed at increasing the oxidative capacity in HIV-infected patients have been sparse . METHODS Levels of mtDNA in fat and peripheral blood mononuclear cells ( P BMC s ) from 25 HIV infected patients and 10 healthy control subjects were studied with real-time PCR analysis . A placebo-controlled and double-blind design was used to assign individuals to receive either 100 mg of coenzyme Q twice daily for 3 months or a matching placebo regimen . Levels of mtDNA and other parameters were assessed before and after the intervention period . RESULTS The mean number of mtDNA copies per cell was lower in fat tissue obtained from patients with peripheral neuropathy ( 1547 mtDNA copies/cell ; P=.045 ) , patients with lipodystrophy ( 1732 mtDNA copies/cell ; P=.003 ) and in HIV patients with no complications associated with highly active antiretroviral therapy ( 2935 mtDNA copies/cell ; P=.078 ) , compared with healthy control subjects ( 6198 mtDNA copies/cell ) . No clear difference was seen in mtDNA content in P BMC s. Coenzyme Q therapy improved the general condition of patients ( P=.005 ) and caused a reversible increase in peripheral neuropathy pain ( P=.048 ) . Compared with placebo , treatment with coenzyme Q did not result in changes in mtDNA levels in fat cells or in P BMC s after the treatment period . CONCLUSIONS Levels of mtDNA in fat tissue , but not in P BMC s , were associated with peripheral neuropathy and lipodystrophy . High-dose coenzyme Q therapy increased well-being in asymptomatic HIV-infected patients and those with lipodystrophy , as well as in control subjects , but aggravated pain in patients with peripheral neuropathy OBJECTIVE Pre clinical data suggest elesclomol increases oxidative stress and enhances sensitivity to cytotoxic agents . The objective of this prospect i ve multicenter phase 2 trial was to estimate the activity of IV elesclomol plus weekly paclitaxel in patients with platinum-resistant recurrent ovarian , tubal or peritoneal cancer through the frequency of objective tumor responses ( ORR ) . METHODS Patients with measurable disease , acceptable organ function , performance status ≤ 2 , and one prior platinum containing regimen were eligible . A two-stage design was utilized with a target sample size of 22 and 30 subjects , respectively . Prior Gynecologic Oncology Group studies within the same population involving single agent taxanes showed an ORR of approximately ( 20 % ) and served as a historical control for direct comparison . The present study was design ed to determine if the regimen had an ORR of ≥40 % with 90 % power . RESULTS Fifty-eight patients were enrolled , of whom 2 received no study treatment and were inevaluable . The median number of cycles was 3 ( 268 total cycles , range 1 - 18 ) . The number of patients responding was 11 ( 19.6 % ; 90 % CI 11.4 % to 30.4 % ) with one complete response . The median progression-free survival and overall survival was 3.6 months and 13.3 months , respectively . The median ORR duration was 9.2 months . Percentages of subjects with grade 3 toxicity included : Neutropenia 9 % ; anemia 5 % ; metabolic 5 % ; nausea 4 % ; infection 4 % ; neurologic ( mostly neuropathy ) 4 % ; and vascular ( mostly thromboembolism ) 4 % . There were no grade 4 toxicities reported . CONCLUSIONS This combination was well tolerated but is unworthy of further investigation based on the proportion responding [ Clinical Trials.gov Identifier : NCT00888615 ] Abstract Purpose : Oxaliplatin causes disabling acute and chronic peripheral neuropathy . We explored the preventive effects of calmangafodipir , mimicking the mitochondrial enzyme manganese superoxide dismutase , thereby protecting cells from oxidative stress , in a placebo-controlled , double-blinded r and omised phase II study ( Clinical Trials.gov . NCT01619423 ) in patients with metastatic colorectal cancer ( mCRC ) . Patient and methods : mCRC patients treated with modified FOLFOX-6 ( folinic acid 200 mg/m2 , 5-fluorouracil bolus 400 mg/m2 , oxaliplatin 85 mg/m2 and 5-fluorouracil 2400 mg/m2 continuous infusion for 46 h ) every fortnight for 8 cycles in first or second line were eligible . Calmangafodipir was given in a phase I dose-finding and in a phase II placebo-controlled study , as a 5-min infusion 10 min prior to oxaliplatin . Neurotoxicity was evaluated by the physician using the Oxaliplatin Sanofi Specific Scale and by the patient using the cold allodynia test and the Leonard scale . Results : Eleven patients were included in phase I without any detectable toxicity to calmangafodipir . In the phase II study , 173 patients were r and omised to placebo ( n = 60 ) , calmangafodipir 2 µmol/kg ( n = 57 ) and calmangafodipir 5 µmol/kg ( n = 45 , initially 10 µmol/kg , n = 11 ) . Calmangafodipir-treated patients ( all three doses pooled ) had less physician grade d neurotoxicity ( odds ratio ( 90 % confidence interval one-sided upper level ) 0.62(1.15 ) , p = .16 ) , significantly less problems with cold allodynia ( mean 1.6 versus 2.3 , p < .05 ) and significantly fewer sensory symptoms in the Leonard scale ( cycle 1–8 mean 1.9 versus 3.0 , p < .05 and during follow-up after 3 and 6 months , mean 3.5 versus 7.3 , p < .01 ) . Response rate , progression-free and overall survival did not differ among groups . Conclusions : Calmangafodipir at a dose of 5 µmol/kg appears to prevent the development of oxaliplatin-induced acute and delayed CIPN without apparent influence on tumour outcomes Glutathione peroxidase-1 ( GPx-1 ) is an endogenous anti-oxidant enzyme . The T allele of the GPx-1 rs1050450 ( C > T ) gene variant is associated with reduced enzyme activity . Our aim was to examine the association between this gene variant and peripheral neuropathy in two cross-sectional sample s of subjects with diabetes : ( i ) 773 Caucasian subjects were genotyped from the UCL Diabetes and Cardiovascular disease Study ( UDACS ) and ( ii ) 382 Caucasian subjects from the Ealing Diabetes Study ( EDS ) . Peripheral neuropathy status ( and oxidised-LDL [ Ox-LDL : LDL ] and plasma Total Ant-ioxidant Status [ TAOS ] in UDACS ) , were analysed in relation to genotype . We observed that : ( i ) In UDACS , the odds ratio ( OR ) for peripheral neuropathy in the T allele carriers compared to the CC genotype was 1.61 [ 1.10 - 2.28 ] , p = 0.01 . This remained significant after adjustment for other risk factors . Ox-LDL : LDL ratio was significantly elevated in T allele carriers ( CC vs. CT/TT : 16.3 ± 2.4 v 18.0 ± 2.9 U/mmol LDL , p = 0.02 ) . ( ii ) In EDS , the OR for peripheral neuropathy in the T allele carriers compared to the CC genotype was 1.95 [ 1.11 - 3.42 ] , p = 0.02 . This remained significant after adjustment for other risk factors . In conclusion , we observed a significant association between the T allele and peripheral neuropathy and LDL oxidation . This is the first paper to examine the rs1050450 variant in two sample s of Caucasian subjects with diabetes . Prospect i ve analysis of the gene variant is required in diabetic and healthy cohorts with measured plasma markers of oxidative stress to investigate the described association further BACKGROUND Diabetes is a chronic disease characterized by elevated blood glucose levels . The appropriate goals in the management of diabetes include maintaining blood glucose levels as close to the normal range as possible , minimizing the adverse effects of free radicals by enhancing antioxidant defenses . Supplementation with appropriate vitamins may therefore be of value in the prevention and treatment of diabetes . METHODS A total of 92 patients with diabetic neuropathy were enrolled in this r and omized controlled study from the general medicine department of a tertiary care hospital . Patients were r and omized into two groups viz . , usual care ( n = 46 ) and intervention group ( n = 46 ) . Usual care group patients received pregabalin with oral hypoglycemic agents . Patients in the intervention group received vitamin-E along with their regular medicines . Pain intensity and quality of life ( QoL ) of patients were assessed using Neuropathy Pain Score and R AND 36 question naire . Blood sample s were analyzed for the levels of r and om blood sugar level and HbA(1c ) at the baseline and on the 12th week . RESULTS Significant ( p < 0.05 ) decrease in the r and om blood sugar level was observed in intervention group when compared with the usual care group and a significant ( p < 0.01 ) reduction in total pain score , and a significant ( p < 0.05 ) improvement in physical health after 12 week treatment of vitamin-E was observed . CONCLUSION The study concluded that vitamin-E is a natural antioxidant and it is found to be effective in reducing pain score in diabetic neuropathy patients . The future studies may be directed towards extended duration of action |
1,836 | 32,367,009 | Olaparib has been the first agent showing a benefit in terms of rPFS and ORR alone or in combination with abiraterone plus prednisone in patients with DDR deficiency prostate cancer . | A great number of DNA-damage repair ( DDR ) pathways have been recognized to be frequently dysregulated in advanced stages of prostate cancer .
DNA-repair defects in prostate cancer represents a clinical ly relevant disease subset .
Tumors whose ability to repair double-str and DNA breaks by homologous recombination is compromised , are highly sensitive to blockade of the repair of DNA single-str and breaks via the inhibition of the enzyme poly(ADP ) ribose polymerase ( PARP ) . | Summary Background Long-term hormone therapy has been the st and ard of care for advanced prostate cancer since the 1940s . STAMPEDE is a r and omised controlled trial using a multiarm , multistage platform design . It recruits men with high-risk , locally advanced , metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy . We report primary survival results for three research comparisons testing the addition of zoledronic acid , docetaxel , or their combination to st and ard of care versus st and ard of care alone . Methods St and ard of care was hormone therapy for at least 2 years ; radiotherapy was encouraged for men with N0M0 disease to November , 2011 , then m and ated ; radiotherapy was optional for men with node-positive non-metastatic ( N+M0 ) disease . Stratified r and omisation ( via minimisation ) allocated men 2:1:1:1 to st and ard of care only ( SOC-only ; control ) , st and ard of care plus zoledronic acid ( SOC + ZA ) , st and ard of care plus docetaxel ( SOC + Doc ) , or st and ard of care with both zoledronic acid and docetaxel ( SOC + ZA + Doc ) . Zoledronic acid ( 4 mg ) was given for six 3-weekly cycles , then 4-weekly until 2 years , and docetaxel ( 75 mg/m2 ) for six 3-weekly cycles with prednisolone 10 mg daily . There was no blinding to treatment allocation . The primary outcome measure was overall survival . Pairwise comparisons of research versus control had 90 % power at 2·5 % one-sided α for hazard ratio ( HR ) 0·75 , requiring roughly 400 control arm deaths . Statistical analyses were undertaken with st and ard log-rank-type methods for time-to-event data , with hazard ratios ( HRs ) and 95 % CIs derived from adjusted Cox models . This trial is registered at Clinical Trials.gov ( NCT00268476 ) and ControlledTrials.com ( IS RCT N78818544 ) . Findings 2962 men were r and omly assigned to four groups between Oct 5 , 2005 , and March 31 , 2013 . Median age was 65 years ( IQR 60–71 ) . 1817 ( 61 % ) men had M+ disease , 448 ( 15 % ) had N+/X M0 , and 697 ( 24 % ) had N0M0 . 165 ( 6 % ) men were previously treated with local therapy , and median prostate-specific antigen was 65 ng/mL ( IQR 23–184 ) . Median follow-up was 43 months ( IQR 30–60 ) . There were 415 deaths in the control group ( 347 [ 84 % ] prostate cancer ) . Median overall survival was 71 months ( IQR 32 to not reached ) for SOC-only , not reached ( 32 to not reached ) for SOC + ZA ( HR 0·94 , 95 % CI 0·79–1·11 ; p=0·450 ) , 81 months ( 41 to not reached ) for SOC + Doc ( 0·78 , 0·66–0·93 ; p=0·006 ) , and 76 months ( 39 to not reached ) for SOC + ZA + Doc ( 0·82 , 0·69–0·97 ; p=0·022 ) . There was no evidence of heterogeneity in treatment effect ( for any of the treatments ) across prespecified subsets . Grade 3–5 adverse events were reported for 399 ( 32 % ) patients receiving SOC , 197 ( 32 % ) receiving SOC + ZA , 288 ( 52 % ) receiving SOC + Doc , and 269 ( 52 % ) receiving SOC + ZA + Doc . Interpretation Zoledronic acid showed no evidence of survival improvement and should not be part of st and ard of care for this population . Docetaxel chemotherapy , given at the time of long-term hormone therapy initiation , showed evidence of improved survival accompanied by an increase in adverse events . Docetaxel treatment should become part of st and ard of care for adequately fit men commencing long-term hormone therapy . Funding Cancer Research UK , Medical Research Council , Novartis , Sanofi-Aventis , Pfizer , Janssen , Astellas , NIHR Clinical Research Network , Swiss Group for Clinical Cancer Research Background Abiraterone acetate plus prednisolone improves survival in men with relapsed prostate cancer . We assessed the effect of this combination in men starting long‐term and rogen‐deprivation therapy ( ADT ) , using a multigroup , multistage trial design . Methods We r and omly assigned patients in a 1:1 ratio to receive ADT alone or ADT plus abiraterone acetate ( 1000 mg daily ) and prednisolone ( 5 mg daily ) ( combination therapy ) . Local radiotherapy was m and ated for patients with node‐negative , nonmetastatic disease and encouraged for those with positive nodes . For patients with nonmetastatic disease with no radiotherapy planned and for patients with metastatic disease , treatment continued until radiologic , clinical , or prostate‐specific antigen ( PSA ) progression ; otherwise , treatment was to continue for 2 years or until any type of progression , whichever came first . The primary outcome measure was overall survival . The intermediate primary outcome was failure‐free survival ( treatment failure was defined as radiologic , clinical , or PSA progression or death from prostate cancer ) . Results A total of 1917 patients underwent r and omization from November 2011 through January 2014 . The median age was 67 years , and the median PSA level was 53 ng per milliliter . A total of 52 % of the patients had metastatic disease , 20 % had node‐positive or node‐indeterminate nonmetastatic disease , and 28 % had node‐negative , nonmetastatic disease ; 95 % had newly diagnosed disease . The median follow‐up was 40 months . There were 184 deaths in the combination group as compared with 262 in the ADT‐alone group ( hazard ratio , 0.63 ; 95 % confidence interval [ CI ] , 0.52 to 0.76 ; P<0.001 ) ; the hazard ratio was 0.75 in patients with nonmetastatic disease and 0.61 in those with metastatic disease . There were 248 treatment‐failure events in the combination group as compared with 535 in the ADT‐alone group ( hazard ratio , 0.29 ; 95 % CI , 0.25 to 0.34 ; P<0.001 ) ; the hazard ratio was 0.21 in patients with nonmetastatic disease and 0.31 in those with metastatic disease . Grade 3 to 5 adverse events occurred in 47 % of the patients in the combination group ( with nine grade 5 events ) and in 33 % of the patients in the ADT‐alone group ( with three grade 5 events ) . Conclusions Among men with locally advanced or metastatic prostate cancer , ADT plus abiraterone and prednisolone was associated with significantly higher rates of overall and failure‐free survival than ADT alone . ( Funded by Cancer Research U.K. and others ; STAMPEDE Clinical Trials.gov number , NCT00268476 , and Current Controlled Trials number , IS RCT N78818544 . |
1,837 | 26,231,507 | The association of prenatal mercury exposure with lower high-frequency b and scores ( thought to reflect parasympathetic activity ) in several studies , in particular the inverse association of cord blood mercury levels with the coefficient of variation of the R-R intervals and with low-frequency and high-frequency b and s at 14 years of age in the Faroe Isl and s birth cohort study , suggests that early mercury exposure could have a long-lasting effect on cardiac parasympathetic activity . | Background Mercury affects the nervous system and has been implicated in altering heart rhythm and function .
We sought to better define its role in modulating heart rate variability , a well-known marker of cardiac autonomic function . | PURPOSE To examine the longitudinal association between age and intraocular pressure ( IOP ) in a large sample of Korean men and women . METHODS We conducted a prospect i ve cohort study of 274,064 young and middle-aged Korean adults with normal fundoscopic findings , following them from January 1 , 2002 , to February 28 , 2010 . Health exams were scheduled annually or biennially . At each visit , IOP was measured in both eyes using automated noncontact tonometers . The longitudinal change in IOP with age was evaluated using three-level mixed models for longitudinal paired-eye data , accounting for correlations between paired eyes and repeated measurements over time . RESULTS In fully adjusted models , the average longitudinal change in IOP per 1-year increase in age was -0.065 mm Hg ( 95 % confidence interval [ CI ] -0.068 to -0.063 ) , with marked sex differences ( P < 0.001 ) . In men , the average annual IOP change was -0.093 mm Hg ( 95 % CI -0.096 to -0.091 ) throughout follow-up . In women , the average annual IOP change was -0.006 mm Hg ( 95 % CI -0.010 to -0.003 ) , with a relatively flat association in the age range of 30 to 59 years and more marked annual decreases at younger and older ages . CONCLUSIONS Intraocular pressure was inversely associated with age in a large cohort of Korean adults attending health-screening visits . For men , this inverse association was observed throughout the entire age range , while for women it was evident only in younger ( < 30 years of age ) and older ( ≥60 years of age ) women , with no association in women aged 30 to 59 . Further research is needed to better underst and the underlying mechanisms and to reconsider cutoffs for defining high IOP by age and sex groups in Asian population OBJECTIVE To vali date an FFQ for the assessment of dietary EPA and DHA against their relative concentrations in red blood cells ( RBC ) . DESIGN Cross-sectional analysis of baseline data . Intakes of marine food products and EPA and DHA were estimated by FFQ on the basis of consumption of marine food products in the last month . Fatty acid composition of RBC membranes was quantified by GC . SETTING Saint-François d'Assise Hospital , Québec , Canada . SUBJECTS A total of sixty-five middle-aged women who participated in a r and omized clinical trial . RESULTS Spearman 's correlation coefficient between intake of EPA , DHA and EPA + DHA and their corresponding concentration in RBC was 0.46 , 0.40 and 0.42 , respectively ( all P < 0.05 ) . Multiple regression analysis of EPA+DHA intake and RBC EPA + DHA concentration indicated positive and significant correlations for oily fish ( beta = 0.44 , 95 % CI 0.16 , 0.72 , P = 0.0027 ) , total fish ( beta = 0.42 , 95 % CI 0.19 , 0.64 , P = 0.0005 ) and marine food products ( beta = 0.42 , 95 % CI 0.20 , 0.64 , P = 0.0003 ) . No other marine food products significantly predicted RBC EPA + DHA concentration . CONCLUSIONS Although the present validation study was undertaken among middle-aged women with low consumption of marine food products ( <3 servings/week ) , our FFQ provided estimates of EPA and DHA intakes that correlated fairly well with their RBC concentrations . However , the absence of correlations between EPA + DHA intakes from different marine species suggests that a minimum EPA + DHA intake is necessary to observe a relationship with RBC EPA + DHA concentrations OBJECTIVE To determine whether heart function in childhood is affected by exposure to methylmercury ( MeHg ) from seafood . STUDY DESIGN Prospect i ve study of a Faroese birth cohort ( N=1022 ) . Examinations at ages 7 and 14 years included blood pressure , heart rate variability ( HRV ) and its frequency components of autonomic origin , and brainstem auditory evoked potentials ( BAEPs ) . Mercury concentrations were determined in cord blood and in the child 's hair . RESULTS Both low-frequency ( LF ) and high-frequency ( HF ) activities decreased by about 25 % from 7 to 14 years ; they correlated well with the blood pressures . A doubling of prenatal MeHg exposure was associated with a decrease in LF and HF powers of about 6.7 % ( P=.04 ) and in the coefficient of variation of the electrocardiographic R-R interval of 2.7 % ( P=.04 ) at age 14 years . No discernible effect on blood pressure was apparent . Decreased LF variability was associated with increased latency of BAEP peak III , but adjustment for MeHg exposure substantially attenuated this correlation . CONCLUSIONS Methylmercury exposure was associated with decreased sympathetic ( LF ) and parasympathetic ( HF ) modulation of the HRV . Parallel MeHg-related delays of BAEP latencies may be caused by underlying MeHg neurotoxicity to brainstem nuclei |
1,838 | 24,470,982 | There was a lack of congruence among studies in the way adherence was measured and reported .
No single intervention has been seen to be universally successful , particularly for patients from ethnic minority background | null | null |
1,839 | 26,681,681 | Compelling evidence from a meta- analysis of trial data of > 18,000 patients supports clinical ly significant benefits of bisphosphonates on the development of bone metastases and breast cancer mortality in post-menopausal women or those receiving ovarian suppression therapy . | Bisphosphonates have been studied in r and omised trials in early breast cancer to investigate their ability to prevent cancer treatment-induced bone loss ( CTIBL ) and reduce the risk of disease recurrence and metastasis .
Treatment benefits have been reported but bisphosphonates do not currently have regulatory approval for either of these potential indications .
This consensus paper provides a review of the evidence and offers guidance to breast cancer clinicians on the use of bisphosphonates in early breast cancer . | BACKGROUND The Austrian Breast and Colorectal Cancer Study Group trial-12 ( ABCSG-12 ) bone sub study assesses zoledronic acid for preventing bone loss associated with adjuvant endocrine therapy and reports on long-term findings of bone-mineral density ( BMD ) during 3 years of treatment and 2 years after completing adjuvant treatment with or without zoledronic acid . The aim of this sub study is to gain insight into bone health in this setting . METHODS ABCSG-12 is a r and omised , open-label , phase III , 4-arm trial comparing tamoxifen ( 20 mg/day orally ) and goserelin ( 3.6 mg subcutaneously every 28 days ) versus anastrozole ( 1 mg/day orally ) and goserelin ( 3.6 mg subcutaneously every 28 days ) , both with or without zoledronic acid ( 4 mg intravenously every 6 months ) for 3 years in premenopausal women with endocrine-responsive breast cancer . This prospect i ve bone sub protocol measured BMD at 0 , 6 , 12 , 36 , and 60 months . The primary endpoint of the bone sub study ( secondary endpoint in the main trial ) was change in BMD at 12 months , assessed by dual-energy X-ray absorptiometry in assessable patients . Analyses were intention to treat . Statistical significance was assessed by t tests . The ABCSG-12 trial is registered on the Clinical Trials.gov website , number NCT00295646 . FINDINGS 404 patients were prospect ively included in the bone sub study and r and omly assigned to endocrine therapy alone ( goserelin and anastrozole or goserelin and tamoxifen ; n=199 ) or endocrine therapy concurrent with zoledronic acid ( goserelin , anastrozole , and zoledronic acid or goserelin , tamoxifen , and zoledronic acid ; n=205 ) . After 3 years of treatment , endocrine therapy alone caused significant loss of BMD at the lumbar spine ( -11.3 % , mean difference -0.119 g/cm(2 ) [ 95 % CI -0.146 to -0.091 ] , p<0.0001 ) and trochanter ( -7.3 % , mean difference -0.053 g/cm(2 ) [ -0.076 to -0.030 ] , p<0.0001 ) . In patients who did not receive zoledronic acid , anastrozole caused greater BMD loss than tamoxifen at 36 months at the lumbar spine ( -13.6 % , mean difference -0.141 g/cm(2 ) [ -0.179 to -0.102 ] vs -9.0 % , mean difference -0.095 g/cm(2 ) [ -0.134 to -0.057 ] , p<0.0001 for both ) . 2 years after the completion of treatment ( median follow-up 60 months [ range 15.5 - 96.6 ] ) , patients not receiving zoledronic acid still had decreased BMD at both sites compared with baseline ( lumbar spine -6.3 % , mean difference -0.067 g/cm(2 ) [ -0.106 to -0.027 ] , p=0.001 ; trochanter -4.1 % , mean difference -0.03 g/cm(2 ) [ -0.062 to 0.001 ] , p=0.058 ) . Patients who received zoledronic acid had stable BMD at 36 months ( lumbar spine + 0.4 % , mean difference 0.004 g/cm(2 ) [ -0.024 to 0.032 ] ; trochanter + 0.8 % , mean difference 0.006 g/cm(2 ) [ -0.018 to 0.028 ] ) and increased BMD at 60 months at both sites ( lumbar spine + 4.0 % , mean difference 0.039 g/cm(2 ) [ 0.005 - 0.075 ] , p=0.02 ; trochanter + 3.9 % , mean difference 0.028 g/cm(2 ) [ 0.003 - 0.058 ] , p=0.07 ) compared with baseline . INTERPRETATION Goserelin plus tamoxifen or anastrozole for 3 years without concomitant zoledronic acid caused significant bone loss . Although there was partial recovery 2 years after completing treatment , patients receiving endocrine therapy alone did not recover their baseline BMD levels . Concomitant zoledronic acid prevented bone loss during therapy and improved BMD at 5 years BACKGROUND Aromatase inhibitors effectively prevent breast cancer recurrence and development of new contralateral tumours in postmenopausal women . We assessed the efficacy and safety of the aromatase inhibitor anastrozole for prevention of breast cancer in postmenopausal women who are at high risk of the disease . METHODS Between Feb 2 , 2003 , and Jan 31 , 2012 , we recruited postmenopausal women aged 40 - 70 years from 18 countries into an international , double-blind , r and omised placebo-controlled trial . To be eligible , women had to be at increased risk of breast cancer ( judged on the basis of specific criteria ) . Eligible women were r and omly assigned ( 1:1 ) by central computer allocation to receive 1 mg oral anastrozole or matching placebo every day for 5 years . R and omisation was stratified by country and was done with blocks ( size six , eight , or ten ) . All trial personnel , participants , and clinicians were masked to treatment allocation ; only the trial statistician was unmasked . The primary endpoint was histologically confirmed breast cancer ( invasive cancers or non-invasive ductal carcinoma in situ ) . Analyses were done by intention to treat . This trial is registered , number IS RCT N31488319 . FINDINGS 1920 women were r and omly assigned to receive anastrozole and 1944 to placebo . After a median follow-up of 5·0 years ( IQR 3·0 - 7·1 ) , 40 women in the anastrozole group ( 2 % ) and 85 in the placebo group ( 4 % ) had developed breast cancer ( hazard ratio 0·47 , 95 % CI 0·32 - 0·68 , p<0·0001 ) . The predicted cumulative incidence of all breast cancers after 7 years was 5·6 % in the placebo group and 2·8 % in the anastrozole group . 18 deaths were reported in the anastrozole group and 17 in the placebo group , and no specific causes were more common in one group than the other ( p=0·836 ) . INTERPRETATION Anastrozole effectively reduces incidence of breast cancer in high-risk postmenopausal women . This finding , along with the fact that most of the side-effects associated with oestrogen deprivation were not attributable to treatment , provides support for the use of anastrozole in postmenopausal women at high risk of breast cancer . FUNDING Cancer Research UK , the National Health and Medical Research Council Australia , Sanofi-Aventis , and AstraZeneca PURPOSE Bisphosphonates prevent skeletal-related events in patients with metastatic breast cancer . Their effect in early breast cancer is controversial . Ib and ronate is an orally and intravenously available amino-bisphosphonate with a favorable toxicity profile . It therefore qualifies as potential agent for adjuvant use . PATIENTS AND METHODS The GAIN ( German Adjuvant Intergroup Node-Positive ) study was an open-label , r and omized , controlled phase III trial with a 2 × 2 factorial design . Patients with node-positive early breast cancer were r and omly assigned 1:1 to two different dose-dense chemotherapy regimens and 2:1 to ib and ronate 50 mg per day orally for 2 years or observation . In all , 2,640 patients and 728 events were estimated to be required to demonstrate an increase in disease-free survival ( DFS ) by ib and ronate from 75 % to 79.5 % by using a two-sided α = .05 and 1-β of 80 % . We report here the efficacy analysis for ib and ronate , which was released by the independent data monitoring committee because the futility boundary was not crossed after 50 % of the required DFS events were observed . RESULTS Between June 2004 and August 2008 , 2,015 patients were r and omly assigned to ib and ronate and 1,008 to observation . Patients r and omly assigned to ib and ronate showed no superior DFS or overall survival ( OS ) compared with patients r and omly assigned to observation ( DFS : hazard ratio , 0.945 ; 95 % CI , 0.768 to 1.161 ; P = .589 ; OS : HR , 1.040 ; 95 % CI , 0.763 to 1.419 ; P = .803 ) . DFS was numerically longer if ib and ronate was used in patients younger than 40 years or older than 60 years compared with patients age 40 to 59 years ( test for interaction P = .093 ) . CONCLUSION Adjuvant treatment with oral ib and ronate did not improve outcome of patients with high-risk early breast cancer who received dose-dense chemotherapy PURPOSE Tamoxifen is an effective treatment for metastatic and primary breast cancer and is now being evaluated as a chemoprevention agent in healthy women . Any long-term effects on estrogen-sensitive tissues such as bone may have important therapeutic implication s. METHODS We measured bone mineral density ( BMD ) in the lumbar spine and hip using dual-energy x-ray absorptiometry ( DXA ) in premenopausal and postmenopausal healthy women who participated in our placebo-controlled tamoxifen chemoprevention of breast cancer trial . RESULTS BMD data are now available from 179 women for this analysis . In premenopausal women , BMD decreased progressively in the lumbar spine ( P < .001 ) and in the hip ( P < .05 ) for women on tamoxifen , but not those on placebo . The mean annual loss in lumbar BMD per year over the 3-year study period in tamoxifen-treated compliant women who remained premenopausal throughout the study period was 1.44 % ( 1.88 % calculated on an intent-to-treat basis ) compared with a small gain of 0.24 % per annum for women on placebo ( P < .001 ) . Tamoxifen had the opposite effect in postmenopausal women . The mean annual increase in BMD for women on tamoxifen was 1.17 % in the spine ( P < .005 ) and 1.71 % in the hip ( P < .001 ) compared with a noninsignificant loss for women on placebo . CONCLUSION These results indicate that tamoxifen treatment is associated with a significant loss of BMD in premenopausal women , whereas it prevents bone loss in postmenopausal women . These adverse and beneficial effects of tamoxifen should be considered in the assessment of the therapeutic benefits for both the adjuvant treatment and the chemoprevention of breast cancer BACKGROUND There is strong evidence for the isolated tumour cells ( ITCs ) in the bone marrow of breast cancer patients having prognostic impact both at primary diagnosis and during recurrence-free follow-up . The goal of this study was to investigate the therapeutic efficacy of zoledronate on the persistence of ITC . PATIENTS AND METHODS A total of 172 primary breast cancer patients without evidence of distant recurrence but detection of ITC in bone marrow were followed up . Zoledronate was administered every 4 weeks for 6 months to 31 patients who had completed surgery and adjuvant chemotherapy . In a matched-pair analysis , these patients were compared to 141 patients who did not receive additional zoledronate treatment . The bone marrow was re-examined after a median of 7.9 months ( SD 0.89 ) and 11.5 months ( SD 12.41 ; p=0.11 ) , respectively . Patients were followed-up prospect ively for a median of 39 months after the first aspiration . RESULTS While ITCs were detected in all 172 patients at the time of first bone marrow aspiration , ITCs were detected in four patients ( 13 % ) following 6 months of zoledronate therapy in contrast to 38 patients ( 27 % ) of the control group ( p=0.099 ) . The reduction in cell numbers between the first and second aspiration reached statistical significance in the zoledronate group ( p=0.02 vs. p=0.14 ) . Persistent ITCs at the follow-up aspiration were associated with reduced recurrence-free survival ( p=0.05 ) . CONCLUSION These results indicate a potential antineoplastic effect of the cell cycle-independent agent zoledronate on persisting ITCs in a dormant state PURPOSE In the majority of premenopausal breast cancer patients , an adjuvant chemotherapy-induced early menopause occurs , which is known to be a strong predictor of osteoporosis . We present data on the effect of adjuvant cyclophosphamide , methotrexate , and fluorouracil ( CMF ) therapy on bone mineral density ( BMD ) and the efficacy of clodronate on the prevention of bone loss in 148 premenopausal breast cancer patients without skeletal metastases . MATERIAL S AND METHODS Patients were r and omized to receive oral clodronate 1,600 mg/d or to a control group . In addition , patients were treated with six cycles of CMF therapy . BMD of the lumbar spine and femoral neck was measured by dual-energy x-ray absorptiometry ( DEXA ) before therapy and at 1 and 2 years . RESULTS Changes in the BMD of lumbar spine and femoral neck were -5.9 % and -2.0 % without clodronate and -2.2 % and + 0.9 % with clodronate at 2 years ( P = .0005 and .017 , respectively ) . Patients who developed amenorrhea after chemotherapy had a rapid bone loss , which was significantly reduced by clodronate . In controls , bone loss was 9.5 % in the lumbar spine and 4.6 % in the femoral neck , while in the clodronate group , bone loss was 5.9 % and 0.4 % , respectively , at 2 years . Patients with preserved menstruation had only marginal changes in BMD . CONCLUSION Chemotherapy-induced ovarian failure causes rapid bone loss in premenopausal breast cancer patients . Women older than 40 years are at particularly high risk . Clodronate significantly reduces this bone loss We present the 5-year results of the effect of adjuvant chemotherapy on bone mineral density ( BMD ) and the efficacy of clodronate in the prevention of bone loss in 73 premenopausal women with primary breast cancer . All patients were treated with cyclophosphamide , methotrexate , 5-fluorouracil ( CMF ) chemotherapy . The patients were r and omised to oral clodronate 1600 mg daily for 3 years or to a control group . At 5 years , patients were divided into those with preserved menstruation and those with amenorrhoea . Changes in BMD correlated significantly with the menstrual function after chemotherapy . The change in the lumbar spine BMD at 3 and 5 years were + 0.6 and -1.3 % in the menstruating group and -7.5 and -10.4 % in the amenorrhoeic group ( P=0.0001 and 0.0001 , respectively ) , and in femoral neck + 1.7 and -0.3 % , and -3.5 and -5.8 % ( P=0.002 and P=0.001 , respectively ) . Three-year clodronate treatment significantly reduced the bone loss in the lumbar spine -3.0 % compared with controls -7.4 % at three years ( P=0.003 ) , but no significant difference was found in the femoral neck : -1.7 % versus -2.8 % , respectively ( P=0.86 ) . These differences between the study groups were still seen at 5 years : in the lumbar spine -5.8 % versus -9.7 % ( P=0.008 ) and femoral neck -3.5 % versus -5.1 % ( P=0.91 ) . In conclusion , chemotherapy-induced ovarian failure in premenopausal women caused a temporary accelerated bone loss of the lumbar spine . Adjuvant clodronate treatment significantly reduced this bone loss . Two years after the termination of treatment , the bone loss was still significantly less in the clodronate group compared with the control group BACKGROUND Breast cancer patients may experience disease relapse even 10 - 20 years after primary diagnosis . Recurrence is caused by dormant disseminated tumor cells ( DTCs ) in the bone marrow ( BM ) . Whereas chemotherapy is unable to eradicate these non-proliferating cells , bisphosponates are currently being discussed as eliminating DTCs . The purpose of our study was to : i ) analyze the presence of DTCs in the BM of breast cancer patients 2 - 10 years after first diagnosis of cancer , and ii ) to study the effect of ib and ronate on DTCs in those patients with DTC persistence . PATIENTS AND METHODS Bilateral BM aspirates of 54 individuals diagnosed 2 - 10 years ago with breast cancer , but currently disease free , were analyzed for DTCs by immunocytochemistry using pan-cytokeratin antibody A45-B/B3 . Patients with DTC persistence received oral ib and ronate treatment ( 50 mg per day ) for six months and bilateral BM aspirates were analyzed for DTCs again after therapy . RESULTS DTCs were found in 18/54 ( 33 % ) of the patients , with a median number of 3 disseminated tumor cells ( range 1 - 6 cells ) . These 18 patients received ib and ronate orally for 6 months and 17/18 patients were analyzed for DTCs again after therapy . Only 3/17 ( 18 % ) patients remained DTC-positive , with the detection of 1 ( n=2 patients ) and 3 DTCs , respectively . These three DTC-positive patients continued their ib and ronate intake for a further six months and re-examination of the BM result ed in no detection of DTCs in any of the three patients . CONCLUSION Our pilot study indicates the potential effect of ib and ronate on DTCs and further studies are needed to demonstrate these findings in a larger patient cohort PURPOSE To determine the effectiveness and safety of the bisphosphonate risedronate in preventing bone loss in young women with breast cancer and early menopause induced by chemotherapy who are at major risk for the development of postmenopausal osteoporosis . PATIENTS AND METHODS Fifty-three white women , aged 36 to 55 years , with breast cancer and artificially induced menopause were stratified according to prior tamoxifen use . Thirty-six patients received tamoxifen ( 20 mg/d ) . Within each stratum , patients were r and omly assigned to receive risedronate ( n = 27 ) or placebo ( n = 26 ) . Treatment consisted of eight cycles oral risedronate 30 mg/d or placebo daily for 2 weeks followed by 10 weeks of no drug ( 12 weeks per cycle ) . Patients were monitored for a third year without treatment . RESULTS Main outcomes of the study were changes in lumbar spine and proximal femur ( femoral neck , trochanter , and Ward 's triangle ) bone mineral density ( BMD ) , and biochemical markers of bone turnover . In contrast to a significant decrease of BMD at the lumbar spine and hip in the placebo group , there was an increase in BMD in the risedronate group . On treatment withdrawal , bone loss ensued , which suggests that treatment needs to be continuous to maintain a protective effect on bone mass . At 2 years , the mean difference ( + /- SEM ) between groups was 2.5 % + /- 1.2 % , ( 95 % confidence interval [ CI ] , 0.2 to 4.9 ) at the lumbar spine ( P = .041 ) and 2.6 % + /- 1.1 % , ( 95 % CI , 0.3 to 4.8 ) at the femoral neck ( P = .029 ) . Similar results were observed at the hip trochanter . Results by stratum indicate a beneficial , although partial , effect of tamoxifen in reducing bone loss . Risedronate was well tolerated and showed a good safety profile , with no evidence of laboratory abnormalities . CONCLUSION Risedronate appears to be a safe treatment that prevents both trabecular and cortical bone loss in women with menopause induced by chemotherapy for breast cancer BACKGROUND Data suggest that the adjuvant use of bisphosphonates reduces rates of recurrence and death in patients with early-stage breast cancer . We conducted a study to determine whether treatment with zoledronic acid , in addition to st and ard adjuvant therapy , would improve disease outcomes in such patients . METHODS In this open-label phase 3 study , we r and omly assigned 3360 patients to receive st and ard adjuvant systemic therapy either with or without zoledronic acid . The zoledronic acid was administered every 3 to 4 weeks for 6 doses and then every 3 to 6 months to complete 5 years of treatment . The primary end point of the study was disease-free survival . A second interim analysis revealed that a prespecified boundary for lack of benefit had been crossed . RESULTS At a median follow-up of 59 months , there was no significant between-group difference in the primary end point , with a rate of disease-free survival of 77 % in each group ( adjusted hazard ratio in the zoledronic acid group , 0.98 ; 95 % confidence interval [ CI ] , 0.85 to 1.13 ; P=0.79 ) . Disease recurrence or death occurred in 377 patients in the zoledronic acid group and 375 of those in the control group . The numbers of deaths--243 in the zoledronic acid group and 276 in the control group -- were also similar , result ing in rates of overall survival of 85.4 % in the zoledronic acid group and 83.1 % in the control group ( adjusted hazard ratio , 0.85 ; 95 % CI , 0.72 to 1.01 ; P=0.07 ) . In the zoledronic acid group , there were 17 confirmed cases of osteonecrosis of the jaw ( cumulative incidence , 1.1 % ; 95 % CI , 0.6 to 1.7 ; P<0.001 ) and 9 suspected cases ; there were no cases in the control group . Rates of other adverse effects were similar in the two study groups . CONCLUSIONS These findings do not support the routine use of zoledronic acid in the adjuvant management of breast cancer . ( Funded by Novartis Pharmaceuticals and the National Cancer Research Network ; AZURE Current Controlled Trials number , IS RCT N79831382 . ) BACKGROUND Women with primary breast cancer who receive systemic therapy may experience ovarian failure or early menopause , leading to a loss of bone mineral density ( BMD ) . Loss of BMD may be reduced by use of bisphosphonates , compounds that inhibit the action of osteoclasts ( cells that absorb or remove bone tissue ) . We have conducted a double-blind , r and omized , two-center trial to evaluate BMD in women with primary breast cancer who were given the bisphosphonate clodronate ( 1600 mg/day orally ) or placebo for 2 years . METHODS From August 31 , 1990 , through March 31 , 1996 , more than 300 eligible patients had been accrued , r and omly assigned to study treatment , given the appropriate primary surgical care and systemic ( chemotherapy and /or tamoxifen ) therapy , and had completed follow-up for at least 1 year . BMD in the lumbar spine and in the hip , including the trochanteric area , was measured by use of dual-energy x-ray absorptiometry at the beginning of treatment and after 1 and 2 years of treatment . Changes in BMD were calculated as percent changes from the initial readings . Treatment effects for clodronate versus placebo ( i.e. , mean percent changes in BMD with clodronate minus mean percent changes in BMD with placebo ) at 1 and 2 years for individual sites were calculated . RESULTS After 1 year , the treatment effects for clodronate versus placebo in the lumbar spine , the total hip , and the trochanter , respectively , were as follows : + 2.38 % ( 95 % confidence interval [ CI ] = 1.36 - 3.41 ) , + 0.74 % ( 95 % CI = -0.13 - 1.60 ) , and + 1.29 % ( 95 % CI = 0.24 - 2.34 ) . After 2 years , the corresponding treatment effects were + 1.72 % ( 95 % CI = 0.12 - 3.34 ) , + 1.85 % ( 95 % CI = 0.51 - 3.20 ) , and + 2.30 % ( 95 % CI = 0.66 - 3.94 ) , respectively . CONCLUSIONS Oral clodronate appears to reduce the loss of BMD in patients who receive treatment for primary breast cancer Introduction In contrast to nonsteroidal aromatase inhibitors , the steroidal aromatase inactivator exemestane does not have detrimental effects on bone in animal models . This study was design ed to compare the effects of exemestane with the nonsteroidal aromatase inhibitors anastrozole and letrozole on serum and urine levels of biomarkers of bone turnover in healthy postmenopausal women . Methods Changes in the concentrations of bone-turnover markers , estrogens , and lipids were assessed after daily administration of exemestane ( 25 mg ) , letrozole ( 2.5 mg ) , anastrozole ( 1 mg ) , or placebo for 24 weeks in healthy postmenopausal women . The primary end point was the percentage change from baseline in bone-turnover-marker levels at week 24 . The baseline-adjusted area under the curve ( AUC ) for weeks 0–12 and 0–24 was calculated to evaluate changes in bone turnover over time , rather than at discrete time points . Results Seventy-four ( 88 % ) of 84 r and omized subjects were evaluable for bone-marker assays . Reductions in plasma estrogen levels and increases in bone-resorption markers were comparable for each aromatase inhibitor . Uniquely , exemestane consistently increased the percentage change from baseline in the level of serum procollagen type I N-terminal propeptide ( PINP ) , a marker of bone formation , at week 24 . In the active-treatment groups , the baseline-adjusted AUC at weeks 0–12 and 0–24 for PINP was significantly greater for exemestane than the other aromatase inhibitors . Conclusion Exemestane increased serum levels of the bone-formation marker PINP after 24 weeks , suggesting a specific bone-formation effect related to its and rogenic structure . Potential effects on cortical bone and reduced fracture risk must be verified in a comparative clinical trial Purpose : The aromatase inhibitor anastrozole is a highly effective well-tolerated treatment for postmenopausal endocrine-responsive breast cancer . However , its use is associated with accelerated bone loss and an increase in fracture risk . The ARIBON trial is a double-blind , r and omized , placebo-controlled study design ed to evaluate the impact of bisphosphonate treatment on bone mineral density ( BMD ) in women taking anastrozole . Experimental Design : BMD was assessed in 131 postmenopausal , surgically treated women with early breast cancer at two U.K. centers . Of these , 50 patients had osteopenia ( T score −1.0 to −2.5 ) at either the hip or lumbar spine . All patients were treated with anastrozole 1 mg once a day and calcium and vitamin D supplementation . In addition , osteopenic patients were r and omized to receive either treatment with ib and ronate 150 mg orally every month or placebo . Results : After 2 years , osteopenic patients treated with ib and ronate gained + 2.98 % ( range −8.9 , + 19.9 ) and + 0.60 % ( range −9.0 , + 6.9 ) at the lumbar spine and hip , respectively . Patients treated with placebo , however , lost −3.22 % ( range −16.0 , + 4.3 ) at the lumbar spine and −3.90 % ( range −12.3 , + 7.2 ) at the hip . The differences between the two treatment arms were statistically significant at both sites ( P < 0.01 ) . At 12 months , urinary n-telopeptide , serum c-telopeptide , and serum bone – specific alkaline phosphatase levels declined in patients receiving ib and ronate ( 30.9 % , 26.3 % , and 22.8 % , respectively ) and increased in those taking placebo ( 40.3 % , 34.9 % , and 37.0 % , respectively ) . Conclusions : Monthly oral ib and ronate improves bone density and normalizes bone turnover in patients treated with anastrozole BACKGROUND Initial findings from the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial ( P-1 ) demonstrated that tamoxifen reduced the risk of estrogen receptor-positive tumors and osteoporotic fractures in women at increased risk for breast cancer . Side effects of varying clinical significance were observed . The trial was unblinded because of the positive results , and follow-up continued . This report up date s our initial findings . METHODS Women ( n = 13,388 ) were r and omly assigned to receive placebo or tamoxifen for 5 years . Rates of breast cancer and other events were compared by the use of risk ratios ( RRs ) and 95 % confidence intervals ( CIs ) . Estimates of the net benefit from 5 years of tamoxifen therapy were compared by age , race , and categories of predicted breast cancer risk . Statistical tests were two-sided . RESULTS After 7 years of follow-up , the cumulative rate of invasive breast cancer was reduced from 42.5 per 1000 women in the placebo group to 24.8 per 1000 women in the tamoxifen group ( RR = 0.57 , 95 % CI = 0.46 to 0.70 ) and the cumulative rate of noninvasive breast cancer was reduced from 15.8 per 1000 women in the placebo group to 10.2 per 1000 women in the tamoxifen group ( RR = 0.63 , 95 % CI = 0.45 to 0.89 ) . These reductions were similar to those seen in the initial report . Tamoxifen led to a 32 % reduction in osteoporotic fractures ( RR = 0.68 , 95 % CI = 0.51 to 0.92 ) . Relative risks of stroke , deep-vein thrombosis , and cataracts ( which increased with tamoxifen ) and of ischemic heart disease and death ( which were not changed with tamoxifen ) were also similar to those initially reported . Risks of pulmonary embolism were approximately 11 % lower than in the original report , and risks of endometrial cancer were about 29 % higher , but these differences were not statistically significant . The net benefit achieved with tamoxifen varied according to age , race , and level of breast cancer risk . CONCLUSIONS Despite the potential bias caused by the unblinding of the P-1 trial , the magnitudes of all beneficial and undesirable treatment effects of tamoxifen were similar to those initially reported , with notable reductions in breast cancer and increased risks of thromboembolic events and endometrial cancer . Readily identifiable subsets of individuals comprising 2.5 million women could derive a net benefit from the drug BACKGROUND The aromatase inhibitor letrozole , as compared with tamoxifen , improves disease-free survival among postmenopausal women with receptor-positive early breast cancer . It is unknown whether sequential treatment with tamoxifen and letrozole is superior to letrozole therapy alone . METHODS In this r and omized , phase 3 , double-blind trial of the treatment of hormone-receptor-positive breast cancer in postmenopausal women , we r and omly assigned women to receive 5 years of tamoxifen monotherapy , 5 years of letrozole monotherapy , or 2 years of treatment with one agent followed by 3 years of treatment with the other . We compared the sequential treatments with letrozole monotherapy among 6182 women and also report a protocol -specified up date d analysis of letrozole versus tamoxifen monotherapy in 4922 women . RESULTS At a median follow-up of 71 months after r and omization , disease-free survival was not significantly improved with either sequential treatment as compared with letrozole alone ( hazard ratio for tamoxifen followed by letrozole , 1.05 ; 99 % confidence interval [ CI ] , 0.84 to 1.32 ; hazard ratio for letrozole followed by tamoxifen , 0.96 ; 99 % CI , 0.76 to 1.21 ) . There were more early relapses among women who were assigned to tamoxifen followed by letrozole than among those who were assigned to letrozole alone . The up date d analysis of monotherapy showed that there was a nonsignificant difference in overall survival between women assigned to treatment with letrozole and those assigned to treatment with tamoxifen ( hazard ratio for letrozole , 0.87 ; 95 % CI , 0.75 to 1.02 ; P=0.08 ) . The rate of adverse events was as expected on the basis of previous reports of letrozole and tamoxifen therapy . CONCLUSIONS Among postmenopausal women with endocrine-responsive breast cancer , sequential treatment with letrozole and tamoxifen , as compared with letrozole monotherapy , did not improve disease-free survival . The difference in overall survival with letrozole monotherapy and tamoxifen monotherapy was not statistically significant . ( Clinical Trials.gov number , NCT00004205 . BACKGROUND Bisphosphonates are thought to act through the osteoclast by changing bone microenvironment . Previous findings of adjuvant clodronate trials in different population s with operable breast cancer have been mixed . The National Surgical Adjuvant Breast and Bowel Project ( NSABP ) protocol B-34 aims to ascertain whether oral clodronate can improve outcomes in women with primary breast cancer . METHODS NSABP B-34 is a multicentre , r and omised , double-blind , placebo-controlled study in 3323 women with stage 1 - 3 breast cancer . After surgery to remove the tumour , patients were stratified by age , axillary nodes , and oestrogen and progesterone receptor status and r and omly assigned in a 1:1 ratio to either oral clodronate 1600 mg daily for 3 years ( n=1662 ) or placebo ( 1661 ) . The primary endpoint was disease-free survival , analysed by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00009945 . FINDINGS Median follow-up was 90·7 months ( IQR 82·7 - 100·0 ) and 3311 patients had data for this period . Disease-free survival did not differ between groups ( 286 events in the clodronate group vs 312 in the placebo group ; hazard ratio 0·91 , 95 % CI 0·78 - 1·07 ; p=0·27 ) . Moreover , no differences were recorded for overall survival ( 0·84 , 0·67 - 1·05 ; p=0·13 ) , recurrence-free interval ( 0·83 , 0·67 - 1·04 ; p=0·10 ) , or bone metastasis-free interval ( 0·77 , 0·55 - 1·07 ; p=0·12 ) . Non-bone metastasis-free interval was slightly increased with clodronate ( 0·74 , 0·55 - 1·00 ; p=0·047 ) . Analyses in women age 50 years or older on study entry showed benefits of clodronate for recurrence-free interval ( 0·75 , 0·57 - 0·99 ; p=0·045 ) , bone metastasis-free interval ( 0·62 , 0·40 - 0·95 ; p=0·027 ) , and non-bone metastasis-free interval ( 0·63 , 0·43 - 0·91 ; p=0·014 ) , but not for overall survival ( 0·80 , 0·61 - 1·04 , p=0·094 ) . Adherence to treatment at 3 years was 56 % for the clodronate group and 60 % for the placebo group . Grade 3 or higher liver dysfunction was noted in 23 of 1612 patients in the clodronate group and 12 of 1623 patients in the placebo group ; grade 3 - 4 diarrhoea was noted in 28 patients in the clodronate group and in ten in the placebo group . There was one possible case of osteonecrosis of the jaw in the clodronate group . INTERPRETATION Findings of NSABP B-34 suggest that bisphosphonates might have anticancer benefits for older postmenopausal women . A meta- analysis of adjuvant bisphosphonate trials is suggested before recommendations for use in non-osteoporotic postmenopausal women with primary breast cancer are made . FUNDING National Cancer Institute , Bayer Oy ( formerly Schering Oy ) BACKGROUND Adjuvant endocrine therapy compromises bone health in patients with breast cancer , causing osteopenia , osteoporosis , and fractures . Antiresorptive treatments such as bisphosphonates prevent and counteract these side-effects . In this trial , we aim ed to investigate the effects of the anti-RANK lig and antibody denosumab in postmenopausal , aromatase inhibitor-treated patients with early-stage hormone receptor-positive breast cancer . METHODS In this prospect i ve , double-blind , placebo-controlled , phase 3 trial , postmenopausal patients with early hormone receptor-positive breast cancer receiving treatment with aromatase inhibitors were r and omly assigned in a 1:1 ratio to receive either denosumab 60 mg or placebo administered subcutaneously every 6 months in 58 trial centres in Austria and Sweden . Patients were assigned by an interactive voice response system . The r and omisation schedule used a r and omly permuted block design with block sizes 2 and 4 , stratified by type of hospital regarding Hologic device for DXA scans , previous aromatase inhibitor use , and baseline bone mineral density . Patients , treating physicians , investigators , data managers , and all study personnel were masked to treatment allocation . The primary endpoint was time from r and omisation to first clinical fracture , analysed by intention to treat . As an additional sensitivity analysis , we also analysed the primary endpoint on the per- protocol population . Patients were treated until the prespecified number of 247 first clinical fractures was reached . This trial is ongoing ( patients are in follow-up ) and is registered with the European Clinical Trials Data base , number 2005 - 005275 - 15 , and with Clinical Trials.gov , number NCT00556374 . FINDINGS Between Dec 18 , 2006 , and July 22 , 2013 , 3425 eligible patients were enrolled into the trial , of whom 3420 were r and omly assigned to receive denosumab 60 mg ( n=1711 ) or placebo ( n=1709 ) subcutaneously every 6 months . Compared with the placebo group , patients in the denosumab group had a significantly delayed time to first clinical fracture ( hazard ratio [ HR ] 0·50 [ 95 % CI 0·39 - 0·65 ] , p<0·0001 ) . The overall lower number of fractures in the denosumab group ( 92 ) than in the placebo group ( 176 ) was similar in all patient subgroups , including in patients with a bone mineral density T-score of -1 or higher at baseline ( n=1872 , HR 0·44 [ 95 % CI 0·31 - 0·64 ] , p<0·0001 ) and in those with a bone mineral density T-score of less than -1 already at baseline ( n=1548 , HR 0·57 [ 95 % CI 0·40 - 0·82 ] , p=0·002 ) . The patient incidence of adverse events in the safety analysis set ( all patients who received at least one dose of study drug ) did not differ between the denosumab group ( 1366 events , 80 % ) and the placebo group ( 1334 events , 79 % ) , nor did the numbers of serious adverse events ( 521 vs 511 [ 30 % in each group ] ) . The main adverse events were arthralgia and other aromatase-inhibitor related symptoms ; no additional toxicity from the study drug was reported . Despite proactive adjudication of every potential osteonecrosis of the jaw by an international expert panel , no cases of osteonecrosis of the jaw were reported . 93 patients ( 3 % of the full analysis set ) died during the study , of which one death ( in the denosumab group ) was thought to be related to the study drug . INTERPRETATION Adjuvant denosumab 60 mg twice per year reduces the risk of clinical fractures in postmenopausal women with breast cancer receiving aromatase inhibitors , and can be administered without added toxicity . Since a main side-effect of adjuvant breast cancer treatment can be substantially reduced by the addition of denosumab , this treatment should be considered for clinical practice . FUNDING Amgen To determine whether zoledronic acid ( ZA ) can prevent bone loss in premenopausal women undergoing adjuvant chemotherapy for breast cancer . In this r and omized , open-label , phase III multicenter trial , premenopausal women > 40 years were r and omly assigned to ZA treatment ( 4 mg IV , every 6 months ) or observation after surgery . All patients were treated with four cycles of AC followed by four cycles of taxane . Between March 2007 and May 2008 , we assessed a total of 112 premenopausal women , all of whom developed amenorrhea at 1 year after chemotherapy . The mean percent change of BMD in the lumbar spine ( LS ) was −1.1 % in the ZA group versus −7.5 % in observation group at 12 months . Differences in percent change of BMD from baseline between the two groups were 6.4 % for the LS , and 3.6 % for the femoral neck . The mean levels of bone turnover at 12 months were significantly lower in the ZA group . ZA was generally well tolerated . Infusion of ZA 4 mg every 6 months effectively prevented bone loss within the first year in premenopausal women receiving adjuvant chemotherapy for early breast cancer . Regular BMD measurements and early bisphosphonate therapy should be considered in these patients Summary This study examined whether 24 months of weight training exercises enhanced the effectiveness of risedronate , calcium , and vitamin D in maintaining or improving bone mineral density ( BMD ) in 223 postmenopausal breast cancer survivors . Subjects who were ≥50 % adherent to exercise had no improvement in BMD but were less likely to lose BMD . Introduction This study examined whether ( 1 ) postmenopausal breast cancer survivors ( BCS ) with bone loss taking 24 months of risedronate , calcium , and vitamin D had increased bone mineral density ( BMD ) at the total hip , femoral neck , L1-L4 spine , total radius and 33 % radius , and decreased bone turnover ; ( 2 ) subjects who also participated in strength/weight training ( ST ) exercises had greater increases in BMD and greater decreases in bone turnover ; and ( 3 ) subjects who also exercised were more likely to preserve ( at least maintain ) BMD . Methods Postmenopausal BCS ( 223 ) were r and omly assigned to exercise plus medication or medication only groups . Both groups received 24 months of 1,200 mg of calcium and 400 IU of vitamin D daily and 35 mg of risedronate weekly , and the exercise group additionally had ST exercises twice weekly . Results After 24 months , women who took medications without exercising had significant improvements in BMD at the total hip ( + 1.81 % ) and spine ( + 2.85 % ) and significant decreases in Alkphase B ( −8.7 % ) and serum NTx ( −16.7 % ) . Women who also exercised had additional increases in BMD at the femoral neck ( + 0.29 % ) , total hip ( + 0.34 % ) , spine ( + 0.23 % ) , total radius ( + 0.30 % ) , and additional decreases in Alkphase B ( −2.4 % ) and Serum NTx ( −6.5 % ) . Additional changes in BMD and bone turnover with exercise were not significant . Subjects who were ≥50 % adherent to exercise were less likely to lose BMD at the total hip ( chi-square [ 1 ] = 4.66 , p = 0.03 ) and femoral neck ( chi-square [ 1 ] = 4.63 , p = 0.03 ) . ConclusionS trength/weight training exercises may prevent loss of BMD in postmenopausal BCS at risk for bone loss Targeted exercise training could reduce risk factors for fracture and obesity-related diseases that increase from breast cancer treatment , but has not been sufficiently tested . We hypothesized that progressive , moderate-intensity resistance + impact training would increase or maintain hip and spine bone mass , lean mass and fat mass and reduce bone turnover compared to controls who participated in a low-intensity , non-weight bearing stretching program . We conducted a r and omized , controlled trial in 106 women with early stage breast cancer who were > 1 year post-radiation and /or chemotherapy , ≥50 years of age at diagnosis and postmenopausal , free from osteoporosis and medications for bone loss , resistance and impact exercise naïve , and cleared to exercise by a physician . Women were r and omly assigned to participate in 1 year of thrice-weekly progressive , moderate-intensity resistance + impact ( jump ) exercise or in a similar frequency and length control program of progressive , low-intensity stretching . Primary endpoints were bone mineral density ( BMD ; g/cm2 ) of the hip and spine and whole body bone-free lean and fat mass ( kg ) determined by DXA and biomarkers of bone turnover — serum osteocalcin ( ng/ml ) and urinary deoxypyrodiniline cross-links ( nmol/mmolCr ) . Women in the resistance + impact training program preserved BMD at the lumbar spine ( 0.47 vs. −2.13 % ; P = 0.001 ) compared to controls . The resistance + impact group had a smaller increase in osteocalcin ( 7.0 vs. 27 % , P = 0.03 ) and a larger decrease in deoxypyrodinoline ( −49.9 vs. −32.6 % , P = 0.06 ) than controls . Increases in lean mass from resistance + impact training were greatest among women currently taking aromatase inhibitors compared to controls not on this therapy ( P = 0.01 ) . Our combined program of resistance + impact exercise reduced risk factors for fracture among postmenopausal breast cancer survivors ( BCS ) and may be particularly relevant for BCS on aromatase inhibitors ( AIs ) because of the additional benefit of exercise on muscle mass that could reduce falls The purpose of this study was to compare changes in bone mineral density ( BMD ) in premenopausal patients with node-positive early breast cancer treated with goserelin ( Zoladex ) or cyclophosphamide , methotrexate and 5-fluorouracil ( CMF ) . Patients ( n=1640 ) were r and omized to goserelin ( 3.6 mg every 28 days for 2 years ) or CMF ( six × 28-day cycles ) treatment . In a protocol ed sub- study involving 96 patients from eight centers ( goserelin : n=53 ; CMF : n=43 ) , lumbar spine ( L2–L4 ) and femoral neck BMD were assessed by dual X-ray absorptiometry at baseline and then annually for 3 years . At the end of the 2-year goserelin-treatment period , mean BMD losses for goserelin-treated and CMF-treated patients were −10.5 % and −6.5 % ( P=0.0005 ) for lumbar spine and −6.4 % and −4.5 % ( P=0.04 ) for femoral neck , respectively . At 3 years , partial recovery of BMD was observed in goserelin recipients . In contrast , mean BMD losses for the CMF group indicated persistent BMD loss . No significant differences in BMD were observed between groups at the 3-year assessment of the spine or femoral neck . In the CMF group , based on amenorrhea status at 48 weeks , BMD losses at the lumbar spine were greater for amenorrheic than non-amenorrheic patients . Ovarian suppression result ing in amenorrhea was closely related to BMD loss in both treatment groups . Overall , patients who received CMF did not show recovery of BMD throughout follow-up , whereas partial recovery was observed 1 year after cessation of goserelin therapy , associated with the return of ovarian function in the majority of patients PURPOSE To up date the ASCO clinical practice guideline on adjuvant endocrine therapy on the basis of emerging data on the optimal duration of treatment , particularly adjuvant tamoxifen . METHODS ASCO convened the Up date Committee and conducted a systematic review of r and omized clinical trials from January 2009 to June 2013 and analyzed three historical trials . Guideline recommendations were based on the Up date Committee 's review of the evidence . Outcomes of interest included survival , disease recurrence , and adverse events . RESULTS This guideline up date reflects emerging data on duration of tamoxifen treatment . There have been five studies of tamoxifen treatment beyond 5 years of therapy . The two largest studies with longest reported follow-up show a breast cancer survival advantage with 10-year duration s of tamoxifen use . In addition to modest gains in survival , extended therapy with tamoxifen for 10 years compared with 5 years was associated with lower risks of breast cancer recurrence and contralateral breast cancer . RECOMMENDATIONS Previous ASCO guidelines recommended treatment of women who have hormone receptor-positive breast cancer and are premenopausal with 5 years of tamoxifen , and those who are postmenopausal a minimum of 5 years of adjuvant therapy with an aromatase inhibitor or tamoxifen followed by an aromatase inhibitor ( in sequence ) . If women are pre- or perimenopausal and have received 5 years of adjuvant tamoxifen , they should be offered 10 years total duration of tamoxifen . If women are postmenopausal and have received 5 years of adjuvant tamoxifen , they should be offered the choice of continuing tamoxifen or switching to an aromatase inhibitor for 10 years total adjuvant endocrine therapy 527 Background : There are three studies available of the effect of adjuvant bisphosphonate treatment on survival in primary operable breast cancer with conflicting results . We here present the extended 10 year follow-up result of the Finnish adjuvant clodronate study . METHODS Between 1990 and 1993 , 299 women with primary node positive breast cancer were r and omized to oral clodronate 1600 mg daily ( 149 ) or control groups ( 150 ) for three years . All patients received adjuvant chemo- or endocrine therapy . The final population was 282 patients . Intent-to-treat analyses were also performed . Pretreatment characteristics were well balanced between the groups except PgR receptor status . In the clodronate group there were more PgR negative patients ( p = 0.03 ) . RESULTS Within ten years bone metastases were detected at the same frequency in the clodronate and control groups : 44 ( 32 % ) vs. 42 ( 29 % ) , respectively , ( p = 0.35 ) . The frequency of nonskeletal recurrences ( visceral and local ) was significantly higher in the clodronate group 69 ( 50 % ) as compared to the controls 51 ( 36 % ) ( p = 0.005 ) . Ten-year disease-free survival ( DFS ) remained significantly lower in the clodronate group ( 45 % vs. 58 % , p = 0.01 , respectively ) . In ER positive patients ten-year DFS was 55 % in the clodronate group , and 59 % in the controls with no difference between the groups ( p = 0.47 ) ; while in ER negative patients the DFS difference was highly significant in favor of the controls : 25 % vs. 58 % ( p = 0.004 ) , respectively . In multivariate analyses of DFS nodal status , tumor size , PgR status and study treatment group remained statistically significant . No significant overall survival difference was found between the groups . CONCLUSIONS As previously reported three-year adjuvant clodronate treatment did not prevent the development of bone metastases in node-positive breast cancer patients . A negative effect of clodronate on DFS by increasing the development of visceral metastases was still seen at 10 years especially in ER negative patients , but this did not significantly compromise overall survival . No significant financial relationships to disclose PURPOSE To examine the effects on bone mineral density of 2 years of treatment with a luteinizing hormone-releasing hormone ( LHRH ) agonist alone or in combination with tamoxifen or tamoxifen alone in premenopausal breast cancer . PATIENTS AND METHODS We recruited 89 women from two centers in Stockholm participating in a r and omized multicenter trial of three different endocrine approaches in the adjuvant setting ( Zoladex in Premenopausal Patients Trial ) . The women were assigned to receive the LHRH agonist goserelin with or without tamoxifen , tamoxifen alone , or no endocrine therapy . The treatment was given for 2 years . We measured total-body bone density before start of treatment and at 12 , 24 , and 36 months . RESULTS After 2 years of treatment , there was a significant loss of bone mineral density ( mean change , -5 % ; P < .001 ) in the women receiving goserelin alone . The combined goserelin and tamoxifen treatment , as well as tamoxifen alone , result ed in a lesser but statistically significant decline in bone mineral density ( mean change , -1.4 % ; P = .02 ; and -1.5 % ; P < .001 ) . One year after cessation of treatment , the goserelin group alone showed a partial recovery from bone loss ( mean change , 1.5 % ; P = .02 ) . CONCLUSION Two years of ovarian ablation from goserelin treatment caused a significant reduction in bone mineral density but there was a partial recovery from the bone loss 1 year after cessation of treatment . The addition of tamoxifen seems to partially counteract the demineralizing effects of goserelin BACKGROUND Treatment with bisphosphonates decreases bone loss and can increase disease-free survival in patients with breast cancer . The aim of our study was to assess the effect of zoledronic acid on clearance of disseminated tumour cells ( DTCs ) from the bone marrow in women undergoing neoadjuvant chemotherapy for breast cancer . METHODS Patients were recruited for this open-label , phase 2 r and omised trial between March 17 , 2003 , and May 19 , 2006 , at a single centre . Eligible patients had clinical stage II-III ( > or = T2 and /or > or = N1 ) newly diagnosed breast cancer , Eastern Cooperative Oncology Group performance status of 0 or 1 , and normal cardiac , renal , and liver function . 120 women were r and omly assigned , using allocation concealment , to receive 4 mg zoledronic acid intravenously every 3 weeks ( n=60 ) , or no zoledronic acid ( n=60 ) , for 1 year concomitant with four cycles of neoadjuvant epirubicin ( 75 mg/m(2 ) ) plus docetaxel ( 75 mg/m(2 ) ) and two cycles of adjuvant epirubicin plus docetaxel . The primary endpoint was the number of patients with detectable DTCs at 3 months . Final analysis was done 1 year after the last patient was enrolled . Analyses were done for all patients with available data at 3 months . This study is registered with Clinical Trials.gov , number NCT00242203 . FINDINGS Of the 120 patients initially enrolled , one withdrew after signing consent and one patient 's baseline bone marrow was not available . Both of these patients were in the control group . At 3 months , 109 bone-marrow sample s were available for analysis . In the zoledronic acid group , bone marrow was not collected from one patient because of disease progression , one patient was taken off study because of severe diarrhoea , and two patients had not consented at the time of surgery . In the control group , bone marrow was not collected from two patients because of disease progression , one patient withdrew consent , and three patients were not consented at the time of surgery . At baseline , DTCs were detected in 26 of 60 patients in the zoledronic acid group and 28 of 58 patients in the control group . At 3 months , 17 of 56 patients receiving zoledronic acid versus 25 of 53 patients who did not receive zoledronic acid had detectable DTCs ( p=0.054 ) . The most common grade 3 - 4 toxicities were infection ( five of 60 patients in the zoledronic acid group and six of 59 in the control group ) and thrombosis ( five of 60 in the zoledronic acid and two of 59 in the control group ) . There was one documented case of osteonecrosis in the zoledronic acid group . INTERPRETATION Zoledronic acid administered with chemotherapy result ed in a decreased proportion of patients with DTCs detected in the bone marrow at the time of surgery . Our study supports the hypothesis that the antimetastatic effects of zoledronic acid may be through effects on DTCs . FUNDING Novartis Pharmaceuticals and Pfizer Purpose and patients . During the period from January 1990 to January 1996 a total of 953 patients with lymph node negative primary breast cancer were r and omised to oral pamidronate ( n=460 ) 150 mg twice daily for 4 years or no adjuvant pamidronate ( n=493 ) in order to investigate whether oral pamidronate can prevent the occurrence of bone metastases and fractures . The patients received adjuvant chemotherapy , loco-regional radiation therapy , but no endocrine treatment . Results . During the follow-up period the number of patients with pure bone metastases was 35 in the control group and 31 in the pamidronate group . The number of patients with a combination of bone and other distant metastases were 22 in the control group and 20 in the pamidronate group . The hazard rate ratio for recurrence in bone in the pamidronate group compared to the control group was 1.03 ( 95 % confidence interval 0.75–1.40 ) and p=0.86 . No effect was observed on overall survival . In a small subgroup of 27 patients from the study , 12 of whom were treated with pamidronate a significant bone preserving effect was observed on bone mineral density in the lumbar spine , but not in the proximal femur . Conclusion . The results from the trial do not support a beneficial effect of oral pamidronate on the occurrence of bone metastases or fractures in patients with primary breast cancer receiving adjuvant chemotherapy PURPOSE To investigate the management of bone health in women with early breast cancer ( EBC ) who were scheduled to receive anastrozole . PATIENTS AND METHODS Postmenopausal women with hormone receptor-positive EBC were assigned to one of three strata by risk of fragility fracture . Patients with the highest risk ( H ) received anastrozole 1 mg/d plus risedronate 35 mg/wk orally . Patients with moderate-risk ( M ) were r and omly assigned in a double-blind manner to anastrozole and risedronate ( A + R ) or to anastrozole and placebo ( A + P ) . Patients with lower-risk ( L ) received anastrozole ( A ) alone . Calcium and vitamin D were recommended for all patients . Lumbar spine and total hip bone mineral density ( BMD ) were assessed at baseline , 12 months , and 24 months . Results At 24 months , in the M group , treatment with A + R result ed in a significant increase in lumbar spine and total hip BMD compared with A + P treatment ( 2.2 % v -1.8 % ; treatment ratio , 1.04 ; P < .0001 ; and 1.8 % v -1.1 % ; treatment ratio , 1.03 ; P < .0001 , respectively ) . In the H stratum , lumbar spine and total hip BMD increased significantly ( 3.0 % ; P = .0006 ; and 2.0 % ; P = .0104 , respectively ) . Patients in the L stratum showed a significant decrease in lumbar spine BMD ( -2.1 % ; P = .0109 ) and a numerical decrease in total hip BMD ( -0.4 % ; P = .5988 ) . Safety profiles for anastrozole and risedronate were similar to those already established . CONCLUSION In postmenopausal women at risk of fragility fracture who were receiving adjuvant anastrozole for EBC , the addition of risedronate at doses established for preventing and treating osteoporosis result ed in favorable effects in BMD during 24 months BACKGROUND The role of adjuvant bisphosphonates in early breast cancer is uncertain . We therefore did a large r and omised trial to investigate the effect of the adjuvant use of zoledronic acid on disease-free survival ( DFS ) in high-risk patients with early breast cancer . METHODS In the AZURE trial , an open-label , international , multicentre , r and omised , controlled , parallel-group phase 3 trial , women ( age ≥18 years ) with stage II or III breast cancer were r and omly assigned ( 1:1 ) by a central automated 24-h computer-generated telephone minimisation system ( balanced for number of involved axillary lymph nodes , tumour stage , oestrogen receptor status , type and timing of systemic therapy , menopausal status , statin use , and treatment centre ) to receive st and ard adjuvant systemic treatment alone ( control group ) or with 4 mg intravenous zoledronic acid every 3 - 4 weeks for six doses , then every 3 months for eight doses , followed by every 6 months for five doses , for a total of 5 years of treatment . The primary endpoint was disease-free survival ( DFS ) . Secondary endpoints were invasive DFS ( IDFS ) , overall survival , time to bone metastases , time to distant recurrence , and subgroup analyses of variables included in the r and omisation . All patients have completed study treatment . Results from the intention-to-treat final analysis of this fully recruited study are presented after a median follow-up of 84 months ( IQR 66 - 93 ) . This final efficacy analysis was planned to take place after 940 DFS events . This trial is registered with Clinical Trials.gov , NCT00072020 . FINDINGS 3360 women were recruited from 174 centres in seven countries between Sept 4 , 2003 , and Feb 16 , 2006 . The number of DFS events did not differ between groups : 493 in the control group and 473 in the zoledronic acid group ( adjusted hazard ratio [ HR ] 0·94 , 95 % CI 0·82 - 1·06 ; p=0·30 ) . IDFS ( HR 0·93 , 95 % CI 0·82 - 1·05 ; p=0·22 ) , overall survival ( 0·93 , 0·81 - 1·08 ; p=0·37 ) , and distant recurrences ( 0·93 , 0·81 - 1·07 ; p=0·29 ) were much the same in both groups . Zoledronic acid reduced the development of bone metastases , both as a first event ( HR 0·78 , 95 % CI 0·63 - 0·96 ; p=0·020 ) and at any time during follow-up ( 0·81 , 0·68 - 0·97 ; p=0·022 ) . The effects of zoledronic acid on DFS were not affected by oestrogen-receptor status . However , zoledronic acid improved IDFS in those who were over 5 years since menopause at trial entry ( n=1041 ; HR 0·77 , 95 % CI 0·63 - 0·96 ) but not in all other ( premenopause , perimenopause , and unknown status ) menopausal groups ( n=2318 ; HR 1·03 , 95 % CI 0·89 - 1·20 ) . 33 cases of suspected osteonecrosis of the jaw have been reported , with 26 confirmed on central review , all in the zoledronic acid group ( 1·7 % , 95 % CI 1·0 - 2·4 ) . INTERPRETATION These results suggest no overall benefit from the addition of zoledronic acid to st and ard adjuvant treatments for early breast cancer . However , zoledronic acid does reduce the development of bone metastases and , for women with established menopause , improved disease outcomes . FUNDING Novartis Global and NIHR Cancer Research Network BACKGROUND Letrozole is a proven and effective adjuvant therapy in postmenopausal women with hormone receptor-positive ( HR(+ ) ) early breast cancer ( EBC ) . As with other aromatase inhibitors ( AIs ) , long-term letrozole administration is associated with decreased bone mineral density ( BMD ) and increased fracture risk . This study compared potential bone-protecting effects of immediate vs. delayed administration of zoledronic acid ( ZOL ) in patients with EBC receiving adjuvant letrozole . PATIENTS AND METHODS Patients with HR(+ ) EBC in whom adjuvant letrozole treatment was initiated ( 2.5 mg/day for 5 years ) were r and omized to immediate ZOL treatment ( immediate ZOL ) or delayed ZOL treatment ( delayed ZOL ) ( both at 4 mg every 6 months ) . Patients in the delayed ZOL group received ZOL only for a BMD T-score that decreased to < -2.0 ( lumbar spine [ LS ] or total hip [ TH ] ) or for fracture . The primary endpoint was percentage change in the LS BMD at month 12 . Patients were stratified by established or recent postmenopausal status , baseline T-scores , and adjuvant chemotherapy history . RESULTS At 12 months , the LS BMD increased in the immediate ZOL group ( + 2.72 % ) but decreased in the delayed ZOL group ( -2.71 % ) ; the absolute difference between groups was significant ( 5.43 % ; P < .0001 ) . Across all subgroups , patients receiving immediate ZOL had significantly increased LS and TH BMD vs. those who received delayed ZOL ( P < .0001 ) . Differences in fracture incidence or disease recurrence could not be ascertained because of early data cutoff and low incidence of events . Adverse events were generally mild , transient , and consistent with the known safety profiles of both agents . CONCLUSION Immediate ZOL administration effectively prevented BMD loss and increased BMD in postmenopausal women with HR(+ ) EBC receiving adjuvant letrozole , regardless of BMD status at baseline PURPOSE Treatment with aromatase inhibitors decreases bone mineral density ( BMD ) and may increase the risk of fractures in postmenopausal women with early-stage breast cancer . The addition of zoledronic acid to adjuvant letrozole therapy may protect against bone loss . PATIENTS AND METHODS Patients receiving adjuvant letrozole were r and omly assigned to receive either upfront or delayed-start zoledronic acid ( 4 mg intravenously every 6 months ) . The delayed group received zoledronic acid when lumbar spine ( LS ) or total hip ( TH ) T score decreased to less than -2.0 or when a nontraumatic fracture occurred . The primary end point of this study was to compare the change in LS BMD at month 12 between the groups . Secondary end points included change in TH BMD and changes in serum bone turnover markers at month 12 . RESULTS The upfront and delayed groups each included 301 patients . At month 12 , LS BMD was 4.4 % higher in the upfront group than in the delayed group ( 95 % CI , 3.7 % to 5.0 % ; P < .0001 ) , and TH BMD was 3.3 % higher ( 95 % CI , 2.8 % to 3.8 % ; P < .0001 ) . In the upfront group , mean serum N-telopeptide and bone-specific alkaline phosphatase concentrations decreased by 15.1 % ( P < .0001 ) and 8.8 % ( P = .0006 ) , respectively , at month 12 , whereas concentrations increased significantly in the delayed group by 19.9 % ( P = .013 ) and 24.3 % ( P < .0001 ) , respectively . CONCLUSION With 1 year of follow-up , results of the primary end point of the Zometa-Femara Adjuvant Synergy Trial ( Z-FAST ) indicate that upfront zoledronic acid therapy prevents bone loss in the LS in postmenopausal women receiving adjuvant letrozole for early-stage breast cancer BACKGROUND This ' Arimidex ' , Tamoxifen , Alone or in Combination ( ATAC ) trial sub- study examined the effects of anastrozole and tamoxifen on bone mineral density ( BMD ) following 5 years of treatment . PATIENTS AND METHODS Lumbar spine and total hip BMD were assessed at years 6 and 7 in a total of 71 eligible patients . In total , 50 patients had evaluable data . RESULTS Following anastrozole treatment , the lumbar spine median BMD increased by 2.35 % ( P=0.04 ) and 4.02 % ( P=0.0004 ) at years 6 and 7 , while total hip median BMD increased by 0.71 % ( P=0.3 ) and 0.5 % ( P=0.8 ) . After tamoxifen treatment , lumbar spine median BMD decreased by 0.79 % ( P=0.2 ) and 0.30 % ( P=0.9 ) at years 6 and 7 , while total hip median BMD decreased by 2.09 % ( P=0.0003 ) and 2.52 % ( P=0.0002 ) . Patients with a normal BMD or who were osteopenic at 5 years did not become osteoporotic . CONCLUSIONS Anastrozole treatment-related bone loss did not continue into the off-treatment follow-up period . The recovery in lumbar spine BMD and absence of further loss at the hip is consistent with the reduction in the annual rate of fracture observed after treatment cessation in the main ATAC trial BACKGROUND Aromatase inhibitors are the preferred adjuvant endocrine therapy for the majority of postmenopausal women with hormone-responsive early breast cancer . Although generally more effective than tamoxifen , aromatase inhibitor therapy is associated with increased bone loss and fracture risk . PATIENTS AND METHODS Postmenopausal women receiving adjuvant letrozole ( 2.5 mg/day for 5 years ; N = 1065 ) were r and omly assigned to immediate zoledronic acid ( zoledronate ) 4 mg every 6 months for 5 years , or delayed zoledronate ( initiated for fracture or on- study bone mineral density [ BMD ] decrease ) . The primary end point was the change in lumbar spine BMD at 12 months . Lumbar spine and total hip BMD at subsequent follow-up , disease-free survival ( DFS ) , and overall survival were assessed as secondary end points . RESULTS At 60 months ( final analysis ) , the mean change in lumbar spine BMD was + 4.3 % with immediate zoledronate and -5.4 % with delayed intervention ( P < 0.0001 ) . Immediate zoledronate reduced the risk of DFS events by 34 % ( hazard ratio [ HR ] = 0.66 ; P = 0.0375 ) with fewer local ( 0.9 % versus 2.3 % ) and distant ( 5.5 % versus 7.7 % ) recurrences versus delayed zoledronate . In the delayed group , delayed initiation of zoledronate substantially improved DFS versus no zoledronate ( HR = 0.46 ; P = 0.0334 ) . CONCLUSIONS Immediate zoledronate in postmenopausal women receiving letrozole preserved BMD and is associated with improved DFS compared with letrozole alone . Clinical Trials Registration No NCT00171340 BACKGROUND Zoledronic acid ( ZOL ) plus adjuvant endocrine therapy significantly improved disease-free survival ( DFS ) at 48- and 62-month follow-up in the ABCSG-12 trial . We present efficacy results of a final additional analysis after 94.4 months . PATIENTS AND METHODS Patients were premenopausal women who had undergone primary surgery for stage I/II estrogen-receptor-positive and /or progesterone-receptor-positive breast cancer with < 10 positive lymph nodes , and were scheduled for st and ard goserelin therapy . All 1803 patients received goserelin ( 3.6 mg every 28 days ) and were r and omized to tamoxifen ( 20 mg/days ) or anastrozole ( 1 mg/days ) , both with or without ZOL ( 4 mg every 6 months ) for 3 years . The primary end point was DFS ; recurrence-free survival and overall survival ( OS ) were secondary end points . RESULTS After 94.4-month median follow-up ( range , 0 - 114 months ) , relative risks of disease progression [ hazard ratio ( HR ) = 0.77 ; 95 % confidence interval ( CI ) 0.60 - 0.99 ; P = 0.042 ] and of death ( HR = 0.66 ; 95 % CI 0.43 - 1.02 ; P = 0.064 ) are still reduced by ZOL although no longer significant at the predefined significance level . Overall , 251 DFS events and 86 deaths were reported . Absolute risk reductions with ZOL were 3.4 % for DFS and 2.2 % for OS . There was no DFS difference between tamoxifen alone versus anastrozole alone , but there was a pronounced higher risk of death for anastrozole-treated patients ( HR = 1.63 ; 95 % CI 1.05 - 1.45 ; P = 0.030 ) . Treatments were generally well tolerated , with no reports of renal failure or osteonecrosis of the jaw . CONCLUSION These final results from ABCSG 12 suggest that twice-yearly ZOL enhances the efficacy of adjuvant endocrine treatment , and this benefit is maintained long-term . CLINICAL TRIALSGOV NCT00295646 ( http://www . clinical trials.gov/ct2/ results ? term=00295646 ) In postmenopausal women , the use of aromatase inhibitors increases bone turnover and induces bone loss at sites rich in trabecular bone at an average rate of 1 - 3 % per year leading to an increase in fracture incidence compared to that seen during tamoxifen use . The bone loss is much more marked in young women with treatment-induced ovarian suppression followed by aromatase inhibitor therapy ( average 7 - 8 % per annum ) . Pre-treatment with tamoxifen for 2 - 5 years may reduce the clinical significance of the adverse bone effects associated with aromatase inhibitors , particularly if this leads to a shortening in the duration of exposure to an aromatase inhibitor . However , skeletal status should still be assessed at the commencement of aromatase inhibitor therapy . The rate of bone loss in women who experience a premature menopause before the age of 45 or are receiving ovarian suppression therapy is accelerated by the concomitant use of aromatase inhibitors . These patients are considered to be at high risk of clinical ly important bone loss and should have a baseline dual energy X-ray absorptiometry ( DXA ) assessment of bone mineral density ( BMD ) . R and omised clinical trials in postmenopausal women indicate that bisphosphonates prevent the bone loss and accelerated bone turnover associated with aromatase inhibitor therapy and are a promising strategy for the prevention and treatment of osteoporosis in this setting . Treatment initiation recommendations are based on a combination of risk factors for osteoporotic fracture and BMD levels . Bisphosphonates , along with a healthy lifestyle and adequate intake of calcium and vitamin D are the treatments of choice to prevent bone loss . Due to the rate of bone loss associated with breast cancer treatments , and uncertainties about the interaction between aromatase inhibitor use and BMD for fracture risk , the threshold for intervention has been set at a higher level than that generally recommended for postmenopausal osteoporosis . Management recommendations have been summarised in two algorithms , one for women experiencing a premature menopause and the other for postmenopausal women requiring adjuvant aromatase inhibitor therapy BACKGROUND Chemotherapy-induced ovarian failure ( CIOF ) is a frequent side-effect of adjuvant chemotherapy that results in rapid bone loss . We hypothesised that zoledronic acid ( ZA ) , a third-generation amino bisphosphonate , would prevent bone loss in premenopausal women who developed CIOF . METHODS Women ( 439 ) were r and omised to intravenous ( i.v . ) ZA 4 mg every 3 months for 2 years starting within 1 - 3 months after r and omization ( arm A ) or 1 year after r and omization ( arm B , controls ) . CIOF was prospect ively defined as ≥ 3 months of amenorrhoea , follicle-stimulating hormone ( FSH ) ≥ 30 MIU/ml and non-pregnant at 1 year . The primary end-point was the percentage change in bone mineral density ( BMD ) in the lumbar spine ( LS ) from baseline to 12 months in the ZA and in control groups in women who developed CIOF ; the secondary end-point was BMD in LS at 3 years in all r and omised women . FINDINGS One hundred and fifty ( 56 % ) met the definition of CIOF at 1 year . Overall , grade 3 toxicities of ZA were fatigue ( 1 % ) arthralgias ( 21 % ) and pain ( 84 % ) . The median percent change ( interquartile range , IQR ) at 1 year was + 1.2 % ( -0.5 % to + 2.8 % ) and -6.7 % ( -9.7 % to -2.9 % ) p<0.001 and at 3 years was + 1.0 % ( -1.6 % to + 5.2 % ) and -0.5 % ( -3.7 % to + 3.2 % ) p=0.019 in arms A and B , respectively . INTERPRETATION ZA every 3 months is well tolerated and prevents rapid bone loss in premenopausal women that develop CIOF . Giving ZA with rather than 1 year after the start of adjuvant chemotherapy is the preferred sequence to prevent bone loss |
1,840 | 26,822,311 | Discussion The principal hypothesis is that reduction of polypharmacy and inappropriate prescribing can improve the clinical composite outcome of hospitalization or death .
A positive result of the trial will contribute substantially to the improvement of care in multimorbidity . | Background Multimorbidity is increasing in aging population s with a corresponding increase in polypharmacy as well as inappropriate prescribing .
Depending on definitions , 25 - 50 % of patients aged 75 years or older are exposed to at least five drugs .
Evidence is increasing that polypharmacy , even when guidelines advise the prescribing of each drug individually , can potentially cause more harm than benefit to older patients , due to factors such as drug-drug and drug-disease interactions .
Several approaches reducing polypharmacy and inappropriate prescribing have been proposed , but evidence showing a benefit of these measures regarding clinical ly relevant endpoints is scarce .
There is an urgent need to implement more effective strategies .
We therefore set out to develop an evidence -based electronic decision support ( eDS ) tool to aid physicians in reducing inappropriate prescribing and test its effectiveness in a large-scale cluster-r and omized controlled trial .
Methods The “ Polypharmacy in chronic diseases – Reduction of Inappropriate Medication and Adverse drug events in older population s ” (PRIMA)-eDS tool is a tool comprising an indication check and recommendations for the reduction of polypharmacy and inappropriate prescribing based on systematic review s and guidelines , the European list of inappropriate medications for older people , the SFINX- data base of interactions , the PHARAO- data base on adverse effects , and the RENBASE- data base on renal dosing . | OBJECTIVES To determine whether a medication review by a specialized team would promote regimen changes in elders taking multiple medications and to measure the effect of regimen changes on monthly cost and functioning . DESIGN A r and omized-controlled trial . SETTING Health center ambulatory clinic . PARTICIPANTS Community-dwelling older adults taking five or more medications were assessed at baseline and 6 weeks . A medication-change intervention group of 57 elders was compared with a control group of 76 elder adults . INTERVENTION The primary intervention was a comprehensive review and recommended modification of a patient 's medication regimen . Changes were endorsed by each patient 's primary physician and discussed with each patient . MEASUREMENTS Measures were the Timed Manual Performance Test , Physical Performance Test , Functional Reach Assessment , subtests from the Wechsler Adult Intelligence Scale , a modified R and t Memory Test , the Center for Epidemiological Studies -Depression Scale , the Self-Rating Anxiety Scale , and the R and 36-item Health Survey 1.0 . Comorbidity was determined using the International Classification of Diseases , Ninth Revision , Clinical Modification . Medication usage was determined using brown bag review . RESULTS Intervention subjects decreased their medications by an average of 1.5 drugs . No differences in functioning were observed between groups . Intervention subjects saved an average $ 26.92 per month in wholesale medication costs ; control subjects saved $ 6.75 per month ( P<.006 ) . CONCLUSION Although the intervention significantly reduced the medications taken and monthly cost , most patients were resistant to reducing medications to the recommended level . Further study is needed to underst and patient resistance to reducing adverse polypharmacy and to devise better strategies for addressing this important problem in geriatric health . Greater focus on prescriber behavior is recommended Background : There is no single generally accepted clinical definition of frailty . Previously developed tools to assess frailty that have been shown to be predictive of death or need for entry into an institutional facility have not gained acceptance among practising clinicians . We aim ed to develop a tool that would be both predictive and easy to use . Methods : We developed the 7-point Clinical Frailty Scale and applied it and other established tools that measure frailty to 2305 elderly patients who participated in the second stage of the Canadian Study of Health and Aging ( CSHA ) . We followed this cohort prospect ively ; after 5 years , we determined the ability of the Clinical Frailty Scale to predict death or need for institutional care , and correlated the results with those obtained from other established tools . Results : The CSHA Clinical Frailty Scale was highly correlated ( r = 0.80 ) with the Frailty Index . Each 1-category increment of our scale significantly increased the medium-term risks of death ( 21.2 % within about 70 mo , 95 % confidence interval [ CI ] 12.5%–30.6 % ) and entry into an institution ( 23.9 % , 95 % CI 8.8%–41.2 % ) in multivariable models that adjusted for age , sex and education . Analyses of receiver operating characteristic curves showed that our Clinical Frailty Scale performed better than measures of cognition , function or comorbidity in assessing risk for death ( area under the curve 0.77 for 18-month and 0.70 for 70-month mortality ) . Interpretation : Frailty is a valid and clinical ly important construct that is recognizable by physicians . Clinical judgments about frailty can yield useful predictive information Background Computer-based decision support systems are a promising method for incorporating research evidence into clinical practice . However , evidence is still scant on how such information technology solutions work in primary healthcare when support is provided across many health problems . In Finl and , we design ed a trial where a set of evidence -based , patient-specific reminders was introduced into the local Electronic Patient Record ( EPR ) system . The aim was to measure the effects of such reminders on patient care . The hypothesis was that the total number of triggered reminders would decrease in the intervention group compared with the control group , indicating an improvement in patient care . Methods From July 2009 to October 2010 all the patients of one health center were r and omized to an intervention or a control group . The intervention consisted of patient-specific reminders concerning 59 different health conditions triggered when the healthcare professional ( HCP ) opened and used the EPR . In the intervention group , the triggered reminders were shown to the HCP ; in the control group , the triggered reminders were not shown . The primary outcome measure was the change in the number of reminders triggered over 12 months . We developed a unique data gathering method , the Repeated Study Virtual Health Check ( RSVHC ) , and used Generalized Estimation Equations ( GEE ) for analysing the incidence rate ratio , which is a measure of the relative difference in percentage change in the numbers of reminders triggered in the intervention group and the control group . Results In total , 13,588 participants were r and omized and included . Contrary to our expectation , the total number of reminders triggered increased in both the intervention and the control groups . The primary outcome measure did not show a significant difference between the groups . However , with the inclusion of patients followed up over only six months , the total number of reminders increased significantly less in the intervention group than in the control group when the confounding factors ( age , gender , number of diagnoses and medications ) were controlled for . Conclusions Computerized , tailored reminders in primary care did not decrease during the 12 months of follow-up time after the introduction of a patient-specific decision support system . Trial registration Clinical Trial.gov OBJECTIVES To describe patterns of comorbidity and multimorbidity in elderly people . DESIGN A community-based survey . SETTING Data were gathered from the Kungsholmen Project , a urban , community-based prospect i ve cohort in Sweden . PARTICIPANTS Adults aged 77 and older living in the community and in institutions of the geographically defined Kungsholmen area of Stockholm ( N=1,099 ) . MEASUREMENTS Diagnoses based on physicians ' examinations and supported by hospital records , drug use , and blood sample s. Patterns of comorbidity and multimorbidity were evaluated using four analytical approaches : prevalence figures , conditional count , logistic regression models , and cluster analysis . RESULTS Visual impairments and heart failure were the diseases with the highest comorbidity ( mean 2.9 and 2.6 co-occurring conditions , respectively ) , whereas dementia had the lowest ( mean 1.4 comorbidities ) . Heart failure occurred rarely without any comorbidity ( 0.4 % ) . The observed prevalence of comorbid pairs of conditions exceeded the expected prevalence for several circulatory diseases and for dementia and depression . Logistic regression analyses detected similar comorbid pairs . The cluster analysis revealed five clusters . Two clusters included vascular conditions ( circulatory and cardiopulmonary clusters ) , and another included mental diseases along with musculoskeletal disorders . The last two clusters included only one major disease each ( diabetes mellitus and malignancy ) together with their most common consequences ( visual impairment and anemia , respectively ) . CONCLUSION In persons with multimorbidity , there exists co-occurrence of diseases beyond chance , which clinicians need to take into account in their daily practice . Some pathological mechanisms behind the identified clusters are well known ; others need further clarification to identify possible preventative strategies BACKGROUND Older people consume an increasing amount of medication . Polypharmacy is associated with an elevated risk of adverse health outcomes result ing in hospitalizations and sometimes death . OBJECTIVES To describe the prevalence of prescribed and over-the-counter ( OTC ) medications among older general practice patients living in the community . To determine predictors of polypharmacy ( five or more prescribed drugs ) from a variety of patient- and doctor-related factors . METHODS Sixty-seven r and omly selected practice s in two areas of Germany and 466 of their older patients ( 70 + years ) were recruited for a geriatric assessment study . A cross-sectional analysis of health problems , GPs ' awareness and their interventions was conducted . In this post hoc analysis , we assessed the medication use as reported by older patients and compared it with doctors ' perceived medication regimens for their respective patients . The detailed assessment of patients ' health and well-being enabled us to explore a variety of predictors of polypharmacy using logistic regression analysis with forward selection . RESULTS Study participants consumed an average of 3.7 prescribed medicines and an additional 1.4 OTC drugs . In all , 26.7 % of patients used five and more chronically prescribed drugs . A set of five determinants predicted polypharmacy best : breathlessness , hypertension , dependency on instrumental activities of daily living , low subjective health and medication disagreement between doctors and patients . CONCLUSION This older general practice population in Germany is among the top pharmaceutical user group of European study sample s. Apart from disease-specific determinants , GPs should be aware that low subjective health and medication disagreement are independent predictors of polypharmacy Abstract Objective To ascertain the current burden of adverse drug reactions ( ADRs ) through a prospect i ve analysis of all admissions to hospital . Design Prospect i ve observational study . Setting Two large general hospitals in Merseyside , Engl and . Participants 18 820 patients aged > 16 years admitted over six months and assessed for cause of admission . Main outcome measures Prevalence of admissions due to an ADR , length of stay , avoidability , and outcome . Results There were 1225 admissions related to an ADR , giving a prevalence of 6.5 % , with the ADR directly leading to the admission in 80 % of cases . The median bed stay was eight days , accounting for 4 % of the hospital bed capacity . The projected annual cost of such admissions to the NHS is £ 466 m ( € 706 m , $ 847 m ) . The overall fatality was 0.15 % . Most reactions were either definitely or possibly avoidable . Drugs most commonly implicated in causing these admissions included low dose aspirin , diuretics , warfarin , and non-steroidal anti-inflammatory drugs other than aspirin , the most common reaction being gastrointestinal bleeding . Conclusion The burden of ADRs on the NHS is high , accounting for considerable morbidity , mortality , and extra costs . Although many of the implicated drugs have proved benefit , measures need to be put into place to reduce the burden of ADRs and thereby further improve the benefit : harm ratio of the drugs Background Disease management programmes ( DMPs ) are costly and impose additional work load on general practitioners ( GPs ) . Data on their effectiveness are inconclusive . We therefore conducted a cluster-r and omised controlled trial to evaluate the effectiveness of the Austrian DMP for diabetes mellitus type 2 on HbA1c and quality of care for adult patients in primary care . Methods All GPs of Salzburg-province were invited to participate . After cluster-r and omisation by district , all patients with diabetes type 2 were recruited consecutively from 7 - 11/2007 . The DMP , consisting mainly of physician and patient education , st and ardised documentation and agreement on therapeutic goals , was implemented in the intervention group while the control group received usual care . We aim ed to show superiority of the intervention regarding metabolic control and process quality . The primary outcome measure was a change in HbA1c after one year . Secondary outcomes were days in the hospital , blood pressure , lipids , body mass index ( BMI ) , enrolment in patient education and regular guideline -adherent examination . Blinding was not possible . Results 92 physicians recruited 1489 patients ( 649 intervention , 840 control ) . After 401 ± 47 days , 590 intervention- patients and 754 controls had complete data . In the intention to treat analysis ( ITT ) of all 1489 patients , HbA1c decreased 0.41 % in the intervention group and 0.28 % in controls . The difference of -0.13 % ( 95 % CI -0.24 ; -0.02 ) was significant at p = 0.026 . Significance was lost in mixed models adjusted for baseline value and cluster-effects ( adjusted mean difference -0.03 ( 95 % CI -0.15 ; 0.09 , p = 0.607 ) . Of the secondary outcome measures , BMI and cholesterol were significantly reduced in the intervention group compared to controls in ITT after adjustments ( -0.53 kg/m² ; 95 % CI -1.03;-0.02 ; p = 0.014 and -0.10 mmol/l ; 95 % CI -0.21 ; -0.003 ; p = 0.043 ) . Additionally , more patients received patient education ( 49.5 % vs. 20.1 % , p < 0.0001 ) , eye- ( 71.0 % vs. 51.2 % , p < 0.0001 ) , foot examinations ( 73.8 % vs. 45.1 % , p < 0.0001 ) , and regular HbA1c checks ( 44.1 % vs. 36.0 % , p < 0.01 ) in the intervention group . Conclusion The Austrian DMP implemented by statutory health insurance improves process quality and enhances weight reduction , but does not significantly improve metabolic control for patients with type 2 diabetes mellitus . Whether the small benefit seen in secondary outcome measures leads to better patient outcomes , remains unclear . Trial Registration Current Controlled trials Ltd. , IS RCT N27414162 INTRODUCTION STOPP ( Screening Tool of Older Persons ' potentially inappropriate Prescriptions ) is a new , systems-defined medicine review tool . We compared the performance of STOPP to that of established Beers ' criteria in detecting potentially inappropriate medicines ( PIMs ) and related adverse drug events ( ADEs ) in older patients presenting for hospital admission . METHODS we prospect ively studied 715 consecutive acute admissions to a university teaching hospital . Diagnoses , reason for admission and concurrent medications were recorded . STOPP and Beers ' criteria were applied . PIMs with clear causal connection or contribution to the principal reason for admission were determined . RESULTS median patient age ( interquartile range ) was 77 ( 72 - 82 ) years . Median number of prescription medicines was 6 ( range 0 - 21 ) . STOPP identified 336 PIMs affecting 247 patients ( 35 % ) , of whom one-third ( n = 82 ) presented with an associated ADE . Beers ' criteria identified 226 PIMs affecting 177 patients ( 25 % ) , of whom 43 presented with an associated ADE . STOPP-related PIMs contributed to 11.5 % of all admissions . Beers ' criteria -related PIMs contributed to significantly fewer admissions ( 6 % ) . CONCLUSION STOPP criteria identified a significantly higher proportion of patients requiring hospitalisation as a result of PIM-related adverse events than Beers ' criteria . This finding has significant implication s for hospital geriatric practice BACKGROUND Previous studies have not demonstrated a consistent association between potentially inappropriate medicines ( PIMs ) in older patients as defined by Beers criteria and avoidable adverse drug events ( ADEs ) . This study aim ed to assess whether PIMs defined by new STOPP ( Screening Tool of Older Persons ' potentially inappropriate Prescriptions ) criteria are significantly associated with ADEs in older people with acute illness . METHODS We prospect ively studied 600 consecutive patients 65 years or older who were admitted with acute illness to a university teaching hospital over a 4-month interval . Potentially inappropriate medicines were defined by both Beers and STOPP criteria . Adverse drug events were defined by World Health Organization-Uppsala Monitoring Centre criteria and verified by a local expert consensus panel , which also assessed whether ADEs were causal or contributory to current hospitalization . Hallas criteria defined ADE avoidability . We compared the proportions of patients taking Beers criteria PIMs and STOPP criteria PIMs with avoidable ADEs that were causal or contributory to admission . RESULTS A total of 329 ADEs were detected in 158 of 600 patients ( 26.3 % ) ; 219 of 329 ADEs ( 66.6 % ) were considered causal or contributory to admission . Of the 219 ADEs , 151 ( 68.9 % ) considered causal or contributory to admission were avoidable or potentially avoidable . After adjusting for age , sex , comorbidity , dementia , baseline activities of daily living function , and number of medications , the likelihood of a serious avoidable ADE increased significantly when STOPP PIMs were prescribed ( odds ratio , 1.847 ; 95 % confidence interval [ CI ] , 1.506 - 2.264 ; P < .001 ) ; prescription of Beers criteria PIMs did not significantly increase ADE risk ( odds ratio , 1.276 ; 95 % CI , 0.945 - 1.722 ; P = .11 ) . CONCLUSION STOPP criteria PIMs , unlike Beers criteria PIMs , are significantly associated with avoidable ADEs in older people that cause or contribute to urgent hospitalization Inappropriate polypharmacy , especially in older people , imposes a substantial burden of adverse drug events , ill health , disability , hospitalization , and even death . The single most important predictor of inappropriate prescribing and risk of adverse drug events in older patients is the number of prescribed drugs . Deprescribing is the process of tapering or stopping drugs , aim ed at minimizing polypharmacy and improving patient outcomes . Evidence of efficacy for deprescribing is emerging from r and omized trials and observational studies . A deprescribing protocol is proposed comprising 5 steps : ( 1 ) ascertain all drugs the patient is currently taking and the reasons for each one ; ( 2 ) consider overall risk of drug-induced harm in individual patients in determining the required intensity of deprescribing intervention ; ( 3 ) assess each drug in regard to its current or future benefit potential compared with current or future harm or burden potential ; ( 4 ) prioritize drugs for discontinuation that have the lowest benefit-harm ratio and lowest likelihood of adverse withdrawal reactions or disease rebound syndromes ; and ( 5 ) implement a discontinuation regimen and monitor patients closely for improvement in outcomes or onset of adverse effects . Whereas patient and prescriber barriers to deprescribing exist , re sources and strategies are available that facilitate deliberate yet judicious deprescribing and deserve wider application OBJECTIVE To describe medication use among older community-dwelling Icel and ers by collecting information on number of medicine , polypharmacy ( > 5 medications ) , and medications by ATC categories . Moreover , to explore the relationship between medication use and various influential factors emphasizing residency in urban and rural areas . MATERIAL AND METHODS Population -based , cross-sectional study . Participants were r and omly selected from the National registry in one urban ( n=118 ) and two rural ( n=68 ) areas . INCLUSION CRITERIA 1 ) ≥ 65 years old , 2 ) community-dwelling , 3 ) able to communicate verbally . Information on medication use was obtained from each person 's medication list and interviews . A question naire and five st and ardized instruments were used to assess the potential influencing factors . RESULTS On average , participants used 3.9 medications and prevalence of polypharmacy was 41 % . Men used 3.5 medications on average and women 4.4 ( p=0.018 ) . Compared to rural residents , urban residents had fewer medical diagnoses , better mobility , less pain , and fewer depressive symptoms . By controlling for the effects of these variables , more medications were associated with urban living ( p<0.001 ) and more medical diagnoses ( p<0.001 ) . Likewise , adjusted odds for polypharmacy increased with urban residency ( p=0.023 ) and more medical diagnoses ( p=0.005 ) . Urban residency , more medical diagnoses , higher age , and male gender were related to use of drugs for blood and blood forming organs . CONCLUSION The results reveal an unexplained regional difference in medications use by older Icel and ers . Further studies are required on why urban residents use at least equal amount of medications as rural residents despite better scores on health assessment BACKGROUND Medication-related problems that lead to hospitalization have been the subject of many studies , many of which were limited to 1 hospital or lacked patient follow-up . Furthermore , little information exists on potential risk factors associated with preventable medication-related hospitalizations . METHODS A prospect i ve multicenter study was conducted to determine the frequency and patient outcomes of medication-related hospital admissions . A case-control design was used to determine risk factors for potentially preventable admissions . All unplanned admissions in 21 hospitals were assessed during 40 days . Controls were patients admitted for elective surgery . Cases and controls were followed up until hospital discharge . The frequency of medication-related hospital admissions , potential preventability , and outcomes were assessed . For potentially preventable medication-related admissions , risk factors were identified in the case-control study . RESULTS Almost 13,000 unplanned admissions were screened , of which 714 ( 5.6 % ) were medication related . Almost half ( 46.5 % ) of these admissions were potentially preventable , result ing in 332 case patients matched with 332 controls . Outcomes were favorable in most patients . The main determinants of preventable medication-related hospital admissions were impaired cognition ( odds ratio , 11.9 ; 95 % confidence interval , 3.9 - 36.3 ) , 4 or more comorbidities ( 8.1 ; 3.1 - 21.7 ) , dependent living situation ( 3.0 ; 1.4 - 6.5 ) , impaired renal function ( 2.6 ; 1.6 - 4.2 ) , nonadherence to medication regimen ( 2.3 ; 1.4 - 3.8 ) , and polypharmacy ( 2.7 ; 1.6 - 4.4 ) . CONCLUSIONS Adverse drug events are an important cause of hospitalizations , and almost half are potentially preventable . The identified risk factors provide a starting point for preventing medication-related hospital admissions BACKGROUND Polypharmacy and inappropriate medication use is a problem in elderly patients , who are more likely to experience adverse effects from multiple treatments and less likely to obtain the same therapeutic benefit as younger population s. The Good Palliative-Geriatric Practice algorithm for drug discontinuation has been shown to be effective in reducing polypharmacy and improving mortality and morbidity in nursing home in patients . This study reports the feasibility of this approach in community-dwelling older patients . METHODS The Good Palliative-Geriatric Practice algorithm was applied to a cohort of 70 community-dwelling older patients to recommend drug discontinuations . Success rates of discontinuation , morbidity , mortality , and changes in health status were recorded . RESULTS The mean ( SD ) age of the 70 patients was 82.8 ( 6.9 ) years . Forty-three patients ( 61 % ) had 3 or more and 26 % had 5 or more comorbidities . The mean follow-up was 19 months . Participants used a mean ( SD ) of 7.7 ( 3.7 ) medications . Protocol indicated that discontinuation was recommended for 311 medications in 64 patients ( 58 % of drugs ; mean [ SD ] , 4.4 [ 2.5 ] drugs per patient overall , 4.9 per patient who had discontinuation ) . Of the discontinued drug therapies , 2 % were restarted because of recurrence of the original indication . Taking nonconsent and failures together , successful discontinuation was achieved in 81 % . Ten elderly patients ( 14 % ) died after a mean follow-up of 13 months , with the mean age at death of 89 years . No significant adverse events or deaths were attributable to discontinuation , and 88 % of patients reported global improvement in health . CONCLUSIONS It is feasible to decrease medication burden in community-dwelling elderly patients . This tool would be suitable for larger r and omized controlled trials in different clinical setting Background Hospital admissions may provide an opportunity to discontinue potentially inappropriate medications ( PIMs ) in older patients . Little is known about the effect of using the Screening Tool of Older People ’s potentially inappropriate Prescriptions ( STOPP ) in this context . This study aim ed to test the hypothesis that specific STOPP recommendations from an inpatient geriatric consultation team ( IGCT ) to the hospital physician leads to reductions in PIMs for patients at discharge . Methods This was a r and omised controlled study in 146 frail in patients ( in 2011 ) . The intervention consisted of STOPP recommendations made by the IGCT to ward physicians to discontinue PIMs , in addition to the st and ard geriatric advice . Results Intervention ( n = 74 ) and control ( n = 72 ) groups were similar in terms of patient characteristics ( median age 85 years ; median number of daily drugs , seven ) and PIM distribution ( 68 and 57 PIMs in 53 and 51 % of patients , respectively ) . At discharge , the reduction in PIMs was twice as high for the intervention group as for the control group ( 39.7 and 19.3 % , respectively ; p = 0.013 ) . The proportion of patients who still had one or more PIM at discharge did not differ between groups . In the 50 patients followed-up a year later , the majority of PIMs that had been stopped during hospitalisation had not been restarted after discharge ( 17/28 ; 61 % ) . The clinical relevance of PIMs identified at baseline in those patients was considered major ( 29 % ) , moderate ( 37 % ) , minor ( 5 % ) , deleterious ( 8 % ) , or not assessed ( 11 % ) . Discontinuation rate was not associated with clinical importance . ConclusionS pecific STOPP recommendations provided to hospital physicians doubled the reduction of PIMs at discharge in frail older in patients . To further improve the appropriateness of prescribing in older patients , clinicians should focus on the STOPP criteria that are of major clinical importance , and general practitioners should be actively involved |
1,841 | 29,299,317 | There was limited evidence found for the reliability and /or validity of 5 m , 10 m , 20 m speed tests , 505 test , modified 505 test , L run test , Sergeant Jump test and bench press repetitions-to-fatigue tests .
There was no information from high- quality studies on the measurement properties of all the other tests identified in stage 1 .
However , there is paucity of information on measurement properties from high- quality studies for the tests . | Background This systematic review was conducted with the first objective aim ed at providing an overview of the physiological characteristics commonly evaluated in rugby and the corresponding tests used to measure each construct .
Secondly , the measurement properties of all identified tests per physiological construct were evaluated with the ultimate purpose of identifying tests with strongest level of evidence per construct .
Conclusion A number of physiological characteristics are evaluated in rugby .
Each physiological construct has multiple tests for measurement . | The aim of the study was to investigate test reliability of the Yo-Yo intermittent recovery test level 1 ( YYIR1 ) in 36 high-level youth soccer players , aged between 13 and 18 years . Players were divided into three age groups ( U15 , U17 and U19 ) and completed three YYIR1 in three consecutive weeks . Pairwise comparisons were used to investigate test reliability ( for distances and heart rate responses ) using technical error ( TE ) , coefficient of variation ( CV ) , intra-class correlation ( ICC ) and limits of agreement ( LOA ) with Bl and -Altman plots . The mean YYIR1 distances for the U15 , U17 and U19 groups were 2024 ± 470 m , 2404 ± 347 m and 2547 ± 337 m , respectively . The results revealed that the TEs varied between 74 and 172 m , CVs between 3.0 and 7.5 % , and ICCs between 0.87 and 0.95 across all age groups for the YYIR1 distance . For heart rate responses , the TEs varied between 1 and 6 bpm , CVs between 0.7 and 4.8 % , and ICCs between 0.73 and 0.97 . The small ratio LOA revealed that any two YYIR1 performances in one week will not differ by more than 9 to 28 % due to measurement error . In summary , the YYIR1 performance and the physiological responses have proven to be highly reliable in a sample of Belgian high-level youth soccer players , aged between 13 and 18 years . The demonstrated high level of intermittent endurance capacity in all age groups may be used for comparison of other prospect i ve young soccer players Validity and Reproducibility of the Sargent Jump Test in the Assessment of Explosive Strength in Soccer Players The purpose of this study was to check the validity and the intra- and inter-evaluators reproducibility of the Sargent Jump Test , as an instrument of explosive strength measurement of soccer players of the sub-15 class . Forty-five soccer players were r and omly selected from different clubs competing in the local soccer championship . All subjects performed one test on the same jump platform model Jumptest ® ( Hidrofit Ltda , Brazil ) and two independent Sargent Jump Tests assessed by the same evaluator . Two days later , another Sargent Jump Test was performed simultaneously assessed by 2 evaluators . In all tests , three jumps were performed and the highest one was registered . In order to check the validity , the first Sargent Jump Test results were compared to those from the jump platform , considered the gold st and ard . To evaluate intra- and inter-evaluator reproducibility , results from the first , second and third Sargent Jump Tests were analyzed . The validity and reproducibility were evaluated by intraclass correlation coefficients ( ICC ) , and by the Bl and and Altman test ( statistical pack SPSS 11.0 ) , with a significance level set at p<0.05 . The values found for validity ( r=0.99 , p=0.001 ) , for intra-evaluator reproducibility ( r=0.99 , p=0.001 ) and for inter-evaluator reproducibility ( r=1.0 , p=0.001 ) , permitted us to conclude that the Sargent Jump Test is a valid and reproducible instrument for measuring the explosive strength in homogeneous groups , such as those used in the present study Objectives For the measurement of patient-reported outcomes , such as ( health-related ) quality of life , often many measurement instruments exist that intend to measure the same construct . To facilitate instrument selection , our aim was to develop a highly sensitive search filter for finding studies on measurement properties of measurement instruments in PubMed and a more precise search filter that needs less abstract s to be screened , but at a higher risk of missing relevant studies . Methods A r and om sample of 10,000 PubMed records ( 01 - 01 - 1990 to 31 - 12 - 2006 ) was used as a gold st and ard . Studies on measurement properties were identified using an exclusion filter and h and search ing . Search terms were selected from the relevant records in the gold st and ard as well as from 100 systematic review s of measurement properties and combined based on sensitivity and precision . The performance of the filters was tested in the gold st and ard as well as in two validation sets , by calculating sensitivity , precision , specificity , and number needed to read . Results We identified 116 studies on measurement properties in the gold st and ard . The sensitive search filter was able to retrieve 113 of these 116 studies ( sensitivity 97.4 % , precision 4.4 % ) . The precise search filter had a sensitivity of 93.1 % and a precision of 9.4 % . Both filters performed very well in the validation sets . Conclusion The use of these search filters will contribute to evidence -based selection of measurement instruments in all medical fields Prediction of adult performance from early age talent identification in sport remains difficult . Talent identification research has generally been performed using univariate analysis , which ignores multivariate relationships . To address this issue , this study used a novel higher-dimensional model to orthogonalize multivariate anthropometric and fitness data from junior rugby league players , with the aim of differentiating future career attainment . Anthropometric and fitness data from 257 Under-15 rugby league players was collected . Players were grouped retrospectively according to their future career attainment ( i.e. , amateur , academy , professional ) . Players were blindly and r and omly divided into an exploratory ( n = 165 ) and validation data set ( n = 92 ) . The exploratory data set was used to develop and optimize a novel higher-dimensional model , which combined singular value decomposition ( SVD ) with receiver operating characteristic analysis . Once optimized , the model was tested using the validation data set . SVD analysis revealed 60 m sprint and agility 505 performance were the most influential characteristics in distinguishing future professional players from amateur and academy players . The exploratory data set model was able to distinguish between future amateur and professional players with a high degree of accuracy ( sensitivity = 85.7 % , specificity = 71.1 % ; p<0.001 ) , although it could not distinguish between future professional and academy players . The validation data set model was able to distinguish future professionals from the rest with reasonable accuracy ( sensitivity = 83.3 % , specificity = 63.8 % ; p = 0.003 ) . Through the use of SVD analysis it was possible to objective ly identify criteria to distinguish future career attainment with a sensitivity over 80 % using anthropometric and fitness data alone . As such , this suggests that SVD analysis may be a useful analysis tool for research and practice within talent identification PURPOSE To examine the physiological response and reproducibility of the Yo-Yo intermittent recovery test and its application to elite soccer . METHODS Heart rate was measured , and metabolites were determined in blood and muscle biopsies obtained before , during , and after the Yo-Yo test in 17 males . Physiological measurements were also performed during a Yo-Yo retest and an exhaustive incremental treadmill test ( ITT ) . Additionally , 37 male elite soccer players performed two to four seasonal tests , and the results were related to physical performance in matches . RESULTS The test-retest CV for the Yo-Yo test was 4.9 % . Peak heart rate was similar in ITT and Yo-Yo test ( 189 + /- 2 vs 187 + /- 2 bpm ) , whereas peak blood lactate was higher ( P < 0.05 ) in the Yo-Yo test . During the Yo-Yo test , muscle lactate increased eightfold ( P < 0.05 ) and muscle creatine phosphate ( CP ) and glycogen decreased ( P < 0.05 ) by 51 % and 23 % , respectively . No significant differences were observed in muscle CP , lactate , pH , or glycogen between 90 and 100 % of exhaustion time . During the precompetition period , elite soccer players improved ( P < 0.05 ) Yo-Yo test performance and maximum oxygen uptake ( [OV0312]O(2max ) ) by 25 + /- 6 and 7 + /- 1 % , respectively . High-intensity running covered by the players during games was correlated to Yo-Yo test performance ( r = 0.71 , P < 0.05 ) but not to [OV0312]O(2max ) and ITT performance . CONCLUSION The test had a high reproducibility and sensitivity , allowing for detailed analysis of the physical capacity of athletes in intermittent sports . Specifically , the Yo-Yo intermittent recovery test was a valid measure of fitness performance in soccer . During the test , the aerobic loading approached maximal values , and the anaerobic energy system was highly taxed . Additionally , the study suggests that fatigue during intense intermittent short-term exercise was unrelated to muscle CP , lactate , pH , and glycogen Markovic , G and Mikulic , P. Discriminative ability of the Yo-Yo intermittent recovery test ( level 1 ) in prospect i ve young soccer players . J Strength Cond Res 25(10 ) : 2931–2934 , 2011—We evaluated the sensitivity of the Yo-Yo intermittent recovery test-level 1 ( Yo-Yo IR1 ) when discriminating among players in varying playing positions and different age categories in youth soccer . One-hundred and six prospect i ve young soccer players , grouped on the basis of chronological age ( under-13 , under-14 , under-15 , under-16 , under-17 , under-18 , and under-19 ) and playing position ( center-backs , fullbacks , center midfielders , wide midfielders , and forwards ) , participated in the study . The players were administered a single Yo-Yo IR1 test at the beginning of the spring season . Analysis of variance revealed significant ( F = 25.3 ; p < 0.001 ) group differences in Yo-Yo IR1 test performance scores among the observed age categories , and a systematic age-related increase in the Yo-Yo IR1 test performance was evident . Subsequent post hoc comparisons identified a number of significant differences among the selected age categories in Yo-Yo IR1 test performance . Analysis of covariance identified significant differences among playing positions ( F = 3.1 ; p < 0.019 ) in the Yo-Yo IR1 test performance after controlling for age ( F = 135.1 ; p < 0.001 ) . Subsequent pairwise comparisons of the adjusted Yo-Yo IR1 test performance identified that center-backs had achieved significantly lower ( all p < 0.01 ) performance scores than center midfielders , wide midfielders , and forwards , but not fullbacks . These results could be of practical value to coaches and scientists for further development of talent selection and profiling procedures in soccer , particularly because ( a ) the endurance performance represents a very important fitness component in selection and profiling of young soccer players and ( b ) the Yo-Yo IR1 test proved to be valid , reliable , and easily available measurement tool of a player 's soccer-specific endurance capacity PURPOSE To examine the physiological response , reliability , and validity of the Yo-Yo intermittent recovery level 2 test ( Yo-Yo IR2 ) . METHODS Thirteen normally trained male subjects carried out four Yo-Yo IR2 tests , an incremental treadmill test ( ITT ) , and various sprint tests . Muscle biopsies and blood sample s were obtained , and heart rate was measured before , during , and after the Yo-Yo IR2 test . Additionally , 119 Sc and inavian elite soccer players carried out the Yo-Yo IR2 test on two to four occasions . RESULTS Yo-Yo IR2 performance was 591 + /- 43 ( 320 - 920 ) m or 4.3 ( 2.6 - 7.9 ) min . Test-retest coefficient of variation in distance covered was 9.6 % ( N = 29 ) . Heart rate ( HR ) at exhaustion was 191 + /- 3 bpm , or 98 + /- 1 % HRmax . Muscle lactate was 41.7 + /- 5.4 and 68.5 + /- 7.6 mmol x kg(-1 ) d.w . at 85 and 100 % of exhaustion time , respectively , with corresponding muscle CP values of 40.4 + /- 5.2 and 29.4 + /- 4.7 mmol x kg(-1 ) d.w . Peak blood lactate was 13.6 + /- 0.5 mM. Yo-Yo IR2 performance was correlated to ITT performance ( r = 0.74 , P < 0.05 ) and VO2max ( r = 0.56 , P < 0.05 ) but not to 30- and 50-m sprint performance . Yo-Yo IR2 performance was better ( P < 0.05 ) for international elite soccer players than for moderate elite players ( 1059 + /- 35 vs 771 + /- 26 m ) and better ( P < 0.05 ) for central defenders ( N = 21 ) , fullbacks ( N = 20 ) , and midfielders ( N = 48 ) than for goal keepers ( N = 6 ) and attackers ( N = 24 ) . Fifteen elite soccer players improved ( P < 0.05 ) Yo-Yo IR2 performance by 42 + /- 8 % during 8 wk of preseasonal training . CONCLUSION This study demonstrates that the Yo-Yo IR2 test is reproducible and can be used to evaluate an athlete 's ability to perform intense intermittent exercise with a high rate of aerobic and anaerobic energy turnover . Specifically , the Yo-Yo IR2 test was shown to be a sensitive tool to differentiate between intermittent exercise performance of soccer players in different seasonal periods and at different competitive levels and playing positions Maximally accumulated oxygen deficit ( MAOD ) has been argued to be currently the best non-invasive method for estimating anaerobic capacity ( Medbø et al. , 1988 , Ramsbottom et al. , 1997 ) . An easy to administer field test that could accurately predict MAOD , would be of great use to many field sport athletes and coaches . Fifteen male rugby union players undertook MAOD testing ( 99.4 + /- 16.9ml x kg(-1 ) ) on a treadmill using a modification of procedure 3 as described by Medbø et al. ( 1988 ) . All subjects also performed a 300 m Shuttle Run Test ( 66.7 + /- 2.2s ) , run over a 20 m distance . Analysis of the MAOD and 300 m Shuttle Run Test time relationship revealed a significant correlation of r = -0.69 [ p<0.01 ) . Furthermore , a one-way analysis of variance ( ANOVA ) revealed that when subjects were split into ' good ' and ' poor ' groups based on 300 m Shuttle Run Test times , the times distinguished between ' good ' and ' poor ' MAOD values ( P<0.05 ) . The findings of the present study support the validity of the 300 m Shuttle Run Test as a useful estimate of anaerobic capacity in football athletes . Unexplained variance could be due to speed and agility factors associated with the 300 m Shuttle Run Test . Method ological issues pertaining to the accurate assessment of MAOD are also discussed This study investigated the physiological and anthropometric characteristics of rugby league players during a competitive season . Sixty-eight rugby league players were allocated into training ( n = 52 ) and nonexercise control ( n = 16 ) groups . The training group participated in 2 field-training sessions per week , with training loads , match loads , and injury rates recorded . Subjects performed measurements of st and ard anthropometry ( height , body mass , and sum of 7 skinfolds ) , muscular power ( vertical jump ) , speed ( 10- , 20- , and 40-m sprint ) , agility ( L run ) , and maximal aerobic power ( multistage fitness test ) in December ( off-season ) , March ( preseason ) , May ( midseason ) , and August ( end season ) . Increases in maximal aerobic power and muscular power and reductions in skinfold thickness were observed during the early phases of the season when training loads were highest . However , reductions in muscular power and maximal aerobic power and increases in skinfold thickness occurred toward the end of the season , when training loads were lowest and match loads and injury rates were highest . These findings suggest that high overall playing intensity and match loads in end-season matches increase in injury rates in the latter half of the season , and residual fatigue associated with limited recovery between successive matches may compromise the physical development of rugby league players |
1,842 | 26,663,955 | Pears , similar to apples , are concentrated in fructose , and the high fiber and fructose in pears probably explain the laxative properties .
Pears contain antioxidants and provide between 27 and 41 mg of phenolics per 100 g. Animal studies with pears suggest that pears may regulate alcohol metabolism , protect against ulcers , and lower plasma lipids . | Fruit consumption is universally promoted , yet consumption of fruit remains low in the United States .
The genus Pyrus L. consists of species of pears cultivated in Europe , parts of Asia , South America , and North America .
Like most fruit , pears are concentrated in water and sugar .
Pears are high in dietary fiber , containing 6 g per serving . | BACKGROUND Fruit and vegetables is a heterogeneous food group with different content of dietary fiber , vitamins , minerals , carotenoids , and bioactive phytochemicals . Our objective was to examine the relation between specific consumption of fruit and vegetable subgroups and stroke risk in a cohort of Swedish women and men . METHODS AND RESULTS We prospect ively followed 74,961 participants ( 34,670 women and 40,291 men ) who had completed a food frequency question naire in the autumn of 1997 and were free from stroke , coronary heart disease , and cancer at baseline . Diagnoses of stroke in the cohort during follow-up were ascertained from the Swedish Hospital Discharge Registry . A total of 4089 stroke cases , including 3159 cerebral infa rct ions , 435 intracerebral hemorrhages , 148 subarachnoid hemorrhages , and 347 unspecified strokes , were ascertained during 10.2 years of follow-up . The multivariable relative risk ( RR ) of total stroke for the highest vs. lowest category of total fruit and vegetable consumption was 0.87 ( 95 % confidence interval [ CI ] 0.78 - 0.97 ; P for trend = 0.01 ) . The association was confined to individuals without hypertension ( corresponding RR , 0.81 ; 95 % CI , 0.71 - 0.93 ; P for trend = 0.01 ) . Among individual fruits and vegetable subgroups , inverse associations with total stroke were observed for apples/pears ( RR , 0.89 ; 95 % CI , 0.80 - 0.98 ; P for trend = 0.02 ) and green leafy vegetables ( RR , 0.92 ; 95 % CI , 0.81 - 1.04 ; P for trend = 0.03 ) . CONCLUSION This study shows an inverse association of fruit and vegetable consumption with stroke risk . Particularly consumption of apples and pears and green leafy vegetables was inversely associated with stroke Increased fruit and vegetable consumption may protect against lung cancer , although epidemiologic findings are inconclusive . The authors prospect ively examined associations between lung cancer risk and intakes of fruit , vegetables , and botanical subgroups in 472,081 participants aged 50 - 71 years in the National Institutes of Health (NIH)-AARP Diet and Health Study . Diet was assessed at baseline ( 1995 - 1996 ) with a 124-item dietary question naire . A total of 6,035 incident lung cancer cases were identified between 1995 and 2003 . Total fruit and vegetable intake was unrelated to lung cancer risk in both men and women . Higher consumption of several botanical subgroups , however , was significantly inversely associated with risk , but only in men . For example , the relative risks of lung cancer among men in the highest versus lowest quintiles of intake of rosaceae , convolvulaceae , and umbelliferae were 0.82 ( 95 % confidence interval ( CI ) : 0.73 , 0.91 ) , 0.86 ( 95 % CI : 0.75 , 0.96 ) , and 0.86 ( 95 % CI : 0.78 , 0.96 ) , respectively ; corresponding relative risks in women were 0.97 ( 95 % CI : 0.85 , 1.12 ) , 0.95 ( 95 % CI : 0.83 , 1.09 ) , and 0.92 ( 95 % CI : 0.80 , 1.06 ) . These results provide support for a protective role of specific botanical subgroups of fruits and vegetables in lung cancer prevention in men , although the findings could also be due to residual confounding by smoking or chance BACKGROUND There is probable evidence that some types of fruit and vegetables provide protection against many cancers . OBJECTIVE We hypothesized that fruit and vegetable intakes are inversely related to the incidence of total cancers among women and men aged > 50 y. DESIGN We performed a prospect i ve study among the cohort of the National Institutes of Health-AARP Diet and Health Study . We merged the MyPyramid Equivalents Data base ( version 1.0 ) with food-frequency- question naire data to calculate cup equivalents for fruit and vegetables . From 1995 to 2003 , we identified 15,792 and 35,071 cancer cases in 195,229 women and 288,109 men , respectively . We used Cox proportional hazards models to estimate multivariate relative risks ( RRs ) and 95 % CIs associated with the highest compared with the lowest quintile ( Q ) of fruit and vegetable intakes . RESULTS Fruit intake was not associated with the risk of total cancer among women ( RR(Q5 vs Q1 ) = 0.99 ; 95 % CI : 0.94 , 1.05 ; P trend = 0.059 ) or men ( RR(Q5 vs Q1 ) = 0.98 ; 95 % CI : 0.95 , 1.02 ; P for trend = 0.17 ) . Vegetable intake was not associated with risk of total cancer among women ( RR(Q5 vs Q1 ) = 1.04 ; 95 % CI : 0.98 , 1.09 ; P for trend = 0.084 ) , but was associated with a significant decrease in risk in men ( RR(Q5 vs Q1 ) = 0.94 ; 95 % CI : 0.91 , 0.97 ; P trend = 0.004 ) . This significant finding among men was no longer evident when we limited the analysis to men who never smoked ( RR(Q5 vs Q1 ) = 0.97 ; 95 % CI : 0.91 , 1.04 ; P for trend = 0.474 ) . CONCLUSIONS Intake of fruit and vegetables was generally unrelated to total cancer incidence in this cohort . Residual confounding by smoking is a likely explanation for the observed inverse association with vegetable intake among men Objectives : To determine the patterns and possible explanations for gender differences in food choices , nutrient intakes and status indices , especially for micronutrients , in a representative sample of older people living in Britain , who participated in the National Diet and Nutrition Survey of people aged 65 y and over during 1994–95 . Design : The Survey procedures included a health- and -lifestyle interview , a four-day weighed diet record , anthropometric measurements and a fasting blood sample for biochemical indices . Setting : Eighty r and omly-selected postcode sectors from mainl and Britain . Subjects : Of 1556 older people not living in institutions who were interviewed , 80 % agreed to provide a complete four-day diet record and 63 % agreed to give a blood sample for status index measurements . Interventions : None . Main result : The most highly significant gender differences in food choices were that women ate more butter , full-fat milk and certain beverages , cakes , apples , pears and bananas , whereas men ate more eggs , sugar , certain meat products and drank more alcoholic drinks , especially beer and lager . When adjusted for energy intakes , the younger women ( 65–79 y ) had higher intakes than the younger men , of fat , retinol , vitamin C and calcium . The older women ( 80+y ) had higher intakes than older men , of fat and vitamin E , but lower intakes of protein , zinc and β-carotene . The younger women had better status indices than the younger men : for α- and β-carotenes , β-cryptoxanthin and vitamin C. Women had higher plasma concentrations of cholesterol and HDL cholesterol , phosphate and copper , but lower indices of iron and vitamin D status , than men . These gender differences in status were not altered by inclusion of the corresponding nutrient intakes in the model . Conclusions : There are gender differences in food choices , in energy and nutrient intakes and in nutritional blood status indices in older British people , especially those aged 65–79 y. Some of the status differences are attenuated in the age group of 80 y and older , whereas others are enhanced . The relationships between the quantity and type of foods or nutrients consumed , and nutrient status , are complex . With respect to suspected risk and protective factors for vascular disease , women aged 65–79 y had significantly better status for plasma α- and β-carotene , ascorbate , HDL-cholesterol and homocysteine ; but , in contrast , they had lower blood haemoglobin concentrations and higher concentrations of total and non-HDL-cholesterol . Sponsorship : The British National Diet and Nutrition Survey series is funded by the Ministry of Agriculture , Fisheries and Food and the Department of Health , and this survey was conducted by Social and Community Planning Research in conjunction with MRC Human Nutrition Research ( formerly MRC Dunn Nutritional Laboratory ) Abstract Epidemiological studies have shown an inverse correlation between a fruit and vegetable-rich diet and cardiovascular diseases ; this beneficial effect of fruits and vegetables is probably due to the presence of antioxidant phytochemicals . In contrast , cigarette smoking is a high risk factor for lung and heart diseases , associated with chronic oxidative stress . In the present study , the effect of the consumption of a pear , an apple and 200 ml orange juice , during 26 days , on total plasma antioxidant capacity ( TAC ) and lipid profile of chronic smokers and non-smoking healthy adults was analyzed . Fruit consumption increased TAC in non-smokers , but not in smokers . In non-smokers , total cholesterol , high-density lipoprotein-cholesterol , and low-density lipoprotein-cholesterol increased significantly ; while in smokers , total cholesterol and low-density lipoprotein-cholesterol decreased . We may conclude fruit/juice supplementation showed different effects , depending on the smoking habit : in non-smokers it increased TAC and cholesterol ; in smokers it reduced cholesterol , whithout inducing a TAC increase The association of fruit and vegetable consumption and lung cancer incidence was evaluated using the most recent data from the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) , applying a refined statistical approach ( calibration ) to account for measurement error potentially introduced by using food frequency question naire data . Between 1992 and 2000 , detailed information on diet and life-style of 478,590 individuals participating in EPIC was collected . During a median follow-up of 6.4 years , 1,126 lung cancer cases were observed . Multivariate Cox proportional hazard models were applied for statistical evaluation . In the whole study population , fruit consumption was significantly inversely associated with lung cancer risk while no association was found for vegetable consumption . In current smokers , however , lung cancer risk significantly decreased with higher vegetable consumption ; this association became more pronounced after calibration , the hazard ratio ( HR ) being 0.78 ( 95 % CI 0.62 - 0.98 ) per 100 g increase in daily vegetable consumption . In comparison , the HR per 100 g fruit was 0.92 ( 0.85 - 0.99 ) in the entire cohort and 0.90 ( 0.81 - 0.99 ) in smokers . Exclusion of cases diagnosed during the first 2 years of follow-up strengthened these associations , the HR being 0.71 ( 0.55 - 0.94 ) for vegetables ( smokers ) and 0.86 ( 0.78 - 0.95 ) for fruit ( entire cohort ) . Cancer incidence decreased with higher consumption of apples and pears ( entire cohort ) as well as root vegetables ( smokers ) . In addition to an overall inverse association with fruit intake , the results of this evaluation add evidence for a significant inverse association of vegetable consumption and lung cancer incidence in smokers BACKGROUND Most infants consume fruit juices by 6 months of age . However , fruit juices containing sorbitol may be associated with carbohydrate malabsorption without clinical symptoms . We hypothesized that increased physical activity and metabolic rate may be associated with carbohydrate malabsorption . METHODS Physical activity and metabolic rate were determined in 14 healthy infants ( [ mean + /- SD ] age , 5.1 + /- 0.8 months ; weight , 7.8 + /- 1.1 kg ; length , 67 + /- 4.2 cm ; and body fat , 26 % + /- 5 % ) for 3 hours in a respiratory chamber . Seven were fed pear juice , and the other 7 were fed white grape juice ( 120 mL ) after a 2-hour fast . Pear juice contains sorbitol and a high fructose-glucose ratio , whereas white grape juice is sorbitol free and has a low fructose-glucose ratio . Carbohydrate absorption was determined by breath hydrogen gas analysis . The study was double-blinded . RESULTS When compared with the infants without carbohydrate malabsorption ( peak breath hydrogen level < 20 ppm above baseline ) , 5 of the 7 infants fed pear juice and 2 of the 7 infants fed white grape juice exhibited carbohydrate malabsorption ( peak breath hydrogen level > or = 20 ppm above baseline ; P < .01 ) . These infants also exhibited both increased physical activity ( P < .001 ) and metabolic rate ( P < .05 ) after juice consumption in comparison with infants with normal carbohydrate absorption . When grouped according to the type of juice consumed , only infants fed pear juice exhibited increases in physical activity ( P < .01 ) . CONCLUSIONS Carbohydrate malabsorption is associated with increased physical activity and metabolic rate in infants . Most of the infants who had carbohydrate malabsorption consumed pear juice . Therefore , fruit juices containing sorbitol and high levels of fructose may not be optimal for young infants 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 |
1,843 | 26,620,578 | Conclusion Restricted protein diet supplemented with keto analogues ( s(v)LPD ) could delay the progression of CKD effectively without causing malnutrition | Background To evaluate the efficacy and safety of the restricted protein diet ( low or very low protein diet ) supplemented with keto analogues in the treatment of chronic kidney disease ( CKD ) . | Ar and omized , controlled study of 12 patients with mild chronic renal failure was design ed to assess the metabolic effects of a low-protein diet supplemented ( n = 6 ) or not ( n = 6 ) with ketoanalogs of amino acids . The protein intake was prescribed so that both groups were isonitrogenous . The dietary survey each month included a 3-d food record and a 24-h urine collection for urea measurement . After a 4- to 6-wk equilibrium period ( st and ard occidental diet , 1.11 g of protein and 32 kcal/kg per d ) , patients reduced their protein intake to reach 0.71 g of protein/kg per d during the third month . Energy intake was kept constant ( 31 kcal/kg per d ) during the 3-mo period . Compliance to the diet was achieved after 2 mo of training . Leucine turnover measurement was performed before and at the end of the 3-mo low-protein period . There was no clinical change , whereas total body flux decreased by 8 % ( P < 0.05 ) and leucine oxidation by 18 % ( P < 0.05 ) . No difference could be attributed to the ketoanalogs themselves . Thus , under sufficient energy intake , a low-protein diet is nutritionally and metabolically safe during chronic renal failure . The nitrogen-sparing effect of a low-protein diet is still present during mild chronic renal insufficiency In 15 ambulatory patients with renal insufficiency ( creatinine clearance , 9.9 + /- 3.0 ml/min ) the effect of oral supplementation with alpha-ketoacids has been compared with that of placebo . The protein intake amounted to 0.55 g protein per kilogram body weight of high biological value , as estimated by dietary recordings . After a control period of 3 months the patients received , in a double-blind study , 1.05 g alpha-ketoacids/10 kg body weight per day or a placebo for 6 weeks with a subsequent cross-over . Fasting blood sample s were analyzed at 3-week intervals for routine laboratory parameters and 17 proteins . Anthropometric and clinical data have been recorded every 3 weeks . While therapy with alpha-ketoacids diminished PO4 levels ( P less than 0.05 ) , no other significant effect could be demonstrated . No signs of protein deficiency existed either before or during alpha-ketoacid therapy . Therefore , supplementation with alpha-ketoacids appears to be superfluous in patients with renal insufficiency maintained on a 40-g protein diet Blood pressure ( BP ) is hardly controlled in chronic kidney disease ( CKD ) . We compared the effect of very low protein diet ( VLPD ) supplemented with ketoanalogs of essential amino acids ( 0.35 g/kg/day ) , low protein diet ( LPD , 0.60 g/kg/day ) , and free diet ( FD ) on BP in patients with CKD stages 4 and 5 . Vegetable proteins were higher in VLPD ( 66 % ) than in LPD ( 48 % ) . LPD was prescribed to 110 consecutive patients ; after run-in , they were invited to start VLPD . Thirty subjects accepted ; 57 decided to continue LPD ; 23 refused either diet ( FD group ) . At baseline , protein intake ( g/kg/day ) was 0.79+/-0.09 in VLPD , 0.78+/-0.11 in LPD , and 1.11+/-0.18 in FD ( P<0.0001 ) . After 6 months , protein intake was lower in VLPD than LPD and FD ( 0.54+/-0.11 , 0.78+/-0.10 , and 1.04+/-0.21 g/kg/day , respectively ; P<0.0001 ) . BP diminished only in VLPD , from 143+/-19/84+/-10 to 128+/-16/78+/-7 mm Hg ( P<0.0001 ) , despite reduction of antihypertensive drugs ( from 2.6+/-1.1 to 1.8+/-1.2 ; P<0.001 ) . Urinary urea excretion directly correlated with urinary sodium excretion , which diminished in VLPD ( from 181+/-32 to 131+/-36 mEq/day ; P<0.001 ) . At multiple regression analysis ( R2=0.270 , P<0.0001 ) , BP results independently related to urinary sodium excretion ( P=0.023 ) and VLPD prescription ( P=0.003 ) , but not to the level of protein intake . Thus , in moderate to advanced CKD , VLPD has an antihypertensive effect likely due to reduction of salt intake , type of proteins , and ketoanalogs supplementation , independent of actual protein intake BACKGROUND AND OBJECTIVES High levels of fibroblast growth factor 23 are associated with mortality , CKD progression , and calcification in CKD patients . The aim of this pilot study is to assess whether a very-low-protein diet ( 0.3 g/kg per day ) with a consequent low intake of phosphorus would reduce fibroblast growth factor 23 compared with a low-protein diet ( 0.6 g/kg per day ) in CKD patients not yet on dialysis . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS A prospect i ve , r and omized , controlled crossover study was performed in which 32 patients were r and omized into two groups . Group A ( 16 patients ) received a very-low-protein diet ( 0.3 g/kg body wt per day ) supplemented with ketoanalogues during the first week and a low-protein diet during the second week , and group B ( 16 patients ) received a low-protein diet during the first week and a very-low-protein diet during the second week . Fibroblast growth factor 23 , seric , and urinary phosphate levels were measured at baseline and the end of each study period . RESULTS After only 1 week of the very-low-protein diet , reductions in fibroblast growth factor 23 levels ( 33.5 % ) , serum phosphate ( 12 % ) , and urinary phosphate ( 34 % ) with the very-low-protein diet compared with the low-protein diet were observed . Serum and urinary phosphate levels and protein intake were significant determinants of fibroblast growth factor 23 ( 95 % confidence interval=1.04 - 1.19 , 1.12 - 1.37 , and 1.51 - 2.23 , respectively ) . CONCLUSIONS A very-low-protein diet supplemented with ketoanalogues reduced fibroblast growth factor 23 levels in CKD patients not yet on dialysis OBJECTIVE To compare a severe protein restriction diet supplemented with ketoanalogues to a moderate protein restriction diet in order to limit glomerular filtration rate ( GFR ) decrease in an advanced renal insufficiency stage . DESIGN Prospect i ve r and omised study conducted to compare a severe protein restriction diet ( 0.30 g/kg/day ) supplemented with a preparation of ketoanalogues , hydroxyanalogues of aminoacids and aminoacids ( Group A ) to a moderate protein restriction diet ( 0.65 g/kg/day ) ( Group B ) . PATIENTS 50 uremic patients included ( 25 in each group ) with GFR is < 20 mL/min/1.73m2 . RESULTS There were no statistically significant differences between the two dietary regimens for the renal survival . But uremia decreased significantly in Group A ( 22.7+/-5.2 to 18.5+/-6.7 mmol/L ) and increased in Group B ( 26.8+/-9.0 to 34.9+/-9.9 mmol/L ) . Calcemia increased in Group A from 2.28+/-0.18 to 2.42+/-0.17 mmol/L , p<0.01 with a stable phosphoremia while calcemia decreased in Group B ( 2.33+/-0.18 to 2.25+/-0.17 mmol/L , p<0.05 ) . At the end of the study , Group A was different from Group B for calcemia ( 2.42+/-0.17 vs. 2.25+/-0.17 mmol/L , p<0.01 ) , phosphoremia ( 1.39+/-0.30 vs. 1.80+/-0.65 mmol/L , p<0.02 ) , alkaline phosphatase ( 61.42+/-22.93 vs. 78.8+/-27.0 , p<0.05 ) and parathormone plasma levels ( 2.71+/-1.55 vs. 5.91+/-1.41 ng/mL , p<0.001 ) . COMMENTS Compared to a moderate protein restriction ( 0.65 g/kg/day ) , a severe protein restriction ( 0.3 g/kg/day ) supplemented by ketoanologues does not limit GFR decrease when GFR is below 20 mL/min/1.73m2 , but improves phosphocalcic plasma parameters The therapeutical effect of keto acids on bone histology was investigated in a prospect i ve r and omized controlled study of 40 patients . A marked improvement in osteofibrotic as well as in osteomalacic changes was found in bone biopsies after 12 months of treatment with keto acids OBJECTIVE To investigate if a-keto/amino acid supplemented low protein diet can slow down the progression of diabetic nephrophathy in comparison with non-supplemented diabetes diet . METHODS A prospect i ve , r and omized , controlled clinical study was conducted . Twenty three cases of type 2 diabetic nephropathy in IV stage were r and omly divided into alpha-keto/amino acid supplemented diet group ( trial group ) and conventional diabetes diet group ( control group ) , The treatment duration was 52 weeks . 24 h urine protein was measured at 0 , 12 , 20 , 36 and 52 weeks . Before and after the 52 weeks treatment , all the patients received the measurement of glomerular filtration rate ( GFR ) , blood glucose , blood lipids , inflammatory markers , as well as nutritional status . RESULTS After the treatment for 20 , 36 , 52 weeks , mean 24 h urine protein decreased significantly in trial groups ( P < 0.05 ) , and 24 h urine protein in trial group were significantly decreased ( P < 0.05 ) compared with control group in 20 weeks after treatment . Either in trial group or in control group , GFR remained relatively stable during the observation period . Nutrition status , inflammatory markers , and serum calcium , phosphorus levels between the two groups were no significantly difference . The adverse events experienced by the patients in trial group were similar and consistent with the patients underlying renal diseases . CONCLUSION Alpha-keto/amino acid can reduce proteinuria more effectively , while improve renal function and nutritional status in diabetic nephropathy patients with well-toleration Objective : To evaluate the effects on the nutritional and metabolic parameters of a very-low-protein diet supplemented with ketoacids ( VLPD+KA ) in comparison with a conventional low-protein diet ( LPD ) in chronic kidney disease ( CKD ) patients . Design : Prospect i ve , r and omized , controlled clinical study . Setting : Outpatient Clinic of the Nephrology Division of Federal University of São Paulo , Brazil . Subjects : The study involved 24 patients with advanced CKD ( creatinine clearance < 25 ml/min ) that were r and omly assigned to either a VLPD+KA ( VLPD+KA group , 12 patients ) or to a conventional LPD with 0.6 g/kg/day ( LPD group , 12 patients ) . The patients were followed for 4 months . Results : Nutritional status was adequately maintained with both diets for the studied period . Protein intake and serum urea nitrogen decreased significantly only in the VLPD+KA group ( from 0.68±0.17 to 0.43±0.12 g/kg/day , P<0.05 ; from 61.4±12.8 to 43.6±14.9 mg/dl , P<0.001 ; respectively ) . Ionized calcium did not change in the VLPD+KA group but tended to decrease in the LPD group . Serum phosphorus tended to decrease in the VLPD+KA group probably as a result of a significant reduction in dietary phosphorus ( 529±109 to 373±125 mg/day , P<0.05 ) associated to the phosphorus-binding effect of the ketoacids . No change in these parameters was found in the LPD group . Serum parathormone increased significantly only in the LPD group ( from 241±138 to 494±390 pg/ml , P<0.01 ) . The change in PTH concentration was negatively correlated with changes in ionized calcium concentration ( r=−0.75 , P=0.02 ) and positively correlated with changes in serum phosphorus ( r=0.71 , P=0.03 ) only in the LPD group . Conclusion : This study indicates that a VLPD+KA can maintain the nutritional status of the patients similarly to a conventional LPD . Besides , an improvement in calcium and phosphorus metabolism and a reduction in serum urea nitrogen were attained only with the VLPD+KA . Thus , VLPD+KA can constitute another efficient therapeutic alternative in the treatment of CKD patients .Sponsorship : This study was supported by CAPES , Oswaldo Ramos Foundation and Fresenius Kabi , Ltda BACKGROUND Recent data suggest that dietary protein restriction improves survival and delays the progression to end-stage renal disease ( ESRD ) in non-diabetic nephropathies . The purpose of our study was to determine the effect of dietary protein restriction on survival and progression to ESRD in diabetic nephropathy . METHODS A four-year prospect i ve , controlled trial with concealed r and omization was performed comparing the effects of a low-protein diet ( 0.6 g/kg/day ) with a usual-protein diet . The study included 82 type 1 diabetic patients with progressive diabetic nephropathy [ pre- study mean decline in glomerular filtration rate ( GFR ) 7.1 mL/min/year ( 95 % CI , 5.8 to 8.5 ) ] . The main outcome measures were decline in GFR and development of ESRD or death . RESULTS During the follow-up period the usual-protein diet group consumed 1.02 g/kg/day ( 95 % CI ; 0.95 to 1.10 ) as compared with 0.89 ( 0.83 to 0.95 ) in the low-protein diet group ( P = 0.005 ) . The mean declines in GFR were 3.9 mL/min/year ( 2.7 to 5.2 ) in the usual-protein diet group and 3.8 ( 2.8 to 4.8 ) in the low-protein diet group . ESRD or death occurred in 27 % of patients on a usual-protein diet as compared with 10 % on a low-protein diet ( log-rank test ; P = 0.042 ) . The relative risk of ESRD or death was 0.23 ( 0.07 to 0.72 ) for patients assigned to a low-protein diet , after an adjustment at baseline for the presence of cardiovascular disease ( P = 0.01 ) . Blood pressure and glycemic control were comparable in the two diet groups during the follow-up period . CONCLUSION Moderate dietary protein restriction improves prognosis in type 1 diabetic patients with progressive diabetic nephropathy in addition to the beneficial effect of antihypertensive treatment ZusammenfassungHINTERGRUND : Die Plasmaspiegel des endogenen Stickoxid-Hemmers asymmetrisches Dimethylarginin ( ADMA ) sind bei chronischem Nierenversagen erhöht und könnten zu den vaskulären Komplikationen beitragen . In dieser Studie wurde die Hypothese überprüft , ob diese erhöhten ADMA-Spiegel bei übergewichtigen CNV-Patienten durch eine Langzeittherapie mit einer Ketosäuren-supplementierten niedrigprotein-Diät ( KA ) vermindert werden könnten . PATIENTEN UND METHOD EN : Insgesamt 111 CNV-Patienten ( 54 M/57 F ) mit Adipositas ( BMI ≥ 30 kg/m2 ) , Alter 22–76 Jahre und einer Inulin-Clearance von 22–40 ml/min/1,73 m2 wurden in eine r and omisiert-kontrollierte doppel-blinden Untersuchung einschlossen . Die Patienten erhielten über 336 Monate eine Niedrig-Protein-Diät ( LPD ) von 0,6 Protein/kg KG/Tag und 120–125/kJ/kg KG/Tag . In 66 Patienten , Gruppe I , wurde diese LPD mit KA ( 100 mg/kg KG/Tag ) supplementiert , 65 Patienten ( Gruppe II ) erhielten Placebo . ERGEBNISSE : Während der Studienperiode nahm die glomeruläre Filtrationsrate leicht ab ( Cin von 32,4 ± 12,6 auf 29,8 ± 8,6 ml/min/1,73m2 und 33,2 ± 12,6 auf 23,2 ± 98,4 ml/min/1,73 m2 in den Gruppen I und II ; dies war ausgeprägter in Grupppe II ( p < 0,01 ) ) . Der BMI verminderte sich in Gruppe I von 32.0 ± 3.3 auf 26.1 ± 4.0 kg/m2 ( p < 0,01 ) , dies war auf einen Rückgang des viszeralen Fettes gemessen mit MRI zurückzuführen ( p < 0,01 ) . Die Änderung des BMI war in Gruppe II nicht signifikant . In Gruppe I f and sich ein Rückgang des Plasmaspiegel von ADMA von 2,5 ± 0,5 auf 1,3 ± 0,4 µmol/l ( p < 0,01 ) , dieser blieb in Gruppe II unverändert . In Gruppe I f and sich auch ein Rückgang der Plasma-Konzentration von Pentosidin ( von 480 ± 170 auf 320 ± 120 µg/L , p < 0,01 ) und der Proteinurie ( von 3,8 ± 2,24 auf 1,6 ± 1,0 g / 24 h , p < 0,02 ) . Plasma Adiponectin ( ADPN ) stieg in Gruppe I an ( p < 0,01 ) . Ausgeprägter in Gruppe I f and sich ein leichter Abfall von Gesamtcholesterin und LDL-Cholesterin ( p < 0,02 ) . In Gruppe I fielen die Plasma-Triglyzeride ( von 3,9 ± 1,6 auf 2,2 ± 0,6 mmol/l , p < 0,01 ) , das glykierte Hämoglobin ( HbAc1 ) von 7,2 ± 1,4 auf 4,2 ± 0,8 % ( p < 0,02 ) . ZUSAMMENFASSUNG : Bei übergewichtigen Patienten mit CNV führt eine Langzeit-Gabe von Ketosäuren zusammen mit einer LPD in Vergleich zu Placebo zu einer Verminderung des viszeralen Körperfettes und zu einer Verzögerung des Nierenfunktionsverlustes . Ein gleichzeitiger Rückgang des Plasmaspiegels von ADMA , aber auch von Pentosidin könnten zusammen mit einem Rückgang der Proteinurie zu einer Vermindung der Progression des Nierenversagens beitragen . Summary BACKGROUND : Levels of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine ( ADMA ) are elevated in chronic kidney disease ( CKD ) and may contribute to vascular complications . In this study we tested the hypothesis that elevated ADMA can be reduced in obese CKD patients by long-term administration of a low-protein diet supplemented with keto-amino acids . PATIENTS AND METHODS : In a long-term prospect i ve double-blind placebo-controlled r and omized trial , we evaluated for a period of 36 months a total of 111 CKD patients ( 54 men , 57 women ) aged 22–76 years with obesity ( BMI ≥ 30 kg/m2 ) and an inulin clearance rate ( Cin ) of 22–40 ml/min/1.73 m2 . All patients were on a low-protein diet containing 0.6 g protein/kg BW per day and 120–125 kJ/kg BW per day . The diet was r and omly supplemented with keto-amino acids at a dosage of 100 mg/kg BW per day ( 66 patients , Group I ) ; 65 patients received placebo ( Group II ) . RESULTS : During the study period , the glomerular filtration rate decreased slightly in Group I ( Cin from 32.4 ± 12.6 to 29.8 ± 8.6 ml/min/1.73 m2 ) and more markedly in Group II ( from 33.2 ± 12.6 to 23.2 ± 98.4 ml/min/1.73m2 , P < 0.01 ) . BMI decreased significantly in Group I ( from 32.0 ± 3.3 to 26.1 ± 4.0 kg/m2 , P < 0.01 ) and was linked to reduced volume of visceral fat measured by MRI ( P < 0.01 ) . Reduction of BMI in Group II was not significant . In Group I , there was a significant decrease in the plasma level of ADMA ( from 2.5 ± 0.5 to 1.3 ± 0.4 µmol/l , P < 0.01 ) , but ADMA remained unchanged in Group II . A further remarkable finding in Group I was reduction in the plasma concentration of pentosidine ( from 480 ± 170 to 320 ± 120 µg/l , P < 0.01 ) and decrease of proteinuria ( from 3.8 ± 2.24 to 1.6 ± 1.0 g/24 h , P < 0.02 ) . Plasma adiponectin rose in Group I ( P < 0.01 ) . Analysis of the lipid spectrum revealed a mild but significant decrease in total cholesterol and LPD-cholesterol ( P < 0.02 ) , more pronounced in Group I. There was also a decrease in plasma triglycerides in Group I ( from 3.9 ± 1.6 down to 2.2 ± 0.6 mmol/l , P < 0.01 ) and a decrease in glycated hemoglobin ( from 7.2 ± 1.4 % to 4.2 ± 0.8 % , P < 0.02 ) . CONCLUSION : Compared with the placebo group , long term co-administration of a low-protein diet and keto-amino acids in CKD patients with obesity led to decreases of ADMA , visceral body fat and proteinuria . Concomitant decreases of glycated hemoglobin , LDL-cholesterol and pentosidine may also contribute to the delay in progression of renal failure BACKGROUND The aim of this study was to evaluate the relationship between uremic state and erythropoiesis in patients with predialytic chronic renal failure ( CRF ) . METHODS We monitored for 2 years the erythropoietin ( EPO ) requirement in patients with advanced CRF ( creatinine clearance < or = 25 mL/min ) , r and omized to either low protein diet ( LPD ) group ( 0.6 g/kg body weight/day , N = 10 ) or very low protein diet ( VLPD ) group ( 0.3 g/kg body weight/day , N = 10 ) supplemented with a mixture of ketoanalogs and essential amino acids , both kept at target hemoglobin levels . RESULTS The achieved protein intake after 6 months was 0.79 + /- 0.02 g/kg body weight/day and 0.50 + /- 0.02 g/kg body weight/day in LPD and VLPD , respectively ; such a difference was maintained up to the end of follow up . The final hemoglobin values did not differ from the basal values in either group ( 11.5 + /- 0.2 g/dL and 11.5 + /- 0.3 g/dL ) . EPO dose , that was similar at baseline ( 62.4 + /- 9.6 UI/kg body weight/week and 61.8 + /- 8.8 UI/kg body weight/week subcutaneously ) , remained unchanged in LPD but progressively decreased in VLPD down to the final value of 41.2 + /- 7.0 UI/kg body weight/week ( P < 0.0001 vs. basal and LPD ) . VLPD was associated with a decrease of urinary excretion and serum levels of urea nitrogen and phosphate ; however , EPO requirement was not correlated with the changes of these parameters . On the contrary , the variation of EPO dose directly correlated with the modification of parathyroid hormone ( PTH ) levels , that diminished from 229 + /- 55 pg/mL to 118 + /- 16 pg/mL ( P < 0.0001 ) in VLPD and did not change in LPD . CONCLUSION In patients with advanced CRF , an effective decrease of protein intake of 0.3 g/kg body weight/day induces a reduction of about 35 % of the EPO dose required to maintain the target hemoglobin levels . This effect appears dependent on the correction of a moderate secondary hyperparathyroidism OBJECTIVE We assessed the effect of a severe hypoproteic diet supplemented with ketoanalogues ( SVLPD ) for 48 weeks on certain metabolic disorders of chronic kidney disease ( CKD ) . DESIGN We performed a prospect i ve , open-label , parallel , r and omized , controlled trial . SETTING The study took place in the Nephrology Department at the Dr Carol Davila Teaching Hospital of Nephrology , Bucharest , Romania . PATIENTS A total of 53 nondiabetic patients with CKD with an estimated glomerular filtration rate less than 30 mL/min/1.73 m(2 ) ( Modification of Diet in Renal Disease formula ) , proteinuria less than 1 g/g urinary creatinine , good nutritional status , and anticipated good compliance with the diet were r and omly assigned to two groups . INTERVENTION Group I ( n = 27 ) received the SVLPD ( 0.3 g/kg/d of vegetable proteins and ketoanalogues , 1 capsule for every 5 kg of ideal body weight per day ) . Group II ( n = 26 ) continued a conventional low mixed protein diet ( 0.6 g/kg/d ) . OUTCOME MEASURES Nitrogen waste products retention and calcium-phosphorus and acid-base disturbances were primary efficacy parameters , and " death " of the kidney or the patient and the estimated glomerular filtration rate were secondary efficacy parameters . The nutritional status and compliance with the diet were predefined as safety variables . There were no differences between groups in any parameter at baseline . RESULTS In the SVLPD group , serum urea significantly decreased ( 56 + /- 7.9 mmol/L vs. 43.2 + /- 10 mmol/L ) , and significant improvements in serum bicarbonate ( 23.4 + /- 2.1 mmol/L vs. 18.1 + /- 1.5 mmol/L ) , serum calcium ( 1.10 + /- 0.17 mmol/L vs. 1.00 + /- 0.15 mmol/L at baseline ) , serum phosphates ( 1.45 + /- 0.66 mmol/L vs. 1.91 + /- 0.68 mmol/L ) , and calcium-phosphorus product ( 1.59 + /- 0.11 mmol(2)/L(2 ) vs. 1.91 + /- 0.10 mmol(2)/L(2 ) ) were noted after 48 weeks . No death was registered in any group . Significantly lower percentages of patients in group I required renal replacement therapy initiation ( 4 % vs. 27 % ) . After 48 weeks , estimated glomerular filtration rate did not significantly change in patients receiving SVLPD ( 0.26 + /- 0.08 mL/s vs. 0.31 + /- 0.08 mL/s at baseline ) , but significantly decreased in controls ( 0.22 + /- 0.09 mL/s vs. 0.30 + /- 0.07 mL/s ) . The compliance with the keto-diet was good in enrolled patients . No significant changes in any of the parameters of the nutritional status and no adverse reactions were noted . CONCLUSION SVLPD seems to ameliorate the nitrogen waste products retention and acid-base and calcium-phosphorus metabolism disturbances and to postpone the renal replacement therapy initiation , preserving the nutritional status in patients with CKD OBJECTIVE To assess whether a ketodiet , a combination of ketoanalogs of essential amino acids ( KAs ) and a very low-protein diet , retards progression of chronic renal failure and maintains nutritional status . DESIGN A prospect i ve , r and omized , double-blind , placebo-controlled trial . SETTING Nephrology outpatient department in Northern Railways Central Hospital , New Delhi , India . PATIENTS Thirty-four patients in predialytic stages of chronic renal failure ( CRF ) , r and omized to 2 comparable groups in terms of age , sex distribution , blood pressure control , etiology , use of angiotensin converting enzyme inhibitors , serum creatinine , glomerular filtration rate ( GFR ) , and body mass index ( BMI ) . INTERVENTION Subjects r and omly received either 0.6 g/kg/d protein plus placebo ( n = 16 ) or 0.3 g/kg/d protein plus tablets of KAs ( Ketosteril ; Fresenius Kabi , Germany ) ( n = 18 ) for 9 months . A dietician administered the diet as well as the KAs or the placebo to the patients . OUTCOME MEASURES Changes in GFR and renal and nutritional parameters were measured . RESULTS Mean ( + /- SD ) GFR measured by the 99mTc-DTPA ( 99 m technetium diethylenetri-aminepenta-aceticacid ) plasma sample method was unchanged in the ketodiet group : 28.1 + /- 8.8 ( before ) and 27.6 + /- 10.1 mL/min/1.73 m2 ( after the study ) ( P = .72 ) . However , it significantly decreased from 28.6 + /- 17.6 to 22.5 + /- 15.9 mL/min/1.73 m2 in the placebo group ( P = .015 ) . Serum creatinine before and after the study in the ketodiet group was 2.26 + /- 1.03 mg/dL and 2.07 + /- 0.8 mg/dL ( P = .90 ) and in the placebo group was 2.37 + /- 0.85 and 3.52 + /- 2.9 mg/dL ( P = .066 ) , respectively . In both groups the mean BMI did not change from 25.4 + /- 4.2 to 24.5 + /- 4.2 kg/m2 ( P = .46 ) for ketodiet and from 25.0 + /- 6.8 to 23.9 + /- 4.1 kg/m2 ( P = .39 ) for the placebo group . Serum total proteins decreased significantly ( P = .038 ) in the placebo group , and serum albumin showed a trend ( P = .061 ) toward reduction , whereas both of these parameters were maintained in the ketodiet group . CONCLUSION Over a 9-month period , very low-protein diet supplemented with ketoanalogs helped CRF patients to preserve GFR and maintain BMI . KAs were safe and efficacious in retarding the progression of renal failure and preserving the nutritional status of CRF patients BACKGROUND The long-term effect of a low-protein diet on the progression of chronic kidney disease is unknown . We evaluated effects of protein restriction on kidney failure and all-cause mortality during extended follow-up of the Modification of Diet in Renal Disease Study . METHODS Study A was a r and omized controlled trial from 1989 to 1993 of 585 patients with predominantly nondiabetic kidney disease and a moderate decrease in glomerular filtration rate ( 25 to 55 mL/min/1.73 m(2 ) [ 0.42 to 0.92 mL/s/1.73 m(2 ) ] ) assigned to a low- versus usual-protein diet ( 0.58 versus 1.3 g/kg/d ) . We used registries to ascertain the development of kidney failure ( initiation of dialysis therapy or transplantation ) or a composite of kidney failure and all-cause mortality through December 31 , 2000 . We used Cox regression models and intention-to-treat principles to compute hazard ratios for the low- versus usual-protein diet , adjusted for baseline glomerular filtration rate and other factors previously associated with the rate of decrease in glomerular filtration rate . We estimated hazard ratios for the entire follow-up period and then , in time-dependent analyses , separately for 2 consecutive 6-year periods of follow-up . RESULTS Kidney failure and the composite outcome occurred in 327 ( 56 % ) and 380 patients ( 65 % ) , respectively . After adjustment for baseline factors , hazard ratios were 0.89 ( 95 % confidence interval [ CI ] , 0.71 to 1.12 ) and 0.88 ( 95 % CI , 0.71 to 1.08 ) , respectively . Adjusted hazard ratios for both outcomes were lower during the first 6 years ( 0.68 ; 95 % CI , 0.51 to 0.93 and 0.66 ; 95 % CI , 0.50 to 0.87 , respectively ) than afterward ( 1.27 ; 95 % CI , 0.90 to 1.80 and 1.29 ; 95 % CI , 0.94 to 1.78 ; interaction P = 0.008 and 0.002 , respectively ) . Limitations include lack of data for dietary intake and clinical conditions after conclusion of the trial . CONCLUSION The efficacy of a 2- to 3-year intervention of dietary protein restriction on progression of nondiabetic kidney disease remains inconclusive . Future studies should include a longer duration of intervention and follow-up |
1,844 | 28,713,656 | Recommendations are made with a view to informing future research to increase st and ardisation in fMRI laterality protocol s. In particular , the findings reinforce the importance of threshold-independent methods for calculating laterality indices , and the benefits of assessing heterogeneity of language laterality across multiple regions of interest and tasks . | The involvement of the right and left hemispheres in mediating language functions has been measured in a variety of ways over the centuries since the relative dominance of the left hemisphere was first known .
Functional magnetic resonance imaging ( fMRI ) presents a useful non-invasive method of assessing lateralisation that is being increasingly used in clinical practice and research .
However , the methods used in the fMRI laterality literature currently are highly variable , making systematic comparisons across studies difficult .
Here we consider the different methods of quantifying and classifying laterality that have been used in fMRI studies since 2000 , with the aim of determining which give the most robust and reliable measurement . | BACKGROUND AND PURPOSE : The optimal paradigm choice for language mapping in clinical fMRI studies is challenging due to the variability in activation among different paradigms , the contribution to activation of cognitive processes other than language , and the difficulties in monitoring patient performance . In this study , we compared language localization and lateralization between 2 commonly used clinical language paradigms and 3 newly design ed dual-choice semantic paradigms to define a streamlined and adequate language -mapping protocol . MATERIAL S AND METHODS : Twelve healthy volunteers performed 5 language paradigms : Silent Word Generation , Sentence Completion , Visual Antonym Pair , Auditory Antonym Pair , and Noun-Verb Association . Group analysis was performed to assess statistically significant differences in fMRI percentage signal change and lateralization index among these paradigms in 5 ROIs : inferior frontal gyrus , superior frontal gyrus , middle frontal gyrus for expressive language activation , middle temporal gyrus , and superior temporal gyrus for receptive language activation . RESULTS : In the expressive ROIs , Silent Word Generation was the most robust and best lateralizing paradigm ( greater percentage signal change and lateralization index than semantic paradigms at P < .01 and P < .05 levels , respectively ) . In the receptive region of interest , Sentence Completion and Noun-Verb Association were the most robust activators ( greater percentage signal change than other paradigms , P < .01 ) . All except Auditory Antonym Pair were good lateralizing tasks ( the lateralization index was significantly lower than other paradigms , P < .05 ) . CONCLUSIONS : The combination of Silent Word Generation and ≥1 visual semantic paradigm , such as Sentence Completion and Noun-Verb Association , is adequate to determine language localization and lateralization ; Noun-Verb Association has the additional advantage of objective monitoring of patient performance Over 90 % of people activate the left hemisphere more than the right hemisphere for language processing . Here , we show that the degree to which language is left lateralized is inversely related to the degree to which left frontal regions drive activity in homotopic right frontal regions . Lateralization was assessed in 60 subjects using functional magnetic resonance imaging ( fMRI ) activation for semantic decisions on verbal ( written words ) and nonverbal ( pictures of objects ) stimuli . Regional interactions between left and right ventral and dorsal frontal regions were assessed using dynamic causal modeling ( DCM ) , r and om-effects Bayesian model selection at the family level , and Bayesian model averaging at the connection level . We found that 1 ) semantic decisions on words and pictures modulated interhemispheric coupling between the left and right dorsal frontal regions , 2 ) activation was more left lateralized for words than pictures , and 3 ) for words only , left lateralization was greater when the coupling from the left to right dorsal frontal cortex was reduced . These results have theoretical implication s for underst and ing how left and right hemispheres communicate with one another during the processing of lateralized functions BACKGROUND AND PURPOSE : Brain tumors affecting language -relevant areas may influence language lateralization . The purpose of this study was to systematic ally investigate language lateralization in brain tumor patients using clinical language fMRI , comparing the results with a group of healthy volunteers . MATERIAL S AND METHODS : Fifty-seven strictly right-h and ed patients with left-hemispheric-space intracranial masses ( mainly neoplastic ) affecting either the Broca area ( n = 19 ) or Wernicke area ( n = 38 ) were prospect ively enrolled in this study . Fourteen healthy volunteers served as a control group . St and ardized clinical language fMRI , using visually triggered sentence- and word-generation paradigms , was performed on a 1.5 T MR scanner . Semiautomated analyses of all functional data were conducted on an individual basis using BrainVoyager . A regional lateralization index was calculated for Broca and Wernicke areas separately versus their corresponding right-hemisphere homologs . RESULTS : In masses affecting the Broca area , a significant decrease in the lateralization index was found when performing word generation ( P = .0017 ) , whereas when applying sentence generation , the decrease did not reach statistical significance ( P = .851 ) . Masses affecting the Wernicke area induced a significant decrease of the lateralization index when performing sentence generation ( P = .0007 ) , whereas when applying word generation , the decrease was not statistically significant ( P = .310 ) . CONCLUSIONS : Clinical language fMRI was feasible for patients with brain tumors and provided relevant presurgical information by localizing essential language areas and determining language dominance . A significant effect of the brain masses on language lateralization was observed , with a shift toward the contralesional , nondominant hemisphere . This may reflect compensatory mechanisms of the brain to maintain communicative abilities Background Functional magnetic resonance imaging ( fMRI ) continues to develop as a clinical tool for patients with brain cancer , offering data that may directly influence surgical decisions . Unfortunately , routine integration of preoperative fMRI has been limited by concerns about reliability . Many pertinent studies have been undertaken involving healthy controls , but work involving brain tumor patients has been limited . To develop fMRI fully as a clinical tool , it will be critical to examine these reliability issues among patients with brain tumors . The present work is the first to extensively characterize differences in activation map quality between brain tumor patients and healthy controls , including the effects of tumor grade and the chosen behavioral testing paradigm on reliability outcomes . Method Test-retest data were collected for a group of low- grade ( n = 6 ) and high- grade glioma ( n = 6 ) patients , and for matched healthy controls ( n = 12 ) , who performed motor and language tasks during a single fMRI session . Reliability was characterized by the spatial overlap and displacement of brain activity clusters , BOLD signal stability , and the laterality index . Significance testing was performed to assess differences in reliability between the patients and controls , and low- grade and high- grade patients ; as well as between different fMRI testing paradigms . Results There were few significant differences in fMRI reliability measures between patients and controls . Reliability was significantly lower when comparing high- grade tumor patients to controls , or to low- grade tumor patients . The motor task produced more reliable activation patterns than the language tasks , as did the rhyming task in comparison to the phonemic fluency task . Conclusion In low- grade glioma patients , fMRI data are as reliable as healthy control subjects . For high- grade glioma patients , further investigation is required to determine the underlying causes of reduced reliability . To maximize reliability outcomes , testing paradigms should be carefully selected to generate robust activation patterns The aim of this work was to determine whether productive and perceptive language functions are differentially affected in homogeneous groups of epilepsy patients with right and left temporal lobe epilepsy ( TLE ) . Eighteen patients with left TLE , 18 with right TLE , and 17 healthy volunteers were studied using fMRI during performance of three tasks assessing the productive and perceptive aspects of language ( covert semantic verbal fluency , covert sentence repetition , and story listening ) . Hemispheric dominance for language was calculated in the frontal and temporal regions using laterality indices ( LI ) . Atypical lateralization was defined as a right-sided LI ( LI<-0.20 ) in the frontal lobes during the verbal fluency task or in the temporal lobes during the story listening task . Control subjects and right TLE patients demonstrated a strong left lateralization for language in the frontal lobes during the fluency task , whereas activation was less lateralized to the left hemisphere in left TLE patients , although the difference did not reach significance . In the story listening and the repetition tasks , activation was significantly more right sided in the temporal lobes of patients with left TLE . Atypical language representation was found in 19 % of TLE patients ( five left and two right TLE ) . The shift toward the right hemisphere was significantly larger in the temporal than the frontal lobes in patients with atypical language lateralization compared to TLE patients with a typical language lateralization . Neuropsychological performances of patients with atypical language patterns were better than those of patients with typical patterns , suggesting that this reorganization may represent a compensatory mechanism Atypical , right-hemisphere language dominance is poorly understood . It is often observed in patients with brain reorganization due to lesions early in life . It can also be encountered in seemingly normal individuals . We compared the patterns of neural language activation in 7 individuals with left- and 7 with right-hemisphere language dominance , none of whom had any evidence of brain lesions . We speculated that incongruencies in the activation patterns in atypical , right-hemisphere language dominance could indicate a reorganized neural language system after undetected early brain damage . Functional magnetic resonance imaging analysis of brain activation during phonetic word generation demonstrated ( 1 ) . no increased activation in the subdominant hemisphere in right compared to left language dominance , ( 2 ) . a similar variability in the pattern of activation in both groups , and ( 3 ) . a mirror reverse pattern of activation in right- compared to left-hemisphere dominant subjects . These findings support the view that in individuals with an unrevealing medical history right-hemispheric dominance constitutes a natural rather than an abortive variant of language lateralization BACKGROUND AND PURPOSE : Functional MR imaging ( fMRI ) is used to determine preoperatively the laterality of cortical language representation along with the relationship of language areas to adjacent brain tumors . The purpose of this study was to determine whether changing the statistical threshold for different language tasks influences the language laterality index ( LI ) for a group of controls , patients with tumor without prior surgery , and patients with tumor and prior surgery . MATERIAL S AND METHODS : Seven controls , 9 patients with tumor without prior surgery , and 4 patients with tumor and prior surgery performed verb-generation , phonemic fluency , and semantic fluency language tasks during fMRI . Interhemispheric activation differences between the left and right Broca regions of interest were determined by calculating language LIs . LIs were compared within each group , between groups , and between language tasks . Intraoperative electrocortical mapping or the presence of aphasia during postoperative neurology examinations or both were used as ground truth . RESULTS : The language LI varied as a result of statistical thresholding , presence of tumor , prior surgery , and language task . Although patients and controls followed a similar shape in the LI curve , there was no optimal P value for determining the LI . Three patients demonstrated a shift in the LI between hemispheres as a function of statistical threshold . Verb generation was the least variable task both between tasks and across groups . CONCLUSION : For preoperative patients with tumor , the LI should be examined across a spectrum of P values and a range of tasks to ensure reliability . Our data suggest that the LI may be threshold- and task-dependent , particularly in the presence of adjacent tumor RATIONALE AND OBJECTIVES The aim of this study was to assess the intrasubject and intersubject reproducibility of functional magnetic resonance imaging ( fMRI ) language paradigms on language localization and lateralization . MATERIAL S AND METHODS Fourteen healthy volunteers were enrolled prospect ively and underwent language fMRI using visually triggered covert and overt sentence generation ( SG ) and word generation ( WG ) paradigms . Semiautomated analysis of all functional data was performed using Brain Voyager on an individual basis . Regions of interest for Broca 's area , Wernicke 's area , and their contralateral homologues were drawn . The Euclidean coordinates of the center of gravidity ( x , y , and z ) of the respective blood oxygenation level-dependent ( BOLD ) activation cluster , and the correlation of the measured hemodynamic response to the applied reference function ( r ) , relative BOLD signal change as BOLD signal characteristics were measured in each region of interest . Regional lateralization indexes were calculated for Broca 's area , Wernicke 's area , and their contralateral homologues separately . Wilcoxon 's signed-rank test was applied for statistical comparisons ( P values < .05 were considered significant ) . Ten of the 14 volunteers had three repeated measurements to test intrasession reproducibility and intersession reproducibility . RESULTS Overall activation rates for the four paradigms were 89 % for covert SG , 82 % for overt SG , 89 % for covert WG , and 100 % for overt WG . When comparing covert and overt paradigms , language localization was significantly different in 17 % ( Euclidean coordinates ) and 19 % ( BOLD signal characteristics ) , respectively . Language lateralization was significantly different in 75 % . Intrasubject and intersubject reproducibility was excellent , with 3.3 % significant differences among all five parameters for language localization and 0 % significant differences for language lateralization using covert paradigms . CONCLUSIONS Covert language paradigms ( SG and WG ) provided highly robust and reproducible localization and lateralization of essential language centers for scans performed on the same and different days . Their overt counterparts achieved confirmatory localization but lower lateralization capabilities . Reference data for presurgical application are provided |
1,845 | 27,127,016 | Non-physician delivered intravitreal therapy seems feasible and safe | INTRODUCTION Non-physicians such as nurses are trained to give injections into the vitreous body of the eye to meet the increasing dem and for intravitreal therapy with vascular endothelial growth factor inhibitors against common eye diseases , e.g. age-related macular degeneration and diabetic retinopathy .
We systematic ally review ed the existing literature to provide an overview of the experiences in this transformational process . | IMPORTANCE Panretinal photocoagulation ( PRP ) is the st and ard treatment for reducing severe visual loss from proliferative diabetic retinopathy . However , PRP can damage the retina , result ing in peripheral vision loss or worsening diabetic macular edema ( DME ) . OBJECTIVE To evaluate the noninferiority of intravitreous ranibizumab compared with PRP for visual acuity outcomes in patients with proliferative diabetic retinopathy . DESIGN , SETTING , AND PARTICIPANTS R and omized clinical trial conducted at 55 US sites among 305 adults with proliferative diabetic retinopathy enrolled between February and December 2012 ( mean age , 52 years ; 44 % female ; 52 % white ) . Both eyes were enrolled for 89 participants ( 1 eye to each study group ) , with a total of 394 study eyes . The final 2-year visit was completed in January 2015 . INTERVENTIONS Individual eyes were r and omly assigned to receive PRP treatment , completed in 1 to 3 visits ( n = 203 eyes ) , or ranibizumab , 0.5 mg , by intravitreous injection at baseline and as frequently as every 4 weeks based on a structured re-treatment protocol ( n = 191 eyes ) . Eyes in both treatment groups could receive ranibizumab for DME . MAIN OUTCOMES AND MEASURES The primary outcome was mean visual acuity change at 2 years ( 5-letter noninferiority margin ; intention-to-treat analysis ) . Secondary outcomes included visual acuity area under the curve , peripheral visual field loss , vitrectomy , DME development , and retinal neovascularization . RESULTS Mean visual acuity letter improvement at 2 years was + 2.8 in the ranibizumab group vs + 0.2 in the PRP group ( difference , + 2.2 ; 95 % CI , -0.5 to + 5.0 ; P < .001 for noninferiority ) . The mean treatment group difference in visual acuity area under the curve over 2 years was + 4.2 ( 95 % CI , + 3.0 to + 5.4 ; P < .001 ) . Mean peripheral visual field sensitivity loss was worse ( -23 dB vs -422 dB ; difference , 372 dB ; 95 % CI , 213 - 531 dB ; P < .001 ) , vitrectomy was more frequent ( 15 % vs 4 % ; difference , 9 % ; 95 % CI , 4%-15 % ; P < .001 ) , and DME development was more frequent ( 28 % vs 9 % ; difference , 19 % ; 95 % CI , 10%-28 % ; P < .001 ) in the PRP group vs the ranibizumab group , respectively . Eyes without active or regressed neovascularization at 2 years were not significantly different ( 35 % in the ranibizumab group vs 30 % in the PRP group ; difference , 3 % ; 95 % CI , -7 % to 12 % ; P = .58 ) . One eye in the ranibizumab group developed endophthalmitis . No significant differences between groups in rates of major cardiovascular events were identified . CONCLUSIONS AND RELEVANCE Among eyes with proliferative diabetic retinopathy , treatment with ranibizumab result ed in visual acuity that was noninferior to ( not worse than ) PRP treatment at 2 years . Although longer-term follow-up is needed , ranibizumab may be a reasonable treatment alternative , at least through 2 years , for patients with proliferative diabetic retinopathy . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01489189 Aims The aims were to compare a novel conjunctival mould used to assist the delivery of intravitreal drugs to a conventional technique with respect to patient , surgeon and cost benefit . Methods A prospect i ve review of 200 intravitreal injections was undertaken , 100 using a ‘ conventional ’ freeh and technique ( group 1 ) and 100 using a novel conjunctival mould ( group 2 ) . Intraoperative visual analogue scale ( VAS ) pain scores , patient preference , surgeon perception of the ease of insertion of the conjunctival mould were recorded as well as a cost comparison . Results VAS pain score in the conventional group was 2.58 compared to 1.38 in the conjunctival mould group ( p<0.01 ) . The surgeon reported the insertion of the conjunctival mould as easy in 89 cases , moderate in 10 cases , and difficult in one case . The cost saving with a conjunctival mould pack compared to a conventional pack was £ 7.70 ; an annual saving of £ 19 250 for the trust . Conclusions The reduction in the VAS pain score with the conjunctival mould was statistically significant ( p<0.01 ) . The surgeons found that the device , which was easy to insert , offered excellent globe stability and a safe , reproducible entry site and angle of needle insertion Background The dramatic increase in need for anti-vascular endothelial growth factor ( anti-VEGF ) intravitreal therapy in the treatment of retinal disease and the absence of an equivalent increase in ophthalmologists to undertake such intravitreal injections created a patient-safety risk . Timing of intravitreal therapy ( IVT ) is critical to prevent vision loss and local clinics lacked capacity to treat patients appropriately . We aim ed to improve capacity for IVT by nurse injections . Material s and methods A multidisciplinary prospect i ve service-improvement process was undertaken at two adjacent general hospitals in the northwest of Engl and . IVT injections by nurses were a principal component of solution development . After we had obtained appropriate institutional approval , experienced ophthalmic nurses were trained , supervised , and assessed to undertake IVT . Ophthalmologists directly supervised the first 200 injections , and a retina specialist was always on site . Results Nurses undertook 3,355 intravitreal injections between June 2012 and November 2013 , with minor adverse events ( 0.3 % subconjunctival hemorrhage and corneal abrasion ) . There were no patient complaints at either hospital . Conclusion Experienced ophthalmic nurses quickly learned how to perform such injections safely . IVT by nurses was well accepted by patients and staff . Hospital A trained three nurses sequentially for improved flexibility in scheduling . Novel use of appropriately trained non-medical staff can improve efficiency and access in an overburdened service with time-sensitive disease . Retinal assessment was undertaken by ophthalmologists only . Improved access to IVT is important , as treatment with anti-VEGF therapy reduces blindness at population levels Objectives To investigate the relationship between foveal morphology and self-perceived visual function in patients with neovascular age-related macular degeneration ( AMD ) and whether foveal characteristics are associated with Ranibizumab treatment response on the self-perceived visual function . Methods This prospect i ve cohort study included patients with newly diagnosed neovascular AMD found eligible for treatment with Ranibizumab . Foveal morphology of both eyes was assessed using spectral-domain optical coherence tomography and all patients were interviewed using the 39-item National Eye Institute Visual Function Question naire ( VFQ ) . Patients were re-interviewed 3 and 12 months after initiation of treatment with Ranibizumab . We evaluated foveal morphology at baseline in relation to VFQ scores at baseline and clinical ly meaningful changes in VFQ after 3 and 12 months . Results VFQ scores correlated with central foveal thickness , central foveal thickness of neuroretina ( CFN ) , foveal RPE elevation , foveal integrity of the photoreceptor inner segment/outer segment junction ( IS/OS ) , and external limiting membrane . In a multiple linear regression model , only best-corrected visual acuity of the better eye ( p<0.001 ) and the IS/OS status in the better eye ( p = 0.012 ) remained significant ( Adjusted R2 = 0.418 ) . Lower baseline VFQ and a baseline CFN within 170–270 µm in the better eye were both associated with a clinical ly meaningful increase in the VFQ scores after 3 and 12 months . An absent foveal IS/OS b and in the better eye was associated with a clinical ly meaningful decrease in the VFQ scores at 12 months . Conclusions Foveal morphology in the better eye influences the self-perceived visual function in patients with neovascular AMD and possesses a predictive value for change in the self-perceived visual function at 3 and 12 months after initiation of treatment . These findings may help clinicians provide patients more individualized information of their disease and treatment prognosis from a patient-perceived point-of-view Background Complicated approval procedures and limited short-term surgical capacities can result in time delays between the definition of a medical indication for ranibizumab treatment in active neovascular age-related macular degeneration ( AMD ) and the starting of treatment . This study aim ed to evaluate changes in visual acuity and central retinal thickness over time , and their consequences for the patients concerned . Methods Sixty-nine patients indicated for first-time ranibizumab treatment and 21 patients with necessary re-treatment were included in the study . Visual acuity and spectral domain optical coherence tomography ( SD-OCT ) central retinal thickness at the time of the indication examination were compared to values at the first-time treatment and during recurrent ranibizumab treatment . Results For first-time treatment , the delay between indication and treatment was significantly higher for patients with vision loss compared to those without vision loss ( 31.6 ± 20.5 vs. 24.0 ± 8.3 days , p = 0.012 ) . The increase in OCT central retinal thickness was 50.4 ± 92.8 μm for patients with vision loss compared to 5.1 ± 63.4 μm for those without vision loss , p = 0.029 . A 1.1 logMAR line difference in vision loss was significant at p = 0.01 for patients with a delay in treatment of less than or equal to 28 days ( 48/69 patients , 69.7 % ) compared to those with a delay of more than 28 days ( 21/69 patients , 30.3 % ) . Conclusions Even though average visual decay was slow at about one logMAR line over 110 days , individual patients ( 8.7 % ) experienced rapid loss of one or more lines within 21 days . Administrative procedures should therefore be expedited so that delays do not exceed 2 weeks for the sake of vision preservation in individual patients Purpose A recently developed ranibizumab prefilled syringe ( PFS ) eliminates several preparatory steps versus the st and ard vial-based method , and is expected to reduce syringe preparation time ( SPT ) and enhance procedural simplicity for intravitreal injections . Methods Syringe preparation times for the ranibizumab PFS and vial were recorded during st and ard treatment sessions at 2 centers , without r and omization . The duration of each step in preparing the syringe was recorded . At each center , total SPT ( mean total duration of all syringe preparation steps ) for each method was compared using a 2-tailed t test . Results In total , 97 SPTs were analyzed across both centers . Center 1 SPTs were 46 seconds ( PFS ) versus 75 seconds ( vial ; difference , 29 seconds ; p<0.001 ) . Center 2 SPTs were 46 seconds ( PFS ) versus 63 seconds ( vial ; difference , 17 seconds ; p<0.001 ) . This equates to a 27%-39 % reduction in SPT when using the PFS rather than the vial , result ing mostly from the reduced number of syringe preparation steps associated with the PFS . Conclusions Syringe preparation times for ranibizumab intravitreal injections are significantly shorter with the PFS than with the vial . The time saved by using the PFS may benefit physicians and nurses , and the simplicity of the injection preparation process with the PFS is advantageous PURPOSE To evaluate the prevalence and causes of visual impairment in an epidemiologic study of aged , urban individuals in Denmark . DESIGN Cross-sectional study . PARTICIPANTS The study population consisted of 1000 r and omly selected residents aged 60 to 80 years in Copenhagen , Denmark . Of 976 eligible persons , 946 ( 96.9 % ) could be examined . Information about best-corrected visual acuity ( VA ) was obtained from 944 cooperative persons ( 96.7 % ) . METHODS Data from the Copenhagen City Eye Study were used to assess the cause-specific prevalence of visual impairment as defined by the World Health Organization ( WHO ) ( VA worse than 20/60 - 20/400 in the better eye ) and the criteria used most commonly in the United States ( VA worse than 20/40 but better than 20/200 in the better eye ) . Eligible subjects underwent an extensive ophthalmologic examination at The National University Hospital of Denmark . MAIN OUTCOME MEASURES Best-corrected VA and primary causes of visual impairment . RESULTS The prevalence of low vision according to the WHO definition ranged from 2.6 % in subjects aged 70 to 74 years to 4.8 % in subjects 75 to 80 years of age , with an age-adjusted relative prevalence of 1.58 % . Using the U.S. definition , the overall age-adjusted prevalence of visual impairment was 2.9 % . The causes of visual impairment according to the WHO criteria were age-related macular degeneration ( AMD ) ( 44.4 % ) , cataract ( 33.3 % ) , glaucoma in combination with cataract ( 11.1 % ) , myopic macular degeneration ( 5.6 % ) , and diabetic retinopathy ( 5.6 % ) . However , according to the U.S. criteria , cataract was the most frequent primary cause ( 50.0 % ) and AMD was the second most frequent primary cause ( 34.4 % ) of visual impairment . Furthermore , using the U.S. criteria diabetic retinopathy was revealed as equally important as AMD and cataract as a cause of visual impairment among persons aged 65 to 69 years ( 33.3 % ) . CONCLUSIONS Increasing age was an independent predictor of visual impairment . Cataract and AMD were the leading causes . Adequate implementation of surgery to treat cataract could reduce visual impairment by 33.3 % according to the WHO criteria and by 50 % according to the U.S. criteria IMPORTANCE Although electronic health record ( EHR ) systems have potential benefits , such as improved safety and quality of care , most ophthalmology practice s in the United States have not adopted these systems . Concerns persist regarding potential negative impacts on clinical workflow . In particular , the impact of EHR operating room ( OR ) management systems on clinical efficiency in the ophthalmic surgery setting is unknown . OBJECTIVE To determine the impact of an EHR OR management system on intraoperative nursing documentation time , surgical volume , and staffing requirements . DESIGN , SETTING , AND PARTICIPANTS For documentation time and circulating nurses per procedure , a prospect i ve cohort design was used between January 10 , 2012 , and January 10 , 2013 . For surgical volume and overall staffing requirements , a case series design was used between January 29 , 2011 , and January 28 , 2013 . This study involved ophthalmic OR nurses ( n = 13 ) and surgeons ( n = 25 ) at an academic medical center . EXPOSURES Electronic health record OR management system implementation . MAIN OUTCOMES AND MEASURES ( 1 ) Documentation time ( percentage of operating time documenting [ POTD ] , absolute documentation time in minutes ) , ( 2 ) surgical volume ( procedures /time ) , and ( 3 ) staffing requirements ( full-time equivalents , circulating nurses/procedure ) . Outcomes were measured during a baseline period when paper documentation was used and during the early ( first 3 months ) and late ( 4 - 12 months ) periods after EHR implementation . RESULTS There was a worsening in total POTD in the early EHR period ( 83 % ) vs paper baseline ( 41 % ) ( P < .001 ) . This improved to baseline levels by the late EHR period ( 46 % , P = .28 ) , although POTD in the cataract group remained worse than at baseline ( 64 % , P < .001 ) . There was a worsening in absolute mean documentation time in the early EHR period ( 16.7 minutes ) vs paper baseline ( 7.5 minutes ) ( P < .001 ) . This improved in the late EHR period ( 9.2 minutes ) but remained worse than in the paper baseline ( P < .001 ) . While cataract procedures required more circulating nurses in the early EHR ( mean , 1.9 nurses/procedure ) and late EHR ( mean , 1.5 nurses/procedure ) periods than in the paper baseline ( mean , 1.0 nurses/procedure ) ( P < .001 ) , overall staffing requirements and surgical volume were not significantly different between the periods . CONCLUSIONS AND RELEVANCE Electronic health record OR management system implementation was associated with worsening of intraoperative nursing documentation time especially in shorter procedures . However , it is possible to implement an EHR OR management system without serious negative impacts on surgical volume and staffing requirements PURPOSE A head-to-head comparison was performed between vascular endothelial growth factor blockade and laser for treatment of diabetic macular edema ( DME ) . DESIGN Two similarly design ed , double-masked , r and omized , phase 3 trials , VISTA(DME ) and VIVID(DME ) . PARTICIPANTS We included 872 patients ( eyes ) with type 1 or 2 diabetes mellitus who presented with DME with central involvement . METHODS Eyes received either intravitreal aflibercept injection ( IAI ) 2 mg every 4 weeks ( 2q4 ) , IAI 2 mg every 8 weeks after 5 initial monthly doses ( 2q8 ) , or macular laser photocoagulation . MAIN OUTCOME MEASURES The primary efficacy endpoint was the change from baseline in best-corrected visual acuity ( BCVA ) in Early Treatment Diabetic Retinopathy Study ( ETDRS ) letters at week 52 . Secondary efficacy endpoints at week 52 included the proportion of eyes that gained ≥ 15 letters from baseline and the mean change from baseline in central retinal thickness as determined by optical coherence tomography . RESULTS Mean BCVA gains from baseline to week 52 in the IAI 2q4 and 2q8 groups versus the laser group were 12.5 and 10.7 versus 0.2 letters ( P < 0.0001 ) in VISTA , and 10.5 and 10.7 versus 1.2 letters ( P < 0.0001 ) in VIVID . The corresponding proportions of eyes gaining ≥ 15 letters were 41.6 % and 31.1 % versus 7.8 % ( P < 0.0001 ) in VISTA , and 32.4 % and 33.3 % versus 9.1 % ( P < 0.0001 ) in VIVID . Similarly , mean reductions in central retinal thickness were 185.9 and 183.1 versus 73.3 μm ( P < 0.0001 ) in VISTA , and 195.0 and 192.4 versus 66.2 μm ( P < 0.0001 ) in VIVID . Overall incidences of ocular and nonocular adverse events and serious adverse events , including the Anti-Platelet Trialists ' Collaboration-defined arterial thromboembolic events and vascular deaths , were similar across treatment groups . CONCLUSIONS At week 52 , IAI demonstrated significant superiority in functional and anatomic endpoints over laser , with similar efficacy in the 2q4 and 2q8 groups despite the extended dosing interval in the 2q8 group . In general , IAI was well-tolerated Purpose To evaluate the safety of a nurse practitioner (NP)-delivered injection service for the treatment of wet age-related macular degeneration ( wAMD ) with ranibizumab . Methods An evaluation of medical staffing re sources for providing an injection service for wAMD highlighted difficulties covering lists . An alternative strategy of an NP-delivered injection service was evaluated . Two suitable NPs with previous extensive experience in minor surgical procedures were identified . The department ’s senior vitreo-retinal consultant supervised the NP ’s training programme . A prospect i ve safety audit was conducted for the first 5.5 years of the service . Results The NPs administered 10 006 injections in the first 5.5 years of the service ( 1 May 2008 to 8 October 2013 ) . This represented 84.1 % of the total injections performed during this period . Four patients developed presumed infectious endophthalmitis ( 1 was culture positive and 3 were culture negative ) . The incidence of post-injection endophthalmitis was 0.04 % . There was no evidence of lens touch , retinal detachment , or systemic thrombo-embolic events . Conclusions Carefully selected and well-trained NPs are capable of delivering a safe and effective wAMD injection treatment service . This work demonstrates how such a service can be established and provides safety data that other units can use as a benchmark when evaluating their own practice PURPOSE To assess the efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema after central retinal vein occlusion ( CRVO ) . DESIGN Prospect i ve , r and omized , sham injection-controlled , double-masked , multicenter clinical trial . PARTICIPANTS A total of 392 patients with macular edema after CRVO . METHODS Eligible patients were r and omized 1:1:1 to receive monthly intraocular injections of 0.3 or 0.5 mg of ranibizumab or sham injections . MAIN OUTCOME MEASURES The primary efficacy outcome measure was mean change from baseline best-corrected visual acuity ( BCVA ) letter score at month 6 . Secondary outcomes included other parameters of visual function and central foveal thickness ( CFT ) . RESULTS Mean ( 95 % confidence interval [ CI ] ) change from baseline BCVA letter score at month 6 was 12.7 ( 9.9 - 15.4 ) and 14.9 ( 12.6 - 17.2 ) in the 0.3 mg and 0.5 mg ranibizumab groups , respectively , and 0.8 ( -2.0 to 3.6 ) in the sham group ( P<0.0001 for each ranibizumab group vs. sham ) . The percentage of patients who gained > or = 15 letters in BCVA at month 6 was 46.2 % ( 0.3 mg ) and 47.7 % ( 0.5 mg ) in the ranibizumab groups and 16.9 % in the sham group ( P<0.0001 for each ranibizumab group vs. sham ) . At month 6 , significantly more ranibizumab-treated patients ( 0.3 mg = 43.9 % ; 0.5 mg = 46.9 % ) had BCVA of > or = 20/40 compared with sham patients ( 20.8 % ; P<0.0001 for each ranibizumab group vs. sham ) , and CFT had decreased by a mean of 434 microm ( 0.3 mg ) and 452 microm ( 0.5 mg ) in the ranibizumab groups and 168 microm in the sham group ( P<0.0001 for each ranibizumab group vs. sham ) . The median percent reduction in excess foveal thickness at month 6 was 94.0 % and 97.3 % in the 0.3 mg and 0.5 mg groups , respectively , and 23.9 % in the sham group . The safety profile was consistent with previous phase III ranibizumab trials , and no new safety events were identified in patients with CRVO . CONCLUSIONS Intraocular injections of 0.3 mg or 0.5 mg ranibizumab provided rapid improvement in 6-month visual acuity and macular edema following CRVO , with low rates of ocular and nonocular safety events pathophysiology in LHON . In this study , we reported that ganglion cell analysis could precisely detect the loss of retinal ganglion cell in a time-dependent manner during early phase of LHON when RNFL thickness had not decreased yet . We also raise the possibility that there might be many more patients > 60 years of age with visual loss owing to LHON than we have supposed previously . It may be worth investigating mtDNA point mutations regardless of age if a patient presents with unknown visual acuity loss with central scotoma |
1,846 | 22,994,715 | Positive expression of tissue VEGF , circulating VEGF , VEGF-C and VEGF-D were all associated with poor prognosis in resected gastric cancer .
However , VEGF demonstrated no significant prognostic value for non-Asian population s. Circulating VEGF may be better than tissue VEGF in predicting prognosis | BACKGROUND AND AIMS Vascular endothelial growth factor ( VEGF ) is a potential prognostic biomarker for patients with resected gastric cancer .
However , its role remains controversial .
The objective of this study was to conduct a systematic review and meta- analysis of published literature . | INTRODUCTION This study evaluated the prognostic role of vascular epidermal growth factor ( VEGF ) , thymidylate synthase ( TS ) , topoisomerase I ( Topo-I ) , topoisomerase IIalpha ( Topo-IIalpha ) and E-cadherin ( E-cadh ) tumor expression , in patients with resectable gastric cancer , who were treated postoperatively with the docetaxel/irinotecan combination . PATIENTS AND METHODS Forty-five patients with resectable gastric cancer were treated with 6 cycles of docetaxel 30 mg/m2 and irinotecan 110 m/m2 on day 1 and d8 every 21 days . All specimens were examined by using immunohistochemistry ( IHC ) for the expression of VEGF , TS , Topo-I , Topo-IIalpha and E-cadh . RESULTS Positivity for TS was significantly correlated with age and for VEGF with diffuse histological type and good PS . No significant correlation was observed among Topo-I , Topo-IIalpha and E-cadh positivity with any of the clinicopathological parameters studied . Median overall survival ( OS ) was 31.7 , and disease-free survival ( DFS ) 26 months , respectively . None of the above-investigated molecular markers were significantly associated with OS and DFS . Finally , according to the univariate analysis for survival , only advanced stages ( III , IV ) of the disease implied risk of death , mainly due to lymph node involvement and , to a lesser extent , tumor size . None of the studied molecular markers were found to be independent prognostic markers . CONCLUSION These results should be interpreted very cautiously , due to the limited number of patients studied , as well as the limitations of the IHC technique Objective To evaluate the correlation between serum vascular endothelial growth factor ( VEGF ) level and the clinicopathologic features in patients with hepatocellular carcinoma ( HCC ) . Summary Background Data VEGF is an important angiogenic factor regulating tumor angiogenesis . A high serum VEGF level has been shown to be associated with tumor progression and metastasis in several human cancers , but its significance in HCC is unclear . The correlation between serum VEGF level and tumor pathologic features in patients with HCC has not been studied before . Methods Preoperative serum sample s and tumor specimens were prospect ively collected in 100 patients undergoing resection of HCC . Serum VEGF level was measured by enzyme-linked immunosorbent assay , and tumor VEGF expression was assessed by immunohistochemical study . Histopathologic examination was performed by a pathologist without prior knowledge of the serum VEGF level or tumor VEGF expression . Results Preoperative serum VEGF levels ranged from 15 to 1,789 pg/mL ( median 269 ) . When serum VEGF levels were compared between groups categorized by different clinicopathologic variables , significant correlation was found between a high serum VEGF level and absence of tumor capsule , presence of intrahepatic metastasis , presence of microscopic venous invasion , and advanced stage . There was a positive correlation between the serum VEGF level and tumor expression of VEGF as well as platelet count . When the 75th percentile serum VEGF level ( 500 pg/mL ) was used as a cutoff level , the frequency of venous invasion in patients with a high serum VEGF level was significantly greater compared with patients with a low serum VEGF level . By multivariate analysis , a serum VEGF level of more than 500 pg/mL and tumor size more than 5 cm were independent preoperative factors predictive of microscopic venous invasion . During a median follow-up of 11.6 months , 48 % of patients with a serum VEGF level of more than 500 pg/mL and 27 % of those with a serum VEGF level of 500 pg/mL or less developed postoperative recurrence . Conclusions These results show that a high preoperative serum VEGF level is a predictor of microscopic venous invasion in HCC , suggesting that the serum VEGF level may be useful as a biologic marker of tumor invasiveness and a prognostic factor in HCC Vascular endothelial growth factor ( VEGF ) is an important regulator of angiogenesis and vascular permeability . Increased serum VEGF concentrations ( S-VEGF ) have been found in patients with various types of human cancer , including cancer of the lung . However , the clinical and prognostic significance of S-VEGF in cancer is unknown . We measured S-VEGF , using enzyme-linked immunosorbent assay , in sera taken from 68 untreated patients with small-cell lung cancer ( SCLC ) at the time of diagnosis . The patients were treated with 6 cycles of cisplatin and etoposide , and were r and omly assigned to receive recombinant interferon , leukocyte interferon or neither . S-VEGF ranged from 70 to 1738 pg/ml ( mean , 527 pg/ml ) . The patients who achieved partial or complete response to treatment had lower pre-treatment S-VEGF than the non-responding patients ( p = 0.0083 , Mann-Whitney test ) . High ( > 527 pg/ml ) S-VEGF was associated with poor survival ( p = 0.012 , Log Rank Test ) , and all 3-year survivors had lower than mean pre-treatment S-VEGF . In a multivariate analysis , S-VEGF and stage were the only independent prognostic factors , and the estimated 3-year survival of the patients with limited stage disease and low pretreatment S-VEGF ( n = 17 , 25 % of all patients ) was 41 % ( p = 0.0055 , log rank test ) . These data show that high pretreatment S-VEGF is associated with poor response to treatment and unfavourable survival in patients with SCLC treated with combination chemotherapy with or without interferon Despite years of research and hundreds of reports on tumor markers in oncology , the number of markers that have emerged as clinical ly useful is pitifully small . Often initially reported studies of a marker show great promise , but subsequent studies on the same or related markers yield inconsistent conclusions or st and in direct contradiction to the promising results . It is imperative that we attempt to underst and the reasons why multiple studies of the same marker lead to differing conclusions . A variety of method ological problems have been cited to explain these discrepancies . Unfortunately , many tumor marker studies have not been reported in a rigorous fashion , and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalizability of study results . The development of guidelines for the reporting of tumor marker studies was a major recommendation of the National Cancer Institute – European Organisation for Research and Treatment of Cancer ( NCI – EORTC ) First International Meeting on Cancer Diagnostics in 2000 . As for the successful CONSORT initiative for r and omized trials and for the STARD statement for diagnostic studies , we suggest guidelines to provide relevant information about the study design , preplanned hypotheses , patient and specimen characteristics , assay methods , and statistical analysis methods . In addition , the guidelines provide helpful suggestions on how to present data and important elements to include in discussion s. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and underst and the context in which the conclusions apply |
1,847 | 16,034,894 | When analysed for change in ss(2 ) microglobulin , a fall was only noted with high-flux membranes .
We found no evidence of benefit when synthetic membranes were compared with cellulose/modified cellulose membranes in terms of reduced mortality no reduction in dialysis-related adverse symptoms .
Despite the relatively large number of RCTs undertaken in this area none of the included studies reported any measures of quality of life | BACKGROUND When the kidney fails the blood-borne metabolites of protein breakdown and water can not be excreted .
The principle of haemodialysis is that such substances can be removed when blood is passed over a semipermeable membrane .
Natural membrane material s include cellulose or modified cellulose , more recently various synthetic membranes have been developed .
Synthetic membranes are regarded as being more " biocompatible " in that they incite less of an immune response than cellulose-based membranes .
OBJECTIVES To assess the effects of different haemodialysis membrane material in patients with end-stage renal disease ( ESRD ) . | One hundred out patients on chronic haemodialysis with polymethylmethacrylate ( PMMA ) membrane dialyzer were r and omly chosen . A control group of 100 likewise r and omly chosen out patients were treated with cuprophane membrane dialyzer . In both groups the treatments lasted for one year . Comparison of the test results revealed that Si , Al and β2M.G levels could be reduced in patients on chronic HD with PMMA This biocompatibility of the new cellulosic membrane hemophane ( HE ) is compared to that of cuprophane ( CU ) in ten maintenance hemodialysis ( HD ) patients dialyzed on the two types of membranes in r and omized order , under otherwise similar technical conditions . Total white blood cell ( WBC ) and differential counts , blood concentrations of C3a , and C3d and histamine are determined at start of dialysis ( TO ) and 10 , 20 and 180 minutes thereafter . HE is distinct from CU in exerting a minor effect on the generation of C3a , a minor drop of leucocytes during the course of dialysis ( P less than 0.01 ) and also by a lesser increase in blood histamine concentration ( P less than 0.05 ) . Histamine liberation is observed on CU together with the generation of anaphylotoxin C3 and with a diminution of circulating basopolymorpho-nuclear cells . According to the variations observed for these three parameters ( C3a , leucocytosis and blood histamine concentration ) , HE appears as being more biocompatible than CU There is increasing evidence that the biochemical and cellular phenomena induced by blood/ membrane/dialysate interactions contribute to dialysis-related intradialytic and long-term complications . However , there is a lack of large , prospect i ve , r and omized trials comparing biocompatible and bioincompatible membranes , and convective and diffusive treatment modalities . The primary aim of this prospect i ve , r and omized trial was to evaluate whether the use of polysulfone membrane with bicarbonate dialysate offers any advantage ( in terms of treatment tolerance , nutritional parameters and pre-treatment beta-microglobulin levels ) over a traditional membrane ( Cuprophan ) . A secondary aim was to assess whether the use of more sophisticated methods consisting of a biocompatible synthetic membrane with different hydraulic permeability at different ultrafiltration rate ( high-flux hemodialysis and hemodiafiltration ) offers any further advantages . Seventy-one Centers were involved and stratified according to the availability of only the first two or all four of the following techniques : Cuprophan hemodialysis ( Cu-HD ) , low-flux polysulfone hemodialysis ( LfPS-HD ) , high-flux polysulfone high-flux hemodialysis ( HfPS-HD ) , and high-flux polysulfone hemodiafiltration ( HfPS-HDF ) . The 380 eligible patients were r and omized to one of the two or four treatments ( 132 to Cu-HD , 147 to LfPS-HD , 51 to HfPS-HD and 50 to HfPS-HDF ) . The follow-up was 24 months . No statistical difference was observed in the algebraic sum of the end points between bicarbonate dialysis with Cuprophan or with low-flux polysulfone , or among the four dialysis methods under evaluation . There was a significant decrease in pre-dialysis plasma beta 2-microglobulin levels in high-flux dialysis of 9.04 + /- 10.46 mg/liter ( 23 % ) and in hemodiafiltration of 6.35 + /- 12.28 mg/liter ( 16 % ) , both using high-flux polysulfone membrane in comparison with Cuprophan and low-flux polysulfone membranes ( P = 0.032 ) . The significant decrease in pre-dialysis plasma beta 2-microglobulin levels could have a clinical impact when one considers that beta 2-microglobulin accumulation and amyloidosis are important long-term dialysis-related complications BACKGROUND Hyperhomocysteinaemia is a putative risk factor for atherothrombotic cardiovascular disease in the haemodialysis population . High-dose vitamin B therapy does not entirely normalize elevated plasma total homocysteine ( tHcy ) levels in haemodialysis patients . Alternative therapies to reduce tHcy further are therefore required . Modifications of the dialysis regimen may result in a better removal of Hcy . We examined the effect of dialyser membrane pore size on tHcy levels in vitamin-replete chronic haemodialysis patients . METHODS Forty-five haemodialysis patients were dialysed during 4 weeks with a low-flux , a high-flux and a super-flux membrane , in r and om order . Pre-dialysis tHcy was determined at baseline and every 4 weeks . In 18 patients , plasma tHcy before and after dialysis and dialysate tHcy concentrations were measured . RESULTS Pre-dialysis tHcy decreased significantly during 4 weeks super-flux dialysis ( -14.6 + /- 2.8 % ) , whereas it remained stable during high-flux ( + 0.5 + /- 2.4 % ) and low-flux dialysis ( + 1.7 + /- 3.2 % ) . The homocysteine reduction ratio was not different for the three membranes : 0.39 + /- 0.03 for the super-flux , 0.47 + /- 0.02 for the high-flux and 0.39 + /- 0.02 for the low-flux dialyser . The amount of Hcy recovered in the dialysate during a single dialysis session was also similar : 117.5 + /- 3.6 micro mol during super-flux , 95.3 + /- 11.5 micro mol during high-flux and 116.5 + /- 11.6 micro mol during low-flux dialysis . CONCLUSION Super-flux dialysis significantly lowers tHcy in chronic haemodialysis patients . Improved removal of middle-molecule uraemic toxins with inhibitory effects on Hcy-metabolizing enzymes , rather than better dialytic clearance of Hcy itself , may explain the beneficial effect of the super-flux membrane Pruritus is one of the major unsolved problems for patients receiving regular hemodialysis . In this study , we conducted a 6 month prospect i ve and crossover trial to investigate the effect of polymethylmethacrylate ( PMMA ) membrane for renal itching . We also examined the role of the tumor necrosis factor (TNF)-alpha system for pruritus in hemodialysis patients . We assessed the degree of skin itching and measured circulating levels of TNF-alpha and soluble TNF receptors ( sTNFR-I , sTNFR-II ) in 19 patients using hemodialysis , complicated by prolonged severe pruritus for 6 months . Serum sTNFR-I and II levels were significantly elevated in hemodialysis patients compared to normal subjects . Serum sTNFR-II levels were significantly and negatively correlated with serum albumin ( r = -0.602 , p = 0.007 ) . A significant positive relationship was also found between sTNFR-I and erythropoietin dosage ( r = 0.554 , p = 0.016 ) . However , no association was found between the degree of pruritus and circulating sTNFR-I and II values . Skin itching scale was significantly decreased from 2.7 + /- 0.2 to 2.1 + /- 0.3 following the use of PMMA membrane for 3 months ( p < 0.05 ) . In contrast , there was no change in itching scales during 3 months of conventional therapy ( 2.2 + /- 0.3 versus 2.2 + /- 0.3 , p = NS ) . PMMA itself did not affect serum TNF-alpha and sTNFR values as well as conventional dialyzer membranes . These findings suggested that the PMMA dialyzer can improve renal itching not mediated through the modification of the TNF-alpha system A crossover study to compare the effects of seven different dialysers on blood gas conditions during dialysis using acetate-containing dialysate was carried out at five centres in four countries . A significant decrease in pO2 was noted at both 15 and 60 min after the start of dialysis for all dialysers , with the greatest decrease at 60 min . Filtral caused the greatest reduction and F 60 the least change at both 15 and 60 min . These differences were statistically significant according to the ANOVA multiple-range test for variance . pCO2 also declined by 1.0 - 2.7 mmHg at 15 min and by 0.7 - 3.8 mmHg at 60 min . The delta pCO2 was comparable across dialysers and no significant differences were found . Although pH showed no change at 15 min , it was slightly but significantly increased at 60 min across all dialysers compared to predialysis values . There were no statistical differences between dialysers . Calculated blood bicarbonate content significantly decreased at 15 min and recovered at 60 min . Along with the greater decrease in pO2 , a larger loss of total CO2 was noted for Filtral . On the other h and F 60 caused the least change in total CO2 . This difference may be due to membrane characteristics affecting the diffusion coefficient for O2 , CO2 , and bicarbonate . Multifactorial mechanisms are likely to be involved , but reflex hypoventilation and an increase in O2 consumption also contributed to hypoxaemia in this study BACKGROUND Half of the dialysis population suffers from hyperphosphataemia , which is now recognized as a major factor of haemodialysis ( HD ) morbidity and mortality . Current control is focussed on reducing dietary phosphate intake and diminishing absorption using phosphate binders , whereas control and quantification of phosphate removal by HD is undervalued . The aim of this prospect i ve study was to develop a simple , bedside formula to estimate dialytic phosphate removal in stable HD patients . METHODS This was a prospect i ve , r and omized trial . Phosphate and urea elimination were assessed in a representative group of patients at two dialysis centres using r and omly different dialysers ( 1.3 - 2.4 m(2 ) ) . Quantification was performed by partial dialysate collection , concentration measurements in blood and effluent dialysate spot sample s , and Kt/V(urea ) during st and ard high-flux HD . Multiple linear regression analyses were used in 77 % of all data sets to generate an equation to predict phosphate removal . The formula was vali date d in the remaining 23 % of data sets , in the same group of patients using a large capillary filter , and in diabetic patients treated with a small dialyser at different blood flows ( 200 , 250 , and 300 ml/min ) . RESULTS A formula allowing quantification of phosphate removal within one HD session was developed in 18 of 74 patients during 41 treatments ( 137 out of 177 data sets ) and was determined as : M(PO4pred)=0.1 t -17 + 50c(ds60)+11c(b60 ) , where t is treatment time in min , c(ds60 ) and c(b60 ) are phosphate concentrations in dialysate and plasma measured 60 min into HD in mmol/l , and M(PO4pred ) is estimated phosphate removed in mmol . The precision was remarkable ( r(2)=0.92 - 0.94 ) . The comparison of phosphate and Kt/V(urea ) showed a significant association ( r(2)=0.28 ) , albeit with remarkable scatter . CONCLUSIONS We present the first approach to quantify phosphate removal during high-flux HD by a bedside formula . Only 28 % of the variation in phosphate removal was explained by Kt/V(urea ) . It appears that other factors not adequately accounted for by Kt/V(urea ) affect phosphate removal . Therefore , we propose an individual control and quantification of phosphate removal in HD In vitro experiments have related anaphylactoid reactions in patients treated with angiotensin-converting enzyme ( ACE ) inhibitors during dialysis with AN69 membranes to excessive bradykinin generation using this negatively charged dialysis membrane . In the present clinical trial plasma bradykinin levels were followed during the early phase of dialysis in 10 patients , not being treated with ACE inhibitors , using AN69 , cuprophane , and polysulfone membranes . Bradykinin was measured after extraction by radioimmunoassay . During this study one episode of anaphylaxis occurred during dialysis with the AN69 membrane . Blood sample s were collected during the first 5 min of the adverse reaction and showed a more than 100-fold increase in the venous effluent of the AN69 dialyzer ( baseline 40 + /- 3 vs. 4,900 + /- 130 fmol/ml after 5 min ) . Even though none of the patients received ACE inhibitors , there were 4 more asymptomatic individuals who displayed a more than two-fold increase in their plasma bradykinin concentrations in the venous effluent of the AN69 dialyzer . When these patients were treated either with cuprophane or with polysulfone dialyzers , no significant bradykinin formation was detected , nor were there any adverse events . Taken together , these findings show that anaphylactoid reactions with the AN69 membrane are due to excessive bradykinin generation which even may occur in the absence of ACE inhibitors We studied the upregulation of the intracellular glycoprotein Mac-1 ( CD11b/CD18 , CR3 ) on monocytes and granulocytes during 36 bicarbonate hemodialyses in 12 patients who were r and omly treated with Cuprophan ( Cu ) , Hemophan ( He ) or Polysulfone ( PS ; low-flux ) membranes . The degree of mobilization of this adhesion protein was related to changes in granulocyte and monocyte count , generation of C3a and production of interleukin-1 beta in plasma . Mac-1 expression on granulocytes was significantly higher after 5 and 15 min of Cu hemodialysis as compared to He or PS dialyses ( p < 0.001 ) and correlated to changes in granulocyte count at 15 min ( r = 0.62 and r = 0.76 , p < 0.001 ) . No differences in early Mac-1 mobilization on circulating monocytes was observed despite a decrease in cell count . Mac-1 expression on monocytes and granulocytes in the venous blood line at 180 min of treatment was significantly higher during Cu dialysis as compared to He and PS dialyses ( p < 0.02 and p < 0.001 , respectively ) . Early generation of C3a was higher in patients on Cu dialysis than in He or PS dialysis ( p < 0.001 ) and correlated both to granulocytopenia ( r = 0.45 , p < 0.01 ) and to the subsequent increase in Mac-1 expression on granulocytes ( r = 0.63 , p < 0.001 ) . An early increase in Mac-1 expression on monocytes was accompanied by an increase in plasma interleukin-1 beta later during dialysis ( p < 0.05 ) . Studies of Mac-1 expression during hemodialysis increased the sensitivity of biocompatibility measurements and correlated better than complement generation to changes in granulocyte count as it mediates adhesion to endothelial cells Hemodialysis induces thrombocytopenia and activation of coagulation . The severity of this reaction depends on the kind of membrane . In this study , we present the results of determination of platelet count , and of different factors of coagulation in 10 stable dialysis patients . Measurements were performed at the start and after 15 and 45 min of dialysis . Sample s were taken before and after the dialyzer . All 10 patients were treated consecutively and in a r and om order during 14 days with the following membranes : polyacrylonitrile ( Filtral 12 , Hospal ) , hemophan ( GFS 120 Plus , Gambro , and Bio-Nephros HF And ante , Organon ) , polysulfone ( F6 , Fresenius ) , cuprammonium ( AM50-BIO , Asahi ) and cellulose acetate ( Duo-Flux , Cordis-Dow ) . The cellulose acetate membrane induced a small but significant drop of mean platelet count [ results are mean ( SEM ) ] : from 245,000 ( 17,000 ) to 224,000 (16,000)/microliters after 15 min . With the same membrane a dramatic increase after 15 min was noted of 6-keto-PGF1 alpha from 56.3 ( 9 ) to 146.7 ( 35.7 ) pg/ml . The other membranes did not influence significantly prostanoid levels and platelet count . During dialysis no significant changes of fibrinopeptide A ( FPA ) and von Willebr and factor ( VWF ) were observed . Nevertheless , predialysis FPA and beta-thromboglobulin ( beta TG ) concentrations were lowest after 14 days of treatment with cellulose acetate and polyacrylonitrile membranes . It is concluded that the activation of coagulation depends on the membrane used . The activation may be dominated by one single system ( e.g. prostanoids ) . The different predialysis concentration of some of the factors suggests interference of the dialysis membrane with the activation of coagulation during the interdialytic period The effect of dialyzer membrane and design on hemostatic parameters during hemodialysis were evaluated in a prospect i ve controlled study . This study demonstrated that hemodialysis is associated with significant platelet activation and loss , which are influenced by both dialyzer configuration and membrane composition . In addition , use of the cuprophan membrane is associated with greater perturbations of the vascular endothelium , as reflected in changes in factor VIII-related von Willebr and factor and 6-keto-prostagl and in F1 alpha concentrations not seen with the polyacrylonitrile membrane . Of the dialyzers studied , the polyacrylonitrile membrane in a hollow-fiber configuration appears to minimize platelet loss and activation , and to minimize increases in factor VIII-related von Willebr and factor and 6-keto-prostagl and in F1 alpha BACKGROUND Anaemia is one of the major clinical characteristics of patients with chronic renal failure , and has a considerable effect on morbidity and mortality . Adequate dialysis is of paramount importance in correcting anaemia by removing small and medium-sized molecules , which may inhibit erythropoiesis . However , high-molecular-weight inhibitors cleared only by means of highly porous membranes have also been found in uraemic serum and it has been cl aim ed from uncontrolled studies that high-flux dialysis could improve anaemia in haemodialysis patients . METHODS We therefore planned this multicentre r and omized controlled trial with the aim of testing whether the use of a large-pore biocompatible membrane for a fixed 12-week follow-up improves anaemia in haemodialysis patients in comparison with the use of a conventional cellulose membrane . Eighty-four ( 5.3 % ) of a total of 1576 adult haemodialysed patients attending 13 Dialysis Units fulfilled the entry criteria and were r and omly assigned to the experimental treatment ( 42 patients ) or conventional treatment ( 42 patients ) . RESULTS Haemoglobin levels increased non-significantly from 9.5+/-0.8 to 9.8+/-1.3 g/dl ( dP=0 . 069 ) in the population as a whole , with no significant difference between the two groups ( P:=0.485 ) . Erythropoietin therapy was given to 32/39 patients ( 82 % ) in the conventional group , and 26/35 ( 74 % ) in the experimental group ( P:=0.783 ) with subcutaneous administration to 26/32 patients in conventional and to 23/26 patients in experimental group , P:=0.495 . Dialysis dose ( Kt/V ) remained constant in both groups ( from 1.30+/-0.17 to 1.33+/-0.20 in the conventional group and from 1.28+/-0.26 to 1.26+/-0.21 in the experimental group , P:=0.242 ) . Median pre- and post-dialysis beta(2)-microglobulin levels remained constant in the conventional group ( 31.9 and 34.1 mg/dl at baseline ) and decreased in the experimental group ( pre-dialysis values from 31.1 to 24.7 mg/dl , P:=0.004 and post-dialysis values from 24.8 to 20.8 mg/dl , P:=0.002 ) . Median erythropoietin doses were not different at baseline ( 70 IU/kg/week in conventional treatment and 90 IU/kg/week in experimental treatment , P:=0.628 ) and remained constant during follow-up ( from 70 to 69 IU/kg/week in the conventional group and from 90 to 91 IU/kg/week in the experimental group , P:=0.410 ) . Median erythropoietin plasma levels were in the normal range and remained constant ( from 12.1 to 12.9 mU/ml in the conventional group and from 13.2 to 14.0 mU/ml in the experimental group , P:=0.550 ) . CONCLUSIONS This study showed no difference in haemoglobin level increase between patients treated for 3 months with a high-flux biocompatible membrane in comparison with those treated with a st and ard membrane . When patients are highly selected , adequately dialysed , and have no iron or vitamin depletion , the effect of a high-flux membrane is much less than might be expected from the results of uncontrolled studies The contributions of membrane biocompatibility , dialysate temperature and sodium concentration to hemodynamic stability during hemodialysis were studied in 8 patients with a high incidence of hemodialysis-induced symptomatic hypotension . Patients were treated during 8 different periods , r and omly ordered in each case , result ing from the combination of the following : the membrane , either Cuprophan or Polyacrylonitrile ; the dialysate temperature , 37 or 35 ° C , and the sodium concentration , 133 or 139 mmol/l . The incidence of symptomatic hypotension was lower at 35 ° C in the entire study with either membrane and either sodium concentration . It was also lower with a sodium concentration of 139 mmol/l with either temperature and either membrane . There was a lower incidence of symptomatic hypotension when using Polyacrylonitrile , but this difference was not significant . We conclude that changes in physicochemical parameters of dialysate lead to worth-while improvement of symptomatic hypotension in hemodialysis patients , but membrane biocompatibility seems to play a minor role There are very few reports in the literature on individual differences in the response to dialysis treatment . We studied the influence of the individual patient , dialysis membrane quality , blood-flow ( Qb ) and surface area on leukocyte activation and complement generation ( C3a ) during 234 hemodialysis treatments using Cuprophan ( CU ) , hemophane ( HE ) and polyamide ( PA ) dialyzers . The most common reaction was a decrease in leukocyte count and an increase in C3a after 15 minutes of treatment . Leukocyte overshoot by the end of dialysis was observed at high Qb for all three membranes but at low Qb only during CU treatments . The reaction patterns were influenced by the quality of the membrane , area and Qb . Analysis of each individual patient showed for a large number of treatments reaction patterns corresponding to those described in the literature . However , some patients reacted differently . In four patients ( 20 % ) , the nadir in leukocyte count and maximum in C3a concentration was reached considerably later during CU-dialysis . Three patients were devoid of pronounced early leukocyte response but presented with the late overshoot during CU-dialysis . Three other patients reacted with an early drop in leukocyte count and a rapid increase in C3a generation during PA treatments but not during HE treatments . Three other patients reacted vice versa . A particular mode of dialysis treatment may thus be biocompatible for some patients but not necessarily for all . In the case biocompatibility is desired the individual response to the particular dialysis mode needs to be identified . The underlying mechanisms warrant further studies Arterial and venous concentrations of complement ( C3a ) and leukocyte count were determined in 17 patients during 201 hemodialysis sessions by 12 different treatment modes executed in r and om order using cuprophan , hemophan , or polyamide membranes with small or large membrane areas and high blood flow ( Qb ) ( 400 mL/min ) for 2 hours or low Qb ( 200 mL/min ) for 4 hours . With all membrane types , the number of leukocytes was significantly higher after 120 minutes of dialysis and by the end of treatment at high Qb compared with low Qb . C3a concentrations ( microgram/mL ) in the arterial and venous blood lines were significantly higher during cuprophan dialysis compared with hemophan and polyamide dialyses ( P < 0.001 ) . In addition , the net generation of C3a ( microgram/min ) was significantly higher during hemodialysis with cuprophan compared with hemophan and polyamide ( P < 0.001 ) . After 2 hours at high Qb for each of the three membranes , the net generation of C3a was significantly higher compared with low Qb ( P < 0.05 for all comparisons ) . Possible reasons for the increase in the net generation of C3a ( microgram/min ) at high Qb are less protein deposition on the membrane at high Qb or the fact that the protein coat is stripped off in the dialyzer , thereby recreating a less biocompatible surface . Hemodialysis at high Qb may thus be less biocompatible than dialysis at low Qb BACKGROUND Hyperleptinaemia in chronic haemodialysis ( CHD ) patients has been associated with malnutrition , which is an independent predictor of morbidity and mortality in this patient group . METHODS To assess the influence of HD on plasma leptin , 10 CHD patients were crossover r and omized to low-flux polysulfone ( PS : F 6HPS ) , high-flux PS ( F 60S ) , super-flux PS ( F 500S ) or super-flux cellulose-tri-acetate ( CTA : Tricea 150 G ) for 12 weeks each . Blood sample s were collected at the start of the study and each 12-week period . In addition , the relationship between patient characteristics , inflammation and leptin was analysed . RESULTS At baseline , all groups showed similar leptin concentrations ( mean 33.6+/-21.7 ng/ml ) . After a single HD session , a significant ( P<0.01 ) decrease was observed with all three high permeable devices ( Tricea 150 G -52.7+/-6.4 % ; F 60S -63.1+/-5.7 % ; F 500S -68.7+/-8.2 % ) , whereas leptin remained stable with low-flux PS . After 12 weeks , a marked increase was observed with low-flux PS ( week 1 , 30.4+/-23.0 ; week 12 , 40.5+/-5.4 ng/ml , P = 0.05 ) , no change with super-flux CTA and high-flux PS ( Tricea 150 G week 1 , 29.4+/-23.7 ; week 12 , 32.0+/-27.9 ng/ml , P = ns ; F 60S week 1 , 36.0+/-31.8 ; week 12 , 33.0+/-31.2 ng/ml , P = ns ) , and a significant decrease with super-flux PS ( week 1 , 38.3+/-33.0 ; week 12 , 29.5+/-31.9 ng/ml , P = 0.02 ) . The change in leptin after 12 weeks was significantly different between super-flux PS , and both low-flux PS ( P = 0.009 ) and super-flux CTA ( P = 0.01 ) . Besides interleukin-6 ( IL-6 ) at the start of the study ( P = 0.006 ) , no correlations were observed between patient characteristics , parameters of inflammation and plasma leptin levels . CONCLUSIONS Apart from low-flux PS , plasma leptin decreased considerably with all three high permeable dialysers after a single HD session . In the long run , leptin levels were lower with high-flux PS than with low-flux PS . Moreover , after switching from high-flux PS to super-flux PS ( but not super-flux CTA ) , an additional decrease in leptin was observed . Apart from IL-6 at the start of the study , neither patient characteristics nor inflammatory parameters correlated with plasma leptin levels in this patient group Introduction Physical properties of filters for continous renal replacement therapy have a great impact on biocompatibility . According to Poiseuille 's law , a filter with more and shorter hollow fibers should offer a decreased pressure drop and , therefore , lower transmembrane pressure ( TMP ) . The aim of this study was to study the effect of a new filter configuration in terms of TMP and clotting compared with the st and ard configuration . Methods In a prospect i ve r and omized cross-over study 2 polysulphone hollow fiber hemofilters , one h and made , which differed only in length and number of hollow fibers were compared . In each group 12 filters were investigated during continous venovenous hemofiltration in patients with acute renal failure due to septic shock . Pressures were measured every 3 hours and running time until filter clotting was documented . Mediators before and after the filter , at the end of treatment and in filtrate were assessed . Results The st and ard filter with longer hollow fibers had significantly lower TMPs ( 106 vs.194 mmHg , p=0.02 ) and longer running times ( 1276 vs. 851 min , p=0,04 ) . There were no differences in hematocrit , total protein , cellular and plasmatic coagulation or blood temperature . No significant elimination of mediators was shown . Conclusion In contrast to our expectations , the filter with the longer hollow fibers had a better performance , as it ran longer and had lower TMP . This may be due to slower blood flow leading to an increase in blood viscosity in a filter with a larger cross section Hypoalbuminemia in end-stage renal disease is a marker of high morbidity and mortality . In some patients , the cause of low serum albumin levels is easily identified and therefore treatable , but in many patients , the cause is not clear . We studied the effect of changing the dialysis membrane from a bioincompatible to a biocompatible membrane on serum albumin level . Stable hemodialysis patients dialyzed with cuprammonium membranes who had serum albumin levels less than 3.5 g/dL were switched to the more biocompatible membrane , polysulfone . Serum albumin levels increased from 3.22 + /- 0.037 to 3.35 + /- 0.038 g/dL ( mean + /- SE ; P < 0.002 ) . The increase was seen in patients both with and without diabetes . Thus , dialyzer membrane may affect serum albumin levels and should be considered in the differential diagnosis of hypoalbuminemia in patients undergoing hemodialysis with bioincompatible membranes . Membrane choice may have an important effect on the outcome of morbidity and mortality of hemodialysis patients Objectives Residual renal function ( RRF ) is of paramount importance to dialysis adequacy , morbidity , and mortality , particularly for long-term continuous ambulatory peritoneal dialysis ( CAPD ) patients . Residual renal function seems to be better preserved in patients on CAPD than in hemodialysis ( HD ) patients . We analyzed RRF in 45 patients with end-stage renal disease ( ESRD ) , commencing either CAPD or HD , to prospect ively define the time course of the decline in RRF , and to evaluate dialysis-technique – related factors such as cardiovascular stability and bioincompatibility . Study Design Single-center prospect i ve investigation in parallel design with matched pairs . Material s Fifteen patients starting CAPD and 15 matched pairs of patients commencing HD were matched according to cause of renal failure and RRF . Hemodialysis patients were assigned to two dialyzer membranes differing markedly in their potential to activate complement and cells ( bioincompatibility ) . Fifteen patients were treated exclusively with the cuprophane membrane ( bioincompatible ) and the other 15 patients received HD with the high-flux polysulfone membrane ( biocompatible ) . Measurements Residual renal function was determined at initiation of dialytic therapy and after 6 , 12 , and 24 months . Dry weight ( by chest x ray and diameter of the vena cava ) was closely recorded throughout the study , and the number of hypotensive episodes counted . Results Residual renal function declined in both CAPD and HD patients , although this decline was faster in HD patients ( 2.8 mL/minute after 6 months and 3.7 mL/min after 12 months ) than in CAPD patients ( 0.6 mL/min and 1.4 mL/ min after 6 and 12 months respectively ) . It declined faster in patients with bioincompatible than with biocompatible HD membranes ( 3.6 mL/min vs 1.9 mL/min after 6 months ) . Eleven percent of the HD sessions were complicated by clinical ly relevant blood pressure reductions , but there were no differences between the two dialyzer membrane groups . None of the CAPD patients had documented hypotensive episodes . None of the study patients suffered severe illness or received nephrotoxic antibiotics or radiocontrast media . Conclusions The better preservation of RRF in stable CAPD patients corresponded with greater cardiovascular stability compared to HD patients , independently of the membrane used . Furthermore , there was a significantly higher preservation of RRF in HD patients on polysulfone versus cuprophane membranes , indicating an additional effect of biocompatibility , such as less generation of nephrotoxic substances by the membrane . Thus , starting ESRD patients on HD prior to elective CAPD should be avoided for better preservation of RRF The solute removal characteristics and haemocompatibility of low-flux dialysers containing Cuprophan , cellulose acetate , polymethylmethacrylate ( PMMA ) , and polycarbonate-polyether ( Gambrane ) membranes were compared in a multicentre cross-over clinical trial . While all four dialysers provided comparable removal of urea and creatinine , the dialyser containing PMMA membrane showed a reduced ability to remove phosphate compared to that containing Cuprophan membrane . Significant beta 2-microglobulin removal was obtained with the dialyser containing Gambrane membrane , whereas the other three dialysers had no impact on plasma beta 2-microglobulin concentrations . The ability to activate complement , measured as changes in the plasma concentrations of C3a des Arg and the terminal complement complex , and to produce leukopenia was greater for the dialyser containing Cuprophan membrane than for the other three . The ability to activate complement and cause leukopenia was not consistent among the remaining three dialysers and the degree of leukopenia could not be predicted from the level of complement activation . Neutrophil degranulation , as indicated by the release of elastase-alpha 1-proteinase inhibitor , occurred to a greater extent with the dialysers containing Cuprophan and Gambrane membranes . None of the dialysers was overtly thrombogenic as judged by changes in platelet count and plasma concentrations of the thrombin-antithrombin III complex . Our results demonstrate that although there are many similarities between dialysers containing low-flux membranes , there are also significant differences . These differences may enable improvements in therapy , while allowing continued use of low-flux dialysers Several studies have shown that patients who have been dialyzed with high-flux biocompatible membranes have a lower plasma level of beta 2-microglobulin and a lower incidence of amyloid disease compared with patients who have been dialyzed with low-flux bioincompatible membranes . However , because high-flux membranes are associated with significant dialytic removal of beta 2-microglobulin , the specific role of membrane biocompatibility in influencing the rate of increase of beta 2-microglobulin has not been previously determined . This study investigated the effect of biocompatibility on the rate of increase of plasma levels of beta 2-microglobulin in 159 new hemodialysis patients from 13 dialysis centers ( ten centers affiliated with Dallas Nephrology Associates and three with V and erbilt University Medical Center ) by using two low-flux membranes with widely different biocompatibilities . These patients were prospect ively r and omized to be dialyzed with either a low-flux biocompatible membrane or a low-flux bioincompatible membrane . Plasma beta 2-microglobulin levels were measured at 0 , 3 , 6 , 9 , 12 , and 18 months . Sixty-six patients completed the 18-month study . Plasma beta 2-microglobulin increased in all patients ; however , the increase was not significantly different from baseline at any time point in the group that used the biocompatible membrane . In this group , beta 2-microglobulin increased from ( mean + /- SD ) 27.8 + /- 14.8 mg/L to 34.0 + /- 10.0 mg/L at 18 months ( P = not significant ) , and the mean increase at 18 months was 2.6 + /- 14.7 mg/L. In contrast , the increase in plasma beta 2-microglobulin level in the bioincompatible membrane group became significant in Month 6 when the levels had increased from a baseline of 24.8 + /- 9.6 mg/L to 29.5 + /- 12.2 mg/L ( P < 0.001 ) ; these increases continued to be significant until Month 18 , when serum beta 2-microglobulin reached 36.8 + /- 13.9 mg/L with an average increase of 11.8 + /- 11.2 mg/L ( P < 0.0001 ) . The higher rate of plasma B2-microglobulin increase in the group that had been dialyzed with the bioincompatible membrane was also evident when only patients who had completed the study were analyzed . There were no significant differences in the actual level of beta 2-microglobulin or in residual renal function between the two groups during the 18 months of the study . It was concluded that over a period of 18 months , the use of biocompatible membranes , even in the low-flux configuration , is associated with a significantly slower increase in plasma beta 2-microglobulin , independent of the influence of residual renal function BACKGROUND Uraemic bone disease is the result of a number of factors modulating bone formation and resorption in a complex manner . In the present study , the hypothesis tested was that the type of haemodialysis membrane used for renal replacement therapy might also play a role . METHODS We conducted a prospect i ve , open study in 24 chronic haemodialysis patients who were r and omized to dialysis treatment with either cellulosic ( CELL group , n=11 ) or polyacrylonitrile ( AN-69 group , n=13 ) membrane for 9 months . Repeated determinations of plasma parameters reflecting bone turnover were done in all patients , and a bone biopsy in a subgroup at the start and end of study . RESULTS At the start , mean plasma intact parathyroid hormone levels were comparable between the two groups and they did not vary significantly at 9 months of treatment . Similarly , plasma bone-specific alkaline phosphatase and osteocalcin ( markers of bone formation ) , and cross-laps ( marker of bone resorption ) remained unchanged . However , plasma insulin-like growth factor-I ( IGF-I ) progressively decreased from 169 to 119 ng/ml in AN-69 group ( P<0.01 ) , whereas it remained unchanged in CELL group . In addition , the levels of IGF binding protein (IGFBP)-1 and IGFBP-2 were increased while the levels of IGFBP-5 were decreased in AN-69 group . In the five patients of each group who had repeat bone biopsies , histomorphometric analysis showed a decrease in osteoblast surface , osteoclast surface and osteoclast number in AN-69 group at 9 months , compared with baseline values measured at the start of the study . In contrast , all three parameters significantly increased in the CELL group at 9 months ( P<0.001 for the difference between each of the three parameters ) . Bone formation rate decreased by 31 % in the AN-69 group , but increased by 50 % in CELL group . However , this latter difference was not statistically significant . Plasma interleukin (IL)-6 and soluble IL-6 receptor levels did not change in the two groups of patients who had undergone bone biopsy . CONCLUSION Dialysis with CELL membrane was associated with increased bone turnover whereas the use of AN-69 membrane was associated with decreased bone turnover , suggesting a beneficial effect of the latter on high-turnover uraemic bone disease . However , as the number of patients with repeat bone biopsies was small , these findings need to be confirmed in a larger study . Further studies are also needed to evaluate whether or not the changes in IGF system components play a role in decreased bone cell activity in patients on dialysis using the AN-69 polyacrylonitrile membrane BACKGROUND In chronic haemodialysis ( HD ) , morbidity may result from repetitive induction of the acute phase response , caused by a bioincompatible dialysis membrane and /or contaminated dialysate . In the present study , cytokine release ( interleukin-6 , IL-6 ) and subsequent production of acute phase proteins ( C-reactive protein , CRP and secretory phospholipase A(2 ) , sPLA(2 ) ) were assessed to investigate whether the HD-induced acute phase reaction depends mainly on the type of membrane or on the sterility of the dialysate . METHODS In 11 patients , IL-6 , CRP and sPLA(2 ) levels were assessed in blood sample s drawn before ( t(0 ) ) , at the end ( t(180 ) ) and 24 h after the start of HD ( t(1440 ) ) . All patients were dialysed on Cuprammonium ( CU ) and Polysulphon ( PS ) dialysers and seven patients underwent an additional HD session on CU plus a dialysate filter ( CUf ) . RESULTS IL-6 levels were increased significantly at t(180 ) compared with t(0 ) ( P<0.02 ) with both CU and CUf . At t(1440 ) , IL-6 levels had returned to baseline . In contrast , marked fluctuations did not occur during HD with PS . At t(180 ) , IL-6 was significantly greater with CU and CUf devices , than with PS ( P<0.02 ) . Following HD with CU and CUf , a significant increase in CRP was observed at t(1440 ) , compared with postdialysis values ( P</=0.05 ) . In addition , sPLA(2 ) values were markedly increased at t(1440 ) , compared with t(180 ) , but only significant in the case of CU ( P=0.01 ) . IL-6 levels at t(180 ) were significantly correlated with CRP ( r=0.50 , P<0.01 ) and sPLA(2 ) ( r=0.47 , P=0.01 ) values at t(1440 ) . During HD with PS membranes , neither CRP nor sPLA(2 ) values were markedly changed . CONCLUSIONS In contrast to PS , both CU and CUf result ed in elevated IL-6 plasma levels at the end of HD , compared with t(0 ) , which correlated with increased CRP and sPLA(2 ) values 24 h later . Therefore , the type of membrane , rather than the bacterial quality of the dialysate , seems to be responsible for the induction of the acute phase response during clinical bicarbonate HD High-flux hemodialysis has been reported to attenuate renal dyslipidemia . To evaluate the contribution of dialysis membrane composition per se , we compared the impact on the lipoprotein profile of hemodialysis ( HD ) with a conventional cellulose dialysis membrane with that of a synthetic high-flux dialysis membrane in st and ard hemodialysis mode . Forty-two patients ( 24 men , 18 women ; mean age , 69 years ; range , 39–85 years ) on maintenance HD with cellulosic dialysis membranes were r and omized and stratified for diabetes mellitus to 12 weeks of HD treatment with either a cellulose acetate ( CA ; n = 23 ) or polyacrylonitrile ( AN69 ; n = 19 ) membrane . HD was performed in a conventional low-flux st and ard HD mode 4–6 hours/session . Plasma levels of lipids ( TC , TG ) , apolipoproteins ( A-I , B , C-III , E ) , lipoprotein ( a ) ( lp(a ) ) , and individual apoA and apoB containing lipoproteins ( LP-A-I , LP-A-I : A-II , LP-B , LP-Bc ) were determined . At baseline , the AN69 group had slightly higher plasma concentrations of apoC-III and C-III/HS , but there were no other differences at entry in study variables between the treatment groups . Twelve week treatment with an AN69 membrane did not result in any significant changes in lipoprotein profile compared with treatment with a cellulose acetate membrane . HD with AN69 dialysis membranes in the conventional low-flux st and ard hemodialysis mode does not affect the lipoprotein This study explored the breathing patterns and arterial blood gases before and during cuprophane ( CU ) bicarbonate and polysulfone ( PS ) bicarbonate dialysis in six chronic dialysis patients with mild chronic obstructive pulmonary disease ( COPD ) . The studies were performed in r and om order during two consecutive dialyses . Breathing patterns were monitored by respiratory impedance plethysmography . Apneic episodes , defined as a decrease in tidal volume of 75 % lasting 10 sec , were present before and during hemodialysis . In these patients with COPD a high number of apneic episodes ( 17 ± 6 [ SE ] ) were observed during CU bicarbonate hemodialysis . Most of these episodes were central rather than obstructive in character . There were fewer events when the same patients were dialyzed with PS membranes ( 10 ± 5 ; p = 0.05 ) . The decrement in PO2 ( baseline to 60 min ) was 17 ± 7 during CU and 4 ± 5 mmHg during PS dialysis ( p = 0.10 ) . Minute ventilation decreased in four of six patients on CU bicarbonate and increased in all six patients on PS bicarbonate . It was concluded that bicarbonate hemodialysis does not completely prevent hypoxemia or apnea during dialysis in patients with COPD . Apneic episodes and hypoxemia appear to be less severe during PS bicarbonate than during CU bicarbonate hemodialysis Tumor necrosis factor-alpha ( TNF-alpha ) has been shown to have somnogenic properties . Plasma levels of this cytokine have been found to increase significantly during dialysis with a bioincompatible ( cuprophane ) membrane in patients with postdialysis fatigue ( PDF ) . We conducted a crossover study with r and om assignment to ascertain whether a biocompatible membrane might attenuate the increase of TNF-alpha and severity of PDF . Sixteen patients on maintenance hemodialysis underwent dialysis with either cuprophane ( n = 8) or polymethylmethacrylate ( PMMA ; n = 8) membranes for 1 week and then switched to the opposite membrane during the second week . Predialysis and postdialysis measurements of plasma TNF-alpha levels were performed during the first and last dialysis treatments of each week . A fatigue score was determined from the sum of duration of fatigue and sleep within 6 hours of the completion of dialysis . TNF-alpha levels increased by an average of 18.3 % during dialysis with cuprophane membranes but only 2.4 % with PMMA membranes ( P = 0.04 ) . Despite this , fatigue scores remained unaltered ( approximately 4 of 6 ) . Hence , the biocompatible membrane , PMMA , failed to alleviate PDF . This suggests that dialytic stimulation of TNF-alpha plays no substantial role in the pathogenesis of PDF Hemodialysis is frequently complicated by hypotension and associated symptoms . It has been suggested that these symptoms may be related to the biochemical changes caused by cellulosic dialysis membranes . In this study , a prospect i ve r and omized crossover trial was conducted comparing the incidence of hypotension and acute symptoms during dialysis with large-surface-area ( 1.6 m2 ) cellulosic ( cuprophane [ CUP ] ) and noncellulosic ( polyacrylonitrile [ PAN ] , AN69 ) membranes . Dialyzers were used for a single use only . There was no difference in predialysis BUN , predialysis blood pressure , intradialytic weight gain , blood flow , dialysis efficiency ( urea reduction ) , dialysis duration , hematocrit , or erythropoietin dose between the two study phases . When these clinical characteristics were matched , there was no difference in the number of episodes of hypotension ( CUP , 19 + /- 3 ; PAN , 22 + /- 3 ; P = not significant [ NS ] ) . The incidence of symptomatic hypotension , as reflected by the number of episodes of hypotension requiring more than 100 mL of saline for correction , was also not different between study phases ( CUP , 10 + /- 1 ; AN69 , 11 + /- 2 ; P = NS ) . The incidence of intradialytic symptoms , including emesis , cramping , headache , angina , pruritus , and bronchospasm , was similar during the two study phases ( CUP , 11 + /- 2 ; AN69 , 10 + /- 1 ; P = NS ) . It was concluded that noncellulosic membranes do not offer any significant advantage over cellulosic membranes in reducing the acute complications of hemodialysis A prospect i ve r and omised clinical study comparing the functional performance and biocompatibility of a new cellulose diacetate variant ( Dicea ) in which the degree of hydroxyl group substitution differs , with cellulose diacetate and low flux polysulfone incorporated into commercially produced hollow fiber hemodialysers with a surface area 1.5 - 1.6 m2 has been undertaken . All dialysers studied demonstrated clinical ly acceptable performance in terms of their small molecular removal characteristics , with minor statistical but not clinical differences . Use of both cellulose diacetate membranes but not low flux polysulfone result ed in a reduction in plasma beta(2 ) microglobulin levels . The membranes were impermeable to albumin , but showed some permeability to low molecular weight proteins . The average protein recovery from the dialysis fluid was 3105 mg for Dicea , 2913 mg for cellulose diacetate and 2842 mg for low flux polysulfone . For Dicea the white cell count by 15 minutes had declined to 68 % of pre treatment value , compared with 59 % and 86 % for cellulose diacetate and low flux polysulfone . The differences between Dicea and cellulose diacetate were not significant , but both cellulose based membranes differed from low flux polysulfone ( p = 0.0015 ) . There was a strong evidence of differences between the membranes in respect of C5a and C5b-9 generation ( p = 0.0001 ) but not for C3a ( p = 0.16 ) furthermore the levels of C5b-9 generated during dialysis also showed a significant positive correlation compared to C5a for all membranes . ( Pearson 's correlation coefficient = 0.856 , p = 0.0001 ) . It is concluded that the two cellulose diacetate membranes are not identical , with the differences observed being a consequence of the degree of acetyl substitution , result ing in alteration of membrane structure and the method of sterilization . The clinical significance of these differences are difficult to characterize but the modification of the cellulose structure appears to be a promising method to improve the biocompatibility of cellulose membranes . The improved biocompatibility offered by this method still falls short of that achieved with low flux synthetic membranes such as Fresenius Polysulfone During dialysis with cuprophane or polycarbonate filters , a fall in neutrophil and eosinophil cell counts is observed . Total complement remains unchanged , but C3a increases indicating complement activation . Release of granular granulocyte proteins is observed indicating granulocyte activation . Patient reactions or biochemical findings indicate no significant difference when polycarbonate or cuprophane membranes are used , except perhaps less complement activation with polycarbonate . The biochemical observations may be due to complement activation or cell contact with the membrane BACKGROUND Polymorphonuclear leukocyte ( PMNL ) production of reactive oxygen species ( ROS ) has been linked to hemodialysis ( HD ) associated morbidity . The effect of dialyzer membrane type and reuse on PMNL function has not been clearly defined . METHODS The present report is a cross-sectional study undertaken in a cohort of patients undergoing regular HD , at enrollment into the Hemodialysis ( HEMO ) Study , to study the association between patient and dialysis-related factors and PMNL function . PMNL function was assessed by measuring PMA- and N-formyl methionyl-leucyl-phenylalanine ( fMLP ) -induced respiratory burst , and phagocytic activity toward Staphylococcus aureus . RESULTS PMNL from patients dialyzed with polysulphone ( PS ) or cuprophane ( CU ) membranes showed higher PMA-induced respiratory burst activity compared with those exposed to substituted cellulose ( cellulose acetate , cellulose triacetate , CA/CT ) membranes , regardless of dialyzer reuse . The use of bleach as a cleansing agent during reuse was associated with higher PMA-induced PMNL superoxide production , as was the use of renalin when compared to aldehydes . In a subgroup of patients using PS dialyzers , reuse itself was associated with higher fMLP-induced superoxide production . The type of bleach-germicide combination during reuse showed that use of renalin as a germicide was also associated with higher PMNL phagocytosis index . The number of years on HD correlated inversely with PMA-induced PMNL superoxide response . Weaker PMNL response to fMLP was associated with greater comorbidity and poor functional status as quantified by Index of Coexisting Diseases ( ICED ) and Karnofsky scores , respectively . CONCLUSION Our results indicate that dialyzer membrane type and the reuse process influence the oxidative response of PMNL among HD patients . The implication s of these observations on clinical morbidity need to be further evaluated in prospect i ve studies BACKGROUND Activation of polymorphonuclear neutrophils ( PMNs ) and monocytes has been described during hemodialysis ( HD ) , which results in the release of reactive oxygen species and cytokines . Acetate-free biofiltration ( AFB ) has been shown to cause less monocyte activation and cytokine release than bicarbonate HD ( BHD ) . No data are available to date on the effect of AFB on PMN activation . METHODS We studied ex vivo superoxide anion release by PMNs isolated from nine patients treated in r and om order with AFB or BHD ( three sessions each ) . Plasma interleukin-1beta ( IL-1beta ) levels and the nitric oxide ( NO ) synthetic pathway also were evaluated . A polyacrylonitrile ( AN69 ; Hospal , Bologna , Italy ) dialyzer was used for both treatments . Fourteen healthy volunteers were used as controls . Blood sample s were drawn predialysis and 5 and 15 minutes after starting dialysis to obtain plasma and PMNs . RESULTS Neither ex vivo superoxide anion release nor blood PMN count was affected by AFB . Conversely , a peak in superoxide anion production associated with a decrease in PMN count was observed at 5 minutes during BHD . Results of superoxide anion production by control PMNs exposed in vitro to AFB or bicarbonate dialysis bath or Hank 's balanced salt solution supplemented with bicarbonate or acetate indicated that BHD-induced PMN activation could be attributed to the amount of bicarbonate present in the dialysis bath . IL-1beta plasma levels did not change during dialysis with AFB and were numerically higher at 5 and 15 minutes with respect to predialysis values during BHD . Uremic plasma obtained during either AFB or BHD induced greater NO synthesis by human umbilical vein endothelial cells than control plasma . CONCLUSION AFB , unlike BHD , does not cause PMN and monocyte activation , which could have a positive impact on dialysis-associated cardiovascular disease of dialyzed patients Summary Leukotriene B4 ( LTB4 ) plays an important role in acute and chronic inflammatory and hypersensitive reactions . We studied the time course of LTB4 bio synthesis in whole blood in 18 patients with end-stage renal failure maintained on regular hemodialysis with two different membranes , cuprophane and polyacrylonitrile ( AN 69 ) . The basal levels of LTB4 from dialysis patients did not differ significantly from a normal control group . Compared to predialytic values , the cuprophane membrane caused a maximal release of LTB4 by a factor of about 4.5 ( p<0.01 ) within the first 10 to 20 minutes . Thereafter the level fell and returned to baseline range at the end of the hemodialysis session . With the use of the AN 69 membrane no significant increase of LTB4 could be demonstrated . The changes in LTB4 concentration showed a close temporal correlation to the alterations in white blood cell count . We conclude that ( 1 ) LTB4 is a biologically important mediator of neutrophil activation during hemodialysis , and ( 2 ) LTB4 may be a sensitive marker of biocompatibility in vivo We conducted a multicenter , r and omized , double-blind , controlled clinical trial to compare the effects of a synthetic , high-flux polysulfone membrane with a st and ard cuprophan one on acute clinical complications during a diffusive dialysis procedure . The principal end-point , that is , the number of hypotensive episodes , was similar in polysulfone ( 39 ; 23.8 % ) and cuprophan ( 32 ; 19.5 % ) . Likewise , no significant difference was found between the two membranes as far as the secondary end-point was concerned , that is , the effect on headache , nausea , pruritus and sense of well-being . We conclude that high-flux polysulfone , acutely used in st and ard diffusive dialysis , has no favorable influence on hypotensive episodes and does not affect some typical dialysis-related symptoms any differently from cuprophan membrane . The need is stressed for well-controlled studies specifically design ed to assess the worth of new dialysis techniques and material s that may vastly raise the cost of dialysis treatment Hemodialysis deteriorates oxidative stress . Vitamin E is an antioxidant whose regeneration is provided for by vitamin C. The authors tested the effects of a vitamin E-modified membrane ( E ) , nonmodified cellulose membrane ( O ) , and vitamin C infusion ( 500 mg , C ) into the arterial blood line during dialysis on parameters of oxidative stress . In a short-term study , 24 patients were subjected to a single dialysis session with E , O , E with C , and O with C protocol s. In a long-term study ( 12 weeks ) , 20 patients were r and omized into groups with C and without C on each dialysis , and both groups had dialysis using O , E , and again O membrane for 4 weeks each . In the short-term study , thiobarbituric acid reacting substances ( TBARS ) in plasma rose after dialysis ( p < 0.02 ) with O , and no changes were observed in the other 3 protocol s. In the long-term study , predialysis TBARS declined when using E both in the groups with C ( p < 0.02 ) and without C ( p < 0.05 ) . A switch over to O result ed in TBARS returning to baseline levels . The E membrane prevented an increase in lipid peroxidation during single dialysis , and long-term use of the E membrane also result ed in a decrease in the predialysis lipid peroxidation level . The antioxidant capacity of the E membrane was not enhanced by vitamin C infusion . High doses of vitamin C administered during dialysis using a nonmodified cellulose membrane prevented an increase in lipid peroxidation , most probably due to the enhanced rate of endogenous vitamin E regeneration BACKGROUND Vitamin E-bonded hemodialyzer is known to improve oxidative stress in patients with hemodialysis . However , there is little information available as to whether or not this membrane clinical ly improves atherosclerosis . Furthermore , it remains unknown whether there is any effect of the membrane on rheology of circulating red blood cells . METHOD We conducted a r and omized , open-labeled , prospect i ve control study ( N = 34 ) for 1 year to investigate the effect of vitamin E-bonded cellulose membrane dialyzer ( EE ) ( N = 17 ) on carotid atherosclerotic changes [ intima-media thickness ( IMT ) of carotid arteries ] and the viscosity , percentage of dysmorphism ( % DMR ) of red blood cells ( RBCs ) and their distribution width-st and ard deviation ( RDW-SD ) , in comparison with cellulose membrane ( SU ) ( N = 17 ) identical to EE without vitamin E-bonded membrane . Erythropoietin ( EPO ) dose used for the treatment of uremic anemia was also calculated . RESULTS The IMT significantly decreased in the EE group , while in the SU group the IMT significantly increased . The viscosity of RBCs in hemodialysis patients ( 4.70 + /- 0.45 cP ) was greater than that in healthy individuals ( 3.73 + /- 0.15 cP ) . EE significantly improved the viscosity ( from 4.84 + /- 0.41 cP to 4.51 + /- 0.54 cP , P < 0.01 ) , % DMR ( from 2.29 + /- 2.17 % to 1.90 + /- 1.49 % , P < 0.01 ) , and RDW-SD ( from 54.4 + /- 7.6 fL to 49.3 + /- 5.9 fL , P < 0.01 ) . On the contrary , these parameters all worsened in the SU group . EPO dose needed for the treatment of anemia was significantly ( P < 0.05 ) reduced from 5383 + /- 2655 U/week to 4235 + /- 3103 U/week in the EE group . During these period , mean blood pressure , Kt/V urea , and serum beta2-microglobulin were not changed between the two groups . CONCLUSION These findings suggest that vitamin E-bonded hemodialyzer is very useful for improving atherosclerosis from a clinical point of view . As one of the underlying mechanisms , as well as antioxidant effects , we want to address an important role of the improvement of rheology of circulating RBCs , which may also help to reduce the requirement of EPO dose in the treatment of anemia of ESRD patients We investigated expression of several antigens on neutrophils and monocytes , involved in cell adhesion , from patients hemodialyzed with cellulosic and polyacrylonitrile membranes . Among the antigens tested only the expression of CD15s and CD11b was significantly increased on neutrophils and monocytes in patients dialyzed with cellulosic membranes . No changes occurred with polyacrylonitrile membranes . Leukocyte counts from patients dialyzed with cuprophane membranes decreased at the same time as expression of cellular CD15s increased , result ing in a significant negative correlation at all time points tested . No correlation was found between the drop of monocytes and their expression of CD11b . When CD15s expression increased on neutrophils and monocytes , we observed a concomitant increase of CD62P , a specific selectin of activated platelets . When whole blood cells were incubated with complement activated serum both antigens increased but not when cells were incubated with hrC5a . We also observed that CD61 , a platelet phenotypic antigen , was present on leukocytes incubated with complement activated serum . At the time when platelet-leukocyte coaggregates decreased , CD62P expression remained stable on leukocytes , suggesting that both neutrophils and monocytes are able to trap either CD62P shed by activated platelets or soluble CD62P present in normal human serum . The present study documents a major role of P-selectin (CD62P)/sialyl-Lewis x ( CD15s ) interaction in the transient leukocyte margination during hemodialysis It has been recently proposed that haemodialysis membrane choice may influence the maintenance of residual renal function . The aim of the present study was to prospect ively analyse the effect of membrane choice on the outcome of renal function in patients entering a chronic haemodialysis programme . Twenty-two patients from four hospitals have been r and omly assigned to be dialysed with either polysulphone (PSF)/polyacrylonitrile ( PAN ) ( group A ; n = 9 ) , or cuprophane membranes ( group B ; n = 13 ) . Basal and monthly serum biochemistry , residual creatinine clearance ( Ccr ) and urine volume ( Vu ) , pharmacological and dialytic treatment , diet , and haemodialysis-related complications were recorded . A significant decrease was observed in the two most relevant variables , i.e. remnant Ccr and Vu , within 3 months of starting haemodialysis , with stabilization during the further follow-up . Such decrease was similar ( P NS ) for both groups A and B throughout the 9-month observation period . In conclusion , our results suggest that the choice of haemodialysis membrane does not influence the outcome of the residual renal function . Renal function decreased significantly within 3 months on haemodialysis , independently of the type of dialyser membrane BACKGROUND In chronic hemodialysis ( HD ) patients , the repetitive induction of the acute phase response ( APR ) may induce a chronic micro-inflammatory state , leading to various long-term complications . METHODS The present prospect i ve study was design ed to assess the alterations in the APR in 74 patients who were r and omized to HD with a high-flux polysulfone ( PS ; F 60S ) , a super-flux PS ( F 500S ) , or a super-flux cellulosic tri-acetate ( CTA and CTA with filtered dialysate , CTA(f ) ) dialyzer . Blood sample s collected at the start of the study and after twelve weeks were analyzed for interleukin-6 ( IL-6 ) and C-reactive protein ( CRP ) . In addition to the microbiological quality of the dialysate , the appearance of a " clinical event " was assessed . RESULTS At baseline , mean IL-6 levels were within the reference range whereas mean CRP levels were slightly elevated . Mean values did not change after 12 weeks of HD with either modality . After subdividing the patients in quartiles with increasing change in plasma CRP , 23.0 % of the patients showed a change of more than 8.0 mg/L. In a multiple regression analysis , CRP levels appeared to be independent of the degree of dialysate contamination , the material and the flux characteristics of the devices . In fact , the variable " clinical events " was the only significant predictor of the plasma CRP levels ( P < 0.001 ) . CONCLUSIONS Based on these results , both PS and CTA super-flux dialyzers appear safe for clinical use . Whether changes in CRP values , which are associated with intercurrent clinical events , influence the long-term prognosis of chronic HD patients remains to be established Membranes used for dialysis therapy activate complement . Complement activation is maximal after initiating dialysis and returns to predialysis values by the end of dialysis . No changes in C3 levels have been detected after dialysis . We hypothesized that although C3 levels were unchanged , C3 activity could be altered by dialysis . We measured complement activation in vitro in serum from patients r and omized to dialysis treatments using different types of membranes . The classical pathway was activated with aggregated immunoglobulin G ( IgG ) , and the alternative pathway was activated with inulin . Both the classical and alternative pathways were suppressed after dialysis using cellulose membranes ( aggregate IgG , P < 0.01 ; inulin , P < 0.001 ) . When polyacrylonitrile ( PAN ) or polyethylene glycol grafted cellulose membranes were used for dialysis , only minor suppression of complement pathways was measured . Levels of the control factor SP-40,40 increased at later times for dialysis using cellulose membranes ( P < 0.05 ) . Factor H levels were also greater after dialysis using cellulose membranes compared with PAN membranes ( P < 0.05 ) . In summary , cellulose membranes suppress complement activation in serum . One suppressing factor may be the complement control factor SP-40,40 Peroxidation of cell membrane ( phosphatidylcholine hydroperoxide , PCOOH ) was quantitatively assessed using a chemiluminescence-HPLC system to clarify whether haemodialysis patients are damaged by oxidative stress . Patients were divided into two groups , one dialysed with conventional cellulose membranes , and the other with cellulose triacetate for 3 months , subsequently followed by a crossover study of each membrane for 3 more months . The mean value of PCOOH in haemodialysis patients was 508.5 + /- 208.7 pmol/ml ( P < 0.01 vs normal controls ) , which showed a statistically insignificant tendency to increase during each haemodialysis session of 4 h. Two years after commencing haemodialysis , PCOOH was maintained within almost the same range , but significantly greater than normal . There was no significant tendency between an index of aortic sclerosis and plasma PCOOH . However , three patients using conventional cellulose membranes died of myocardial infa rct ion . Plasma PCOOH increased after the commencement of haemodialysis . This tendency was more notable in patients using conventional cellulose membrane compared to the cellulose triacetate . Cellulose triacetate , which we thought to be more biocompatible , did not necessarily produce lipid peroxide . We conclude that it is very important to check production of oxygen radicals when developing new membranes Protein malnutrition , a condition associated with an albumin concentration less than 3.5 g/dL , has been shown to be a major risk factor for increased mortality in hemodialysis patients . The aim of this cross-over study was to evaluate the relationship between the type of membrane adopted and serum albumin changes by measuring peripheral blood mononuclear cells ( P BMC ) interleukin-6 ( IL-6 ) release , serum albumin , and plasma concentrations of C-reactive protein ( CRP ) in 18 patients dialyzed with different membranes . During the study , all patients were dialyzed with cuprophan ( CU ) , synthetically modified cellulosic ( SMC ) membrane ( a new cellulosic membrane with lesser complement activation ) , and cellulose diacetate ( CD ) membrane , and have served as their own controls . IL-6 spontaneous release by P BMC result ed after 3 months of SMC ( 436.2 + /- 47.4 pg/mL ) significantly ( P < 0.05 ) reduced as compared with CU ( 569.3 + /- 24.5 pg/mL ) . This effect was more evident after 6 months of dialysis with SMC ( 220 + /- 35.3 pg/mL , P < 0.01 versus CU and versus 3 months of SMC ) . The passage to CD membrane was followed by a progressive new increase in the IL-6 P BMC release ( 332.3 + /- 30.7 after 3 months , and 351.2 + /- 35.8 pg/mL after 6 months , respectively ) that , however , remained significantly ( P < 0.05 ) lower than CU . The behavior of CRP plasma levels resembled that of IL-6 P BMC release ( 23.3 + /- 4.7 in CU , 11.0 + /- 2.1 after 3 months in SMC , and 7.9 + /- 1.5 after 6 months in SMC , respectively ) . IL-6 release values were positively correlated with circulating levels of CRP ( r = 0.3264 , P < 0.002 ) . Serum albumin increased after 6 months of dialysis with SMC membranes ( 3.25 + /- 0.09 g/dL in CU and 3.64 + /- 0.07 g/dL in SMC , P < 0.05 ) . When the patients were switched to CD , serum albumin showed a slight , though not statistically significant , decrease . Serum albumin concentrations negatively correlated with both IL-6 release values ( r = -0.247 , P < 0.05 ) and CRP plasma levels ( r = -0.433 , P < 0.001 ) . In conclusion , our data clearly show that a significant relationship exists between biocompatibility of the membranes and serum albumin changes ; serum albumin levels , in fact , are negatively correlated with the P BMC spontaneous IL-6 release values and CRP circulating levels We studied the influence of different modes of hemodialysis ( HD ) on plasma levels of beta 2-microglobulin ( P-beta 2-m ) and its correlation to changes in leukocyte count , complement activation ( C3a ) , and elastase generation . The influence of dialyzer membrane , membrane surface area , duration of treatment , and blood flow was analyzed with respect to post-HD levels of P-beta 2-m . Twenty patients underwent 12 modes of bicarbonate hemodialysis in r and om order ( n = 252 ) using three different membranes ( Cuprophan [ CU ] , hemophan [ HE ] , or polyamide [ PA ] , two dialyzer areas , and fast ( 400 mL/min ) or slow ( 200 mL/min ) blood flow ( Qb ) for 2 or 4 hours , respectively . All dialysate was collected and beta 2-m was analyzed ( D-beta 2-m ) . After correction for hemoconcentration , P-beta 2-m concentrations were found to have decreased significantly during treatment with all three membranes ( CU , 0.9 + /- 0.3 mg/L , P = 0.002 ; HE , 1.2 + /- 0.3 mg/L , P < 0.001 ; and PA , 8.3 + /- 0.3 mg/L , P < 0.001 ) . Elimination of P-beta 2-m was influenced by type of membrane ( P < 0.001 ) and ultrafiltration volume ( P = 0.0019 ) but not by membrane area or Qb . The largest reduction in P-beta 2-m ( -10.4 mg/L ) was achieved by the following treatment combination : PA membrane , large dialyzer area , and low Qb for 4 hours . P-beta 2-m decreased more during PA dialysis at low Qb for 4 hours ( -9.9 + /- 0.5 mg/L ) than during high Qb for 2 hours ( -6.8 + /- 0.5 mg/L , P < 0.001 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Twenty-two patients were dialysed in a cross-over design using Hemophan ® or cellulose acetate membranes . The dialysate buffer was acetate ( n = 12 ) or bicarbonate ( n = 10 ) . Blood was sample d at 0 , 15 , 60 and 180 min and mean values were adjusted for changes in total protein in each sample . At 15 min during dialysis a decrease in leukocytes and platelets occurred with both membranes , irrespective of the buffer ( Wilcoxon , p < 0.006 ) . During dialysis , increases were found in granulocyte elastase inhibitor complex ( E-α1-PI ) , β-thromboglobulin and C3d . β2-microgrobulin was not significantly changed in blood after dialysis with Hemophan ® or cellulose acetate membranes with bicarbonate buffer . Side effects were more pronounced at 180 min during dialysis with bicarbonate in patients using cellulose acetate than with Hemophan ® ( p = 0.021 , n = 8) . Hemophan ® seemed to be more favourable than cellulose acetate membranes in regard to leukopenia and E- α1-PI . The dialysate buffer may also alter membrane biocompatibility Little attention has been given to the effects of reuse on the permeability of low-flux membranes , especially regarding middle molecules . We studied two different types of low-flux membranes at reuses 0 , 6 , and 12 in five patients undergoing hemodialysis with the following combinations of membrane and sterilant : cellulose diacetate membrane and formaldehyde , polysulfone membrane and formaldehyde , cellulose diacetate membrane and peracetic acid , and polysulfone and peracetic acid . The permeability of the membranes was assessed through the hydraulic ultrafiltration coefficient ( K(UF ) ) , sieving coefficient for beta(2)-microglobulin ( B2 M ) , and vitamin B(12 ) and albumin concentrations in ultrafiltrate . After 12 reuses , total cell volume ( TCV ) tended to be reduced in both cellulose diacetate and polysulfone dialyzers irrespective of the sterilant used , but significance was only found for the first set of dialyzers . Cellulose diacetate dialyzers reprocessed with either formaldehyde or peracetic acid showed an important reduction in K(UF ) ( 31 % [ P < 0.05 ] and 23 % [ P < 0.05 ] , respectively ) . A significant elevation in K(UF ) was found in polysulfone membranes reprocessed with peracetic acid ( 41 % ; P < 0.05 ) , but no alterations in K(UF ) were found in polysulfone membranes reprocessed with formaldehyde . Cellulose diacetate membranes were intrinsically more permeable to B2 M than polysulfone membranes ( sieving coefficient , 6 . 85 + /- 2.53 versus 0.04 + /- 0.02 x 10(-2 ) ; P < 0.001 ) , which was not modified by any of the sterilants . Vitamin B(12 ) levels in ultrafiltrate decreased to an undetectable level in four of five sample s collected after 12 reuses in polysulfone membranes reprocessed with peracetic acid ( 90 + /- 71 to 3 + /- 8 pg/mL ; P < 0 . 05 versus reuse 0 ) . Albumin leakage occurred in two of five sample s after the 12th reuse , but only in polysulfone membranes reprocessed with peracetic acid . Our findings suggest that reuse of low-flux polysulfone dialyzers reprocessed with peracetic acid is associated with structural damage of the membrane and a reduced permeability to middle molecules BACKGROUND Oxidant stress has a pathogenic role in uremic anemia , possibly interfering with erythropoietin ( EPO ) function and red blood cell ( RBC ) survival . Therefore , it is expected that antioxidant therapy might exert a beneficial effect on these parameters . METHODS To test this hypothesis , we investigated some oxidant stress indices , anemia levels , and RBC survival in 47 hemodialysis ( HD ) patients r and omly assigned to three groups . Patients in groups A ( n = l8 ) and B ( n = 20 ) were on dialysis therapy using conventional cellulosic and synthetic membranes and were administered high and low doses of recombinant human EPO ( rHuEPO ) , respectively . Patients in group C ( n = 9 ) were dialyzed with vitamin E-modified membranes ( CL-Es ) and investigated in a two-step prospect i ve study . In step Cl , patients were administered rHuEPO doses similar to those of group A. In step C2 , rHuEPO doses were reduced to those of group B. As oxidant stress markers , we determined in plasma the susceptibility of lipids to undergo iron-catalyzed oxidation ( reactive oxygen molecules [ ROMs ] test ) and malondialdehyde-4-hydroxynonenal ( MDA-4HNE ) , alpha-tocopherol ( alpha-T ) , total thiol ( -SH ) , and total antioxidant activity . RBC survival was measured using the chromium 51 T/2 technique in 22 patients . RESULTS Results show that : ( 1 ) high rHuEPO doses ( groups A and C1 ) were associated with decreased ROM production , low alpha-T levels , and slightly increased -SH levels compared with corresponding groups on low rHuEPO doses ( groups B and C2 ) ; ( 2 ) treatment with CL-Es ( group C ) increased plasma alpha-T and decreased -SH levels ; these data were associated with decreased indices of lipid peroxidation , particularly MDA-4HNE 1evels , only in patients administered low rHuEPO doses ; ( 3 ) alpha-T concentration influenced RBC survival , which was remarkably decreased in HD patients ; patients treated with CL-Es showed a better degree of anemia correction ; and ( 4 ) alpha-T level correlated negatively with -SH level and seemed to be independent of the extent of peroxidation and oxidizability of plasma lipids . CONCLUSION Both EPO and CL-E can influence plasma antioxidants and , to an extent , lipid peroxidation processes . However , this study shows that even in patients treated with low rHuEPO doses , RBC survival close to normal and sufficient correction of anemia are achieved only when appropriate alpha-T levels are reached BACKGROUND Dialysis-related amyloidosis is an important complication of long-term hemodialysis ( HD ) therapy with several pathogenetic factors . One of them is the influence of the dialyzer membrane type on the synthesis of beta2-microglobulin ( beta2 m ) . In vitro results are controversial . Thus , the hypothesis of whether in vivo beta2 m generation is induced by the HD procedure and whether this induction depends on the type of the used dialyzer membrane should be tested . The aim of the present study was to investigate the influence of " biocompatible " high-flux versus " bioincompatible " low-flux HD on in vivo beta2 m generation as well as the induction of the early activation gene c-fos in peripheral blood cells . METHODS Six nondiabetic HD patients [ mean age 46 ( 21 to 69 ) years ; Kt/V > 1.2 ] were included in a r and omized crossover study using either a low-flux ( cellulosic/cuprophan ) or a high-flux ( polyamide ) dialyzer membrane . At the end of a four-week run-in period for each membrane , whole blood sample s were taken before , immediately at , and four hours after the end of the dialysis session . MRNA was extracted , and after transcription to cDNA , quantitative polymerase chain reaction was performed for the beta2 m gene , the early response gene c-fos , and the GAP-DH housekeeping gene . RESULTS Based on the applied method for detection of specific mRNA , the results were given as ratio of beta2 m or c-fos cDNA per GAP-DH cDNA . General cell activation during HD was indicated by increasing mRNA expression of c-fos related to the time course of the dialysis session , whereas beta2 m did not change significantly . However , no difference was found when comparing the low-flux and the high-flux dialyzer membranes . Despite the evidence for activation of peripheral blood cells , as indicated by increasing c-fos message , no sign of beta2 m mRNA induction during HD procedure with different dialyzer membranes was seen . CONCLUSIONS Our results suggest that there is post-transcriptional regulation of beta2 m generation and /or release as well as the influence of the dialyzer membrane type on post-translational processes , that is , advance glycation end products ( AGE ) or conformational modification of the beta2 m protein . Furthermore , our data demonstrate that gene expression patterns during dialysis and /or uremia are not homogenous and need to be investigated further , especially with respect to the proinflammatory role of early leukocyte activation signals Malnutrition is highly prevalent in chronic hemodialysis patients and is an important determinant of their morbidity and mortality . Several recent studies have suggested that the inflammatory response associated with the biocompatibility of the dialysis membranes is a potential contributing factor . In a prospect i ve study of 159 new hemodialysis patients from two centers r and omized to either a low-flux biocompatible ( BCM ) membrane or a low-flux bioincompatible ( BICM ) membrane , we measured the long-term effects of biocompatibility on several nutritional parameters , including estimated dry weight , serum albumin , insulin-like growth factor-1 ( IGF-1 ) , and prealbumin over 18 months . Our results show that the BCM group had a mean ( + /- SD ) increase in their dry weight of 2.96 + /- 6.88 kg at month 12 and 4.36 + /- 8.57 kg at month 18 ( P < 0.05 vs. baseline for both ) , whereas no change in mean weight was observed in BICM group . Following initiation of hemodialysis , a significant increase was observed in serum albumin levels in both groups of patients . However , the biocompatible group had an earlier and more marked increase in serum albumin levels compared to the BICM group . The average increase in serum albumin compared to baseline was consistently greater than 0.25 g/dl after seven months in the BCM group , but did not reach this level until 12 months after initiation of dialysis in the BICM group . The difference between the groups was statistically significant at months 7 , 8 , and 10 ( P < 0.05 , higher in the BCM group ) . Furthermore , the overall difference in serum albumin concentration between the two groups was larger in the center where the dose of dialysis was equivalent ( P < 0.001 ) . A consistently higher value was also observed in IGF-1 levels for BCM patients compared to BICM group ( P = NS ) . In a further analysis , changes in IGF-1 levels , but not prealbumin , predicted the subsequent changes in serum albumin . We conclude that biocompatible hemodialysis membranes favorably impact on the nutritional status of chronic hemodialysis patients , independently of the flux characteristics of the membranes , and that IGF-1 may be an early marker of nutritional status In vitro studies have shown that some dialysis membranes significantly adsorb erythropoietin ( EPO ) , a fact that might have an effect on anemia in long-term hemodialysis ( HD ) patients and on anemia treatment with recombinant human EPO . The purpose of the study was to determine whether the ability of adsorption demonstrated in vitro also has an effect on EPO concentrations in vivo . In a crossover study , the plasma concentrations of EPO were examined in 11 patients on chronic HD during HD using a polyacrylonitrile ( AN69 ) membrane ( high in vitro adsorption ) plus EPO administered subcutaneously after the HD session , HD using a Cuprophan membrane ( low in vitro adsorption ) plus EPO administered subcutaneously after the HD session , HD using an AN69 membrane plus EPO administered subcutaneously after the HD session plus EPO administered intravenously immediately before HD , or HD using a Cuprophan membrane plus EPO administered subcutaneously after the HD session plus EPO intravenously immediately before HD . The intradialysis plasma concentrations of EPO ( not detectable in the dialysate ) determined at the dialyzer inlet and outlet at Minutes 5 and 240 of the procedure did not differ significantly after its subcutaneous administration from its predialysis concentrations with either the Cuprophan or AN69 membrane . A comparison of EPO concentrations between AN69 and Cuprophan did not reveal marked differences either . The course of concentrations after additional EPO intravenous administration was similar with no statistically demonstrable difference between the 2 membranes . In conclusion , under clinical conditions , AN69 and Cuprophan membranes do not differ in their effects on plasma EPO concentrations . The differences in EPO adsorption between AN69 and Cuprophan , demonstrated in vitro , do not seem to be of clinical importance & NA ; The biocompatibility and performance of two high flux membranes ( modified cellulosic : cellulose‐triacetate ( CTA ) , and a synthetic material : polysulphon [ PS ] ) were assessed in 31 stable patients on hemodialysis ( HD ) in a r and omized crossover study . Parameters evaluated included leukocytes , complement activation products C3a and C5a , cytokines , lymphocyte sub population s , urea , creatinine , phosphate , and beta2 microglobulin . Considering biocompatibility , the drop in the number of leukocytes was more pronounced during CTA HD compared with PS ( p = 0.045 ) , although both were low in comparison with cuprammonium dialysis in the same patients , as observed during a separate study . Both membranes induced a low and transient state of complement activation . Interleukin 1&bgr ; and interleukin 6 could not be detected at all , whereas tumor necrosis factor & agr ; levels were marginally elevated before and after HD with both membranes . During the first 30 min of HD with either membrane , the numbers of CD8 + cells decreased significantly , result ing in an increase in the CD4/CD8 ratios ; in addition , the number of NK cells decreased . Performance , as measured by extraction ratios for small molecular weight solutes and Kt/V urea , was significantly better during CTA dialysis ( p < 0.001 ) , but almost similar after correction for membrane surface area . On the basis of these data , it seems justified to conclude that , whereas biocompatibility of the PS dialyzer appeared slightly superior to CTA , performance of both dialyzers was comparable . ASAIO Journal 1995 ; 41:215‐220 BACKGROUND Membrane biocompatibility has long been thought to be relevant to hemodialysis outcomes and , possibly , renal anemia . METHODS We performed a r and omized , controlled , single-center study comparing the consequences on renal anemia of 2 dialyzers of equivalent performance , but different composition , during 7 months . Two hundred eleven patients of an unselected dialysis population of 235 patients gave informed consent to undergo r and om assignment to either group A ( SF170E ; modified cellulose triacetate/midflux membrane ; Nipro , Osaka , Japan ) or group B ( HF80LS ; polysulfone/high-flux membrane ; Fresenius , Bad Homburg , Germany ) . Anemia management was identical in both treatment groups and followed strict clinical protocol s managed by computer algorithms . Dialysis adequacy , hemoglobin ( Hb ) level , ferritin level , percentage of red blood cell hypochromicity , C-reactive protein ( CRP ) level , and intravenous iron and epoetin doses were monitored monthly . RESULTS One hundred seventy-seven patients completed the 7-month study . Equilibrated Kt/V increased in both groups . Hb outcome improved overall , but did not differ between the 2 study groups . Epoetin dose was not significantly different after 7 months compared with baseline in either group . Hb level , epoetin dose , iron status , CRP level , dialysis Kt/V , and residual renal function did not differ between the 2 groups . A slight but significant negative correlation was identified between dialysis Kt/V and Hb level in the population as a whole ( Spearman 's correlation , -0.16 ; P = 0.04 ) . CONCLUSION No significant epoetin-sparing effect was identified through the use of the high-flux polysulfone HF80LS membrane over the modified cellulose triacetate SF170E membrane . Although not a primary outcome for this study , there was a suggestion of benefit of improved Hb level , without increased need for epoetin , through increasing delivered dialysis dose BACKGROUND Cardiovascular disease is the major cause of death in the end-stage renal disease population . Novel risk factors such as homocysteine ( Hcy ) are of considerable interest in this group as hyperhomocysteinaemia is highly prevalent in the setting of renal impairment . Folic acid-vitamin B group therapies are only partially effective treatments . Hcy is highly protein-bound and thus poorly dialysed . Dialyzers with albumin-leaking properties have been shown to result in lowering of plasma Hcy . As the FX-class ( Advanced Fresenius Polysulfone dialyzer ) has greater clearance of larger molecular weight substances but is non-albumin-leaking , we explored the capacity of this new technology membrane to reduce plasma Hcy levels . METHODS A prospect i ve r and omized cross-over trial in 35 prevalent haemodialysis patients , one group receiving 12 weeks dialysis using FX dialyzer then 12 weeks with st and ard high flux dialysis ( SHF ) and the other group SHF followed by FX dialyzer . All patients received vitamin B(6 ) 25 mg and folic acid 5 mg daily throughout the study . RESULTS The primary outcome was plasma Hcy pre-dialysis at week 12 . FX vs SHF showed no significant difference , 25+/-6.6 vs 25.9+/-5.8 microg/l , Delta95 % CI = -2.77 to 4.59 , P = 0.31 . There was a non-significant trend toward a decrease in Hcy in both groups ( 27.43+/-7.68 to 25.91+/-5.78 micromol/l for SHF , P = 0.23 and 26.0+/-4.58 to 25.0+/-6.61 micromol/l for FX , P = 0.28 ) . Analysis by repeated measures method demonstrated a statistically significantly lower Hcy with FX vs SHF dialyzer ( adjusted beta = -1.30 , 95 % CI = -2.41 to -0.19 , P = 0.022 ) . K(t)/V(urea ) was higher in FX vs SHF ( 1.35+/-0.18 vs 1.22+/-0.2 ; P = 0.013 ) . Folate and B(6 ) levels did not change . CONCLUSIONS The primary outcome analysis did not show any significant difference in pre-Hcy comparing FX and SHF membranes . Although our secondary analysis demonstrated a statistically significant difference between membranes , the magnitude of the difference ( 1.3 mumol/l ) is not clinical ly significant . Thus the use of the FX dialyzer did not result in a clinical ly significant benefit in relation to improving pre-dialysis Hcy compared with st and ard high-flux dialysis Hemodialysis with complement-activating membranes , such as cuprophane , induces neutropenia and expression of the granulocyte adhesion receptor Mac-1 ( CD11b/CD18 ) , while hemodialysis with noncomplement-activating membranes does not . Increased expression of CD11b by neutrophils may mediate cuprophane-induced leukopenia . However , the rebound granulocytosis that follows leukopenia is not fully understood . Ten patients on regular hemodialysis were included in a cross-over study . Hemodialysis was performed for 2 weeks with cuprophane and 2 weeks with polyamide , a high-flux noncomplement-activating membrane . At the end of each period , the following parameters were determined during a hemodialysis session : C5a concentration by enzyme immunoassay and the neutrophil expression of CD11b , LFA-1 ( CD11a/CD18 ) , and the antigen recognized by MoF11 ( MoF11 Ag ) , a monoclonal antibody that recognizes activated neutrophils , by immunofluorescence flow cytometry . Hemodialysis with cuprophane induced an increase in C5a concentration and in the expression of CD11b and MoF11 Ag , which were maximal after 15 minutes of hemodialysis , at the nadir of neutropenia . CD11b expression was maintained throughout hemodialysis , despite the reversal of neutropenia . Conversely , after peak expression , C5a and MoF11 Ag decreased as the neutrophil count increased to baseline values . Polyamide hemodialysis did not induce variations in C5a concentration , nor in CD11b and MoF11 Ag expression . CD11a/CD18 expression remained stable during hemodialysis with both membrane types . Neutrophil activation , as determined by MoF11 Ag expression , was correlated with the evolution of neutrophil count and C5a concentration during cuprophane hemodialysis , while CD11b expression was not correlated with neutrophil count throughout dialysis . A decrease in neutrophil activation could explain in part the detachment of neutrophils previously bound to endothelium and , therefore , the reversal of neutropenia . ( ABSTRACT TRUNCATED AT 250 WORDS A major cause of the morbidity and mortality of patients with end-stage renal disease ( ESRD ) is related to disorders of large blood vessels , especially coronary heart disease . Atherosclerosis , the most common form of this disease , is known to result from abnormalities in plasma lipoproteins , as well as from factors that damage the vessel wall . Two well-known risk factors for coronary heart disease are elevated plasma concentrations of LDL and reduced concentrations of HDL . This latter disorder is often accompanied by elevated triglycerides . Low HDL and elevated triglycerides are commonly associated with ESRD . Dialysis with high flux membranes differs from conventional dialysis in a number of ways . These include better biocompatibility and increased flux of larger molecules . Although several previous studies had suggested that dialysis with high flux membranes improves plasma lipoprotein profiles , a definitive cross-over design ed study to assess the roles of high flux versus biocompatibility in altering lipoprotein profiles had not been done . Preliminary data from such a study are presented . These data confirm the beneficial effects of high flux membranes to reduce plasma triglycerides and suggest that this effect is primarily due to the high flux , and not the biocompatible , feature of the membranes Hemodialysis ( HD ) membrane biocompatibility is defined as absence of complement activation . We have recently shown that circulating levels of interleukin ( IL ) 1 and IL-2 predict death and survival , respectively , of HD patients . Studies have assessed IL-1 in treatments with biocompatible and less biocompatible dialysis membranes , but no study has correlated circulating levels of all these immunoreactants . We assessed these immunoreactants , and temperature as an outcome , during HD in patients treated with different membranes . Twelve stable patients , receiving thrice-weekly chronic bicarbonate HD , were r and omly dialyzed with three different types of membranes , composed of : Cuprophan , cuprammonium rayon modified cellulose , and Hemophan . Blood was drawn from the arterial line port before ( Pre ) and 15 , 30 , and 60 min during and after ( Post ) HD . Patients ’ temperatures were measured before and after each treatment . The plasma concentrations of IL-1 and IL-2 and factors C3a and C5a were assessed by ELISA . There were no differences between baseline levels of any of the immunoreactants in patients treated with different dialyzers . C3a , C5a , and IL-1 levels increased significantly during HD treatments with all three different membranes . C3a , C5a , and IL-1 levels during Cuprophan and Hemophan treatments were significantly higher than the levels during modified cellulose treatment at 30 and 60 min and Post ( p < 0.01 ) . For all the immunoreactants , however , the Post levels were higher than the Pre levels . In contrast to IL-1 , there were no differences in mean IL-2 levels during treatments when different membranes were compared . There were few correlations of plasma C3a and C5a levels with plasma IL-1 levels , but there was only one treatment time in one dialyzer group during which IL-2 and any of the other factors were correlated . Pre and Post temperature values and percent change in temperature were not correlated with any of the immunoreactants measured . These data show that C3a , C5a , and IL-1 responses are similar , but not identical , during treatments with different membranes . The response of circulating IL-2 levels to treatments is quite different from that of plasma C3a , C5a and IL-1 levels and suggests that these changes are not solely due to treatment factors . Treatment with modified cellulose membranes is associated with a different immunoreactive profile as compared with patients dialyzed using other cellulose membranes . We suggest that circulating IL-1 levels are good biocompatibility markers Leukocyte response to phagocytic challenge was assessed in uremic and hemodialysis patients in a prospect i ve and cross sectional study . Using latex , zymosan and staphylococcus as phagocytic challenge , the utilization of glucose-I-C14 and the generation of reactive oxygen species was measured in these patients . In uremic , non-dialysis dependent patients , the response to phagocytosis was significantly reduced when creatinine exceeded 6 mg/dl and prior to initiation of dialysis ( mean serum creatinine 9.3 + /- 0.3 mg/dl ) was less than half that of patients with normal renal function ( P less than 0.01 ) . In a prospect i ve study of 15 patients initiated on dialysis , the metabolic response of their leukocytes was assessed sequentially . In eight patients , initiation of dialysis with cuprophane ( Cu ) membrane lead to a further decline ( 60 % ) in their metabolic response to phagocytosis at the end of four weeks of dialysis compared to pre-initiation of dialysis ( P less than 0.01 ) , whereas in seven other patients , dialysis with non-complement activating membranes did not result in a significant decline . Prospect i ve cross-over studies of chronic hemodialysis patients corroborated these findings ; eight patients dialyzed with new CU membranes had a significant decline of their metabolic response to phagocytic challenge acutely at the end of each dialysis and in pre-dialysis sample s after two weeks of Cu dialysis , whereas their response returned back to baseline after two weeks of dialysis with non-complement activating membrane . In prospect i ve and cross sectional studies , a decreased response to phagocytic stimulus was a predictor of hospitalization , primarily for infectious reasons . ( ABSTRACT TRUNCATED AT 250 WORDS The high incidence of cardiovascular disease in hemodialyzed ( HD ) patients is well established and oxidative stress has been involved in this phenomenon . The aim of our study was to evaluate if a vitamin E-coated dialyzer could offer protection to HD patients against oxidative stress . Sixteen HD patients were successively assessed for one month ( i ) on a high biocompatible synthetic dialyzer ( AN ) and ( ii ) on a vitamin E-coated dialyzer ( VE ) . Blood sample s were taken before and after the dialysis session at the end of each treatment period . HD session conducted with the AN dialyzer was responsible for acute oxidative stress , significantly assessed after HD by a decreased plasma vitamin C level and an increased ascorbyl free radical (AFR)/vitamin C ratio used as an index of oxidative stress . Plasma elastase activity , reflecting neutrophil activation , was also increased ; soluble P-selectin , reflecting platelet activation , did not show any variation . The use of the VE dialyzer was associated with a less extended oxidative stress compared with the AN membrane : basal vitamin C level was higher , and after the HD session AFR/vitamin C ratio and elastase activity were not significantly increased . Plasma vitamin E levels were not affected . Our study demonstrates that HD is associated with oxidative stress , which can be partially prevented by the use of a vitamin E-coated dialyzer . Our data suggest that this dialyzer may exert a site-specific scavenging effect on free radical species in synergy with a reduced activation of neutrophils The International Cooperative Biocompatibility Study was planned to analyse the symptomatic and laboratory response to seven different dialysers studied in five centres in four countries . The dialysers used were the G10 - 3N , G120 M , CD 4000 , T 150 , Duo-Flux , F 60 , and Filtral ( see below for full description ) . A total of 37 patients in the Veterans Administration Lakeside Medical Center , Chicago ; Henry Ford Hospital , Detroit ; Osaka City University Hospital , Osaka ; Wilhelm Pieck University Hospital , Rostock ; and Huddinge University Hospital , Stockholm were studied . All patients had been dialysed for a minimum of 6 months , were non-diabetic , stable , and compliant ; and most were middle-aged and male . Patients were treated three times per week for 2 weeks with each new dialyser with r and om assignment to one of four orders of dialyser use . The same manufacturing lot of each dialyser , blood line sets and needles were used by all centres . Delivery systems were volumetric controlled except for some patients in Osaka treated with negative-pressure equipment . Individual patient prescriptions ( Kt/Vs for urea ) , in use prior to the study , were continued . Kt/Vs for all treatments were derived from reported blood flows and blood water corrected mass transfer coefficients multiplied by dialyser surface area . Clinical data were measure pre- , intra- and postdialysis . Hourly signs , symptoms , drugs , and nursing interventions were recorded using the identical treatment record at all centres . In addition , patients completed a question naire form ( translated into the appropriate language ) at least weekly , relating symptoms experienced with each dialyser . Laboratory investigations were performed during the sixth consecutive treatment . ( ABSTRACT TRUNCATED AT 250 WORDS Adverse cardiac and pulmonary events are frequently observed during hemodialysis and contribute to significant morbidity and mortality . The temporal relationship between these events during the intradialytic period has not been well defined . To examine the event rate and timing of silent ischemia , cardiac ectopy , and hypoxemia , we conducted a prospect i ve , single-blind , r and omized study of 10 subjects undergoing maintenance hemodialysis with four contiguous combinations of dialysis membranes ( cuprammonium or polysulfone ) and dialysates ( acetate or bicarbonate ) . The frequency of oxygen desaturation events peaked during the first 2 hours , whereas silent myocardial ischemia and supraventricular ectopies occurred more often in the later hours . Ventricular ectopy occurred steadily throughout the intradialytic period . The combination of acetate dialysis and cuprammonium membrane is associated with the most frequent events . We conclude that cardiopulmonary events can occur frequently during hemodialysis , and the frequency is dependent on the type of dialysis membrane and dialysate buffer used The aim of this crossover clinical study was to gain basic information on the hemocompatibility and effectiveness of recently developed high-flux membranes made of cuprammonium rayon with ultrafiltration coefficients of 10 , 17 , and 19 ml/mm Hg/h ( S12W , SU12W , and SS12W dialyzers , respectively ) , and to identify any possible differences from a conventional membrane made of the same material with an ultrafiltration coefficient of 6 ml/mm Hg/h ( C12W dialyzer ) . All the tested membranes led to an abrupt drop in leukocyte count in the initial phase of hemodialysis . In high-flux membranes , C5a anaphylatoxin would pass into the dialysate , but mean C5a anaphylatoxin concentrations in the dialysate were lower by orders of magnitude than its plasma concentrations , which behaved , in high- and low-flux membranes alike , typically of those made of nonsubstituted cellulose with no intermembrane differences . As judged by the concentrations of the thrombin-antithrombin III complex , the coagulation system was activated -- again , without differences between membranes . The reduction rates for urea , creatinine , and phosphates were comparable for all the tested membranes . Compared with baseline , the post-dialysis serum concentrations of beta 2-microglobulin in high-flux membranes , unlike the low-flux membrane , were significantly lower . We conclude that there are no significant differences between the tested high- and low-flux membranes made of cuprammonium rayon in the monitored hemocompatibility parameters , and that high-flux membranes are capable of reducing serum beta 2-microglobulin concentrations We evaluated the biocompatibility of a newly developed vitamin E hemodialyzer ( CL-EE ; Terumo Co Ltd , Tokyo , Japan ) by neutrophil function and oxidant stress in patients with end-stage renal failure in a r and omized crossover study . Ten patients underwent hemodialysis using either the CL-EE or a control dialyzer membrane identical to the CL-EE except for vitamin E binding for 12 weeks in a crossover fashion after a 1-month washout period with hemophane membranes . White blood cell counts , serum oxidized low-density lipoprotein ( Ox-LDL ) levels , and malondialdehyde ( MDA ) levels during hemodialysis sessions were measured at the initiation and end of the CL-EE and control trials . Superoxide anion production by neutrophils just before and 4 hours after starting the session also was measured . Leukocytopenia at 1 hour after starting the session was detected to a similar extent in both membranes . However , the degree of reduction was less in the CL-EE trial after repeated use . Superoxide anion production by neutrophils just before a hemodialysis session was reduced after repeated use of the CL-EE membrane . Serum Ox-LDL levels increased , whereas serum MDA levels decreased during sessions to a similar extent in both trials . However , these parameters were significantly lower in the CL-EE trial after repeated use . Serum LDL concentrations significantly decreased with repeated use of the CL-EE membrane . These data suggest that repeated use of the CL-EE membrane for 3 months improves neutrophil function , oxidant stress , and LDL concentrations in patients with renal failure . This membrane may be useful to reduce the incidence of cardiovascular events in patients with renal failure The relationship between hemodialysis ( HD ) symptoms and dialyzer membrane composition and area , blood-flow , treatment duration , urea removal , ultrafiltration volume , leukocyte activation , and complement generation ( C3a ) was studied in 20 patients undergoing 234 HD treatments by 12 different modes in r and om order using Cuprophan , hemophane , or polyamide membranes with small or large membrane areas with high Qb ( 400 ml/min ) and short duration ( 2 h ) or low Qb ( 200 ml/min ) and long duration ( 4 h ) . Fewer symptoms occurred during the 2-h HD at high Qb than during the 4-h HD with low Qb ( 19 % vs. 32 % , p = 0.0351 ) . No differences were observed between different dialyzer membranes or areas . More intradialytic symptoms occurred when urea elimination was high than it was low ( p = 0.0044 ) . Leukocyte activation ( leukocyte drop ) after 15 min of dialysis and complement generation did not influence symptom incidence . Blood pressure changes were mainly influenced by ultrafiltration volume ( p < 0.001 ) . Symptoms between dialyses were determined by urea removal and ultrafiltration . Membrane , area , or Qb were of no importance . Thus , duration of dialysis , urea removal , and dem and for ultrafiltration , but not membrane composition , area , or biocompatability , are important for the development of HD-related symptoms A crossover study to compare the effects of seven different dialysers on intradialytic symptoms in 37 patients during dialysis with acetate-containing dialysate was performed at five centres in four countries . The same manufacturing lot of each dialyser and of blood line sets were used by all centres . The same clinical data ( duration of dialysis , blood pressure , weights , temperature , drugs , symptoms , and treatments ) and technical data ( blood flow , dialyser clearance , and ultrafiltration rate ) were collected . Kt/V for urea was used to determine dialysis prescribed . Intradialytic symptoms and signs were measured hourly or when observed by staff using the haemodialysis treatment form ( see Introduction ) . After each week of treatment with a particular dialyser , patients completed a question naire relating to the presence and severity of symptoms . ( Only presence or absence of symptoms are presented . ) Wide differences in dialysis duration and blood flow between centres were noted . These may have contributed to the differences between centres in relationship to staff reported responses to different dialyser : Dialysers with the lowest incidence of both signs and symptoms and of chest pain , back pain , and itching ( arbitrarily design ated bioincompatibility symptoms ) were the Duo-Flux and Filtral , with the G120 M , the CD 4000 , and the T 150 having the highest incidence . By patient question naire the most biocompatible dialysers were the T 150 , F 60 , and the Filtral , with the most symptom producing being the G120 M and the G10 - 3N . Perceptions of symptoms between patients and staff differed substantially overall and between centres . Hypersensitivity reactions were noted in two patients , both occurring with cuprammonium cellulose hollow-fibre dialysis , despite adherence to manufacturers ' instructions concerning saline priming and removal . Both patients showed antibody titres greater than 1:160 against ethylene oxide-HSA . Ethylene oxide was not detected ( limit of detection 1 part per million ) in dialysers , blood line sets , or fistula needles . The study suggests that dialysis symptom reporting is complicated by individual perceptions , staff reactions , and the efficiency of recording . In this study ethnic and cultural differences must be added to the haemodynamic differences and other prescription-related elements in influencing symptoms . Despite these problems a hierarchy of dialyser-related symptoms and signs could be discerned which largely paralleled laboratory findings of biocompatibility . Future comparative studies relating symptomatology to membrane and dialyser structure should consider the variables identified as influencing symptoms and their reporting High molecular weight ( MW ) solutes are not removed during conventional hemodialysis ( HD ) , and their accumulation is thought to play a role in some long-term HD complications ( anemia , bone and joint pain , neuropathy , itching ) . The present trial was conducted to evaluate the removal capacity during in vivo HD of a new polymethylmethacrylate ( PMMA ) membrane ( Filtryzer BK-F , 1.3 m2 ) compared to conventional PMMA ( BK-P , 1.6 m2 ) and to cellulose acetate ( CA , 1.3 m2 ) . BK-F dialyzers , with a pore size of 100 A ° and 62 % porosity , are design ed to remove high MW substances . Ten stable anuric RDT patients ( 53 ± 13 years ) were treated for one week with each membrane in a r and omized sequence . Plasma concentrations of creatinine , BUN and beta2-microglobulin ( beta2-M ) were measured before ( b ) and after ( a ) HD to determine the reduction rate for these substances ( % ) . Beta2-M concentration after HD was corrected for changes in distribution volume . Sample s of spent dialysate were collected after 3 minutes , 120 minutes and at the end of HD sessions , and appropriately treated and concentrated for HPLC analysis . The reduction rate for BUN and creatinine was similar for the 3 membranes . BK-F showed a higher beta2-M reduction rate than BK-P ( p<0.005 ) or CA ( p<0.0001 ) . HPLC analysis of dialysate showed prevalent peaks < 4 kilodaltons ( kDa ) throughout HD for BK-P and CA . Solutes > 10 kDa were infrequently detected . Peak profile during HD with BK-F was quite different , showing a predominant peak > 50 kDa which also included albumin . However , albumin loss significantly decreased after 120 minutes and at the end of dialysis compared with the 3-minute values , and was lower than that reported in CAPD patients . With BK-F a peak of MW > 500 kDa was also detected which previous studies indicated as a range characterized by the presence of erythropoiesis inhibitors . Use of the BK-F membrane in HD could afford satisfactory removal of high MW substances , thereby preventing or controlling some long-term HD complications such as anemia or beta2-M amyloid formation The biocompatibility and solute permeability characteristics of a high-permeability modified cellulose membrane ( Hemophan-HP ) ( He-HP ) were compared with those of two synthetic membranes ( poly(ethylene-co-vinyl alcohol ) ( EVAL ) and poly(acrylonitrile-co-sodium methallyl sulphonate ) ( AN69 ) ) and Cuprophan in a multicentre , four-way cross-over clinical trial . Cuprophan membranes caused significant complement activation , leukopenia , and granulocyte elastase release . He-HP membranes demonstrated a lesser effect , which was similar to that observed for the EVAL membrane , although less than that seen with the AN69 membrane . A similar order for the four membranes was seen for their effect on platelets . Cuprophan membranes provided superior small-molecule removal to the other three membranes . In contrast , Cuprophan was essentially impermeable to beta 2-microglobulin , whereas He-HP , EVAL , and AN69 allowed the removal of 60 - 90 mg of beta 2-microglobulin per treatment . However , a decrease in the plasma concentration of beta 2-microglobulin was observed only with the AN69 membrane , most probably as a result of the ability of that membrane to adsorb proteins . Our results demonstrate that high-permeability membranes of comparable biocompatibility to some synthetic membranes can be fabricated from cellulose derivatives Anaphylatoxins generated by complement activation by filter membranes are present in plasma during hemodialysis ( HD ) . In the presence of endotoxins which may contaminate the dialysate , they can trigger monocytes to produce interleukin-1 ( IL-1 ) and tumor necrosis factor ( TNF ) , with detrimental effects for the patients . We have investigated whether or not the use of complement activating ( cuprophan ) and non- ( or less- ) activating membranes ( polysulfone , polymethylmethacrylate or polyacrylonitrile ) per se influences cytokine levels in HD patients . Our results indicate that if a sterile bicarbonate solution is used as dialysate , there are no significant increases in IL-1 , TNF , interleukin-2 ( IL-2 ) and soluble IL-2 receptors ( sIL-2r ) throughout HD , even with cuprophan membranes . Moreover even a prolonged use of this membrane ( three months ) did not change pre-dialysis levels of cytokines and receptors . Use of complement activating membranes also does not influence β2 microglobulin levels In a controlled prospect i ve trial , the effect of a switch from cellulose-based , low-flux dialysis membranes to polysulphone , high-flux membranes on lipid parameters was evaluated . Baseline values of lipid parameters were identical in the study group and the control group in which the dialysis membrane remained unchanged . After 6 wk , total triglyceride , very low-density lipoprotein ( VLDL ) triglyceride , and VLDL cholesterol decreased , respectively , 28 + /- 17 ( P < 0.01 ) , 38 + /- 17 ( P < 0.01 ) , and 24 + /- 21 % ( P < 0.05 ) , and the proportion of total cholesterol that was high-density lipoprotein cholesterol increased from 15 + /- 5 to 18 + /- 5 % ( P < 0.05 ) in the high-flux polysulphone group , whereas these variables remained unchanged in the control group . Low-density lipoprotein and total cholesterol as well as Kt/V , protein catabolic rate , parathyroid hormone , albumin , and body weight did not change . No change in lipoprotein lipase activity was found . In a second study , the effects of a single hemodialysis session with high-flux polysulphone and low-flux , cellulose-based membranes on lipid parameters and lipolytic activity were compared in a cross-over fashion . Treatment with both membranes result ed in a significant decrease in plasma triglyceride , VLDL triglyceride , and VLDL cholesterol . Lipoprotein lipase activity increased during hemodialysis . Changes in lipid parameters and lipolytic activity were identical during the two treatments The clinical performance during first use of a new membrane manufactured from a blend of polyarylethersulfone and polyvinylpyrrolidone ( Arylane ; Hospal Renal Care , Lyon , France ) , in which the microstructure of the membrane has been tailored by the manufacturing process and polymer blend , has been compared with Fresenius Polysulfone ( Fresenius Medical Care , Bad Homburg , Germany ) in a prospect i ve , r and omized , crossover study . Small-molecular clearances were similar . A reduction in plasma beta(2)-microglobulin levels was present using both membranes , with a significantly greater removal by Arylane such that the mean postdialysis plasma level difference between the membranes at the end of dialysis was 8 . 7 mg/L ( 95 % confidence interval , 3.9 to 13.5 ; P = 0.004 ) . Recovery of beta(2)-microglobulin from the dialysis fluid was similar : 170 + /- 70 mg for Arylane and 110 + /- 60 mg for Fresenius Polysulfone ( P = 0.04 ) . Both membranes were impermeable to albumin but allowed the passage of low-molecular-weight proteins , with 10,046 + /- 3,239 mg for Arylane and 7,285 + /- 2,353 mg for Fresenius Polysulfone recovered from the dialysis fluid ( P = 0.07 ) . Neutropenia and platelet adhesion to the membrane were minimal , and time-averaged complement levels during dialysis for C3a and C5b-9 were 207 + /- 92 and 62 + /- 24 ng/mL for Arylane and 223 + /- 68 and 45 + /- 24 ng/mL for Fresenius Polysulfone , respectively , and were membrane independent . This study indicates that the membrane using polyarylethersulfone in conjunction with PVP has complement-activation potential and neutropenia similar to Fresenius Polysulfone but has an enhanced capacity to remove beta(2)-microglobulin . This enhanced removal arises from transmembrane transport augmented by adsorption within the membrane matrix The h and ling of low , middle and high molecular weight markers was examined in seven stable dialysis patients during hemofiltration with different membranes . Four membranes were examined in a r and omized , crossover order ( polysulfone , polyamide , AN69 polyacrylonitrile , Asahi polyacrylonitrile ) by measuring plasma and dialysate concentrations of phosphate , creatinine , vitamin B12 , β2-microglobulin , furanic acid , hippuric acid , retinolbinding protein , alpha-1-antitrypsin , and albumin . Sieving coefficients and plasma clearances of β-microglobulin or retinol-binding protein were markedly or slightly lower during hemofiltration with the Asahi polyacrylonitrile membrane than with the other membranes ( highest removal with polysulfone/AN69 polyacrylonitrile membranes ) . No differences of obvious clinical relevance could be seen between the four membranes . A high β2-microglobulin removal rate might be important to prevent dialysis-associated amyloidosis Cytokine induction by dialyzer membranes has been related to several acute and chronic side effects of hemodialysis treatment , among them being immune dysfunction and progressive atherosclerosis . Surface modification of cuprophane dialyzers with the antioxidant vitamin E is a new approach to enhance biocompatibility and improve cytokine levels , as well as immune function . Twenty-one patients undergoing treatment with hemophane ( HE ) dialyzers were enrolled onto a crossover study with a vitamin E-coated ( VE ) dialyzer or a synthetic polyamide ( PA ) dialyzer . In vitro assays of lymphocyte activation and measurements of cytokine induction were performed to evaluate biocompatibility . Four weeks of treatment with either VE or PA dialyzers enhanced in vitro proliferation of peripheral blood leukocytes in comparison to treatment with HE membranes used before study entry . Enhancement of lymphocyte function was independent of dialysis efficiency , which was kept constant during the study . In the interdialytic interval , preactivation of monocytes for the production of interleukin-6 ( IL-6 ) did not differ between VE or PA dialysis . In contrast , the VE membrane reduced acute production of IL-6 during a dialysis treatment , whereas the PA membrane did not . Unlike IL-6 , the regulatory cytokine IL-10 is not inhibited by either membrane . This is important because IL-10 is believed to have a beneficial effect on immune function in dialysis patients . The VE membrane , despite being based on a cuprophane backbone , is similar to the highly biocompatible PA dialyzer in terms of its effect on lymphocyte function , whereas it exerts an additional suppressive effect on the overproduction of proinflammatory cytokines BACKGROUND The generation during hemodialysis of activated complement fragments and reactive oxygen species , including nitric oxide ( NO ) , may affect peripheral blood mononuclear cell ( P BMC ) function . Currently , little is known about signal transduction pathways involved in P BMC activation . Jun N-terminal kinase ( JNK ) is a novel mitogen-activated protein ( MAP ) kinase phosphorylated and activated in response to oxidative stress and directly involved in cell activation . METHODS The present study evaluated the activation of JNK in P BMC s isolated from eight uremic patients undergoing , in a r and omized manner , three month-subsequent periods of hemodialysis with a low-flux cellulose acetate ( CA ) and a vitamin E-modified cellulose membrane ( CL-E ) . After each period of treatment , P BMC s were harvested before ( T0 ) , during ( T15 ) and after three hours ( T180 ) of dialysis . At the indicated time points , plasma C5b-9 generation by ELISA and inducible NO synthase ( iNOS ) gene expression by in situ hybridization were evaluated also . The activation of JNK was studied by Western blotting using a specific monoclonal anti-phospho-JNK antibody , which recognizes the activated form of JNK . RESULTS At T0 , a significant increase in plasma C5b-9 levels was found in CA patients compared to CL-E-treated patients . During hemodialysis , C5b-9 levels rose more significantly in CA patients than in CL-E patients and returned to baseline values only in CL-E patients . At the same time , in CA patients an increased iNOS gene expression was observed at T180 together with a striking activation of JNK . By contrast , P BMC from CL-E-treated patients showed undetectable levels of phospho-JNK and a significant reduction in iNOS expression . Interestingly , incubation of P BMC s with normal human plasma ( 10 % ) , activated by contact with a cellulosic membrane , induced a time-dependent increase in JNK phosphorylation that was completely inhibited by blocking complement cascade activation . CONCLUSION Our data suggest that JNK phosphorylation is strikingly increased in P BMC s obtained from CA-treated patients and may represent a key cellular event in P BMC activation during dialysis with bioincompatible membranes . The activation of this signaling enzyme , mediated by active complement fragments and P BMC -dialyzer interaction , can be significantly reduced by the use of vitamin E-coated membrane By the use of flow cytometric techniques , this prospect i ve , r and omized crossover study was design ed to analyze intradialytic granulocyte reactive oxygen species ( ROS ) formation in whole blood with complement-activating and noncomplement-activating hollow fiber membranes . Dialysis with a complement-activating membrane result ed in a 6.5-fold increase in granulocyte hydrogen peroxide production 15 min after dialysis initiation and remained significantly elevated ( P < 0.01 ) through the first 30 min with this membrane in comparison to both predialysis values and simultaneous values with a noncomplement-activating membrane . Further studies demonstrated that blood obtained at 15 min with a complement-activating membrane generated significantly less granulocyte ROS production in response to Staphylococcus aureus incubation than blood obtained either predialysis or at the same time in dialysis with a noncomplement-activating membrane . Both complement-activating and noncomplement-activating dialysis membranes caused slightly decreased granulocyte responsiveness to phorbol myristate acetate . It was concluded that hemodialysis with complement-activating membranes results in increased granulocyte ROS production and decreased responsiveness to S. aureus challenge during the dialysis procedure . These results document the potential role of ROS in hemodialysis-associated pathology and susceptibility to infection In order to test whether dialyzer membrane biocompatibility influences systemic cardiovascular function , we treated 8 hemodialysis patients ( 4 men and 4 women , aged 24 - 73 years ) with a low-biocompatible ( cuprophane ) and a high-biocompatible ( polyacrylonitrile ) membrane in a r and omized double-blind crossover protocol using bicarbonate hemodialysis without ultrafiltration for the first 60 min and with ultrafiltration for the remaining treatment time . Left ventricular function and systemic hemodynamics were assessed noninvasively at baseline and during treatment by Doppler echocardiography combined with external subclavian artery pulse trace calibrated with oscillometrically measured brachial artery blood pressures . There was no significant difference in the cardiovascular response to the 2 membranes , neither during isolated hemodialysis nor when ultrafiltration was added . Mean arterial pressure increased 10 % ( p < 0.001 ) during isolated hemodialysis and returned to baseline levels with ultrafiltration . The cardiac index decreased 22 % ( p < 0.001 ) during ultrafiltration , due to the greater decrease in left ventricular stroke index ( 30 % , p < 0.001 ) than increase in heart rate ( 9 % , p < 0.05 ) . Total peripheral resistance increased 10 % ( p < 0.05 ) during isolated hemodialysis and a further 19 % ( p < 0.01 ) when ultrafiltration was added . Hence , profound cardiovascular alterations were observed during hemodialysis treatment ; however , these changes were not related to the biocompatibility of the membranes The effect of high flux hemodialysis on left ventricular function in ESRD patients was evaluated in a double blind , single cross-over , study comparing conventional to high flux hemodialysis . The subjects were 21 stable chronic hemodialysis patients . Ten were r and omly allocated to the conventional-high flux sequence and 11 to the reverse sequence . The conventional membrane was the CD 3,500 or 4,000 ; the high flux membrane was the Duoflux ( Althin Medical Inc. , Miami Lakes , Fla. ) . Both were cellulose acetate and both were sterilized with ethylene oxide . The dialysate bicarbonate and sodium were held constant for the study . The ultrafiltration rates were 3.5 - 5.0 ml/h/mm Hg transmembrane pressure for the conventional and 15 ml/h/mm for the high flux membrane . The beta-2-microglobulin sieving coefficient was 0 for conventional and 0.27 for the high-flux membrane . The modest improvements in estimates of systolic function suggest a cardiac advantage in high-flux dialysis , the clinical impact of which requires further study |
1,848 | 19,727,032 | PT/NT was effective at increasing functionality as well as at decreasing the incidence of recurrent injuries and " giving way " episodes after ankle sprains and in conservative treatment of anterior cruciate ligament injuries .
However , conflicting results or no efficacy of training were reported for static postural control , joint position sense , neuromuscular control , joint laxity , and lower extremity strength .
From this review , it can be concluded that proprioceptive and neuromuscular interventions after ankle and knee joint injuries can be effective for the prevention of recurrent injuries and the improvement of joint functionality | PURPOSE Although proprioceptive and neuromuscular exercises are considered to be part and parcel of rehabilitation programs after sport injuries , there is an uncertainty regarding the effectiveness of corresponding training interventions .
The objective of this review was to evaluate the effectiveness of proprioceptive and neuromuscular training ( PT/NT ) for the treatment of ankle , knee , and shoulder joint injuries . | Objective To examine the effects of coordination training with and without stochastic resonance ( SR ) stimulation on dynamic postural stability . Design Experimental with repeated measures . Setting Research Laboratory . Participants Thirty subjects with functional ankle instability ( FAI ) and 30 healthy subjects . Interventions Subjects were assigned to a conventional coordination training group , SR stimulation coordination training group , or control group . Training groups performed coordination exercises for 6 weeks . Single leg jump-l and ing tests were performed before training began ( pretest ) , and then once every 2 weeks . Jump-l and ing tests required subjects to l and on a single leg on a force plate and stabilize quickly . Main Outcome Measures Anterior/posterior ( A/P ) and medial/lateral ( M/L ) time-to-stabilization ( TTS ) . Results The FAI group improved their A/P TTS over their pretest by 16 % ( test 2 ) , 22 % ( test 3 ) , and 22 % ( posttest ) . They also improved their M/L TTS over their pretest by 16 % ( test 3 ) and 22 % ( posttest ) . Control groups did not improve their TTS ( P>0.05 ) . SR stimulation did not statistically influence TTS ( P>0.05 ) . Effect sizes ( ES ) , however , for our 3-way interaction analyses for A/P TTS ( ES=0.40 ) and M/L TTS ( ES=0.30 ) suggested that SR stimulation improved the FAI group 's M/L TTS after 2 weeks of training , and improved their A/P TTS and M/L TTS to a greater degree after 4 weeks than coordination training alone . Conclusion Coordination training can improve dynamic postural instabilities associated with FAI . SR stimulation might be an alternative therapy for FAI , as this stimulation might improve dynamic postural stability more quickly and to a greater extent than coordination training without SR stimulation UNLABELLED The efficacy of a 6-week rehabilitation program was evaluated in 100 consecutive patients , age 15 - 42 years , with acute anterior cruciate ligament ( ACL ) injury . Arthroscopy revealed associated lesions in 82 % of the patients . Except for resections on menisci with large and unstable lesions , no surgery was performed . The patients were r and omly assigned to supervised training or self-monitored training after instruction . RESULTS At the 6-week follow-up there was no difference between the groups with regard to pain at rest , pain during walking , or experience of giving-way episodes , Tegner activity level of Lysholm knee score . Only 2 of the 100 patients were observed without joint mobility restriction . The only significant difference between the groups was the improvement of muscle function in men in the supervised training group . CONCLUSION Six weeks ' rehabilitation is too short a time period from original injury to obtain normal mobility and restored knee function Background Training of neuromuscular control has become increasingly important and plays a major role in rehabilitation of subjects with an injury to the anterior cruciate ligament ( ACL ) . Little is known , however , of the influence of this training on knee stiffness during loading . Increased knee stiffness occurs as a loading strategy of ACL-injured subjects and is associated with increased joint contact forces . Increased or altered joint loads contribute to the development of osteoarthritis . The aim of the study was to determine if knee stiffness , defined by changes in knee kinetics and kinematics of gait , step activity and cross-over hop could be reduced through a knee-specific 12-week training programme . Methods A 3-dimensional motion analysis system ( VICON ) and a force plate ( AMTI ) were used to calculate knee kinetics and kinematics before and after 12 weeks of knee-specific training in 12 males recruited from a cohort with ACL injury 16 years earlier . Twelve uninjured males matched for age , sex , BMI and activity level served as a reference group . Self-reported patient-relevant data were obtained by the KOOS question naire . Results There were no significant changes in knee stiffness during gait and step activity after training . For the cross-over hop , increased peak knee flexion during l and ing ( from 44 to 48 degrees , p = 0.031 ) and increased internal knee extensor moment ( 1.28 to 1.55 Nm/kg , p = 0.017 ) were seen after training , indicating reduced knee stiffness . The KOOS sport and recreation score improved from 70 to 77 ( p = 0.005 ) and was significantly correlated with the changes in knee flexion during l and ing for the cross-over hop ( r = 0.6 , p = 0.039 ) . Conclusion Knee-specific training improved lower extremity kinetics and kinematics , indicating reduced knee stiffness during dem and ing hop activity . Self-reported sport and recreational function correlated positively with the biomechanical changes supporting a clinical importance of the findings . Further studies are needed to confirm these results in women and in other ACL injured population Improvement of ankle proprioception through physiotherapy ( a.k.a . proprioceptive training ) is a widely accepted conservative treatment modality of chronic functional lateral ankle instability . Clinical studies provided controversial data on its proprioceptive effect . Aim of this study was to gain evidence on the efficacy of proprioceptive training on ankle joint position sense . Ten patients ( five males and five females , aged 23.3±5.4 years ) were treated conservatively for chronic lateral ankle instability with a special training programme over 6 weeks . For the assessment of joint position sense we used the slope-box test , first applied and described by Robbins et al. ( Br J Sports Med 29:242–247 , 1995 ) . The test was performed before the start and after the end of the training programme , measuring joint position sense on 11 different slope amplitudes in four directions ( anterior , posterior , lateral and medial ) in r and om order each on both ankles . Comparisons were made between pre- and post-training results as well as versus a control-group of ten healthy athletes . Overall the proprioceptive sensory function of the studied group has improved , but this improvement was not significant in all directions . Only two patients have shown significant improvement of joint position sense in all directions ( mean estimate error improvement : 2.47 ° ) , while conservative treatment was partially successful in five others ( mean estimate error improvement : 0.73 ° ) . The follow-up results of these seven patients were comparable with the values measured in the control-group . Three patients did not show any improvements ( mean estimate error improvement : −0.55 ° ) ( overall difference between improving and non-improving patients : P<0.0001 ) . Mean absolute estimate error profiles of the seven improving patients became similar to the profiles of healthy athletes , while these changes could not be observed in the case of the three non-improving participants . Proprioceptive rehabilitation programme can be an effective method in order to improve impaired joint position sense function . After 6 weeks non-responding patients can be well identified , and considered for other treatment modalities . The determination of the effective length of the programme however needs further evaluation . Still , changes in the proprioceptive sensory function of the ankle plantarflectors indicate the preventive effect of the training programme . Furthermore , our results support the theory of simultaneous function of different mechanoreceptor-systems STUDY DESIGN A nonr and omized 2-group pretest-posttest design . OBJECTIVES To determine the effects of a 4-week balance training program during stance on a single leg . BACKGROUND Individuals who have experienced multiple episodes of inversion ankle sprains often participate in balance training programs . Balance training is performed to treat existing proprioceptive deficits and to restore ankle joint stability , presumably by retraining altered afferent neuromuscular pathways . The effectiveness of such programs on individuals with functionally unstable ankles has yet to be established . METHODS AND MEASURES Prior to and following training , subjects with self-reported functionally unstable ankles ( 5 women and 8 men , mean age = 21.9 + /- 3.1 years ) and nonimpaired subjects ( 6 women and 7 men , mean age = 21.2 + /- 2.5 years ) completed a static balance assessment for both limbs as well as the ankle joint functional assessment tool question naire ( AJFAT ) . The subjects from both groups participated in a unilateral , multilevel , static and dynamic balance training program 3 times a week for 4 weeks . Subjects from the experimental group trained only the involved limb , and the nonimpaired group trained a r and omly selected limb . A stability index ( SI ) was calculated during the balance assessment to indicate the amount of platform motion . Compared to low stability indices , high stability indices indicate greater platform motion during stance and therefore less stability . RESULTS Following training , subjects from both groups demonstrated significant improvements in balance ability . When balance was assessed at a low resistance to platform tilt ( stability level 2 ) , the posttraining scores of both the subjects with unstable ankles ( mean SI = 2.63 + /- 1.92 ) and the nonimpaired subjects ( mean SI = 2.69 + /- 2.32 ) were significantly better than their pretraining scores ( mean SIs = 5.93 + /- 3.65 and 4.67 + /- 3.43 , respectively ) . Assessed at a high resistance to platform tilt ( stability level 6 ) , the posttraining scores of both subjects with unstable ankles ( mean SI = 1.27 + /- 0.66 ) and the nonimpaired subjects ( mean SI = 1.37 + /- 0.66 ) were significantly better than their pretraining scores ( mean SIs = 2.30 + /- 1.88 and 2.04 + /- 1.43 , respectively ) . Additionally , the posttraining AJFAT scores of subjects with unstable ankles ( 25.78 + /- 3.80 ) and the nonimpaired subjects ( 29.15 + /- 5.27 ) were significantly greater than their pretraining scores ( 17.11 + /- 3.44 and 22.92 + /- 5.22 , respectively ) , indicating an overall improvement in perceived ankle joint functional stability . CONCLUSIONS This study suggests that balance training is an effective means of improving joint proprioception and single-leg st and ing ability in subjects with unstable and nonimpaired ankles A bi-directional bicycle pedal that combines proprioceptive training and evertor strengthening has been developed for the treatment of residual instability after ankle sprains . A prospect i ve r and omized study was carried out on 19 subjects with recurrent ankle sprains and positive stress X-ray films . The subjects were r and omized to use either a bi-directional test pedal or a traditional uni-directional bicycle pedal and then completed a 6-week high-intensity training program on a cycle ergometer . Assessment of training intensity level was based on maximum oxygen uptake values , heart rate and lactate concentration in blood at various submaximal workloads . After completion of the training program , the subjects who had used the test pedal increased peak eversion torque at 180 degrees degrees s-1 by 14.2 % ( P = 0.020 ) , reduced figure-of-eight running time by 0.24 s ( P = 0.003 ) , improved single leg stance speed from 72.5 % to the maximum speed of 80 % ( P = 0.005 ) , and improved Karlsson functional score by 5.1 points ( P = 0.005 ) . In the control group , single leg stance improved from 56.1 to 67.8 % ( P = 0.018 ) , but otherwise no significant effects were found . This study indicates that short-term high-intensity training with a bi-directional pedal improves ankle performance and may be an option in the treatment of recurrent ankle sprains Objectives : To examine the effect of six weeks of strength and proprioception training on eversion to inversion isokinetic strength ratios ( E/I ratios ) in subjects with unilateral functional ankle instability . Methods : Thirty eight subjects were r and omly assigned to one of four treatment groups : strength training ( S ) ; proprioception training ( P ) ; strength + proprioception training ( B ) ; control ( C ) . Isokinetic strength was tested before and after training using a Kin Com 125 automatic positioning isokinetic dynamometer . Subtalar joint eversion and inversion motions were tested both concentrically and eccentrically through a range of motion involving 40 ° . All peak torque and average torque values were normalised for body mass . E/I ratios were calculated from average torque and peak torque measures by taking the concentric eversion value and combining it with the eccentric inversion value . Data were analysed using a mixed model analysis of variance with repeated measures on the test factor . Average torque and peak torque E/I ratios at 30 and 120 ° /s were analysed separately . Results : There were no significant differences in average torque and peak torque E/I ratios of the functionally unstable ankle for any of the groups after training compared with before . Conclusions : Six weeks of strength and proprioception training ( either alone or combined ) had no effect on isokinetic measures of strength in subjects with self reported unilateral functional instability . Further studies examining this agonist ( concentric ) to antagonist ( eccentric ) muscle group strength ratio are needed Background and Purpose The purpose of this study was to determine the effect of a 6-month neuromuscular training ( NT ) program versus a traditional strength training ( ST ) program following anterior cruciate ligament ( ACL ) reconstruction . Subjects Seventy-four subjects with ACL reconstruction participated in the study . Methods The study was a r and omized , single-blinded , controlled trial . The NT and ST groups were tested preoperatively and at 3 and 6 months . The main outcome measure was the Cincinnati Knee Score . Secondary outcome measures were visual analog scales ( VASs ) for pain and function , the 36-Item Short-Form Health Survey ( SF-36 ) , hop tests , isokinetic muscle strength , proprioception , and static and dynamic balance tests . Results The NT group demonstrated significantly improved Cincinnati Knee Scores and VAS scores for global knee function compared with the ST group at the 6-month follow-up . There were no significant differences between the groups for the other outcome measures ( ie , hop , balance , proprioception , and muscle strength tests ) . Discussion and Conclusion The results of this study suggest that exercises included in the NT program should be part of the rehabilitation program following ACL reconstruction Exercises to improve joint proprioception and coordination of the functionally unstable ankle are advocated throughout the literature , yet there is little evidence that these exercise have any effect on proprioception and balance . The purpose of this study was to determine the effects of a 6-week coordination and balance training program on proprioception of subjects with functional ankle instability . Forty-five subjects ( age = 22.53 + /- 3.95 years , height = 172.04 + /- 10.0 cm , weight = 71.72 + /- 15.7 kg ) were r and omly placed into a control ( Group 1 ) , sham ( Group 2 ) , or experimental ( Group 3 ) group . The experimental group trained 3 days per week , 10 minutes each day , performing various balance and proprioception exercises . Postural sway and active and passive joint position sense were assessed . Analysis of variance for postural sway modified equilibrium score for anterior and posterior sway , as well as medial and lateral sway revealed significant four-way interactions . Tukey post hoc analyses revealed that Group 3 performed significantly better ( p < .05 ) than Group 1 and Group 2 on the posttests . There were no significant differences for joint position sense or postural sway index . Results suggest that balance and coordination training can improve some measures of postural sway . It is still unclear if joint position sense can be improved in the functionally unstable ankle 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 STUDY DESIGN Prospect i ve , r and omized controlled trial . OBJECTIVE To examine the effects of a 4-week rehabilitation program for chronic ankle instability ( CAI ) on postural control and lower extremity function . BACKGROUND CAI is associated with residual symptoms , performance deficits , and reinjury . Managing CAI is challenging and more evidence is needed to guide effective treatment . METHODS AND MEASURES Subjects with unilateral CAI were r and omly assigned to the rehabilitation ( CAI-rehab , n=16 ) or control ( CAI-control , n=13 ) group . Subjects without CAI were assigned to a healthy group ( n=19 ) . Baseline testing included the ( 1 ) center of pressure velocity ( COPV ) , ( 2 ) star excursion balance test ( SEBT ) , and ( 3 ) Foot and Ankle Disability index ( FADI ) and FADI-Sports Subscale ( FADI-Sport ) . The CAI-rehab group completed 4 weeks of rehabilitation that addressed range of motion , strength , neuromuscular control , and functional tasks . After 4 weeks , all subjects were retested . Nonparametric analyses for group differences and between-group comparisons were performed . RESULTS Subjects with CAI demonstrated deficits in postural control and SEBT reach tasks of the involved limb compared to the uninvolved limb and reported functional deficits of the involved limb compared to healthy subjects . Following rehabilitation , the CAI-rehab group had greater SEBT reach improvements on the involved limb than the other groups and greater improvements in FADi and FADI-Sport scores . CONCLUSIONS These results demonstrate postural control and functional limitations exist in individuals with CAl . In addition , rehabilitation appears to improve these functional limitations . Finally , there is evidence to suggest the SEBT may be a good functional measure to monitor change after rehabilitation for CAI 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 A r and omised controlled trial ( 29 participants ) was used to compare a 6-week proprioceptive and balance exercise program with a 6-week strengthening program in the early phases of rehabilitation after anterior cruciate ligament ( ACL ) reconstruction . Measurements of functional activity were taken by a blinded assessor before the intervention and at the end of the 6 weeks . Results demonstrated that there were no significant differences between groups on hop testing at 6 weeks . For several items in the Cincinnati knee rating system and the patient specific functional scale however , the strengthening group improved more than the proprioceptive and balance group ( p < .05 ) . The hypothesis that proprioceptive and balance training would improve functional activity more than strengthening exercises was not supported . There was either no difference between the two forms of exercise or strength training may be more beneficial than proprioceptive and balance training in the early phase of rehabilitation after ACL reconstructive surgery OBJECTIVES To study the effects of Star Excursion Balance training on functional stability of athletes with ankle sprain . MATERIAL AND METHOD Thirty-two male athletes with grade 2 ankle sprain , aged 15 - 22 years old were enrolled . They were r and om sampling into training group ( n=15 ) and control group ( n=17 ) . All received conventional physical therapy program for 4 weeks . The training group also underwent the Star Excursion Balance training 3 days per week for 4 weeks . Single leg stance time ( SLST ) was assessed at pre- and post-training . Re-injuries were recorded during 3 months follow-up . RESULTS After the program , subjects from both groups demonstrated significant improvement in SLST The training group gained SLST of the injured sides 2 times more than the control group ( p = 0.002 tested with eyes closed , p = 0 . 007 tested with eyes open ) , and also improved the SLST during eyes closed of the normal sides ( p = 0.015 ) . Re-injuries were found in 1/15 of the training group and 2/17 of the control group . CONCLUSION Star Excursion Balance training is more effective than the conventional therapy program in improving functional stability of the sprained ankle Twenty-two university students with unilateral functional instability of the ankle participated in this study . They were r and omly assigned to one of two experimental groups . Subjects in both groups were trained to st and on the affected limb on an ankle disk . In group 1 , two pieces of 1-cm wide nonelastic adhesive tape were applied to the skin around the lateral malleolus from the distal third of the lower leg to the sole of the foot before the training sessions . Subjects in group 2 participated in the training sessions without the application of the adhesive tape . Training was performed for 10 minutes a day , five times per week , for a period of 10 weeks . Subjects were tested for postural sway while st and ing on the affected limb before , during , and after the training period . In group 1 , postural sway values decreased significantly after 4 weeks compared with the pretraining performance , and they were within the normal range after not more than 6 weeks of training . In group 2 , the values did not improve significantly compared with the pretraining performance until after 6 weeks of training , and they were not within the normal range until after 8 weeks of training . The findings suggest that the 2-week earlier correction of postural sway in group 1 was due to an increased afferent input from skin receptors that were stimulated by the traction of the adhesive tape Ankle sprains are often complicated by functional instability and repeated sprains . Rehabilitation with wobble boards in patients with functional instability has been tested , and significant improvement has been found compared to no training . The aim of this study was to investigate whether the number of patients with residual symptoms following ankle sprains could be reduced by training on a wobble board during 12-week recovery period . In addition , the influence of training in the time course reduction of edema was investigated . We performed a prospect i ve study including 61 patients , all active in sports for more than 2 hours a week with primary ankle sprains . The effect of a 12-week training program with wobble board was compared with no training . Forty-eight patients completed the study . In the follow-up period ( mean X = 230 days ) , we found significantly fewer recurrent sprains , and significantly fewer patients in the training group had functional instability of the ankle compared with the no training group . There were no differences in the two groups in the time which elapsed before patients were painless at walking , during running , or at sports . Volumetric measurements revealed no difference in the speed of reduction of hematoma and edema of the ankle and foot between the two groups . We conclude that training on a wobble board early after primary stage 2 ankle sprains is effective in reducing residual symptoms following this lesion and that training does not seem to affect the time course reduction in edema 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 Total sagittal knee laxity and postural control in the sagittal and frontal planes were measured in 25 patients at a mean of 36 months ( range , 27 to 44 ) after anterior cruciate ligament reconstruction and in a control group consisting of 20 uninjured age- and activity-matched subjects . Body sway was measured in the sagittal plane on a stable and on a sway-referenced force plate in single-legged stance , double-legged stance , or both , with the eyes open and closed . Postural reactions to perturbations in the sagittal and frontal planes were recorded in the single-legged stance with the eyes open . Total sagittal plane laxity was significantly greater in the anterior cruciate ligament-reconstructed knee ( 11.2 mm ; range , 6 to 15 ) than in the uninjured knee ( 8.9 mm ; range , 6 to 12 ) or in the control group ( 6.0 mm ; range , 5 to 8) . In spite of this , the patients , in comparison with the controls , exhibited normal postural control except in two variables — the reaction time and the latency between the start of force movement to maximal sway in the sagittal plane perturbations . This supports the hypothesis that rehabilitation , with proprioceptive and agility training , is an important component in restoring the functional stability in the anterior cruciate ligament-reconstructed knee Health status measures are being used with increasing frequency in clinical research . Up to now the emphasis has been on the reliability and validity of these measures . Less attention has been given to the sensitivity of these measures for detecting clinical change . As health status measures are applied more frequently in the clinical setting , we need a useful way to estimate and communicate whether particular changes in health status are clinical ly relevant . This report considers effect sizes as a useful way to interpret changes in health status . Effect sizes are defined as the mean change found in a variable divided by the st and ard deviation of that variable . Effect sizes are used to translate “ the before and after changes ” in a “ one group ” situation into a st and ard unit of measurement that will provide a clearer underst and ing of health status results . The utility of effect sizes is demonstrated from four different perspectives using three health status data sets derived from arthritis population s administered the Arthritis Impact Measurement Scales ( AIMS ) . The first perspective shows how general and instrument-specific benchmarks can be developed and how they can be used to translate the meaning of clinical change . The second perspective shows how effect sizes can be used to compare traditional clinical measures with health status measures in a st and ard clinical drug trial . The third application demonstrates the use of effect sizes when comparing two drugs tested in separate drug trials and shows how they can facilitate this type of comparison . Finally , our health status results show how effect sizes can supplement st and ard statistical testing to give a more complete and clinical ly relevant picture of health status change . We conclude that effect sizes are an important tool that will facilitate the use and interpretation of health status measures in clinical research in arthritis and other chronic diseases PURPOSE The aim of the present study was to investigate the effects of a 6-wk multi-station proprioceptive exercise program that is easy to integrate in normal training programs . METHODS Patients with chronic ankle instability were used , and results of three testing procedures before and afterward were compared : joint position sense , postural sway , and muscle reaction times to sudden inversion events on a tilting platform . A total of 30 subjects with 48 unstable feet were evaluated ( exercise group : N = 31 ; control group : N = 17 ) . RESULTS In the exercise group , the results showed a significant improvement in joint position sense and postural sway as well as significant changes in muscle reaction times . CONCLUSION Based on the present results , a multi-station proprioceptive exercise program can be recommended for prevention and rehabilitation of recurrent ankle inversion injuries BACKGROUND AND PURPOSE Dynamic knee stabilization strategies of people who successfully compensate for the absence of an anterior cruciate ligament ( ACL ) ( " copers " ) are different from those of people who do not compensate well for the injury ( " noncopers " ) . Early after injury , certain patients ( " potential copers " ) can increase the likelihood of successfully compensating for the injury by participating in 10 sessions of perturbation training . The purpose of this study was to determine how perturbation training alters muscle co-contraction and knee kinematics in potential copers . SUBJECTS Seventeen individuals with acute , unilateral ACL rupture who were categorized as potential copers and 17 subjects without injuries who were matched by age , sex , and activity level were recruited for this study . METHODS Motion analysis and electromyographic data were collected as subjects walked across a stationary or moving platform ( horizontal translation ) before and after perturbation training . RESULTS Before training , potential copers had higher co-contraction indexes and lower peak knee flexion angles than subjects without injuries . After training , potential copers ' movement patterns more closely resembled those of subjects without injuries ( ie , they showed reduced co-contraction indexes and increased peak knee flexion angles during stance ) . DISCUSSION AND CONCLUSION Perturbation training reduced quadriceps femoris-hamstring muscle and quadriceps femoris-gastrocnemius muscle co-contractions and normalized knee kinematics in individuals with ACL rupture who were classified as potential copers . Findings from this study provide evidence for a mechanism by which perturbation training acts as an effective intervention for promoting coordinated muscle activity in a select population of people with ACL rupture The purpose of the present study was to evaluate the effectiveness of a special sensorimotor exercise rehabilitation program on shoulder function . In a prospect i ve intervention study we evaluated 32 patients with subacromial pain syndrome , all of whom took part in a conservative rehabilitation program . No patient had surgery on the shoulder involved prior to the study . All patients performed a st and ardised sensorimotor training for the glenohumeral joint , which involved , in particular , the glenohumeral and scapulothoracal stabilisers . In this rehabilitation program special proprioceptive exercise tools ( body-blade , BOING ) were used as well as Tai Chi and aquatic gymnastics . The entire program lasted 4 weeks and was performed and supervised by the same physiotherapist . Prior to and after the program all patients underwent a st and ardised series of tests . These included the Constant- and the UCLA-Score tests and sensorimotor functions with an angle reproduction test , a threshold to motion test as well as isometric strength testing with a Cybex unit . Prior to the rehabilitation program all subjects showed decreased proprioceptive capabilities . This was particularly evident in the threshold to motion test . After 4 weeks of rehabilitation , significant increases in the Constant- and UCLA-Score tests were found . The sensorimotor test also showed an increased proprioceptive capability especially in the threshold to motion test . The angle reproduction test showed only moderate improvement , whereas the isokinetic strength test showed no improvement at all . The present study shows that patients with subacromial pathology suffer from a proprioceptive deficit which can be improved by a special rehabilitation program within only 4 weeks The efficacy of two non-operative rehabilitation programs was studied in a consecutive r and omized controlled clinical trial of 100 patients after 12 months subsequent to an acute anterior cruciate ligament ( ACL ) injury . Follow up of r and omization to two training models was evaluated after 3 and 12 months : A self-monitored training program ( SM ) of traditional mobility and muscle strength training of the injured leg was compared to a supervised ( SV ) training model exercising postural function in closed kinetic-chains . Nearly 50 % of the patients in the SM group required supervision after 6 weeks . An intention-to-treat analysis was performed and showed significantly better values in most of the results of the supervised group at 3 and 12 months . An alternative analysis of subgroups showed a significant difference between transferred male patients and original SV male patients at 3 months but not at 12 months , indicating the importance of initial guiding after an ACL injury . No such difference was observed in the female patients Eight patients with patellar pain underwent knee proprioceptive training . The maximal knee extension torque associated with the Vastus Lateralis EMG signal increased ( p 0.001 and 0.039 ) . Although muscle balance was not improved , all the patients improved their clinical scores The effect of an early rehabilitation program , including postural training , on ankle joint function after an ankle ligament sprain was investigated prospect ively . Ninety-two subjects , matched for age , sex , and level of sports activity , were r and omized to a control or training group . All subject received the same st and ard information regarding early ankle mobilization . In addition , the training group participated in supervised physical therapy rehabilitation ( 1 h , twice weekly ) with emphasis on balance training . Postural sway , position sense and isometric ankle strength were measured 6 weeks and 4 months after the injury , and at 12 months re-injury data were obtained . In the training group , there was a significant difference between the injured and uninjured side for plantar flexion ( P < 0.01 ) , eversion ( P < 0.01 ) and inversion ( P < 0.05 ) , but not for dorsiflexion at 6 weeks . In the control group , there was a significant difference between the injured and uninjured side for plantar flexion ( P < 0.01 ) , eversion ( P < 0.01 ) , inversion ( P < 0.01 ) , and dorsiflexion ( P < 0.05 ) at 6 weeks . Postural sway , but not position sense , differed between the injured and uninjured side in both groups ( P < 0.01 ) at 6 weeks . The side-to-side percent differences were similar in both groups for all variables ( P > 0.05 ) at 6 weeks , and there were no side-to-side differences at 4 months in either group . In the control group , 11/38 ( 29 % ) suffered a re-injury , while this number was only 2/29 ( 7 % ) in the training group ( P < 0.05 ) . These data showed that an ankle injury result ed in reduced ankle strength and postural control at 6 weeks , but that these variables had normalized at 4 months , independent of the supervised rehabilitation . However , the findings also demonstrated that supervised rehabilitation may reduce the number of re-injuries , and therefore may play a role in injury prevention OBJECTIVES The purpose of this study was to determine the effects of a proprioceptive training program ( PT ) vs. a strength training ( ST ) program on neuromuscular function after anterior cruciate ligament ( ACL ) reconstruction . The second purpose was to establish the determinants of functional ability for the operated limb . METHODS Ten participants with unilateral ACL reconstructions were r and omly assigned to one of the following 12-week training protocol s : ( 1 ) isotonic ST , and ( 2 ) PT . The outcome measures were : ( 1 ) peak torque time of the hamstring muscles ( PeakTT ) , ( 2 ) average concentric and eccentric torques of the quadriceps and hamstring muscles , ( 3 ) one-legged single hop for distance ( SLHD ) , ( 4 ) one-legged time hop ( TH ) , and ( 5 ) subjective scores . RESULTS : There was a significant group by time interaction effect for PeakTT ( P = 0.017 ) . The PT group demonstrated greater percent change in isokinetic torques than the ST group at the end of the 12 weeks ( P < or = 0.05 ) . Participants in both groups demonstrated similar significant gains in functional ability and subjective scores ( P < or = 0.014 ) . Quadriceps strength is a determinant of functional ability for the operated limb ( R2 = 0.72 ) . CONCLUSIONS : Both training protocol s influenced PeakTT . The beneficial effects of ST on PeakTT appear to be load-dependent , while sufficient practice may be crucial in maintaining PeakTT improvements induced by PT . Proprioceptive training alone can induce isokinetic strength gains . Restoring and increasing quadriceps strength is essential to maximize functional ability of the operated knee joint CONTEXT Improving postural stability through balance training may prevent ankle sprains . Exercise S and als may increase the dem and s placed on ankle muscles during rehabilitation , which could improve postural stability . OBJECTIVE To examine the effects of functional balance training , with and without the use of Exercise S and als , on postural stability in subjects with stable or unstable ankles . DESIGN Prospect i ve , nonr and omized clinical trial . SETTING Sports medicine research laboratory . PATIENTS OR OTHER PARTICIPANTS Sixteen subjects with functional ankle instability and 16 subjects with no history of ankle sprains . INTERVENTION(S ) Subjects were assigned to an Exercise S and al functional balance training group or a shoe functional balance training group . Subjects trained 3 times per week for 8 weeks and then performed a single-limb stance posttest . MAIN OUTCOME MEASURE(S ) Subjects were required to remain as motionless as possible during a single-limb stance pretest . Anterior-posterior and medial-lateral center-of-pressure excursions were measured . RESULTS Exercise S and al balance training improved anterior-posterior postural stability in both ankle groups ( P < .05 ) . Both training interventions improved medial-lateral postural stability in stable and unstable ankles ( P < .05 ) . CONCLUSIONS Postural stability improved after subjects performed functional balance training programs , both with and without Exercise S and als . Training with Exercise S and als might not be any more effective in improving postural stability than performing functional balance training without Exercise S and als . However , Exercise S and als did not impair postural stability and , consequently , might serve as an alternative therapy to improve postural stability STUDY DESIGN Prospect i ve r and omized longitudinal clinical trial with matched controls . OBJECTIVES To investigate the long-term effect of training on postural control and extremity function after an acute anterior cruciate ligament ( ACL ) injury . BACKGROUND ACL injuries may cause severe problems with recurrent giving way of the knee and reduced functional capacity . The effect of an acute ACL injury and the effect of various training programs on postural control , as well as the relation between postural control and extremity function after such an injury , have not been studied longitudinally . METHODS Sixty-three consecutive patients , 35 men and 28 women ( median age 24 years , quartiles 19 - 33 years ) , with an acute nonoperated ACL injury , r and omized to neuromuscular supervised or self-monitored training , were examined with stabilometry ( amplitude and average speed of center of pressure movements ) and a one-leg hop test for distance after 6 weeks ( stabilometry only ) , and after 3 , 12 , and 36 months , and were compared to a control group . RESULTS Regardless of treatment , center of pressure amplitude was persistently higher in both the injured and uninjured legs during the 3-year follow-up , but average speed was less affected or unaffected compared to the control group . The one-leg hop had normalized in the neuromuscular group at the 12-month follow-up , but was shorter in both legs throughout the 3-year period in the self-monitored group . The median value ( quartiles ) for injured/uninjured legs at 3 months was 150 cm ( 120 - 174 cm)/177 cm ( 140 - 199 cm ) , at 12 months was 174 cm ( 140 - 200 cm)/180 cm ( 150 - 202 cm ) , and at 36 months was 172 cm ( 146 - 200 cm)/178 cm ( 150 - 200 cm ) in the self-monitored group , compared to the control group ( median 186 cm , quartiles 177 - 216 cm ) . CONCLUSIONS The higher center of pressure amplitude in both legs over the 3-year period indicate persistently impaired postural control in single-limb stance . However , functional performance , as measured with the one-leg hop test , was restored by neuromuscular training , but not by self-monitored training |
1,849 | 22,895,956 | There were no significant differences between groups for persistent symptoms , recurrence following treatment , or re-infection following treatment .
There was insufficient data to analyse the effect of antibiotics on renal parenchymal damage , compliance , development of resistant organisms or adverse events .
Although antibiotic treatment is effective for children with UTI , there are insufficient data to answer the question of which type of antibiotic or which duration is most effective to treat symptomatic lower UTI .
This review found that 10-day antibiotic treatment is more likely to eliminate bacteria from the urine than single-dose treatments .
No differences were observed for persistent bacteriuria , recurrence or re-infection between short and long-course antibiotics where the antibiotic differed between groups .
This data adds to an existing Cochrane review comparing short and long-course treatment of the same antibiotic who also reported no evidence of difference between short and long-course antibiotics | BACKGROUND Urinary tract infection ( UTI ) is one of the most common bacterial infections in infants and children .
Lower UTI is the most commonly presenting and in the majority of cases can be easily treated with a course of antibiotic therapy with no further complications .
A number of antimicrobials have been used to treat children with lower UTIs ; however is it unclear what are the specific benefits and harms of such treatments .
OBJECTIVES This review aims to summarise the benefits and harms of antibiotics for treating lower UTI in children . | Abstract Urinary tract infections ( UTI ) can cause acute morbidity and may result in severe problems , including hypertension and reduced renal function . Diagnosis of UTI is extremely important since prompt treatment may prevent damage . In the present study we compared the efficacy of oral cefixime to initial intramuscular ceftizoxime followed by cefixime for the treatment of UTI in children . Fifty-four children were studied . They were r and omized to receive either oral cefixime 8 mg/kg/day for 10 days or initial intramuscular ceftizoxime ( Cefızox ) 50 mg/kg twice a day for 2 days followed by oral cefixime for 8 days . Treatment groups were comparable regarding age , sex , clinical , and laboratory findings . Escherichia coli was isolated from 80 % of patients . Repeat urine cultures were sterile within 24 hours in all children . Cure rates were comparable in both groups ( 92 % vs 86 % at the end of treatment ) . No serious adverse effects were observed . We concluded that oral cefixime is a safe and effective alternative treatment OBJECTIVES To compare the efficacy of 3-day vs 10-day treatment with a combination of amoxicillin and clavulanate potassium for children with uncomplicated urinary tract infections and to determine the role of host factors , including vesicoureteral reflux , and of bacterial virulence factors , including adhesins , in treatment outcome . DESIGN R and omized , double-blind , controlled trial . SETTING A pediatric infectious diseases clinic at an urban medical center . PATIENTS Thirty-seven children with uncomplicated urinary tract infections . INTERVENTIONS Treatment with 3 days or 10 days of antibiotics at a dosage of 20 mg/kg per day of amoxicillin and 5 mg/kg per day of clavulanate potassium in three divided doses . MEASUREMENTS AND MAIN RESULTS The success rate for 10-day treatment was 82 % ( 14/17 ) compared with 55 % ( 11/20 ) for 3-day treatment ( P = .09 ) . Among the 35 patients infected with Escherichia coli , all 10 patients infected with adhesin-negative isolates were treated successfully regardless of the duration of treatment , whereas only 14 ( 56 % ) of the 25 infections involving adhesin-positive isolates were clinical ly cured ( P = .015 ) . Two of the three failures in the 10-day treatment group were in patients with reflux . CONCLUSIONS We conclude that 3-day treatment with amoxicillin and clavulanate is insufficient for afebrile childhood urinary tract infections and that both bacterial and host factors affect treatment outcome Background . The st and ard recommendation for treatment of young , febrile children with urinary tract infection has been hospitalization for intravenous antimicrobials . The availability of potent , oral , third-generation cephalosporins as well as interest in cost containment and avoidance of nosocomial risks prompted evaluation of the safety and efficacy of outpatient therapy . Methods . In a multicenter , r and omized clinical trial , we evaluated the efficacy of oral versus initial intravenous therapy in 306 children 1 to 24 months old with fever and urinary tract infection , in terms of short-term clinical outcomes ( sterilization of the urine and defervescence ) and long-term morbidity ( incidence of reinfection and incidence and extent of renal scarring documented at 6 months by99mTc-dimercaptosuccinic acid renal scans ) . Children received either oral cefixime for 14 days ( double dose on day 1 ) or initial intravenous cefotaxime for 3 days followed by oral cefixime for 11 days . Results . Treatment groups were comparable regarding demographic , clinical , and laboratory characteristics . Bacteremia was present in 3.4 % of children treated orally and 5.3 % of children treated intravenously . Of the short-term outcomes , 1 ) repeat urine cultures were sterile within 24 hours in all children , and 2 ) mean time to defervescence was 25 and 24 hours for children treated orally and intravenously , respectively . Of the long-term outcomes , 1 ) symptomatic reinfections occurred in 4.6 % of children treated orally and 7.2 % of children treated intravenously , 2 ) renal scarring at 6 months was noted in 9.8 % children treated orally versus 7.2 % of children treated intravenously , and 3 ) mean extent of scarring was ∼8 % in both treatment groups . Mean costs were at least twofold higher for children treated intravenously ( $ 3577 vs $ 1473 ) compared with those treated orally . Conclusions . Oral cefixime can be recommended as a safe and effective treatment for children with fever and urinary tract infection . Use of cefixime will result in substantial reductions of health care expenditures Objective To compare the efficacy of oral antibiotic treatment alone with treatment started parenterally and completed orally in children with a first episode of acute pyelonephritis . Design Multicentre , r and omised controlled , open labelled , parallel group , non-inferiority trial . Setting 28 paediatric units in north east Italy . Participants 502 children aged 1 month to < 7 years with clinical pyelonephritis . Intervention Oral co-amoxiclav ( 50 mg/kg/day in three doses for 10 days ) or parenteral ceftriaxone ( 50 mg/kg/day in a single parenteral dose ) for three days , followed by oral co-amoxiclav ( 50 mg/kg/day in three divided doses for seven days ) . Main outcomes measures Primary outcome was the rate of renal scarring . Secondary measures of efficacy were time to defervescence ( < 37 � C ) , reduction in inflammatory indices , and percentage with sterile urine after 72 hours . An exploratory subgroup analysis was conducted in the children in whom pyelonephritis was confirmed by dimercaptosuccinic acid ( DMSA ) scintigraphy within 10 days after study entry . Results Intention to treat analysis showed no significant differences between oral ( n=244 ) and parenteral ( n=258 ) treatment , both in the primary outcome ( scarring scintigraphy at 12 months 27/197 ( 13.7 % ) v 36/203 ( 17.7 % ) , difference in risk −4 % , 95 % confidence interval −11.1 % to 3.1 % ) and secondary outcomes ( time to defervescence 36.9 hours ( SD 19.7 ) v 34.3 hours ( SD 20 ) , mean difference 2.6 ( −0.9 to 6.0 ) ; white cell count 9.8 � 109/l ( SD 3.5 ) v 9.5 � 109/l ( SD 3.1 ) , mean difference 0.3 ( −0.3 to 0.9 ) ; percentage with sterile urine 185/186 v 203/204 , risk difference −0.05 % ( −1.5 % to 1.4 % ) ) . Similar results were found in the subgroup of 278 children with confirmed acute pyelonephritis on scintigraphy at study entry . Conclusions Treatment with oral antibiotics is as effective as parenteral then oral treatment in the management of the first episode of clinical pyelonephritis in children . Trial registration Clinical Trials NCT00161330 Urinary tract infection in children is usually treated with orally administered antibiotics for 10 to 14 days . Because of the unreliability of patient compliance with prescribed medications and because single-dose aminoglycoside therapy has been shown to be effective in women with cystitis , we assessed the efficacy of single-dose amikacin for treatment of first episodes of Escherichia coli lower urinary tract infection in girls . Upper and lower urinary tract infections were presumptively differentiated by simple criteria such as clinical symptoms , fever , and erythrocyte sedimentation rate . Fifty-four girls ( ages 1 to 12 years ) with two positive urine cultures ( greater than 10(5 ) CFU/ml E. coli ) were assigned by a table of r and om numbers to receive treatment with either sulfisoxazole 150 mg/kg/day orally for 10 days or a single dose of amikacin 7.5 mg/kg intramuscularly . Six of 23 patients ( 26 % ) in the amikacin group and four of 21 ( 19 % ) in the sulfisoxazole group had at least one positive urine culture within 40 days after completion of therapy . This difference was not statistically significant ( P greater than 0.5 ) . This suggests that a single dose of amikacin is as effective as a 10-day course of sulfisoxazole in the treatment of presumed first lower urinary tract infection in girls . Additional potential advantages of single-dose therapy are fewer side effects and less toxicity , excellent compliance , and reduced potential for selecting resistant organisms 31 patients with a urinary infection were treated with a single oral dose ( 3 g for adults and 100 mg/kg for children ) of amoxycillin ; 23 ( 74 % ) were cured . 20 women and 26 children were then r and omly allocated to either a single dose of amoxycillin of a 5- to 7-day conventional course of the same antibiotic . The results of both treatment regimens were comparable . Single-dose therapy for the treatment of urinary-tract infections was simple , effective and well tolerated . Patients preferred taking their treatment in this manner . Failure of single-dose therapy to eradicate bacteriuria may indicate which patients require subsequent investigations of their urinary tract Objective . To undertake population pharmacokinetic modeling and to determine the safety and efficacy of once daily ( OD ) gentamicin dosing in children with severe urinary tract infections ( UTI ) . Methods . An open , r and omized , controlled trial comparing OD with three times daily ( TD ) gentamicin dosing in hospitalized children ages 1 month to 12 years with UTI . Daily doses ( milligrams per kg per day ) of gentamicin in both groups were 7.5 ( < 5 years old ) , 6.0 ( 5 to 10 years old ) and 4.5 ( > 10 years old ) . Results . There were 179 children enrolled ( 90 OD , 89 TD ) . Baseline clinical characteristics and pathogens were similar , except that circulatory compromise and renal cortical scintigraphic defects were more common in the OD group . Median gentamicin treatment duration s were 3.0 ( OD ) and 2.7 ( TD ) days . Mean peak gentamicin concentrations were 17.3 ( OD ) vs. 6.4 ( TD ) mg/l ; 99 % of peak concentrations were > 7 mg/l in the OD group whereas 16 % of peak concentrations were < 5 mg/l in the TD group . Mean trough concentrations were 0.35 ( OD ) vs. 0.55 ( TD ) mg/l . In the OD group 4 % of trough concentrations were ≥2 mg/l , whereas in the TD group only 0.7 % were ≥2 mg/l . Age or prior elevated peak concentrations did not predict high trough concentrations . Population pharmacokinetic modeling of the data fitted a one-compartment model with first order elimination . There were no clinical or bacteriologic failures . The two disease-related complications were confined to the OD group . No nephro- or ototoxicity was identified . Conclusions . With age-appropriate dosing and measurement of serum trough concentrations before the second dose , OD gentamicin is safe and effective for the treatment of UTI requiring parenteral treatment in children aged 1 month to 12 years The pharmacokinetics of a low dose of sulfadiazine ( SD 4 mg/kg twice a day , loading dose 8 mg/kg ) were studied and acute urinary tract infection in children treated with this reduced dose . The concentrations of active SD in serum and urine were found to exceed those assumed to be sufficient for the treatment of acute urinary tract infections ( 10 x MIC and 100 x MIC against E. coli , respectively ; MIC = minimum inhibitory concentration ) . The urinary concentrations of both acetylated and non-acetylated SD remained lower than those considered to crystallize in the urinary tract . This suggests that renal damage earlier due to SD overdosage can be avoided by using the present administration . No difference was found in treatment results of acute urinary tract infections in children between SD ( 4 mg/kg twice a day ) and fulfafurazole ( SF ; 50 mg/kg four times a day ) . Only infections caused by sulfonamide-sensitive micro-organisms were treated and all cases were cured . No side-effects could be recorded . SD in lower than the usual dosage would appear to be a practical alternative in the treatment of acute urinary tract infections caused by sulfonamide-sensitive micro-organisms in children Forty-nine ambulatory children between 2 - 1/2 and 12 years of age with acute , clinical ly uncomplicated urinary tract infections caused by susceptible organisms were r and omized to receive a single dose of amoxicillin based on weight or a 10-day course of amoxicillin therapy ( conventional therapy ) . Patients receiving single doses of amoxicillin had a cure rate of 63 % , which compares unfavorably with the cure rate of 92 % in patients given conventional therapy . A failure of single-dose therapy predicted underlying radiologic abnormalities with a sensitivity of 60 % and a specificity of 58 % , making it a poor screening test for detecting those patients at risk for renal parenchymal damage . The antibody-coated bacteria assay had no predictive value in separating upper and lower tract disease , although it may predict underlying radiologic abnormalities . The data indicate that the response to single-dose amoxicillin therapy fails to separate upper from lower tract disease reliably and has a limited role in predicting response to conventional antimicrobial therapy A r and omized , prospect i ve study was done to assess the efficacy of single-dose nu conventional treatment of acute urinary tract infection ( UTI ) in female adolescents . Thirty-one 12- to 18-year-old female adolescents with symptoms of an acute UTI and a urine culture with greater than 10(5 ) organisms were treated with amoxicillin , either as a 3.0-g single dose or 250-mg three times daily for ten days . Urine cultures obtained three days after completing therapy in each group , showed bacteriologic cure rate of 69 % ( 11/16 ) with single-dose treatment compared with a cure rate of 87 % ( 13/15 ) in the conventional treatment group ( P = .23 ) . When patients with resistant organisms were excluded , the cure rate was 85 % in both groups . Complete symptom resolution in less than two days after commencing treatment occurred in 36 % of single-dose group nu none of the patients in the conventional-dose group . The finding has not been previously reported in single-dose trials . C and ida vaginitis occurred in 20 % of the conventional-dose group nu none of the single-dose group . All patients in the single-dose group kept their first scheduled follow-up appointment , whereas 40 % in the conventional group required reminders and rescheduling . Perfect compliance with the medication regimen was reported by 27 % of the patients taking ten days of medicine . Although single-dose cure rates may not be superior to conventional-dose rates , the advantages of single-dose treatment include increased compliance with medication and follow-up , decreased side effects , and more rapid resolution of symptoms The carbapenem antibiotic ertapenem has been shown to be safe , well tolerated and effective in treating adults with complicated urinary tract infection , skin and soft-tissue infection and community-acquired pneumonia . In this study , we evaluated ertapenem for treating these infections in children in a r and omised , double-blind , active-controlled clinical trial . The primary outcome was the incidence of clinical and laboratory drug-related serious adverse events ( AEs ) . Children were r and omised in a 3:1 ratio ( ertapenem : ceftriaxone ) stratified by index infection and age to receive ertapenem or ceftriaxone ; 303 children received ertapenem and 100 children received ceftriaxone . The median duration of parenteral therapy was 4 days for both treatments . The most commonly reported drug-related clinical AEs during parenteral therapy were diarrhoea ( 5.9 % ertapenem , 10 % ceftriaxone ) , infusion site erythema ( 3 % ertapenem , 2 % ceftriaxone ) and infusion site pain ( 5 % ertapenem , 1 % ceftriaxone ) . One child in each group reported a serious drug-related clinical AE . No serious drug-related laboratory AEs were reported . In children aged 3 months to 17 years , ertapenem was well tolerated and had a comparable safety profile to that of ceftriaxone Aim : To examine the safety and efficacy of once‐daily ( OD ) gentamicin treatment compared with conventional 8‐hourly dosing ( TDS ) for urinary tract infection ( UTI ) . Methods : This was a prospect i ve , r and omized , controlled trial of children 1 mo to 13 y of age with presumed UTI . Children were r and omly assigned to OD gentamicin 5 mg kg−1 d−1 or TDS gentamicin 6 mg kg−1 d−1 divided 8 hourly . Microbiological efficacy , nephrotoxicity , ototoxicity and renal scarring were assessed at the end of treatment . Results : 210 patients with presumed UTI were recruited , of whom 172 were analysable ( OD 84 , TDS 88 ) . The median age was 7 mo , 50 % were male and 74 % ( n= 127 ) of patients had pyelonephritis . The majority of infections were due to Escherichia coli ( n= 153 , 89 % ) , of which 9 ( 5.2 % ) were bacteraemic . Comparing the two groups , there was no significant difference in age , gender , duration of fever before admission , pyuria , nitrite positivity or initial total white blood cell count . All patients had negative urine cultures after 2–3 d of treatment , demonstrating 100 % microbiological efficacy . There was no difference between the two groups in terms of ototoxicity , nephrotoxicity , duration of gentamicin treatment or time to fever defervescence A r and omised clinical trial of single dose trimethoprim against a seven day course of co-trimoxazole ( trimethoprim/sulphamethoxazole ) for the treatment of uncomplicated urinary tract infection was carried out in 106 children aged between 2 and 16 years . Of the 50 children with confirmed urinary tract infections who were followed up 48 hours after treatment with a single dose of trimethoprim all were free of infection , whereas two of the 56 who received the course of co-trimoxazole ( 4 % ) had persisting infections . At follow up after 10 days , however , significantly more of the group treated with trimethoprim had evidence of recurrent urinary tract infection compared with those who had received co-trimoxazole ( 10 of 44 , 23 % , compared with one of 46 , 2 % ) . Of the recurrences in the trimethoprim group , six were asymptomatic . We conclude that single dose trimethoprim is effective in clearing the urine of bacteria , but the risk of asymptomatic bacteriuria soon after treatment is high Seventy-nine children with symptoms of urinary tract infections were r and omly allocated to treatment with a single dose or a 7-day course of trimethoprim-sulphamethoxazole . Of the 42 patients ( 39 girls , 3 boys ) who fulfilled the criteria for the trial , 23 were given a single-dose regimen and 19 of them a 7-day regimen . Both groups of patients had sterile urine cultures 2 days after starting treatment . Eight patients had underlying structural renal abnormalities ( n = 3 , single-dose regimen ; n = 5 , 7-day regimen ) . One patient in the single dose group had a recurrence of infection on day 7 . These results show that single dose trimethoprim-sulphamethoxazole is as effective as the conventional 7-day course in children with symptomatic urinary tract infection . Further investigation of the renal tract is necessary regardless of the fact that the infection has been eradicated by single-dose treatment We conducted a r and omized prospect i ve multicenter study to compare the safety and efficacy of once daily oral cefixime ( 8 mg/kg ) to twice daily oral trimethoprim/sulfamethoxazole ( TMP/SMX ) ( 8/10 mg/kg/day ) for the treatment of acute urinary traet infection in children ages 6 months to 13 years . Seventy-six patients ( 38 in each group ) were studied . Thirty-seven percent were younger than 3 years of age . Escherichia coli was the most common isolate in both groups ( 85 % ) . Eighty-five percent of all Gramnegative organisms were susceptible to TMP/SMX and all were susceptible to cefixime . Seventy-two percent of all patients were febrile at the time of diagnosis . Both groups were treated for 7 to 10 days . Peripheral white blood In a prospect i ve study of children with an acute infection of the lower urinary tract , the effectiveness of a 3-day course of cephalexin , 25 - 50 mg/kg body weight and day was compared with that of a 10-day course of nitrofurantoin , 3 - 4 mg/kg/day . 19 children were allotted to treatment with cephalexin and 24 were treated with nitrofurantoin . The immediate cure rates were 90 % and 96 % , respectively . Two relapses were noted in the cephalexin group and 1 in the nitrofurantoin group . During a mean follow-up period of 7 - 8 months 2 of the cephalexin treated patients and 4 patients treated with nitrofurantoin had a reinfection . No side effects were noted in either of the treatment groups . The results suggest that treatment with cephalexin for 3 days is a reasonable alternative in children with an acute lower urinary tract infection when commonly used medications for one reason or another are less well tolerated The safety and efficacy of cefetamet pivoxil , an oral cephalosporin of the third generation , have been studied in open , prospect i ve , r and omized comparative , clinical trials including 301 toddlers ( children aged 1 to 2 years ) with upper and lower respiratory tract infections , and urinary tract infections . Cefetamet pivoxil ( CAT ) syrup formulation was given to 177 toddlers either in the st and ard dose of 10 mg/kg b.i.d . [ n = 116 ] or 20 mg/kg b.i.d . [ n = 61 ] and 124 toddlers have been treated with comparator drugs [ cefaclor , n = 98 ; phenoxymethylpenicillin , n = 18 ; amoxicillin plus clavulanic acid ; n = 8 ] . The treatment period was 7 days mainly , except for pharyngotonsillitis for which the treatment duration was 7 or 10 days . The assessment of treatment was based on clinical signs and symptoms primarily in infections of lower respiratory tract and acute otitis media , whereas in patients with pharyngotonsillitis and acute urinary tract infections the bacteriological findings were the main evaluation criteria . The overall therapeutic outcome was successful in 148 ( 95.4 % ) of the 155 toddlers to whom CAT was administered and in 87 ( 85.3 % ) out of 102 toddlers receiving st and ard drugs . Adverse events of mild to moderate severity , mainly of gastro-intestinal type ( vomiting or diarrhoea ) occurred in 14.7 % in the patient group receiving CAT , 11.2 % in the toddlers receiving the st and ard dose of CAT , and in 12.9 % with the comparator drugs . From the data presented it is concluded that cefetamet pivoxil is efficient and safe in toddlers presenting with community-acquired respiratory and urinary infections mainly caused by S. pneumoniae , H. influenzae , Group A beta-haemolytic streptococci , M. catarrhalis , E. coli , Proteus spp . and K. pneumoniae A r and omized , open , coordinated multi-center trial compared the bacteriological and clinical efficacy and safety of orally administered ceftibuten and trimethoprim-sulfamethoxazole ( TMP-SMX ) in children with febrile urinary tract infection ( UTI ) . Children aged 1 month to 12 years presenting with presumptive first-time febrile UTI were eligible for enrolment . A 2:1 assignment to treatment with ceftibuten 9 mg/kg once daily ( n = 368 ) or TMP-SMX ( 3 mg + 15 mg)/kg twice daily ( n = 179 ) for 10 days was performed . Escherichia coli was recovered in 96 % of the cases . Among the E. coli isolates , 14 % were resistant to TMP-SMX but none to ceftibuten . In the modified intention-to-treat population , the bacteriological elimination rates at follow-up did not differ significantly between patients treated with ceftibuten and those treated with TMP-SMX [ 91 vs. 95 % , with a 95 % confidence interval ( CI ) for difference of −9.7 to 1.0 ] . However , the clinical cure rate was significantly higher among those treated with ceftibuten ( 93 vs. 83 % , with a 95 % CI for difference of 2.4 to 17.0 ) . Adverse events were similar for both regimens and consisted mainly of gastrointestinal disturbances . In conclusion , ceftibuten is a safe and effective drug for the empirical treatment of febrile UTI in young children Forty-nine girls between the ages of 2 and 18 years with a symptomatic urinary tract infection documented by two clean-catch urine cultures completed a double-blind study comparing the effectiveness of three days versus ten days of nitrofurantoin macrocrystal therapy . Localization of the infection to the lower urinary tract was presumed on the basis of clinical presentation . All patients had sterile urine on day two or three of therapy . In the ten-day group , two of 23 patients ( 8.7 % ) experienced a single relapse , and seven patients ( 30 % ) had 12 episodes of reinfection during a six-month follow-up . In the three-day group , two of 26 patients ( 7.7 % ) had a single relapse , and six patients ( 23 % ) had 12 episodes of reinfection . The rates of relapse and reinfection in the compared groups were not statistically significantly different ( P greater than 0.05 ) . Three days of treatment with nitrofurantoin macrocrystals is an effective regimen for symptomatic girls presumed to have uncomplicated lower urinary tract infections Thirty-seven patients with a median age of 5 years with symptomatic lower or upper urinary tract infection , documented by a clean-catch midstream urine culture and sediment examination , completed a r and omized study comparing the effectiveness of a single dose of cefotaxime with 10-day treatment with an antibiotic chosen by in-vitro sensitivities . Eighteen patients were r and omly assigned to the cefotaxime group ( 50 mg/kg/im route ) and 19 patients were placed in the 10-day therapy group . In the cefotaxime group 4/18 patients had an upper urinary tract infection and 11/18 had a history of recurrences . The causal organisms were Escherichia coli ( 16 cases ) and Klebsiella pneumoniae ( two cases ) . All patients had sterile urine 48 hours after therapy , and 2/18 cases had recurred 28 days later . In the 10-day treatment group , 7/19 patients had an upper urinary tract infection , 6/19 had a history of recurrences , 17 cases were caused by E. coli , one case by Citrobacter freundii and one case by K. pneumoniae . Eighteen of 19 patients had sterile urine 48 hours after therapy and 1 case remained symptomatic with positive culture . The other 18 patients had no recurrences . Rates of cures and recurrence in the compared groups were not statistically different ( P greater than 0.05 ) This study was design ed to determine whether serum C-reactive protein ( CRP ) concentrations could be used to identify children with uncomplicated lower urinary tract infection who would respond favorably to short-term antibiotic therapy . A one-day or ten-day regimen of cefadroxil ( 30 mg/kg/day in two divided doses ) was assigned r and omly to 80 children who had acute urinary tract infection and CRP concentrations less than 28 microgram/ml ( CRP-negative group ) . Ten days of cefadroxil therapy was used to treat 44 children with urinary tract infection and CRP values greater than or equal to 28 microgram/ml ( CRP-positive group ) . The clinical and laboratory characteristics of the children in the two CRP-negative therapy groups were similar to , but different from those of children with CRP-positive infections . Recurrent infections occurred significantly more often at four to five days after completion of therapy in CRP-negative children who received one day ( 44.4 % ) compared to ten days ( 20 % ) of cefadroxil therapy ( P less than .05 ) . When data from this study were combined with those from our previously published investigation of short-term antibiotic therapy in CRP-negative children , a significantly larger percentage of recurrences was documented immediately after one or four days of antibiotics ( 79 % ) compared to recurrences after the st and ard ten-day regimen ( 41 % ) . Additionally , the total rate of recurrent infections for all children in both studies was significantly larger in those who received short-term therapy ( 48 % ) as opposed to conventional therapy ( 34 % ) . These data indicate that short-term antibiotic therapy is less effective than the conventional ten-day regimen in children with CRP-negative urinary tract infection Summary Ampicillin and trimethoprim/sulfamethoxazole were shown to be of similar efficacy in the treatment of acute urinary tract infection of children . It was of interest to determine the effects of these antimicrobial drugs on the periurethral flora and recurrence rates . To this end , seventeen girls with twenty-two separate infections of the urinary tract were treated r and omly with a ten-day course of either ampicillin or trimethoprim/sulfamethoxazole . Cultures of the urine and periurethral area were obtained before , during ( third day ) , and after ( seventeenth day ) therapy . AllEscherichia coli strains were serotyped . Both treatments result ed in the disappearance of the pathogens from the urine by the third day in all cases , and in all but one patient on the seventeenth day . The causative agents persisted more frequently in the periurethral area than in the urine on both the third and seventeenth days in patients treated with either ampicillin or trimethoprim/sulfamethoxazole . The recurrence rates by the seventeenth day were 50 % ( 4/8 ) in the ampicillin group , and 14 % ( 2/14 ) in the trimethoprim/sulfamethoxazole group . Although suggestive in favor of the latter treatment , the difference is not statistically significant . In two of the three re-infections in the ampicillin group the microorganisms causing the second attack were present in the periurethral area on the third day . Sixteen of the seventeen girls were studied radiologically ; six ( 37 % ) had radiologic abnormalities . ZusammenfassungEs wurde gezeigt , daß Ampicillin und Trimethoprim/Sulfamethoxazol eine ähnliche Wirkung in der Beh and lung der akuten Harnwegsinfektion bei Kindern haben . Es war unser Anliegen , die Wirkung dieser antimikrobiellen Substanzen auf die periurethrale Flora und die Rückfallraten zu bestimmen . Dazu wurden siebzehn Mädchen mit 22 abgegrenzten Harnwegsinfektionen nach R and om-Verfahren zehn Tage lang mit Ampicillin oder Trimethoprim/Sulfamethoxazol beh and elt . Kulturen von Urin und periurethraler Region wurden vor , während ( dritter Tag ) und nach ( siebzehnter Tag ) der Beh and lung angelegt . AlleEscherichia coli-Stämme wurden serotypisiert . Beide Beh and lungsformen führten zu einem Verschwinden der pathogenen Keime aus dem Urin am dritten Tag in allen Fällen und bei allen außer einem Patienten am siebzehnten Tag . Die Entzündungserreger persistierten häufiger in der periurethralen Region als i m Urin sowohl am dritten Tag als auch am siebzehnten Tag bei Patienten , die entweder mit Ampicillin oder Trimethoprim/Sulfamethoxazol beh and elt wurden . Die Rückfallraten am siebzehnten Tag betrugen 50 % ( 4/8 ) in der Ampicillin-Gruppe und 14 % ( 2/14 ) in der Trimethoprim/Sulfamethoxazol-Gruppe . Obwohl sich eine Tendenz zugunsten des letztgenannten Beh and lungsmodus annehmen läßt , ist der Unterschied nicht statistisch signifikant . Bei zwei der drei Reinfektionen in der Ampicillin-Gruppe waren die Mikroorganismen , die den zweiten Schub auslösten , am dritten Tag in der periurethralen Region anwesend . Sechzehn der siebzehn Mädchen wurden röntgenologisch untersucht . Sechs ( 37 % ) hatten röntgenologische Zeichen für Fehlbildungen Summary In a prospect i ve study , 43 children between three months and 16 years of age and suffering from an acute infection of the lower urinary tract , were treated for either three or ten days with 4/16 mg trimethoprim/sulphadiazine/kgBW/day in two doses . Twenty-three were allotted to treatment for three days , whereas 20 were treated for ten days . Irrespective of the duration of therapy , the urine of all patients was sterile when urinary cultures were made three to seven days after the cessation of therapy . An early recurrence within the two months following the completion of treatment occurred in two children in each treatment group . In no case of recurrence was the organism resistant to trimethoprim/sulphadiazine . During a mean follow-up period of 11 months , 21.7 % of the children treated for three days and 35 % of those treated for ten days experienced a recurrence . The results suggest that children with an uncomplicated lower urinary tract infection can be successfully treated with a three-day course of trimethoprim/sulphadiazine in a conventional dosage . ZusammenfassungIn einer prospektiven Studie erhielten 43 Kinder mit Infektionen der unteren Harnwege , i m Alter zwischen 3 Monaten und 16 Jahren , 4/16 mg Trimethoprim/Sulphadiazin/kgKG/Tag in zwei Dosen . Die Therapiedauer betrug entweder drei oder zehn Tage . 23 Kindern wurde eine dreitägige , 20 eine zehntägige Therapie verordnet . Unabhängig von der Therapiedauer waren bei allen Patienten die Urinkulturen drei bis sieben Tage nach Therapieende steril . In beiden Gruppen trat bei je zwei Kindern ein Frührezidiv innerhalb der ersten beiden Monate nach Therapieende auf . In keinem dieser Fälle war der pathogene Erreger resistent gegenüber Trimethoprim/Sulphadiazin . Während einer mittleren Beobachtungszeit von elf Monaten trat bei 21,7 % der über drei Tage beh and elten Kinder ein Rezidiv auf . Aus den Ergebnissen läßt sich schließen , daß Kinder mit unkomplizierter Harnwegsinfektion mit einer dreitägigen Therapie mit Trimethoprim/Sulphadiazin in der üblichen Dosierung erfolgreich beh and elt werden können The efficacy of 3-day therapy with nalidixic acid in 16 children , and trimethoprim/sulphamethoxazole in 19 children , was studied prospect ively in children with an acute infection of the lower urinary tract and compared with that of a conventional 10-day course with the same drugs . The immediate cure rate was 97 % in the 3-day group and 90 % in the 10-day group . During 3 months of follow-up there were altogether six re-infections in children given short-term treatment and six in the conventionally treated group . The results give further support for the suggestion that 3-day therapy is equivalent to 10-day treatment in uncomplicated urinary infections in children and that both nalidixic acid and trimethoprim/sulphamethoxazole are good alternatives in such an approach Thirty-five children with a history of vesicoureteric reflux or with recurrent urinary tract infections were r and omly allocated to low-dose prophylactic treatment with pivmecillinam or nitrofurantoin . After 6 - 10 months they were crossed over to the alternate drug for another 6 months , but only 24 completed the study because of lack of compliance or intolerance to nitrofurantoin . There was no significant difference in the long-term prophylactic effect between the two drugs , the overall infection rate being 0.7/patient-year . Pivmecillinam was significantly better tolerated than nitrofurantoin ( P = 0.01 ) . Nitrofurantoin effected no major change in the faecal flora , and nearly all urinary infections occurring during long-term treatment were caused by Escherichia coli . In contrast , a marked reduction of E. coli and a marked increase in Gram-positive cocci were found in the faecal flora during treatment with pivmecillinam . Seventy per cent of infections were caused by Streptococcus faecalis and only 20 % by E. coli during pivmecillinam treatment ( P = 0.001 ) OBJECTIVE To determine whether the addition of a single dose of ceftriaxone sodium to a 10-day course of trimethoprim and sulfamethoxazole hastens urine sterilization or resolution of clinical symptoms in febrile children with urinary tract infections . DESIGN Prospect i ve , single-blind , r and omized study . SETTING Tertiary care children 's hospital emergency department . PATIENTS Febrile children aged 6 months to 12 years with a presumptive urinary tract infection based on history , physical examination , and urinalysis findings . INTERVENTIONS A history was taken , a physical examination and urinalysis and culture were performed , and a white blood cell count and erythrocyte sedimentation rate were obtained . Children were r and omized to receive an intramuscular dose of ceftriaxone then 10 days of trimethoprim-sulfamethoxazole ( IM + PO group ) or oral trimethoprim-sulfamethoxazole alone ( PO group ) . After receiving study medication , patients were discharged from the hospital to return in 48 hours for a follow-up evaluation and urine culture . Treatment failure was defined as the persistence of a positive culture at 48 hours or the need for hospital admission for intravenous rehydration or antibiotic therapy . RESULTS Sixty-nine children were enrolled , 34 in the IM + PO group and 35 in the PO group . The 2 groups were similar at the initial visit with respect to age , sex , clinical degrees of illness , white blood cell count , and erythrocyte sedimentation rate ( P>.05 ) . At the 48-hour follow-up visit , there were no differences between the 2 treatment groups in resolution of vomiting , fever , general appearance , abdominal tenderness , and hydration state ( P>.05 ) . There were 9 treatment failures , 4 in the IM + PO group and 5 in the PO group ( P = .93 ) . CONCLUSION The addition of a single dose of intramuscular ceftriaxone to a 10-day course of oral trimethoprim-sulfamethoxazole for urinary tract infection with fever result ed in no difference at 48 hours in the urine sterilization rate , degree of clinical improvement , or subsequent hospital admission rate The effect of trimethorpim-sulfamethoxazole was compared with that of sulfamethoxazole alone in 26 children with urinary tract infection , r and omly assigned according to a double-blind procedure to two equally sized groups . TMX-SMX was found to be superior in rendering the urine culture negative for the 3 months after the start of treatment . Also , over 12-month follow-up period there were fewer recurrences in the patients who received TMP-SMX but here the difference between the two groups did not reach statistical significance Results of single-dose therapy of urinary tract infections in pediatric patients have been contradictory mainly because of selection criteria . We evaluated the efficacy of a single dose of gentamicin in patients with normal urinary tracts and in whom urinary tract infections were recurrent . Twenty-one patients were included in the study , and a similar number in a conventional group given treatment for 10 days . Cure rate was 100 % in both groups . The recurrence rates of 67 % in the study and 52 % in the conventional group were comparable . Single-dose therapy seems to have a role in the treatment of urinary tract infection in the absence of urinary tract malformation 28 children with initial episodes of urinary tract infection were treated with cotrimoxazole or cotrifamole ( dose ratio 3 : 2 ) for 14 days in a prospect i ve r and omized double blind trial . The two groups did not differ as regards clinical signs . The efficacy and cure rates of each regimen were similar . Laboratory studies ( hemoglobin , WBC , liver , and renal function ) showed no differences between both groups before and after therapy ; an alteration of the laboratory values could not be observed during therapy . The number of children with X-ray abnormalities of kidneys and urinary tract was similar in both groups . During an observation time of up to 12 months after the first urinary tract infection no differences in the number of reinfections and relapses were observed . As a result of this study , we recommend cotrifamole in a lower dose ( ratio 2 : 3 ) than cotrimoxazole for the treatment of urinary tract infection ABSTRACT . The efficacy of single dose treatment with trimethoprim compared to a 5‐day course with the same drug was investigated in 100 children , 3–12 years , with isolated episodes of symptomatic non‐febrile urinary tract infection . Cure , defined as sterile urine during the first week after treatment , was achieved in 74 % ( 37150 ) in the single dose group compared to 8696 ( 43/50 ) in the 5day treatment group . The difference was not statistically significant ( χ2= 2.25 , p=0.134 two‐tailed ) . The cure rates in relation to P‐fimbriation of the infecting E. coli strains were similar in the two groups . During the 6 month follow‐up , six children in each treatment group had one or more reinfections . Extended studies are needed to conclude if single dose and conventional treatment courses are equally effective Fourty-nine patients aged 6 months to 12 years old with suspected urinary tract infection ( UTI ) were evaluated in this open r and omized study . Twenty-seven patients received gentamicin 4.5 mg/kg/d once daily ( OD group ) and 22 patients received the same daily dose in three divided doses ( TID group ) for 3 days before being switched to amoxy-clavulanic acid . Ninety-six per cent ( 26/27 ) of the OD group had peak gentamicin within therapeutic level while 40 per cent ( 9/22 ) of the TID group had peak gentamicin within therapeutic level . One in OD group had high gentamicin level due to technical error in obtaining blood sample . None in neither group had trough level in toxic level . Only 24 patients had confirmed UTI and were evaluated for clinical efficacy and toxicity . Demographic data were the same in both groups except there were more males in OD group ( 8:3 vs 4:9 ) . Patients in OD group became afebrile earlier than TID group ( 8.69 vs 15.31 hours ) but no statistically significant difference . All patients had negative urine culture results within 48 hours . None had clinical nephrotoxicity in both groups . More patients in TID group had laboratory nephrotoxicity ( 5/11 vs 2/13 ) but no statistically significant difference . We conclude that gentamicin can be given safely and efficiently as single daily dose or thrice daily but more cost effective and less time consuming in once daily dose A total of 118 children between 6 months and 10 years of age with acute urinary tract infection were treated in a r and om ; double-blind manner with 12 mg/kg/day of trimethoprim-sulfamethoxazole ( 61 patients ) or 50 mg/kg/day of sulfamethoxazole ( 57 patients ) for ten days . Mean trimethoprim and sulfamethoxazole susceptibilities of Escherichia coli isolated from these patients were 1.2 and 0.6 microgram/ml , respectively . Mean serum concentrations of trimethoprim and sulfamethoxazole were 1.8 and 62 microgram/ml , respectively , one hour after the dose . Of the children who completed the ten days of prescribed medication , clinical and bacteriological cure was confirmed immediately after treatment for all but one patient in each group . Most patients in each treatment group with recurrent infections had underlying urological abnormalities . Severe hematological , renal , or hepatic toxicity requiring interruption of treatment was not encountered . No advantage of trimethoprim-sulfamethoxazole over sulfamethoxazole alone for acute urinary tract infection was demonstrated The aim of the study was to determine the efficiency of Uro-Vaxom in the treatment of recurrent urinary tract infection in children . We examined 19 girls in aged 4 - 17 years treated in our Department since Jan 1998 until Jan 1999 for of recurrent urinary tract infection induced by E. coli ( RUTI ) . All girls have been cured with Uro-Vaxom in single daily dose for 3 months . Disappearance of RUTI in 47 % of children and decrease in RUTI in 42 % reveals that Uro-Vaxom plays significant role in the treatment of this disease The patients were 117 children ( aged 4 months to 14 years ) with uncomplicated urinary tract infections caused by co-trimoxazole-sensitive Escherichia coli . The patients were r and omly assigned to receive treatment with co-trimoxazole for 3 days ( n = 58 ) or 7 days ( n = 59 ) . Urine was analyzed for bacteria before and immediately after treatment and again at 1 and 2 months . After 3 days ' treatment , infection persisted in 14 of 31 patients with P-fimbriated strains of E coli and in 1 of 27 patients with non-P-fimbriated strains . After 7 days ' treatment , infection persisted in 2 of 40 patients with fimbriated strains and in none of the 19 patients with nonfimbriated strains . One or 2 months after treatment , 3 days ' treatment was rated successful in 26 of 27 patients with nonfimbriated strains and in none of the patients with fimbriated strains . Seven days ' treatment was rated successful in all patients with nonfimbriated strains and in 32 of 40 patients with fimbriated strains . The results indicate that the length of treatment of urinary tract infections in children should be adjusted according to the presence of bacterial P-fimbriae in addition to the patients ' clinical condition Abstract The aim of this study was to compare the efficacy of prophylactic trimethoprimsulfamethoxazole ( TMP/SMZ ) , cefprozil and cephadroxil treatments in children who have recurrent urinary tract infection , but no urinary tract pathology . After acute urinary tract infections ( UTIs ) were treated , the patients were divided into 3 groupsr and omly and TMP/SMZ was given to 21 patients , cephadroxil was given to 25 patients and cefprozil was given to 34 patients for 3 months — one dose at night . All patients were followed for 6 months following prophylaxis . The frequency of symptomatic UTIs among groups during prophylaxis was not statistically different , however the number of symptomatic UTIs in the cephadroxil group was lower than the other groups . Asymptomatic bacteriuria episodes were detected in TMP/SMZ and cefprozil groups , whereas no asymptomatic bacteriuria episodes were seen in the cephadroxil group . The number of patients with symptomatic UTI during the follow-up period was not different between groups , however all the asymptomatic bacteriuria episodes were encountered in the cefprozil group . In conclusion , in this study cephadroxil was found to be slightly superior to TMP/SMZ and cefprozil in preventing asymptomatic bacteriuria episodes and symptomatic UTIs in children with recurrent UTI and normal urinary tract system Sixty-nine children with urinary tract infections were r and omly allocated to single dose gentamicin therapy ( n = 39 ) or a seven day course of an appropriate antibiotic ( n = 30 ) . During the following six weeks the response to treatments did not differ and this was not altered by the child 's clinical diagnosis , past history of infection or presence of radiological abnormalities . The poorest response was in those children with a history of recurrent infections ( p less than 0.01 ) and /or radiological abnormality ( p less than 0.02 ) . Single dose therapy had significantly less suppression upon rectal ( p less than 0.001 ) and periurethral ( p less than 0.02 ) flora . There was a tendency for those not cured by single dose treatment to relapse whereas those treated by conventional therapy tended to be reinfected PATIENTS AND METHODS In a prospect i ve cohort study from 251 centers in Germany patients with age of 4 years or above who were treated due to acute sinusitis , bronchitis or urinary tract infections ( UTI ) in the period from 1st March 2004 - 30th July 2005 , were elected . They were included in the study analysis , if they had no exclusion criteria ( severe diseases , need for antibiotic therapy , participation in another trial ) and came to the final investigation . The patients were treated either with the nasturtium herb and horseradish root containing herbal drug Angocin Anti-Infekt N ( test group , n = 1223 ) or with st and ard antibiotic therapy ( control group , n = 426 ) . Treatment , dosage and treatment duration were determined by the physician in accordance with the patient . 536 subjects ( 408 test , 128 control patients ) suffered from acute sinusitis , 634 subjects ( 469 test , 165 control patients ) from acute bronchitis and 479 subjects ( 346 test , 133 control patients ) from UTI . At study start and end the severity of the symptoms were judged by the investigator and quantified with 4 scores ( 0 = no symptom , 3 severe symptom ) . During the treatment information on use of medication , concomitant procedures and adverse events ( AEs ) in a patient diary . At the end of the study ( disease free or after 7 - 14 days ) the patient returned to the investigator , who recorded the vital parameters , finally judged the treatment efficacy and potential persisting symptoms on the basis of score values . Primary efficacy criterion was the change of the complaints quantified by the change of the relative symptom score averaged over all symptoms and related to the baseline value . RESULTS In patients with acute sinusitis the mean relative reduction of the averaged symptom score was 81.3 % for the test group and 84.6 % for the control group , in patients with acute bronchitis the mean reduction was 78.3 % for the test group and 80.3 % for the control group , in patients with UTI 81.2 % for the test group and 87.9 % for the control group . The 95 % confidence interval for the difference of the expected reductions between test and control group was -8.5 % to 1.8 % for acute sinusitis , 7.6 % to 3.6 % for acute bronchitis and -13.1 % to -0.1 % for UTI . Non-inferiority of the test treatment , i.e. if the lower limit of the 95 % confidence interval is greater than 10 % , could be stated for acute sinusitis and bronchitis . In UTI the non-inferiority level was exceeded only by 3 % . Complementary procedures were less in the test group than in the control group . For 1.5 % of test patients and 6.8 % of control patients AEs were observed CONCLUSION Therapy with the herbal drug in the indications acute sinusitis , acute bronchitis und acute urinary tract infection is - with regard to its efficacy comparable to the treatment with st and ard antibiotics . The application of supportive procedures and the administration of concurrent medication were less expressed in the group treated with the herbal drug . In the above mentioned indications the group treated with the herbal drug displayed a clear advantageous safety profile compared to the group treated with st and ard antibiotics In a double-blind trial 45 children aged 6 months to 14 years with Escherichia coli infections of the urinary tract were given co-trimoxazole for two weeks and then allotted at r and om to one of two treatment groups for the remainder of six months ; one continued with the active drug and the other with dummy tablets of identical appearance . Of the 24 children who took co-trimoxazole for two weeks and the 21 who took it for six months , 11 and 10 , respectively , remained without further infections for at least a year . Over 90 % of the reinfections occurred within five months of stopping the antibiotics , and the longer treatment did not cause any delay in their appearance . Thus probably a six-month course of treatment is no more likely to achieve a cure than a two-week course ; nevertheless , no infection occurred during treatment , and there may be an advantage in continuing with antibiotics in small dosage 16 children , aged 1 - 10 years , suffering from urinary tract infection were r and omly divided into two groups . Ten children were treated with ampicillin pediatric suspension in a dose of 100 mg ampicillin/kg/24 hours divided in 4 doses , and 6 children with pivampicillin base pediatric suspension in a dose of 64.8 mg/kg/24 hours divided in 4 doses ( approximately 50 mg ampicillin/kg ) . The treatment period was 14 days with all infections being cured . Despite the fact that pivampicillin was administered in half of the dosage of ampicillin the result ing peak serum concentration was 65 % higher and was achieved more rapidly . The bioavailability and urine concentration were also greater . A marked change in the rectal aerobic bacterial flora occurred during both treatment regimens . In 13 children ( 81 % ) a shift took place from ampicillin-sensitive E. coli to ampicillin-resistant Klebsiella strains as the predominating microbe , equally often in both groups of treatment . Ampicillin-resistant E. coli appeared in one child in each group A double blind , comparative study of the efficacy of cephalexin versus sulfis oxazole was conducted on 100 children with initial episodes of urinary tract infections . The overall bacteriologic and clinical cure rates were comparable for both antimicrobials . Children treated with cephalexin had a clinical cure rate of 86 per cent and a bacterial cure rate of 84 per cent , while those given sulfisoxazole were found to have rates of 82 and 92 per cent respectively . However , cephalexin was noted to have a rather high rate of failure in the therapy of Proteus mirabilis infections ( 4/8 ) , casting some doubt on its use in urinary infections caused by this organism . Untoward effects associated with either medication were minimal In nine separate clinical trials , 382 patients having symptoms of either prostatitis , acute cystitis , urethritis , and /or trigonitis were r and omly assigned to treatment with flavoxate or phenazopyridine . Over-all response was evaluated in 384 patients after five days of therapy . In patients having prostatitis , response was satisfactory in 66 per cent treated with flavoxate and 31 per cent treated with phenazopyridine . In all other patients , satisfactory responses were reported in 80 per cent on flavoxate compared with 56 per cent on phenazopyridine . Similarly , symptom-severity evaluations at two and five days of therapy showed most symptoms improved in more of the patients on flavoxate therapy than on phenazopyridine therapy . Although more adverse effects were reported in patients treated with phenazopyridine than with flavoxate , the difference between medications was not statistically significant Thirty-six girls , aged two to 17 years , with culture-proven , acute , uncomplicated lower urinary tract infections and without signs or symptoms of upper urinary tract infection , were r and omized to receive either single-dose amoxicillin or conventional therapy for ten days . Twenty-six patients completed the study , ten in the single-dose group and 16 in the conventional therapy group . The patients treated with single-dose therapy had cure rates ( 70 % vs 75 % ) , relapse rates ( 30 % vs 25 % ) , and reinfection rates ( 0 % vs 12 % ) comparable to those of conventionally treated patients . A significant difference in the induction of resistant organisms was seen between treatment groups ( P less than .05 ) . All single-dose relapses were due to failure to clear a sensitive organism from the urinary tract . All relapses on conventional therapy result ed from an initially sensitive organism becoming resistant to amoxicillin during treatment . Single-dose antibiotic therapy of uncomplicated urinary tract infections in children is effective in patients with culture-proven infections selected by clinical criteria , and appears to be safe when combined with conscientious long-term follow up and radiographic evaluation . Single-dose therapy offers the advantage of selecting significantly fewer resistant organisms from the gut flora than do conventional antibiotic regimens The activity of pidotimod ( (R)-3-[(S)-(5-oxo-2-pyrrolidinyl ) carbonyl]-thiazolidine-4-carboxylic acid , PGT/1A , CAS 121808 - 62 - 6 ) was studied vs. placebo in a double-blind , r and omized , multicentre trial , involving 60 pediatric patients with recurrent urinary tract infections . Recovery from acute events was quicker with pidotimod than with placebo ( 9.6 vs. 12.3 days ) . In treated patients antibiotic therapy was shorter ( 6.9 vs. 8.3 days ) and main symptomatic parameters ( body temperature , vesical tenesmus , stranguria , pollakiuria , total number of symptoms , total symptomatic intensity , rate of asymptomatic patients , haematuria , leukocyturia , positive urinary culture ) receded quickly . In patients receiving the drug as well as in patients treated with placebo changes in laboratory parameters were observed , indicating recovery from the acute infectious disease . A significant trend to normalization of the immune response , expressed by chemotaxis and index of leukocyte phagocytosis , was found only in patients treated with pidotimod . After the acute episode a significant decrease of risk of relapses ( 69 % ) was observed in these patients . If a relapse occurs , the response of treated patients is quicker ( duration of fever , total time of relapses ) than for control patients . These findings allow to correlate the individual immune response activation to the resistance to recurrent infections and also to a better response to therapy if the disease occurs and becomes clinical ly relevant . No side effects were observed . Mild reactions ( 4 nausea/vomiting , 1 erythema ) occurred only in 5 patients ( 2 pidotimod , 3 placebo ) but were attributed to concomitant antibiotic therapy . No alterations of main laboratory parameters were found . These findings confirm the tolerability of the drug also in long-term treatment . ( ABSTRACT TRUNCATED AT 250 WORDS We conducted a prospect i ve r and omized study to evaluate the efficacy of a single daily dose of 4 mg/kg of trimethoprim coupled with 17.5 mg/kg of sulphadiazine for three ( group 1 ) or 10 days ( group 2 ) in the treatment of uncomplicated urinary tract infections in children . Forty patients ( nine boys and 31 girls ) aged 2.5‐18 years , presenting with a urinary tract infection were allocated to one of the two groups . Patients were seen three , 10 , and 38 days after the initiation of treatment . Control urine cultures were negative in all patients at days 3 and 10 . Two patients in group 1 and one patient in group 2 suffered a relapse within a month . Single doses of trimethoprim/sulphadiazine for three or 10 days are effective in the treatment of uncomplicated urinary tract infections in children One hundred thirty-two children with acute urinary tract infection were r and omly assigned to receive trimethoprim-sulfamethoxazole in one dose , two doses daily for 3 days or two doses daily for 7 days . The patient characteristics , etiologic agents and frequency of roentgenologic abnormalities were similar for the three treatment groups . There was no significant difference in bacteriologic cure rates for the single dose regimen ( 93 % ) and multidose regimens ( 96 % ) . The difference in rates of recurrent urinary tract infection between the single dose ( 20.5 % ) and 3-day ( 5.6 % ) and 7-day ( 8 % ) regimens was statistically significant ( P = 0.033 ) . A single dose of trimethoprim-sulfamethoxazole is inadequate treatment for infants and children with acute urinary tract infection It is very important to treat patients with upper urinary tract infections ( UTIs ) promptly and effectively because of the potential sequelae . In the present study we compare the efficacy of the two cephalosporins , ceftriaxone and cefotaxime , in childhood pyelonephritis . The study protocal included 10 days of drug therapy . Both in patients receiving ceftriaxone and cefotaxime , successful eradication was achieved at the second day of therapy . The overall cure rate was significantly better in the ceftriaxone group than the cefotaxime group in terms of recurrence and reinfections ( p < 0.05 ) . Furthermore , in the complicated group , ceftriaxone was slightly superior to cefotaxime , approaching significance in terms of preventing recurrent infections . No serious adverse effects were observed in either of the groups . The present study has shown that ceftriaxone exhibits favorable clinical and bacteriologic efficacy in patients with complicated and uncomplicated upper UTI . Once-daily injection of ceftriaxone in children is also an attractive advantage of the drug when compared to twice-daily cefotaxime Abstract Children older than one year of age with urinary-tract infection were r and omly allocated to treatment for three weeks with co-trimoxazole or ampicillin . Those with a raised serum-creatinine or with bacteria resistant to the allocated drug were excluded . During or within four days of the end of treatment , 11 out of 40 children treated with ampicillin developed recurrent bacteriuria , compared with only 3 out of 55 with co-trimoxazole ; the difference seemed to be more prominent in patients with abnormalities of the urinary tract . In vitro , of 11 strains cultured during recurrent bacteriuria in children treated with ampicillin , all were resistant to ampicillin but all except 1 were sensitive to co-trimoxazole . Of 3 strains appearing in the group treated with co-trimoxazole , 2 were resistant and 1 sensitive to both drugs . For the next three months , prophylactic nitrofurantoin was prescribed ; the rate of recurrent bacteriuria four days after the end of this prophylaxis was not different in the groups treated earlier with either ampicillin or co-trimoxazole . The broader spectrum of antibacterial action is believed to cause the better efficacy of co-trimoxazole . Thrombocytes decreased progressively to below 150,000 per c.mm . in 10 out of 55 children treated with co-trimoxazole , compared with only 1 out of 44 receiving ampicillin . As early as four days after the end of treatment with co-trimoxazole , counts returned to more than 150,000 in all children save 1 . No bleeding occurred in any child . Trimethoprim-induced interference with folate metabolism by inhibition of dihydrofolate reductase is supposed to cause the depression of thrombocytes Abstract . Pylkkänen , J. , Vilska , J. and Koskimies , O. ( The Children 's Hospital , University of Helsinki , Helsinki , Finl and ) . The length of antimicrobial therapy in upper vs. wer urinary tract infection of childhood . Acta Paediatr Sc and , 70 : 885 , 1981.‐235 infants and children were r and omized to a 10‐day and 42‐day treatment group and followed‐up for 12 months after their first urinary tract infection . The anatomical level of each symptomatic infection was determined using simple laboratory criteria . The two regimens prescribed were equally effective in eradicating the infection , but after the discontinuation of the 10‐day treatment with sulfafurazole , 17 ( 23 % ) of 73 patients with their first upper urinary tract infection experienced a recurrence within one month , as compared to only one ( 1 ) of 76 subjects in the 42‐day therapy group . After the phase of early recurrence , there was no difference in recurrence rate between these groups . The early recurrences were associated with the patient 's early age and a short duration of symptoms before therapy . The recurrence rate of first lower UTI after 10‐day therapy was significantly lower than that after 42‐day treatment . The duration of antimicrobial therapy for childhood urinary tract infection should be adjusted according to the patient 's age and the anatomical level of the infection . 10‐day treatment may not be sufficient to prevent early recurrence of pyelonephritic infections in infants under 6 months of age Subjects were in- patients with bacterial urinary tract infections , ranging in age 4 months to 11 years 4 months . As a rule , daily dose was either four 125 mg ( in potency ) suppositories or four 125 mg ( in potency ) oral form given at 6-hour intervals over a period of 5 days . The number of children subjected to this study was 105 . These children were divided into 2 groups ( suppository 54 ; oral form 51 ) with matched pretreatment background factors . Therapeutic effectiveness rates were 70.4 % for the suppository and 66.7 % for the oral form , and no significant difference was observed between the 2 groups . Rates of efficacy by severity , presence or absence of underlying and /or complication diseases , daily dose and causative microorganisms did not differ significantly between the 2 groups . There was no significant difference in time-courses of improvement of clinical signs and symptoms between the 2 groups . Eradication rates for causative microorganisms were 65.9 % for the suppository and 62.5 % for the oral form . Most frequently isolated causative microorganisms were Escherichia coli and Proteus mirabilis . No significant differences were recognized in the therapeutic effect and usefulness evaluated by physicians in charge . The frequency of side effects did not differ significantly between the suppository group ( 6 with diarrhea and 1 with anal pain : 12.1 % ) and the oral form group ( 5 with diarrhea , 1 with displeasure and 1 with vomiting : 12.7 % ) . Abnormal laboratory findings appeared in 6 cases ( 2 with eosinophilia , 2 with increased GOT and 2 with increased GPT ) in the suppository group and 7 cases ( 2 with eosinophilia , 2 with thrombocytosis , 2 with increased GOT and 1 with increased GPT ) in the oral form group Short-course therapy for pediatric urinary tract infection ( UTI ) remains controversial . The present study was undertaken to compare the effectiveness of cefuroxime axetil ( Ceftin ) as short-course ( 2-day ) versus conventional ( 10-day ) therapy for uncomplicated pediatric UTIs . In a r and omized , controlled , prospect i ve study , we enrolled 50 children , 2 - 11 years of age , to receive oral cefuroxime axetil , 125 mg twice a day , for either 2 or 10 days . UTI was defined as at least 10(5 ) colonies/ml of a single pathogen isolated on clean catch , or at least 10(4 ) colonies/ml on a catheterized specimen . A 10-fold or greater reduction in colony count of the initially isolated organism ( 3 - 5 ) days after stopping therapy was considered a bacteriologic success , as long as the absolute colony count was below the threshold for UTI described above . Patients were followed for 15 months with multiple repeat urine cultures and radiologic studies . Twenty-five of the 50 patients enrolled were withdrawn , including 12 for initially inadequate colony counts . Eight of 12 patients in the short-course group ( 67 % ) , versus 12 of 14 in the conventional-therapy group ( 86 % ) , were initial bacteriological successes , a nonsignificant difference . All 37 initially isolated uropathogens were sensitive to cefuroxime axetil in vitro . Cefuroxime axetil is an effective antimicrobial for uncomplicated pediatric UTIs . Two-day therapy with cefuroxime axetil appears to be as effective as 10-day therapy , although sample size was limited in this study |
1,850 | 29,039,970 | There were clear indications for non-linear dose-response relationships between whole grains , fruits , nuts , dairy , and red meat and CHD .
Conclusion : An optimal intake of whole grains , vegetables , fruits , nuts , legumes , dairy , fish , red and processed meat , eggs and SSB showed an important lower risk of CHD , stroke , and HF | ABSTRACT Background : Despite growing evidence for food-based dietary patterns ' potential to reduce cardiovascular disease risk , knowledge about the amounts of food associated with the greatest change in risk of specific cardiovascular outcomes and about the quality of meta- evidence is limited .
Therefore , the aim of this meta- analysis was to synthesize the knowledge about the relation between intake of 12 major food groups ( whole grains , refined grains , vegetables , fruits , nuts , legumes , eggs , dairy , fish , red meat , processed meat , and sugar-sweetened beverages [ SSB ] ) and the risk of coronary heart disease ( CHD ) , stroke and heart failure ( HF ) . | BACKGROUND Fruit and vegetables is a heterogeneous food group with different content of dietary fiber , vitamins , minerals , carotenoids , and bioactive phytochemicals . Our objective was to examine the relation between specific consumption of fruit and vegetable subgroups and stroke risk in a cohort of Swedish women and men . METHODS AND RESULTS We prospect ively followed 74,961 participants ( 34,670 women and 40,291 men ) who had completed a food frequency question naire in the autumn of 1997 and were free from stroke , coronary heart disease , and cancer at baseline . Diagnoses of stroke in the cohort during follow-up were ascertained from the Swedish Hospital Discharge Registry . A total of 4089 stroke cases , including 3159 cerebral infa rct ions , 435 intracerebral hemorrhages , 148 subarachnoid hemorrhages , and 347 unspecified strokes , were ascertained during 10.2 years of follow-up . The multivariable relative risk ( RR ) of total stroke for the highest vs. lowest category of total fruit and vegetable consumption was 0.87 ( 95 % confidence interval [ CI ] 0.78 - 0.97 ; P for trend = 0.01 ) . The association was confined to individuals without hypertension ( corresponding RR , 0.81 ; 95 % CI , 0.71 - 0.93 ; P for trend = 0.01 ) . Among individual fruits and vegetable subgroups , inverse associations with total stroke were observed for apples/pears ( RR , 0.89 ; 95 % CI , 0.80 - 0.98 ; P for trend = 0.02 ) and green leafy vegetables ( RR , 0.92 ; 95 % CI , 0.81 - 1.04 ; P for trend = 0.03 ) . CONCLUSION This study shows an inverse association of fruit and vegetable consumption with stroke risk . Particularly consumption of apples and pears and green leafy vegetables was inversely associated with stroke Background There is some evidence that the association of fish and marine fatty acids with stroke risk differs between men and women . We investigated the gender-specific associations of habitual intake of the marine fatty acids eicosapentaenoic acid ( EPA ) plus docosahexaenoic acid ( DHA ) and fish on incident stroke in a population -based study in the Netherl and s. Methods We prospect ively followed 20,069 men and women , aged 20–65 years , without cardiovascular diseases at baseline . Habitual diet was assessed with a vali date d 178-item food frequency question naire . Incidence of stroke was assessed through linkage with mortality and morbidity registers . Cox proportional hazards models were used to estimate multivariable-adjusted hazard ratios ( HR ) and 95 % confidence intervals ( 95%CI ) . Results During 8–13 years of follow-up , 221 strokes occurred . In women , an inverse dose-response relation ( P-trend = 0.02 ) was observed between EPA-DHA intake and incident stroke , with an HR of 0.49 ( 95 % CI : 0.27–0.91 ) in the top quartile of EPA-DHA ( median 225 mg/d ) as compared to the bottom quartile ( median 36 mg/d ) . In men , the HR ( 95%CI ) for the top quartile of EPA-DHA intake was 0.87 ( 0.51–1.48 ) ( P-trend = 0.36 ) . Similar results were observed for fish consumption and stroke incidence . Conclusion A higher EPA-DHA and fish intake is related to a lower stroke risk in women , while for men an inverse association could not be demonstrated CONTEXT Although increased intake of grain products has been recommended to prevent cardiovascular disease ( CVD ) , prospect i ve data examining the relation of whole grain intake to risk of ischemic stroke are sparse , especially among women . OBJECTIVE To examine the hypothesis that higher whole grain intake reduces the risk of ischemic stroke in women . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve cohort of 75,521 US women aged 38 to 63 years without previous diagnosis of diabetes mellitus , coronary heart disease , stroke , or other CVDs in 1984 , who completed detailed food frequency question naires ( FFQs ) in 1984 , 1986 , 1990 , and 1994 , and were followed up for 12 years as part of the Nurses ' Health Study . MAIN OUTCOME MEASURE Incidence of ischemic stroke , confirmed by medical records , by quintile of whole grain intake according to FFQ responses . RESULTS During 861,900 person-years of follow-up , 352 confirmed incident cases of ischemic stroke occurred . We observed an inverse association between whole grain intake and ischemic stroke risk . The age-adjusted relative risks ( RRs ) from the lowest to highest quintiles of whole grain intake were 1.00 ( referent ) , 0.68 ( 95 % confidence interval [ CI ] , 0.49 - 0.94 ) , 0.69 ( 95 % CI , 0.51 - 0.95 ) , 0.49 ( 95 % CI , 0.35 - 0.69 ) , and 0.57 ( 95 % CI , 0.42 - 0.78 ; P = .003 for trend ) . Adjustment for smoking modestly attenuated this association ( RR comparing extreme quintiles , 0.64 ; 95 % CI , 0.47 - 0.89 ) . This inverse association remained essentially unchanged with further adjustment for known CVD risk factors , including saturated fat and transfatty acid intake ( multivariate-adjusted RR comparing extreme quintiles , 0.69 ; 95 % CI , 0.50 - 0.98 ) . The inverse relation between whole grain intake and risk of ischemic stroke was also consistently observed among subgroups of women who never smoked , did not drink alcohol , did not exercise regularly , or who did not use postmenopausal hormones . No significant association was observed between total grain intake and risk of ischemic stroke . CONCLUSIONS In this cohort , higher intake of whole grain foods was associated with a lower risk of ischemic stroke among women , independent of known CVD risk factors . These prospect i ve data support the notion that higher intake of whole grains may reduce the risk of ischemic stroke BACKGROUND The evidence supporting recommendations to limit intake of cholesterol rich foods is inconclusive . We aim ed to examine the association between egg consumption and carotid atherosclerosis phenotypes , and the association with clinical vascular events in a prospect i ve , urban , multi-ethnic population . METHODS AND RESULTS The Northern Manhattan Study is a population based cohort to determine stroke incidence , risk factors and prognosis . A sub-cohort of 1429 NOMAS participants with both carotid ultrasounds and comprehensive dietary information was evaluated ( mean ± SD age of participants 65.80 ± 8.80 , 40 % male , 18 % white , 20 % black , 60 % Hispanic ) . The association between egg consumption and carotid intima media thickness ( cIMT ) was assessed with linear regression . Logistic and quantile regression was used to examine the association between egg consumption and carotid plaque presence , thickness , and area . The relation between egg consumption and clinical vascular events ( N = 2669 ) was examined with Cox models . The mean total cIMT was 0.91 ± 0.08 mm and 58 % had carotid plaque present . Increasing egg consumption was inversely associated with cIMT , plaque presence , thickness , and area , in models adjusted for demographics , vascular risk factors and diet . For every additional egg consumed per week , the risk of plaque decreased by 11 % ( 95 % CI 3%-18 % ) . No association was detected between egg consumption and risk of clinical vascular outcomes , over a mean follow up of 11 years and after adjustment for covariates . CONCLUSIONS Frequency of egg consumption in the low to moderate range was inversely related to several markers of carotid atherosclerosis . No association with clinical vascular events , including stroke , was detected . Our findings do not support current vascular health guidelines suggesting the extreme limitation or avoidance of egg consumption due to its cholesterol content BACKGROUND Data on the relation of plasma and dietary omega-3 ( n-3 ) fatty acids ( FAs ) with heart failure ( HF ) risk have been inconsistent . OBJECTIVE We evaluated the relation of n-3 FAs with HF in US male physicians . DESIGN We used nested case-control ( n = 1572 ) and prospect i ve cohort study design s ( n = 19,097 ) . Plasma phospholipid n-3 FAs were measured by using gas chromatography , and food-frequency question naires were used to assess dietary n-3 FAs and fish intake . Incident HF was ascertained via annual follow-up question naires and vali date d in a sub sample . RESULTS The mean age was 58.7 y at blood collection . In a multivariable model , plasma α-linolenic acid ( ALA ) was associated with a lower risk of HF in a nonlinear fashion ( P-quadratic trend = 0.02 ) , and the lowest OR was observed in quintile 4 ( 0.66 ; 95 % CI : 0.47 , 0.94 ) . Plasma EPA and DHA were not associated with HF , whereas plasma docosapentaenoic acid ( DPA ) showed a nonlinear inverse relation with HF for quintile 2 ( OR : 0.55 ; 95 % CI : 0.39 , 0.79 ) . Dietary marine n-3 FAs showed a trend toward a lower risk of HF in quintile 4 ( HR : 0.81 ; 95 % CI : 0.64 , 1.02 ) and a nonlinear pattern across quintiles . Fish intake was associated with a lower risk of HF , with RRs of ~0.70 for all categories of fish consumption greater than one serving per month . CONCLUSIONS Our data are consistent with an inverse and nonlinear relation of plasma phospholipid ALA and DPA , but not EPA or DHA , with HF risk . Fish consumption greater than once per month was associated with a lower HF risk Background — Sugar-sweetened beverage consumption is associated with weight gain and risk of type 2 diabetes mellitus . Few studies have tested for a relationship with coronary heart disease ( CHD ) or intermediate biomarkers . The role of artificially sweetened beverages is also unclear . Methods and Results — We performed an analysis of the Health Professionals Follow-Up Study , a prospect i ve cohort study including 42 883 men . Associations of cumulatively averaged sugar-sweetened ( eg , sodas ) and artificially sweetened ( eg , diet sodas ) beverage intake with incident fatal and nonfatal CHD ( myocardial infa rct ion ) were examined with proportional hazard models . There were 3683 CHD cases over 22 years of follow-up . Participants in the top quartile of sugar-sweetened beverage intake had a 20 % higher relative risk of CHD than those in the bottom quartile ( relative risk=1.20 ; 95 % confidence interval , 1.09–1.33 ; P for trend < 0.01 ) after adjustment for age , smoking , physical activity , alcohol , multivitamins , family history , diet quality , energy intake , body mass index , pre-enrollment weight change , and dieting . Artificially sweetened beverage consumption was not significantly associated with CHD ( multivariate relative risk=1.02 ; 95 % confidence interval , 0.93–1.12 ; P for trend=0.28 ) . Adjustment for self-reported high cholesterol , high triglycerides , high blood pressure , and diagnosed type 2 diabetes mellitus slightly attenuated these associations . Intake of sugar-sweetened but not artificially sweetened beverages was significantly associated with increased plasma triglycerides , C-reactive protein , interleukin-6 , and tumor necrosis factor receptors 1 and 2 and decreased high-density lipoprotein , lipoprotein(a ) , and leptin ( P<0.02 ) . Conclusions — Consumption of sugar-sweetened beverages was associated with increased risk of CHD and some adverse changes in lipids , inflammatory factors , and leptin . Artificially sweetened beverage intake was not associated with CHD risk or biomarkers The authors aim ed to evaluate the association of the traditional Mediterranean diet and major food groups with incidence of and mortality from cerebrovascular disease ( CBVD ) in a Mediterranean population . The study population was a cohort of 23,601 participants from the Greek segment of the EPIC Study ( European Prospect i ve Investigation into Cancer and Nutrition ) who were free of cardiovascular diseases and cancer at baseline ( 1994 - 1999 ) . Diet was assessed by means of a vali date d food frequency question naire . A 10-point scale integrating key Mediterranean diet characteristics was used to assess the participants ' degree of adherence to this diet . During a median follow-up period of 10.6 years ( 1994 - 2009 ) , 395 confirmed incident cases and 196 deaths from CBVD were recorded . Using Cox proportional hazards regression and adjusting for potential confounders , increased adherence to the Mediterranean diet , as measured by 2-point increments in score , was inversely associated with CBVD incidence ( adjusted hazard ratio = 0.85 , 95 % confidence interval : 0.74 , 0.96 ) and mortality ( adjusted hazard ratio = 0.88 , 95 % CI : 0.73 , 1.06 ) . These inverse trends were mostly evident among women and with respect to ischemic rather than hemorrhagic CBVD and were largely driven by consumption of vegetables , legumes , and olive oil . These data provide support for an inverse association of adherence to the Mediterranean diet with CBVD incidence and mortality BACKGROUND Previous studies have suggested that a high dietary intake of fruit and vegetables is associated with a reduced risk of ischemic stroke . The magnitude of the effect is uncertain , and only one study reported data on the intake of specific fruit and vegetables and the risk of stroke . OBJECTIVE We examined whether the intake of fruit and vegetables is associated with a reduced risk of ischemic stroke , with particular attention paid to specific fruit and vegetables and subtypes of ischemic stroke . DESIGN In a prospect i ve cohort study of 54,506 men and women who were included in the Danish Diet , Cancer , and Health study from 1993 to 1997 , estimated total intakes of fruit and vegetables ( in g/d ) were extracted from a semiquantitative food-frequency question naire completed at baseline . Data about subjects hospitalized with ischemic stroke were obtained from the Danish National Registry of Patients and were verified later by record review s. The follow-up for ischemic stroke ended on the date of a first hospital admission for stroke or transient ischemic attack , the date of death or emigration , or the end of the study , whichever came first . RESULTS We identified 266 cases of ischemic stroke involving hospitalization during 168,388 person-years of follow-up ( median follow-up : 3.09 y ; range : 0.02 - 5.10 y ) . After adjustment for potential confounders , persons in the top quintile of fruit and vegetable intake ( median : 673 g/d ) had a risk ratio of ischemic stroke of 0.72 ( 95 % CI : 0.47 , 1.12 ) relative to persons in the bottom quintile of intake ( median : 147 g/d ) ( P for trend = 0.04 ) . When comparing the top quintile with the bottom quintile , an inverse association was most evident for fruit intake ( risk ratio : 0.60 ; 95 % CI : 0.38 , 0.95 ; P for trend = 0.02 ) . Similar risk estimates were seen for most types of fruit and vegetables , although the risks were significant only for citrus fruit . CONCLUSION An increased intake of fruit may reduce the risk of ischemic stroke BACKGROUND Prospect i ve data relating fruit and vegetable intake to cardiovascular disease ( CVD ) risk are sparse , particularly for women . OBJECTIVE In a large , prospect i ve cohort of women , we examined the hypothesis that higher fruit and vegetable intake reduces CVD risk . DESIGN In 1993 we assessed fruit and vegetable intake among 39876 female health professionals with no previous history of CVD or cancer by use of a detailed food-frequency question naire . We subsequently followed these women for an average of 5 y for incidence of nonfatal myocardial infa rct ion ( MI ) , stroke , percutaneous transluminal coronary angioplasty , coronary artery bypass graft , or death due to CVD . RESULTS During 195647 person-years of follow-up , we documented 418 incident cases of CVD including 126 MIs . After adjustment for age , r and omized treatment status , and smoking , we observed a significant inverse association between fruit and vegetable intake and CVD risk . For increasing quintiles of total fruit and vegetable intake ( median servings/d : 2 . 6 , 4.1 , 5.5 , 7.1 , and 10.2 ) , the corresponding relative risks ( RRs ) were 1.0 ( reference ) , 0.78 , 0.72 , 0.68 , and 0.68 ( 95 % CI comparing the 2 extreme quintiles : 0.51 , 0.92 ; P : for trend = 0.01 ) . An inverse , though not statistically significant , trend remained after additional adjustment for other known CVD risk factors , with RRs of 1.0 , 0.75 , 0.83 , 0.80 , and 0.85 ( 95 % CI for extreme quintiles : 0.61 , 1.17 ) . After excluding participants with a self-reported history of diabetes , hypertension , or high cholesterol at baseline , the multivariate-adjusted RR was 0.45 when extreme quintiles were compared ( 95 % CI : 0.22 , 0.91 ; P : for trend = 0.09 ) . Higher fruit and vegetable intake was also associated with a lower risk of MI , with an adjusted RR of 0.62 for extreme quintiles ( 95 % CI : 0.37 , 1.04 ; P : for trend = 0.07 ) . CONCLUSION These data suggest that higher intake of fruit and vegetables may be protective against CVD and support current dietary guidelines to increase fruit and vegetable intake BACKGROUND A reduction in dietary cholesterol is recommended to prevent cardiovascular disease ( CVD ) . Although eggs are important sources of cholesterol and other nutrients , limited and inconsistent data are available on the effects of egg consumption on the risk of CVD and mortality . OBJECTIVE We aim ed to examine the association between egg consumption and the risk of CVD and mortality . DESIGN In a prospect i ve cohort study of 21,327 participants from Physicians ' Health Study I , egg consumption was assessed with an abbreviated food question naire . Cox regression was used to estimate relative risks . RESULTS In an average follow-up of 20 y , 1550 new myocardial infa rct ions ( MIs ) , 1342 incident strokes , and 5169 deaths occurred . Egg consumption was not associated with incident MI or stroke in a multivariate Cox regression . In contrast , adjusted hazard ratios ( 95 % CI ) for mortality were 1.0 ( reference ) , 0.94 ( 0.87 , 1.02 ) , 1.03 ( 0.95 , 1.11 ) , 1.05 ( 0.93 , 1.19 ) , and 1.23 ( 1.11 , 1.36 ) for the consumption of < 1 , 1 , 2 - 4 , 5 - 6 , and > or = 7 eggs/wk , respectively ( P for trend < 0.0001 ) . This association was stronger among diabetic subjects , in whom the risk of death in a comparison of the highest with the lowest category of egg consumption was twofold ( hazard ratio : 2.01 ; 95 % CI : 1.26 , 3.20 ; P for interaction = 0.09 ) . CONCLUSIONS Infrequent egg consumption does not seem to influence the risk of CVD in male physicians . In addition , egg consumption was positively related to mortality , more strongly so in diabetic subjects , in the study population BACKGROUND Heart failure is highly prevalent among older adults and is associated with high cost and societal burden . Although previous studies have reported beneficial effects of dietary factors on heart failure predictors , no previous study has examined whether frequent consumption of nuts is associated with a lower risk of heart failure in a large prospect i ve cohort . OBJECTIVE We examined the association between nut consumption and incident heart failure to determine whether such a relation is modified by overweight or obesity . DESIGN This was a prospect i ve cohort study of 20,976 participants from the Physicians ' Health Study I. Nut consumption was assessed with a simple abbreviated food question naire , and self-reported heart failure was ascertained by follow-up question naires . We used Cox regression to estimate relative risks of heart failure . RESULTS After an average follow-up of 19.6 y , 1,093 new cases of heart failure occurred . Nut consumption was not associated with the risk of developing heart failure in this cohort : multivariable adjusted hazard ratios were 1.0 ( reference ) , 0.98 ( 95 % CI : 0.83 , 1.15 ) , 1.06 ( 95 % CI : 0.89 , 1.27 ) , and 1.01 ( 95 % CI : 0.84 , 1.22 ) for nut consumption of < 1 , 1 , and > or = 2 servings/wk , respectively ( P for linear trend : 0.64 ) . The lack of a meaningful relation between nut intake and incident heart failure was seen in both lean and overweight or obese participants ( P for interaction : 0.96 ) . CONCLUSION Our data do not provide evidence for an association between nut consumption and incident heart failure in US male physicians . However , our data can not rule out possible benefits of nut consumption on subtypes of heart failure not prevalent in this cohort BACKGROUND Previous studies have suggested that a daily intake of 3 servings of whole-grain foods is associated with a reduced risk of coronary heart disease ( CHD ) . However , methods for the assessment of whole-grain intake differ . Furthermore , any additional effects of added bran and germ , which are components of whole grains , have not been reported . OBJECTIVE The objective was to evaluate the association of whole-grain , bran , and germ intakes ( with the use of new quantitative measures ) with the incidence of CHD . DESIGN This was a prospect i ve cohort study of 42,850 male health professionals aged 40 - 75 y at baseline in 1986 who were free from cardiovascular disease , cancer , and diabetes . Daily whole-grain , bran , and germ intakes were derived in grams per day from a detailed semiquantitative dietary question naire . RESULTS During 14 y of follow-up , we documented 1818 incident cases of CHD . After cardiovascular disease risk factors and the intakes of bran and germ added to foods were controlled for , the hazard ratio of CHD between extreme quintiles of whole-grain intake was 0.82 ( 95 % CI : 0.70 , 0.96 ; P for trend=0.01 ) . The hazard ratio of CHD in men with the highest intake of added bran was 0.70 ( 95 % CI : 0.60 , 0.82 ) compared with men with no intake of added bran ( P for trend < or = 0.001 ) . Added germ was not associated with CHD risk . CONCLUSION This study supports the reported beneficial association of whole-grain intake with CHD and suggests that the bran component of whole grains could be a key factor in this relation OBJECTIVE The objective of the present study was to examine the relationship of dietary fried fish consumption and risk of cardiovascular events and all-cause mortality . DESIGN Prospect i ve cohort study among participants of the REasons for Geographic And Racial Differences in Stroke ( REGARDS ) study who resided in the USA . SETTING The primary outcome measures included the hazard ratios ( HR ) of incident CVD including first incident fatal or non-fatal ischaemic stroke or myocardial infa rct ion and all-cause mortality , based on cumulative average fish consumption ascertained at baseline . SUBJECTS Participants ( n 16 479 ) were enrolled between 2003 and 2007 , completed the self-administered Block98 FFQ and were free of CVD at baseline . RESULTS There were 700 cardiovascular events over a mean follow-up of 5·1 years . After adjustment for sociodemographic variables , health behaviours and other CVD risk factors , participants eating ≥2 servings fried fish/week ( v. < 1 serving/month ) were at a significantly increased risk of cardiovascular events ( HR=1·63 ; 95 % CI 1·11 , 2·40 ) . Intake of non-fried fish was not associated with risk of incident CVD . There was no association found with dietary fried or non-fried fish intake and cardiovascular or all-cause mortality . CONCLUSIONS Fried fish intake of two or more servings per week is associated with an increased risk of cardiovascular events . Given the increased intake of fried fish in the stroke belt and among African Americans , these data suggest that dietary fried fish intake may contribute to geographic and racial disparities in CVD Adherence to the Mediterranean diet ( MD ) has been reported to improve CHD prognosis and to be inversely associated with CHD mortality . The aim of the present study was to investigate the association of adherence to the MD with CHD incidence and mortality in the Greek European Prospect i ve Investigation into Cancer and Nutrition cohort , a population with traditional Mediterranean roots . In a general population sample of 23,929 adult men and women with no CVD or cancer at enrolment , a vali date d FFQ was interviewer-administered , sociodemographic , physical activity and other characteristics were recorded , and arterial blood pressure and anthropometric characteristics were measured . In a median period of 10 years , 636 incident CHD cases and 240 CHD deaths were recorded . Associations of adherence to the MD , operationalised through a nine-component score ( 0 , poor ; 9 , excellent ) , with CHD incidence and mortality were evaluated through Cox regression controlling for potentially confounding variables . A two-point increase in the MD score was associated with lower CHD mortality by 25 % ( 95 % CI 0.57 , 0.98 ) among women and 19 % ( 95 % CI 0.67 , 0.99 ) among men . The association of adherence to the MD with CHD incidence was again inverse , but weaker ( hazard ratios 0.85 ( 95 % CI 0.71 , 1.02 ) among women and 0.98 ( 95 % CI 0.87 , 1.10 ) among men ) . With respect to score components , only meat among men ( positively ) and fruits and nuts among women ( inversely ) were associated with both the incidence of and mortality from CHD . The MD , as an integral entity , is inversely associated with CHD incidence and , particularly , mortality BACKGROUND Previous studies have linked full-calorie sugar-sweetened beverages ( SSBs ) with greater weight gain and an increased risk of type 2 diabetes . OBJECTIVE We prospect ively examined the association between consumption of SSBs and the risk of coronary heart disease ( CHD ) in women . DESIGN Women ( n = 88,520 ) from the Nurses ' Health Study aged 34 - 59 y , without previously diagnosed coronary heart disease ( CHD ) , stroke , or diabetes in 1980 , were followed from 1980 to 2004 . Consumption of SSBs was derived from 7 repeated food-frequency question naires administered between 1980 and 2002 . Relative risks ( RRs ) for CHD were calculated by using Cox proportional hazards models and adjusted for known cardiovascular disease risk factors . RESULTS During 24 y of follow-up , we ascertained 3105 incident cases of CHD ( nonfatal myocardial infa rct ion and fatal CHD ) . After st and ard and dietary risk factors were adjusted for , the RRs ( and 95 % CIs ) of CHD according to categories of cumulative average of SSB consumption ( < 1/mo , 1 - 4/mo , 2 - 6/wk , 1/d , and > or = 2 servings/d ) were 1.0 , 0.96 ( 0.87 , 1.06 ) , 1.04 ( 0.95 , 1.14 ) , 1.23 ( 1.06 , 1.43 ) , and 1.35 ( 1.07 , 1.69 ) ( P for trend < 0.001 ) . Additional adjustment for body mass index , energy intake , and incident diabetes attenuated the associations , but they remained significant . Artificially sweetened beverages were not associated with CHD . CONCLUSION Regular consumption of SSBs is associated with a higher risk of CHD in women , even after other unhealthful lifestyle or dietary factors are accounted for The objective of this study was to derive food-based dietary guidelines for the Dutch population . The dietary guidelines are based on 29 systematic review s of English language meta-analyses in PubMed summarizing r and omized controlled trials and prospect i ve cohort studies on nutrients , foods and food patterns and the risk of 10 major chronic diseases : coronary heart disease , stroke , heart failure , diabetes , breast cancer , colorectal cancer , lung cancer , chronic obstructive pulmonary disease , dementia and depression . The committee also selected three causal risk factors for cardiovascular diseases or diabetes : systolic blood pressure , low-density lipoprotein cholesterol and body weight . Findings were categorized as strong or weak evidence , inconsistent effects , too little evidence or effect unlikely for experimental and observational data separately . Next , the committee selected only findings with a strong level of evidence for deriving the guidelines . Convincing evidence was based on strong evidence from the experimental data either or not in combination with strong evidence from prospect i ve cohort studies . Plausible evidence was based on strong evidence from prospect i ve cohort studies only . A general guideline to eat a more plant food-based dietary pattern and limit consumption of animal-based food and 15 specific guidelines have been formulated . There are 10 new guidelines on legumes , nuts , meat , dairy produce , cereal products , fats and oils , tea , coffee and sugar-containing beverages . Three guidelines on vegetables , fruits , fish and alcoholic beverages have been sharpened , and the 2006 guideline on salt stayed the same . A separate guideline has been formulated on nutrient supplements . Completely food-based dietary guidelines can be derived in a systematic and transparent way BACKGROUND High intake of fruit and vegetables as well as high plasma vitamin C concentrations have been associated with low risk of ischemic heart disease in prospect i ve studies , but results from r and omized clinical trials have been inconsistent . OBJECTIVE We tested the hypothesis that genetically high concentrations of plasma vitamin C , such as with high intake of fruit and vegetables , are associated with low risk of ischemic heart disease and all-cause mortality . DESIGN We used a Mendelian r and omization approach and genotyped for solute carrier family 23 member 1 ( SLC23A1 ) rs33972313 in the sodium-dependent vitamin C transporter 1 in 97,203 white individuals of whom 10,123 subjects had ischemic heart disease , and 8477 subjects died . We measured plasma vitamin C in 3512 individuals and included dietary information on 83,256 individuals . RESULTS The SLC23A1 rs33972313 G allele was associated with 11 % higher plasma vitamin C. The multivariable adjusted HRs for highest compared with lowest fruit and vegetable intakes were 0.87 ( 95 % CI : 0.78 , 0.97 ; P = 0.01 ) for ischemic heart disease and 0.80 ( 95 % CI : 0.73 , 0.88 ; P < 0.001 ) for all-cause mortality . Corresponding HRs for rs33972313 GG ( 93 % ) compared with AA plus AG ( 7 % ) genotypes were 0.95 ( 95 % CI : 0.88 , 1.02 ; P = 0.21 ) and 0.96 ( 0.88 , 1.03 ; P = 0.29 ) , respectively . In an instrumental variable analysis , the OR for genetically determined 25 % higher plasma vitamin C concentrations was 0.90 ( 95 % CI : 0.75 , 1.08 ; P = 0.27 ) for ischemic heart disease and 0.88 ( 0.72 , 1.08 ; P = 0.22 ) for all-cause mortality . CONCLUSIONS High intake of fruit and vegetables was associated with low risk of ischemic heart disease and all-cause mortality . Although the 95 % CI for genetically high plasma vitamin C concentrations overlapped 1.0 , which made certain statistical inferences difficult , effect sizes were comparable to those for fruit and vegetable intake . Thus , judging by the effect size , our data can not exclude that a favorable effect of high intake of fruit and vegetables could in part be driven by high vitamin C concentrations BACKGROUND Prospect i ve studies evaluating associations between food intake and risk of heart failure ( HF ) in diverse population s are needed . OBJECTIVES Relationships between incident HF ( death or hospitalization ) and intake of seven food categories ( whole grains , fruits/vegetables , fish , nuts , high-fat dairy , eggs , red meat ) were investigated in an observational cohort of 14,153 African-American and white adults , age 45 to 64 years , sample d from four US communities . METHODS Between baseline ( 1987 - 1989 ) and Exam 3 ( 1993 - 1995 ) , dietary intake was based on responses to a 66-item food frequency question naire administered at baseline ; thereafter , intake was based on averaged baseline and Exam 3 responses . Hazard ratios ( HR [ 95 % CI ] ) for HF were calculated per 1-daily serving difference in food group intake . RESULTS During a mean of 13 years , 1,140 HF hospitalizations were identified . After multivariable adjustment ( energy intake , demographics , lifestyle factors , prevalent cardiovascular disease , diabetes , hypertension ) , HF risk was lower with greater whole-grain intake ( 0.93 [ 0.87 , 0.99 ] ) , but HF risk was higher with greater intake of eggs ( 1.23 [ 1.08 , 1.41 ] ) and high-fat dairy ( 1.08 [ 1.01 , 1.16 ] ) . These associations remained significant independent of intakes of the five other food categories , which were not associated with HF . CONCLUSIONS In this large , population -based sample of African-American and white adults , whole-grain intake was associated with lower HF risk , whereas intake of eggs and high-fat dairy were associated with greater HF risk after adjustment for several confounders Objectives The goal of this study was to determine the relative contribution of major lifestyle factors on the development of heart failure ( HF ) in older adults . Background HF incurs high morbidity , mortality , and health care costs among adults ≥65 years of age , which is the most rapidly growing segment of the U.S. population . Methods We prospect ively investigated separate and combined associations of lifestyle risk factors with incident HF ( 1,380 cases ) over 21.5 years among 4,490 men and women in the Cardiovascular Health Study , which is a community-based cohort of older adults . Lifestyle factors included 4 dietary patterns ( Alternative Healthy Eating Index , Dietary Approaches to Stop Hypertension , an American Heart Association 2020 dietary goals score , and a Biologic pattern , which was constructed using previous knowledge of cardiovascular disease dietary risk factors ) , 4 physical activity metrics ( exercise intensity , walking pace , energy expended in leisure activity , and walking distance ) , alcohol intake , smoking , and obesity . Results No dietary pattern was associated with developing HF ( p > 0.05 ) . Walking pace and leisure activity were associated with a 26 % and 22 % lower risk of HF , respectively ( pace > 3 mph vs. < 2 mph ; hazard ratio [ HR ] : 0.74 ; 95 % confidence interval [ CI ] : 0.63 to 0.86 ; leisure activity ≥845 kcal/week vs. < 845 kcal/week ; HR : 0.78 ; 95 % CI : 0.69 to 0.87 ) . Modest alcohol intake , maintaining a body mass index < 30 kg/m2 , and not smoking were also independently associated with a lower risk of HF . Participants with ≥4 healthy lifestyle factors had a 45 % ( HR : 0.55 ; 95 % CI : 0.42 to 0.74 ) lower risk of HF . Heterogeneity by age , sex , cardiovascular disease , hypertension medication use , and diabetes was not observed . Conclusions Among older U.S. adults , physical activity , modest alcohol intake , avoiding obesity , and not smoking , but not dietary patterns , were associated with a lower risk of HF BACKGROUND It is important to underst and whether eating eggs , which are a major source of dietary choline , results in increased exposure to trimethylamine-N-oxide ( TMAO ) , which is purported to be a risk factor for developing heart disease . OBJECTIVE We determined whether humans eating eggs generate TMAO and , if so , whether there is an associated increase in a marker for inflammation [ ie , high-sensitivity C-reactive protein ( hsCRP ) ] or increased oxidation of low-density lipoprotein ( LDL ) . DESIGN In a longitudinal , double-blind , r and omized dietary intervention , 6 volunteers were fed breakfast doses of 0 , 1 , 2 , 4 , or 6 egg yolks . Diets were otherwise controlled on the day before and day of each egg dose with a st and ardized low-choline menu . Plasma TMAO at timed intervals ( immediately before and 1 , 2 , 4 , 8 , and 24 h after each dose ) , 24-h urine TMAO , predose and 24-h postdose serum hsCRP , and plasma oxidized LDL were measured . Volunteers received all 5 doses with each dose separated by > 2-wk washout periods . RESULTS The consumption of eggs was associated with increased plasma and urine TMAO concentrations ( P < 0.01 ) , with ∼14 % of the total choline in eggs having been converted to TMAO . There was considerable variation between individuals in the TMAO response . There was no difference in hsCRP or oxidized LDL concentrations after egg doses . CONCLUSIONS The consumption of ≥2 eggs results in an increased formation of TMAO . Choline is an essential nutrient that is required for normal human liver and muscle functions and important for normal fetal development . Additional study is needed to both confirm the association between TMAO and atherosclerosis and identify factors , microbiota and genetic , that influence the generation of TMAO before policy and medical recommendations are made that suggest reduced dietary choline intake BACKGROUND Few population -based longitudinal studies on diet and stroke have been conducted , and associations between dietary fat and fish intake and risk of stroke are unclear . OBJECTIVES To prospect ively examine relationships between intakes of total fat , saturated fat , unsaturated fat , white fish and oily fish and risk of stroke in a well-defined population of 2710 middle-aged men . STUDY DESIGN Prospect i ve cohort study . METHODS Detailed information on health and lifestyle factors was collected via interview , and diet was assessed on three occasions using a food frequency question naire . Stroke ascertainment was by self-report and inspection of clinical records . Extracted data were assessed by two independent experts . RESULTS During a median follow-up of 18 years , 225 strokes ( 209 ischaemic and 19 haemorrhagic ) were eligible for inclusion in the analyses . For most recent diet ( i.e. food frequency question naire data collected immediately prior to the stroke event ) , there was a slightly lower risk of stroke with higher intakes of unsaturated fat and oily fish . Multiple adjusted hazard ratios ( HRs ) for the lowest vs highest quintiles of unsaturated fat and oily fish intakes were 0.66 [ 95 % confidence interval ( CI ) 0.41 - 1.05 , P trend = 0.13 ] and 0.66 ( 95 % CI 0.41 - 1.05 , P trend = 0.09 ) , respectively . Baseline and cumulative diets showed a slightly higher risk of stroke with higher intake of white fish ; HRs for the lowest vs highest quintiles were 1.16 ( 95 % CI 0.76 - 1.77 , P trend = 0.22 ) and 1.28 ( 95 % CI 0.77 - 2.13 , P trend = 0.48 ) , respectively . CONCLUSIONS Overall , strong associations were not found between intakes of different types of fat and fish and risk of stroke in middle-aged men . The inverse associations between unsaturated fat and oily fish intakes and risk of stroke were weak , but the direction of association was broadly consistent with other studies ; however , these relatively weak associations were not conventionally statistically significant Background : Health concerns have been raised about rice consumption , which may significantly contribute to arsenic exposure . However , little is known regarding whether habitual rice consumption is associated with cardiovascular disease ( CVD ) risk . Objective : We examined prospect ively the association of white rice and brown rice consumption with CVD risk . Design : We followed a total of 207,556 women and men [ 73,228 women from the Nurses ’ Health Study ( 1984–2010 ) , 92,158 women from the Nurses ’ Health Study II ( 1991–2011 ) , and 42,170 men from the Health Professionals Follow-Up Study ( 1986–2010 ) ] who were free of CVD and cancer at baseline . Vali date d semiquantitative food-frequency question naires were used to assess consumption of white rice , brown rice , and other food items . Fatal and nonfatal CVD ( coronary artery disease and stroke ) was confirmed by medical records or self-reports . Results : During 4,393,130 person-years of follow-up , 12,391 cases of CVD were identified . After adjustment for major CVD risk factors , including demographics , lifestyle , and other dietary intakes , rice consumption was not associated with CVD risk . The multivariable-adjuted HR of developing CVD comparing ≥5 servings/wk with < 1 serving/wk was 0.98 ( 95 % CI : 0.84 , 1.14 ) for white rice , 1.01 ( 0.79 , 1.28 ) for brown rice , and 0.99 ( 0.90 , 1.08 ) for total rice . To minimize the potential impact of racial difference in rice consumption , we restricted the analyses to whites only and obtained similar results : the HRs of CVD for ≥5 servings/wk compared with < 1 serving/wk were 1.04 ( 95 % CI : 0.88 , 1.22 ) for white rice and 1.01 ( 0.78 , 1.31 ) for brown rice . Conclusions : Greater habitual consumption of white rice or brown rice is not associated with CVD risk . These findings suggest that rice consumption may not pose a significant CVD risk among the U.S. population when consumed at current amounts . More prospect i ve studies are needed to explore these associations in other population Background / Objectives : High intakes of unprocessed red or processed meat may increase the risk of stroke . We aim ed to examine the association between unprocessed red meat , processed meat and total red meat consumption and risk of total stroke and ischaemic stroke . Subjects/ Methods : Cox proportional hazards regression analyses were conducted based on the data for 41 020 men and women aged 29–69 years at baseline . Results : During a mean follow-up of 13.8 years , 674 incident cases of stroke ( 531 ischaemic strokes , 79 haemorrhagic strokes , 42 subarachnoid haemorrhages and 22 mixed or unspecified events ) were identified . After multiple adjustment , unprocessed red meat , processed meat and total red meat consumption were not correlated with incidence of total stroke or ischaemic stroke in either men or women . The hazard ratios ( HRs ) for unprocessed red meat and processed meat and risk of total stroke comparing the highest with the lowest quintiles were , respectively , 0.81 ( 95 % confidence interval ( CI ) 0.54–1.21 ; P-trend=0.15 ) and 0.92 ( 95 % CI 0.64–1.32 ; P-trend=0.82 ) in men and 1.21 ( 95 % CI 0.79–1.85 ; P-trend=0.10 ) and 0.81 ( 95 % CI 0.51–1.27 ; P-trend=0.17 ) in women . The HRs for unprocessed red meat and processed meat and risk of ischaemic stroke were , respectively , 0.80 ( 95 % CI 0.51–1.25 ; P-trend=0.51 ) and 0.86 ( 95 % CI 0.57–1.29 ; P-trend=0.77 ) in men and 1.24 ( 95 % CI 0.74–2.05 ; P-trend=0.13 ) and 0.82 ( 95 % CI 0.47–1.42 ; P-trend=0.31 ) in women . Conclusions : In the Spanish European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) cohort , unprocessed red meat and processed meat consumption were not associated with risk of stroke in men or women Fruit and vegetable consumption is associated with low CHD risk in the USA and Northern Europe . There is , in contrast , little information about these associations in other regions of Europe . The goal of the present study was to assess the relationship between frequency of fruit and vegetable intake and CHD risk in two European population s with contrasting cardiovascular incidence rates ; France and Northern Irel and . The present prospect i ve study was in men aged 50 - 59 years , free of CHD , who were recruited in France ( n 5982 ) and Northern Irel and ( n 2105 ) . Fruit and vegetable intake was assessed by a food-frequency question naire . Incident cases of acute coronary events and angina were recorded over a 5-year follow-up . During follow-up there was a total of 249 ischaemic events . After adjustment on education level , smoking , physical activity , alcohol consumption , employment status , BMI , blood pressure , serum total and HDL-cholesterol , the relative risks ( RR ) of acute coronary events were 0.67 ( 95 % CI 0.44 , 1.03 ) and 0.64 ( 95 % CI 0.41 , 0.99 ) in the 2nd and 3rd tertiles of citrus fruit consumption , respectively ( P for trend < 0.03 ) . Similar results were observed in France and Northern Irel and . In contrast , the RR of acute coronary events for ' other fruit ' consumption were 0.70 ( 95 % CI 0.31 , 1.56 ) and 0.52 ( 95 % CI 0.24 , 1.14 ) respectively in Northern Irel and ( trend P<0.05 ) and 1.29 ( 95 % CI 0.69 , 2.4 ) and 1.15 ( 95 % CI 0.68 , 1.94 ) in France ( trend P=0.5 ; interaction P<0.04 ) . There was no evidence for any association between vegetable intake and total CHD events . In conclusion , frequency of citrus fruit , but not other fruits , intake is associated with lower rates of acute coronary events in both France and Northern Irel and , suggesting that geographical or related factors might affect the relationship between fruit consumption and CHD risk BACKGROUND In general population s , the effects of dietary cholesterol on blood cholesterol concentrations are modest . However , the relation is stronger in those with an ɛ4 allele in the apolipoprotein E gene ( APOE ) . There is little information on the association between cholesterol intake and the risk of coronary artery disease ( CAD ) among those with the ApoE4 phenotype . OBJECTIVE We investigated the associations of intakes of cholesterol and eggs , a major source of dietary cholesterol , with carotid intima-media thickness and the risk of incident CAD in middle-aged and older men from eastern Finl and . DESIGN The study included 1032 men aged 42 - 60 y in 1984 - 1989 at the baseline examinations of the prospect i ve , population -based Kuopio Ischaemic Heart Disease Risk Factor Study . Data on common carotid artery intima-media thickness ( CCA-IMT ) were available for 846 men . Dietary intakes were assessed with 4-d food records . Associations with incident CAD and baseline CCA-IMT were analyzed by using Cox regression and ANCOVA , respectively . RESULTS The ApoE4 phenotype was found in 32.5 % of the men . During the average follow-up of 20.8 y , 230 CAD events occurred . Egg or cholesterol intakes were not associated with the risk of CAD . Each 1 additional egg ( 55 g)/d was associated with a multivariable-adjusted HR of 1.17 ( 95 % CI : 0.85 , 1.61 ) in the ApoE4 noncarriers and an HR of 0.93 ( 95 % CI : 0.50 , 1.72 ) in the ApoE4 carriers ( P-interaction = 0.34 ) . Each 100-mg/d higher cholesterol intake was associated with an HR of 1.04 ( 95 % CI : 0.89 , 1.22 ) in the ApoE4 noncarriers and an HR of 0.95 ( 95 % CI : 0.73 , 1.25 ) in the ApoE4 carriers ( P-interaction = 0.81 ) . Egg or cholesterol intakes were also not associated with increased CCA-IMT . CONCLUSION Egg or cholesterol intakes were not associated with increased CAD risk , even in ApoE4 carriers ( i.e. , in highly susceptible individuals ) CONTEXT Reduction in egg consumption has been widely recommended to lower blood cholesterol levels and prevent coronary heart disease ( CHD ) . Epidemiologic studies on egg consumption and risk of CHD are sparse . OBJECTIVE To examine the association between egg consumption and risk of CHD and stroke in men and women . DESIGN AND SETTING Two prospect i ve cohort studies , the Health Professionals Follow-up Study ( 1986 - 1994 ) and the Nurses ' Health Study ( 1980 - 1994 ) . PARTICIPANTS A total of 37851 men aged 40 to 75 years at study outset and 80082 women aged 34 to 59 years at study outset , free of cardiovascular disease , diabetes , hypercholesterolemia , or cancer . MAIN OUTCOME MEASURES Incident nonfatal myocardial infa rct ion , fatal CHD , and stroke corresponding to daily egg consumption as determined by a food-frequency question naire . RESULTS We documented 866 incident cases of CHD and 258 incident cases of stroke in men during 8 years of follow-up and 939 incident cases of CHD and 563 incident cases of stroke in women during 14 years of follow-up . After adjustment for age , smoking , and other potential CHD risk factors , we found no evidence of an overall significant association between egg consumption and risk of CHD or stroke in either men or women . The relative risks ( RRs ) of CHD across categories of intake were less than 1 per week ( 1.0 ) , 1 per week ( 1.06 ) , 2 to 4 per week ( 1.12 ) , 5 to 6 per week ( 0.90 ) , and > or = 1 per day ( 1.08 ) ( P for trend = .75 ) for men ; and less than 1 per week ( 1.0 ) , 1 per week ( 0.82 ) , 2 to 4 per week ( 0.99 ) , 5 to 6 per week ( 0.95 ) , and > or = 1 per day ( 0.82 ) ( P for trend = .95 ) for women . In subgroup analyses , higher egg consumption appeared to be associated with increased risk of CHD only among diabetic subjects ( RR of CHD comparing more than 1 egg per day with less than 1 egg per week among diabetic men , 2.02 [ 95 % confidence interval , 1.05 - 3.87 ; P for trend = .04 ] , and among diabetic women , 1.49 [ 0.88 - 2.52 ; P for trend = .008 ] ) . CONCLUSIONS These findings suggest that consumption of up to 1 egg per day is unlikely to have substantial overall impact on the risk of CHD or stroke among healthy men and women . The apparent increased risk of CHD associated with higher egg consumption among diabetic participants warrants further research Background Prospect i ve data examining the relationship between dietary protein intake and incident coronary heart disease ( CHD ) are inconclusive . Most evidence is derived from homogenous population s such as health professionals . Large community-based analyses in more diverse sample s are lacking . Methods We studied the association of protein type and major dietary protein sources and risk for incident CHD in 12,066 middle-aged adults ( aged 45–64 at baseline , 1987–1989 ) from four U.S. communities enrolled in the Atherosclerosis Risk in Communities ( ARIC ) Study who were free of diabetes mellitus and cardiovascular disease at baseline . Dietary protein intake was assessed at baseline and after 6 years of follow-up by food frequency question naire . Our primary outcome was adjudicated coronary heart disease events or deaths with following up through December 31 , 2010 . Cox proportional hazard models with multivariable adjustment were used for statistical analyses . Results During a median follow-up of 22 years , there were 1,147 CHD events . In multivariable analyses total , animal and vegetable protein were not associated with an increased risk for CHD before or after adjustment . In food group analyses of major dietary protein sources , protein intake from red and processed meat , dairy products , fish , nuts , eggs , and legumes were not significantly associated with CHD risk . The hazard ratios [ with 95 % confidence intervals ] for risk of CHD across quintiles of protein from poultry were 1.00 [ ref ] , 0.83 [ 0.70–0.99 ] , 0.93 [ 0.75–1.15 ] , 0.88 [ 0.73–1.06 ] , 0.79 [ 0.64–0.98 ] , P for trend = 0.16 ) . Replacement analyses evaluating the association of substituting one source of dietary protein for another or of decreasing protein intake at the expense of carbohydrates or total fats did not show any statistically significant association with CHD risk . Conclusion Based on a large community cohort we found no overall relationship between protein type and major dietary protein sources and risk for CHD BACKGROUND Previous studies of diet and coronary heart disease ( CHD ) have focused on intake of nutrients rather than whole foods . Because of the findings that dietary fibre , folate and antioxidants may be protective for CHD , increased intake of vegetables has been recommended . However , due to the chemical and physical complexity of vegetables , the effects of individual nutrients may differ if eaten as whole foods . Moreover , little is known about the direct association between vegetable intake and risk of CHD . METHODS We prospect ively evaluated the relation between vegetable intake and CHD risk in the Physicians ' Health Study , a r and omized trial of aspirin and beta-carotene among 22 071 US male physicians aged 40 - 84 years in 1982 . In this analysis , we included 15 220 men without heart disease , stroke or cancer at baseline who provided information on their vegetable intake at baseline , and in the 2nd , 4th and 6th years of follow-up using a simple semiquantitative food frequency question naire including eight vegetables . We confirmed 1148 incident cases of CHD ( 387 incident cases of myocardial infa rct ion and 761 incident cases of coronary artery bypass grafting or percutaneous transluminal coronary angioplasty ) during 12 years of follow-up . RESULTS After adjusting for age , r and omized treatment , body mass index ( BMI ) , smoking , alcohol intake , physical activity , history of diabetes , history of hypertension , history of high cholesterol , and use of multivitamins , men who consumed at least 2.5 servings/day of vegetables had a relative risk ( RR ) of 0.77 ( 95 % CI : 0.60 - 0.98 ) for CHD , compared with men in the lowest category ( < 1 serving/day ) . Adjusting for the same covariates in an analysis of the overall trend that considered intake of vegetables as a continuous variable , we found a RR of 0.83 ( 95 % CI : 0.71 - 0.98 ) for risk of CHD for each additional serving/day of vegetables . The inverse relation between vegetable intake and CHD risk was more evident among men with a BMI > or = 25 ( RR = 0.71 , 95 % CI : 0.51 - 0.99 ) or current smokers ( RR = 0.40 , 95 % CI : 0.18 - 0.86 ) comparing highest to the lowest categories of intake . CONCLUSIONS Our results suggest an inverse association between vegetable intake and risk of CHD . These prospect i ve data support current dietary guidelines to increase vegetable intake for the prevention of CHD BACKGROUND We prospect ively studied iron intake in relation to the incidence of coronary disease in a 4-year follow-up of 44,933 men ( with no previous history of cardiovascular disease ) aged 40 to 75 years in 1986 who completed a food frequency question naire at baseline . METHODS AND RESULTS We documented 844 incident cases of coronary disease ( 249 nonfatal myocardial infa rct ions , 137 coronary disease fatalities , and 458 bypass operations or angioplasties ) . After adjustment for established risk factors , there was no significant association between total iron intake and risk of coronary heart disease . Men in the highest quintile of total intake ( median , 37 mg/d ) had a relative risk ( RR ) of fatal coronary disease or nonfatal myocardial infa rct ion of 0.73 ( 95 % confidence intervals [ CI ] , 0.51 , 1.06 ) compared with men in the lowest quintile of intake ( median , 11 mg/d ) . Dietary intake of heme iron -- mainly from red meat -- also was not significantly associated with risk of coronary heart disease . However , incidence of fatal coronary disease or nonfatal myocardial infa rct ion was higher among men in the top quintile of heme iron intake compared with men in the lowest quintile ( RR , 1.42 ; 95 % CI , 1.02 , 1.98 ) . This association remained after adjustment for dietary cholesterol and fats . Heme iron but not total iron intake was positively correlated with serum ferritin among 123 members of the cohort who participated in a validation study . CONCLUSIONS These results do not support the hypothesis that dietary iron in general increases coronary risk in men ; they are consistent , however , with an increased risk of myocardial infa rct ion among men with higher intake of heme iron , which is itself positively associated with iron stores Background and Purpose — Few dietary protein sources have been studied prospect ively in relation to stroke . We examined the relation between foods that are major protein sources and risk of stroke . Methods — We prospect ively followed 84 010 women aged 30 to 55 years at baseline and 43 150 men aged 40 to 75 years at baseline without diagnosed cancer , diabetes , or cardiovascular disease . Diet was assessed repeatedly by a st and ardized and vali date d question naire . We examined the association between protein sources and incidence of stroke using a proportional hazard model adjusted for stroke risk factors . Results — During 26 and 22 years of follow-up in women and men , respectively , we documented 2633 and 1397 strokes , respectively . In multivariable analyses , higher intake of red meat was associated with an elevated risk of stroke , whereas a higher intake of poultry was associated with a lower risk . In models estimating the effects of exchanging different protein sources , compared with 1 serving/day of red meat , 1 serving/day of poultry was associated with a 27 % ( 95 % CI , 12%–39 % ) lower risk of stroke , nuts with a 17 % ( 95 % CI . 4%–27 % ) lower risk , fish with a 17 % ( 95 % CI , 0%–30 % ) lower risk , low-fat dairy with an 11 % ( 95 % CI , 5%–17 % ) lower risk , and whole-fat dairy with a 10 % ( 95 % CI , 4%–16 % ) lower risk . We did not see significant associations with exchanging legumes or eggs for red meat . Conclusions — These data suggest that stroke risk may be reduced by replacing red meat with other dietary sources of protein BACKGROUND Associations between fish consumption and stroke risk have been inconsistent , possibly because of the differences in types of fish meals consumed . Additionally , such relationships have not been specifically evaluated in the elderly , in whom disease burden may be high and diet less influential . METHODS Among 4775 adults 65 years or older ( range , 65 - 98 years ) and free of known cerebrovascular disease at baseline in 1989 - 1990 , usual dietary intake was assessed using a food frequency question naire . In a subset , consumption of tuna or other broiled or baked fish , but not fried fish or fish s and wiches ( fish burgers ) , correlated with plasma phospholipid long-chain n-3 fatty acid levels . Incident strokes were prospect ively ascertained . RESULTS During 12 years of follow-up , participants experienced 626 incident strokes , including 529 ischemic strokes . In multivariate analyses , tuna/other fish consumption was inversely associated with total stroke ( P = .04 ) and ischemic stroke ( P = .02 ) , with 27 % lower risk of ischemic stroke with an intake of 1 to 4 times per week ( hazard ratio [ HR ] , 0.73 ; 95 % confidence interval [ CI ] , 0.55 - 0.98 ) and 30 % lower risk with intake of 5 or more times per week ( HR , 0.70 ; 95 % CI , 0.50 - 0.99 ) compared with an intake of less than once per month . In contrast , fried fish/fish s and wich consumption was positively associated with total stroke ( P = .006 ) and ischemic stroke ( P = .003 ) , with a 44 % higher risk of ischemic stroke with consumption of more than once per week ( HR , 1.44 ; 95 % CI , 1.12 - 1.85 ) compared with consumption of less than once per month . Fish consumption was not associated with hemorrhagic stroke . CONCLUSIONS Among elderly individuals , consumption of tuna or other broiled or baked fish is associated with lower risk of ischemic stroke , while intake of fried fish or fish s and wiches is associated with higher risk . These results suggest that fish consumption may influence stroke risk late in life ; potential mechanisms and alternate explanations warrant further study Background and Purpose Epidemiological studies of the associations of low-fat dairy and specific dairy food consumption with risk of stroke are sparse . Our aim was to examine the association between consumption of total , low-fat , full-fat , and specific dairy foods and risk of stroke in a prospect i ve cohort study . Methods We followed 74 961 Swedish women and men who were free from cardiovascular disease and cancer and who completed a 96-item food frequency question naire in 1997 . Incident cases of stroke were ascertained from the Swedish Hospital Discharge Registry . Results During a mean follow-up of 10.2 years , we ascertained 4089 cases of stroke , including 3159 cerebral infa rct ions , 583 hemorrhagic strokes , and 347 unspecified strokes . Consumption of low-fat dairy foods was inversely associated with risk of total stroke ( P for trend=0.03 ) and cerebral infa rct ion ( P for trend=0.03 ) . The multivariable relative risks for the highest compared with the lowest quintile of low-fat dairy consumption were 0.88 ( 95 % CI , 0.80–0.97 ) for total stroke and 0.87 ( 95 % CI , 0.78–0.98 ) for cerebral infa rct ion . Consumption of total dairy , full-fat dairy , milk , sour milk/yogurt , cheese , and cream/crème fraiche was not associated with stroke risk . Conclusions These results suggest that low-fat dairy consumption is inversely associated with the risk of stroke Coronary heart disease is associated with diet . Nutritional recommendations are frequently provided , but few long term studies on the effect of food choices on heart disease are available . We followed coronary heart disease morbidity and mortality in a cohort of rural men ( N = 1,752 ) participating in a prospect i ve observational study . Dietary choices were assessed at baseline with a 15-item food question naire . 138 men were hospitalized or deceased owing to coronary heart disease during the 12 year follow-up . Daily intake of fruit and vegetables was associated with a lower risk of coronary heart disease when combined with a high dairy fat consumption ( odds ratio 0.39 , 95 % CI 0.21–0.73 ) , but not when combined with a low dairy fat consumption ( odds ratio 1.70 , 95 % CI 0.97–2.98 ) . Choosing wholemeal bread or eating fish at least twice a week showed no association with the outcome OBJECTIVE Consuming a variety of fruit and vegetables provides many different micronutrients and bioactive compounds . Whether this contributes to the beneficial association between fruit and vegetables and incident CHD and stroke is unknown . DESIGN Prospect i ve population -based cohort study . SETTING The Netherl and s. SUBJECTS Men and women ( n 20 069 ) aged 20 - 65 years . Participants completed a vali date d 178-item FFQ , including nine fruit and thirteen vegetable items . Variety in fruit and vegetables was defined as the sum of different items consumed at least once per 2 weeks over the previous year . Hazard ratios ( HR ) for variety in relation to incident CHD and stroke were calculated using multivariable Cox proportional hazards models additionally adjusted for quantity of fruit and vegetables . RESULTS Variety and quantity in fruit and vegetables were highly correlated ( r = 0.81 ) . Variety was not associated with total energy intake ( r = -0.01 ) and positively associated with nutrient intakes , particularly vitamin C ( r = 0.70 ) . During 10 years of follow-up , 245 cases of CHD and 233 cases of stroke occurred . Variety in vegetables ( HR per 2 items = 1.05 ; 95 % CI 0.94 , 1.17 ) and in fruit ( HR per 2 items = 1.00 ; 95 % CI 0.87 , 1.15 ) were not related to incident CHD . Variety in vegetables ( HR per 2 items = 0.93 ; 95 % CI 0.83 , 1.04 ) and in fruit ( HR per 2 items = 1.03 ; 95 % CI 0.89 , 1.18 ) were also not related to incident stroke . CONCLUSIONS More variety in fruit and vegetable consumption was associated with higher intakes of fruit and vegetables and micronutrients . Independently of quantity , variety in fruit and vegetables was related neither to incident CHD nor to incident stroke Background and Purpose — High red meat consumption has been associated with increased risk of some cancers and may also be a risk factor for cardiovascular diseases . However , epidemiological studies of red meat consumption in relation to risk of stroke are very limited . Our objective was to examine the association between red meat consumption and stroke incidence in the Swedish Mammography Cohort . Methods — We prospect ively followed 34 670 women without cardiovascular disease and cancer at baseline . Participants completed a self-administered question naire on diet and other risk factors for cardiovascular diseases in 1997 . Cox proportional hazards models were used to estimate multivariable-adjusted relative risks ( RR ) and 95 % CI . Results — During a mean follow-up of 10.4 years , we ascertained 1680 incident cases of stroke , comprising 1310 cerebral infa rct ion , 154 intracerebral hemorrhage , 79 subarachnoid hemorrhage , and 137 unspecified stroke . Total red meat and processed meat consumption was associated with a statistically significant increased risk of cerebral infa rct ion , but not of total stroke , intracerebral hemorrhage , or subarachnoid hemorrhage . The multivariable RR of cerebral infa rct ion for the highest versus the lowest quintile of consumption were 1.22 ( 95 % CI , 1.01–1.46 ) for red meat and 1.24 ( 95 % CI , 1.04–1.49 ) for processed meat . Fresh ( unprocessed ) meat consumption was not associated with total stroke or with any stroke subtype . Conclusion — Findings from this study suggest that red and processed meat consumption may increase the risk of cerebral infa rct ion in women BACKGROUND Although dietary factors are suspected to be important determinants of coronary heart disease ( CHD ) risk , the direct evidence is relatively sparse . METHODS The Adventist Health Study is a prospect i ve cohort investigation of 31,208 non-Hispanic white California Seventh-Day Adventists . Extensive dietary information was obtained at baseline , along with the values of traditional coronary risk factors . These were related to risk of definite fatal CHD or definite nonfatal myocardial infa rct ion . RESULTS Subjects who consumed nuts frequently ( more than four times per week ) experienced substantially fewer definite fatal CHD events ( relative risk , 0.52 ; 95 % confidence interval [ CI ] , 0.36 to 0.76 ) and definite nonfatal myocardial infa rct ions ( relative risk , 0.49 ; 95 % CI , 0.28 to 0.85 ) , when compared with those who consumed nuts less than once per week . These findings persisted on covariate adjustment and were seen in almost all of 16 different subgroups of the population . Subjects who usually consumed whole wheat bread also experienced lower rates of definite nonfatal myocardial infa rct ion ( relative risk , 0.56 ; 95 % CI , 0.35 to 0.89 ) and definite fatal CHD ( relative risk , 0.89 ; 95 % CI , 0.60 to 1.33 ) when compared with those who usually ate white bread . Men who ate beef at least three times each week had a higher risk of definite fatal CHD ( relative risk , 2.31 ; 95 % CI , 1.11 to 4.78 ) , but this effect was not seen in women or for the nonfatal myocardial infa rct ion end point . CONCLUSION Our data strongly suggest that the frequent consumption of nuts may protect against risk of CHD events . The favorable fatty acid profile of many nuts is one possible explanation for such an effect The potential long-term association between carbohydrate intake and the risk of coronary heart disease ( CHD ) remains unclear , especially among population s who habitually have high-carbohydrate diets . We prospect ively examined intakes of carbohydrates and staple grains as well as glycemic index and glycemic load in relation to CHD among 117,366 Chinese women and men ( 40 - 74 years of age ) without history of diabetes , CHD , stroke , or cancer at baseline in Shanghai , China . Diet was assessed using vali date d food frequency question naires . Incident CHD cases were ascertained during follow-ups ( in women , the mean was 9.8 years and in men , the mean was 5.4 years ) and confirmed by medical records . Carbohydrate intake accounted for 67.5 % of the total energy intake in women and 68.5 % in men . Seventy percent of total carbohydrates came from white rice and 17 % were from refined wheat products . Positive associations between carbohydrate intakess and CHD were found in both sexes ( all P for heterogeneity > 0.35 ) . The combined multivariate-adjusted hazard ratios for the lowest to highest quartiles of carbohydrate intake , respectively , were 1.00 , 1.38 , 2.03 , and 2.88 ( 95 % confidence interval : 1.44 , 5.78 ; P for trend = 0.001 ) . The combined hazard ratios comparing the highest quartile with the lowest were 1.80 ( 95 % confidence interval : 1.01 , 3.17 ) for refined grains and 1.87 ( 95 % confidence interval : 1.00 , 3.53 ) for glycemic load ( both P for trend = 0.03 ) . High carbohydrate intake , mainly from refined grains , is associated with increased CHD risk in Chinese adults Objectives To investigate whether sweetened beverage consumption is associated with risk of heart failure ( HF ) in a large prospect i ve population -based study of men . Methods and results A population -based cohort comprising 42 400 men , 45–79 years of age , was followed from 1998 through 2010 . Sweetened beverage consumption was assessed by utilising a food frequency question naire . Incident events of HF were identified through linkage to the Swedish National Patient Register and the Cause of Death Register . Cox regression analyses were implemented to investigate the association between sweetened beverage consumption and HF . During a mean follow-up time of 11.7 years , a total of 4113 HF events were identified . We observed a positive association between sweetened beverage consumption and risk of HF after adjustment for other risk factors ( p for trend < 0.001 ) . Men who consumed two or more servings of sweetened beverages per day had a statistically significant higher risk of developing HF ( 23 % , 95 % CI 1.12 to 1.35 ) compared to men who were non-consumers . Conclusions Our finding that sweetened beverage consumption is associated with higher risk of HF could have implication s for HF prevention strategies . Additional prospect i ve studies investigating the link between sweetened beverage consumption and HF are therefore needed BACKGROUND AND AIMS Heart failure ( HF ) remains a major public health issue . Red meat and dietary heme iron have been associated with an increased risk of coronary heart disease and hypertension , two major risk factors for HF . However , it is not known whether red meat intake influences the risk of HF . We therefore examined the association between red meat consumption and incident HF . METHODS AND RESULTS We prospect ively studied 21,120 apparently healthy men ( mean age 54.6 y ) from the Physicians ' Health Study ( 1982 - 2008 ) . Red meat was assessed by an abbreviated food question naire and incident HF was ascertained through annual follow-up question naires . We used Cox proportional hazard models to estimate hazard ratios . In a multivariable model , there was a positive and grade d relation between red meat consumption and HF [ hazard ratio ( 95 % CI ) of 1.0 ( reference ) , 1.02 ( 0.85 - 1.22 ) , 1.08 ( 0.90 - 1.30 ) , 1.17 ( 0.97 - 1.41 ) , and 1.24 ( 1.03 - 1.48 ) from the lowest to the highest quintile of red meat , respectively ( p for trend 0.007 ) ] . This association was observed for HF with ( p for trend 0.035 ) and without ( p for trend 0.038 ) antecedent myocardial infa rct ion . CONCLUSION Our data suggest that higher intake of red meat is associated with an increased risk of HF CONTEXT Few studies have evaluated the relationship between fruit and vegetable intake and cardiovascular disease . OBJECTIVE To examine the associations between fruit and vegetable intake and ischemic stroke . DESIGN , SETTING , AND SUBJECTS Prospect i ve cohort studies , including 75 596 women aged 34 to 59 years in the Nurses ' Health Study with 14 years of follow-up ( 1980 - 1994 ) , and 38683 men aged 40 to 75 years in the Health Professionals ' Follow-up Study with 8 years of follow-up ( 1986 - 1994 ) . All individuals were free of cardiovascular disease , cancer , and diabetes at baseline . MAIN OUTCOME MEASURE Incidence of ischemic stroke by quintile of fruit and vegetable intake . RESULTS A total of 366 women and 204 men had an ischemic stroke . After controlling for st and ard cardiovascular risk factors , persons in the highest quintile of fruit and vegetable intake ( median of 5.1 servings per day among men and 5.8 servings per day among women ) had a relative risk ( RR ) of 0.69 ( 95 % confidence interval [ CI ] , 0.52 - 0.92 ) compared with those in the lowest quintile . An increment of 1 serving per day of fruits or vegetables was associated with a 6 % lower risk of ischemic stroke ( RR , 0.94 ; 95 % CI , 0.90 - 0.99 ; P = .01 , test for trend ) . Cruciferous vegetables ( RR , 0.68 for an increment of 1 serving per day ; 95 % CI , 0.49 - 0.94 ) , green leafy vegetables ( RR , 0.79 ; 95 % CI , 0.62 - 0.99 ) , citrus fruit including juice ( RR , 0.81 ; 95 % CI , 0.68 - 0.96 ) , and citrus fruit juice ( RR , 0.75 ; 95 % CI , 0.61 - 0.93 ) contributed most to the apparent protective effect of total fruits and vegetables . Legumes or potatoes were not associated with lower ischemic stroke risk . The multivariate pooled RR for total stroke was 0.96 ( 95 % CI , 0.93 - 1.00 ) for each increment of 2 servings per day . CONCLUSIONS These data support a protective relationship between consumption of fruit and vegetables-particularly cruciferous and green leafy vegetables and citrus fruit and juice- and ischemic stroke risk Background It is still unclear whether carbohydrate consumption is associated with cardiovascular disease ( CVD ) risk . Genetic susceptibility might modify the associations between dietary intakes and disease risk . Objectives The aim was to examine the association between the consumption of carbohydrate-rich foods ( vegetables , fruits and berries , juice , potatoes , whole grains , refined grains , cookies and cakes , sugar and sweets , and sugar-sweetened beverages ) and the risk of incident ischemic CVD ( iCVD ; coronary events and ischemic stroke ) , and whether these associations differ depending on genetic susceptibility to dyslipidemia . Methods Among 26,445 individuals ( 44–74 years ; 62 % females ) from the Malmö Diet and Cancer Study cohort , 2,921 experienced an iCVD event during a mean follow-up time of 14 years . At baseline , dietary data were collected using a modified diet history method , and clinical risk factors were measured in 4,535 subjects . We combined 80 vali date d genetic variants associated with triglycerides and HDL-C or LDL-C , into genetic risk scores and examined the interactions between dietary intakes and genetic risk scores on the incidence of iCVD . Results Subjects in the highest intake quintile for whole grains had a 13 % ( 95 % CI : 3–23 % ; p-trend : 0.002 ) lower risk for iCVD compared to the lowest quintile . A higher consumption of foods rich in added sugar ( sugar and sweets , and sugar-sweetened beverages ) had a significant cross-sectional association with higher triglyceride concentrations and lower HDL-C concentrations . A stronger positive association between a high consumption of sugar and sweets on iCVD risk was observed among those with low genetic risk score for triglycerides ( p-interaction=0.05 ) . Conclusion In this prospect i ve cohort study that examined food sources of carbohydrates , individuals with a high consumption of whole grains had a decreased risk of iCVD . No convincing evidence of an interaction between genetic susceptibility for dyslipidemia , measured as genetic risk scores of dyslipidemia-associated variants , and the consumption of carbohydrate-rich foods on iCVD risk was observed OBJECTIVE Studies examining the association of dairy consumption with incident CHD have yielded inconsistent results . The current prospect i ve study examined the association between dairy consumption and CHD in a population -based sample of older community-dwelling adults . DESIGN Baseline CHD risk factors were assessed and an FFQ was self-administered . Participants were followed for morbidity and mortality with periodic clinic visits and annual mailed question naires for an average of 16?2 years , with a 96 % follow-up rate for fatal and non-fatal CHD . SETTING Community . SUBJECTS Participants were 751 men and 1008 women aged 50–93 years who attended a clinic visit in 1984–1987 . RESULTS At baseline the mean age was 70.6 ( SD 9.8 ) years for men and 70.1 ( SD 9.3 ) years for women . Participants who developed CHD during follow-up were significantly older ( P < 0.001 ) , had higher BMI ( P = 0.035 ) and higher total cholesterol ( P = 0.050 ) , and were more likely to be male ( P < 0.001 ) , diabetic ( P = 0.011 ) and hypertensive ( P < 0.001 ) , than those who did not develop CHD . Multivariate regression analyses adjusting for age , BMI , diabetes , hypertension , LDL-cholesterol and oestrogen use ( in women ) indicated that women who consumed low-fat cheese ‘ sometimes/often ’ and women who consumed non-fat milk ‘ sometimes/often ’ had an increased risk of incident CHD ( hazard ratio 52.32 ; 95 % CI 1.57 , 3.41 ) and CHD ( hazard ratio 51.48 ; 95 % CI 1.02 , 2.16 ) compared with women who ‘ never/rarely ’ ate these dairy products . CONCLUSIONS Woman with higher intake of low-fat cheese and non-fat milk seem to have a higher risk of incident CHD . This needs further investigation considering recent evidence of cardiovascular benefits from certain dairy fat BACKGROUND Few studies have examined associations of fish consumption with ischemic heart disease ( IHD ) risk among older adults or how different types of fish meals relate to IHD risk . METHODS AND RESULTS In a population -based prospect i ve cohort study , usual fish consumption was ascertained at baseline among 3910 adults aged > or = 65 years and free of known cardiovascular disease in 1989 and 1990 . Consumption of tuna and other broiled or baked fish correlated with plasma phospholipid long-chain n-3 fatty acids , whereas consumption of fried fish or fish s and wiches ( fish burgers ) did not . Over 9.3 years ' mean follow-up , there were 247 IHD deaths ( including 148 arrhythmic deaths ) and 363 incident nonfatal myocardial infa rct ions ( MIs ) . After adjustment for potential confounders , consumption of tuna or other broiled or baked fish was associated with lower risk of total IHD death ( P for trend=0.001 ) and arrhythmic IHD death ( P=0.001 ) but not nonfatal MI ( P=0.44 ) , with 49 % lower risk of total IHD death and 58 % lower risk of arrhythmic IHD death among persons consuming tuna/other fish 3 or more times per week compared with less than once per month . In similar analyses , fried fish/fish s and wich consumption was not associated with lower risk of total IHD death , arrhythmic IHD death , or nonfatal MI but rather with trends toward higher risk . CONCLUSIONS Among adults aged > or = 65 years , modest consumption of tuna or other broiled or baked fish , but not fried fish or fish s and wiches , is associated with lower risk of IHD death , especially arrhythmic IHD death . Cardiac benefits of fish consumption may vary depending on the type of fish meal consumed Flavonols and flavones are antioxidant polyphenolic compounds found in tea , vegetables , fruits , and wine . In experimental studies they have been effective free radical scavengers , metal chelators , and antithrombotic agents . In the few epidemiologic studies of these agents , some have suggested an inverse association between intake of flavonols and flavones and the risk of cardiovascular disease . Our study population comprised 25,372 male smokers , 50–69 years of age , with no previous myocardial infa rct ion . They were participants of the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study , which was a r and omized , double-blind , placebo-controlled trial with daily supplementation of alpha-tocopherol ( 50 mg per day ) and /or beta-carotene ( 20 mg per day ) . The men completed a vali date d dietary question naire at baseline . After 6.1 years of follow-up , there were 1,122 nonfatal myocardial infa rct ions and 815 coronary deaths . In the multivariate model , the relative risk of nonfatal myocardial infa rct ion was 0.77 ( 95 % confidence interval = 0.64–0.93 ) among men in the highest ( median 18 mg per day ) compared with the lowest ( median 4 mg per day ) quintile of flavonol and flavone intake . The respective relative risk for coronary death was 0.89 ( 95 % confidence interval = 0.71–1.11 ) . Thus , intake of flavonols and flavones was inversely associated with nonfatal myocardial infa rct ion , whereas there was a weaker association with coronary death Objective : To test the hypothesis that milk drinking increases the risk of ischaemic heart disease ( IHD ) and ischaemic stroke in a prospect i ve study . Design : In the Caerphilly Cohort Study dietary data , including milk consumption , were collected by a semiquantitative food frequency question naire in 1979–1983 . The cohort has been followed for 20–24 y and incident IHD and stroke events identified . Subjects : A representative population sample in South Wales , of 2512 men , aged 45–59 y at recruitment . Main outcome measures : In total , 493 men had an IHD event and 185 an ischaemic stroke during follow-up . Results : After adjustment , the hazard ratio in men with a milk consumption of one pint ( 0.57 l ) or more per day , relative to men who stated that they consumed no milk , is 0.71 ( 0.40–1.26 ) for IHD and 0.66 ( 0.24–1.81 ) for ischaemic stroke . At baseline , 606 men had had clinical or ECG evidence of vascular disease , and in these the vascular risk was even lower ( 0.37 ; 0.15–0.90 ) . The hazard ratio for IHD and ischaemic stroke combined is 0.64 ( 0.39–1.06 ) in all men and 0.37 ( 0.15–0.90 ) in those who had had a prior vascular event . Conclusion : The data provide no convincing evidence that milk consumption is associated with an increase in vascular disease risk . Evidence from an overview of all published cohort studies on this topic should be informative . Sponsorship : The Medical Research Council , the University of Wales College of Medicine and Bristol University . Current support is from the Food St and ards Agency BACKGROUND There are no previous studies investigating the effect of all dietary antioxidants in relation to myocardial infa rct ion . The total antioxidant capacity of diet takes into account all antioxidants and synergistic effects between them . The aim of this study was to examine how total antioxidant capacity of diet and antioxidant-containing foods were associated with incident myocardial infa rct ion among middle-aged and elderly women . METHODS In the population -based prospect i ve Swedish Mammography Cohort of 49 - 83-year-old women , 32,561 were cardiovascular disease-free at baseline . Women completed a food-frequency question naire , and dietary total antioxidant capacity was calculated using oxygen radical absorbance capacity values . Information on myocardial infa rct ion was identified from the Swedish Hospital Discharge and the Cause of Death registries . Hazard ratios ( HR ) and 95 % confidence intervals ( CI ) were calculated using Cox proportional hazard models . RESULTS During the follow-up ( September 1997-December 2007 ) , we identified 1114 incident cases of myocardial infa rct ion ( 321,434 person-years ) . In multivariable-adjusted analysis , the HR for women comparing the highest quintile of dietary total antioxidant capacity to the lowest was 0.80 ( 95 % CI , 0.67 - 0.97 ; P for trend=0.02 ) . Servings of fruit and vegetables and whole grains were nonsignificantly inversely associated with myocardial infa rct ion . CONCLUSIONS These data suggest that dietary total antioxidant capacity , based on fruits , vegetables , coffee , and whole grains , is of importance in the prevention of myocardial infa rct ion Prospect i ve epidemiological studies have reported that a higher fruit and vegetable intake is associated with a lower risk of CHD . The aim of the present study was to examine associations between fruit and vegetable consumption , in particular the subgroupings citrus fruits , apples and cruciferous vegetables , and the risk of acute coronary syndrome ( ACS ) . During a median follow-up of 7.7 years , 1075 incident ACS cases were identified among 53 383 men and women , aged 50 - 64 years at recruitment into the Diet , Cancer and Health cohort study in 1993 - 7 . Fruit and vegetable intake was estimated from a vali date d FFQ , and ACS incidence rate ratios ( IRR ) were estimated using Cox proportional hazards models . Overall , a tendency towards a lower risk of ACS was observed for both men and women with higher fruit and vegetable consumption . For men , we found an inverse association for apple intake ( IRR per 25 g/d : 0.97 ; 95 % CI 0.94 , 0.99 ) . This association was also seen among women , albeit borderline significant . However , a higher risk was seen among women with higher fruit juice intake ( IRR per 25 g/d : 1.04 ; 95 % CI 1.00 , 1.08 ) . The present results provide some support for previously observed inverse associations between fresh fruit intake , particularly apples , and ACS risk BACKGROUND : Beverages are contributing an increased proportion of energy to the diet . Because they elicit a weak compensatory dietary response , they may increase risk of positive energy balance . OBJECTIVES : This study aim ed to document the differential effects of matched liquid and solid carbohydrate loads on diet and body weight . DESIGN : In a cross-over design , seven males and eight females consumed dietary carbohydrate loads of 1880 kJ/day as a liquid ( soda ) or solid ( jelly beans ) during two 4 week periods separated by a 4 week washout . Subjects were permitted to consume the loads however they chose . In addition to baseline measurements , diet records were obtained on r and om days throughout the study , body composition was measured weekly , physical activity was assessed before and after treatments and hunger was assessed during washout and midway through each treatment . RESULTS : Free-feeding energy intake during the solid period was significantly lower than intake prior to this period . Dietary energy compensation was precise ( 118 % ) . No decrease in free-feeding energy intake occurred during the liquid period . Total daily energy intake increased by an amount equal to the load result ing in dietary compensation of −17 % . Consequently , body weight and BMI increased significantly only during the liquid period . Physical activity and hunger were unchanged . CONCLUSIONS : This study indicates that liquid carbohydrate promotes positive energy balance , whereas a comparable solid carbohydrate elicits precise dietary compensation . Increased consumption of energy-yielding fluids may promote positive energy balance BACKGROUND Epidemiologic studies of fish consumption in relation to risk of stroke have yielded inconsistent results . OBJECTIVE In this study , we examined the association between fish consumption and stroke incidence in women . DESIGN We analyzed data from a population -based prospect i ve cohort of 34,670 women in the Swedish Mammography Cohort who were free of cardiovascular disease and cancer at baseline . Information on fish consumption was obtained by a self-administered question naire in 1997 . Incident cases of stroke were ascertained from the Swedish Hospital Discharge Registry . We used Cox proportional hazards regression to estimate relative risks ( RRs ) and 95 % CIs . RESULTS Over a mean follow-up of 10.4 y , we ascertained 1680 incident cases of stroke , including 1310 cerebral infa rct ions , 233 hemorrhagic strokes , and 137 unspecified strokes . Fish consumption was significantly inversely associated with risk of total stroke but not with cerebral infa rct ion or hemorrhagic stroke . Compared with women in the lowest quintile of fish consumption ( < 1.0 serving of fish/wk ) , the multivariable RR of total stroke for women in the highest quintile ( > 3.0 servings of fish/wk ) was 0.84 ( 95 % CI : 0.71 , 0.98 ; P for trend = 0.049 ) . Consumption of lean fish but not of other fish types was inversely associated with risk of stroke . The multivariable RR of total stroke was 0.67 ( 95 % CI : 0.49 , 0.93 ; P for trend = 0.07 ) for ≥3 servings of lean fish/wk compared with that for no consumption . CONCLUSION These results suggest that the consumption of fish , especially of lean fish , may reduce risk of stroke in women . This trial was registered at clinical trials.gov as NCT01127698 BACKGROUND AND AIMS The Mediterranean diet , which is palatable and easily achievable , has been associated with lower all-cause and cardiovascular disease ( CVD ) incidence and mortality . Data on heart failure ( HF ) and stroke types are lacking . The aim was to examine a Mediterranean diet in relation to incidence of myocardial infa rct ion ( MI ) , HF and stroke types in a Swedish prospect i ve cohort . METHODS In a population -based cohort of 32,921 women , diet was assessed through a self-administered question naire . The modified Mediterranean diet ( mMED ) score was created based on high consumption of vegetables , fruits , legumes , nuts , whole grains , fermented dairy products , fish and monounsaturated fat , moderate intakes of alcohol and low consumption of red meat , on a 0 - 8 scale . Relative risks ( RR ) with 95 % confidence intervals ( CI ) , adjusted for potential confounders , were estimated by Cox proportional hazards regression models . RESULTS During 10 y of follow-up ( 1998 - 2008 ) , 1109 MIs , 1648 HFs , 1270 ischemic strokes and 262 total hemorrhagic strokes were ascertained . A high adherence to the mMED score ( 6 - 8 ) , compared to low , was associated with a lower risk of MI ( RR : 0.74 , 95 % CI : 0.61 - 0.90 , p = 0.003 ) , HF ( RR : 0.79 , 95 % CI : 0.68 - 0.93 , p = 0.004 ) and ischemic stroke ( RR : 0.78 , 95 % CI : 0.65 - 0.93 , p = 0.007 ) , but not hemorrhagic stroke ( RR : 0.88 , 95 % CI : 0.61 - 1.29 , p = 0.53 ) . CONCLUSIONS Better adherence to a Mediterranean diet was associated with lower risk of MI , HF and ischemic stroke . The Mediterranean diet is most likely to be beneficial in primary prevention of all major types of atherosclerosis-related CVD BACKGROUND Consumption of sugar-sweetened soda has been associated with an increased risk of cardiometabolic disease . The relation with cerebrovascular disease has not yet been closely examined . OBJECTIVE Our objective was to examine patterns of soda consumption and substitution of alternative beverages for soda in relation to stroke risk . DESIGN The Nurses ' Health Study , a prospect i ve cohort study of 84,085 women followed for 28 y ( 1980 - 2008 ) , and the Health Professionals Follow-Up Study , a prospect i ve cohort study of 43,371 men followed for 22 y ( 1986 - 2008 ) , provided data on soda consumption and incident stroke . RESULTS We documented 1416 strokes in men during 841,770 person-years of follow-up and 2938 strokes in women during 2,188,230 person-years of follow-up . The pooled RR of total stroke for ≥ 1 serving of sugar-sweetened soda/d , compared with none , was 1.16 ( 95 % CI : 1.00 , 1.34 ) . The pooled RR of total stroke for ≥ 1 serving of low-calorie soda/d , compared with none , was 1.16 ( 95 % CI : 1.05 , 1.28 ) . Compared with 1 serving of sugar-sweetened soda/d , 1 serving of decaffeinated coffee/d was associated with a 10 % ( 95 % CI : 1 % , 19 % ) lower risk of stroke and 1 serving of caffeinated coffee/d with a 9 % ( 95 % CI : 0 % , 17 % ) lower risk . Similar estimated reductions in risk were seen for substitution of caffeinated or decaffeinated coffee for low-calorie soda . CONCLUSIONS Greater consumption of sugar-sweetened and low-calorie sodas was associated with a significantly higher risk of stroke . This risk may be reduced by substituting alternative beverages for soda OBJECTIVE To prospect ively assess the associations between lean fish , fatty fish and total fish intakes and risk of stroke in the Spanish cohort of the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC-Spain ) . DESIGN Fish intake was estimated from a vali date d dietary question naire . Cox proportional hazards regression models were used to assess the association between the intakes of lean fish , fatty fish and total fish and stroke risk . Models were run separately for men and women . SETTING Five Spanish regions ( Asturias , San Sebastian , Navarra , Granada and Murcia ) . SUBJECTS Individuals ( n 41 020 ; 15 490 men and 25 530 women ) aged 20 - 69 years , recruited from 1992 to 1996 and followed-up until December 2008 ( December 2006 in the case of Asturias ) . Only participants with definite incident stroke were considered as cases . RESULTS During a mean follow-up of 13·8 years , 674 strokes were identified and subsequently vali date d by record linkage with hospital discharge data bases , primary -care records and regional mortality registries , comprising 531 ischaemic , seventy-nine haemorrhagic , forty-two subarachnoid and twenty-two unspecific strokes . After multiple adjustments , no significant associations were observed between lean fish , fatty fish and total fish consumption and the risk of stroke in men or women . In men , results revealed a non-significant trend towards an inverse association between lean fish ( hazard ratio=0·84 ; 95 % CI 0·55 , 1·29 , P trend=0·06 ) and total fish consumption ( hazard ratio=0·77 ; 95 % CI 0·51 , 1·16 , P trend=0·06 ) and risk of total stroke . CONCLUSIONS In the EPIC-Spain cohort , no association was found between lean fish , fatty fish and total fish consumption and risk of stroke BACKGROUND Dietary nut intake has been associated with a reduced risk of coronary heart disease mortality ; however , the mechanism is unclear . Since components of nuts may have antiarrhythmic properties , part of the benefit may be due to a reduction in sudden cardiac death . METHODS We prospect ively assessed whether increasing frequency of nut consumption , as ascertained by an abbreviated food frequency question naire at 12 months of follow-up , was associated with a lower risk of sudden cardiac death and other coronary heart disease end points among 21 454 male participants enrolled in the US Physicians ' Health Study . Participants were followed up for an average of 17 years . RESULTS Dietary nut intake was associated with a significantly reduced risk of sudden cardiac death after controlling for known cardiac risk factors and other dietary habits ( P for trend,.01 ) . Compared with men who rarely or never consumed nuts , those who consumed nuts 2 or more times per week had reduced risks of sudden cardiac death ( relative risk , 0.53 ; 95 % confidence interval , 0.30 - 0.92 ) and total coronary heart disease death ( relative risk , 0.70 ; 95 % confidence interval , 0.50 - 0.98 ) . In contrast , nut intake was not associated with significantly reduced risks of nonsudden coronary heart disease death or nonfatal myocardial infa rct ion . CONCLUSION These prospect i ve data in US male physicians suggest that the inverse association between nut consumption and total coronary heart disease death is primarily due to a reduction in the risk of sudden cardiac death OBJECTIVE To assess the relationship between habitual fish intake and fatty acid levels in serum as well as in the LDL fractions of serum phospholipids and cholesteryl esters . DESIGN Cross-sectional study . SETTING Cohort of Gipuzkoa ( Basque Country , northern Spain ) included in the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) project . SUBJECTS R and om sample of 120 healthy volunteers of both sexes aged 35 - 65 y , divided into various consumption groups according to daily fish intake . METHODS Data on habitual intake over the previous year was collected by trained interviewers by means of a computerized question naire based on the diet history method . Fasting venous blood sample s were drawn and fatty acids were measured by gas-liquid chromatography . RESULTS Lean fish accounted for 78 % of all fish consumption in the highest consumption group ( > 115 g/day ) and for 60 % in the lowest ( < 31 g/day ) . The mean concentrations of omega-3 polyunsaturated fatty acids ( PUFA ) , eicosapentaenoic acid ( EPA , C20:5 , omega-3 ) , and docosahexaenoic acid ( DHA , C22:6 , omega-3 ) in serum and in the LDL fractions of serum phospholipids and cholesteryl esters increased significantly from the lowest to the highest fish consumption categories . Fish intake showed a statistically significant relationship with omega-3 PUFA , EPA and DHA in serum and in the LDL fractions of serum phospholipids and cholesteryl esters both in the simple linear regression analysis and in a multiple regression model adjusted by age , body mass index ( BMI ) and vegetable intake . CONCLUSIONS Habitual fish intake is reflected in the content of EPA and DHA in serum and in the LDL phospholipid and cholesteryl esters fractions . The concentrations of very-long-chain omega-3 fatty acids are useful biomarkers for dietary fish intake , mainly lean fish . SPONSORSHIP Europe Against Cancer Programme of the European Union ( agreement SOC 97 200302 05F02 ) ; ' Fondo de Investigaciones Sanitarias ' , Spanish Ministry of Health ( FIS grant 99/0024 - 05 ) ; Government of the Basque Country ; and ' Fundación Científica de la Asociación Española contra el Cáncer ' BACKGROUND & AIMS While nut consumption has been shown to lower the risk of hypertension and coronary disease , it is not known whether nut consumption is associated with the risk of stroke . We sought to examine whether nut consumption is associated with total and subtypes of stroke . METHODS Prospect i ve cohort of 21,078 participants from the Physicians ' Health Study ( 1982 - 2008 ) who were free of stroke at baseline . Nut consumption was assessed using a simple 19-item food question naire and stroke cases were confirmed after review ing medical records . We used Cox 's proportional hazards regression to estimate relative risks of total , ischemic , and hemorrhagic stroke according to consumption of any nuts . RESULTS During a mean follow up of 21.1 years , 1424 incident cases of stroke occurred ( 219 hemorrhagic , 1189 ischemic , and 16 of undetermined cause ) . There was no statistically significant association between nut consumption and total or ischemic stroke . In contrast , there was a suggestive non-linear relation between nut intake and hemorrhagic stroke : compared to subjects who did not consume nuts , multivariable-adjusted hazard ratios ( 95 % CI ) for hemorrhagic stroke for subjects consuming nuts < 1 , 1 , 2 - 4 , 5 - 6 , and ≥7 times/week were 1.13 ( 0.78 - 1.62 ) , 1.05 ( 0.70 - 1.58 ) , 0.49 ( 0.27 - 0.89 ) , 1.50 ( 0.79 - 2.84 ) , and 1.84 ( 0.95 - 3.57 ) , respectively ( p for quadratic trend 0.12 ) . CONCLUSIONS Our data showed no association between nuts and ischemic stroke and suggested a J-shaped relation between nut consumption and hemorrhagic stroke . Replication of our findings in the general population is warranted BACKGROUND A beneficial role of fish consumption on the risk of myocardial infa rct ion ( MI ) has been reported and is mostly ascribed to n-3 ( omega-3 ) fatty acids . However , fish also contains methylmercury , which may increase the risk of MI . OBJECTIVE The objective was to determine how fish consumption and erythrocyte concentrations of mercury ( Ery-Hg ) and selenium ( Ery-Se ) are related to the risk of MI and whether n-3 fatty acids ( eicosapentaenoic and docosahexaenoic acids ) in plasma phospholipids ( P-EPA+DHA ) are protective . DESIGN This was a case-control study nested within the northern Sweden cohort , in which data and sample s were collected prospect ively . The study included 431 cases with an MI after data and sample collection , including 81 sudden cardiac deaths ( SCDs ) and 499 matched controls . Another 69 female cases with controls from a breast cancer screening registry were included in sex-specific analyses . RESULTS Odds ratios for the third compared with the first tertile were 0.65 ( 95 % CI : 0.46 , 0.91 ) for Ery-Hg , 0.75 ( 95 % CI : 0.53 , 1.06 ) for Ery-Se , and 0.78 ( 95 % CI : 0.54 , 1.11 ) for P-EPA+DHA . Ery-Hg and P-EPA+DHA were intercorrelated ( Spearman 's R = 0.34 ) . No association was seen for reported fish consumption . Multivariate modeling did not change these associations significantly . Sex-specific analyses showed no differences in risk associations . High concentrations of Ery-Se were associated with an increased risk of SCD . CONCLUSIONS The biomarker results indicate a protective effect of fish consumption . No harmful effect of mercury was indicated in this low-exposed population in whom Ery-Hg and P-EPA+DHA were intercorrelated Recent meta-analyses have confirmed that fish consumption is related to decreased risks of ischaemic stroke and fatal CHD , while there seem to be no clear associations between fish consumption and the risks of haemorrhagic stroke and non-fatal CHD . As no studies in German population s have been reported to date , we assessed whether fish consumption as recorded by FFQ between 1994 and 1998 was related to incident myocardial infa rct ion ( MI ) and stroke within the German arm of the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) study . Cox proportional hazards regression analyses were conducted based on the data of 48 315 participants aged 35–65 years at baseline . The median fish intake was 16·4 g/d ( 25th–75th percentile 8·2–28·8 g/d ) . During a mean follow-up of 8·1 years , 605 incident MI and 525 incident strokes have been documented . After multiple adjustment , fish consumption was not related to incident MI ( hazard ratio ( HR ) 0·84 , 95 % CI 0·66 , 1·08 , P trend= 0·21 ) or stroke ( HR 0·96 , 95 % CI 0·73 , 1·26 , P trend= 0·67 ) . Separate analyses for fatal MI , ischaemic stroke and haemorrhagic stroke did not show significant associations , either . With regard to non-fatal MI , there was a non-significant trend for an inverse association ( HR 0·78 , 95 % CI 0·59 , 1·03 , P trend= 0·07 ) . Overall , fish consumption was not related to the risks of MI and stroke in the EPIC-Germany study BACKGROUND Rice consumption has been associated with risk of type 2 diabetes , but its relation with cardiovascular disease ( CVD ) is limited . OBJECTIVE We examined the association between rice consumption and risk of CVD incidence and mortality in a Japanese population . DESIGN This was a prospect i ve study in 91,223 Japanese men and women aged 40 - 69 y in whom rice consumption was determined and up date d from 3 self-administered food-frequency question naires , each 5 y apart . Follow-up for incidence was from 1990 to 2009 in cohort I and 1993 to 2007 in cohort II and for mortality was from 1990 to 2009 in cohort I and 1993 to 2009 in cohort II . HRs and 95 % CIs of CVD incidence and mortality were calculated according to quintiles of cumulative average rice consumption . RESULTS In 15 - 18 y of follow-up , we ascertained 4395 incident cases of stroke , 1088 incident cases of ischemic heart disease ( IHD ) , and 2705 deaths from CVD . Rice consumption was not associated with risk of incident stroke or IHD ; the multivariable HR ( 95 % CI ) in the highest compared with lowest rice consumption quintiles was 1.01 ( 0.90 , 1.14 ) for total stroke and 1.08 ( 0.84 , 1.38 ) for IHD . Similarly , there was no association between rice consumption and risk of mortality from CVD ; the HR ( 95 % CI ) for mortality from total CVD was 0.97 ( 0.84 , 1.13 ) . There were no interactions with sex or effect modifications by body mass index for any endpoint . CONCLUSION Rice consumption is not associated with risk of CVD morbidity or mortality BACKGROUND Soft drink intake has been associated with obesity and diabetes , but its relation with risk of cardiovascular disease ( CVD ) is limited . OBJECTIVE We examined the association between soft drink intake and risk of CVD in a Japanese population . DESIGN This was a prospect i ve study in 39,786 Japanese men and women aged 40 - 59 y in which soft drink intake was determined by using a self-administered food-frequency question naire . Follow-up was from 1990 to 2008 . HRs and 95 % CIs of incidence were calculated according to categories of soft drink intake . RESULTS During 18 y of follow-up , we ascertained 453 incident cases of ischemic heart disease ( IHD ) and 1922 cases of stroke , including 859 hemorrhagic and 1047 ischemic strokes . Soft drink intake was positively associated with risk of total stroke and more specifically ischemic stroke for women ; the multivariable HR ( 95 % CI ) in the highest soft drink intake ( almost every day ) category compared with the lowest intake ( never or rarely ) category was 1.21 ( 0.88 , 1.68 ; P-trend = 0.02 ) for total stroke and 1.83 ( 1.22 , 2.75 ; P-trend = 0.001 ) for ischemic stroke . That association did not change significantly after the exclusion of early incident cases within 3 - 9 y from baseline . A nonsignificant inverse trend for risks of total and ischemic strokes was shown for men , and it was weakened after the exclusion of early incident cases or after the exclusion of participants with baseline comorbidities . Soft drink intake was not associated with risk of IHD or hemorrhagic stroke for either sex . CONCLUSION Soft drink intake is associated with higher risk of ischemic stroke for women BACKGROUND Soybean protein and dietary fiber supplementation reduce serum cholesterol in r and omized controlled trials . Consumption of legumes , which are high in bean protein and water-soluble fiber , may be associated with a reduced risk of coronary heart disease ( CHD ) . METHODS A total of 9632 men and women who participated in the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study ( NHEFS ) and were free of cardiovascular disease ( CVD ) at their baseline examination were included in this prospect i ve cohort study . Frequency of legume intake was estimated using a 3-month food frequency question naire , and incidence of CHD and CVD was obtained from medical records and death certificates . RESULTS Over an average of 19 years of follow-up , 1802 incident cases of CHD and 3680 incident cases of CVD were documented . Legume consumption was significantly and inversely associated with risk of CHD ( P = .002 for trend ) and CVD ( P = .02 for trend ) after adjustment for established CVD risk factors . Legume consumption 4 times or more per week compared with less than once a week was associated with a 22 % lower risk of CHD ( relative risk , 0.78 ; 95 % confidence interval , 0.68 - 0.90 ) and an 11 % lower risk of CVD ( relative risk , 0.89 ; 95 % confidence interval , 0.80 - 0.98 ) . CONCLUSIONS Our study indicates a significant inverse relationship between legume intake and risk of CHD and suggests that increasing legume intake may be an important part of a dietary approach to the primary prevention of CHD in the general population The relation between dairy foods , particularly specific foods , and risk of cardiovascular disease ( CVD ) remains unclear . We examined the association between total , as well as specific , dairy food intakes and incidence of myocardial infa rct ion ( MI ) in a prospect i ve population -based cohort . We followed 33,636 women ( aged 48 - 83 y ) , free from CVD , cancer , and diabetes at baseline ( 1997 ) , in the Swedish Mammography Cohort . Consumption of milk , cultured milk/yogurt , cheese , cream , crème fraiche , and butter was obtained from a vali date d self-administered FFQ at baseline . We used Cox proportional hazards regression models to estimate HRs and 95 % CIs , adjusted for relevant CVD risk factors . MI incidence was ascertained from national registries . Over 11.6 y of follow-up , we ascertained 1392 cases of MI . When the highest quintile was compared with the lowest quintile , total dairy food intake was inversely associated with MI risk [ multivariable adjusted HR : 0.77 ( 95 % CI : 0.63 , 0.95 ) ] . Among specific dairy food products , total cheese was inversely associated [ HR : 0.74 ( 95 % CI : 0.60 , 0.91 ) ] and butter used on bread but not on cooking was positively associated [ HR : 1.34 ( 95 % CI : 1.02 , 1.75 ) ] with MI risk . Other specific dairy food products were not significantly associated with MI risk . No differences were observed between consumption of specific low-fat and high-fat dairy foods , expressed as either absolute intakes or intakes relative to the total , and MI risk . Failure to consider dairy foods as a heterogeneous group in future studies could hamper important insights of relevance for the development of dietary guidelines BACKGROUND Heart failure ( HF ) is the leading cause of hospitalization among the elderly population in the United States . Consumption of grain products and dietary fiber has been shown to reduce the risk of hypertension and myocardial infa rct ion . However , it is not known whether a higher consumption of breakfast cereals is associated with risk of HF . METHODS This study evaluated prospect ively the association between breakfast cereal intake and incident HF among 21 376 participants of the Physicians ' Health Study I. Cereal consumption was estimated using a semiquantitative food frequency question naire . Incident HF was ascertained through annual follow-up question naires and vali date d using Framingham criteria . We used Cox regression models to estimate adjusted relative risk of HF across categories of cereal intake . RESULTS During an average follow-up of 19.6 years , 1018 incident cases of HF occurred . For average weekly cereal consumption of 0 servings , 1 or fewer , 2 to 6 , and 7 or more , hazard ratios ( 95 % confidence intervals ) for HF were 1 ( reference ) , 0.92 ( 0.78 - 1.09 ) , 0.79 ( 0.67 - 0.93 ) , and 0.71 ( 0.60 - 0.85 ) , respectively ( P<.001 for trend ) , adjusting for age , smoking , alcohol consumption , vegetable consumption , use of multivitamins , exercise , and history of atrial fibrillation , valvular heart disease , and left ventricular hypertrophy . However , the association was limited to the intake of whole grain cereals ( P < .001 for trend ) but not refined cereals ( P = .70 for trend ) . CONCLUSIONS Our data demonstrate that a higher intake of whole grain breakfast cereals is associated with a lower risk of HF . Additional studies are warranted to confirm these findings and determine specific nutrients that are responsible for such a protection OBJECTIVES Our aim was to investigate the relation between fish consumption and incidence of congestive heart failure ( CHF ) . BACKGROUND The incidence and health burden of CHF are rising , particularly in older persons . Although n-3 fatty acids have effects that could favorably influence risk of CHF , the relation between fish intake and CHF incidence is unknown . METHODS Among 4,738 adults age > or = 65 years and free of CHF at baseline in 1989 - 90 , usual dietary intake was assessed using a food frequency question naire . In a participant sub sample , consumption of tuna or other broiled or baked fish , but not fried fish , correlated with plasma phospholipid n-3 fatty acids . Incidence of CHF was prospect ively adjudicated . RESULTS During 12 years ' follow-up , 955 participants developed CHF . In multivariate-adjusted analyses , tuna/other fish consumption was inversely associated with incident CHF , with 20 % lower risk with intake 1 to 2 times/week ( hazard ratio [ HR ] = 0.80 , 95 % confidence interval [ CI ] = 0.64 to 0.99 ) , 31 % lower risk with intake 3 to 4 times/week ( HR = 0.69 , 95 % CI = 0.52 to 0.91 ) , and 32 % lower risk with intake > or = 5 times/week ( HR = 0.68 , 95 % CI = 0.45 to 1.03 ) , compared with intake < 1 time/month ( p trend = 0.009 ) . In similar analyses , fried fish consumption was positively associated with incident CHF ( p trend = 0.01 ) . Dietary long-chain n-3 fatty acid intake was also inversely associated with CHF ( p trend = 0.009 ) , with 37 % lower risk in the highest quintile of intake ( HR = 0.73 , 95 % CI = 0.57 to 0.94 ) compared with the lowest . CONCLUSIONS Among older adults , consumption of tuna or other broiled or baked fish , but not fried fish , is associated with lower incidence of CHF . Confirmation in additional studies and evaluation of potential mechanisms is warranted Few prospect i ve studies have examined the effects of different types of dairy food on the risks of type 2 diabetes , CHD and mortality . We examined whether intakes of total dairy , high-fat dairy , low-fat dairy , milk and fermented dairy products were related to these outcomes in the Whitehall II prospect i ve cohort study . At baseline , dairy consumption was assessed by FFQ among 4526 subjects ( 72 % men ) with a mean age 56 ( sd 6 ) years . Death certificates and medical records were used to ascertain CHD mortality and non-fatal myocardial infa rct ion . Incident diabetes was detected by the oral glucose tolerance test or self-report . Incidence data were analysed using Cox proportional hazards models , adjusted for lifestyle and dietary factors . During approximately 10 years of follow-up , 273 diabetes , 323 CHD and 237 all-cause mortality cases occurred . In multivariable models , intakes of total dairy and types of dairy products were not significantly associated with incident diabetes or CHD ( all P values for trend > 0·1 ) . Fermented dairy products was inversely associated with overall mortality ( hazard ratios approximately 0·7 in the middle and highest tertiles ; P for trend < 0·01 ) but not with incident CHD or diabetes ( P>0·3 ) . In conclusion , intakes of total dairy and types of dairy products showed no consistent relationship with incident diabetes , CHD or all-cause mortality BACKGROUND High intake of whole grains has been associated with lower risk of coronary heart disease ; however , the research that has been used to evaluate different effects of different whole-grain cereals ( e.g. , wheat , rye , and oats ) has been sparse . OBJECTIVE We investigated the association between whole-grain intake in terms of total intake and intakes of different cereals and myocardial infa rct ion . DESIGN This prospect i ve study included 54,871 Danish adults aged 50 - 64 y , of whom 2329 individuals developed myocardial infa rct ion ( 13.6 y of follow-up ) . Detailed information on daily intake of whole-grain products was available from a self-administered food-frequency question naire , and intakes of total whole grain and whole-grain species ( wheat , rye , and oats ) were estimated . The association between intake of whole grains and risk of myocardial infa rct ion was examined with the use of a Cox proportional hazards model adjusted for potential confounders . RESULTS For both men and women with total whole-grain intake in the highest quartile , lower risks of myocardial infa rct ion were shown [ HRs : 0.75 ( 95 % CI : 0.65 , 0.86 ) and 0.73 ( 95 % CI : 0.58 , 0.91 ) , respectively ] than for individuals with intake in the lowest quartile . When the specific cereal species were considered , rye and oats , but not wheat , were associated with lower myocardial infa rct ion risk in men . No significant associations were seen in women . For total whole-grain products , significantly lower myocardial infa rct ion risks were seen with higher intakes in both men and women . Rye bread ( in men and women ) and oatmeal ( in men ) were associated with significantly lower risk of myocardial infa rct ion , whereas no significant association was shown for whole-grain bread , crispbread , and wheat . CONCLUSION In this study , we provide support for the hypothesis that whole-grain intake is related to lower risk of myocardial infa rct ion and suggest that the cereals rye and oats might especially hold a beneficial effect BACKGROUND Observationally , reports on the association between milk intake and risk of ischaemic heart disease ( IHD ) and myocardial infa rct ion ( MI ) have produced conflicting results ; and no previous large-scale study using the lactase persistent/non-persistent LCT-13910 C/T genotype as a largely unconfounded proxy for milk intake free of reverse causation has been conducted . We tested the hypothesis that milk intake observationally and genetically through the LCT-13910 C/T genotype is associated with risk of IHD and MI in a Mendelian r and omization design . METHODS We included 98,529 White individuals of Danish descent , aged 20 - 100 years , from three studies of the general population . Information on IHD ( N = 10,372 ) and MI ( N = 4188 ) were obtained from national Danish registries . First , we investigated observational associations between milk intake and incident IHD and MI . Second , we confirmed the association between the rs4988235 genetic variant LCT-13910 C/T , associated with lactase persistence/non-persistence , and milk intake . Finally , we tested whether LCT-13910 C/T genotype was associated with risk of IHD and MI as well as with cardiovascular risk factors . RESULTS During a mean follow-up time of 5.4 years , the observational hazard ratio for a 1 glass/week higher milk intake was 1.00 [ 95 % confidence interval ( CI ) : 1.00,1.01 ] for both IHD and MI . Median milk intake was 3 glasses/week ( interquartile range : 0 - 7 ) in lactase CC non-persistent individuals compared with 5 glasses/week ( 0 - 10 ) in lactase TC/TT persistent individuals ( P = 3 * 10(-60 ) ) . In the dominant genetic model comparing lactase TC/TT persistent individuals with lactase CC non-persistent individuals , the odds ratio was 1.00 ( 0.92,1.09 ) for IHD and 0.96 ( 0.84,1.09 ) for MI . Finally , in the dominant genetic model genotype was not associated convincingly with plasma levels of total cholesterol , low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , triglycerides or glucose , nor with blood pressure . CONCLUSION Milk intake was not associated with risk of IHD or MI , observationally or genetically Background — Reduction in dietary cholesterol is widely recommended for the prevention of cardiovascular disease . Although eggs are important sources of dietary cholesterol and other nutrients , little is known about the association between egg consumption and heart failure ( HF ) risk . Methods and Results — In a prospect i ve cohort study of 21 275 participants from the Physicians ' Health Study I , we examined the association between egg consumption and the risk of HF . Egg consumption was assessed with the use of a simple abbreviated food question naire , and we used Cox regression to estimate relative risks of HF . After an average follow-up of 20.4 years , a total of 1084 new HF cases occurred in this cohort . Although egg consumption up to 6 times per week was not associated with incident HF , egg consumption of ≥7 per week was associated with an increased risk of HF . Compared with subjects who reported egg consumption of < 1 per week , hazard ratios ( 95 % confidence intervals ) for HF were 1.28 ( 1.02 to 1.61 ) and 1.64 ( 1.08 to 2.49 ) for egg consumption of 1 per day and ≥2 per day , respectively , after adjustment for age , body mass index , smoking , alcohol consumption , exercise , and history of atrial fibrillation , hypertension , valvular heart disease , and hypercholesterolemia . Similar results were obtained for HF without antecedent myocardial infa rct ion . Conclusions — Our data suggest that infrequent egg consumption is not associated with the risk of HF . However , egg consumption of ≥1 per day is related to an increased risk of HF among US male physicians This study investigate the relation between fish consumption , all-cause mortality , and incidence of coronary heart disease ( CHD ) . A total of 4,513 men and 3,984 women aged 30 - 70 years , sample d r and omly from the population in Copenhagen County , Denmark , with initially examination in 1982 - 1992 was followed until 2000 for all-cause mortality and until 1997 for first admission to hospital or death from CHD . Information on fish consumption was obtained from a self-administered food-frequency question naire . Cox proportional hazard analysis gave no evidence for an inverse association between fish consumption and all-cause mortality or incident CHD after adjustment for confounders . Among subjects with a priory-defined high risk of CHD there was a nonsignificant inverse relation between fish intake and CHD morbidity ( Hazard Ratio 1.28 ( 0.92 - 1.80 ) for a consumption of fish of less than two times per month or less compared with once a week ) , but there was relatively few cases in this subgroup . These data provides no evidence for a protective effect of fish consumption on all-cause mortality or incident CHD in the population as a whole , but it can not be excluded that frequent consumption of fish benefits those at high risk for CHD OBJECTIVES To examine the association between fish consumption and stroke risk . DESIGN Prospect i ve population cohort study . SETTING Norfolk , UK cohort of the European Prospect i ve Investigation into Cancer ( EPIC-Norfolk ) . SUBJECTS Subjects were 24 312 men and women aged 40 - 79 years who had no previous history of stroke at baseline . METHODS Fish consumption was assessed using a food-frequency question naire at baseline in 1993 - 1997 and stroke incidence ascertained to 2004 . RESULTS A total of 421 incident strokes were identified ( mean follow-up=8.5 years , total person-years=209 238 ) . There were no significant relationships between total fish , shellfish or fish roe consumption and risk of stroke in men and women after adjusting for age , systolic blood pressure , body mass index , smoking , cholesterol , diabetes , physical activity , alcohol consumption , fish oil supplement use and total energy intake using Cox regression analyses . Oily fish consumption was significantly lower in women who subsequently had a stroke ( odds ratio ( OR ) for consumers vs. non-consumers=0.69 , 95 % confidence interval ( CI ) 0.51 - 0.94 , P=0.02 ) . The trend in men was similar but not significant ( OR for consumers vs. non-consumers=0.88 , 95 % CI 0.65 - 1.19 , P=0.41 ) . CONCLUSIONS There was no consistent relationship between fish consumption and stroke in this British population . Inconsistencies in the observed health effects of fish consumption in different population s may reflect different patterns and type of fish consumed and preparation methods BACKGROUND The joint effects of different lifestyle factors on stroke risk are still to some extent unclear , especially regarding hemorrhagic stroke . METHODS We prospect ively investigated the association of different indicators of lifestyle ( smoking , body mass index , physical activity , and vegetable and alcohol consumption ) with total and type-specific stroke incidence among 36 686 Finnish participants who were 25 to 74 years old and free of coronary heart disease and stroke at baseline . RESULTS During a mean follow-up period of 13.7 years , 1478 people developed an incident stroke event ( 1167 ischemic and 311 hemorrhagic ) . The multivariate-adjusted ( age , sex , education , family history of stroke , history of diabetes mellitus , systolic blood pressure , and serum total cholesterol level ) hazard ratios associated with adherence to 0 to 1 ( reference group ) , 2 , 3 , 4 , and 5 healthy lifestyle indicators were 1 , 0.66 , 0.57 , 0.51 , and 0.33 ( P < .001 for trend ) for total stroke ; 1 , 0.67 , 0.60 , 0.50 , and 0.30 ( P < .001 for trend ) for ischemic stroke ; and 1 , 0.63 , 0.49 , 0.49 , and 0.40 ( P < .001 for trend ) for hemorrhagic stroke , respectively . These inverse associations were similar in both men and women . The partial population attributable risk percentages associated with adherence to 3 , 4 , and 5 healthy lifestyle indicators were 26.3 % , 43.8 % , and 54.6 % for total stroke ; 22.7 % , 45.3 % , and 59.7 % for ischemic stroke ; and 35.0 % , 35.0 % , and 36.1 % for hemorrhagic stroke , respectively . CONCLUSION Healthy lifestyle factors are associated with a lower risk of stroke , and there is a grade d inverse association between the number of healthy lifestyle indicators and the risks of total , ischemic , and hemorrhagic stroke Studies of the beneficial role of fish consumption in the prevention of CVD are not consistent in their findings , particularly those studies that focus on the risk of stroke . The aim of the present study is to investigate the relationship between the consumption of different types of fish and the subsequent incidence of cerebrovascular disease ( CVA ) . We prospect ively evaluated the association between consumption of different types of fish and CVA in 3958 men and women aged 40 - 79 years who were free of heart disease and had participated in a health examination survey from 1967 to 1972 . A total of 659 incident cases of CVA occurred during a follow-up until the end of 1994 . A dietary history interview method provided data on habitual consumption of fish and other foods over the preceding year at baseline . Total fish intake did not predict CVA , but consumption of salted fish suggested an increased risk of intracerebral haemorrhage . The relative risk of intracerebral haemorrhage between the highest tertile of salted fish consumption and non-consumers was 1.98 ( 95 % CI 1.02 , 3.84 ; P for trend = 0.06 ) after adjustment for age , sex , energy intake , smoking , BMI , physical activity , geographic area , occupation , diabetes , use of post-menopausal hormones , serum cholesterol , hypertension , and consumptions of butter , vegetables , fruits and berries . The relationship between fish consumption and stroke risk is not straightforward . How the fish is prepared for consumption may play an important role , affecting the association The protective effects of fruits and vegetables against CHD have been suggested by many epidemiological studies among Western population s. However , prospect i ve data are lacking for Asian population s. In the present study , we examined the associations of fruit and vegetable intake with CHD incidence among 67 211 women ( aged 40 - 70 years ) and 55 474 men ( aged 40 - 74 years ) living in Shanghai , China . Food intake was assessed using vali date d FFQ through in-person interviews . Coronary events ( non-fatal myocardial infa rct ion or fatal CHD ) were identified by biennial home visits and further confirmed by medical record review . During a mean follow-up period of 9·8 and 5·4 years , 148 events in women and 217 events in men were documented and verified . After adjustment for potential confounders , women in the highest quartile of total fruit and vegetable intake ( median 814 g/d ) had a hazard ratio ( HR ) of 0·62 ( 95 % CI 0·38 , 1·02 ) for CHD ( P for trend = 0·04 ) compared with those in the lowest quartile ( median 274 g/d ) . This association was primarily driven by fruits ( HR for the highest v. the lowest intake in women : 0·62 , 95 % CI 0·37 , 1·03 ) . The strength of the association was attenuated after further controlling for history of diabetes or hypertension . For men , no significant association was found for fruit and vegetable intake when analysed either in combination or individually . The present findings suggest that a high consumption of fruits may reduce CHD risk in Chinese women BACKGROUND Epidemiologic studies of red meat consumption in relation to risk of heart failure ( HF ) are limited . We examined the associations between long-term unprocessed red meat and processed red meat consumption and incidence of HF in women . METHODS The population -based prospect i ve Swedish Mammography Cohort included 34,057 women , aged 48 - 83 years , with no history of HF or ischemic heart disease at baseline ( in 1997 ) . Meat consumption was assessed using a self-administered food-frequency question naire ( FFQ ) in 1997 as well as FFQ administered in 1987 - 90 . Cox proportional hazard regression models were used to estimate hazard ratios ( HRs ) with 95 % confidence intervals ( CIs ) . RESULTS During a mean follow-up of 13.2 years , 2806 women were diagnosed with HF . Consumption of processed meat ( FFQ 1997 ) was statistically significant positively associated with HF incidence . Women who consumed ≥ 50 g/day processed red meat compared to those who consumed < 25 g/day had a 1.23 ( 95 % CI : 1.09 - 1.39 , P-trend=0.003 ) higher risk of HF . Long-term high consumption of processed red meat ( average from 1987 to 1997 ) ≥ 50 g/day in comparison to < 25 g/day was associated with HR : 1.30 ( 95 % CI : 1.05 - 1.60 , P-trend=0.002 ) . Women who consistently consumed ( in both 1987 and 1997 ) ≥ 50 g/day vs. < 25 g/day had a 1.78 ( 95 % CI : 1.00 - 3.16 ) higher risk of HF . Consumption of unprocessed meat was not associated with increased risk of HF incidence . CONCLUSIONS Findings from this prospect i ve study of women indicate that processed red meat , but not unprocessed red meat , consumption is associated with an increased risk of HF incidence No known cohort study has investigated whether the Mediterranean diet can reduce incident coronary heart disease ( CHD ) events in a Mediterranean population . This study examined the relation between Mediterranean diet adherence and risk of incident CHD events in the 5 Spanish centers of the European Prospect i ve Investigation into Cancer and Nutrition . Analysis included 41,078 participants aged 29 - 69 years , recruited in 1992 - 1996 and followed up until December 2004 ( mean follow-up:10.4 years ) . Confirmed incident fatal and nonfatal CHD events were analyzed according to Mediterranean diet adherence , measured by using an 18-unit relative Mediterranean diet score . A total of 609 participants ( 79 % male ) had a fatal or nonfatal confirmed acute myocardial infa rct ion ( n = 468 ) or unstable angina requiring revascularization ( n = 141 ) . After stratification by center and age and adjustment for recognized CHD risk factors , high compared with low relative Mediterranean diet score was associated with a significant reduction in CHD risk ( hazard ratio = 0.60 , 95 % confidence interval : 0.47 , 0.77 ) . A 1-unit increase in relative Mediterranean diet score was associated with a 6 % reduced risk of CHD ( 95 % confidence interval : 0.91 , 0.97 ) , with similar risk reductions by sex . Mediterranean diet adherence was associated with a significantly reduced CHD risk in this Mediterranean country , supporting its role in primary prevention of CHD in healthy population Background / Objectives : Nuts have beneficial effects on coronary heart disease and many cardiovascular risk factors . However , their effect on stroke is less established , and no studies on the topic are available in Northern and Central European population s. Therefore , we aim ed at investigating the association between nut consumption and the risk of stroke in a German population .Subjects/ Methods : We used data from a prospect i ve cohort of 26 285 participants of the European Prospect i ve Investigation into the Cancer and Nutrition Potsdam Study . During a median follow-up time of 8.3 years ( interquartile range : 7.5–9.2 ) , 288 incident cases of stroke occurred . Nut consumption ( st and ard portion size of 50 g ) was assessed at baseline with a semiquantitative food-frequency question naire . Results : The median nut intake was 0.82 g per day , interquartile range : 0.41–4.11 . In the multivariable model , an increased risk of stroke was observed among participants who never consumed nuts ( hazard ratio ( HR ) : 1.56 , 95 % confidence interval : 1.17–2.08 ) , compared with those consuming < ½ portion/week . However , there was no evidence of a dose – response relationship between nut consumption and stroke . Compared with those who consumed < ½ portion/week , the multivariable HR for total stroke was 1.06 ( 0.75–1.52 ) among those who consumed ½ to 1 portion/week and 1.37 ( 0.92–2.05 ) for those who consumed > 1 portion/week . Similar nonsignificant associations were observed in stratified analysis for gender , or for fatal and nonfatal stroke . Conclusions : We could not observe an association between nut consumption and the risk of developing stroke ( fatal/nonfatal ) in a population with low habitual nut consumption The authors examined the association between dietary intake of fish and omega 3 fatty acids from seafood and the risk of cardiovascular disease in a prospect i ve cohort study of 21,185 US male physicians who are participants in the Physicians ' Health Study . In 4 years of follow-up , there were 281 incident cases of total ( fatal and nonfatal ) myocardial infa rct ion , 173 cases of stroke , and 121 cardiovascular deaths . There was no evidence for association between dietary intake of fish and any cardiovascular endpoint , including myocardial infa rct ion , stroke , and cardiovascular death . The relative risks of total myocardial infa rct ion , adjusted for age and r and omized treatment assignment , for categories of fish intake were : 1.0 for < 1 meal/week ( referent ) , 1.6 ( 95 % confidence interval ( Cl ) 1.1 - 2.3 ) for 1 fish meal/week ; 1.4 ( 95 % Cl 1.0 - 2.0 ) for 2 - 4 fish meals/week ; and 1.2 ( 95 % Cl 0.6 - 2.2 ) for > or = 5 fish meals/week ; chi 2 for trend = 0.9 , p = 0.34 . The relative risks were similar for omega 3 fatty acid intake and for specific types of fish , and did not change after adjustment for history of hypertension , hypercholesterolemia , diabetes mellitus , or angina pectoris , parental history of myocardial infa rct ion before age 60 years , obesity , exercise , smoking , alcohol use , saturated fat intake , and vitamin supplement use . These data do not support the hypothesis that moderate fish consumption lowers the risk of cardiovascular disease BACKGROUND Some studies have found that egg consumption is associated with a higher risk of ischemic heart disease in patients with diabetes . Epidemiologic studies of egg consumption in relation to risk of heart failure ( HF ) and stroke types are scarce . OBJECTIVE The aim of this study was to examine whether egg consumption is associated with incidence of HF , myocardial infa rct ion ( MI ) , or stroke types . DESIGN In prospect i ve cohorts of 37,766 men ( Cohort of Swedish Men ) and 32,805 women ( Swedish Mammography Cohort ) who were free of cardiovascular disease ( CVD ) , egg consumption was assessed at baseline with a food-frequency question naire . Incident CVD cases were identified through linkage with the Swedish National Patient and Cause of Death Registers . The data were analyzed with the use of a Cox proportional hazards regression model . RESULTS During 13 y of follow-up , we ascertained 1628 HFs , 3262 MIs , 2039 ischemic strokes , and 405 hemorrhagic strokes in men and 1207 HFs , 1504 MIs , 1561 ischemic strokes , and 294 hemorrhagic strokes in women . There was no statistically significant association between egg consumption and risk of MI or any stroke type in either men or women or HF in women . In men , consumption of ≤6 eggs/wk was not associated with HF risk ; however , daily egg consumption ( ≥1/d ) was associated with a 30 % higher risk of HF ( RR : 1.30 ; 95 % CI : 1.01 , 1.67 ) . Egg consumption was not associated with any CVD outcome in individuals with diabetes . CONCLUSIONS Daily egg consumption was not associated with risk of MI or any stroke type in either men or women or with HF in women . Consumption of eggs ≥1 time/d , but not less frequent consumption , was associated with an elevated risk of HF in men BACKGROUND Many observational studies support the recommendation to eat sufficient amounts of fruit and vegetables as part of a healthy diet . OBJECTIVE The present study aim ed to investigate the association between consumption of fruit , vegetables , and olive oil and the incidence of coronary heart disease ( CHD ) in 29,689 women enrolled between 1993 and 1998 in 5 European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) cohorts in northern ( Turin and Varese ) , central ( Florence ) , and southern ( Naples and Ragusa ) Italy . DESIGN Baseline dietary , anthropometric , and lifestyle characteristics were collected . Major events of CHD ( fatal and nonfatal myocardial infa rct ion and coronary revascularization ) were identified through a review of clinical records . Analyses were stratified by center and adjusted for hypertension , smoking , education , menopause , physical activity , anthropometric measures , nonalcohol energy , alcohol , total meat , vegetables in analyses for fruit , and fruit in analyses for vegetables . RESULTS During a mean follow-up of 7.85 y , 144 major CHD events were identified . A strong reduction in CHD risk among women in the highest quartile of consumption of leafy vegetables ( hazard ratio : 0.54 ; 95 % CI : 0.33 , 0.90 ; P for trend = 0.03 ) and olive oil ( hazard ratio : 0.56 ; 95 % CI : 0.31 , 0.99 ; P for trend = 0.04 ) was found . In contrast , no association emerged between fruit consumption and CHD risk . CONCLUSION An inverse association between increasing consumption of leafy vegetables and olive oil and CHD risk emerged in this large cohort of Italian women Background —Epidemiological studies of red meat consumption in relation to risk of heart failure ( HF ) are scarce . We examined the associations of unprocessed and processed red meat consumption with HF incidence and mortality in men . Methods and Results —The population -based prospect i ve Cohort of Swedish Men included 37 035 men , aged 45 to 79 years , with no history of HF , ischemic heart disease , or cancer at baseline . Meat consumption was assessed with a self-administered question naire in 1997 . During a mean follow-up of 11.8 years , 2891 incidences and 266 deaths from HF were ascertained . Consumption of processed meat was statistically significant positively associated with risk of HF in both age- and multivariable-adjusted models . Men who consumed ≥75 g/d processed meat compared with those who consumed < 25 g/d had a 1.28 ( 95 % confidence interval , 1.10–1.48 , P trend=0.01 ) higher risk of HF incidence and 2.43 ( 95 % confidence interval , 1.52–3.88 , P trend<0.001 ) higher risk of HF mortality . The consumption of unprocessed meat was not associated with increased risk of incidence of HF or mortality from HF . Conclusions — Findings from this prospect i ve study of men with low to moderate red meat consumption indicate that processed red meat consumption , but not unprocessed red meat , is associated with an increased risk of HF BACKGROUND Indexes to quantify adherence to recommended dietary patterns have been developed for Western population s , but it is unclear whether these indexes can predict acute myocardial infa rct ion ( AMI ) in Asian population s. OBJECTIVES We aim ed to investigate the association between the Alternative Healthy Eating Index (AHEI)-2010 and risk of AMI and to evaluate potential mediation by traditional cardiovascular risk factors in a Chinese population . METHODS A nested case-control study in 751 incident cases of AMI ( 564 nonfatal and 288 fatal ) and 1443 matched controls was conducted within the prospect i ve Singapore Chinese Health Study , a cohort of ethnic Chinese men and women aged 45 - 75 y. At baseline , habitual diet was assessed by using a vali date d , semiquantitative food-frequency question naire . AMI cases were ascertained via linkage with nationwide hospital data bases ( confirmed through medical record review ) and the Singapore Birth and Death Registry . We evaluated the association between the AHEI-2010 and cardiovascular risk factors , including glycated hemoglobin , high-sensitivity C-reactive protein , creatinine , plasma lipids ( LDL and HDL cholesterol , triglycerides ) , and blood pressure . ORs and 95 % CIs were computed by using multivariable-adjusted conditional logistic regression models . RESULTS Higher AHEI-2010 scores were associated with a lower risk of AMI ( OR for the highest quartile compared with the lowest quartile : 0.62 ; 95 % CI : 0.47 , 0.81 ; P-trend < 0.001 ) , with similar associations for fatal ( OR : 0.60 ; 95 % CI : 0.39 , 0.94 ; P-trend = 0.009 ) and nonfatal ( OR : 0.59 ; 95 % CI : 0.43 , 0.81 ; P-trend = 0.002 ) AMI . This association was only slightly attenuated after adjustment for potential biological intermediates ( OR : 0.64 ; 95 % CI : 0.48 , 0.86 ; P-trend = 0.003 ) . CONCLUSIONS Adherence to dietary recommendations as reflected in the AHEI-2010 was associated with a substantially lower risk of fatal and nonfatal AMI in an Asian population , and this association was largely independent of traditional cardiovascular risk factors BACKGROUND Epidemiological studies suggested that consumption of fruit and vegetables may protect against stroke . The hypothesis that dietary antioxidant vitamins and flavonoids account for this observation is investigated in a prospect i ve study . METHODS A cohort of 552 men aged 50 to 69 years was examined in 1970 and followed up for 15 years . Mean nutrient and food intake was calculated from cross-check dietary histories taken in 1960 , 1965 , and 1970 . The association between antioxidants , selected foods , and stroke incidence was assessed by Cox proportional hazards regression analysis . Adjustment was made for confounding by age , systolic blood pressure , serum cholesterol , cigarette smoking , energy intake , and consumption of fish and alcohol . RESULTS Forty-two cases of first fatal or nonfatal stroke were documented . Dietary flavonoids ( mainly quercetin ) were inversely associated with stroke incidence after adjustment for potential confounders , including antioxidant vitamins . The relative risk ( RR ) of the highest vs the lowest quartile of flavonoid intake ( > or = 28.6 mg/d vs < 18.3 mg/d ) was 0.27 ( 95 % confidence interval [ CI ] , 0.11 to 0.70 ) . A lower stroke risk was also observed for the highest quartile of beta-carotene intake ( RR , 0.54 ; 95 % CI , 0.22 to 1.33 ) . The intake of vitamin C and vitamin E was not associated with stroke risk . Black tea contributed about 70 % to flavonoid intake . The RR for a daily consumption of 4.7 cups or more of tea vs less than 2.6 cups of tea was 0.31 ( 95 % CI , 0.12 to 0.84 ) . CONCLUSION The habitual intake of flavonoids and their major source ( tea ) may protect against stroke AIMS Although numerous studies have investigated fruit and vegetable consumption in association with cardiovascular diseases ( CVD ) such as coronary heart disease and stroke , a limited number of studies have investigated the association with heart failure . The aim of this study was to assess the association between fruit and vegetable intake and the incidence of heart failure among women . METHODS AND RESULTS In September 1997 , a total of 34,319 women ( aged 49 - 83 years ) from the Swedish Mammography Cohort , free of cancer and CVD at baseline , completed a food-frequency question naire . Women were followed for incident heart failure ( diagnosis as primary or secondary cause ) through December 2011 using administrative health registries . Over 12.9 years of follow-up ( 442,348 person-years ) , we identified 3051 incident cases of heart failure . Total fruit and vegetable consumption was inversely associated with the rate of heart failure { the multivariable-adjusted rate ratio ( RR ) in the highest quintile compared with the lowest was 0.80 [ 95 % confidence interval ( CI ) 0.70 - 0.90]}. Fruit ( mutually adjusted for vegetables ) were not significantly associated with rate of heart failure ( RR 0.94 ; 95 % CI 0.83 - 1.07 ) , whereas vegetables showed an inverse association ( RR 0.83 ; 95 % CI 0.73 - 0.95 ) . When investigating the shape of association , we found evidence of a non-linear association ( P = 0.01 ) , and the lowest rates of heart failure were observed among women consuming ≥5 servings/day of fruit and vegetables , without further decrease with increasing intake . CONCLUSIONS In this population -based prospect i ve cohort study of women , higher total consumption of fruit and vegetables was inversely associated with the incidence of heart failure BACKGROUND Red and processed meat consumption has been implicated in several diseases . However , data on meat consumption in relation to stroke incidence are sparse . OBJECTIVE Our objective was to examine the associations of red meat and processed meat consumption with stroke incidence in men . DESIGN We prospect ively followed 40,291 men aged 45 - 79 y who had no history of cardiovascular disease or cancer at baseline . Meat consumption was assessed with a self-administered question naire in 1997 . RESULTS During a mean follow-up of 10.1 y , 2409 incident casesof stroke ( 1849 cerebral infa rct ions , 350 hemorrhagic strokes , and 210 unspecified strokes ) were identified from the Swedish Hospital Discharge Registry . Consumption of processed meat , but not of fresh red meat , was positively associated with risk of stroke . The multivariable relative risks ( RRs ) of total stroke for the highest compared with the lowest quintiles of consumption were 1.23 ( 95 % CI : 1.07 , 1.40 ; P for trend = 0.004 ) for processed meat and 1.07 ( 95 % CI : 0.93 , 1.24 ; P for trend = 0.77 ) for fresh red meat . Processed meat consumption was also positively associated with risk of cerebral infa rct ion in a comparison of the highest with the lowest quintile ( RR : 1.18 ; 95 % CI : 1.01 , 1.38 ; P for trend = 0.03 ) . CONCLUSION The findings from this prospect i ve cohort of men indicate that processed meat consumption is positively associated with risk of stroke . The Cohort of Swedish Men is registered at clinical trials.gov as NCT01127711 AIMS Fatty fish and marine omega-3 fatty acids were associated with lower rates of heart failure ( HF ) among US elderly , but this has not been confirmed in broader age ranges or other population s where source and type of fish may differ . We therefore conducted a population -based , prospect i ve study of 39 367 middle-aged and older Swedish men . METHODS AND RESULTS Diet was measured using food-frequency question naires . Men were followed for HF through Swedish inpatient and cause-of-death registers from 1 January 1998 to 31 December 2004 . We used proportional hazards models adjusted for age and other covariates to estimate hazard ratios ( HR ) . Compared with no consumption , men who ate fatty fish once per week had an HR of 0.88 ( 95 % CI 0.68 - 1.13 ) . Hazard ratios for consumption two times per week and > or =3 times per week were 0.99 and 0.97 , respectively . Hazard ratios across quintiles of marine omega-3 were 1 , 0.94 ( 95 % CI 0.74 - 1.20 ) , 0.67 ( 95 % CI 0.50 - 0.90 ) , 0.89 ( 95 % CI 0.68 - 1.16 ) , 1.00 ( 95 % CI 0.77 - 1.29 ) . CONCLUSION In this population , moderate intake of fatty fish and marine omega-3 fatty acids was associated with lower rates of HF , though the association for fish intake was not statistically significant ; higher intake was not associated with additional benefit AIM This study aim ed to investigate the relationship between total dairy intake and dairy subtypes ( high-fat dairy , low-fat dairy , milk and milk products , cheese and fermented dairy ) with incident coronary heart disease ( CHD ) and stroke . METHODS EPIC-NL is a prospect i ve cohort study among 33,625 Dutch men and women . At baseline ( 1993 - 1997 ) , dairy intake was measured with a vali date d food frequency question naire ( FFQ ) . The incidence of both fatal and non-fatal CHD and stroke was obtained by linkage to the national registers . RESULTS During 13 years follow-up , 1648 cases of CHD and 531 cases of stroke were documented . Total dairy intake was not significantly associated with risk of CHD ( hazard ratio per st and ard deviation ( SD ) increase=0.99 ; 95%-CI : 0.94 - 1.05 ) or stroke ( 0.95 ; 0.85 - 1.05 ) adjusted for lifestyle and dietary factors . None of the dairy subtypes was to CHD , while only fermented dairy tended to be associated ( p=0.07 ) with a lower risk of stroke ( 0.92 ; 0.83 - 1.01 ) . Hypertension appeared to modify the association of total and low-fat dairy with CHD ( p interaction<0.02 ) . Among participants without hypertension , but not among hypertensive participants , total ( 0.92 ; 0.85 - 1.02 ) and low-fat ( 0.94 ; 0.87 - 1.02 ) dairy tended to be associated with a lower risk of CHD . CONCLUSION Our results provide no evidence that dairy products are associated with risk of CHD or stroke . High intakes of total and low-fat dairy may be associated with a lower risk of CHD among participants without hypertension , while fermented dairy could be associated with a reduced risk of stroke BACKGROUND AND AIM The Mediterranean diet is considered a model for healthy eating . However , prospect i ve evidence in Mediterranean countries evaluating the relationship between this dietary pattern and non-fatal cardiovascular events is scarce . The aim of the present study was to evaluate the association between the adherence to the Mediterranean diet and the incidence of fatal and non-fatal cardiovascular events among initially healthy middle-aged adults from the Mediterranean area . METHODS AND RESULTS We followed-up 13,609 participants ( 60 percent women , mean age : 38 years ) initially free of cardiovascular disease ( CVD ) during 4.9 years . Participants were part of a prospect i ve cohort study of university graduates from all regions of Spain . Baseline diet was assessed using a vali date d 136-item food-frequency question naire . A 9-point score was used to appraise adherence to the Mediterranean diet . Incident clinical events were confirmed by a review of medical records . We observed 100 incident cases of CVD . In multivariate analyses , participants with the highest adherence to the Mediterranean diet ( score>6 ) exhibited a lower cardiovascular risk ( hazard ratio=0.41 , 95 % confidence interval [ CI ] : 0.18 - 0.95 ) compared to those with the lowest score ( <3 ) . For each 2-point increment in the score , the adjusted hazard ratios were 0.80 ( 95 % CI : 0.62 - 1.02 ) for total CVD and 0.74 ( 0.55 - 0.99 ) for coronary heart disease . CONCLUSIONS There is an inverse association between adherence to the Mediterranean diet and the incidence of fatal and non-fatal CVD in initially healthy middle-aged adults BACKGROUND Dietary guidelines recommend increasing fruit and vegetable intake and , most recently , have also suggested increasing variety . OBJECTIVE We prospect ively examined the independent roles of quantity and variety in fruit and vegetable intake in relation to incident coronary heart disease ( CHD ) . DESIGN We prospect ively followed 71,141 women from the Nurses ' Health Study ( 1984 - 2008 ) and 42,135 men from the Health Professionals Follow-Up Study ( 1986 - 2008 ) who were free of diabetes , cardiovascular diseases , and cancer at baseline . Diet was assessed by using a vali date d question naire and up date d every 4 y. Variety was defined as the number of unique fruit and vegetables consumed at least once per week . Potatoes , legumes , and fruit juices were not included in our definition of fruit and vegetables . RESULTS During follow-up , we documented 2582 CHD cases in women and 3607 cases in men . In multivariable analyses , after adjustment for dietary and nondietary covariates , those in the highest quintile of fruit and vegetable intake had a 17 % lower risk ( 95 % CI : 9 % , 24 % ) of CHD . A higher consumption of citrus fruit , green leafy vegetables , and β-carotene- and vitamin C-rich fruit and vegetables was associated with a lower CHD risk . Conversely , quantity-adjusted variety was not associated with CHD . CONCLUSIONS Our data suggest that absolute quantity , rather than variety , in fruit and vegetable intake is associated with a significantly lower risk of CHD . Nevertheless , consumption of specific fruit and vegetable subgroups was associated with a lower CHD risk |
1,851 | 25,989,478 | For febrile neutropenia , septicemia , and renal toxicity , a statistically significant difference in favor of the st and ard treatment arm was identified ; for all other early toxicities no clear evidence of a difference between treatment groups was identified .
For endocrine complications and neurocognitive complications , a statistically significant difference in favor of the rapid COJEC arm was found ; for all other late non-hematological toxicities no clear evidence of a difference between treatment groups was identified .
Therefore , based on the currently available evidence , we are uncertain about the effects of rapid COJEC and st and ard induction therapy in patients with high-risk neuroblastoma . | BACKGROUND Neuroblastoma is a rare malignant disease and mainly affects infants and very young children .
The tumors mainly develop in the adrenal medullary tissue and an abdominal mass is the most common presentation .
The high-risk group is characterized by metastasis and other characteristics that increase the risk for an adverse outcome .
In the rapid COJEC induction schedule , higher single doses of selected drugs than st and ard induction schedules are administered over a substantially shorter treatment period , with shorter intervals between cycles .
Shorter intervals and higher doses increase the dose intensity of chemotherapy and might improve survival .
OBJECTIVES The aim of this study was to evaluate the efficacy and adverse events of the rapid COJEC induction schedule as compared to st and ard induction schedules in patients with high-risk neuroblastoma ( as defined by the International Neuroblastoma Risk Group ( INRG ) classification system ) .
Outcomes of interest were complete response , early toxicity and treatment-related mortality as primary endpoints and overall survival , progression- and event-free survival , late non-hematological toxicity , and health-related quality of life as secondary endpoints . | BACKGROUND To evaluate long-term survival of the first cohort of stage-4 neuroblastoma patients treated with the N7 induction chemotherapy , surgery of the primary tumor and high-dose chemotherapy ( HDC ) containing Busulfan-Melphalan ( Bu-Mel ) followed by autologous stem cell transplantation ( ASCT ) . PROCEDURE From 1998 to 1999 , 47 children were included in the NB97 trial and treated with induction chemotherapy according to the N7 protocol , followed by surgery of the primary tumor . HDC ( Busulfan , 600 mg/m(2 ) Melphalan , 140 mg/m(2 ) ) was administered in patients with partial response of metastases with no more than 3 mIBG spots . Radiotherapy was delivered to the primary tumor site when tumors displayed MYCN amplification . RESULTS Thirty-nine patients received Bu-Mel ( 83 % ) : 23 who had achieved complete response ( CR ) of metastases , 20 after induction treatment and 3 after second-line chemotherapy , and 16 in partial response ( PR ) . The toxicity of the whole treatment was manageable . The main HDC related-toxicity was hepatic veno-occlusive disease grade > 2 occurring in 15 % of the patients . The 8-year EFS of the whole cohort was 34 % ( 95 % CI , 22 - 48 % ) . The 8-year EFS of the 39 patients who received Bu-Mel and ASCT was 41 % ( 95 % CI , 27 - 57 % ) . Patients who achieved a CR of metastases at the end of induction chemotherapy had a significantly better outcome than the others ( 8-year EFS , 52 % vs. 20 % ; P = 0.02 ) . CONCLUSIONS The long-term results of this first prospect i ve cohort of patients with metastatic disease treated with the N7 induction chemotherapy and HDC ( Bu-Mel ) confirm published data with stable survival curves but with a longer follow-up BACKGROUND Myeloablative megatherapy is commonly used to improve the poor outlook of children with high-risk neuroblastoma , yet its role is poorly defined . We aim ed to assess whether megatherapy with autologous stem-cell transplantation could increase event-free survival and overall survival compared with maintenance chemotherapy . METHODS 295 patients with high-risk neuroblastoma ( ie , patients with stage 4 disease aged older than 1 year or those with MYCN-amplified tumours and stage 1 , 2 , 3 , or 4S disease or stage 4 disease and < 1 year old ) were r and omly assigned to myeloablative megatherapy ( melphalan , etoposide , and carboplatin ) with autologous stem-cell transplantation ( n=149 ) or to oral maintenance chemotherapy with cyclophosphamide ( n=146 ) . The primary endpoint was event-free survival . Secondary endpoints were overall survival and the number of treatment-related deaths . Analyses were done by intent to treat , as treated , and treated as r and omised . FINDINGS Intention-to-treat analysis showed that patients allocated megatherapy had increased 3-year event-free survival compared with those allocated maintenance therapy ( 47 % [ 95 % CI 38 - 55 ] vs 31 % [ 95 % CI 23 - 39 ] ; hazard ratio 1.404 [ 95 % CI 1.048 - 1.881 ] , p=0.0221 ) , but did not have significantly increased 3-year overall survival ( 62 % [ 95 % CI 54 - 70 ] vs 53 % [ 95 % CI 45 - 62 ] ; 1.329 [ 0.958 - 1.843 ] , p=0.0875 ) . Improved 3-year event-free survival and 3-year overall survival were also recorded for patients given megatherapy in the as-treated group ( n=212 ) and in the treated-as-r and omised group ( n=145 ) . Two patients died from therapy-related complications during induction treatment . No patients given maintenance therapy died from acute treatment-related toxic effects . Five patients given megatherapy died from acute complications related to megatherapy . INTERPRETATION Myeloablative chemotherapy with autologous stem-cell transplantation improves the outcome for children with high-risk neuroblastoma despite the raised risk of treatment-associated death BACKGROUND The current st and ard treatment for patients with high-risk neuroblastoma includes initial induction chemotherapy with a 21-day interval between induction treatments . We aim ed to assess whether an intensive chemotherapy protocol that had a 10-day interval between treatments would improve event-free survival ( EFS ) in patients aged 1 year or over with high-risk neuroblastoma . METHODS Between Oct 30 , 1990 , and March 18 , 1999 , patients with stage 4 neuroblastoma who had not received previous chemotherapy were enrolled from 29 centres in Europe . Patients were r and omly assigned to rapid treatment ( cisplatin [ C ] , vincristine [ O ] , carboplatin [ J ] , etoposide [ E ] , and cyclophosphamide [ C ] , known as COJEC ) or st and ard treatment ( vincristine [ O ] , cisplatin [ P ] , etoposide [ E ] , and cyclophosphamide [ C ] , ie , OPEC , alternated with vincristine [ O ] , carboplatin [ J ] , etoposide [ E ] , and cyclophosphamide [ C ] , ie , OJEC ) . Both regimens used the same total cumulative doses of each drug ( except vincristine ) , but the dose intensity of the rapid regimen was 1.8-times higher than that of the st and ard regimen . The st and ard regimen was given every 21 days if patients showed haematological recovery , whereas the rapid regimen was given every 10 days irrespective of haematological recovery . Response to chemotherapy was assessed according to the conventional International Neuroblastoma Response Criteria ( INRC ) . In responders , surgical excision of the primary tumour was attempted , followed by myeloablation ( with 200 mg/m2 of melphalan ) and haemopoietic stem-cell rescue . Primary endpoints were 3-year , 5-year , and 10-year EFS . Data were analysed by intention to treat . This trial is registered on the clinical trials site of the US National Cancer Institute website , number NCT00365755 , and also as EU-20592 and CCLG-NB-1990 - 11 . FINDINGS 262 patients , of median age 2.95 years ( range 1.03 - 20.97 ) , were r and omly assigned-132 patients to st and ard and 130 patients to rapid treatment . 111 patients in the st and ard group and 109 patients in the rapid group completed chemotherapy . Chemotherapy doses were recorded for 123 patients in the st and ard group and 126 patients in the rapid group . 97 of 123 ( 79 % ) patients in the st and ard group and 84 of 126 ( 67 % ) patients in the rapid group received at least 90 % of the scheduled chemotherapy , and the relative dose intensity was 1.94 compared with the st and ard regimen . 3-year EFS was 24.2 % for patients in the st and ard group and 31.0 % for those in the rapid group ( hazard ratio [ HR ] 0.86 [ 95 % CI 0.66 - 1.14 ] , p=0.30 . 5-year EFS was 18.2 % in the st and ard group and 30.2 % in the rapid group , representing a difference of 12.0 % ( 1.8 to 22.3 ) , p=0.022 . 10-year EFS was 18.2 % in the st and ard group and 27.1 % in the rapid group , representing a difference of 8.9 % ( -1.2 to 19.0 ) , p=0.085 . Myeloablation was given a median of 55 days earlier in patients assigned rapid treatment than those assigned st and ard treatment . Infective complications ( numbers of patients with febrile neutropenia and septicaemia , and if given , time on antibiotic and antifungal treatment ) and time in hospital were greater with rapid treatment . Occurrence of fungal infection was the same in both regimens . INTERPRETATION Dose intensity can be increased with a rapid induction regimen in patients with high-risk neuroblastoma . There was no significant difference in OS between the rapid and st and ard regimens at 5 years and 10 years . However , an increasing difference in EFS after 3 years suggests that the efficacy of the rapid regimen is better than the st and ard regimen . A rapid induction regimen enables myeloablation to be given much earlier , which might contribute to a better outcome UNLABELLED PURPOSE We assessed the long-term outcome of patients enrolled on CCG-3891 , a high-risk neuroblastoma study in which patients were r and omly assigned to undergo autologous purged bone marrow transplantation ( ABMT ) or to receive chemotherapy , and subsequent treatment with 13-cis-retinoic acid ( cis-RA ) . PATIENTS AND METHODS Patients received the same induction chemotherapy , with r and om assignment ( N = 379 ) to consolidation with myeloablative chemotherapy , total-body irradiation , and ABMT versus three cycles of intensive chemotherapy . Patients who completed consolidation without disease progression were r and omly assigned to receive no further therapy or cis-RA for 6 months . Results The event-free survival ( EFS ) for patients r and omly assigned to ABMT was significantly higher than those r and omly assigned to chemotherapy ; the 5-year EFS ( mean + /- SE ) was 30 % + /- 4 % versus 19 % + /- 3 % , respectively ( P = .04 ) . The 5-year EFS ( 42 % + /- 5 % v 31 % + /- 5 % ) from the time of second r and om assignment was higher for cis-RA than for no further therapy , though it was not significant . Overall survival ( OS ) was significantly higher for each r and om assignment by a test of the log(-log ( . ) ) transformation of the survival estimates at 5 years ( P < .01 ) . The 5-year OS from the second r and om assignment of patients who underwent both r and om assignments and who were assigned to ABMT/cis-RA was 59 % + /- 8 % ; for ABMT/no cis-RA , it was 41 % + /- 8 % [ corrected ] ; for continuing chemotherapy/cis-RA , it was 38 % + /- 7 % ; and for chemotherapy/no cis-RA , it was 36 % + /- 7 % . CONCLUSION Myeloablative therapy and autologous hematopoietic cell rescue result in significantly better 5-year EFS than nonmyeloablative chemo therapy ; neither myeloablative therapy with [ corrected ] autologous hematopoietic cell rescue nor cis-RA given after consolidation therapy significantly improved OS BACKGROUND The N7 protocol for poor-risk neuroblastoma uses dose-intensive chemotherapy ( as in N6 protocol [ Kushner et al. : J Clin Oncol 12:2607 - 2613 , 1994 ] but with lower dosing of vincristine ) for induction , surgical resection and 2100 cGy hyperfractionated radiotherapy for local control , and for consolidation , targeted radioimmunotherapy with 131I-labeled anti-GD2 3F8 monoclonal antibody and immunotherapy with unlabeled/unmodified 3F8 ( 400 mg/m2 ) . PROCEDURE The chemotherapy consists of : cyclophosphamide 70 mg/kg/d x 2 and a 72-hr infusion of doxorubicin 75 mg/m2 plus vincristine 2 mg/m2 , for courses 1 , 2 , 4 , and 6 ; and cisplatin 50 mg/m2/d x 4 and etoposide 200 mg/m2/d x 3 , for courses 3 , 5 , and 7 . 131I-3F8 is dosed at 20 mCi/kg , which is myeloablative and therefore necessitates stem-cell support . RESULTS Of the first 24 consecutive previously untreated patients more than 1 year old at diagnosis , 22 were stage 4 and two were unresectable stage 3 with MYCN amplification . Chemotherapy achieved CR/VGPR in 21 of 24 patients . Twenty patients to date have completed treatment with 131I-3F8 , and 15 patients have completed all treatment . With a median follow-up of 19 months , 18 of 24 patients remain progression-free . CONCLUSIONS Major toxicities were grade 4 myelosuppression and mucositis during chemotherapy , and self-limited pain and urticaria during antibody treatment . Late effects include hearing deficits and hypothyroidism BACKGROUND Myeloablative chemoradiotherapy and immunomagnetically purged autologous bone marrow transplantation has been shown to improve outcome for patients with high-risk neuroblastoma . Currently , peripheral blood stem cells ( PBSC ) are infused after myeloablative therapy , but the effect of purging is unknown . We did a r and omised study of tumour-selective PBSC purging in stem-cell transplantation for patients with high-risk neuroblastoma . METHODS Between March 16 , 2001 , and Feb 24 , 2006 , children and young adults ( < 30 years ) with high-risk neuroblastoma were r and omly assigned at diagnosis by a web-based system ( in a 1:1 ratio ) to receive either non-purged or immunomagnetically purged PBSC . R and omisation was done in blocks stratified by International Neuroblastoma Staging System stage , age , MYCN status , and International Neuroblastoma Pathology classification . Patients and treating physicians were not masked to treatment assignment . All patients were treated with six cycles of induction chemotherapy , myeloablative consolidation , and radiation therapy to the primary tumour site plus meta-iodobenzylguanidine avid metastases present before myeloablative therapy , followed by oral isotretinoin . PBSC collection was done after two induction cycles . For purging , PBSC were mixed with carbonyl iron and phagocytic cells removed with samarium cobalt magnets . Remaining cells were mixed with immunomagnetic beads prepared with five monoclonal antibodies targeting neuroblastoma cell surface antigens and attached cells were removed using samarium cobalt magnets . Patients underwent autologous stem-cell transplantation with PBSC as r and omly assigned after six cycles of induction therapy . The primary endpoint was event-free survival and was analysed by intention-to-treat . The trial is registered with Clinical Trials.gov , number NCT00004188 . FINDINGS 495 patients were enrolled , of whom 486 were r and omly assigned to treatment : 243 patients to receive non-purged PBSC and 243 to received purged PBSC . PBSC were collected from 229 patients from the purged group and 236 patients from the non-purged group , and 180 patients from the purged group and 192 from the non-purged group received transplant . 5-year event-free survival was 40 % ( 95 % CI 33 - 46 ) in the purged group versus 36 % ( 30 - 42 ) in the non-purged group ( p=0·77 ) ; 5-year overall survival was 50 % ( 95 % CI 43 - 56 ) in the purged group compared with 51 % ( 44 - 57 ) in the non-purged group ( p=0·81 ) . Toxic deaths occurred in 15 patients during induction ( eight in the purged group and seven in the non-purged group ) and 12 during consolidation ( eight in the purged group and four in the non-purged group ) . The most common adverse event reported was grade 3 or worse stomatitis during both induction ( 87 of 242 patients in the purged group and 93 of 243 patients in the non-purged group ) and consolidation ( 131 of 177 in the purged group vs 145 of 191 in the non-purged group ) . Serious adverse events during induction were grade 3 or higher decreased cardiac function ( four of 242 in the purged group and five of 243 in the non-purged group ) and elevated creatinine ( five of 242 in the purged group and six of 243 non-purged group ) and during consolidation were sinusoidal obstructive syndrome ( 12 of 177 in the purged group and 17 of 191 in the non-purged group ) , acute vascular leak ( 11 of 177 in the purged group and nine of 191 in the non-purged group ) , and decreased cardiac function ( one of 177 in the purged group and four of 191 in the non-purged group ) . INTERPRETATION Immunomagnetic purging of PBSC for autologous stem-cell transplantation did not improve outcome , perhaps because of incomplete purging or residual tumour in patients . Non-purged PBSC are acceptable for support of myeloablative therapy of high-risk neuroblastoma PURPOSE The excellent prognosis of localized neuroblastoma in infants , the overdiagnosis observed in neuroblastoma screening studies , and several case reports of regression of localized neuroblastoma prompted us to initiate a prospect i ve cooperative trial on observation of localized neuroblastoma without cytotoxic treatment . PATIENTS AND METHODS For infants with localized neuroblastoma without MYCN amplification , chemotherapy was scheduled only in cases with threatening symptoms ; otherwise , the tumor was either resected or observed by ultrasound and magnetic resonance imaging ( MRI ) . RESULTS Of 340 eligible participants , 190 underwent resection , 57 were treated with chemotherapy , and 93 were observed with gross residual tumor . Of those 93 patients with unresected tumors , spontaneous regression was seen in 44 , local progression in 28 , progression to stage 4S in seven , and progression to stage 4 in four . Time to regression was quite variable , with first signs of regression noted 1 to 18 months after diagnosis and in 15 of 44 patients even after the first year of life . So far , complete regression was observed in 17 of 44 patients 4 to 20 months after diagnosis . Known clinical risk factors were not able to differentiate between patients with regression and regional or metastatic progression . Overall survival ( OS ; 3-year OS , 0.99 + /- 0.01 ) and metastases-free survival ( rate at 3 years , 0.94 + /- 0.03 ) for patients with unresected tumors was excellent and was not different from patients treated with surgery or chemotherapy . CONCLUSION Spontaneous regression is regularly seen in infants with localized neuroblastoma and is not limited to the first year of life . A wait- and -see strategy is justified in those patients PURPOSE To assess the feasibility of adding dose-intensive topotecan and cyclophosphamide to induction therapy for newly diagnosed high-risk neuroblastoma ( HRNB ) . PATIENTS AND METHODS Enrolled patients received two cycles of topotecan ( approximately 1.2 mg/m(2)/d ) and cyclophosphamide ( 400 mg/m(2)/d ) for 5 days followed by four cycles of multiagent chemotherapy ( Memorial Sloan-Kettering Cancer Center [ MSKCC ] regimen ) . Pharmacokinetically guided topotecan dosing ( target systemic exposure with area under the curve of 50 to 70 ng/mL/hr ) was performed . Peripheral-blood stem cell ( PBSC ) harvest and surgical resection of residual primary tumor occurred after cycles 2 and 5 , respectively . Patients achieving at least a partial response received myeloablative chemotherapy with PBSC rescue and radiation to the presurgical primary tumor volume . Oral 13-cis-retinoic acid maintenance therapy was administered twice daily for 14 days in six 28-day cycles . RESULTS Thirty-one patients were enrolled onto the study . No deaths related to toxicity or dose-limiting toxicities occurred during induction . Mucositis rarely occurred after topotecan cycles ( 9.7 % ) in contrast to 30 % after MSKCC cycles . Thirty patients underwent PBSC collection with median 31.1 × 10(6 ) CD34 + cells/kg ( range , 1.8 to 541.8 × 10(6 ) CD34 + cells/kg ) , all negative for tumor contamination by immunocytochemical analysis . Targeted topotecan systemic exposure was achieved in 26 ( 84 % ) of 31 patients . At the end of induction , 26 patients ( 84 % ) had tumor response and one patient had progressive disease . In the overall cohort , 3-year event-free and overall survival were 37.8 % ± 9.4 % and 57.1 % ± 9.4 % , respectively . CONCLUSION This pilot induction regimen was well tolerated with expected and reversible toxicities . These data support investigation of efficacy in a phase III clinical trial for newly diagnosed HRNB PURPOSE We previously reported a high response rate with a dose-intensive chemotherapy regimen in 24 children with high-risk neuroblastoma ( NB ) . We now describe similar results with changes that reduce toxicity ( fewer cycles , less vincristine , use of granulocyte colony-stimulating factor ) . PATIENTS AND METHODS Eighty-seven consecutive newly diagnosed children with high-risk NB underwent induction that initially had seven cycles ( 57 patients ) but was later limited to five ( 30 patients ) . Cycles 1 , 2 , 4 , and 6 used cyclophosphamide ( 140 mg/kg)/doxorubicin ( 75 mg/m(2))/vincristine ( 0.15 mg/kg in the first 27 patients , 0.067 mg/kg subsequently ) . Cycles 3 , 5 , and 7 used cisplatin ( 200 mg/m(2))/etoposide ( 600 mg/m(2 ) ) . Tumor resection followed a minimum of three cycles . The induction was eventually modified to include anti-G(D2 ) immunotherapy after each of the last three cycles ( 38 patients ) . RESULTS Bone marrow disease resolved in 70 ( 91 % ) of 77 patients and was not detected pre- and postinduction in 10 patients . After cycle 3 or 4 , 86 % of primary tumors were more than 50 % smaller . Postinduction metaiodobenzylguanidine scans showed normal radiotracer distribution in metastatic sites in 74 ( 87 % ) of 85 patients . Overall results were : 68 ( 79 % ) complete/very good partial responses ( CR/VGPR ) ; 14 ( 16 % ) partial responses ( PR ) ; three ( 3 % ) less than PR ; one ( 1 % ) death from infection ; and one patient not assessable for response . Five cycles yielded a CR/VGPR rate of 83 % , compared with a 77 % rate from seven cycles . Side effects were myelosuppression , mucositis , and hearing deficits ; neurotoxicity was insignificant with the lower vincristine dosage . Four patients ( each received seven cycles ) developed myelodysplasia/leukemia . CONCLUSION Five cycles of this induction regimen , plus surgery , suffice to achieve CR/VGPR in approximately 80 % of children with high-risk NB PURPOSE To reduce the incidence of febrile neutropenia during rapid COJEC ( cisplatin , vincristine , carboplatin , etoposide , and cyclophosphamide given in a rapid delivery schedule ) induction . In the High-Risk Neuroblastoma-1 ( HR-NBL1 ) trial , the International Society of Paediatric Oncology European Neuroblastoma Group ( SIOPEN ) r and omly assigned patients to primary prophylactic ( PP ) versus symptom-triggered granulocyte colony-stimulating factor ( GCSF ; filgrastim ) . PATIENTS AND METHODS From May 2002 to November 2005 , 239 patients in 16 countries were r and omly assigned to receive or not receive PPGCSF . There were 144 boys with a median age of 3.1 years ( range , 1 to 17 years ) of whom 217 had International Neuroblastoma Staging System ( INSS ) stage 4 and 22 had stage 2 or 3 MYCN-amplified disease . The prophylactic arm received a single daily dose of 5 microg/kg GCSF , starting after each of the eight COJEC chemotherapy cycles and stopping 24 hours before the next cycle . Chemotherapy was administered every 10 days regardless of hematologic recovery , provided that infection was controlled . RESULTS The PPGCSF arm had significantly fewer febrile neutropenic episodes ( P = .002 ) , days with fever ( P = .004 ) , hospital days ( P = .017 ) , and antibiotic days ( P = .001 ) . Reported Common Toxicity Criteria ( CTC ) grade d toxicity was also significantly reduced : infections per cycle ( P = .002 ) , fever ( P < .001 ) , severe leucopenia ( P < .001 ) , neutropenia ( P < .001 ) , mucositis ( P = .002 ) , nausea/vomiting ( P = .045 ) , and constipation ( P = .008 ) . Severe weight loss was reduced significantly by 50 % ( P = .013 ) . Protocol compliance with the rapid induction schedule was also significantly better in the PPGCSF arm shown by shorter time to completion ( P = .005 ) . PPGCSF did not adversely affect response rates or success of peripheral-blood stem-cell harvest . CONCLUSION Following these results , PPG-GSF was advised for all patients on rapid COJEC induction One hundred nine newly treated patients with advanced neuroblastoma were entered in this study between January 1985 and May 1989 . The eligible patients included infants younger than 12 months of age with Stage IVA disease ( bone cortex , distant lymph node , and /or remote organ metastases ) and patients aged 12 months or older with Stage III or IV disease ( IVA plus IVB with tumor crossing the mid‐line and with metastases confined to bone marrow , liver , and skin ) . The patients first received six cyclic course of intensive chemotherapy ( regimen A1 ) , consisting of cyclophosphamide ( 1200 mg/m2 ) , vincristine ( 1.5 mg/m2 ) , tetrahydropyranyl adriamycin ( pyrarubicin ; 40 mg/m2 ) , and cisplatin ( 90 mg/m2 ) . Original tumors and the regional lymph node metastases were removed some time during these first six cycles of chemotherapy . The patients were further divided into three groups . Patients in course 1 received alternating treatment by regimen B ( cyclophosphamide and ACNU ) and intensified regimen A1 , and those in course 2 were treated with alternating administration of regimen C ( cyclophosphamide and DTIC ) and intensified A1 . Patients in course 3 were treated with bone marrow transplantation ( BMT ) preceded by high‐dose preconditioning chemotherapy . Survival rates were 77 % in Stage III and 54 % in Stage IV at 2 years , and 70 % in Stage III and 45 % in Stage IV at 3 years . The major toxicities encountered were bone marrow suppression with leukocyte counts down to 100/mm3 , mild cystitis , and hearing impairment . The 2‐year survival rate was 78 % in 21 patients who underwent BMT when complete remission was achieved . We concluded that our intensive induction chemotherapy is of significant value in increasing the rate of complete response , and in widening the indications for and achieving improved results of treatment with BMT 9511 Background : A semi-quantitative reporting method developed by an international expert panel ( J Nucl Med 2009;50:1379 ) was used to evaluate the role ofI-123 meta-IodoBenzylGuanidine [ 123I mIBG ] imaging in high risk neuroblastoma [ HR-NBL ] . METHOD Patterns of skeletal 123I mIBG uptake were assignednumerical scores ( Mscore ) ranging from 0 ( no metastasis ) to 72 ( diffuse metastases ) within 12 body areas as described previously ( J Nucl Med 2009;50:1379 ) . 271 anonymised , paired image data sets acquired at diagnosis and on completion of Rapid COJEC induction chemotherapy were review ed , constituting a representative sample of 1602 children treated prospect ively within the HR-NBL1/SIOPEN trial . Pre- and post-treatment Mscores were compared with bone marrow cytology ( BM ) and 3 year event free survival ( EFS ) . RESULTS 224/271 patients showed skeletal mIBG uptake at diagnosis and were evaluable for mIBG response . Complete skeletal mIBG response ( CR ) to Rapid COJEC induction was achieved by 66 % , 34 % and 15 % of patients who had pre-treatment Mscores of < 18 ( n=65 , 29 % ) , 18 - 44 ( n=95,42 % ) and ≥45 ( n=64 , 28.5 % ) respectively ( p<.0001 ) . Mscore at diagnosis correlated with post treatment score ( p<0.001 ) and with BM involvement ( p<0.0001 ) . The 3 year EFS in 47 children with Mscore 0 at diagnosis was 0.68 ( ±0.07 ) , by comparison with 0.42 ( ±0.06 ) , 0.35 ( ±0.05 ) and 0.25 ( ±0.06 ) for patients in pre-treatment Mscore groups < 18 , 18 - 44 and ≥45 , respectively ( p<0.001 ) . An Mscore threshold of ≥45 at diagnosis was associated with significantly worse outcome by comparison with all other Mscore groups ( p=0.029 ) . Patients who achieved metastatic CR ( mIBG and BM ) after Rapid COJEC had a significantly longer 3 year EFS of 0.53 ( ±0.07 ) compared with 0.24 ( ±0.04 ) observed in children who did not reach CR ( p=0.005 ) . CONCLUSIONS SIOPEN scoring of 123I mIBG imaging at diagnosis in children with HR-NBL predicts response to induction chemotherapy and outcome . ( 1 ) Lewington V et al. Development of a semi-quantitative I -123 mIBG reporting method in HR-NBL BACKGROUND This paper reports the toxicity of OPEC/OJEC chemotherapy in stage 4 neuroblastoma patients over 1 year of age . PROCEDURE Ninety-five patients with stage 4 neuroblastoma received alternating courses of OPEC/OJEC -- vincristine 1.5 mg/m2 ( O ) , cisplatin 80 mg/m2 ( P ) , etoposide 200 mg/m2 ( E ) , cyclophosphamide 600 mg/m2 ( C ) , and carboplatin 500 mg/m2 ( J ) , every 21 days if there was haematological recovery . RESULTS Seventy out of ninety-five ( 74 % ) patients completed seven or more courses and were evaluable for toxicity . Of these 70 patients , 33 % had more than three episodes of fever and sepsis , 35 % required more than five blood or platelet transfusions , 36 % had grade 2 or more gastrointestinal toxicity and 9 % had neurotoxicity . There was a median reduction in GFR of 32 ml/min/1.73 m2 ( -46 to 134 ) and there was one toxic death . CONCLUSIONS OPEC/OJEC is a well-tolerated therapy for stage 4 neuroblastoma over 1 year of age BACKGROUND Children with high-risk neuroblastoma have a poor outcome . In this study , we assessed whether myeloablative therapy in conjunction with transplantation of autologous bone marrow improved event-free survival as compared with chemotherapy alone , and whether subsequent treatment with 13-cis-retinoic acid ( isotretinoin ) further improves event-free survival . METHODS All patients were treated with the same initial regimen of chemotherapy , and those without disease progression were then r and omly assigned to receive continued treatment with myeloablative chemotherapy , total-body irradiation , and transplantation of autologous bone marrow purged of neuroblastoma cells or to receive three cycles of intensive chemotherapy alone . All patients who completed cytotoxic therapy without disease progression were then r and omly assigned to receive no further therapy or treatment with 13-cis-retinoic acid for six months . RESULTS The mean ( + /-SE ) event-free survival rate three years after the first r and omization was significantly better among the 189 patients who were assigned to undergo transplantation than among the 190 patients assigned to receive continuation chemotherapy ( 34+/-4 percent vs. 22+/-4 percent , P=0.034 ) . The event-free survival rate three years after the second r and omization was significantly better among the 130 patients who were assigned to receive 13-cis-retinoic acid than among the 128 patients assigned to receive no further therapy ( 46+/-6 percent vs. 29+/-5 percent , P=0.027 ) . CONCLUSIONS Treatment with myeloablative therapy and autologous bone marrow transplantation improved event-free survival among children with high-risk neuroblastoma . In addition , treatment with 13-cis-retinoic acid was beneficial for patients without progressive disease when it was administered after chemotherapy or transplantation BACKGROUND Therapy for high-risk neuroblastoma is intensive and multimodal , and significant long-term adverse effects have been described . The aim of this study was to identify the nature and severity of late complications of metastatic neuroblastoma survivors included in the ENSG5 clinical trial . PROCEDURE The trial protocol included induction chemotherapy ( r and omized " St and ard " OPEC/OJEC vs. " Rapid " COJEC ) , surgery of primary tumor and high-dose melphalan with stem cell rescue . Two hundred and sixty-two children were r and omized , 69 survived > 5 years , and 57 were analyzed . Data were obtained from the ENSG5 trial data base and verified with question naires sent to participating centers . RESULTS Median follow-up was 12.9 ( 6.9 - 16.5 ) years . No differences were found in late toxicities between treatment arms . Twenty-eight children ( 49.1 % ) developed hearing loss . Nine patients ( 15.8 % ) developed glomerular filtration rate < 80 ml/min/1.73 m(2 ) , but no cases of chronic renal failure were documented . Endocrine complications ( 28.1 % of children ) included mainly hypogonadism and delayed growth . Four children developed second malignancies , three of them 5 years after diagnosis : one osteosarcoma , one carcinoma of the parotid gl and and one ependymoma . There were no hematological malignancies or deaths in remission . CONCLUSIONS This study analyzed a wide cohort of high-risk neuroblastoma survivors from a multi-institutional r and omized trial and established the profile of long-term toxicity within the setting of an international clinical trial The percentage of chemotherapy-induced necrosis in primary tumors corresponds with outcome in several childhood malignancies , including high-risk metastatic diseases . In this retrospective pilot study , the authors assessed the importance of postchemotherapy necrosis in high-risk neuroblastoma with a histological and case notes review of surgically resected specimens . The authors review ed all available histology of 31 high-risk neuroblastoma cases treated with COJEC ( dose intensive etoposide and vincristine with either cyclophosphamide , cisplatin or carboplatin ) or OPEC/OJEC ( etoposide , vincristine and cyclosphosphamide with alternating cisplatin [ OPEC ] or carboplatin [ OJEC ] ) induction chemotherapy in 2 Children 's Cancer & Leukaemia Group ( CCLG ) pediatric oncology centers . The percentage of postchemotherapy necrosis was assessed and compared with MYCN amplification status and overall survival . The median percentage of postchemotherapy tumor necrosis was 60 % . MYCN status was available for 28 cases , of which 12 were amplified ( 43 % ) . Survival in cases with ≥60 % necrosis or ≥90 % necrosis was not better than those with less necrosis , nor was percentage necrosis associated with survival using Cox regression . However , MYCN-amplified tumors showed a higher percentage of necrosis than non – MYCN-amplified tumors , 71.3 % versus 37.2 % ( P = .006 ) . This effect was not related to prechemotherapy necrosis and did not confer improved overall survival . Postchemotherapy tumor necrosis is higher in patients with MYCN amplification . In this study , postchemotherapy necrosis did not correlate with overall survival and should not lead to modification of postoperative treatment . However , these findings need to be confirmed in a larger prospect i ve study of children with high-risk neuroblastoma |
1,852 | 30,129,139 | Deprescribing interventions were effective in reducing number of drugs and inappropriate prescribing , but a large heterogeneity in effects was observed .
In general , deprescribing interventions effectively reduce medication use and inappropriate prescribing in older people .
Successful deprescribing is facilitated by the combination of BCTs involving a range of intervention components | AIMS Deprescribing interventions safely and effectively optimize medication use in older people .
However , questions remain about which components of interventions are key to effectively reduce inappropriate medication use .
This systematic review examines the behaviour change techniques ( BCTs ) of deprescribing interventions and summarizes intervention effectiveness on medication use and inappropriate prescribing . | BACKGROUND Adverse drug-related events are common in the elderly , and inappropriate prescribing is a preventable risk factor . Our objective was to determine whether inappropriate prescribing could be reduced when primary care physicians had computer-based access to information on all prescriptions dispensed and automated alerts for potential prescribing problems . METHODS We r and omly assigned 107 primary care physicians with at least 100 patients aged 66 years and older ( total 12 560 ) to a group receiving computerized decision-making support ( CDS ) or a control group . Physicians in the CDS group had access to information on current and past prescriptions through a dedicated computer link to the provincial seniors ' drug-insurance program . When any of 159 clinical ly relevant prescribing problems were identified by the CDS software , the physician received an alert that identified the nature of the problem , possible consequences and alternative therapy . The rate of initiation and discontinuation of potentially inappropriate prescriptions was assessed over a 13-month period . RESULTS In the 2 months before the study , 31.8 % of the patients in the CDS group and 33.3 % of those in the control group had at least 1 potentially inappropriate prescription . During the study the number of new potentially inappropriate prescriptions per 1000 visits was significantly lower ( 18 % ) in the CDS group than in the control group ( relative rate [ RR ] 0.82 , 95 % confidence interval [ CI ] 0.69 - 0.98 ) , but differences between the groups in the rate of discontinuation of potentially inappropriate prescriptions were significant only for therapeutic duplication by the study physician and another physician ( RR 1.66 , 95 % CI 0.99 - 2.79 ) and drug interactions caused by prescriptions written by the study physician ( RR 2.15 , 95 % CI 0.98 - 4.70 ) . INTERPRETATION Computer-based access to complete drug profiles and alerts about potential prescribing problems reduces the rate of initiation of potentially inappropriate prescriptions but has a more selective effect on the discontinuation of such prescriptions OBJECTIVES To evaluate the effect of pharmaceutical care provided in addition to acute Geriatric Evaluation and Management ( GEM ) care on the appropriateness of prescribing . DESIGN R and omized , controlled trial , with the patient as unit of r and omization . SETTING Acute GEM unit . PARTICIPANTS Two hundred three patients aged 70 and older . INTERVENTION Pharmaceutical care provided from admission to discharge by a specialist clinical pharmacist who had direct contacts with the GEM team and patients . MEASUREMENTS Appropriateness of prescribing on admission , at discharge , and 3 months after discharge , using the Medication Appropriateness Index ( MAI ) , Beers criteria , and Assessing Care of Vulnerable Elders ( ACOVE ) underuse criteria and mortality , readmission , and emergency visits up to 12 months after discharge . RESULTS Intervention patients were significantly more likely than control patients to have an improvement in the MAI and in the ACOVE underuse criteria from admission to discharge ( odds ratio (OR)=9.1 , 95 % confidence interval (CI)=4.2 - 21.6 and OR=6.1 , 95 % CI=2.2 - 17.0 , respectively ) . The control and intervention groups had comparable improvements in the Beers criteria . CONCLUSION Pharmaceutical care provided in the context of acute GEM care improved the appropriate use of medicines during the hospital stay and after discharge . This is an important finding , because only limited data exist on the effect of various strategies to improve medication use in elderly in patients . The present approach has the potential to minimize risk and improve patient outcomes OBJECTIVES To determine whether a medication review by a specialized team would promote regimen changes in elders taking multiple medications and to measure the effect of regimen changes on monthly cost and functioning . DESIGN A r and omized-controlled trial . SETTING Health center ambulatory clinic . PARTICIPANTS Community-dwelling older adults taking five or more medications were assessed at baseline and 6 weeks . A medication-change intervention group of 57 elders was compared with a control group of 76 elder adults . INTERVENTION The primary intervention was a comprehensive review and recommended modification of a patient 's medication regimen . Changes were endorsed by each patient 's primary physician and discussed with each patient . MEASUREMENTS Measures were the Timed Manual Performance Test , Physical Performance Test , Functional Reach Assessment , subtests from the Wechsler Adult Intelligence Scale , a modified R and t Memory Test , the Center for Epidemiological Studies -Depression Scale , the Self-Rating Anxiety Scale , and the R and 36-item Health Survey 1.0 . Comorbidity was determined using the International Classification of Diseases , Ninth Revision , Clinical Modification . Medication usage was determined using brown bag review . RESULTS Intervention subjects decreased their medications by an average of 1.5 drugs . No differences in functioning were observed between groups . Intervention subjects saved an average $ 26.92 per month in wholesale medication costs ; control subjects saved $ 6.75 per month ( P<.006 ) . CONCLUSION Although the intervention significantly reduced the medications taken and monthly cost , most patients were resistant to reducing medications to the recommended level . Further study is needed to underst and patient resistance to reducing adverse polypharmacy and to devise better strategies for addressing this important problem in geriatric health . Greater focus on prescriber behavior is recommended OBJECTIVES to evaluate specialist geriatric input and medication review in patients in high-dependency continuing care . DESIGN prospect i ve , r and omised , controlled trial . SETTING two residential continuing care hospitals . PARTICIPANTS two hundred and twenty-five permanent patients . INTERVENTION patients were r and omised to either specialist geriatric input or regular input . The specialist group had a medical assessment by a geriatrician and medication review by a multidisciplinary expert panel . Regular input consisted of review as required by a medical officer attached to each ward . Re assessment occurred after 6 months . RESULTS one hundred and ten patients were r and omised to specialist input and 115 to regular input . These were comparable for age , gender , dependency levels and cognition . After 6 months , the total number of medications per patient per day fell from 11.64 to 11.09 in the specialist group ( P = 0.0364 ) and increased from 11.07 to 11.5 in the regular group ( P = 0.094 ) . There was no significant difference in mortality or frequency of acute hospital transfers ( 11 versus 6 in the specialist versus regular group , P = 0.213 ) . CONCLUSION specialist geriatric assessment and medication review in hospital continuing care result ed in a reduction in medication use , but at a significant cost . No benefits in hard clinical outcomes were demonstrated . However , qualitative benefits and lower costs may become evident over longer periods AIMS This study aims to determine if potentially inappropriate prescribing ( PIP ) is associated with increased healthcare utilization , functional decline and reduced quality of life ( QoL ) in a community-dwelling older cohort . METHOD This prospect i ve cohort study included participants aged ≥65 years from The Irish Longitudinal Study on Ageing ( TILDA ) with linked administrative pharmacy cl aims data who were followed up after 2 years . PIP was defined by the Screening Tool for Older Persons Prescriptions ( STOPP ) and Screening Tool to Alert doctors to Right Treatment ( START ) . The association with number of emergency department ( ED ) visits and GP visits reported over 12 months was analyzed using multivariate negative binomial regression adjusting for confounders . Marginal structural models investigated the presence of time-dependent confounding . RESULTS Of participants followed up ( n = 1753 ) , PIP was detected in 57 % by STOPP and 41.8 % by START , 21.7 % reported an ED visit and 96.1 % visited a GP ( median 4 , IQR 2.5 - 6 ) . Those with any STOPP criterion had higher rates of ED visits ( adjusted incident rate ratio ( IRR ) 1.30 , 95 % confidence interval ( CI ) 1.02 , 1.66 ) and GP visits ( IRR 1.15 , 95%CI 1.06 , 1.24 ) . Patients with two or more START criteria had significantly more ED visits ( IRR 1.45 , 95%CI 1.03 , 2.04 ) and GP visits ( IRR 1.13 , 95%CI 1.01 , 1.27 ) than people with no criteria . Adjusting for time-dependent confounding did not affect the findings . CONCLUSIONS Both STOPP and START were independently associated with increased healthcare utilization and START was also related to functional decline and QoL. Optimizing prescribing to reduce PIP may provide an improvement in patient outcomes BACKGROUND The pharmaceutical care approach serves as a model for medication review , involving collaboration between GPs , pharmacists , patients , and carers . Its use is advocated with older patients who are typically prescribed several drugs . However , it has yet to be thoroughly evaluated . AIM To estimate the effectiveness of pharmaceutical care for older people , shared between GPs and community pharmacists in the UK , relative to usual care . DESIGN OF STUDY Multiple interrupted time-series design in five primary care trusts which implemented pharmaceutical care at 2-month intervals in r and om order . Patients acted as their own controls , and were followed over 3 years including their 12 months ' participation in pharmaceutical care . SETTING In 2002 , 760 patients , aged > or = 75 years , were recruited from 24 general practice s in East and North Yorkshire . Sixty-two community pharmacies also took part . A total of 551 participants completed the study . METHOD Pharmaceutical care was undertaken by community pharmacists who interviewed patients , developed and implemented pharmaceutical care plans together with patients ' GPs , and thereafter undertook monthly medication review s. Pharmacists and GPs attended training before the intervention . Outcome measures were the UK Medication Appropriateness Index , the Short Form-36 Health Survey ( SF-36 ) , and serious adverse events . RESULTS The intervention did not lead to any statistically significant change in the appropriateness of prescribing or health outcomes . Although the mental component of the SF-36 decreased as study participants become older , this trend was not affected by pharmaceutical care . CONCLUSION The RESPECT model of pharmaceutical care ( R and omised Evaluation of Shared Prescribing for Elderly people in the Community over Time ) shared between community pharmacists and GPs did not significantly change the appropriateness of prescribing or quality of life in older patients Abstract Objective : To determine whether a pharmacist can effectively review repeat prescriptions through consultations with elderly patients in general practice . Design : R and omised controlled trial of clinical medication review by a pharmacist against normal general practice review . Setting : Four general practice s. Participants : 1188 patients aged 65 or over who were receiving at least one repeat prescription and living in the community . Intervention : Patients were invited to a consultation at which the pharmacist review ed their medical conditions and current treatment . Main outcome measures : Number of changes to repeat prescriptions over one year , drug costs , and use of healthcare services . Results : 590 ( 97 % ) patients in the intervention group were review ed compared with 233 ( 44 % ) in the control group . Patients seen by the pharmacist were more likely to have changes made to their repeat prescriptions ( mean number of changes per patient 2.2 v 1.9 ; difference=0.31 , 95 % confidence interval 0.06 to 0.57 ; P=0.02 ) . Monthly drug costs rose in both groups over the year , but the rise was less in the intervention group ( mean difference £ 4.72 per 28 days , −£7.04 to -£2.41 ) ; equivalent to £ 61 per patient a year . Intervention patients had a smaller rise in the number of drugs prescribed ( 0.2 v 0.4 ; mean difference −0.2 , −0.4 to −0.1 ) . There was no evidence that review of treatment by the pharmacist affected practice consultation rates , outpatient consultations , hospital admissions , or death rate . Conclusions : A clinical pharmacist can conduct effective consultations with elderly patients in general practice to review their drugs . Such review results in significant changes in patients ' drugs and saves more than the cost of the intervention without affecting the workload of general practitioners . What is already known on this topic Review of patients on long term drug treatment is important but is done inadequately Evidence from the United States shows that pharmacists can improve patient care by review ing drug treatment What this study adds Consultations with a clinical pharmacist are an effective method of review ing the drug treatment of older patients Review by a pharmacist results in more drug changes and lower prescribing costs than normal care plus a much higher review rate Use of healthcare services by patients is not OBJECTIVE Inappropriate drug prescription is a common problem in people living in nursing homes and is linked to adverse health outcomes . This study assessed the effect of an educational intervention directed to nursing home physicians in reducing inappropriate prescription and improving health outcomes and re source utilization . DESIGN Prospect i ve , r and omized , multicenter study . SETTING A private organization of nursing homes in Spain . PARTICIPANTS Sixty nursing home physicians caring for approximately 3900 nursing home residents in 37 centers were r and omized to receive an educational intervention ( 30 ) or as a control group ( 30 ) . INTERVENTION 10 hours educational program , followed by on dem and support by phone . OUTCOME MEASUREMENTS Outcomes were assessed in 1018 r and omly selected nursing home residents . Appropriateness of drug use [ measured by the Screening Tool of Older Persons Prescriptions ( STOPP ) and Screening Tool to Alert Doctors to Right Treatment ( START ) criteria ] , incidence of selected geriatric syndromes ( falls , delirium ) and health re source utilization ( visits to physicians and nursing homes , visits to the emergency room , days of hospitalization ) were recorded for 3 months before the intervention started and 3 months after the intervention finished . RESULTS O total of 716 residents finished the study ( 344 cared for by the intervention group physicians , 372 cared for by control physicians ) . Mean age was 84.4 ± 12.7 years ; 73 % were women . The mean number of inappropriate drugs ( STOPP criteria ) was higher at the end of the study in the control than in the intervention group ( 1.29 ± 1.56 vs 0.81 ± 1.13 ) , as was the number of residents on 6 or more drugs ( 76.5 % vs.67.0 % ) , using antipsychotics ( 9.1 % vs 3.2 % ) or duplicate medications ( 32.5 % vs 9.2 % ) . The number of fallers increased in the control group ( from 19.3 % to 28 % ) and did not significantly change in the intervention group ( from 25.3 % to 23.9 % ) ; the number of residents with delirium increased in the control group ( from 3.8 % to 9.1 % ) and decreased in the intervention group ( from 6.1 % to 3.2 % ) . The number of visits to a physician did not change in the control group ( -0.22 , P = .3 ) but were significantly reduced in the intervention group ( -0.76 , P = .01 ) , the same happened with the number of visits to a nurse ( -0.38 , P = .4 in controls , -1.43 in the intervention group , P < .001 ) . Visits to the emergency room and days in hospital significantly increased in the control group ( + 0.12 and + 0.38 ) but were unchanged in the intervention group ( + 0.03 and + 0.01 ) . CONCLUSIONS An educational intervention on drug use is feasible in nursing home physicians and improves the use of inappropriate drugs , use of antipsychotics , and drug duplications in their residents . It may also improve the risk of delirium and falls , and reduce the use of health care re sources Background Polypharmacy in the Swedish elderly population is currently a prioritised area of research with a focus on reducing the use of potentially inappropriate medications ( PIMs ) . Multi-professional interventions have previously been tested for their ability to improve drug therapy in frail elderly patients . Objective This study aim ed to assess a structured model for pharmacist-led medication review s in primary health care in southern Sweden and to measure its effects on numbers of patients with PIMs ( using the definition of the Swedish National Board of Health and Welfare ) using ≥10 drugs and using ≥3 psychotropics . Methods This study was a r and omised controlled clinical trial performed in a group of patients aged ≥75 years and living in nursing homes or the community and receiving municipal health care . Medication review s were performed by trained clinical pharmacists based on nurse-initiated symptom assessment s with team-based or distance feedback to the physician . Data were collected from the patients ’ electronic medication lists and medical records at baseline and 2 months after the medication review . Results A total of 369 patients were included : 182 in the intervention group and 187 in the control group . One-third of the patients in both groups had at least one PIM at baseline . Two months after the medication review s , the number of intervention group patients with at least one PIM and the number of intervention group patients using ten or more drugs had decreased ( p = 0.007 and p = 0.001 , respectively ) , while there were no statistically significant changes in the control patients . No changes were seen in the number of patients using three or more psychotropic drugs , although the dosages of these drugs tended to decrease . Drug-related problems ( DRPs ) were identified in 93 % of the 182 patients in the intervention group . In total , there were 431 DRPs in the intervention group ( a mean of 2.5 DRPs per patient , range 0–9 , SD 1.5 at 95 % CI ) and 16 % of the DRPs were related to PIMs . Conclusions Medication review s involving pharmacists in primary health care appear to be a feasible method to reduce the number of patients with PIMs , thus improving the quality of pharmacotherapy in elderly patients Purpose To evaluate the effect of a combined or a single educational intervention on the prescribing behaviour of general practitioners ( GPs ) . The primary endpoint was effect on inappropriate prescribing according to the Medication Appropriateness Index ( MAI ) . Methods General practitioners were r and omised to either ( 1 ) a combined intervention consisting of an interactive educational meeting plus feedback on participating patients ’ medication , ( 2 ) a single intervention with an interactive educational meeting or ( 3 ) a control group ( no intervention ) . Elderly ( > 65 years ) patients exposed to polypharmacy ( ≥5 medications ) were identified and approached for inclusion . Data on medications prescribed over a 3-month period were collected , and the GPs provided detailed information on their patients before and after the intervention . A pre- and post-MAI were scored for all medications . Results Of the 277 GPs invited to participate ; 41 ( 14.8 % ) volunteered . Data were obtained from 166 patients before and after the intervention . Medication appropriateness improved in the combined intervention group but not in the single intervention group . The mean change in MAI and number of medications was −5 [ 95 % confidence interval ( CI ) −7.3 to −2.6 ] and −1.03 ( 95 % CI −1.7 to −0.30 ) in the combined intervention group compared with the group with the educational meeting only and the no intervention group . Conclusions A combined intervention consisting of an interactive educational meeting plus recommendations given by clinical pharmacologists/pharmacists concerning specific patients can improve the appropriateness of prescribing among elderly patients exposed to polypharmacy . This study adds to the limited number of well-controlled , r and omised studies on overall medication appropriateness among elderly patients in primary care . Important limitations to the study include variability in data provided by participating GPs and a low number of GPs volunteering for the study Objectives Deprescribing has been proposed as a way to reduce polypharmacy in frail older people . We aim ed to reduce the number of medicines consumed by people living in residential aged care facilities ( RACF ) . Secondary objectives were to explore the effect of deprescribing on survival , falls , fractures , hospital admissions , cognitive , physical , and bowel function , quality of life , and sleep . Methods Ninety-five people aged over 65 years living in four RACF in rural mid-west Western Australia were r and omised in an open study . The intervention group ( n = 47 ) received a deprescribing intervention , the planned cessation of non-beneficial medicines . The control group ( n = 48 ) received usual care . Participants were monitored for twelve months from r and omisation . Primary outcome was change in the mean number of unique regular medicines . All outcomes were assessed at baseline , six , and twelve months . Results Study participants had a mean age of 84.3±6.9 years and 52 % were female . Intervention group participants consumed 9.6±5.0 and control group participants consumed 9.5±3.6 unique regular medicines at baseline . Of the 348 medicines targeted for deprescribing ( 7.4±3.8 per person , 78 % of regular medicines ) , 207 medicines ( 4.4±3.4 per person , 59 % of targeted medicines ) were successfully discontinued . The mean change in number of regular medicines at 12 months was -1.9±4.1 in intervention group participants and + 0.1±3.5 in control group participants ( estimated difference 2.0±0.9 , 95%CI 0.08 , 3.8 , p = 0.04 ) . Twelve intervention participants and 19 control participants died within 12 months of r and omisation ( 26 % versus 40 % mortality , p = 0.16 , HR 0.60 , 95%CI 0.30 to 1.22 ) There were no significant differences between groups in other secondary outcomes . The main limitations of this study were the open design and small participant numbers . Conclusions Deprescribing reduced the number of regular medicines consumed by frail older people living in residential care with no significant adverse effects on survival or other clinical outcomes . Trial Registration Australian New Zeal and Clinical Trials Registry Purpose This study aims to compare the prevalence of potentially inappropriate medicines ( PIMs ) and potential prescribing omissions ( PPOs ) using several screening tools in an Irish community-dwelling older cohort , to assess if the prevalence changes over time and to determine factors associated with any change . Methods This is a prospect i ve cohort study of participants aged ≥65 years in The Irish Longitudinal Study on Ageing ( TILDA ) with linked pharmacy cl aims data ( n = 2051 ) . PIM and PPO prevalence was measured in the year preceding participants ’ TILDA baseline interviews and in the year preceding their follow-up interviews using the Screening Tool for Older Persons ’ Prescriptions ( STOPP ) , Beers criteria ( 2012 ) , Assessing Care of Vulnerable Elders ( ACOVE ) indicators and the Screening Tool to Alert doctors to Right Treatment ( START ) . Generalised estimating equations were used to determine factors associated with change in prevalence over time . Results Depending on the screening tool used , between 19.8 % ( ACOVE indicators ) and 52.7 % ( STOPP ) of participants received a PIM at baseline , and PPO prevalence ranged from 38.2 % ( START ) to 44.8 % ( ACOVE indicators ) , while 36.7 % of participants had both a PIM and PPO . Common criteria were aspirin for primary prevention ( 19.6 % ) and omission of calcium/vitamin D in osteoporosis ( 14.7 % ) . Prevalence of PIMs and PPOs increased at follow-up ( PIMs range 22–56.1 % , PPOs range 40.5–49.3 % ) , and this was associated with patient age , female sex , and numbers of medicines and chronic conditions . Conclusions Sub-optimal prescribing is common in older patients . Ongoing prescribing review to optimise care is important , particularly as patients get older , receive more medicines or develop more illnesses Background Method ological guidelines for intervention reporting emphasise describing intervention content in detail . Despite this , systematic review s of quality improvement ( QI ) implementation interventions continue to be limited by a lack of clarity and detail regarding the intervention content being evaluated . We aim ed to apply the recently developed Behaviour Change Techniques Taxonomy version 1 ( BCTTv1 ) to trials of implementation interventions for managing diabetes to assess the capacity and utility of this taxonomy for characterising active ingredients . Methods Three psychologists independently coded a r and om sample of 23 trials of healthcare system , provider- and /or patient-focused implementation interventions from a systematic review that included 142 such studies . Intervention content was coded using the BCTTv1 , which describes 93 behaviour change techniques ( BCTs ) grouped within 16 categories . We supplemented the generic coding instructions within the BCTTv1 with decision rules and examples from this literature . Results Less than a quarter of possible BCTs within the BCTTv1 were identified . For implementation interventions targeting providers , the most commonly identified BCTs included the following : adding objects to the environment , prompts/cues , instruction on how to perform the behaviour , credible source , goal setting ( outcome ) , feedback on outcome of behaviour , and social support ( practical ) . For implementation interventions also targeting patients , the most commonly identified BCTs included the following : prompts/cues , instruction on how to perform the behaviour , information about health consequences , restructuring the social environment , adding objects to the environment , social support ( practical ) , and goal setting ( behaviour ) . The BCTTv1 mapped well onto implementation interventions directly targeting clinicians and patients and could also be used to examine the impact of system-level interventions on clinician and patient behaviour . Conclusions The BCTTv1 can be used to characterise the active ingredients in trials of implementation interventions and provides specificity of content beyond what is given by broader intervention labels . Identification of BCTs may provide a more helpful means of accumulating knowledge on the content used in trials of implementation interventions , which may help to better inform replication efforts . In addition , prospect i ve use of a behaviour change techniques taxonomy for developing and reporting intervention content would further aid in building a cumulative science of effective implementation interventions OBJECTIVES To assess the effect of a Screening Tool of Older Persons potentially inappropriate Prescriptions/Screening Tool to Alert doctors to Right Treatment ( STOPP/START ) medication intervention on clinical and economic outcomes . DESIGN Parallel-group r and omized trial . SETTING Chronic care geriatric facility . PARTICIPANTS Residents aged 65 and older prescribed with at least one medication ( N = 359 ) were r and omized to receive usual pharmaceutical care or undergo medication intervention . INTERVENTION Screening medications with STOPP/START criteria followed up with recommendations to the chief physician . MEASUREMENTS The outcome measures assessed at the initiation of the intervention and 1 year later were number of hospitalizations and falls , Functional Independence Measure ( FIM ) , quality of life ( measured using the Medical Outcomes Study 12-item Short-Form Health Survey ) , and costs of medications . RESULTS The average number of drugs prescribed was significantly lower in the intervention than in the control group after 1 year ( P < .001 ) . The average drug costs in the intervention group decreased by 103 shekels ( US$ 29 ) per participant per month ( P < .001 ) . The average number of falls in the intervention group dropped significantly ( P = .006 ) . Rates of hospitalization , FIM scores , and quality of life measurements were similar for both groups . CONCLUSION Implementation of STOPP/START criteria reduced the number of medications , falls , and costs in a geriatric facility . Their incorporation in those and similar setting s is recommended BACKGROUND The administration of many drugs concurrently to elderly patients is a well-known problem in geriatrics and involves numerous risks . One way to reduce polypharmacy is to provide information to physicians in order to modify their prescribing practice s. The main objective of this study was to evaluate the impact of an intervention program that targeted physicians with the aim of reducing the number of potentially inappropriate prescriptions ( PIPs ) given to elderly patients . METHODS A r and omized controlled trial was carried out among community-dwelling elderly people in Sherbrooke , Que . The participants were 266 patients over 75 years of age ( experimental group : n = 136 , control group : n = 130 ) . A team comprising 2 physicians , a pharmacist and a nurse review ed the list of drugs and the diagnoses of a subgroup of the experimental group in a case conference . Suggestions were formulated and mailed to the patients ' physicians together with relevant scientific documentation justifying the recommendations . The main outcome measure was the number of PIPs . RESULTS The mean number of PIPs per patient declined by 0.24 in the experimental group ( n = 127 ) and by 0.15 in the control group ( n = 116 ) . The decline in PIPs was even larger in the experimental group that had case conferences ( n = 80 ) , in which the mean number of PIPs per patient declined by 0.31 . However , this difference between the experimental group and the control group was not statistically significant in the intent-to-treat analysis . The number of drugs prescribed was not modified by the intervention , nor were the results of the global assessment of the patients ' drug profiles . INTERPRETATION This study suggests that the intervention program had no effect on the prescribing of PIPs Background Falls are the leading cause of injury-related deaths in the aging population . Electronic medical record ( EMR ) systems can identify at-risk patients and enable interventions to decrease risk factors for falls . Objective The objectives of this study were to evaluate an EMR-based intervention to reduce overall medication use , psychoactive medication use , and occurrence of falls in an ambulatory elderly population at risk for falls . Design Prospect i ve , r and omized by clinic site . Patients / Participants Six-hundred twenty community-dwelling patients over 70 at risk for falls based on age and medication use . Interventions A st and ardized medication review was conducted and recommendations made to the primary physician via the EMR . Measurements and Main Results Patients were contacted to obtain self reports of falls at 3-month intervals over the 15-month period of study . Fall-related diagnoses and medication data were collected through the EMR . A combination of descriptive analyses and multivariate regression models were used to evaluate differences between the 2 groups , adjusting for baseline medication patterns and comorbidities . Although the intervention did not reduce the total number of medications , there was a significant negative relationship between the intervention and the total number of medications started during the intervention period ( p < .01 , regression estimate −0.199 ) and the total number of psychoactive medications ( p < .05 , regression estimate −0.204 . ) The impact on falls was mixed ; with the intervention group 0.38 times as likely to have had 1 or more fall-related diagnosis ( p < .01 ) ; when data on self-reported falls was included , a nonsignificant reduction in fall risk was seen . Conclusions The current study suggests that using an EMR to assess medication use in the elderly may reduce the use of psychoactive medications and falls in a community-dwelling elderly population Inappropriate polypharmacy , especially in older people , imposes a substantial burden of adverse drug events , ill health , disability , hospitalization , and even death . The single most important predictor of inappropriate prescribing and risk of adverse drug events in older patients is the number of prescribed drugs . Deprescribing is the process of tapering or stopping drugs , aim ed at minimizing polypharmacy and improving patient outcomes . Evidence of efficacy for deprescribing is emerging from r and omized trials and observational studies . A deprescribing protocol is proposed comprising 5 steps : ( 1 ) ascertain all drugs the patient is currently taking and the reasons for each one ; ( 2 ) consider overall risk of drug-induced harm in individual patients in determining the required intensity of deprescribing intervention ; ( 3 ) assess each drug in regard to its current or future benefit potential compared with current or future harm or burden potential ; ( 4 ) prioritize drugs for discontinuation that have the lowest benefit-harm ratio and lowest likelihood of adverse withdrawal reactions or disease rebound syndromes ; and ( 5 ) implement a discontinuation regimen and monitor patients closely for improvement in outcomes or onset of adverse effects . Whereas patient and prescriber barriers to deprescribing exist , re sources and strategies are available that facilitate deliberate yet judicious deprescribing and deserve wider application OBJECTIVE To explore the current use of conventional and complementary medicines in Australians aged ≥ 50 years . DESIGN , SETTING AND PARTICIPANTS Cross-sectional postal survey sent to a r and om sample of 4500 Australians aged ≥ 50 years between June 2009 and February 2010 . MAIN OUTCOME MEASURES Prevalence of medicines use , reasons for medicines use and sources of medicines . RESULTS Response rate was 37.3 % . Medicines use was very common ; 87.1 % of participants took one or more medicines and 43.3 % took five or more in the previous 24 hours . Complementary medicines were used by 46.3 % of participants , 87.4 % of whom used both conventional and complementary medicines . The most commonly used medicines were antihypertensive agents ( 43.2 % of participants ) , natural marine and animal products including fish oil and glucosamine ( 32.4 % ) and lipid-lowering agents ( 30.4 % ) . Doctors recommended 79.3 % of all medicines and 93.0 % of conventional medicines . Pharmacists commonly recommended occasional medicines ( ie , as needed ) , while friends , family and media most often influenced use of complementary medicines . CONCLUSIONS The use of multiple medicines is common and higher than reported in the 1995 National Health Survey . Today , much medicines use is to prevent future disease by influencing risk factors . High levels of polypharmacy highlight the need to support the safe and effective use of medicines in the community . Although doctors recommend or prescribe most medicines , self-directed medication use is common . This highlights the need for consumer access to accurate information and strategies to improve health literacy about medicines PURPOSE To determine if inpatient or outpatient geriatric evaluation and management , as compared with usual care , reduces adverse drug reactions and suboptimal prescribing in frail elderly patients . METHODS The study employed a r and omized 2 x 2 factorial controlled design . Subjects were patients in 11 Veterans Affairs ( VA ) hospitals who were > or = 65 years old and met criteria for frailty ( n = 834 ) . Inpatient geriatric unit and outpatient geriatric clinic teams evaluated and managed patients according to published guidelines and VA st and ards . Patients were followed for 12 months . Blinded physician-pharmacist pairs rated adverse drug reactions for causality ( using Naranjo 's algorithm ) and seriousness . Suboptimal prescribing measures included unnecessary and inappropriate drug use ( Medication Appropriateness Index ) , inappropriate drug use ( Beers criteria ) , and underuse . RESULTS For serious adverse drug reactions , there were no inpatient geriatric unit effects during the inpatient or outpatient follow-up periods . Outpatient geriatric clinic care result ed in a 35 % reduction in the risk of a serious adverse drug reaction compared with usual care ( adjusted relative risk = 0.65 ; 95 % confidence interval : 0.45 to 0.93 ) . Inpatient geriatric unit care reduced unnecessary and inappropriate drug use and underuse significantly during the inpatient period ( P < 0.05 ) . Outpatient geriatric clinic care reduced the number of conditions with omitted drugs significantly during the outpatient period ( P < 0.05 ) . CONCLUSION Compared with usual care , outpatient geriatric evaluation and management reduces serious adverse drug reactions , and inpatient and outpatient geriatric evaluation and management reduces suboptimal prescribing , in frail elderly patients Inappropriate prescribing is particularly common in older patients and is associated with adverse drug events ( ADEs ) , hospitalization , and wasteful utilization of re sources . We r and omized 400 hospitalized patients aged ≥65 years to receive either the usual pharmaceutical care ( control ) or screening with STOPP/START criteria followed up with recommendations to their attending physicians ( intervention ) . The Medication Appropriateness Index ( MAI ) and Assessment of Underutilization ( AOU ) index were used to assess prescribing appropriateness , both at the time of discharge and for 6 months after discharge . Unnecessary polypharmacy , the use of drugs at incorrect doses , and potential drug – drug and drug – disease interactions were significantly lower in the intervention group at discharge ( absolute risk reduction 35.7 % , number needed to screen to yield improvement in MAI = 2.8 ( 95 % confidence interval 2.2–3.8 ) ) . Underutilization of clinical ly indicated medications was also reduced ( absolute risk reduction 21.2 % , number needed to screen to yield reduction in AOU = 4.7 ( 95 % confidence interval 3.4–7.5 ) ) . Significant improvements in prescribing appropriateness were sustained for 6 months after discharge OBJECTIVES The objectives of this study were ( 1 ) to investigate the effect of nurse training on the use of potentially harmful medications ; and ( 2 ) to explore the effect of nurse training on residents ' health-related quality of life ( HRQoL ) , health service utilization , and mortality . DESIGN A r and omized controlled trial . SETTING AND PARTICIPANTS In total , 227 residents in 20 wards of assisted living facilities in Helsinki were recruited . The 20 wards were r and omized into those in which ( 1 ) staff received two 4-hour training sessions on appropriate medication treatment ( intervention group ) , and ( 2 ) staff received no additional training and continued to provide routine care ( control group ) . INTERVENTION Two 4-hour interactive training sessions for nursing staff based on constructive learning theory to recognize potentially harmful medications and corresponding adverse drug events . MEASUREMENTS Use of potentially harmful medications , HRQoL assessed using the 15 dimensional instrument of health-related quality of life , health service utilization , and mortality assessed at baseline , and 6 and 12 months . RESULTS During the 12-month follow-up , the mean number of potentially harmful medications decreased in the intervention wards [ -0.43 , 95 % confidence interval ( CI ) -0.71 to -0.15 ] but remained constant in the control wards ( + 0.11 , 95 % CI -0.09 to + 0.31 ) ( P = .004 , adjusted for age , sex , and comorbidities ) . HRQoL declined more slowly in the intervention wards ( -0.038 ( 95 % CI -0.054 to -0.022 ) than in the control wards ( -0.072 ( 95 % CI -0.089 to -0.055 ) ( P = .005 , adjusted for age , sex , and comorbidities ) . Residents of the intervention wards had significantly less hospital days ( 1.4 days/person/year , 95 % CI 1.2 - 1.6 ) than in the control wards ( 2.3 days/person/year ; 95 % CI 2.1 - 2.7 ) ( relative risk 0.60 , 95 % CI 0.49 - 0.75 , P < .001 , adjusted for age , sex , and comorbidities ) . CONCLUSIONS Activating learning methods directed at nurses in charge of comprehensive care can reduce the use of harmful medications , maintain HRQoL , and reduce hospitalization in residents of assisted living facilities OBJECTIVE To assess whether home-based medication review by a pharmacist for at-risk older patients in a primary care setting can reduce hospital admissions . DESIGN R and omised controlled trial comparing home-based medication review with st and ard care . SETTING Home-based medication review of 136 patients registered with one general practice . METHOD Study participants were over 80 years of age , living at home , taking four or more medicines , and had at least one additional medicines-related risk factor . The intervention comprised two home visits by a community pharmacist who educated the patient/carer about their medicines , noted any pharmaceutical care issues , assessed need for an adherence aid , and subsequently met with the lead GP to agree on actions . MAIN OUTCOME MEASURE Total non-elective hospital admissions within 6 months . Secondary outcomes included number of deaths , care home admissions and quality of life ( EQ-5d ) . Impact on number of medicines prescribed was also assessed . RESULTS At 6 months , no difference in hospital admissions ( 21 intervention versus 20 control P = 0.80 ) , and no difference in care home admissions or deaths were detected between groups . There was a small ( non-significant ) decrease in quality of life in the intervention group . There was a statistically significant reduction in the mean number of medicines prescribed ( -0.87 items in favour of the intervention group , 95 % confidence interval -1.66 to -0.08 , P = 0.03 ) . CONCLUSIONS No positive impact on clinical outcomes or quality of life was demonstrated , however , this intervention did appear to reduce prescribing . This is in line with other evidence and suggests that this form of intervention may not have a clear health gain , but may lead to modest savings in terms of reduced prescribing . Future research should focus on whether such a prescribing effect would make this type of intervention cost effective PURPOSE To evaluate the effect of sustained clinical pharmacist interventions involving elderly out patients with polypharmacy and their primary physicians . PATIENTS AND METHODS R and omized , controlled trial of 208 patients aged 65 years or older with polypharmacy ( > or = 5 chronic medications ) from a general medicine clinic of a Veterans Affairs Medical Center . A clinical pharmacist met with intervention group patients during all scheduled visits to evaluate their drug regimens and make recommendations to them and their physicians . Outcome measures were prescribing appropriateness , health-related quality of life , adverse drug events , medication compliance and knowledge , number of medications , patient satisfaction , and physician receptivity . RESULTS Inappropriate prescribing scores declined significantly more in the intervention group than in the control group by 3 months ( decrease 24 % versus 6 % , respectively ; P = 0.0006 ) and was sustained at 12 months ( decrease 28 % versus 5 % , respectively ; P = 0.0002 ) . There was no difference between groups at closeout in health-related quality of life ( P = 0.99 ) . Fewer intervention than control patients ( 30.2 % ) versus 40.0 % ; P = 0.19 ) experienced adverse drug events . Measures for most other outcomes remained unchanged in both groups . Physicians were receptive to the intervention and enacted changes recommended by the clinical pharmacist more frequently than they enacted changes independently for control patients ( 55.1 % versus 19.8 % ; P < 0.001 ) . CONCLUSIONS This study demonstrates that a clinical pharmacist providing pharmaceutical care for elderly primary care patients can reduce inappropriate prescribing and possibly adverse drug effects without adversely affecting health-related quality of life IMPORTANCE The American Board of Internal Medicine Foundation Choosing Wisely Campaign recommends against the use of benzodiazepine drugs for adults 65 years and older . The effect of direct patient education to catalyze collaborative care for reducing inappropriate prescriptions remains unknown . OBJECTIVE To compare the effect of a direct-to-consumer educational intervention against usual care on benzodiazepine therapy discontinuation in community-dwelling older adults . DESIGN , SETTING , AND PARTICIPANTS Cluster r and omized trial ( EMPOWER [ Eliminating Medications Through Patient Ownership of End Results ] study [ 2010 - 2012 , 6-month follow-up ] ) . Community pharmacies were r and omly allocated to the intervention or control arm in nonstratified , blocked groups of 4 . Participants ( 303 long-term users of benzodiazepine medication aged 65 - 95 years , recruited from 30 community pharmacies ) were screened and enrolled prior to r and omization : 15 pharmacies r and omized to the educational intervention included 148 participants and 15 pharmacies r and omized to the " wait list " control included 155 participants . Participants , physicians , pharmacists , and evaluators were blinded to outcome assessment . INTERVENTIONS The active arm received a deprescribing patient empowerment intervention describing the risks of benzodiazepine use and a stepwise tapering protocol . The control arm received usual care . MAIN OUTCOMES AND MEASURES Benzodiazepine therapy discontinuation at 6 months after r and omization , ascertained by pharmacy medication renewal profiles . RESULTS A total of 261 participants ( 86 % ) completed the 6-month follow-up . Of the recipients in the intervention group , 62 % initiated conversation about benzodiazepine therapy cessation with a physician and /or pharmacist . At 6 months , 27 % of the intervention group had discontinued benzodiazepine use compared with 5 % of the control group ( risk difference , 23 % [ 95 % CI , 14%-32 % ] ; intracluster correlation , 0.008 ; number needed to treat , 4 ) . Dose reduction occurred in an additional 11 % ( 95 % CI , 6%-16 % ) . In multivariate subanalyses , age greater than 80 years , sex , duration of use , indication for use , dose , previous attempt to taper , and concomitant polypharmacy ( 10 drugs or more per day ) did not have a significant interaction effect with benzodiazepine therapy discontinuation . CONCLUSIONS AND RELEVANCE Direct-to-consumer education effectively elicits shared decision making around the overuse of medications that increase the risk of harm in older adults . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01148186 OBJECTIVES To test the efficacy of a medication use improvement program developed specifically for home health agencies . The program addressed four medication problems identified by an expert panel : unnecessary therapeutic duplication , cardiovascular medication problems , use of psychotropic drugs in patients with possible adverse psychomotor or adrenergic effects , and use of nonsteroidal antiinflammatory drugs ( NSAIDs ) in patients at high risk of peptic ulcer complications . It used a structured collaboration between a specially trained clinical pharmacist and the patients ' home-care nurses to improve medication use . DESIGN Parallel-group , r and omized controlled trial . SETTING Two of the largest home health agencies in the United States . PARTICIPANTS Study subjects were consenting Medicare patients aged 65 and older admitted to participating agency offices from October 1996 through September 1998 , with a projected home healthcare duration of at least 4 weeks and at least one study medication problem . INTERVENTION Qualifying patients were r and omized to usual care or usual care with the medication improvement program . MEASUREMENTS Medication use was measured during an in-home interview , with container inspection at baseline and at follow-up ( between 6 and 12 weeks ) by interviewers unaware of treatment assignment . The trial endpoint was the proportion of patients with medication use improvement according to predefined criteria at follow-up . RESULTS There were 259 r and omized patients with completed follow-up interviews : 130 in the intervention group and 129 with usual care . Medication use improved for 50 % of intervention patients and 38 % of control patients , an attributable improvement of 12 patients per 100 ( 95 % confidence interval ( CI ) = 0.0 - 24.0 , P = .051 ) . The intervention effect was greatest for therapeutic duplication , with improvement for 71 % of intervention and 24 % of control patients , an attributable improvement of 47 patients per 100 ( 95 % CI = 20 - 74 , P = .003 ) . Use of cardiovascular medications also improved more frequently in intervention patients : 55 % vs 18 % , attributable improvement 37 patients per 100 ( 95 % CI = 9 - 66 , P = .017 ) . There were no significant improvements for the psychotropic medication or NSAID problems . There was no evidence of adverse intervention effects : new medication problems , more agency nurse visits , or increased duration of home health care . CONCLUSIONS A program congruent with existing personnel and practice s of home health agencies improved medication use in a vulnerable population and was particularly effective in reducing therapeutic duplication Objective This study 's objective was to determine whether patients treated in a geriatric evaluation and management unit ( GEMU ) had a more appropriate drug profile than patients treated in the general medical wards ( MW ) . Methods Frail elderly patients admitted as emergencies to the medical department were r and omised to treatment in the GEMU ( n=127 ) or MW ( n=127 ) . Drugs used at inclusion and discharge were registered retrospectively and analysed with regard to polypharmacy , number of drugs withdrawn or started , potential drug-drug interactions ( DDIs ) , number of anticholinergic drugs prescribed , and the number of inappropriate drug prescriptions according to Beers ' criteria . Utilisation of psychotropic and cardiovascular drugs was compared in detail according to prespecified hypotheses . Results The number of patients with polypharmacy did not differ significantly between the GEMU and MW . The median number of scheduled drugs withdrawn per patient was higher in the GEMU than in the MW ( p=0.005 ) . Drugs with anticholinergic effects ( p=0.003 ) ; cardiovascular drugs ( p<0.001 ) , particularly digitalis glycosides ( p<0.001 ) ; and antipsychotic drugs ( p=0.009 ) were withdrawn more often in the GEMU . The median number of scheduled drugs started was higher in the GEMU than in the MW ( p=0.03 ) . In particular , antidepressants ( p<0.001 ) and estriol ( p=0.001 ) were started more often in the GEMU than in the MW . Fewer GEMU than MW patients had potential DDIs at discharge ( p=0.009 ) . Conclusion Drug treatment in the GEMU as compared with the MW was more appropriate in terms of prescription of fewer drugs with anticholinergic effects and fewer potential DDIs . There were distinct differences in treatment patterns of cardiovascular and psychotropic drugs 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 R and omised controlled trials are widely accepted as the most reliable method of determining effectiveness , but most trials have evaluated the effects of a single intervention such as a drug . Recognition is increasing that other , non-pharmacological interventions should also be rigorously evaluated.1 - 3 This paper examines the design and execution of research required to address the additional problems result ing from evaluation of complex interventions —that is , those “ made up of various interconnecting parts.”4 The issues dealt with are discussed in a longer Medical Research Council paper ( www.mrc.ac.uk/complex_packages.html ) . We focus on r and omised trials but believe that this approach could be adapted to other design s when they are more appropriate . # # # # Summary points Complex interventions are those that include several components The evaluation of complex interventions is difficult because of problems of developing , identifying , documenting , and reproducing the intervention A phased approach to the development and evaluation of complex interventions is proposed to help research ers define clearly where they are in the research process Evaluation of complex interventions requires use of qualitative and quantitative evidence There are specific difficulties in defining , developing , documenting , and reproducing complex interventions that are subject to more variation than a drug . A typical example would be the design of a trial to evaluate the benefits of specialist stroke units . Such a trial would have to consider the expertise of various health professionals as well as investigations , drugs , treatment guidelines , and arrangements for discharge and follow up . Stroke units may also vary in terms of organisation , management , and skill mix . The active components of the stroke unit may be difficult to specify , making it difficult to replicate the intervention . The box gives other examples of complex interventions . # # # # Examples of complex interventions Service delivery and organisation : Stroke units Hospital at home Interventions directed at health professionals ' behaviour : Strategies for implementing guidelines Computerised decision support Community interventions : Community BACKGROUND Despite progress in describing the problem of potentially inappropriate medication ( PIM ) use , there have been few prospect i ve studies demonstrating that interventions with specific medication criteria can make a difference in decreasing the use of problematic drugs in older adults . OBJECTIVE To design an intervention study to change physician behavior regarding PIM prescribing to older patients . STUDY DESIGN AND METHODS A prospect i ve r and omized block design was used during an 18-month period from January 2001 to June 2002 . The study population was primary care physicians ( n = 355 ) in the Medicare + Choice product line of a southeastern managed care organization and their patients 65 years and older . There were 170 physicians in the treatment group and 185 in the control group . Physicians were assigned to the treatment or usual-care , groups using a r and omization table , and each group included physicians who had and had not prescribed a PIM . RESULTS Approximately 71 % ( 84/118 ) of the physicians in the intervention group who prescribed a PIM completed and faxed back at least 1 potentially inappropriate medication form to the managed care organization . On 15.4 % ( 260/1692 ) of the medication forms , physicians made some change regarding PIM use . CONCLUSIONS Although many studies have addressed medication use among older adults , intervention studies aim ed at influencing physician prescribing in this population are limited . This study describes a low-cost , replicable method to contact and educate physicians on drug therapy issues in older adults Background Hospital admissions may provide an opportunity to discontinue potentially inappropriate medications ( PIMs ) in older patients . Little is known about the effect of using the Screening Tool of Older People ’s potentially inappropriate Prescriptions ( STOPP ) in this context . This study aim ed to test the hypothesis that specific STOPP recommendations from an inpatient geriatric consultation team ( IGCT ) to the hospital physician leads to reductions in PIMs for patients at discharge . Methods This was a r and omised controlled study in 146 frail in patients ( in 2011 ) . The intervention consisted of STOPP recommendations made by the IGCT to ward physicians to discontinue PIMs , in addition to the st and ard geriatric advice . Results Intervention ( n = 74 ) and control ( n = 72 ) groups were similar in terms of patient characteristics ( median age 85 years ; median number of daily drugs , seven ) and PIM distribution ( 68 and 57 PIMs in 53 and 51 % of patients , respectively ) . At discharge , the reduction in PIMs was twice as high for the intervention group as for the control group ( 39.7 and 19.3 % , respectively ; p = 0.013 ) . The proportion of patients who still had one or more PIM at discharge did not differ between groups . In the 50 patients followed-up a year later , the majority of PIMs that had been stopped during hospitalisation had not been restarted after discharge ( 17/28 ; 61 % ) . The clinical relevance of PIMs identified at baseline in those patients was considered major ( 29 % ) , moderate ( 37 % ) , minor ( 5 % ) , deleterious ( 8 % ) , or not assessed ( 11 % ) . Discontinuation rate was not associated with clinical importance . ConclusionS pecific STOPP recommendations provided to hospital physicians doubled the reduction of PIMs at discharge in frail older in patients . To further improve the appropriateness of prescribing in older patients , clinicians should focus on the STOPP criteria that are of major clinical importance , and general practitioners should be actively involved |
1,853 | 30,765,785 | When comparing the caries arrest lesions of SDF and NaF , SDF was found to be statistically more effective in dentine caries arrest of primary teeth during the 18 and 30 month clinical examinations . | Dental caries can compromise quality of life and is associated with demineralization of tooth structure by organic acids produced by microorganisms .
This study systematic ally review ed the dentine caries arrest capabilities of silver diamine fluoride ( SDF ) and sodium fluoride ( NaF ) . | 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 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 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 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 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 Dental caries in Chinese pre-school children is common , and restorative treatment is not readily available . This prospect i ve controlled clinical trial investigated the effectiveness of topical fluoride applications in arresting dentin caries . We divided 375 children ( aged 3 - 5 yrs ) with carious upper anterior teeth into five groups . Children in the first and second groups received annual applications of silver diamine fluoride solution ( 44,800 ppm F ) . NaF varnish ( 22,600 ppm F ) was applied every three months onto 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 . We followed 341 children for 18 months . The mean numbers of new caries surfaces in the five groups were 0.4 , 0.4 , 0.8 , 0.6 , and 1.2 , respectively ( p = 0.001 ) . The respective mean numbers of arrested carious tooth surfaces were 2.8 , 3.0 , 1.7 , 1.5 , and 1.0 ( p < 0.001 ) |
1,854 | 28,262,917 | Women on partial bed rest in hospital were less likely to develop gestational hypertension compared with women without activity restriction at home ( RR 0.30 , 95 % CI 0.16 to 0.59 , P = 0.0004 , 141 women).Strict or partial bed rest in hospital was found to have no impact on other secondary outcomes . | BACKGROUND Strict or partial bed rest in hospital or at home is commonly recommended for women with multiple pregnancy to improve pregnancy outcomes .
In order to advise women to rest in bed for any length of time , a policy for clinical practice needs to be supported by reliable evidence and weighed against possible adverse effects result ing from prolonged activity restriction .
OBJECTIVES The objective of this review is to assess the effectiveness of bed rest in hospital or at home to improve perinatal outcomes in women with a multiple pregnancy . | Summary . Women attending a twin pregnancy antenatal clinic underwent cervical palpation to calculate a cervical score by subtracting dilatation from length . Those with a score of −2 or less at or before 34 weeks are at especially high risk of preterm labour . A total of 139 such women were r and omly allocated either to receive bed‐rest in hospital or to continue conventional outpatient management . No beneficial effect of bed‐rest could be identified in prolonging twin pregnancy or improving fetal outcome Nineteen women attending a special multiple pregnancy antenatal clinic with a triplet pregnancy were r and omly allocated to either bed rest in hospital from 24 weeks gestation onwards until delivery , or to continue conventional outpatient management . Conclusions are limited by the trial size , but the study suggests that routine hospitalization for bed rest decreases the incidence of preterm delivery and light-for-gestational age infants and reduces the need for intensive neonatal care . Although still compatible with change variation , the observations , if confirmed in a larger r and omized study , would have considerable implication s for clinical practice . The policy needs further evaluation in a large multicentered collaborative study The study evaluates the benefit of elective hospitalization in preventing premature deliveries of twin gestations . Three groups of women with twin gestations , having no other complications of pregnancy which could cause premature delivery , were evaluated . The study group was comprised of 43 women who were electively hospitalized between 30 - 32 and 36 weeks of gestation . Control group 1 was comprised of 55 women who were not hospitalized but were instructed to rest at home . Control group 2 was comprised of 53 women who were not hospitalized and were not instructed to rest at home . Our results showed that elective hospitalization did not significantly affect the gestational duration or the prematurity rate . However the mean birthweight difference between the study group and the two control groups were 143 + /- 83 g and 205 + /- 84 g , respectively . This result was more significant in multiparous women . The slight increase in birthweight of the hospitalized women compared to the controls , does not seem to justify the cost of hospitalization OBJECTIVE The purpose of the study was to determine whether the use of prophylactic oral ritodrine or hospitalization for bed rest can prolong pregnancy in multiple pregnancy . METHODS The study was conducted over a period of 8 years and included 189 cases of multiple pregnancy , all of which were delivered at the King Fahd Hospital of the University , Al-Khobar , Saudi Arabia , between July 1986 and August 1994 . The patients were divided into three groups : the first group included 64 patients who received oral ritodrine from the 25th to the end of the 37th week of gestation ; the second group included 57 patients who were hospitalized from the 28th to the 32nd week of gestation ; and the third group , considered the control group , included 68 patients who were managed on an outpatient basis only . Forty-six cases of multiple pregnancy were excluded from the study for a variety of reasons . RESULTS The study showed an increase in gestational age at delivery , an increase in mean birth weight and a reduction in preterm delivery in the group treated with prophylactic ritodrine ( P = 0.03 ) . In the hospitalized group there was no effect on duration of gestation or reduction in preterm delivery , but there was an increase in mean birth weight ( P = 0.04 ) . Several patients experienced troublesome side effects with ritodrine . CONCLUSION Our study indicates that the prophylactic use of beta-sympathomimetics is more effective , beneficial and less expensive than hospitalization for bed rest in prevention of preterm labor and delivery in multiple pregnancy Summary . After admission to hospital for bed rest , 200 women with multiple pregnancies were r and omly allocated to receive either 4 mg of salbutamol orally five times daily , or to receive no drug . After an average of 6 weeks treatment , no difference between the experimental groups could be detected with respect to duration of gestation , birth‐weight or any other of the outcomes of pregnancy observed Objective –To test whether a policy of hospitalization for bed rest , from 28–30 weeks gestation until delivery , lengthens the duration of gestation , improves fetal growth and decreases neonatal morbidity in twin pregnancy Of 141 women with twin pregnancies , 72 were r and omly assigned to outpatient care and 69 to hospital admission between 26 and 30 weeks ' gestation . There were no differences between the groups in the frequencies of major maternal complications in pregnancy and labour but more of those admitted to hospital than of the outpatient group had to be admitted after 30 weeks . There were no differences between the groups in the mean birthweights of the twins by birth order , or in their mean gestation at birth whether analysed by intention to treat or by the treatment given . 22 infants were delivered before 32 weeks ' gestation in the inpatient group compared with 10 in the outpatient group . With the exception of small-for- date s infants , any trend towards greater morbidity or mortality was seen in the inpatient group . The policy of routine hospital admission of women with twin pregnancies from 26 weeks ' gestation is not beneficial to mother or babies and should be ab and oned 212 women with twin pregnancies were r and omly allocated either to receive advice to rest in hospital from 32 weeks ' gestation until delivery , or to be part of a control group in which hospital admission was offered selectively ( and , on average , 5 weeks later ) . Preterm delivery was more common among women admitted routinely for bed rest than among controls , and this difference was unlikely to have occurred by chance . There is at present no scientifically acceptable evidence that this common , disruptive , and expensive obstetric policy does more good than harm A prospect i ve study was carried out to evaluate the significance and efficacy of routine hospital bed rest in prevention of premature birth and pregnancy complications compared to specialized antenatal care at the outpatient clinic of 73 twin pregnancies . The twin pregnancies were screened in health centers by means of symphysis-fundus measurement , and the diagnosis was confirmed by ultrasound examination at the outpatient clinic . On the average the ultrasonic diagnosis was performed during the 23rd gestational week ; at this visit the women were divided into two groups with similar follow-up to the end of the 29th gestational week . At this stage one of the groups was hospitalized unless there had been indications for earlier admission . In the hospital group , the mean for gestational week at delivery was 36.7 ( + /- 2.4 ) and in the outpatient group 37.4 ( + /- 1.8 ) respectively ( N.S. ) . There was no difference in the rate of pregnancy complications between the groups too . No statistical differences in the perinatal mortality ( 7.1 % and 1.1 % respectively ) or birthweights of the newborns were found , either . Present results do not support the idea of using routine hospital bed rest . It could not be proved to have positive effects on the gestational age , birth weight and perinatal mortality of the newborns , nor to the pregnancy complications . In our opinion early diagnosis of twin pregnancy is of decisive importance and specialized ambulatory follow-up could be employed instead of routine bed rest in antenatal care of twin pregnancy |
1,855 | 20,846,219 | The disease-specific instruments showed limitations in relation to their applicability to venous ulcer patients because of flaws in design or validation .
The literature on quality of life related to venous ulceration failed to sufficiently distinguish between those with different causes of leg ulceration .
There appeared to be problems with the ability of current quality of life instruments to detect changes in quality of life related to ulcer healing .
There appears to be an opportunity for nurses to develop a health-related quality of life health-related quality of life instruments to evaluate their impact on patient outcomes .
Such instruments could potentially allow nursing interventions to be assessed more effectively than the recently proposed nursing metrics | AIMS AND OBJECTIVES To review the quality of life question naires used to measure the impact of venous ulceration and to evaluate their psychometric properties .
BACKGROUND Venous leg ulcers have a negative impact on quality of life .
Health-related quality of life can be measured using structured question naires .
Nurses are the primary care providers for patients with venous ulceration and are ideally placed to assess and develop these types of question naires .
There may also be an opportunity to use such quality of life instruments to measure the impact of nursing interventions in other areas where nurses are the key care providers . | A prospect i ve study was conducted to assess the prevalence , severity and diagnostic utility of pain in patients with venous leg ulcers . A semi-structured question naire was completed by 140 consecutive patients in two specialist centres caring for patients with leg ulcers . A high proportion ( 64 % ) of the 94 patients with ulcers of purely venous aetiology reported severe pain ; 50 % of these patients were taking either mild analgesia or none at all . In 10 of 72 cases , leg elevation made the pain worse . Venous ulcers are painful . Pain in three distinct locations was reported by patients -within ulcers , around ulcers and elsewhere in the leg . The presence of severe pain does not necessarily indicate arterial disease or infection . Pain is , in general , inadequately controlled in these patients 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 This study compared the rate of leg ulcer recurrence using two types of compression stockings and examined the factors underlying Introduction : The effect on quality of life by healing leg ulcers is not known and no vali date d disease-specific tool is available for measuring health-related quality of life ( HRQoL ) for people with venous leg ulcers . The objective of this paper was to compare four generic instruments [ MOS 36-Item Short-Form Health Survey ( SF-36 ) ; EuroQol ( EQ ) ; McGill Short Form Pain Question naire ( SF-MPQ ) and the Frenchay Activities Index ( FAI ) ] used for measuring HRQoL in people with venous leg ulcers , and to offer guidance on the most appropriate tool for research ers . Methods : Two hundred and thirty-three patients with venous leg ulcers were recruited as part of a r and omised controlled trial of the cost-effectiveness of community leg ulcer clinics . Subjects completed question naires containing the four instruments on three occasions ( initial assessment , 3 and 12 months ) . The discriminative and evaluative properties of the four instruments were compared . Results : All four instruments were acceptable to patients , taking a mean of 19.3 ( SD 6.3 ) min to complete . At initial assessment , the SF-MPQ had poorer discriminative properties than the other three instruments and was not able to distinguish between the different patient groups in relation to age and ulcer duration . The FAI was good at discriminating between the different patient groups ( at initial assessment ) in relation to age , mobility and ulcer size . At the three-month follow-up , the SF-MPQ was more responsive than the other measures and detected changes in HRQoL , whereas the EQ and SF-36 did not . At 12 months , the SF-MPQ still identified differences and the SF-36 and EQ also did at this stage . Conclusion : In the absence of a vali date d condition-specific tool for measuring changes in general health status for patients with venous leg ulcers , we make the following recommendations . For evaluating the outcome of interventions with a short-term follow-up ( three months ) in a clinical study we recommend the SF-MPQ and for 12-month follow-up in a clinical study the SF-36 , with or without the SF-MPQ STUDY OBJECTIVE To observe changes in perceived health in patients during a clinical trial of treatments for venous leg ulceration . DESIGN R and omised prospect i ve factorial trial in patients with venous ulceration . Each patient r and omised to a b and age , dressing and a drug . Perceived health assessed at entry and after 24 weeks . SETTING Outpatient departments and patient 's home . PATIENTS Two hundred patients presenting to two vascular services in Falkirk and Edinburgh with chronic ( duration > 2 months ) non-healing venous ulceration . STATISTICAL ANALYSIS AND MAIN RESULTS : Analysis using the Nottingham Health Profile revealed that after 24 weeks there were significant improvements in all subscores ( p < 0.01 ) with the exception of social isolation ( p = 0.081 ) . Patients with healed ulceration had improved in energy , pain , emotion , sleep and mobility compared with those whose ulceration failed to heal ( p < 0.05 ) . Patients r and omised to four layer b and aging had significantly better energy ( diff = 7.9 , 95 % CI 0.2 , 15.6 , p = 0.04 ) and mobility ( diff = 4.5 , 95 % CI 0.0 , 9.0 , p = 0.046 ) . This difference could be explained largely by the improved healing of patients r and omised to this b and age system ( 67/97 vs. 50/103 , OR = 2.37 , 95 % CI 1.31 , 4.27 ) . CONCLUSIONS Improvements in perceived health were significantly greater in patients whose ulcers had completely healed . Methods of treatment which offer improved healing for patients with venous leg ulceration are likely to improve patients ' perceived health status OBJECTIVES To quantify the effect of leg ulceration on health-related quality of life and to estimate a health state value for leg ulceration . DESIGN Population based case-control study . SETTING Two New Zeal and health districts ( population 540,468 people ) . SUBJECTS 241 people with a leg ulcer of any aetiology , and 224 controls r and omly selected from the electoral roll using stratified sampling . MAIN OUTCOME MEASURES health-related quality of life as measured by the eight domains of the Short Form 36 question Health Survey , adjusted for age , sex and confounding co-morbidities ; the physical component summary and mental component summary scores of the Short Form 36 question Health Survey st and ardised for age and sex ; preference-based health state value derived from the Short Form 36 question Health Survey . RESULTS Completed Short Form 36 question Health Survey question naires were available for 230 cases ( 95 % ) and 218 controls ( 97 % ) . Cases reported significantly lower mean scores than controls across all eight domains of the Short Form 36 question Health Survey ( P < 0.0005 ) . Mean domain scores for cases were also significantly lower than population norms . The mean physical component summary score for cases and controls was 45.2 versus 50.1 ( P < 0.0001 ) and the mean mental component summary score was 48.1 for cases versus 51 for controls ( P < 0.0001 ) . The mean health state values ( adjusted for age and sex ) were 0.80 for cases and 0.89 for controls . CONCLUSION Leg ulcers reduce quality of life to a similar extent as other common chronic conditions , such as arthritis and diabetes Wound pain is a serious problem for elderly patients suffering from chronic leg ulcers , and it may lead to reduced wound healing rates and reduced quality of life . Biatain-Ibu Non-adhesive ( Coloplast A/S ) , a new pain-reducing moist wound healing dressing containing ibuprofen was tested for pain reduction , safety , and efficacy on 10 + 2 patients in a single-blinded crossover study against Biatain Non-adhesive ( Coloplast A/S ) . Pain was measured with a Numeric Box Scale before , during , and after dressing change . Quality of life was measured using the World Health Organization-5 Well-Being Index . Dressing moist wound healing properties such as absorption capacity and leakage were tested together with assessment of wound exu date and blood plasma content of ibuprofen . Use of the Biatain-Ibu foam dressing correlated with a decrease in pain intensity scores from 7 in the run-in period to approximately 2.5 in the Biatain-Ibu treatment phase . Quality of life measures were improved which together with the reduced pain could contribute to faster wound healing . The moist wound healing properties of Biatain-Ibu were similar to that of the Biatain Non-adhesive and ulcer size was reduced by 24 % during the treatment period . Neither side effects nor systemic plasma concentrations of ibuprofen were observed . These data indicate that Biatain-Ibu could reduce persistent and temporary wound pain , increase Quality of life , was found safe to use , and had excellent moist wound healing properties OBJECTIVE This descriptive phenomenological study explored patients ' experiences of living with a leg ulcer . METHOD Eight participants ( five female and three male ) were recruited from a secondary care leg ulcer clinic in a large UK teaching hospital . All had current venous leg ulceration , lasting between five months and 34 years . Data collection was via in-depth semi-structured interviews . Data categories were : symptoms ; treatment ; perceptions , emotions and coping strategies ; and restrictions . RESULTS Leg ulcers have a significant impact on individuals ' lives . The degree to which this occurs varies between each person . CONCLUSION Patients need consistent treatment that incorporates benchmarking . A support network to address the needs of those living with a leg ulcer should be considered . This study 's findings should be promoted to raise awareness among health-care professionals , enabling them to provide more responsive care OBJECTIVE Health-related quality of life ( HRQOL ) affects outcome in chronic diseases such as inflammatory bowel disease ( IBD ) . The inflammatory bowel disease question naire ( IBDQ ) , a disease-specific HRQOL question naire , can define changes in health status in IBD , but simple instruments are needed for daily application . The present study proposed to develop a short version of the IBDQ , the SIBDQ , for community physicians . METHODS Using data from a clinical trial in 149 patients with Crohn 's disease , 10 items were selected ( by forward stepwise regression ) that best explained the variance of the IBDQ or dimensional scores ( bowel , systemic , social , emotional ) . The validity , reliability , and responsiveness of the SIBDQ were then assessed in 150 different patients with Crohn 's disease and 45 with ulcerative colitis . All scores were reported with a 7-point scale ( 1 = poor HRQOL , 7 = optimum HRQOL ) . RESULTS Mean SIBDQ scores were similar ( p = 0.22 ) in Crohn 's patients among 14 participating centers at study entry . Mean scores were lower in active Crohn 's disease ( range 4.00 - 4.92 ) than inactive disease ( range 4.67 - 5.83 ; p = 0.0015 ) . In active ulcerative colitis , the mean SIBDQ was 4.79 + /- 1.17 compared to 5.90 + /- 0.80 ( p = 0.0006 ) in inactive disease . The SIBDQ explained 92 % and 90 % of the IBDQ variance in Crohn 's disease and ulcerative colitis , respectively . In patients with stable Crohn 's disease , the test-retest reliability coefficient was 0.65 and Crohnbach 's alpha was 0.78 , indicating good reliability . In patients with Crohn 's disease who relapsed during follow-up , the mean SIBDQ decreased by -0.93 + 0.55 ( p = 0.001 ) . CONCLUSION The SIBDQ is valid , reliable , and able to detect meaningful clinical changes in HRQOL that might occur in the office setting AIM To explore the characteristics of venous and arterial leg ulcer pain among people cared for in the community . BACKGROUND There is little information available concerning the different characteristics of pain result ing from venous and arterial leg ulcers . The identification of clear differences in pain experience might aid recognition of arterial deterioration and provide a useful adjunct for existing diagnostic procedures . DESIGN This was a prospect i ve interview-based survey . METHOD Structured interviews were conducted with each of the participants in their home . Ulcer history , pain ( McGill pain question naire and verbal rating scale ) and factors influencing pain were assessed . RESULTS Fifty-two women and 27 men aged 77.7 ( SD 8.9 ) took part . Pain scores for least , average , worst and present pain varied widely , and arterial ulcers were associated with the highest average pain scores . Pain tended to be worst at night and least in the afternoon ; arterial ulcers were more painful than venous ulcers on lying down . Venous leg ulcers were frequently described as throbbing , burning and itchy , while arterial ulcer pain tended to be described as sharp and hurting . CONCLUSIONS Some characteristics of pain appeared to be suggestive of the leg ulcer type . Differences were found in the words chosen to describe the pain as well as the temporal and postural aspects of arterial and venous leg ulcer pain . More research is needed to confirm these preliminary findings . RELEVANCE TO CLINICAL PRACTICE Patients ' descriptions of pain have the potential to supplement other methods of differentiating between types of leg ulcer and provide an early-warning indicator for transition from venous to arterial ulceration 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 |
1,856 | 28,672,933 | Therefore , the treatment with Clop + ASA seems safe as well as effective for decreasing stroke recurrence .
In addition , this is related to a statistically insignificant trend in increasing vascular mortalities , MI , and primary hemorrhagic events . | The use of antiplatelet agents in patients with ischemic stroke is recommended .
In this study , we compared the efficacy and safety of the treatment of clopidogrel plus aspirin ( ASA ) and that of ASA alone in patients with mild stroke/transient ischemic attack ( TIA ) . | Objective : To assess whether adding clopidogrel to acetylsalicylic acid ( ASA ) has a long-term protective vascular effect in patients with lacunar stroke while taking ASA . Methods : Post hoc analysis of 838 patients with ASA failure and recent lacunar stroke from the Secondary Prevention of Small Subcortical Strokes Trial ( SPS3 ) cohort r and omly allocated to aspirin ( 325 mg/day ) and clopidogrel ( 75 mg/day ) or placebo . Primary efficacy outcome was stroke recurrence ( ischemic and intracranial hemorrhage ) and main safety outcome was major extracranial hemorrhage . Patients were followed for a mean period of 3.5 years . Results : The ASA failure group had a significantly higher risk of vascular events including ischemic stroke when compared with the non – ASA failure group ( n = 2,151 ) in SPS3 ( p = 0.03 ) . Mean age was 65.6 years and 65 % were men . The risk of recurrent stroke was not reduced in the dual antiplatelet group , 3.1 % per year , compared to the aspirin-only group , 3.3 % per year ( hazard ratio [ HR ] 0.91 ; 95 % confidence interval [ CI ] 0.61–1.37 ) . There was also no difference between groups for ischemic stroke ( HR 0.90 ; 95 % CI 0.59–1.38 ) . The risk of gastrointestinal bleeding was higher in the dual antiplatelet group ( HR 2.7 ; 95 % CI 1.1–6.9 ) ; however , the risk of intracranial hemorrhage was not different . Conclusions : In patients with a recent lacunar stroke while taking ASA , the addition of clopidogrel did not result in reduction of vascular events vs continuing ASA only . Classification of evidence : This study provides Class I evidence that for patients with recent lacunar stroke while taking ASA , adding clopidogrel as compared to continuing ASA alone does not reduce the risk of recurrent stroke BACKGROUND Patients with transient ischaemic attack ( TIA ) or minor stroke are at high immediate risk of stroke . The optimum early treatment options for these patients are not known . METHODS Within 24 h of symptom onset , we r and omly assigned , in a factorial design , 392 patients with TIA or minor stroke to clopidogrel ( 300 mg loading dose then 75 mg daily ; 198 patients ) or placebo ( 194 patients ) , and simvastatin ( 40 mg daily ; 199 patients ) or placebo ( 193 patients ) . All patients were also given aspirin and were followed for 90 days . Descriptive analyses were done by intention to treat . The primary outcome was total stroke ( ischaemic and haemorrhagic ) within 90 days . Safety outcomes included haemorrhage related to clopidogrel and myositis related to simvastatin . This study is registered as an International St and ard R and omised Controlled Trial ( number 35624812 ) and with Clinical Trials.gov ( NCT00109382 ) . FINDINGS The median time to stroke outcome was 1 day ( range 0 - 62 days ) . The trial was stopped early due to a failure to recruit patients at the prespecified minimum enrolment rate because of increased use of statins . 14 ( 7.1 % ) patients on clopidogrel had a stroke within 90 days compared with 21 ( 10.8 % ) patients on placebo ( risk ratio 0.7 [ 95 % CI 0.3 - 1.2 ] ; absolute risk reduction -3.8 % [ 95 % CI -9.4 to 1.9 ] ; p=0.19 ) . 21 ( 10.6 % ) patients on simvastatin had a stroke within 90 days compared with 14 ( 7.3 % ) patients on placebo ( risk ratio 1.3 [ 0.7 - 2.4 ] ; absolute risk increase 3.3 % [ -2.3 to 8.9 ] ; p=0.25 ) . The interaction between clopidogrel and simvastatin was not significant ( p=0.64 ) . Two patients on clopidogrel had intracranial haemorrhage compared with none on placebo ( absolute risk increase 1.0 % [ -0.4 to 2.4 ] ; p=0.5 ) . There was no difference between groups for the simvastatin safety outcomes . INTERPRETATION Immediately after TIA or minor stroke , patients are at high risk of stroke , which might be reduced by using clopidogrel in addition to aspirin . The haemorrhagic risks of the combination of aspirin and clopidogrel do not seem to offset this potential benefit . We were unable to provide evidence of benefit of simvastatin in this setting . This aggressive prevention approach merits further study BACKGROUND Few r and omised clinical trials have investigated the use of antithrombotic drugs for early secondary prevention of stroke or transient ischaemic attack in patients with intracranial atherosclerotic stenosis . Microembolic signals , detected by transcranial doppler , are a surrogate marker of future stroke risk and have been used to show treatment efficacy in patients with extracranial carotid stenosis . We aim ed to investigate whether treatment with clopidogrel plus aspirin reduced the number of microembolic signals detected with transcranial doppler ultrasound compared with aspirin alone in patients with recent stroke . METHODS The clopidogrel plus aspirin for infa rct ion reduction in acute stroke or transient ischaemic attack patients with large artery stenosis and microembolic signals ( CLAIR ) trial was a r and omised , open-label , blinded-endpoint trial . Between Oct 28 , 2003 , and Nov 19 , 2008 , patients with acute ischaemic stroke or transient ischaemic attack who had symptomatic large artery stenosis in the cerebral or carotid arteries and in whom microembolic signals were present on transcranial doppler were r and omly assigned within 7 days of symptom onset to receive clopidogrel ( 300 mg for the first day , then 75 mg daily ) plus aspirin ( 75 - 160 mg daily ) or aspirin alone ( 75 - 160 mg daily ) for 7 days . Patients were r and omly assigned in blocks of four or six by use of a r and omisation website . Monitoring of microembolic signals on transcranial doppler was done on days 2 and 7 . The primary endpoint was the proportion of patients who had microembolic signals on day 2 . Analysis was by modified intention to treat . All analyses were done by an investigator masked to both patient identity and the day the recording was taken . This trial is registered with the Centre for Clinical Trials , Chinese University of Hong Kong , number CUHK_CCT00164 . FINDINGS 100 patients were r and omly assigned to clopidogrel plus aspirin ( n=47 ) or aspirin monotherapy ( n=53 ) . 93 of 100 patients had symptomatic intracranial stenosis in either the intracranial internal carotid artery or the middle cerebral artery : 45 of 46 in the dual therapy group and 48 of 52 in the monotherapy group . At day 2 , 14 of 45 patients in the dual therapy group and 27 of 50 patients in the monotherapy group for whom data were available had at least one microembolic signal on transcranial doppler ( relative risk reduction 42.4 % , 95 % CI 4.6 - 65.2 ; p=0.025 ) . Adverse events were similar in the two groups . No patients had intracranial or severe systemic haemorrhage , but two patients in the dual therapy group had minor haemorrhages . INTERPRETATION Combination therapy with clopidogrel and aspirin is more effective than aspirin alone in reducing microembolic signals in patients with predominantly intracranial symptomatic stenosis . Clinical trials are now warranted to investigate whether this combination treatment also results in a reduction in stroke incidence Background — Evidence for efficacy of dual antiplatelet therapy in stroke is limited . Symptomatic carotid stenosis patients are at high risk of early recurrent stroke . In this group , asymptomatic microembolic signals ( MES ) , detected by transcranial Doppler ultrasound ( TCD ) , are markers of future stroke and transient ischemic attack ( TIA ) risk . They offer a surrogate marker to evaluate antiplatelet therapy , but no multicenter study has evaluated the feasibility of this approach . Methods and Results —Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis ( CARESS ) is a r and omized , double-blind study in subjects with recently symptomatic ≥50 % carotid stenosis . Patients were screened with TCD , and if MES were detected , they were r and omized to clopidogrel and aspirin or aspirin monotherapy . Repeated TCD recordings were made on days 2 and 7 . MES were detected in 110 of 230 patients by online analysis at baseline , of whom 107 were r and omized . Intention-to-treat analysis revealed a significant reduction in the primary end point : 43.8 % of dual-therapy patients were MES positive on day 7 , as compared with 72.7 % of monotherapy patients ( relative risk reduction 39.8 % ; 95 % CI , 13.8 to 58.0 ; P=0.0046 ) . The secondary end point of MES frequency per hour was reduced ( compared with baseline ) by 61.4 % ( 95 % CI , 31.6 to 78.2 ; P=0.0013 ) in the dual-therapy group at day 7 and by 61.6 % ( 95 % CI , 34.9 to 77.4 ; P=0.0005 ) on day 2 . There were 4 recurrent strokes and 7 TIAs in the monotherapy group versus no stroke and 4 TIAs in the dual-therapy group that were treatment emergent and ipsilateral to the qualifying carotid stenosis ; 2 additional ipsilateral TIAs occurred before treatment started . MES frequency was greater in the 17 patients with recurrent ipsilateral events compared with the 90 without ( mean±SD : 24.4±27.7 versus 8.9±11.5 per hour ; P=0.0003 ) . Conclusions —In patients with recently symptomatic carotid stenosis , combination therapy with clopidogrel and aspirin is more effective than aspirin alone in reducing asymptomatic embolization . Doppler MES detection is a feasible method to evaluate the efficacy of antiplatelet therapy in multicenter studies Background : Little information is available about public knowledge of TIA and prevalence of a TIA diagnosis . Methods : The National Stroke Association sponsored a telephone survey by single-stage r and om-digit dialing of noninstitutionalized US residents ≥18 years old , which was conducted in 1999 . Demographic characteristics of participants were compared to the US population to produce weights for projections . Independent predictors of knowledge and diagnosis of TIA were determined by including all demographic characteristics in logistic regression models . Results : Among 10,112 participants , 2.3 % reported having been told by a physician that they had a TIA . Older age , lower income , and fewer years of education were independently associated with a diagnosis of TIA . Of those with TIA , only 64 % saw a physician within 24 hours of the event . A physician diagnosis of stroke was reported by 2.3 % of participants , of whom 19 % recalled having had a TIA before the stroke . An additional 3.2 % of participants recalled symptoms consistent with TIA but did not seek medical attention . Only 8.2 % correctly related the definition of TIA and 8.6 % could identify a typical symptom . Men , nonwhites , and those with lower income and fewer years of education were less likely to be knowledgeable about TIA . Conclusions : An estimated 4.9 million people in the US report a diagnosis of TIA , and many more recall symptoms consistent with TIA but do not seek medical attention . Reducing stroke risk after TIA could have substantial impact on public health but will require public education about the importance of having stroke symptoms evaluated , even if they resolve BACKGROUND Evidence is available on the effectiveness and costs of treatments to reduce stroke risk in long-term secondary prevention . However , there are few data on the costs and outcomes of urgent assessment and treatment after the onset of transient ischaemic attack ( TIA ) or minor stroke . The Early use of eXisting PREventive Strategies for Stroke ( EXPRESS ) study showed that urgent assessment and treatment reduced the 90-day risk of recurrent stroke by about 80 % . We now report the effect of the EXPRESS intervention on admissions to hospital , costs , and disability . METHODS EXPRESS was a prospect i ve population -based before ( phase 1 : April 1 , 2002 , to Sept 30 , 2004 ) versus after ( phase 2 : Oct 1 , 2004 , to March 31 , 2007 ) study of the effect of early assessment and treatment of TIA or minor stroke on the risk of early recurrent stroke . This report assesses the effect of the introduction of the phase 2 clinic on admissions to hospital within 90 days , hospital bed-days , hospital costs , and 6-month new disability ( progression from no disability before event [ modified Rankin scale score < or = 2 points ] to disability at 6 months [ modified Rankin scale score > 2 points ] ) or death , compared with the phase 1 clinic . To assess the main predictors of these outcomes , multivariate regression analyses were done . FINDINGS The 90-day risk of fatal or disabling stroke was reduced in phase 2 ( 1 of 281 vs 16 of 310 ; p=0.0005 ) . Hospital admissions for recurrent stroke were also lower in phase 2 than in phase 1 ( 5 vs 25 ; p=0.001 ) , which reduced the overall number of hospital bed-days compared with phase 1 ( 672 vs 1957 days ; p=0.017 ) . Hospital bed-days for admissions to hospital due to vascular causes were also lower in phase 2 ( 427 vs 1365 days ; p=0.016 ) , which generated savings of 624 pounds per patient referred to the phase 2 clinic ( p=0.028 ) . Results from the multivariate analyses showed that assessment in phase 2 was an independent predictor of reduced disability , days in hospital , and costs . INTERPRETATION Urgent assessment and treatment of patients with TIA or minor stroke who were referred to a specialist outpatient clinic reduced subsequent hospital bed-days , acute costs , and 6-month disability BACKGROUND Lacunar infa rcts are a frequent type of stroke caused mainly by cerebral small-vessel disease . The effectiveness of antiplatelet therapy for secondary prevention has not been defined . METHODS We conducted a double-blind , multicenter trial involving 3020 patients with recent symptomatic lacunar infa rcts identified by magnetic resonance imaging . Patients were r and omly assigned to receive 75 mg of clopidogrel or placebo daily ; patients in both groups received 325 mg of aspirin daily . The primary outcome was any recurrent stroke , including ischemic stroke and intracranial hemorrhage . RESULTS The participants had a mean age of 63 years , and 63 % were men . After a mean follow-up of 3.4 years , the risk of recurrent stroke was not significantly reduced with aspirin and clopidogrel ( dual antiplatelet therapy ) ( 125 strokes ; rate , 2.5 % per year ) as compared with aspirin alone ( 138 strokes , 2.7 % per year ) ( hazard ratio , 0.92 ; 95 % confidence interval [ CI ] , 0.72 to 1.16 ) , nor was the risk of recurrent ischemic stroke ( hazard ratio , 0.82 ; 95 % CI , 0.63 to 1.09 ) or disabling or fatal stroke ( hazard ratio , 1.06 ; 95 % CI , 0.69 to 1.64 ) . The risk of major hemorrhage was almost doubled with dual antiplatelet therapy ( 105 hemorrhages , 2.1 % per year ) as compared with aspirin alone ( 56 , 1.1 % per year ) ( hazard ratio , 1.97 ; 95 % CI , 1.41 to 2.71 ; P<0.001 ) . Among classifiable recurrent ischemic strokes , 71 % ( 133 of 187 ) were lacunar strokes . All-cause mortality was increased among patients assigned to receive dual antiplatelet therapy ( 77 deaths in the group receiving aspirin alone vs. 113 in the group receiving dual antiplatelet therapy ) ( hazard ratio , 1.52 ; 95 % CI , 1.14 to 2.04 ; P=0.004 ) ; this difference was not accounted for by fatal hemorrhages ( 9 in the group receiving dual antiplatelet therapy vs. 4 in the group receiving aspirin alone ) . CONCLUSIONS Among patients with recent lacunar strokes , the addition of clopidogrel to aspirin did not significantly reduce the risk of recurrent stroke and did significantly increase the risk of bleeding and death . ( Funded by the National Institute of Neurological Disorders and Stroke and others ; SPS3 Clinical Trials.gov number , NCT00059306 . ) BACKGROUND Stroke is common during the first few weeks after a transient ischemic attack ( TIA ) or minor ischemic stroke . Combination therapy with clopidogrel and aspirin may provide greater protection against subsequent stroke than aspirin alone . METHODS In a r and omized , double-blind , placebo-controlled trial conducted at 114 centers in China , we r and omly assigned 5170 patients within 24 hours after the onset of minor ischemic stroke or high-risk TIA to combination therapy with clopidogrel and aspirin ( clopidogrel at an initial dose of 300 mg , followed by 75 mg per day for 90 days , plus aspirin at a dose of 75 mg per day for the first 21 days ) or to placebo plus aspirin ( 75 mg per day for 90 days ) . All participants received open-label aspirin at a clinician-determined dose of 75 to 300 mg on day 1 . The primary outcome was stroke ( ischemic or hemorrhagic ) during 90 days of follow-up in an intention-to-treat analysis . Treatment differences were assessed with the use of a Cox proportional-hazards model , with study center as a r and om effect . RESULTS Stroke occurred in 8.2 % of patients in the clopidogrel-aspirin group , as compared with 11.7 % of those in the aspirin group ( hazard ratio , 0.68 ; 95 % confidence interval , 0.57 to 0.81 ; P<0.001 ) . Moderate or severe hemorrhage occurred in seven patients ( 0.3 % ) in the clopidogrel-aspirin group and in eight ( 0.3 % ) in the aspirin group ( P=0.73 ) ; the rate of hemorrhagic stroke was 0.3 % in each group . CONCLUSIONS Among patients with TIA or minor stroke who can be treated within 24 hours after the onset of symptoms , the combination of clopidogrel and aspirin is superior to aspirin alone for reducing the risk of stroke in the first 90 days and does not increase the risk of hemorrhage . ( Funded by the Ministry of Science and Technology of the People 's Republic of China ; CHANCE Clinical Trials.gov number , NCT00979589 . ) Background Ischemic stroke and other vascular outcomes occur in 10–20 % of patients in the three-months following a transient ischemic attack or minor ischemic stroke , and many are disabling . The highest risk period for these outcomes is the early hours and days immediately following the ischemic event . Aspirin is the most common antithrombotic treatment used for these patients . Aim The aim of POINT is to determine whether clopidogrel plus aspirin taken < 12 h after transient ischemic attack or minor ischemic stroke symptom onset is more effective in preventing major ischemic vascular events at 90 days in the high-risk , and acceptably safe , compared with aspirin alone . Design POINT is a prospect i ve , r and omized , double-blind , multicenter trial in patients with transient ischemic attack or minor ischemic stroke . Subjects are r and omized to clopidogrel ( 600 mg loading dose followed by 75 mg/day ) or matching placebo , and all will receive open-label aspirin 50–325 mg/day , with a dose of 162 mg daily for five-days followed by 81 mg daily strongly recommended . Study Outcomes The primary efficacy outcome is the composite of new ischemic vascular events — ischemic stroke , myocardial infa rct ion , or ischemic vascular death — by 90 days . The primary safety outcome is major hemorrhage , which includes symptomatic intracranial hemorrhage . Discussion Aspirin is the most common antithrombotic given to patients with a stroke or transient ischemic attack , as it reduces the risk of subsequent stroke . This trial expects to determine whether more aggressive antithrombotic therapy with clopidogrel plus aspirin , initiated acutely , is more effective than aspirin alone BACKGROUND The risk of recurrent stroke is up to 10 % in the week after a transient ischaemic attack ( TIA ) or minor stroke . Modelling studies suggest that urgent use of existing preventive treatments could reduce the risk by 80 - 90 % , but in the absence of evidence many health-care systems make little provision . Our aim was to determine the effect of more rapid treatment after TIA and minor stroke in patients who are not admitted direct to hospital . METHODS We did a prospect i ve before ( phase 1 : April 1 , 2002 , to Sept 30 , 2004 ) versus after ( phase 2 : Oct 1 , 2004 , to March 31 , 2007 ) study of the effect on process of care and outcome of more urgent assessment and immediate treatment in clinic , rather than subsequent initiation in primary care , in all patients with TIA or minor stroke not admitted direct to hospital . The study was nested within a rigorous population -based incidence study of all TIA and stroke ( Oxford Vascular Study ; OXVASC ) , such that case ascertainment , investigation , and follow-up were complete and identical in both periods . The primary outcome was the risk of stroke within 90 days of first seeking medical attention , with independent blinded ( to study period ) audit of all events . FINDINGS Of the 1278 patients in OXVASC who presented with TIA or stroke ( 634 in phase 1 and 644 in phase 2 ) , 607 were referred or presented direct to hospital , 620 were referred for outpatient assessment , and 51 were not referred to secondary care . 95 % ( n=591 ) of all outpatient referrals were to the study clinic . Baseline characteristics and delays in seeking medical attention were similar in both periods , but median delay to assessment in the study clinic fell from 3 ( IQR 2 - 5 ) days in phase 1 to less than 1 ( 0 - 3 ) day in phase 2 ( p<0.0001 ) , and median delay to first prescription of treatment fell from 20 ( 8 - 53 ) days to 1 ( 0 - 3 ) day ( p<0.0001 ) . The 90-day risk of recurrent stroke in the patients referred to the study clinic was 10.3 % ( 32/310 patients ) in phase 1 and 2.1 % ( 6/281 patients ) in phase 2 ( adjusted hazard ratio 0.20 , 95 % CI 0.08 - 0.49 ; p=0.0001 ) ; there was no significant change in risk in patients treated elsewhere . The reduction in risk was independent of age and sex , and early treatment did not increase the risk of intracerebral haemorrhage or other bleeding . INTERPRETATION Early initiation of existing treatments after TIA or minor stroke was associated with an 80 % reduction in the risk of early recurrent stroke . Further follow-up is required to determine long-term outcome , but these results have immediate implication s for service provision and public education about TIA and minor stroke |
1,857 | 29,190,987 | Conclusions The findings of this study show that elderly HCC patients who relapsed after a first-line sorafenib treatment obtains a survival benefits from anti-VEGF agents rechallenge . | Purpose We aim ed to investigate the role of anti-vascular endothelial growth factor ( VEGF ) agents , including tyrosine-kinase inhibitors or monoclonal anti-bodies , in the treatment of elderly hepatocellular carcinoma ( HCC ) patients . | BACKGROUND VEGF and VEGF receptor-2-mediated angiogenesis contribute to hepatocellular carcinoma pathogenesis . Ramucirumab is a recombinant IgG1 monoclonal antibody and VEGF receptor-2 antagonist . We aim ed to assess the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma following first-line therapy with sorafenib . METHODS In this r and omised , placebo-controlled , double-blind , multicentre , phase 3 trial ( REACH ) , patients were enrolled from 154 centres in 27 countries . Eligible patients were aged 18 years or older , had hepatocellular carcinoma with Barcelona Clinic Liver Cancer stage C disease or stage B disease that was refractory or not amenable to locoregional therapy , had Child-Pugh A liver disease , an Eastern Cooperative Oncology Group performance status of 0 or 1 , had previously received sorafenib ( stopped because of progression or intolerance ) , and had adequate haematological and biochemical parameters . Patients were r and omly assigned ( 1:1 ) to receive intravenous ramucirumab ( 8 mg/kg ) or placebo every 2 weeks , plus best supportive care , until disease progression , unacceptable toxicity , or death . R and omisation was stratified by geographic region and cause of liver disease with a stratified permuted block method . Patients , medical staff , investigators , and the funder were masked to treatment assignment . The primary endpoint was overall survival in the intention-to-treat population . This study is registered with Clinical Trials.gov , number NCT01140347 . FINDINGS Between Nov 4 , 2010 , and April 18 , 2013 , 565 patients were enrolled , of whom 283 were assigned to ramucirumab and 282 were assigned to placebo . Median overall survival for the ramucirumab group was 9·2 months ( 95 % CI 8·0 - 10·6 ) versus 7·6 months ( 6·0 - 9·3 ) for the placebo group ( HR 0·87 [ 95 % CI 0·72 - 1·05 ] ; p=0·14 ) . Grade 3 or greater adverse events occurring in 5 % or more of patients in either treatment group were ascites ( 13 [ 5 % ] of 277 patients treated with ramucirumab vs 11 [ 4 % ] of 276 patients treated with placebo ) , hypertension ( 34 [ 12 % ] vs ten [ 4 % ] ) , asthenia ( 14 [ 5 % ] vs five [ 2 % ] ) , malignant neoplasm progression ( 18 [ 6 % ] vs 11 [ 4 % ] ) , increased aspartate aminotransferase concentration ( 15 [ 5 % ] vs 23 [ 8 % ] ) , thrombocytopenia ( 13 [ 5 % ] vs one [ < 1 % ] ) , hyperbilirubinaemia ( three [ 1 % ] vs 13 [ 5 % ] ) , and increased blood bilirubin ( five [ 2 % ] vs 14 [ 5 % ] ) . The most frequently reported ( ≥1 % ) treatment-emergent serious adverse event of any grade or grade 3 or more was malignant neoplasm progression . INTERPRETATION Second-line treatment with ramucirumab did not significantly improve survival over placebo in patients with advanced hepatocellular carcinoma . No new safety signals were noted in eligible patients and the safety profile is manageable . FUNDING Eli Lilly and PURPOSE This phase II study of sorafenib , an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases , assessed efficacy , toxicity , pharmacokinetics , and biomarkers in advanced hepatocellular carcinoma ( HCC ) patients . METHODS Patients with inoperable HCC , no prior systemic treatment , and Child-Pugh ( CP ) A or B , received continuous , oral sorafenib 400 mg bid in 4-week cycles . Tumor response was assessed every two cycles using modified WHO criteria . Sorafenib pharmacokinetics were measured in plasma sample s. Biomarker analysis included phosphorylated extracellular signal regulated kinase ( pERK ) in pretreatment biopsies ( immunohistochemistry ) and blood-cell RNA expression patterns in selected patients . RESULTS Of 137 patients treated ( male , 71 % ; median age , 69 years ) , 72 % had CP A , and 28 % had CP B. On the basis of independent assessment , three ( 2.2 % ) patients achieved a partial response , eight ( 5.8 % ) had a minor response , and 46 ( 33.6 % ) had stable disease for at least 16 weeks . Investigator-assessed median time to progression ( TTP ) was 4.2 months , and median overall survival was 9.2 months . Grade 3/4 drug-related toxicities included fatigue ( 9.5 % ) , diarrhea ( 8.0 % ) , and h and -foot skin reaction ( 5.1 % ) . There were no significant pharmacokinetic differences between CP A and B patients . Pretreatment tumor pERK levels correlated with TTP . A panel of 18 expressed genes was identified that distinguished " nonprogressors " from " progressors " with an estimated 100 % accuracy . CONCLUSION Although single-agent sorafenib has modest efficacy in HCC , the manageable toxicity and mechanisms of action support a role for combination regimens with other anticancer agents PURPOSE Open-label , phase III trial evaluating whether sunitinib was superior or equivalent to sorafenib in hepatocellular cancer . PATIENTS AND METHODS Patients were stratified and r and omly assigned to receive sunitinib 37.5 mg once per day or sorafenib 400 mg twice per day . Primary end point was overall survival ( OS ) . RESULTS Early trial termination occurred for futility and safety reasons . A total of 1,074 patients were r and omly assigned to the study ( sunitinib arm , n = 530 ; sorafenib arm , n = 544 ) . For sunitinib and sorafenib , respectively , median OS was 7.9 versus 10.2 months ( hazard ratio [ HR ] , 1.30 ; one-sided P = .9990 ; two-sided P = .0014 ) ; median progression-free survival ( PFS ; 3.6 v 3.0 months ; HR , 1.13 ; one-sided P = .8785 ; two-sided P = .2286 ) and time to progression ( TTP ; 4.1 v 3.8 months ; HR , 1.13 ; one-sided P = .8312 ; two-sided P = .3082 ) were comparable . Median OS was similar among Asian ( 7.7 v 8.8 months ; HR , 1.21 ; one-sided P = .9829 ) and hepatitis B-infected patients ( 7.6 v 8.0 months ; HR , 1.10 ; one-sided P = .8286 ) , but was shorter with sunitinib in hepatitis C-infected patients ( 9.2 v 17.6 months ; HR , 1.52 ; one-sided P = .9835 ) . Sunitinib was associated with more frequent and severe adverse events ( AEs ) than sorafenib . Common grade 3/4 AEs were thrombocytopenia ( 29.7 % ) and neutropenia ( 25.7 % ) for sunitinib ; h and -foot syndrome ( 21.2 % ) for sorafenib . Discontinuations owing to AEs were similar ( sunitinib , 13.3 % ; sorafenib , 12.7 % ) . CONCLUSION OS with sunitinib was not superior or equivalent but was significantly inferior to sorafenib . OS was comparable in Asian and hepatitis B-infected patients . OS was superior in hepatitis C-infected patients who received sorafenib . Sunitinib-treated patients reported more frequent and severe toxicity BACKGROUND The efficacy and safety of axitinib , a potent and selective vascular endothelial growth factor receptors 1 - 3 inhibitor , combined with best supportive care ( BSC ) was evaluated in a global , r and omized , placebo-controlled phase II trial in patients with locally advanced or metastatic hepatocellular carcinoma ( HCC ) . PATIENTS AND METHODS Patients with HCC and Child-Pugh Class A who progressed on or were intolerant to one prior antiangiogenic therapy were stratified by tumour invasion ( presence/absence of extrahepatic spread and /or vascular invasion ) and region ( Asian/non-Asian ) and r and omized ( 2:1 ) to axitinib/BSC ( starting dose 5 mg twice-daily ) or placebo/BSC . The primary end point was overall survival ( OS ) . RESULTS The estimated hazard ratio for OS was 0.907 [ 95 % confidence interval ( CI ) 0.646 - 1.274 ; one-sided stratified P = 0.287 ] for axitinib/BSC ( n = 134 ) versus placebo/BSC ( n = 68 ) , with the median ( 95 % CI ) of 12.7 ( 10.2 - 14.9 ) versus 9.7 ( 5.9 - 11.8 ) months , respectively . Results of prespecified subgroup analyses in Asian versus non-Asian patients or presence versus absence of tumour invasion were consistent with the overall population . Improvements favouring axitinib/BSC ( P < 0.01 ) were observed in secondary efficacy end point analyses [ progression-free survival ( PFS ) , time to tumour progression ( TTP ) , and clinical benefit rate ( CBR ) ] , and were retained among Asian patients in the prespecified subgroup analyses . Overall response rate did not differ significantly between treatments and patient-reported outcomes favoured placebo/BSC . Most common all-causality adverse events with axitinib/BSC were diarrhoea ( 54 % ) , hypertension ( 54 % ) , and decreased appetite ( 47 % ) . Baseline serum analyses identified potential new prognostic ( interleukin-6 , E-selectin , interleukin-8 , angiopoietin-2 , migration inhibitory factor , and c-MET ) or predictive ( E-selectin and stromal-derived factor-1 ) factors for survival . CONCLUSIONS Axitinib/BSC did not improve OS over placebo/BSC in the overall population or in stratification subgroups . However , axitinib/BSC result ed in significantly longer PFS and TTP and higher CBR , with acceptable toxicity in patients with advanced HCC . TRIAL REGISTRATION Clinical Trials.gov , NCT01210495 BACKGROUND Ramucirumab is a human IgG1 monoclonal antibody that targets the extracellular domain of VEGFR-2 . We aim ed to assess efficacy and safety of treatment with docetaxel plus ramucirumab or placebo as second-line treatment for patients with stage IV non-small-cell-lung cancer ( NSCLC ) after platinum-based therapy . METHODS In this multicentre , double-blind , r and omised phase 3 trial ( REVEL ) , we enrolled patients with squamous or non-squamous NSCLC who had progressed during or after a first-line platinum-based chemotherapy regimen . Patients were r and omly allocated ( 1:1 ) with a central ised , interactive voice-response system ( stratified by sex , region , performance status , and previous maintenance therapy [ yes vs no ] ) to receive docetaxel 75 mg/m(2 ) and either ramucirumab ( 10 mg/kg ) or placebo on day 1 of a 21 day cycle until disease progression , unacceptable toxicity , withdrawal , or death . The primary endpoint was overall survival in all patients allocated to treatment . We assessed adverse events according to treatment received . This study is registered with Clinical Trials.gov , number NCT01168973 . FINDINGS Between Dec 3 , 2010 , and Jan 24 , 2013 , we screened 1825 patients , of whom 1253 patients were r and omly allocated to treatment . Median overall survival was 10·5 months ( IQR 5·1 - 21·2 ) for 628 patients allocated ramucirumab plus docetaxel and 9·1 months ( 4·2 - 18·0 ) for 625 patients who received placebo plus docetaxel ( hazard ratio 0·86 , 95 % CI 0·75 - 0·98 ; p=0·023 ) . Median progression-free survival was 4·5 months ( IQR 2·3 - 8·3 ) for the ramucirumab group compared with 3·0 months ( 1·4 - 6·9 ) for the control group ( 0·76 , 0·68 - 0·86 ; p<0·0001 ) . We noted treatment-emergent adverse events in 613 ( 98 % ) of 627 patients in the ramucirumab safety population and 594 ( 95 % ) of 618 patients in the control safety population . The most common grade 3 or worse adverse events were neutropenia ( 306 patients [ 49 % ] in the ramucirumab group vs 246 [ 40 % ] in the control group ) , febrile neutropenia ( 100 [ 16 % ] vs 62 [ 10 % ] ) , fatigue ( 88 [ 14 % ] vs 65 [ 10 % ] ) , leucopenia ( 86 [ 14 % ] vs 77 [ 12 % ] ) , and hypertension ( 35 [ 6 % ] vs 13 [ 2 % ] ) . The numbers of deaths from adverse events ( 31 [ 5 % ] vs 35 [ 6 % ] ) and grade 3 or worse pulmonary haemorrhage ( eight [ 1 % ] vs eight [ 1 % ] ) did not differ between groups . Toxicities were manageable with appropriate dose reductions and supportive care . INTERPRETATION Ramucirumab plus docetaxel improves survival as second-line treatment of patients with stage IV NSCLC . FUNDING Eli Lilly UNLABELLED The prognosis of untreated patients with hepatocellular carcinoma ( HCC ) is heterogeneous , and survival data were mainly obtained from control arms of r and omized studies . Clinical practice data on this topic are urgently needed , so as to help plan studies and counsel patients . We assessed the prognosis of 600 untreated patients with HCC managed by the Italian Liver Cancer Group . Prognosis was evaluated by subdividing patients according to the Barcelona Clinic Liver Cancer ( BCLC ) classification . We also assessed the main demographic , clinical , and oncological determinants of survival in the subgroup of patients with advanced HCC ( BCLC C ) . Advanced ( BCLC C : n = 138 ; 23.0 % ) and end-stage HCC ( BCLC D ; n = 210 ; 35.0 % ) represented the majority of patients . Overall median survival was 9 months , and the principal cause of death was tumor progression ( n = 279 ; 46.5 % ) . Patients ' median survival progressively and significantly decreased as BCLC stage worsened ( BCLC 0 : 38 months ; BCLC A : 25 months ; BCLC B : 10 months ; BCLC C : 7 months ; BCLC D : 6 months ; P < 0.0001 ) . Female gender ( hazard ratio [ HR ] = 0.55 ; 95 % confidence interval [ CI ] = 0.33 - 0.90 ; P = 0.018 ) , ascites ( HR = 1.81 ; 95 % CI = 1.21 - 2.71 ; P = 0.004 ) , and multinodular ( > 3 ) HCC ( HR = 1.79 ; 95 % CI = 1.21 - 2.63 ; P = 0.003 ) were independent predictors of survival in patients with advanced HCC ( BCLC C ) . CONCLUSION BCLC adequately predicts the prognosis of untreated HCC patients . In untreated patients with advanced HCC , female gender , clinical decompensation of cirrhosis , and multinodular tumor are independent prognostic predictors and should be taken into account for patient stratification in future therapeutic studies BACKGROUND In Japan and South Korea , transarterial chemoembolisation ( TACE ) is an important locoregional treatment for patients with unresectable hepatocellular carcinoma ( HCC ) . Sorafenib , a multikinase inhibitor , has been shown effective and safe in patients with advanced HCC . This phase III trial assessed the efficacy and safety of sorafenib in Japanese and Korean patients with unresectable HCC who responded to TACE . METHODS Patients ( n=458 ) with unresectable HCC , Child-Pugh class A cirrhosis and ≥25 % tumour necrosis/shrinkage 1 - 3 months after 1 or 2 TACE sessions were r and omised 1:1 to sorafenib 400 mg bid or placebo and treated until progression/recurrence or unacceptable toxicity . Primary end-point was time to progression/recurrence ( TTP ) . Secondary end-point was overall survival ( OS ) . FINDINGS Baseline characteristics in the two groups were similar ; > 50 % of patients started sorafenib>9 weeks after TACE . Median TTP in the sorafenib and placebo groups was 5.4 and 3.7 months , respectively ( hazard ratio ( HR ) , 0.87 ; 95 % confidence interval ( CI ) , 0.70 - 1.09 ; P=0.252 ) . HR ( sorafenib/placebo ) for OS was 1.06 ( 95 % CI , 0.69 - 1.64 ; P=0.790 ) . Median daily dose of sorafenib was 386 mg , with 73 % of patients having dose reductions and 91 % having dose interruptions . Median administration of sorafenib and placebo was 17.1 and 20.1 weeks , respectively . No unexpected adverse events were observed . INTERPRETATION This trial , conducted prior to the reporting of registration al phase III trials , found that sorafenib did not significantly prolong TTP in patients who responded to TACE . This may have been due to delays in starting sorafenib after TACE and /or low daily sorafenib doses PURPOSE This open-label phase III trial evaluated efficacy and tolerability of linifanib versus sorafenib in patients with advanced hepatocellular carcinoma ( HCC ) without prior systemic therapy . PATIENTS AND METHODS Patients were r and omly assigned in a 1:1 ratio to linifanib 17.5 mg once daily or sorafenib 400 mg twice daily . Patients were stratified by region ( Outside Asia , Japan , and rest of Asia ) , Eastern Cooperative Oncology Group performance score ( ECOG PS ; 0 or 1 ) , vascular invasion or extrahepatic spread ( yes or no ) , and hepatitis B virus ( HBV ) infection ( yes or no ) . The primary end point of the study was overall survival ( OS ) . Secondary end points were time to progression ( TTP ) and objective response rate ( ORR ) per RECIST v1.1 . RESULTS We r and omly assigned 1,035 patients ( median age , 60 years ; Asian , 66.6 % ; ECOG PS 0 , 65.2 % ; HBV , 49.1 % ; vascular invasion or extrahepatic spread , 70.1 % ) . Median OS was 9.1 months on the linifanib arm ( 95 % CI , 8.1 to 10.2 ) and 9.8 months on the sorafenib arm ( 95 % CI , 8.3 to 11.0 ; hazard ratio [ HR ] , 1.046 ; 95 % CI , 0.896 to 1.221 ) . For prespecified stratification subgroups , OS HRs ranged from 0.793 to 1.119 and the 95 % CI contained 1.0 . Median TTP was 5.4 months on the linifanib arm ( 95 % CI , 4.2 to 5.6 ) and 4.0 months on the sorafenib arm ( 95 % CI , 2.8 to 4.2 ; HR , 0.759 ; 95 % CI , 0.643 to 0.895 ; P = .001 ) . Best response rate was 13.0 % on the linifanib arm versus 6.9 % on the sorafenib arm . Grade 3/4 adverse events ( AEs ) ; serious AEs ; and AEs leading to discontinuation , dose interruption , and reduction were more frequent with linifanib ( all P < .001 ) . CONCLUSION Linifanib and sorafenib had similar OS in advanced HCC . Predefined superiority and noninferiority OS boundaries were not met for linifanib and the study failed to meet the primary end point . TTP and ORR favored linifanib ; safety results favored sorafenib BACKGROUND Angiogenesis is known to be essential to the survival , growth , invasion , and metastasis of tumor cells . Vascular endothelial growth factor ( VEGF ) are an important angiogenic factor regulating tumor angiogenesis , but its significance and tumor pathologic features are unclear in hepatocellular carcinoma ( HCC ) . In the present study , we analyzed expression of tissue VEGF , alteration of microvascular density ( MVD ) in microvessel angiogenesis , development and metastasis of HCC , and level of serum VEGF in differential diagnosis of benign and malignant liver diseases . METHODS Tumor specimens were prospect ively collected from HCC patients undergoing resection . Total RNAs were extracted and the expression levels were detected from different parts of HCC tissues . The cellular distributions of VEGF and MVD of liver tumors and their paracancerous and distal cancerous tissues were investigated by streptavidin peroxidase ( S-P ) immunohistochemistry , respectively . The VEGF levels of circulating blood and hepatoma tissues were measured by enzyme-linked immunosorbent assay . RESULTS The incidence of VEGF expression was 63.9 % in HCCs ( 23/36 cases ) , 78.3 % in non-encapsulated HCCs ( 18/23 ) , and 90.9 % in HCCs with extrahepatic metastasis ( 10/11 ) , respectively . The VEGF expression was tightly correlated with MVD ( P<0.01 ) . The MVD in HCC with metastasis , low differentiation or non-encapsulation was significantly higher than that in HCC with intact capsule , high differentiation , or no metastasis . No significant difference was found between VEGF , MVD , tumor size , and hepatitis virus infection . The level of total RNA in HCC tissues was significantly lower but the VEGF level significantly higher than those in paracancerous or distal cancerous ones ( P<0.01 ) . The abnormal expression levels of VEGF in sera of HCC patients were directly correlated with the metastasis and recurrence of tumors . CONCLUSION The high expression of VEGF and abnormality of tissue MVD are useful predictors for vascular invasion and metastasis of liver tumors BACKGROUND Most cases of hepatocellular carcinoma occur in the Asia-Pacific region , where chronic hepatitis B infection is an important aetiological factor . Assessing the efficacy and safety of new therapeutic options in an Asia-Pacific population is thus important . We did a multinational phase III , r and omised , double-blind , placebo-controlled trial to assess the efficacy and safety of sorafenib in patients from the Asia-Pacific region with advanced ( unresectable or metastatic ) hepatocellular carcinoma . METHODS Between Sept 20 , 2005 , and Jan 31 , 2007 , patients with hepatocellular carcinoma who had not received previous systemic therapy and had Child-Pugh liver function class A , were r and omly assigned to receive either oral sorafenib ( 400 mg ) or placebo twice daily in 6-week cycles , with efficacy measured at the end of each 6-week period . Eligible patients were stratified by the presence or absence of macroscopic vascular invasion or extrahepatic spread ( or both ) , Eastern Cooperative Oncology Group performance status , and geographical region . R and omisation was done central ly and in a 2:1 ratio by means of an interactive voice-response system . There was no predefined primary endpoint ; overall survival , time to progression ( TTP ) , time to symptomatic progression ( TTSP ) , disease control rate ( DCR ) , and safety were assessed . Efficacy analyses were done by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00492752 . FINDINGS 271 patients from 23 centres in China , South Korea , and Taiwan were enrolled in the study . Of these , 226 patients were r and omly assigned to the experimental group ( n=150 ) or to the placebo group ( n=76 ) . Median overall survival was 6.5 months ( 95 % CI 5.56 - 7.56 ) in patients treated with sorafenib , compared with 4.2 months ( 3.75 - 5.46 ) in those who received placebo ( hazard ratio [ HR ] 0.68 [ 95 % CI 0.50 - 0.93 ] ; p=0.014 ) . Median TTP was 2.8 months ( 2.63 - 3.58 ) in the sorafenib group compared with 1.4 months ( 1.35 - 1.55 ) in the placebo group ( HR 0.57 [ 0.42 - 0.79 ] ; p=0.0005 ) . The most frequently reported grade 3/4 drug-related adverse events in the 149 assessable patients treated with sorafenib were h and -foot skin reaction ( HFSR ; 16 patients [ 10.7 % ] ) , diarrhoea ( nine patients [ 6.0 % ] ) , and fatigue ( five patients [ 3.4 % ] ) . The most common adverse events result ing in dose reductions were HFSR ( 17 patients [ 11.4 % ] ) and diarrhoea ( 11 patients [ 7.4 % ] ) ; these adverse events rarely led to discontinuation . INTERPRETATION Sorafenib is effective for the treatment of advanced hepatocellular carcinoma in patients from the Asia-Pacific region , and is well tolerated . Taken together with data from the Sorafenib Hepatocellular Carcinoma Assessment R and omised Protocol ( SHARP ) trial , sorafenib seems to be an appropriate option for the treatment of advanced hepatocellular carcinoma PURPOSE Brivanib is a dual inhibitor of vascular-endothelial growth factor and fibroblast growth factor receptors that are implicated in the pathogenesis of hepatocellular carcinoma ( HCC ) . Our multinational , r and omized , double-blind , phase III trial compared brivanib with sorafenib as first-line treatment for HCC . PATIENTS AND METHODS Advanced HCC patients who had no prior systemic therapy were r and omly assigned ( ratio , 1:1 ) to receive sorafenib 400 mg twice daily orally ( n = 578 ) or brivanib 800 mg once daily orally ( n = 577 ) . Primary end point was overall survival ( OS ) . Secondary end points included time to progression ( TTP ) , objective response rate ( ORR ) , disease control rate ( DCR ) based on modified Response Evaluation Criteria in Solid Tumors ( mRECIST ) , and safety . RESULTS The primary end point of OS noninferiority for brivanib versus sorafenib in the per- protocol population ( n = 1,150 ) was not met ( hazard ratio [ HR ] , 1.06 ; 95.8 % CI , 0.93 to 1.22 ) , based on the prespecified margin ( upper CI limit for HR ≤ 1.08 ) . Median OS was 9.9 months for sorafenib and 9.5 months for brivanib . TTP , ORR , and DCR were similar between the study arms . Most frequent grade 3/4 adverse events for sorafenib and brivanib were hyponatremia ( 9 % and 23 % , respectively ) , AST elevation ( 17 % and 14 % ) , fatigue ( 7 % and 15 % ) , h and -foot-skin reaction ( 15 % and 2 % ) , and hypertension ( 5 % and 13 % ) . Discontinuation as a result of adverse events was 33 % for sorafenib and 43 % for brivanib ; rates for dose reduction were 50 % and 49 % , respectively . CONCLUSION Our study did not meet its primary end point of OS noninferiority for brivanib versus sorafenib . However , both agents had similar antitumor activity , based on secondary efficacy end points . Brivanib had an acceptable safety profile , but was less well-tolerated than sorafenib BACKGROUND Hepatocellular carcinoma ( HCC ) tumour spread is partly dependent on neoangiogenesis . In this open-label , multicentre , phase II trial done in Europe and Asia , sunitinib , a multitargeted tyrosine-kinase inhibitor with anti-angiogenic properties , was assessed in patients with advanced unresectable HCC . METHODS Between February and July , 2006 , eligible patients were enrolled and treated with repeated cycles of oral sunitinib ( 50 mg/day for 4 weeks , followed by 2 weeks off treatment ) . The primary endpoint of this Simon two-stage phase II trial was objective response rate according to Response Evaluation Criteria in Solid Tumours ( RECIST ) criteria , with an expected response rate of 15 % . This trial is registered with Clinical Trials.gov , number NCT00247676 . FINDINGS Of 37 patients enrolled , one ( 2.7 % ) patient experienced a confirmed partial response , giving an overall objective response rate of 2.7 % ( 95 % CI 0.1 - 14.2 ) ; on the basis of this , the trial did not proceed to the second stage . 13 ( 35 % ) of 37 patients achieved stable disease for over 3 months . Commonly observed grade 3 and 4 adverse events included thrombocytopenia ( 14 of 37 ; 37.8 % ) , neutropenia ( nine of 37 ; 24.3 % ) , asthenia ( five of 37 ; 13.5 % ) , h and -foot syndrome ( four of 37 ; 10.8 % ) , and anaemia ( four of 37 ; 10.8 % ) . There were four deaths among the 37 patients ( 10.8 % ) that were possibly related to treatment . INTERPRETATION Sunitinib showed pronounced toxicities at a dose of 50 mg/day in patients with unresectable HCC . The response rate was low , and the study did not meet the primary endpoint based on RECIST criteria . FUNDING Pfizer Oncology BACKGROUND Tivantinib ( ARQ 197 ) , a selective oral inhibitor of MET , has shown promising antitumour activity in hepatocellular carcinoma as monotherapy and in combination with sorafenib . We aim ed to assess efficacy and safety of tivantinib for second-line treatment of advanced hepatocellular carcinoma . METHODS In this completed , multicentre , r and omised , placebo-controlled , double-blind , phase 2 study , we enrolled patients with advanced hepatocellular carcinoma and Child-Pugh A cirrhosis who had progressed on or were unable to tolerate first-line systemic therapy . We r and omly allocated patients 2:1 to receive tivantinib ( 360 mg twice-daily ) or placebo until disease progression . The tivantinib dose was amended to 240 mg twice-daily because of high incidence of treatment-emergent grade 3 or worse neutropenia . R and omisation was done central ly by an interactive voice-response system , stratified by Eastern Cooperative Oncology Group performance status and vascular invasion . The primary endpoint was time to progression , according to independent radiological review in the intention-to-treat population . We assessed tumour sample s for MET expression with immunohistochemistry ( high expression was regarded as ≥2 + in ≥50 % of tumour cells ) . This study is registered with Clinical Trials.gov , number NCT00988741 . FINDINGS 71 patients were r and omly assigned to receive tivantinib ( 38 at 360 mg twice-daily and 33 at 240 mg twice-daily ) ; 36 patients were r and omly assigned to receive placebo . At the time of analysis , 46 ( 65 % ) patients in the tivantinib group and 26 ( 72 % ) of those in the placebo group had progressive disease . Time to progression was longer for patients treated with tivantinib ( 1·6 months [ 95 % CI 1·4 - 2·8 ] ) than placebo ( 1·4 months [ 1·4 - 1·5 ] ; hazard ratio [ HR ] 0·64 , 90 % CI 0·43 - 0·94 ; p=0·04 ) . For patients with MET-high tumours , median time to progression was longer with tivantinib than for those on placebo ( 2·7 months [ 95 % CI 1·4 - 8·5 ] for 22 MET-high patients on tivantinib vs 1·4 months [ 1·4 - 1·6 ] for 15 MET-high patients on placebo ; HR 0·43 , 95 % CI 0·19 - 0·97 ; p=0·03 ) . The most common grade 3 or worse adverse events in the tivantinib group were neutropenia ( ten patients [ 14 % ] vs none in the placebo group ) and anaemia ( eight [ 11 % ] vs none in the placebo group ) . Eight patients ( 21 % ) in the tivantinib 360 mg group had grade 3 or worse neutropenia compared with two ( 6 % ) patients in the 240 mg group . Four deaths related to tivantinib occurred from severe neutropenia . 24 ( 34 % ) patients in the tivantinib group and 14 ( 39 % ) patients in the placebo group had serious adverse events . INTERPRETATION Tivantinib could provide an option for second-line treatment of patients with advanced hepatocellular carcinoma and well-compensated liver cirrhosis , particularly for patients with MET-high tumours . Confirmation in a phase 3 trial is needed , with a starting dose of tivantinib 240 mg twice-daily . FUNDING ArQule , Daiichi Sankyo ( Daiichi Sankyo Group ) BACKGROUND There is no st and ard of care for adjuvant therapy for patients with hepatocellular carcinoma . This trial was design ed to assess the efficacy and safety of sorafenib versus placebo as adjuvant therapy in patients with hepatocellular carcinoma after surgical resection or local ablation . METHODS We undertook this phase 3 , double-blind , placebo-controlled study of patients with hepatocellular carcinoma with a complete radiological response after surgical resection ( n=900 ) or local ablation ( n=214 ) in 202 sites ( hospitals and research centres ) in 28 countries . Patients were r and omly assigned ( 1:1 ) to receive 400 mg oral sorafenib or placebo twice a day , for a maximum of 4 years , according to a block r and omisation scheme ( block size of four ) using an interactive voice-response system . Patients were stratified by curative treatment , geography , Child-Pugh status , and recurrence risk . The primary outcome was recurrence-free survival assessed after data base cut-off on Nov 29 , 2013 . We analysed efficacy in the intention-to-treat population and safety in r and omly assigned patients receiving at least one study dose . The final analysis is reported . This study is registered with Clinical Trials.gov , number NCT00692770 . FINDINGS We screened 1602 patients between Aug 15 , 2008 , and Nov 17 , 2010 , and r and omly assigned 1114 patients . Of 556 patients in the sorafenib group , 553 ( > 99 % ) received the study treatment and 471 ( 85 % ) terminated treatment . Of 558 patients in the placebo group , 554 ( 99 % ) received the study treatment and 447 ( 80 % ) terminated treatment . Median duration of treatment and mean daily dose were 12·5 months ( IQR 2·6 - 35·8 ) and 577 mg per day ( SD 212·8 ) for sorafenib , compared with 22·2 months ( 8·1 - 38·8 ) and 778·0 mg per day ( 79·8 ) for placebo . Dose modification was reported for 497 ( 89 % ) of 559 patients in the sorafenib group and 206 ( 38 % ) of 548 patients in the placebo group . At final analysis , 464 recurrence-free survival events had occurred ( 270 in the placebo group and 194 in the sorafenib group ) . Median follow-up for recurrence-free survival was 8·5 months ( IQR 2·9 - 19·5 ) in the sorafenib group and 8·4 months ( 2·9 - 19·8 ) in the placebo group . We noted no difference in median recurrence-free survival between the two groups ( 33·3 months in the sorafenib group vs 33·7 months in the placebo group ; hazard ratio [ HR ] 0·940 ; 95 % CI 0·780 - 1·134 ; one-sided p=0·26 ) . The most common grade 3 or 4 adverse events were h and -foot skin reaction ( 154 [ 28 % ] of 559 patients in the sorafenib group vs four [ < 1 % ] of 548 patients in the placebo group ) and diarrhoea ( 36 [ 6 % ] vs five [ < 1 % ] in the placebo group ) . Sorafenib-related serious adverse events included h and -foot skin reaction ( ten [ 2 % ] ) , abnormal hepatic function ( four [ < 1 % ] ) , and fatigue ( three [ < 1 % ] ) . There were four ( < 1 % ) drug-related deaths in the sorafenib group and two ( < 1 % ) in the placebo group . INTERPRETATION Our data indicate that sorafenib is not an effective intervention in the adjuvant setting for hepatocellular carcinoma following resection or ablation UNLABELLED Transarterial chemoembolization ( TACE ) is the current st and ard of treatment for unresectable intermediate-stage hepatocellular carcinoma ( HCC ) . Brivanib , a selective dual inhibitor of vascular endothelial growth factor and fibroblast growth factor signaling , may improve the effectiveness of TACE when given as an adjuvant to TACE . In this multinational , r and omized , double-blind , placebo-controlled , phase III study , 870 patients with TACE-eligible HCC were planned to be r and omly assigned ( 1:1 ) after the first TACE to receive either brivanib 800 mg or placebo orally once-daily . The primary endpoint was overall survival ( OS ) . Secondary endpoints included time to disease progression ( TTDP ; a composite endpoint based on development of extrahepatic spread or vascular invasion , deterioration of liver function or performance status , or death ) , time to extrahepatic spread or vascular invasion ( TTES/VI ) , rate of TACE , and safety . Time to radiographic progression ( TTP ) and objective response rate were exploratory endpoints . The trial was terminated after r and omization of 502 patients ( brivanib , 249 ; placebo , 253 ) when two other phase III studies of brivanib in advanced HCC patients failed to meet OS objectives . At termination , median follow-up was approximately 16 months . Intention-to-treat analysis showed no improvement in OS with brivanib versus placebo ( median , 26.4 [ 95 % confidence interval { CI } : 19.1 to not reached ] vs. 26.1 months [ 19.0 - 30.9 ] ; hazard ratio [ HR ] : 0.90 [ 95 % CI : 0.66 - 1.23 ] ; log-rank P=0.5280 ) . Brivanib improved TTES/VI ( HR , 0.64 [ 95 % CI : 0.45 - 0.90 ] ) , TTP ( 0.61 [ 0.48 - 0.77 ] ) , and rate of TACE ( 0.72 [ 0.61 - 0.86 ] ) , but not TTDP ( 0.94 [ 0.72 - 1.22 ] ) versus placebo . Most frequent grade 3 - 4 adverse events included hyponatremia ( brivanib , 18 % vs. placebo , 5 % ) and hypertension ( 13 % vs. 3 % ) . CONCLUSIONS In this study , brivanib as adjuvant therapy to TACE did not improve OS BACKGROUND There are no systemic treatments for patients with hepatocellular carcinoma ( HCC ) whose disease progresses during sorafenib treatment . We aim ed to assess the efficacy and safety of regorafenib in patients with HCC who have progressed during sorafenib treatment . METHODS In this r and omised , double-blind , parallel-group , phase 3 trial done at 152 sites in 21 countries , adults with HCC who tolerated sorafenib ( ≥400 mg/day for ≥20 of last 28 days of treatment ) , progressed on sorafenib , and had Child-Pugh A liver function were enrolled . Participants were r and omly assigned ( 2:1 ) by a computer-generated r and omisation list and interactive voice response system and stratified by geographical region , Eastern Cooperative Oncology Group performance status , macrovascular invasion , extrahepatic disease , and α-fetoprotein level to best supportive care plus oral regorafenib 160 mg or placebo once daily during weeks 1 - 3 of each 4-week cycle . Investigators , patients , and the funder were masked to treatment assignment . The primary endpoint was overall survival ( defined as time from r and omisation to death due to any cause ) and analysed by intention to treat . This trial is registered with Clinical Trials.gov , number NCT01774344 . FINDINGS Between May 14 , 2013 , and Dec 31 , 2015 , 843 patients were screened , of whom 573 were enrolled and r and omised ( 379 to regorafenib and 194 to placebo ; population for efficacy analyses ) , and 567 initiated treatment ( 374 received regorafenib and 193 received placebo ; population for safety analyses ) . Regorafenib improved overall survival with a hazard ratio of 0·63 ( 95 % CI 0·50 - 0·79 ; one-sided p<0·0001 ) ; median survival was 10·6 months ( 95 % CI 9·1 - 12·1 ) for regorafenib versus 7·8 months ( 6·3 - 8·8 ) for placebo . Adverse events were reported in all regorafenib recipients ( 374 [ 100 % ] of 374 ) and 179 ( 93 % ) of 193 placebo recipients . The most common clinical ly relevant grade 3 or 4 treatment-emergent events were hypertension ( 57 patients [ 15 % ] in the regorafenib group vs nine patients [ 5 % ] in the placebo group ) , h and -foot skin reaction ( 47 patients [ 13 % ] vs one [ 1 % ] ) , fatigue ( 34 patients [ 9 % ] vs nine patients [ 5 % ] ) , and diarrhoea ( 12 patients [ 3 % ] vs no patients ) . Of the 88 deaths ( grade 5 adverse events ) reported during the study ( 50 patients [ 13 % ] assigned to regorafenib and 38 [ 20 % ] assigned to placebo ) , seven ( 2 % ) were considered by the investigator to be related to study drug in the regorafenib group and two ( 1 % ) in the placebo group , including two patients ( 1 % ) with hepatic failure in the placebo group . INTERPRETATION Regorafenib is the only systemic treatment shown to provide survival benefit in HCC patients progressing on sorafenib treatment . Future trials should explore combinations of regorafenib with other systemic agents and third-line treatments for patients who fail or who do not tolerate the sequence of sorafenib and regorafenib . FUNDING Bayer |
1,858 | 23,180,344 | The major conclusion is that the absence of regulations concerning the application of the efficiency criterion in decision-making on the subject of price and financing and , most importantly , the fact that these are not included in Spanish hospitals forms make it difficult to analyse the real impact of economic evaluations of cancer treatments on such decisions | Economic evaluation of pharmacological cancer treatment is a critical clinical problem currently under consideration worldwide . | The study consisted of a cost-minimisation analysis since the findings from a multicentre r and omised phase III trial showed that pegylated liposomal doxorubicin hydrochloride was at least as efficacious as topotecan . An economic model from the Spanish hospitals perspective was constructed to compare the costs derived from the treatment using both drugs in patients with recurrent epithelial ovarian cancer who failed a first-line platinum-containing regimen . The cost evaluation included direct medical costs : drug , drug administration and costs of managing adverse events . Estimation of re sources used in managing adverse events was made retrospectively through an expert panel . Results obtained per patient were : cost of drug and administration , 8647.70 euros for pegylated liposomal doxorubicin hydrochloride and 8519.94 euros for topotecan , while cost of managing adverse events was 967.02 euros in the pegylated liposomal doxorubicin hydrochloride arm and 3304.75 euros for topotecan . The total cost per patient was therefore estimated to be 9614.72 euros for pegylated liposomal doxorubicin hydrochloride and 11 824.69 euros for topotecan , showing that pegylated liposomal doxorubicin hydrochloride produces a cost saving of 2209.97 euros per patient in comparison to topotecan . Sensitivity analyses verified the robustness of the results . These findings suggest that pegylated liposomal doxorubicin hydrochloride is an efficient therapy and can be used as a cost-saving option for treatment of patients with recurrent epithelial ovarian cancer who have failed a first-line platinum-containing regimen In the r and omised clinical trial E1684 , the administration of interferon ( IFN ) alpha-2b result ed in prolonged disease-free and overall survival in high-risk melanoma patients following surgical resection . However , and considering the cost and toxicity of IFN , the convenience of its widespread use should be evaluated . The aim of this study was to analyse the cost-effectiveness ratio of adjuvant therapy with IFN alpha-2b in melanoma patients versus an untreated control group . A Markov model was used to compare two hypothetical cohorts of 1000 patients aged 50 years , according to the clinical outcome of the E1684 study . The cohort of patients treated with IFN alpha-2b has an increased overall survival of 1.90 years during the patient 's lifetime . The incremental discounted cost per life year gained of IFN versus observation is 9015 Euros according to the projection generated by the model . The sensitivity analysis demonstrated that changes in the most relevant study end-points do not modify the study outcome . In conclusion , in high-risk melanoma patients following surgical resection , the cost-effectiveness of IFN alpha-2b ( at a dose of 20 MU/m2/day , 5 days per week for one month , followed by 10 MU/m2 TIW , up to one complete year of therapy ) versus an untreated control group is within the limits established in health economics to determine if adoption of a new treatment is economically justified and is comparable with other interventions in which cost-effectiveness is acceptable to the National Health System Introduction The r and omised controlled trial BCIRG001 has recently demonstrated that docetaxel in combination with doxorubicin and cyclophosphamide ( TAC ) has better efficacy than the st and ard treatment ( FAC , i.e. , 5-fluorouracil , doxorubicin and cyclophosphamide ) in the adjuvant treatment of patients with node-positive breast cancer . The cost-effectiveness of TAC vs. FAC in the Spanish setting is analysed . Patients and methods Clinical outcomes from trial BCIRG001 were combined with Spanish costs and long-term efficacy of FAC and TAC extrapolated up to 5 years by means of a Markov model . Results are shown as cost per life year gained ( C/LYG ) and cost per quality -adjusted life year ( C/QALY ) . Costs and effects were discounted at a rate of 3 % . Results Mean survival was 17.8 and 16.5 years for TAC and FAC , with total costs of € 14,611 and € 11,586 , respectively . The results of the cost-effectiveness analysis showed that TAC achieves a C/LYG and a C/QALY of only € 2345 and € 2631 , respectively . Sensitivity analysis confirmed the robustness of the results . Conclusions Combined therapy based on docetaxel ( TAC ) is not only an effective option , but also presents a favourable cost-effectiveness ratio , clearly below the Spanish efficiency threshold in all the scenarios considered A large r and omized clinical trial in advanced , previously untreated , non-small cell lung cancer ( NSCLC ) patients revealed better response rates and better tolerance for paclitaxel+cisplatin ( TAXCIS ) compared to teniposide+cisplatin ( TENCIS ) . Since economic evidence is receiving increasing attention in health care , we conducted an economic evaluation based on the trial results in The Netherl and s , Belgium , France and Spain . The evaluation was based on ( i ) differences in drug costs , ( ii ) differences in chemotherapy administration and ( iii ) the economic consequences of significantly different clinical outcomes in the trial : anemia , thrombocytopenia , neutropenia , neuropathy and arthralgia/myalgia . Data regarding medical re source utilization were obtained from clinician interviews using a Delphi technique and vali date d by patient charts analysis . Differences in medical management occurred across countries , but TAXCIS was cost-additive in all countries , i.e. the extra cost of chemotherapy was only partially compensated by savings in medical re source use , result ing in a net cost per patient of US$ 2311 . In the trial , TAXCIS therapy produced a 37 % response rate compared to 26 % for TENCIS . The cost per extra responder for TAXCIS is on average US$ 21011 , which is comparable to the cost per responder obtained with TENCIS ( US$ 27266 ) . Thus , the cost-effectiveness of TAXCIS , expressed in cost per responder , is similar to the cost-effectiveness obtained with TENCIS INTRODUCTION Information on the relative cost-effectiveness of treatments for cancer is being increasingly sought as pressure on health care re sources increases . The objective of this study was to assess the cost-effectiveness of gemcitabine/cisplatin ( GC ) versus cisplatin/etoposide ( CE ) in patients with advanced non-small cell lung cancer ( NSCLC ) , using re source utilization data collected in conjunction with the first r and omized clinical trial comparing both combinations . METHODS Efficacy and medical care re source utilization data were collected prospect ively in an open-label , multicenter , r and omized , comparative , phase III trial conducted in Spain which compared gemcitabine/cisplatin and cisplatin/etoposide in 135 chemonaive patients with Stage IIIB or IV NSCLC . There were no differences between both regimens when survival was used as primary end-point , so a cost-minimization analysis was used to compare them . In addition , cost-effectiveness analyses were conducted when percentage of responses and time to progression were used as secondary end-points . RESULTS There were no differences between both regimens when survival was selected as the efficacy end-point . Despite the higher chemotherapy cost of GC when compared to CE , there were no differences in total direct costs ( 584523 pts for GC and 589630 pts for CE ; P = NS ) between both regimens . Potential savings with GC were mainly associated with a decrease in hospitalization rate . There were differences in favor of GC when response rate ( 40.6 % for GC and 21.9 % for CE ; P<0.05 ) and time to disease progression ( 8.7 months for GC and 7.2 months for CE ; P<0 . 05 ) were used as clinical end-points . GC presented a favorable cost-effectiveness profile when compared to CE . CONCLUSIONS This prospect i ve economic evaluation conducted alongside a clinical trial offers valuable preliminary information on the potential efficiency of the combination gemcitabine-cisplatin in NSCLC . Future assessment s based on larger clinical trials focused on survival and naturalistic economic studies conducted in real clinical practice setting s are necessary to confirm these findings |
1,859 | 27,879,472 | Narrative synthesis suggested that feedback of PROM data tended to increase discussion s between patients and professionals about pain and /or symptoms overall .
Conclusions Interventions that assess and feedback cancer pain data to patients and /or professionals have so far led to modest reductions in cancer pain intensity . | Purpose Cancer pain is a distressing and complex experience .
It is feasible that the systematic collection and feedback of patient-reported outcome measurements ( PROMs ) relating to pain could enhance cancer pain management .
We aim ed to conduct a systematic review of interventions in which patient-reported pain data were collected and fed back to patients and /or professionals in order to improve cancer pain control . | ABSTRACT A prospect i ve controlled intervention cohort study in cancer pain patients ( n = 50 per group ) admitted to radiation oncology wards ( 62 beds , 3 wards ) was conducted in a 1621‐bed university hospital . We investigated the effect of an intervention consisting of daily pain assessment using the numeric visual analog scale ( NVAS ) and pain therapy counseling to clinicians based on a computerized clinical decision support system ( CDSS ) to correct deviations from pain therapy guidelines . Effects on guideline adherence ( primary outcome ) , pain relief ( NVAS ) at rest and during physical activity ( both groups : cross‐sectional assessment on day 5 ; intervention group : every day assessment ) , co‐analgesic prescription , and acceptance rates of recommendations ( secondary outcomes ) were assessed . The number of patients with at least one deviation from guidelines at discharge was decreased by the intervention from 37 ( 74 % ) in controls to 7 ( 14 % , p < 0.001 ) . In the intervention group , pain ( NVAS ) decreased during hospital stay at rest from 3.0 ( Δ0.5 ( Q75 % − Q25 % ) = 3.0 ) on admission to 1.5 ( Δ0.5 = 1.0 ) at discharge ( p < 0.01 ) and during physical activity from 7.0 ( Δ0.5 = 4.0 ) on admission to 2.5 ( Δ0.5 = 3.8 ) at discharge ( p < 0.001 ) . At discharge , the number of patients treated with co‐analgesics increased from 23 ( 46 % ) in controls to 33 ( 66 % ) in the intervention group ( p = 0.04 ) . From 279 recommendations issued in the intervention 85 % were fully accepted by the physicians . Deviations from well‐established guidelines are frequent in pain therapy . A multidisciplinary pain management increased adherence to pain management guidelines Introduction The prevalence of pain in patients with cancer is still too high . Factors relating to ineffective pain treatment fall into three categories : the health care system , professional care providers , and patients . In patients , various barriers lead to noncompliance . Previous educational interventions have increased their knowledge of pain and decreased short-term pain levels . In this r and omized controlled trial , the authors investigated how an intensive home-based education program given by nurses affected short-term and long-term pain levels . Material s and methods One hundred and twenty cancer patients were r and omized to receive either the pain education program ( PEP ) or usual care . Pain , knowledge , quality of life , anxiety , and depression were measured at baseline and after 4 and 8 weeks . In the intervention group , effects on symptom levels were communicated to the treating physician . Results The level of pain had decreased at 4 weeks , but not at 8 weeks . Significant decreases in pain only persisted in those patients with a high pain score at baseline . Knowledge of pain significantly increased in the intervention group . No correlation was found between increased pain knowledge and decreased pain levels . Conclusions The PEP given by nurses lowered pain intensity levels in cancer patients and increased their knowledge of pain . More attention should be paid to patient education and to communication between patients and health professionals regarding pain and pain management OBJECTIVE To test a pathway through which a tailored , pain management education-coaching intervention could contribute to better cancer pain control through the effects of patients ' communication about pain on physician prescribing of pain medication . METHODS Secondary analysis of data from a r and omized controlled trial that tested the effects of a tailored education-coaching intervention on pain control for patients with advanced cancer . The current analysis focused on a subset of the patients ( n = 135 ) who agreed to have their consultations audio-recorded . Patients ' active communication about pain ( e.g. , expressing questions , concerns , and preferences about pain-related issues ) was coded from audio-recordings . Change in pain medication was measured by patient self-report . Improvement in pain control was scored as the difference between baseline pain score and pain reported at 6 weeks . RESULTS Patients ' pain-related communication was a significant predictor of patient-reported changes in physician prescribing of pain medication ( p < .0001 ) and mediated the effect of baseline pain on medication change . Other predictors of change in pain medication were age ( younger ) and having participated in the intervention ( as opposed to usual care ) . Of the patients reporting adjustment in pain medications , 49 % experienced better pain control compared with only 27 % of patients reporting no change in pain management ( p < .02 ) . CONCLUSIONS Cancer patients who ask questions , express concerns , and state preferences about pain-related matters can prompt physicians to change their pain management regimen , which in turn may lead to better pain control . Future research should model pathways through which clinician-patient communication can lead to better cancer outcomes PURPOSE To describe a r and omized trial of a cognitive behavioral intervention on reducing symptom severity among patients diagnosed with solid tumors and undergoing a first course of chemotherapy and to determine whether the intervention had an additive or interactive effect on symptom severity in the presence of supportive care medications . PATIENTS AND METHODS Patients ( N = 237 ) were accrued from comprehensive and community cancer centers , interviewed , and r and omly assigned to either the experimental intervention ( n = 118 ) or conventional care ( n = 119 ) . A symptom severity index , based on summed severity scores across 15 symptoms , was the primary outcome . Each patient 's site of cancer , stage at diagnosis , chemotherapy protocol s , and use of supportive medications were learned from medical records . RESULTS Groups were equivalent at baseline , and attrition by characteristics by group was not different . The proportion of patients not receiving chemotherapy at 10 and 20 weeks did not differ by group . At the 10- and 20-week observations , there was a significant interaction between the experimental group and baseline symptom severity . Patients in the experimental group who entered the trial with higher symptom severity reported significantly lower severity at 10 and 20 weeks . Controlling for chemotherapy treatment status at follow-up and supportive care medications did not alter the effect of the experimental intervention . CONCLUSION Compared with conventional care alone , the experimental intervention was effective among patients who entered the trial with higher levels of symptom severity . Age , sex , site or stage of cancer , and supportive medications did not modify the effect of this cognitive behavioral intervention on symptom severity Background The electronic self report assessment - cancer ( ESRA-C ) , has been shown to reduce symptom distress during cancer therapy The purpose of this analysis was to evaluate aspects of how the ESRA-C intervention may have result ed in lower symptom distress ( SD ) . Methods Patients at two cancer centers were r and omized to ESRA-C assessment only ( control ) or the Web-based ESRA-C intervention delivered to patients ’ homes or to a tablet in clinic . The intervention allowed patients to self-monitor symptom and quality of life ( SxQOL ) between visits , receive self-care education and coaching to report SxQOL to clinicians . Summaries of assessment s were delivered to clinicians in both groups . Audio-recordings of clinic visits made 6 weeks after treatment initiation were coded for discussion s of 26 SxQOL issues , focusing on patients ’ /caregivers ’ coached verbal reports of SxQOL severity , pattern , alleviating/aggravating factors and requests for help . Among issues identified as problematic , two measures were defined for each patient : the percent SxQOL reported that included a coached statement , and an index of verbalized coached statements per SxQOL . The Wilcoxon rank test was used to compare measures between groups . Clinician responses to problematic SxQOL were compared . A mediation analysis was conducted , exploring the effect of verbal reports on SD outcomes . Results 517 ( 256 intervention ) clinic visits were audio-recorded . General discussion of problematic SxQOL was similar in both groups . Control group patients reported a median 75 % of problematic SxQOL using any specific coached statement compared to a median 85 % in the intervention group ( p = .0009 ) . The median report index of coached statements was 0.25 for the control group and 0.31 for the intervention group ( p = 0.008 ) . Fatigue , pain and physical function issues were reported significantly more often in the intervention group ( all p < .05 ) . Clinicians ' verbalized responses did not differ between groups . Patients ' verbal reports did not mediate final SD outcomes ( p = .41 ) . Conclusions Adding electronically-delivered , self-care instructions and communication coaching to ESRA-C promoted specific patient descriptions of problematic SxQOL issues compared with ESRA-C assessment alone . However , clinician verbal responses were no different and subsequent symptom distress group differences were not mediated by the patients ' reports . Trial registration NCT00852852 ; 26 Feb PURPOSE Although patient-reported cancer symptoms and quality -of-life issues ( SQLIs ) have been promoted as essential to a comprehensive assessment , efficient and efficacious methods have not been widely tested in clinical setting s. The purpose of this trial was to determine the effect of the Electronic Self-Report Assessment -Cancer ( ESRA-C ) on the likelihood of SQLIs discussed between clinicians and patients with cancer in ambulatory clinic visits . Secondary objectives included comparison of visit duration between groups and usefulness of the ESRA-C as reported by clinicians . PATIENTS AND METHODS This r and omized controlled trial was conducted in 660 patients with various cancer diagnoses and stages at two institutions of a comprehensive cancer center . Patient-reported SQLIs were automatically displayed on a graphical summary and provided to the clinical team before an on-treatment visit ( n = 327 ) ; in the control group , no summary was provided ( n = 333 ) . SQLIs were scored for level of severity or distress . One on-treatment clinic visit was audio recorded for each participant and then scored for discussion of each SQLI . We hypothesized that problematic SQLIs would be discussed more often when the intervention was delivered to the clinicians . RESULTS The likelihood of SQLIs being discussed differed by r and omized group and depended on whether an SQLI was first reported as problematic ( P = .032 ) . Clinic visits were similar with regard to duration between groups , and clinicians reported the summary as useful . CONCLUSION The ESRA-C is the first electronic self-report application to increase discussion of SQLIs in a US r and omized clinical trial 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 CONTEXT Pain and depression are 2 of the most prevalent and treatable cancer-related symptoms , yet they frequently go unrecognized , undertreated , or both . OBJECTIVE To determine whether central ized telephone-based care management coupled with automated symptom monitoring can improve depression and pain in patients with cancer . DESIGN , SETTING , AND PATIENTS R and omized controlled trial conducted in 16 community-based urban and rural oncology practice s involved in the Indiana Cancer Pain and Depression ( INCPAD ) trial . Recruitment occurred from March 2006 through August 2008 and follow-up concluded in August 2009 . The participating patients had depression ( Patient Health Question naire-9 score > or = 10 ) , cancer-related pain ( Brief Pain Inventory [ BPI ] worst pain score > or = 6 ) , or both . INTERVENTION The 202 patients r and omly assigned to receive the intervention and 203 to receive usual care were stratified by symptom type . Patients in the intervention group received central ized telecare management by a nurse-physician specialist team coupled with automated home-based symptom monitoring by interactive voice recording or Internet . MAIN OUTCOME MEASURES Blinded assessment at baseline and at months 1 , 3 , 6 , and 12 for depression ( 20-item Hopkins Symptom Checklist [ HSCL-20 ] ) and pain ( BPI ) severity . RESULTS Of the 405 participants enrolled in the study , 131 had depression only , 96 had pain only , and 178 had both depression and pain . Of the 274 patients with pain , 137 patients in the intervention group had greater improvements in BPI pain severity over the 12 months of the trial whether measured as a continuous severity score or as a categorical pain responder ( > or = 30 % decrease in BPI ) than the 137 patients in the usual-care group ( P < .001 for both ) . Similarly , of the 309 patients with depression , the 154 patients in the intervention group had greater improvements in HSCL-20 depression severity over the 12 months of the trial whether measured as a continuous severity score or as a categorical depression responder ( > or = 50 % decrease in HSCL ) than the 155 patients in the usual care group ( P < .001 for both ) . The st and ardized effect size for between-group differences at 3 and 12 months was 0.67 ( 95 % confidence interval [ CI ] , 0.33 - 1.02 ) and 0.39 ( 95 % CI , 0.01 - 0.77 ) for pain , and 0.42 ( 95 % CI , 0.16 - 0.69 ) and 0.41 ( 95 % CI , 0.08 - 0.72 ) for depression . CONCLUSION Central ized telecare management coupled with automated symptom monitoring result ed in improved pain and depression outcomes in cancer patients receiving care in geographically dispersed urban and rural oncology practice s. TRIAL REGISTRATION clinical trials.gov Identifier : NCT00313573 The purpose of this r and omized controlled community trial is to evaluate the effects of a community intervention utilizing opinion leaders and educational strategies on the cancer pain management knowledge , attitudes , and the practice s of physicians and nurses , and cancer pain reported by patients . Six Minnesota communities participated in the study . The three communities r and omized to the intervention received educational programs over 15 months . The clinical community opinion leaders participated in a minifellowship , developed community task forces , and interacted with their peers . This strategy was reinforced with community outreach programs , clinical practice guidelines , educational material s , and media events . The primary study end point was patients ' pain intensity score . Comparing intervention to control communities , pain prevalence declined slightly , pain management index improved slightly , pain intensity scores increased slightly , patient and family attitude scores did not change , and physicians ' and nurses ' knowledge and attitude scores improved slightly . None of these changes , however , reached statistical significance . Participation in at least one intervention program improved physicians ' and nurses ' knowledge and attitude scores that approached statistical significance . Our results suggest that community opinion leaders combined with other educational programs may improve cancer pain management , but this strategy requires further study . The results suggest that more intense intervention application may be effective . Effective strategies to improve cancer pain management remain elusive CONTEXT For patients with cancer-related pain and their physicians , routine oncology visits are an opportunity to adjust the analgesic regimen and secure better pain control . However , treatment intensification occurs haphazardly in practice . OBJECTIVES To estimate the effect of patient-centered tailored education and coaching ( TEC ) on the likelihood of analgesic treatment adjustment during oncology visits , and in turn , the influence of treatment adjustment on subsequent cancer pain control , we studied patients enrolled in a r and omized trial of TEC . METHODS Just before a scheduled oncology visit , 258 patients with at least moderate baseline pain received TEC or control ; just after the same visit , they reported on whether the physician recommended a new pain medicine or a change in dose of an existing medicine . Pain severity and pain-related impairment were measured two , six , and 12 weeks later . RESULTS Patients assigned to TEC were more likely than controls to report a change in the analgesic treatment regimen ( 60 % vs. 36 % , P<0.01 ) ; significant effects persisted after adjustment for baseline pain , study site , and physician ( adjusted odds ratio 2.61 , 95 % confidence interval 1.55 , 4.40 , P<0.01 ) . In a mixed-effects repeated measures regression , analgesic change ( but not TEC itself ) was associated with a sustained decrease in pain severity ( P<0.05 ) . CONCLUSION TEC increases the likelihood of self-reported , physician-directed adjustments in analgesic prescribing , and treatment intensification is associated with better cancer pain outcomes PURPOSE / OBJECTIVES To assess the effect of an educational homecare program on pain relief in patients with advanced cancer . DESIGN Quasi-experimental ( pretest post-test , nonequivalent group ) . SETTING Four community-based primary care centers providing social and healthcare services in the Quebec City region of Canada . SAMPLE 80 homecare patients with advanced cancer who were free of cognitive impairment , who presented with pain or were taking analgesics to relieve pain , and who had a life expectancy of six weeks or longer . METHODS The educational intervention included information regarding pain assessment and monitoring using a daily pain diary and the provision of specific recommendations in case of loss of pain control . Pain intensity data were collected prior to the intervention , and re assessment s were made two and four weeks later . Data on beliefs were collected at baseline and two weeks . All data were collected by personal interviews . MAIN RESEARCH VARIABLES Patients beliefs about the use of opioids ; average and maximum pain intensities . FINDINGS Patients beliefs regarding the use of opioids were modified successfully following the educational intervention . Average pain was unaffected in the control group and was reduced significantly in patients who received the educational program . The reduction remained after controlling for patients initial beliefs . Maximum pain decreased significantly over time in both the experimental and control groups . CONCLUSIONS An educational intervention can be effective in improving the monitoring and relief of pain in patients with cancer living at home . IMPLICATION S FOR NURSING Homecare nurses can be trained to effectively administer the educational program during their regular homecare visits OBJECTIVE To examine the effects of a computer-assisted , interactive tailored patient assessment ( ITPA ) tool in oncology practice on : documented patient care , symptom distress , and patients ' need for symptom management support during treatment and rehabilitation . DESIGN AND METHODS For this repeated measures clinical trial at a university hospital in Norway , 145 patients starting treatment for leukemia or lymphoma were r and omly assigned to either an intervention ( n=75 ) or control group ( n=70 ) . Both groups used the ITPA for symptom assessment s prior to inpatient and outpatient visits for up to one year . The assessment summary , which displayed patients ' self-reported symptoms , problems , and distress in rank-order of the patient 's need for support , was provided to physicians and nurses in the intervention group only but not in the control group . RESULTS Significantly more symptoms were addressed in the intervention group patient charts versus those of the control group . Symptom distress in the intervention group decreased significantly over time in 11 ( 58 % ) of 19 symptom/problem categories versus 2 ( 10 % ) for the control group . Need for symptom management support over time also decreased significantly more for the intervention group than the control group in 13 ( 68 % ) symptom categories . CONCLUSION This is the first study to show that an ITPA used in an interdisciplinary oncology practice can significantly improve patient-centered care and patient outcomes , including reduced symptom distress and reduced need for symptom management support Purpose Monitoring patient-reported symptoms is necessary to adjust and improve supportive care during chemotherapy . Continuing advances in computerized approaches to symptom monitoring can enhance communication about unrelieved symptoms between patients and oncology providers and may facilitate intensified symptom treatment . Methods An automated IT-based telephone monitoring system was developed to enable oncology providers to receive and act on alert reports from patients about unrelieved symptoms during chemotherapy treatment . Daily , 250 participants ( r and omized to treatment or attentional control ) were asked to call the automated system to report presence , severity , and distress for common chemotherapy-related symptoms ( 1–10 scale if present ) . For the treatment group , symptoms exceeding preset thresholds for moderate-to-severe intensity levels generated emailed alert reports to both the patient ’s oncologist and oncology nurse . Results Patients reported high satisfaction and ease of use of the automated system . Over 80 % of providers reported usefulness of the symptom alert reports . Ten monitored symptoms result ed in , on average , nine moderate-to-severe intensity alerts per patient over 45 study days . However , providers rarely contacted patients after receiving alerts . There were no significant differences in change of symptom severity between the two groups ( mean difference = 0.06 , p = 0.58 ) . Conclusion Despite patients ’ use of a daily symptom monitoring system and providers ’ receipt of information about unrelieved symptoms of moderate-to-severe intensity , oncology physicians and nurses did not contact patients to intensify symptom treatment nor did symptoms improve . Further research is indicated to determine if oncology providers initiated follow-up to intensify symptom treatment , whether symptom outcomes would improve BACKGROUND The European Pain in Cancer survey sought to increase underst and ing of cancer-related pain and treatment across Europe . PATIENTS AND METHODS Patients with all stages of cancer participated in a two-phase telephone survey conducted in 11 European countries and Israel in 2006 - 2007 . The survey screened for patients experiencing pain at least weekly , then r and omly selected adult patients with pain of at least moderate intensity occurring several times per week for the last month completed a detailed attitudinal question naire . RESULTS Of 5084 adult patients contacted , 56 % suffered moderate-to-severe pain at least monthly . Of 573 patients r and omly selected for the second survey phase , 77 % were receiving prescription-only analgesics , with 41 % taking strong opioids either alone or with other drugs for cancer-related pain . Of those prescribed analgesics , 63 % experienced breakthrough pain . In all , 69 % reported pain-related difficulties with everyday activities ; however , 50 % believed that their quality of life was not considered a priority in their overall care by their health care professional . CONCLUSIONS Across Europe and Israel , treatment of cancer pain is suboptimal . Pain and pain relief should be considered integral to the diagnosis and treatment of cancer ; management guidelines should be revised to improve pain control in patients with cancer This r and omized controlled trial investigated the effect of reporting physical symptoms by using a systematic symptom monitoring instrument , the Symptom Monitor , on symptom prevalence and severity among patients with cancer in the palliative phase . The overall objective was to achieve symptom relief through systematic and regular symptom reporting by patients themselves . One hundred forty-six patients with cancer in the palliative phase were r and omized to either the intervention group ( n = 69 with Symptom Monitor ) or the control group ( n = 77 without Symptom Monitor ) . Ten physical symptoms with regard to prevalence and severity were monitored . After 2 months , the prevalence of symptoms was lower in the intervention group compared to the control group ( prevalent differences 2.1 - 24.3 % ) for 9 out of 10 symptoms ( except coughing ) . The intervention group scored a statistically significantly lower prevalence in constipation and vomiting ( prevalence differences 24.3 % and 18.0 % , respectively ) . In four symptoms ( fatigue , lack of appetite , shortness of breath , and nausea ) , the intervention group had a lower , although not statistically significant , severity score ( median differences 0.5 - 1 ) . In four symptoms ( pain , coughing , sleeplessness , and diarrhea ) , the severity score was the same in both groups ( medians 2 - 4 ) . In two symptoms ( constipation and vomiting ) , the severity score was lower in the control group ( median differences -1 and -2 ) . A comparison between the study groups on improved , deteriorated , or steady-state cases showed that the severity score had deteriorated less for 8 out of 10 symptoms in a larger proportion of patients in the intervention group . Although statistical significance was not reached , the prevalence as well as severity of symptoms in the palliative phase of cancer can be influenced by using the Symptom Monitor The authors have examined the effects of coaching sensory self-monitoring and reporting on pain-related variables in patients with lung cancer . R and omly assigned to coached or not-coached groups , 215 patients have their interactions with their providers audiotaped and complete study measures pre- and postintervention . Of the 151 patients who complete the 4-week study , those coached are more likely than those not coached to give their providers unsolicited sensory pain information and to mention it before their providers ask for it . The mean number of pain parameters discussed during the audiotaped clinic visit is statistically larger at study end for the coached group . Scores for analgesic adequacy , all pain indices except one , anxiety , depression , and catastrophizing coping are not significantly different . Although coaching increases the amount of pain data communicated to providers by patients with lung cancer , the magnitude is small and does not lead to improved adequacy of analgesics prescribed for each patient ’s pain level PURPOSE Regularly collecting patient-reported outcomes ( PROs ) of health-related quality of life with feedback to oncologists may assist in eliciting and monitoring patients ' problems during cancer treatment . This study examined how PRO feedback had an impact on patient-physician communication over time to gain a better underst and ing of how it may influence patient care . PATIENTS AND METHODS Exploratory analyses were performed on a data set from a previous study . Patients were r and omly assigned to intervention ( regular completion of European Organisation for Research and Treatment of Cancer Quality of Life Question naire-Core 30 and Hospital Anxiety and Depression Scale with feedback to oncologists ) , attention-control ( completion of same question naires without feedback ) , and control ( st and ard care ) arms . The content of consultation audio recordings between 28 oncologists and 198 patients over four consecutive visits ( 792 consultations ) was analyzed . Mixed-effects models and multivariate regressions were used to examine the longitudinal impact of the intervention on patient-physician communication , dynamics of patient-physician interaction , and the association between PROs and the content of clinic discussion . RESULTS Patients in the intervention arm discussed more symptoms over time compared with patients in the attention-control ( P = .008 ) and control ( P = .04 ) arms . No study arm effect was observed for function discussion s. Discussion topics were predominantly raised by patients /relatives , regardless of arm allocation . Clinic discussion s were associated with severity of patient-reported symptoms but not with patient-reported functional concerns . CONCLUSION A positive longitudinal impact of the intervention on symptom discussion was observed , but not for function discussion , suggesting that potentially serious problems may remain unaddressed . Training oncologists in responding to patient-reported functional concerns may increase the impact of this intervention & NA ; We aim ed to determine the effectiveness of a lay‐administered tailored education and coaching ( TEC ) intervention ( aim ed at reducing pain misconceptions and enhancing self‐efficacy for communicating with physicians ) on cancer pain severity , pain‐related impairment , and quality of life . Cancer patients with baseline “ worst pain ” of ⩾4 on a 0–10 scale or at least moderate functional impairment due to pain were r and omly assigned to TEC or enhanced usual care ( EUC ) during a telephone interview conducted in advance of a planned oncology office visit ( 265 patients r and omized to TEC or EUC ; 258 completed at least one follow‐up ) . Patients completed question naires before and after the visit and were interviewed by telephone at 2 , 6 , and 12 weeks . Mixed effects regressions were used to evaluate the intervention adjusting for patient , practice , and site characteristics . Compared to EUC , TEC was associated with increased pain communication self‐efficacy after the intervention ( P < .001 ) ; both groups showed significant ( P < .0001 ) , similar , reductions in pain misconceptions . At 2 weeks , assignment to TEC was associated with improvement in pain‐related impairment ( −0.25 points on a 5‐point scale , 95 % confidence interval −0.43 to −0.06 , P = .01 ) but not in pain severity ( −0.21 points on an 11‐point scale , −0.60 to 0.17 , P = .27 ) . The improvement in pain‐related impairment was not sustained at 6 and 12 weeks . There were no significant intervention by subgroup interactions ( P > .10 ) . We conclude that TEC , compared with EUC , result ed in improved pain communication self‐efficacy and temporary improvement in pain‐related impairment , but no improvement in pain severity . Compared with control , tailored education and coaching for patients with cancer‐related pain improved communication self‐efficacy and reduced pain‐related impairment in the short term but had no sustained benefits PURPOSE To determine the effectiveness of a multicomponent clinical intervention to reduce pain in out patients with cancer . METHODS AND MATERIAL S Sixty-four patients were r and omly assigned to receive either a clinical intervention including an information session , the use of a pain diary , and the possibility to contact a physician to adjust the pain medication , or the usual treatment of pain by the staff radiation oncologist . All patients reported their average and worst pain levels at baseline and 2 and 3 weeks after the start of the intervention . RESULTS The study groups were similar with respect to their baseline characteristics and pain levels at r and omization . After 3 weeks , the average and worst pain experienced by patients r and omized to the clinical intervention group was significantly inferior to the average pain experienced by patients in the control group ( 2.9/10 vs. 4.4/10 and 4.2/10 vs. 5.5/10 , respectively ) . Results showed that the experimental group patients decreased their pain levels more than the control group patients did over time . CONCLUSION An intervention including patient education , a pain diary , and defining a procedure for therapeutic adjustments can be effective to improve pain relief in out patients with cancer BACKGROUND Communication problems impede effective symptom management during chemotherapy . The primary aim of this pilot r and omized controlled trial was to test the effects of a personal digital assistant-delivered communication intervention on pain , depression , and fatigue symptoms among breast cancer patients undergoing chemotherapy . Secondary aims included assessment of 1 ) study feasibility , 2 ) patient and clinician responses to study participation , and 3 ) intervention effects on health-related quality of life ( HRQoL ) and communication self-efficacy . METHODS Intervention group participants ( n = 27 ) completed symptom inventories at baseline , once per week during treatment , and at posttreatment . Depending on symptom severity , they viewed race-concordant videos on how to communicate about pain , depression and /or fatigue , using the personal digital assistant . Symptom records were tracked and shared with clinicians . Control group participants ( n = 23 ) received usual care . Longitudinal r and om effects modeling assessed the changes in average symptom scores over time . Descriptive statistics assessed study feasibility and intervention effects on HRQoL and communication self-efficacy . Postintervention focus groups , interviews , and surveys assessed responses to study participation . RESULTS Mean age of the participants was 51.0 years ; 42 participants ( 84 % ) were white . In comparison with control , intervention group participants reported lower average pain severity over time ( P = .015 ) . Mean pain interference scores over time were marginally different between groups ( P = .07 ) ; mean depression and fatigue scores over time were statistically nonsignificant . Feasibility outcomes and perspectives about study participation were positive . Mean pre-post decreases in HRQoL were generally higher among intervention group participants ; pre-post changes in communication self-efficacy were equivalent . CONCLUSION Mixed findings of the study indicate the need for future research Background Precisely defining the different applications of patient-reported outcome measures ( PROs ) in clinical practice can be difficult . This is because the intervention is complex and varies amongst different studies in terms of the type of PRO used , how the PRO is fed back , and to whom it is fed back . Methods A theory-driven approach is used to describe six different applications of PROs in clinical practice . The evidence for the impact of these applications on the process and outcomes of care are summarised . Possible explanations for the limited impact of PROs on patient management are then discussed and directions for future research are highlighted . Results The applications of PROs in clinical practice include screening tools , monitoring tools , as a method of promoting patient-centred care , as a decision aid , as a method of facilitating communication amongst multidisciplinary teams ( MDTs ) , and as a means of monitoring the quality of patient care . Evidence from r and omised controlled trials suggests that the use of PROs in clinical practice is valuable in improving the discussion and detection of HRQoL problems but has less of an impact on how clinicians manage patient problems or on subsequent patient outcomes . Many of the reasons for this may lie in the ways in which PROs fit ( or do not fit ) into the routine ways in which patients and clinicians communicate with each other , how clinicians make decisions , and how healthcare as a whole is organised . Conclusions Future research needs to identify ways in with PROs can be better incorporated into the routine care of patients by combining qualitative and quantitative methods and adopting appropriate trial design PURPOSE / OBJECTIVES To evaluate the effectiveness of a psychoeducational program ( i.e. , PRO-SELF Pain Control Program ) compared to st and ard care in increasing patients ' knowledge regarding cancer pain management . DESIGN R and omized clinical trial . SETTING Seven outpatient setting s in northern California . SAMPLE 174 out patients with cancer and pain from bone metastasis . METHODS Following r and omization into either the PRO-SELF or st and ard care group , patients completed the Pain Experience Scale ( PES ) prior to and at the completion of the intervention . MAIN RESEARCH VARIABLES Total and individual item scores on the PES . FINDINGS Total PES knowledge scores increased significantly in the PRO-SELF group ( 21 % ) compared to the st and ard care group ( 0.5 % ) . Significant improvements in knowledge scores for patients in the PRO-SELF group were found on five of the nine PES items when compared to baseline scores . CONCLUSIONS The PRO-SELF Pain Control Program was an effective approach to increase patients ' knowledge of cancer pain management . IMPLICATION S FOR NURSING The use of a structured paper- and -pencil question naire , such as the PES , as part of a psychoeducational intervention provides an effective foundation for patient education in cancer pain management . Oncology nurses can use patients ' responses to this type of question naire to individualize the teaching and to spend more time on the identified knowledge deficits . This individualized approach to education about pain management may save staff time and improve patient outcomes & NA ; The effectiveness of a Pain Education Program in cancer patients with chronic pain offered by nurses was investigated in a r and omized controlled clinical trial . A multi‐ method approach was used in which verbal instruction , written material , an audio cassette tape , and the use of a pain diary were combined to inform and instruct patients about pain and pain management . The Pain Education Program was tailored to the needs of the individual patient and consisted of three elements : ( 1 ) educating patients about the basic principles regarding pain and pain management ; ( 2 ) instructing patients how to report their pain in a pain diary ; and ( 3 ) instructing patients how to communicate about pain and how to contact health care providers . Following pretesting in 313 patients , patients who needed district nursing and who did not need district nursing at home were r and omly assigned to a control or intervention group . Intervention group patients received the Pain Education Program in the hospital , and 3 and 7 days postdischarge by telephone ; this was done by nurses who were specially trained as pain counselors . Follow‐up assessment s were at 2 , 4 and 8 weeks postdischarge . Results of the pretest showed that many patients lacked knowledge about pain and pain management . The majority of pain topics had to be discussed . The Pain Education Program proved to be feasible : 75.0 % of the patients had read the entire pain brochure , 55.7 % had listened to the audio cassette , and 85.6 % of pain scores were completed in the pain diary . Results showed a significant increase in pain knowledge in patients who received the Pain Education Program and a significant decrease in pain intensity . However , pain relief was mainly found in the intervention group patients without district nursing . It can be concluded that the tailored Pain Education Program is effective for cancer patients in chronic pain . The use of the Pain Education Program by nurses should be seriously considered on oncology units PURPOSE Pain and symptom management is an integral part of the clinical practice of oncology . A number of guidelines have been developed to assist the clinician in optimizing comfort care . We implemented clinical guidelines for cancer pain management in the community setting and evaluated whether these guidelines improved care . PATIENTS AND METHODS Eighty-one cancer patients , aged 37 to 76 years , were enrolled onto a prospect i ve , longitudinal , r and omized controlled study from the outpatient clinic setting s of 26 western Washington-area medical oncologists . A multilevel treatment algorithm based on the Agency for Health Care Policy and Research Guidelines for Cancer Pain Management was compared with st and ard- practice ( control ) pain and symptom management therapies used by community oncologists . The primary outcome of interest was pain ( Brief Pain Inventory ) ; secondary outcomes of interest were all other symptoms ( Memorial Symptom Assessment Scale ) and quality of life ( Functional Assessment of Cancer Therapy Scale ) . RESULTS Patients r and omized to the pain algorithm group achieved a statistically significant reduction in usual pain intensity , measured as slope scores , when compared with st and ard community practice ( P < .02 ) . Concurrent chemotherapy and patient adherence to treatment were significant mediators of worst pain . There were no significant differences in other symptoms or quality of life between the two treatment groups . CONCLUSION This guideline implementation study supports the use of algorithmic decision making in the management of cancer pain . These findings suggest that comprehensive pain assessment and evidence -based analgesic decision-making processes do enhance usual pain outcomes Educational interventions , aim ing to increase patients ' knowledge and attitude regarding pain , can affect pain treatment . The purpose of this study was to evaluate the effects of a Pain Education Programme ( PEP ) , on adequacy of pain treatment , and to describe characteristics predicting change in adequacy . The PEP consists of a multi- method approach in which patients are educated about the basic principles regarding pain , instructed how to report pain in a pain diary , how to communicate about pain , and how to contact healthcare providers . The effects of the PEP were evaluated taking into consideration the lack of well-established outcome measures to evaluate adequacy of pain treatment , the lack of long-term follow-up , and the influence of missing data .A prospect i ve , r and omized study was utilized in which 313 chronic cancer patients were followed-up until 8 weeks postdischarge . Adequacy of pain treatment was evaluated by means of the Amsterdam Pain Management Index ( APMI ) , consisting of an integrated score of patients ' Present Pain Intensity , Average Pain Intensity , and Worst Pain Intensity , corrected for patients ' Tolerable Present Pain , with the analgesics used by the patient . At pretest , 60 % of the patients in the hospital were treated inadequately for their pain . Postdischarge , the control group patients were significantly more inadequately treated at 2 weeks after discharge ( 56 % vs 41 % ) , at 4 weeks after discharge ( 62 % vs 42 % ) and at 8 weeks after discharge ( 57 % vs 51 % ) than the intervention group patients . While the level of inadequacy in the control groups remained relatively stable at all assessment points , a slight increase in the percentage of patients being treated inadequately was found in the intervention group patients over time . A beneficial effect of the PEP was found for patients both with and without district nursing . Variables predicting an improvement in adequacy of pain treatment consisted of the PEP , the APMI score at baseline , patients ' level of physical functioning , patients ' level of social functioning , the extent of adherence to pain medication , patients ' pain knowledge , and the amount of analgesics used . These findings suggest that quality of pain treatment in cancer patients with chronic pain can be enhanced by educating patients about pain and improving active participation in their own pain treatment . The benefit from the PEP , however , decreases slightly over time , pointing at a need for ongoing education PURPOSE This r and omized clinical trial tested the effectiveness of the PRO-SELF Pain Control Program compared with st and ard care in decreasing pain intensity scores , increasing appropriate analgesic prescriptions , and increasing analgesic intake in oncology out patients with pain from bone metastasis . PATIENTS AND METHODS Patients were r and omly assigned to the PRO-SELF intervention ( n = 93 ) or st and ard care ( n = 81 ) . Patients in the st and ard care arm were seen by a research nurse three times and were called three times by phone between the home visits . PRO-SELF group patients were seen by specially trained intervention nurses and received a psychoeducational intervention , were taught how to use a pillbox , and were given written instructions on how to communicate with their physician about unrelieved pain and the need for changes in their analgesic prescriptions . Patients were coached during two follow-up home visits and three phone calls on how to improve their cancer pain management . RESULTS Pain intensity scores decreased significantly from baseline ( all P < .0001 ) in the PRO-SELF group ( ie , least pain , 28.4 % ; average pain , 32.5 % ; and worst pain , 27.0 % ) compared with the st and ard care group ( ie , least increased by 14.6 % , average increased by 1.9 % , and worst decreased by 1.2 % ) . The percentage of patients in the PRO-SELF group with the most appropriate type of analgesic prescription increased significantly from 28.3 % to 37.0 % ( P = .008 ) compared with a change from 29.6 % to 32.5 % in the st and ard care group . CONCLUSION The use of a psychoeducational intervention that incorporates nurse coaching within the framework of self-care can improve the management of cancer pain PURPOSE To examine the effects on process of care and patient well-being , of the regular collection and use of health-related quality -of-life ( HRQL ) data in oncology practice . PATIENTS AND METHODS In a prospect i ve study with repeated measures involving 28 oncologists , 286 cancer patients were r and omly assigned to either the intervention group ( regular completion of European Organization for Research and Treatment of Cancer-Core Quality of Life Question naire version 3.0 , and Hospital Anxiety and Depression Scale on touch-screen computers in clinic and feedback of results to physicians ) ; attention-control group ( completion of question naires , but no feedback ) ; or control group ( no HRQL measurement in clinic before encounters ) . Primary outcomes were patient HRQL over time , measured by the Functional Assessment of Cancer Therapy-General question naire , physician-patient communication , and clinical management , measured by content analysis of tape-recorded encounters . Analysis employed mixed-effects modeling and multiple regression . RESULTS Patients in the intervention and attention-control groups had better HRQL than the control group ( P = .006 and P = .01 , respectively ) , but the intervention and attention-control groups were not significantly different ( P = .80 ) . A positive effect on emotional well-being was associated with feedback of data ( P = .008 ) , but not with instrument completion ( P = .12 ) . A larger proportion of intervention patients showed clinical ly meaningful improvement in HRQL . More frequent discussion of chronic nonspecific symptoms ( P = .03 ) was found in the intervention group , without prolonging encounters . There was no detectable effect on patient management ( P = .60 ) . In the intervention patients , HRQL improvement was associated with explicit use of HRQL data ( P = .016 ) , discussion of pain , and role function ( P = .046 ) . CONCLUSION Routine assessment of cancer patients ' HRQL had an impact on physician-patient communication and result ed in benefits for some patients , who had better HRQL and emotional functioning PURPOSE : To determine the effectiveness of a clinical - practice intervention in improving the control of pain in out patients with cancer . METHOD : Between July 5 and September 30 , 1995 , a r and omized , controlled trial of 510 cancer out patients and 13 oncologists was conducted at 23 clinics in Indiana . All the patients completed assessment s of their pain , their pain regimens , and the degrees of relief received ; they were surveyed again by mail four weeks after their clinic visits . The intervention group 's clinical charts contained a summary of the completed pain scales ; the oncologists who treated these patients were instructed to review the summary sheet prior to an evaluation . This summary was not available for the oncologists treating the patients in the control group . Each patient 's pain management index ( PMI ) was calculated : the patient 's pain medication level was rated on a scale of 0 to 3 ; the patients 's pain level was rated on a scale of 0 to 3 and then subtracted from the first rating . A negative PMI was interpreted as representing insufficient treatment . Data were analyzed with several statistical tests . RESULTS : In all , only 320 patients who reported cancer-related pain were used in the analysis : 160 to 260 in the control group and 160 of 250 in the intervention group . The groups were similar with respect to demographics , cancer sites , and performance status . A significant difference ( p = .0162 ) in the physicians ' prescription patterns was found . In the control group , prescriptions for 86 % of the patients did not change , with no decrease in analgesic prescriptions ; for 14 % of the patients analgesic prescriptions increased . In the intervention group , analgesic prescriptions changed for 25 % of the patients , decreasing for 5 % and increasing for 20 % . A decrease in the incidence of pain described as more than life 's usual aches and pains was found for the intervention group ( p = .05 ) . No significant difference was found between the groups for the patients undertreated for pain , as measured by PMIs . CONCLUSION : Although analgesic regimens were altered significantly when the physicians understood more about the patient 's pain , cancer pain management remains a complex problem . Future studies should focus on the long-term systematic incorporation of simple pain- assessment tools into daily outpatient oncology practice s as well as on innovative ways to address other aspects of managing cancer pain Background : The undertreatment of cancer pain remains a significant clinical problem . Objective : The aim of this r and omized controlled trial was to evaluate the efficacy of the PRO-SELF Pain Control Program that was modified for Norwegian cancer patients in decreasing pain and increasing opioid intake compared with control care . Interventions / Methods : Oncology out patients with pain from bone metastasis were r and omized into the PRO-SELF ( n = 87 ) or control ( n = 92 ) groups . A nurse visited patients in the PRO-SELF group in their home at weeks 1 , 3 , and 6 and conducted telephone interviews at weeks 2 , 4 , and 5 . Patients in both groups completed a daily diary of pain intensity ratings and analgesic intake . Results : For both groups , significant decreases in pain intensity scores and in hours per day in pain ( both , P < .001 ) were found over the 6 weeks of the study . However , no significant group × time interactions were found for any of the pain measures . In both groups , total dose of opioid taken increased over time . However , no significant group × time interactions were found for changes over time in the total dose , around-the-clock dose , or as-needed dose of opioid analgesics taken . Conclusions : Possible reasons for the lack of efficacy include an inadequate dose of the psychoeducational intervention , inadequate changes in analgesic prescriptions , and /or the impact of attention provided to the control group . Implication s for Practice : Coaching , nursing support , and the use of a pain diary may be important interventions to reduce pain intensity PURPOSE Patients receiving cancer-related thoracotomy are highly symptomatic in the first weeks after surgery . This study examined whether at-home symptom monitoring plus feedback to clinicians about severe symptoms contributes to more effective postoperative symptom control . PATIENTS AND METHODS We enrolled 100 patients receiving thoracotomy for lung cancer or lung metastasis in a two-arm r and omized controlled trial ; 79 patients completed the study . After hospital discharge , patients rated symptoms twice weekly for 4 weeks via automated telephone calls . For intervention group patients , an e-mail alert was forwarded to the patient 's clinical team for response if any of a subset of symptoms ( pain , disturbed sleep , distress , shortness of breath , or constipation ) reached a predetermined severity threshold . No alerts were generated for controls . Group differences in symptom threshold events were examined by generalized estimating equation modeling . RESULTS The intervention group experienced greater reduction in symptom threshold events than did controls ( 19 % v 8 % , respectively ) and a more rapid decline in symptom threshold events . The difference in average reduction in symptom interference between groups was -0.36 ( SE , 0.078 ; P = .02 ) . Clinicians responded to 84 % of e-mail alerts . Both groups reported equally high satisfaction with the automated system and with postoperative symptom control . CONCLUSION Frequent symptom monitoring with alerts to clinicians when symptoms became moderate or severe reduced symptom severity during the 4 weeks after thoracic surgery . Methods of automated symptom monitoring and triage may improve symptom control after major cancer surgery . These results should be confirmed in a larger study PURPOSE The purpose of this trial was to evaluate the effect of a Web-based , self-report assessment and educational intervention on symptom distress during cancer therapy . PATIENTS AND METHODS A total of 752 ambulatory adult participants were r and omly assigned to symptom/ quality -of-life ( SxQOL ) screening at four time points ( control ) versus screening , targeted education , communication coaching , and the opportunity to track/graph SxQOL over time ( intervention ) . A summary of the participant-reported data was delivered to clinicians at each time point in both groups . All participants used the assessment before a new therapeutic regimen , at 3 to 6 weeks and 6 to 8 weeks later , completing the final assessment at the end of therapy . Change in Symptom Distress Scale-15 ( SDS-15 ) score from pretreatment to end of study was compared using analysis of covariance and regression analysis adjusting for selected variables . RESULTS We detected a significant difference between study groups in mean SDS-15 score change from baseline to end of study : 1.27 ( st and ard deviation [ SD ] , 6.7 ) in the control group ( higher distress ) versus -0.04 ( SD , 5.8 ) in the intervention group ( lower distress ) . SDS-15 score was reduced by an estimated 1.21 ( 95 % CI , 0.23 to 2.20 ; P = .02 ) in the intervention group . Baseline SDS-15 score ( P < .001 ) and clinical service ( P = .01 ) were predictive . Multivariable analyses suggested an interaction between age and study group ( P = .06 ) ; in subset analysis , the benefit of intervention was strongest in those age > 50 years ( P = .002 ) . CONCLUSION Web-based self-care support and communication coaching added to SxQOL screening reduced symptom distress in a multicenter sample of participants with various diagnoses during and after active cancer treatment . Participants age > 50 years , in particular , may have benefited from the intervention |
1,860 | 26,825,411 | Antibiotics were the most efficacious therapy but with a higher incidence of systemic side effects .
Vaginal estrogen appeared to be inferior to continuous oral antibiotic suppression ; however , use of multiple formulations of both treatment options precludes meta- analysis .
This review supports the use of antibiotic suppression , vaginal estrogen , and oral lactobacillus for prevention of recurrent UTIs in postmenopausal women .
However , the overall dearth of data suggests that this is an important but understudied population . | OBJECTIVES The purpose of this systematic review was to evaluate and summarize pharmacological interventions evaluated in r and omized clinical trials design ed to prevent recurrent episodes of urinary tract infections ( UTIs ) in postmenopausal women . | Objective To assess the efficacy and safety of intravaginal estriol administration on urinary incontinence , urogenital atrophy , and recurrent urinary tract infections in postmenopausal women . Design Eighty-eight postmenopausal women with urogenital aging symptoms were enrolled in this prospect i ve , r and omized , placebo-controlled study . Participants were r and omly divided into two groups , with each group consisting of 44 women . Women in the treatment group received intravaginal estriol ovules : 1 ovule ( 1 mg ) once daily for 2 weeks and then 2 ovules once weekly for a total of 6 months as maintenance therapy . Women in the control group received inert placebo vaginal suppositories in a similar regimen . We evaluated urogenital symptomatology , urine cultures , colposcopic findings , urethral cytologic findings , urethral pressure profiles , and urethrocystometry before as well as after 6 months of treatment . Results After therapy , the symptoms and signs of urogenital atrophy significantly improved in the treatment group in comparison with the control group . Thirty ( 68 % ) of the treated participants , and only seven ( 16 % ) of the control participants registered a subjective improvement of their incontinence . In the treated participants , we observed significant improvements of colposcopic findings , and there were statistically significant increases in mean maximum urethral pressure , in mean urethral closure pressure as well as in the abdominal pressure transmission ratio to the proximal urethra . Urethrocystometry showed positive but not statistically significant modifications . Conclusions Our results show that intravaginal administration of estriol may represent a satisfactory therapeutic choice for those postmenopausal women with urogenital tract disturbances who have contraindications or refuse to undergo st and ard hormone therapy Abstract Purpose To assess the effects of the combination of pelvic floor rehabilitation , intravaginal estriol and Lactobacillus acidophli administration on stress urinary incontinence ( SUI ) , urogenital atrophy and recurrent urinary tract infections in postmenopausal women . Methods 136 postmenopausal women with urogenital aging symptoms were enrolled in this prospect i ve r and omized study . Patients : r and omly divided into two groups and each group consisted of 68 women . Interventions : Subjects in the triple therapy ( group I ) received 1 intravaginal ovule containing 30 mcg estriol and Lactobacilli acidophili ( 50 mg lyophilisate containing at least 100 million live bacteria ) such as once daily for 2 weeks and then two ovules once weekly for a total of 6 months as maintenance therapy plus pelvic floor rehabilitation . Subjects in the group II received one intravaginal estriol ovule ( 1 mg ) plus pelvic floor rehabilitation in a similar regimen . Mean outcome measures : We evaluated urogenital symptomatology , urine cultures , colposcopic findings , urethral cytologic findings , urethral pressure profiles and urethrocystometry before , as well as after 6 months of treatment . Results After therapy , the symptoms and signs of urogenital atrophy significantly improved in both groups . 45/59 ( 76.27 % ) of the group I and 26/63 ( 41.27 % ) of the group II referred a subjective improvement of their incontinence . In the patients treated by triple therapy with lactobacilli , estriol plus pelvic floor rehabilitation , we observed significant improvements of colposcopic findings , and there were statistically significant increases in mean maximum urethral pressure , in mean urethral closure pressure , as well as in the abdominal pressure transmission ratio to the proximal urethra . Conclusions Our results showed that triple therapy with L. acidophili , estriol plus pelvic floor rehabilitation was effective and should be considered as first-line treatment for symptoms of urogenital aging in postmenopausal women We compared the efficacy and safety of estriol-containing vaginal pessary use with those of oral nitrofurantoin macrocrystal ( NM ) therapy for preventing urinary tract infection ( UTI ) in postmenopausal women with recurrent UTI . Over a period of 9 months , 86 women received an estriol-containing vaginal pessary ( 0.5 mg estriol ) twice weekly , and 85 women received NM ( 100 mg ) once daily . We recorded 124 episodes of UTI in women who received estriol-releasing pessaries and 48 episodes of UTI in women treated with NM ( P=.0003 ) . Twenty-eight women ( 32.6 % ) who received estriol had no episodes of UTI versus 41 women ( 48.2 % ) in the NM group . There was a significant increase in the number of superficial cells in women who received estriol , whereas in the NM group , no such changes occurred . However , there was no change in the extent of Lactobacillus colonization and in the vaginal pH in women who received estriol . Use of an estriol-containing pessary is less effective than oral NM therapy in the prevention of bacteriuria in postmenopausal women because of its failure to restore the population of lactobacilli and to reduce the vaginal pH in these women OBJECTIVE The primary objective was to detect a difference in time until the first recurrence of urinary tract infection during treatment with an estradiol-releasing silicone vaginal ring ( Estring ; Pharmacia & Upjohn , Inc , Uppsala , Sweden ) compared with no estrogen treatment . The secondary objective was to detect any differences in improvement of urethral and vaginal mucosal atrophy and in the subjective assessment of urogenital symptoms . The study also sought to detect a difference in decrease of vaginal pH to < 5.5 and to record adverse events . STUDY DESIGN This was a multicenter , r and omized , open , parallel-group study with an untreated control group . Postmenopausal women with recurrent symptomatic , bacteriologically confirmed urinary tract infections were r and omly assigned to receive either Estring ( 2 mg estradiol ) or no estrogen treatment . One ring was carried vaginally for 12 weeks . The duration of treatment was 36 weeks for the Estring group and either 36 weeks or until the first recurrence for the control group . Both intent-to-treat and per- protocol analyses were performed to evaluate efficacy , whereas the safety analysis was limited to the intent-to-treat group . The primary variable was analyzed by survival analysis with the Kaplan-Meier method for estimating the survival density function . To compare the survival curves for the 2 treatment groups a log-rank test was performed for time until first recurrence . RESULTS A total of 108 women were r and omly assigned , 53 to the Estring group and 55 to the control group . The cumulative proportion of women remaining free of urinary tract infection was significantly higher in the Estring group than in the control group ( P = .008 ) . After 36 weeks of study the cumulative likelihood of remaining free of disease was approximately 45 % in the women with the vaginal ring compared with approximately 20 % in the control group . Estring lowered vaginal pH , and the time to first recurrence was effectively prolonged by Estring treatment . Vaginal and , to a lesser extent , urethral mucosal cells were significantly more mature in the Estring group . No unexpected adverse events were found . CONCLUSION Estring is useful to prolong the time to next recurrence among postmenopausal women with recurrent urinary tract infection and to decrease the number of recurrences per year . The silicone vaginal ring also has a clinical ly significant ability to alleviate other postmenopausal urogenital symptoms . Estring is safe and well tolerated A block r and omized , double-blind , group-comparative , placebo-controlled study was conducted to assess the effect of oestriol on recurrent urinary tract infections in postmenopausal women . 40 women , median age 78 years ( 66 - 91 ) , 20 in each group , were treated with oestriol three mg p.o . per day or corresponding placebo for four weeks , followed by one mg per day for eight weeks . The main response parameter was the number of urinary tract infections per week in the two treatment periods . Both oestriol and placebo reduced the number of infections per week significantly in both periods , compared with the pretreatment period . There was no difference between oestriol and placebo treatment in the first period . In the second period , however , oestriol treatment was significantly more effective than placebo ( p = 0.05 ) . Correspondingly , there was a significant difference between the two groups in the vaginal pH at the end of the study ( p less than 0.05 ) . We conclude that oestriol reduces recurrent urinary tract infections in postmenopausal women BACKGROUND Growing antibiotic resistance warrants study ing nonantibiotic prophylaxis for recurrent urinary tract infections ( UTIs ) . Use of lactobacilli appears to be promising . METHODS Between January 2005 and August 2007 , we r and omized 252 postmenopausal women with recurrent UTIs taking part in a double-blind noninferiority trial to receive 12 months of prophylaxis with trimethoprim-sulfamethoxazole , 480 mg , once daily or oral capsules containing 109 colony-forming units of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 twice daily . Primary end points were the mean number of symptomatic UTIs , proportion of participants with at least 1 UTI during 12 months , time to first UTI , and development of antibiotic resistance by Escherichia coli . RESULTS The mean number of symptomatic UTIs in the year preceding r and omization was 7.0 in the trimethoprim-sulfamethoxazole group and 6.8 in the lactobacilli group . In the intention-to-treat analysis , after 12 months of prophylaxis , these numbers were 2.9 and 3.3 , respectively . The between-treatment difference of 0.4 UTIs per year ( 95 % CI , -0.4 to 1.5 ) was outside our noninferiority margin . At least 1 symptomatic UTI occurred in 69.3 % and 79.1 % of the trimethoprim-sulfamethoxazole and lactobacilli participants , respectively ; median times to the first UTI were 6 and 3 months , respectively . After 1 month of trimethoprim-sulfamethoxazole prophylaxis , resistance to trimethoprim-sulfamethoxazole , trimethoprim , and amoxicillin had increased from approximately 20 % to 40 % to approximately 80 % to 95 % in E coli from the feces and urine of asymptomatic women and among E coli causing a UTI . During the 3 months after trimethoprim-sulfamethoxazole discontinuation , resistance levels gradually decreased . Resistance did not increase during lactobacilli prophylaxis . CONCLUSIONS In postmenopausal women with recurrent UTIs , L rhamnosus GR-1 and L reuteri RC-14 do not meet the noninferiority criteria in the prevention of UTIs when compared with trimethoprim-sulfamethoxazole . However , unlike trimethoprim-sulfamethoxazole , lactobacilli do not increase antibiotic resistance . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N50717094 BACKGROUND Recurrent urinary tract infections are a problem for many postmenopausal women . Estrogen replacement restores atrophic mucosa , lowers vaginal pH , and may prevent urinary tract infections . METHODS We enrolled 93 postmenopausal women with a history of recurrent urinary tract infections in a r and omized , double-blind , placebo-controlled trial of a topically applied intravaginal estriol cream . Midstream urine cultures were obtained at enrollment , monthly for eight months , and whenever urinary symptoms occurred . Vaginal cultures and pH measurements were obtained at entry and after one and eight months . The women were assigned to receive either estriol ( n = 50 ) or placebo ( n = 43 ) , both administered intravaginally ; 36 and 24 , respectively , completed the eight months of follow-up . RESULTS The incidence of urinary tract infection in the group given estriol was significantly reduced as compared with that in the group given placebo ( 0.5 vs. 5.9 episodes per patient-year , P < 0.001 ) . Survival analysis showed that more of the women in the estriol group than in the placebo group remained free of urinary tract infection ( P < 0.001 ) . Lactobacilli were absent in all vaginal cultures before treatment and reappeared after one month in 22 of 36 estriol-treated women ( 61 percent ) but in none of the 24 placebo recipients ( P < 0.001 ) . With estriol the mean vaginal pH declined from 5.5 to 3.8 ( P < 0.001 ) , whereas there was no significant change with placebo . The rate of vaginal colonization with Enterobacteriaceae fell from 67 percent to 31 percent in estriol recipients but was virtually unchanged ( from 67 to 63 percent ) in the placebo recipients ( P < 0.005 ) . Side effects were minor , but caused 10 estriol recipients ( 28 percent ) and 4 placebo recipients ( 17 percent ) to discontinue treatment . CONCLUSIONS The intravaginal administration of estriol prevents recurrent urinary tract infection in postmenopausal women , probably by modifying the vaginal flora This study evaluated patient-initiated single-dose antibiotic prophylaxis and continuous long-term low-dose daily antibiotic use for the prevention of recurrent urinary tract infections ( UTI ) in 68 postmenopausal women . The women were r and omized to take a low-dose antibiotic each night ( continuous group , n = 37 ) or a single-dose antibiotic each time they experienced conditions predisposing to UTI ( intermittent group , n = 31 ) . During the 12-month study , 1.4 and 1.9 UTIs/patient developed in the continuous and the intermittent groups , respectively , which was significantly lower than the incidence of UTIs in the previous 12 months in these patients ( 4.7 and 5.1 UTIs/patient , respectively ) . The incidence of gastrointestinal adverse events was significantly lower in the intermittent group compared with the continuous group ( 9.1 % versus 30.0 % ) . In conclusion , patient-initiated single-dose intermittent antibiotic prophylaxis was as effective as low-dose daily antibiotic prophylaxis in the treatment of recurrent UTIs in postmenopausal women and was associated with fewer gastrointestinal adverse events Acute lower urinary tract infections ( UTIs ) are common in adult women , and as many as 6 % of members of the adult female population experience 3 or more episodes during a given year.1 In 1995 , an estimated 11.3 million women in the United States received antibiotic treatment for at least 1 presumed UTI , result ing in associated costs of $ 1.6 billion during that year.2 Women with frequently recurrent cystitis may need prophylactic antibacterial treatment . However , such treatment may result in development of antimicrobial resistance , which is a medical problem of increasing concern.3 A recent study indicated that the rate of cystitis among cystitis-prone women treated with acupuncture was one third the rate among untreated women and half the rate among women treated by sham acupuncture ( shallow needling outside known acupuncture points).4 In the present study , we sought to evaluate the effect of acupuncture treatment in preventing uncomplicated recurrent lower UTIs among adult nonpregnant women OBJECTIVE To assess the efficacy of oral oestriol in the prevention of recurrent urinary tract infections in elderly women . DESIGN Double-blind , r and omised , parallel group , placebo controlled trial SETTING Urogynaecology Unit at King 's College Hospital with some women recruited from the geriatric units of St. Pancras Hospital and Dulwich Hospital , London ( UK ) . PARTICIPANTS Seventy-two postmenopausal women older than 60 years of age ( mean 73.2 years ) suffering from recurrent urinary tract infections . INTERVENTION Oral oestriol ( 3 mg per day ) or placebo for six months . MAIN : outcome measures Urinary tract infection rates . RESULTS The study was difficult to conduct because of its design and the age of the participants . Oral oestriol ( 3 mg per day ) was not shown to be superior to placebo in the prevention of recurrent urinary tract infections , but both oestriol and placebo improved urinary symptoms during the trial . CONCLUSION The power of the study might have been too low to detect a significant difference between the groups , or oral oestriol ( 3 mg per day ) may have been either the wrong dose or the wrong route of administration for this indication UNLABELLED Lack of estrogen affects the urinary tract mainly by diminishing vascular , muscular and epithelial trophism , result ing in negative effects on continence in postmenopausal women . Therefore , the use of estrogens in these patients may revert these alterations and lead to an expressive improvement of the urinary symptoms . OBJECTIVE Study the effect of topical estrogen therapy ( conjugated equine estrogens , estriol or promestriene ) in periurethral vessels detected by Dopplervelocimetric analysis using , as parameters : the number of vessels , resistance and pulsatility indexes , as well as the minimum diastolic value . METHODS Forty-one postmenopausal women with stress urinary incontinence were r and omized into three groups according to different types of topical estrogen received during 3 months . Group 1 received conjugated equine estrogens , group 2 received estriol and group 3 received promestriene . Periurethral Dopplervelocimetry analysis was done before estrogen administration and during treatment in all groups . RESULTS We observed an increase in the number of the periurethral vessels in group 1 and group 2 , being higher in group 1 than in group 2 . The pulsatility index remained unchanged in all three groups . The resistance index at the periurethral vessels reduced only at the conjugated estrogen group ( group 1 ) . In this same group we noticed an increase in the mean minimal diastolic value , meaning a better periurethral vascularization . CONCLUSION Topical conjugated equine estrogens and estriol were effective in increasing the number of periurethral vessels in postmenopausal women with urinary stress incontinence , with the conjugated equine estrogens being the most effective intervention studied |
1,861 | 25,064,039 | Based on our results we can conclude that there is evidence for exercise-induced increase in voluntary activation related to strength gains in the lower extremities in elderly persons . | Age-related muscle weakness is only partially related to muscle atrophy , due to neuromuscular changes including reduced voluntary muscle activation and antagonist muscle co-activation .
The respective contribution of these mechanisms in exercise-induced strength gains at higher age is unclear . | The purpose of this study was to determine whether strength training could reduce the deficit in plantarflexion ( PF ) maximal voluntary contraction ( MVC ) torque observed in previous studies in older subjects relative to young adults . Accordingly , the effects of a 6-month strength training program on the muscle and neural properties of the major muscle groups around the ankle were examined . PF and dorsiflexion ( DF ) isometric MVC torques were measured and surface electromyographic activity of the triceps surae and tibialis anterior muscles was recorded . The strength training program was very effective in improving strength in PF ( + 24.5 % ) , and it thus reduced the DF-to-PF MVC torque ratio ; in addition , it also induced gains in DF ( + 7.6 % ) . Thus , there must be an improvement in ankle joint stability . In PF , gains were due particularly to a modification of the agonist neural drive ; in DF , the gains appeared to be the consequence of a reduction in antagonist coactivation . Our findings indicate that the investigation of one muscle group should always be accompanied by examination of its antagonist muscle group Effects of 6 mo of heavy-resistance training combined with explosive exercises on neural activation of the agonist and antagonist leg extensors , muscle cross-sectional area ( CSA ) of the quadriceps femoris , as well as maximal and explosive strength were examined in 10 middle-aged men ( M40 ; 42 + /- 2 yr ) , 11 middle-aged women ( W40 ; 39 + /- 3 yr ) , 11 elderly men ( M70 ; 72 + /- 3 yr ) and 10 elderly women ( W70 ; 67 + /- 3 yr ) . Maximal and explosive strength remained unaltered during a 1-mo control period with no strength training . After the 6 mo of training , maximal isometric and dynamic leg-extension strength increased by 36 + /- 4 and 22 + /- 2 % ( P < 0 . 001 ) in M40 , by 36 + /- 3 and 21 + /- 3 % ( P < 0.001 ) in M70 , by 66 + /- 9 and 34 + /- 4 % ( P < 0.001 ) in W40 , and by 57 + /- 10 and 30 + /- 3 % ( P < 0.001 ) in W70 , respectively . All groups showed large increases ( P < 0.05 - 0.001 ) in the maximum integrated EMGs ( iEMGs ) of the agonist vastus lateralis and medialis . Significant ( P < 0.05 - 0.001 ) increases occurred in the maximal rate of isometric force production and in a squat jump that were accompanied with increased ( P < 0.05 - 0 . 01 ) iEMGs of the leg extensors . The iEMG of the antagonist biceps femoris muscle during the maximal isometric leg extension decreased in both M70 ( from 24 + /- 6 to 21 + /- 6 % ; P < 0.05 ) and in W70 ( from 31 + /- 9 to 24 + /- 4 % ; P < 0.05 ) to the same level as recorded for M40 and W40 . The CSA of the quadriceps femoris increased in M40 by 5 % ( P < 0.05 ) , in W40 by 9 % ( P < 0.01 ) , in W70 by 6 % ( P < 0.05 ) , and in M70 by 2 % ( not significant ) . Great training-induced gains in maximal and explosive strength in both middle-aged and elderly subjects were accompanied by large increases in the voluntary activation of the agonists , with significant reductions in the antagonist coactivation in the elderly subjects . Because the enlargements in the muscle CSAs in both middle-aged and elderly subjects were much smaller in magnitude , neural adaptations seem to play a greater role in explaining strength and power gains during the present strength-training protocol Twenty sedentary male university students were r and omly assigned to an experimental or a control group . The experimental group trained the knee extensors of one leg by producing 30 isometric extension maximal voluntary contractions ( MVC ) per day , three times per week for 8 wk . After 8 wk of training , extensor MVC in the trained leg increased 32.8 % ( P less than 0.05 ) , but there was no change in vastus lateralis maximal integrated electromyographic activity ( IEMGmax ) . The most important finding was that the degree of hamstring coactivation during extension MVC decreased by approximately 20 % ( P less than 0.05 ) after the 1st wk of training . Less pronounced adaptations occurred in the untrained leg : extension MVC force increased 16.2 % ( P less than 0.05 ) , hamstring coactivity decreased 13 % ( P less than 0.05 ) after 2 wk of training , and vastus lateralis IEMGmax was unchanged . The same measures in legs of the control group were not changed during the study . There were no changes in flexion MVC , biceps femoris IEMGmax , or the degree of quadriceps coactivity during flexion MVC in either leg of the control or experimental group . A reduction in hamstring coactivity in the trained and untrained legs indicates that these muscles provide less opposing force to the contracting quadriceps . We conclude that this small but significant decrease in hamstring coactivation that occurs during the early stages of training is a nonhypertrophic adaptation of the neuromuscular system in response to static resistance training of this type We compared the effect of a 10‐week resistance training program on peak isometric torque , muscle hypertrophy , voluntary activation and electromyogram signal amplitude ( EMG ) of the knee extensors between young and elderly women . Nine young women ( YW ; range 20–30 years ) and eight elderly women ( EW ; 64–78 years ) performed three sets of ten repetitions at 75 % 1 repetition maximum for the bilateral leg extension and bilateral leg curl 3 days per week for 10 weeks . Peak isometric torque , EMG and voluntary activation were assessed before , during , and after the training period , while knee extensor lean muscle cross‐sectional area ( LCSA ) and lean muscle volume ( LMV ) were assessed before and after the training period only . Similar increases in peak isometric torque ( 16 % and 18 % ) , LCSA ( 13 % and 12 % ) , LMV ( 10 % and 9 % ) and EMG ( 19 % and 21 % ) were observed between YW and EW , respectively , at the completion of training ( P<0·05 ) , while the increase in voluntary activation in YW ( 1·9 % ) and EW ( 2·1 % ) was not significant ( P>0·05 ) . These findings provide evidence to indicate that participation in regular resistance exercise can have significant neuromuscular benefits in women independent of age . The lack of change in voluntary activation following resistance training in both age groups despite the increase in EMG may be related to differences between measurements in their ability to detect resistance training‐induced changes in motor unit activity . However , it is possible that neural adaptation did not occur and that the increase in EMG was due to peripheral adaptations The aim of this study was to enquire whether older adults , who continue plantar-flexion ( PF ) strength training for an additional 6-month period , would achieve further improvements in neuromuscular performance , in the ankle PFs , and in the antagonist dorsi-flexors ( DFs ) . Twenty-three healthy older volunteers ( mean age 77.4 ± 3.7 years ) took part in this investigation and 12 of them followed a 1-year strength-training program . Both neural and muscular factors were examined during isometric maximal voluntary contraction ( MVC ) torques in ankle PF and DF pre-training , post 6 and post 12 months . The main finding was that 6 months of additional strength training of the PFs , beyond 6 months , allowed further improvements in neuromuscular performance at the ankle joint in older adults . Indeed , during the first 6 months of progressive resistance training , there was an increase in the PF MVC torque of 11.1 ± 19.9 N m , and then of 11.1 ± 17.9 N m in the last 6-month period . However , it was only after 1 year that there was an improvement in the evoked contraction at rest in PF ( + 8 % ) . The strength training of the agonist PF muscles appeared to have an impact on the maximal result ant torque in DF . However , it appeared that this gain was first due to modifications occurring in the trained PFs muscles , then , it seemed that the motor drive of the DFs per se was altered . In conclusion , long-term strength training of the PFs result ed in continued improvements in neuromuscular performance at the ankle joint in older adults , beyond the initial 6 months 1 . The adaptations of the ankle dorsiflexor muscles and the behaviour of single motor units in the tibialis anterior in response to 12 weeks of dynamic training were studied in five human subjects . In each training session ten series of ten fast dorsiflexions were performed 5 days a week , against a load of 30 - 40 % of the maximal muscle strength . 2 . Training led to an enhancement of maximal voluntary muscle contraction ( MVC ) and the speed of voluntary ballistic contraction . This last enhancement was mainly related to neural adaptations since the time course of the muscle twitch induced by electrical stimulation remained unaffected . 3 . The motor unit torque , recorded by the spike-triggered averaging method , increased without any change in its time to peak . The orderly motor unit recruitment ( size principle ) was preserved during slow ramp contraction after training but the units were activated earlier and had a greater maximal firing frequency during voluntary ballistic contractions . In addition , the high frequency firing rate observed at the onset of the contractions was maintained during the subsequent spikes after training . 4 . Dynamic training induced brief ( 2 - 5 ms ) motor unit interspike intervals , or ' doublets ' . These doublets appeared to be different from the closely spaced ( + /-10 ms ) discharges usually observed at the onset of the ballistic contractions . Motor units with different recruitment thresholds showed doublet discharges and the percentage of the sample of units firing doublets was increased by training from 5.2 to 32.7 % . The presence of these discharges was observed not only at the onset of the series of spikes but also later in the electromyographic ( EMG ) burst . 5 . It is likely that earlier motor unit activation , extra doublets and enhanced maximal firing rate contribute to the increase in the speed of voluntary muscle contraction after dynamic training Explosive-type strength training may alter kinetics and neuromuscular activity during stair ascent in elderly women . This may improve functional ability . Nineteen women ( 69.7 ± 3.4 yr ) were r and omly allocated to strength training ( TG ; twice per wk , 12 wk ) or a control group ( CG ) . Stair ascent was assessed at self-chosen ( AFV ) , st and ardized ( ASV ) , and maximal velocity ( AMV ) pre- and posttraining . Ground-reaction force ( GRF ) and EMG quantified kinetics and neuromuscular activity . After training , TG increased AMV and AFV velocity by 8 % ( p = .02 ) and 17 % ( p= .007 ) , respectively ( TG vs. CG ; p < .05 ) . This was accompanied by elevated rectus femoris EMG ( from 21 % to 48 % , p < .047 ) . At AFV , TG increased GRF first peak force 4 % ( p= .047 ) , and CG increased second peak force 5 % ( p = .036 ) . Muscle coactivation remained unaltered in both groups . Explosive-type strength training led to enhanced stair-climbing performance at maximal and self-chosen speed , reflecting an improved functional ability PURPOSE To test the ability of a combination high-velocity/high-resistance training program to enhance knee extensor muscle strength , power , nervous activation of muscle , and muscle activation time in inactive women and compare the response to training between young and old women . METHODS The study involved 49 inactive women , with young ( 18 - 33 yr , n = 25 ) and old ( 65 - 84 yr , n = 24 ) distributed to training and control groups using blocked r and omization . Electrically evoked muscle twitches were measured for the knee extensors ; then maximal , voluntary , isometric knee extensions were performed in a visually cued reaction time ( RT ) task , followed by 8 wk of explosive resistance training . RESULTS Training increased peak torque ( + 12 % , P = 0.03 ) and reduced antagonist coactivation ( -13 % , P = 0.02 ) similarly for both age groups . Young training group increased the rate of torque development by 34 % compared to young controls ( -7 % ) , old training ( + 9 % ) , and old controls ( + 8 % ) ( P = 0.002 ) . Young training group increased impulse by 53 % , which was greater than young controls ( -11 % ) , old training ( + 12 % ) , and old controls ( + 9 % ) ( P = 0.001 ) . Resistance training did not change electrically evoked twitch , RT ( premotor time , motor time , or reaction time ) , or nervous activation measures ( onset EMG amplitude or rate of EMG rise ) . CONCLUSIONS Explosive force training was ineffective at enhancing muscle twitch characteristics , neural drive , or RT in young or old women . It did enhance peak muscle force in both young and old , modulated through a reduction in antagonist coactivation . Older participants showed less of an improvement in the rate of torque development and contractile impulse than young , indicating either that this sample of older women had a reduced capacity to develop muscle power or that the 8-wk isokinetic resistance training program used in this study was not a sufficient stimulus for adaptation Six young ( mean = 23 years ) and 6 older ( mean = 76 years ) adults participated in isometric resistance training 5 days/week for 6 weeks . The task involved isometric fifth finger abduction . Maximal motor unit discharge rates ( MUDRs ) were obtained from the abductor digiti minimi of each h and at 0 , 2 , 14 , and 42 days of training using a quadrifilar needle electrode and automatic spike recognition software . In agreement with previous findings , maximal MUDR at baseline was significantly lower in older adults ( P < 0.001 ) , averaging 51.5 ( + /-17.13 ) HZ in young and 43.3 ( + /-14.88 ) HZ in older adults . In response to resistance training , maximal voluntary force increased 25 % in young and 33 % in older subjects ( P < 0.001 ) . Maximal MUDR increased significantly ( 11 % young , 23 % older ) on day 2 [ F(3,36 ) = 2.58 , P < 0.05 ] , but in older subjects returned to baseline levels thereafter . These adaptations in abductor digiti minimi MUDR suggest a two-part response to strengthening fifth finger abduction : early disinhibition followed by altered MU activation This study investigated changes in elderly muscle joint angle-torque relation induced by resistance training . Older adults were assigned to either training ( n = 9 , age 74.3 + /- 3.5 years ; mean + /-s.d . ) or to control groups ( n = 9 , age 67.1 + /- 2 years ) . Leg-extension and leg-press exercises were performed three times per week for 14 weeks . Maximal isometric knee extension torque was measured across the knee joint angle range of movement . Vastus lateralis muscle architecture was examined in vivo using ultrasonography . The vastus lateralis muscle fascicle force was estimated from the measured joint torque , enabling construction of the fascicle length-force relation . Electromyographic ( EMG ) activity was measured from representative agonist and antagonist muscles . Training altered the angle-torque relation : ( a ) displacing it by 9 - 31 % towards higher torque values ( P < 0.05 ) ; and ( b ) shifting the optimal angle from 70 deg ( corresponding torque : 121.4 + /- 61 N m ) before to 60 deg ( 134.2 + /- 57.2 N m ; P < 0.05 ) after training . Training also altered the fascicle length-force relation : ( a ) displacing it by 11 - 35 % towards higher force values ; and ( b ) shifting the optimal fascicle length from 83.7 + /- 8 mm ( corresponding force : 847.9 + /- 365.3 N ) before to 93.2 + /- 12.5 mm ( 939.3 + /- 347.8 N ; P < 0.01 ) after training . The upward displacement of the angle-torque relation was mainly due to a training-induced increase in agonist activation , whilst the shift in the optimal angle was associated with changes in muscle-tendon properties |
1,862 | 26,991,855 | Oligomeric alpha-synuclein might be helpful in the separation of PD from controls .
Neurofilament light chain ( NfL ) has a significant role in distinguishing PD from other neurodegenerative diseases .
Several oxidative stress markers are related to disease severity , with the antioxidant urate also having a prognostic value in terms of disease severity .
Increased levels of amyloid and tau-proteins correlate with cognitive decline and may have prognostic value for cognitive deficits in PD . | Diagnosis of Parkinson 's disease ( PD ) relies on clinical history and physical examination , but misdiagnosis is common in early stages .
Identification of biomarkers for PD may allow early and more precise diagnosis and monitoring of dopamine replacement strategies and disease modifying treatments .
Developments in analytical chemistry allow the detection of large numbers of molecules in plasma or cerebrospinal fluid , associated with the pathophysiology or pathogenesis of PD .
Through metabolomics , changes in purine and tryptophan metabolism have been discovered in patients with PD . | Neuropsychological ( mostly posterior-cortical ) deficits , quantitative magnetic resonance imaging ( MRI ) atrophy patterns , and low cerebrospinal fluid ( CSF ) levels of amyloid-β have been separately related to worsening cognition in Parkinson 's disease ( PD ) . However , these biomarkers have not been longitudinally assessed in combination as PD-dementia predictors . In this prospect i ve longitudinal study , 27 non-demented PD patients underwent CSF , neuropsychological and 3-T brain-MRI studies at baseline and were re-assessed 18 months later in terms of progression to dementia ( primary outcome ) and longitudinal neuropsychological and cortical thickness changes ( secondary outcomes ) . At follow-up 11 patients ( 41 % ) had progressed to dementia . Lower CSF amyloid-β , worse verbal learning , semantic fluency and visuoperceptual scores , and thinner superior-frontal/anterior cingulate and pre central regions were significant baseline dementia predictors in binary logistic regressions as quantitative and /or dichotomised traits . All participants without baseline biomarker abnormalities remained non-demented whereas all with abnormalities in each biomarker type progressed to dementia , with intermediate risk for those showing abnormalities in a single to two biomarker types ( p = 0.006 ) . Both the dementia- outcome and low baseline CSF amyloid-β were prospect ively associated with limbic and posterior-cortical neuropsychological decline and frontal , limbic and posterior-cortical thinning from baseline to follow-up . These findings suggest that the combination of CSF amyloid-β , neuropsychological and cortical thickness biomarkers might provide a basis for dementia-risk stratification and progression monitoring in PD Objective : To test in vivo the proposal from clinicopathologic studies that β-amyloid ( Aβ ) pathology shortens the time to dementia in Parkinson disease ( PD ) , and to explore the utility of CSF Aβ and related measures as early prognostic biomarkers of dementia in an incident PD cohort . Methods : We assessed a population -based incident cohort of 104 patients with PD who underwent lumbar puncture at diagnosis . We analyzed CSF concentrations of Aβ42 , Aβ40 , and Aβ38 using a multiplexed immunoassay with electrochemiluminescence ( ECL ) detection and levels of Aβ42 , total tau , and phosphorylated tau using ELISA . Patients were followed prospect ively for 5 years . Dementia was diagnosed according to published criteria . Results : CSF levels of Aβ42 were significantly decreased in patients who developed dementia ( n = 20 , 19.2 % ) compared to those who did not ( n = 84 , 80.8 % ) , as measured by ECL ( −33 % , p = 0.006 ) as well as ELISA ( −36 % , p < 0.001 ) . No differences were observed for other markers . Low Aβ42 values predicted a substantially increased risk for subsequent dementia at high sensitivity ( ≥85 % ) , with hazard ratios of 9.9 ( 95 % confidence interval 2.3–43.5 , p = 0.002 ) for Aβ42ECL < 376 pg/mL and 7.6 ( 2.2–26.4 , p = 0.001 ) for Aβ42ELISA < 443 pg/mL , after adjustment for baseline age and PD – mild cognitive impairment ( MCI ) status . Aβ42 reductions tended to precede the onset of PD-MCI that progressed to dementia . Conclusions : These in vivo data support the role of Aβ pathology in the etiology and highlight the potential utility of CSF Aβ42 as an early prognostic biomarker of dementia associated with PD Few detailed clinico-pathological correlations of Parkinson 's disease have been published . The pathological findings in 100 patients diagnosed prospect ively by a group of consultant neurologists as having idiopathic Parkinson 's disease are reported . Seventy six had nigral Lewy bodies , and in all of these Lewy bodies were also found in the cerebral cortex . In 24 cases without Lewy bodies , diagnoses included progressive supranuclear palsy , multiple system atrophy , Alzheimer 's disease , Alzheimer-type pathology , and basal ganglia vascular disease . The retrospective application of recommended diagnostic criteria improved the diagnostic accuracy to 82 % . These observations call into question current concepts of Parkinson 's disease as a single distinct morbid entity Cerebrospinal fluid ( CSF ) biomarkers for Alzheimer ’s disease ( AD ) reflect brain biochemistry . Using combined immunoprecipitation and mass spectrometry , we have shown that amyloid beta 1 - 15 ( Aβ1 - 15 ) is produced by concerted β- and α-secretase cleavage of amyloid precursor protein ( APP ) and that the relative levels of Aβ1 - 16 in AD compared to controls are increased . Furthermore , drug-induced γ-secretase inhibition enhances the relative levels of Aβ1 - 15 and Aβ1 - 16 . Here , we investigate a novel immunoassay for Aβ1 - 15/16 in a broad range of neurodegenerative conditions . The CSF level of Aβ1 - 15/16 was measured by the bead-based amplified luminescent proximity homogeneous assay ( Alpha technology ) . Concentrations of Aβ1 - 15/16 were analyzed in subjects with Parkinson disease ( PD ; n = 90 ) , PD with dementia ( PDD ) ( n = 32 ) , dementia with Lewy bodies ( DLB ) ( n = 68 ) , AD ( n = 48 ) , progressive supranuclear palsy ( PSP ) ( n = 45 ) , multiple system atrophy ( MSA ) ( n = 46 ) , and corticobasal degeneration ( CBD ) ( n = 12 ) . The detecting antibody is specific to the C-terminal epitope of Aβ15 . We found that a carboxypeptidase ( CPB ) present in fetal bovine serum ( FBS ) , a component of the buffers used , de grade s Aβ1 - 16 to Aβ1 - 15 , which is then detected by the Aβ1 - 15/16 assay . Significantly , lower levels of Aβ1 - 15/16 were detected in PD , PDD , PSP , and MSA compared to other neurodegenerative diseases and controls . Using the specific Aβ1 - 15/16 assay , a reliable quantification of Aβ1 - 15 or Aβ1 - 15/16 in CSF sample s is obtained . We found reduced levels of Aβ1 - 15 in parkinsonian disease groups . The molecular mechanism behind this reduction is at present unknown Differential diagnosis between Parkinson 's disease ( PD ) and multiple system atrophy ( MSA ) is difficult , particularly at early disease stages , but is important for therapeutic management . The protein DJ-1 is implicated in the pathology of PD but little is known about its involvement in MSA . We aim ed to determine the diagnostic value of CSF DJ-1 and tau proteins for discriminating PD and MSA . DJ-1 and total tau levels were quantified in the CSF of 43 PD patients , 23 MSA patients and 30 non-neurological controls matched for age and gender . Patients were part of a study with a 3-year prospect i ve design with extended case- review follow-up of up to 9 years , ensuring maximum accuracy of the clinical diagnosis . Our results showed that CSF DJ-1 levels could distinguish MSA from PD with a 78 % sensitivity and 78 % specificity ( AUC = 0.84 ) . The combination of DJ-1 and tau proteins significantly improved this discrimination to 82 % sensitivity and 81 % specificity to identify MSA from PD ( AUC = 0.92 ) . Our results highlight the potential benefits of a combination of DJ-1 and total tau as biomarkers for differential diagnosis of MSA and PD In order to investigate the possible role of oxidative RNA damage in the pathogenesis of Parkinson 's disease ( PD ) , the concentrations of the oxidative stress marker 8-hydroxyguanosine ( 8-OHG ) were measured in the cerebrospinal fluid ( CSF ) and the serum of patients with PD and control subjects . The concentration of 8-OHG in CSF in PD patients was approximately three-fold that in controls ( P < 0.001 ) . The concentration of 8-OHG in CSF decreased significantly with the duration of disease ( r(s ) = -0.46 , P < 0.05 ) . However , the concentration of 8-OHG in serum was not significantly altered in PD patients compared to that in controls . In addition , the concentration of 8-OHG in CSF showed no correlation with that in serum in both the controls and PD patients suggesting that the 8-OHG concentrations in the CSF do not reflect those in serum and may be probably reflect those in brain tissue . These in vivo findings suggest a possible role of 8-OHG and increased oxidative RNA damage in the early stage of the development of PD Objective : Cognitive decline associated with Parkinson disease ( PD ) is common and highly disabling . Biomarkers that help identify patients at risk for cognitive decline would be useful additions to the clinical management of the disease . Methods : A total of 45 patients with PD were enrolled in this prospect i ve cohort study and had at least 1 yearly longitudinal follow-up evaluation . CSF was collected at baseline and cognition was assessed at baseline and follow-up visits using the Mattis Dementia Rating Scale ( DRS-2 ) . CSF was tested for amyloid β 1 - 42 ( Aβ1 - 42 ) , p-tau181p , and total tau levels using the Luminex xMAP platform . Mixed linear models were used to test for associations between baseline CSF biomarker levels and change in cognition over time . Results : Lower baseline CSF Aβ1 - 42 was associated with more rapid cognitive decline . Subjects with CSF Aβ1 - 42 levels ≤192 pg/mL declined an average of 5.85 ( 95 % confidence interval 2.11–9.58 , p = 0.002 ) points per year more rapidly on the DRS-2 than subjects above that cutoff , after adjustment for age , disease duration , and baseline cognitive status . CSF total tau and p-tau181p levels were not significantly associated with cognitive decline . Conclusions : Reduced CSF Aβ1 - 42 was an independent predictor of cognitive decline in patients with PD . This observation is consistent with previous research showing that Alzheimer disease pathology contributes to cognitive impairment in PD . This biomarker may provide clinical ly useful prognostic information , particularly if combined with other risk factors for cognitive impairment in PD Abstract – DATA TOP is a double‐blind , multi‐center , placebo‐controlled clinical trial aim ed at slowing the decline of patients who are in the early stages of Parkinson 's disease ( PD ) . The specific aim is to determine whether or not chronic administration of deprenyl 10 mg per day and /or tocopherol 2000 IU per day to early , otherwise untreated PD patients will prolong the time until levodopa therapy is required to treat emerging disability . Deprenyl and tocopherol exert antioxidative effects through separate but complementary mechanisms of action . A 2 X 2 factorial design allocates eligible subjects to one of four treatment groups : 1 ) deprenyl alone , 2 ) tocopherol alone , 3 ) deprenyl plus tocopherol , or 4 ) placebo . Eligible subjects include early PD patients ( illness duration less than 5 years and in stages I and II ) , aged 30 to 79 , who are not taking or requiring any anti‐PD medications . The major response variable is the time period from r and omization until the blinded investigator judges levodopa necessary to treat emerging parkinsonian disability . R and omization is stratified to ensure that treatment assignments are balanced for each blinded investigator . Cerebrospinal fluid is sample d just prior to r and omization and one month after washout of experimental medications in order to help distinguish between symptomatic and protective effects of interventions . Based on pilot studies it is estimated that approximately 85 % of untreated PD patients will require levodopa within two years and a total sample size of 800 subjects will provide a 95 % likelihood for detecting a 10 % “ survival'’difference between experimental medications and placebo . Between September 1987 and November 1988 , 800 eligible subjects were enrolled in DATA TOP by 34 investigators of the Parkinson Study Group , representing research centers in the United States and Canada . Primary analyses of DATA TOP should be completed in 1991 |
1,863 | 17,636,709 | Although both trials reported a positive effect from occupational therapy , all of the improvements were small .
Considering the significant method ological flaws in the studies , the small number of patients examined , and the possibility of publication bias , there is insufficient evidence to support or refute the efficacy of occupational therapy in Parkinson 's disease . | BACKGROUND Despite drug and surgical therapies for Parkinson 's disease , patients develop progressive disability .
It has both motor and non-motor symptomatology , and their interaction with their environment can be very complex .
The role of the occupational therapist is to support the patient and help them maintain their usual level of self-care , work and leisure activities for as long as possible .
When it is no longer possible to maintain their usual activities , occupational therapists support individuals in changing and adapting their relationship with their physical and social environment to develop new valued activities and roles .
OBJECTIVES To compare the efficacy and effectiveness of occupational therapy with placebo or no interventions ( control group ) in patients with Parkinson 's disease . | There is some evidence that rehabilitation therapies may be useful in progressive neurological conditions , but this usefulness has not been studied in multiple system atrophy ( MSA ) to date . The aim of this small pilot study was to identify the feasibility of a larger r and omized controlled trial of occupational therapy and to report preliminary data on the impact of occupational therapy on disability , mood , and health-related quality of life in patients with MSA . Patient groups were comparable for age , gender distribution , type of MSA , and severity . The active occupational therapy intervention group experienced a significant reduction of Unified Parkinson 's Disease Rating Scale ( total score and Activities of Daily Living [ ADL ] section ) , and PDQ-39 scores ( total scores and ADL subsection ) . An occupational therapy program may improve functional abilities in patients with mild to moderate MSA . A larger multicenter study is needed BACKGROUND Several previous studies have examined the health of carers , but they have usually focused on elderly subjects and have often not had representative control sample s. AIM To determine whether caring for a partner with Parkinson 's disease is associated with a worsening social , psychological and physical well-being than people with partners who do not suffer with Parkinson 's disease . METHOD One hundred and fifty-four carer spouses of subjects with Parkinson 's disease , and 124 non-carer spouses of r and omly selected population controls recruited from a national case-control study of early-onset Parkinson 's disease in the Republic of Irel and , between 1992 - 1994 , were studied . Outcome was measured along three dimensions : social functioning , assessed by the frequency of social contacts , outings and holidays ; psychological well-being , measured by the General Health Question naire ; and physical health , measured by the career 's use of medical services , medications and episodes of chronic illness . RESULTS Carer spouses were less likely to get out of the house once a week at least ( odds ratio 1.79 , 95 % confidence intervals 1.00 - 3.20 ) or to have had a holiday in the last year ( odds ratio 1.71 , 95 % confidence intervals 1.01 - 2.90 ) . Contact with friends and neighbours decreased with increasing care provision . For spouses providing a lot of care , there was an almost fivefold increase in psychiatric morbidity ( odds ratio 4.86 , 95 % confidence intervals 1.5 - 15.9 ) after adjusting for other variables . Most of the medical outcomes were less favourable among carers , but only the use of tranquilizers ( odds ratio 3.73 , 95 % confidence intervals 1.18 - 11.8 ) and episodes of chronic illness ( odds ratio 2.96 , 95 % confidence intervals 1.27 - 6.94 ) were significant . CONCLUSIONS Overall , career spouses have slightly worse social , psychological and physical profiles . For social outcomes , increasing care provision is associated with fewer contacts , outings and holidays . For psychological and physical measures , carers providing a lot of care experience worse health . These results have implication s for targeting appropriate interventions The medical treatment of idiopathic Parkinson 's disease has improved the quality of life and increased survival of patients with Parkinson 's disease . However , as the illness progresses , impairments in daily living activities occur . A clinical trial for a group rehabilitation program was initiated to maintain the functional status of these patients . The research protocol consisted of a pretreatment evaluation , r and om assignment to experimental or control groups , and posttreatment evaluations after therapy , at 6 months and at 1 year . The results showed that the subjects of the treated experimental group maintained their functional status after 1 year , demonstrated a significant decrease of bradykinesia , and perceived a significant improvement in their psychological well-being . This study confirms the value of an occupational therapy group approach and its benefits to the functional independence , to the improvement of physical and motor symptoms , and to the quality of life of persons with Parkinson 's disease The development and validation of a short and simple measure of perceived health problems is described . Extensive testing with selected groups , including the elderly , the chronically ill , pregnant women , fracture victims , and a r and om sample of the community has established the face , content and criterion validity , and the reliability of the instrument . The Nottingham Health Profile is intended as a st and ardized tool for the survey of health problems in a population , but is equally valid and useful as a means of evaluating the outcome of medical and /or social interventions and as an adjunct to the clinical interview In a controlled clinical study , we investigated the effects of behavioral treatment on postural and gait initiation problems idiopathic Parkinson 's disease ( PD ) . Comparable groups of patients received therapy ( experimental group , n = 15 ) and nonspecific psychological treatment ( control group , n = 14 ) for 10 weeks . We monitored various variables reflecting properties of posture and gait initiation by using an optoelectronic motion analyzer ( electronic movement analysis system , ELITE ) . A clinician blind to group membership of the patients assessed PD severity with the United Parkinson 's Disease Rating Scale ( UPDRS ) before and after the treatment period . ELITE measures of postural stability and movement initiation revealed treatment-specific effects . In addition , UPDRS motor scores showed significant improvement only after behavioral treatment . We conclude that behavioral treatment in Parkinson 's disease may improve motor disabilities in moderately advanced PD patients Objective : To perform a pilot trial of occupational therapy ( OT ) to optimise functional independence in Parkinson disease ( PD ) to assess accrual/withdrawal rates , acceptability , outcome measures , and inform sample -size calculation . Method : Non-demented patients with idiopathic PD and difficulties with activities of daily living ( ADL ) were recruited provided they had not received OT in the last 2 years and /or physiotherapy in the last year . Patients were r and omised to immediate OT or OT after completion of the trial . Patients r and omised to OT were assessed at home by an experienced therapist and then received six home treatment sessions over 2 months . Interventions were targeted at functional independence and mobility goals . Outcome measures were : Nottingham Extended Activity of Daily Living Scale , Rivermead Mobility Index , Unified Parkinson ’s Disease Rating Scale ADL scale , Parkinson ’s Disease Question naire 39 , EuroQol-EQ-5D , Hospital Anxiety and Depression Scale , and health economics analysis . Results : 39 patients ( 25 male ; mean age 73 years ) were recruited from four centres over 16 months . The mean difference in NEADL at 8 months was 3.5 ( 95 % CI −3.2 to 10.2 ) . The mean difference in PDQ-39 Summary Score was 3.8 ( 95 % CI −4.94 to 12.6 ) . There were strong correlations between the PDQ-39 and other outcomes . The intervention was acceptable to patients , with a low withdrawal rate and good question naire completion . Conclusion : R and omisation to a trial of OT in PD is feasible . NEADL and PDQ-39 are relevant outcomes and provided data to inform sample size for an adequately powered r and omised trial for which there is pressing need Objective : To evaluate the effects of weights on postural h and tremor related to self-feeding in subjects with Parkinson 's disease ( PD ) . Design : In a repeated- measures design , postural h and tremor was recorded three times in each of three weight conditions in a single session for each subject . The order of all recording conditions was r and omized . Setting : Intervention was applied and measurement was conducted in a university-based motor performance laboratory . Subjects : Fourteen men and two women diagnosed with PD and having h and tremor participated ( mean age 67.1 years , mean duration of PD 4.6 years ) . All were community-dwelling . Intervention : The control condition consisted of holding a built-up spoon ( 108 g ) . There were two experimental conditions : holding a weighted spoon ( 248 g ) ; and holding the built-up spoon while wearing a weighted wrist cuff ( 470 g ) . Main outcome measures : Three measures of tremor amplitude and two measures of tremor frequency were calculated from recordings of displacement of the spoon obtained from laser displacement sensors . Results : Repeated- measures analyses of variance revealed no signi”cant differences across conditions in any measure of tremor amplitude or in either measure of tremor frequency . Correlational and Mann – Whitney U-test analyses revealed that none of age , disease duration or medication intake had any signi”cant relationship with tremor amplitude in the control condition or with whether amplitude was altered by weights . Conclusions : The ” ndings suggest that there is no support for the clinical recommendation of using weighted utensils or weighted wrist cuffs to alleviate postural h and tremor in PD In a r and omized , single-blind , crossover study , we evaluated physical disability in moderately advanced Parkinson 's disease ( PD ) patients after 4 weeks of normal physical activity and 4 weeks of an intensive physical rehabilitation program . We used a timed motor task and a st and ard assessment of PD severity ( the Unified Parkinson 's Disease Rating Scale [ UPDRS ] with subscales for mentation , activities of daily living [ ADL ] , and motor function ) completed by an investigator blinded to the physical rehabilitation status of the patient . Following physical rehabilitation , there was significant improvement in the UPDRS ADL and motor scores , but no change in mentation score . During the 6 months following physical rehabilitation , patients did not regularly exercise , and the UPDRS scores returned to baseline . We conclude that physical disability in moderately advanced PD objective ly improves with a regular physical rehabilitation program , but this improvement is not sustained when normal activity is resumed Gibberd and others ( 11 April , p 1196 ) and sympathise over the problems they encountered . In a similar controlled trial ' we had difficulty in making due allowance for spontaneous fluctuations in motor performance and concentration which characterise this illness and particularly in assessing the influence of depression and motivation . We had to ab and on attempts to measure the latter factors with appropriate question naires because we often found that the patients fell asleep during assessment . Transport difficulties can prove a major obstacle and tend to influence selection of patients . Exhausting journeys to hospital made some patients underst and ably reluctant to attend twice weekly for outpatient physiotherapy and some became so rigid in anticipation of belated transport that they were unable to leave their home . In addition to organisational difficulties , there seems to be little agreement concerning the principles and methods of physiotherapy appropriate for Parkinsonian disabilities . Nevertheless , we found modest but unequivocal improvement in 10 of 21 patients , and in seven benefit was sustained for at least five weeks after the cessation of treatment . We could not determine whether improvement was physical , psychological , or both . Now that the limitations as well as the potential of antiParkinsonian medication has been determined , clinicians will want to know how best to use diminishing physiotherapy re sources . Clearly there is a need for further trials to clarify these common practical problems of management Ottenbacher KJ , Hinderer SR : Evidence -based practice : methods to evaluate individual patient improvement . Am J Phys Med Rehabil 2001;80:786–796.The expectations and dem and s associated with evidence -based practice in medical rehabilitation require the use of research procedures that are practice based and practitioner oriented . Traditional research methods , including r and omized clinical trials , are powerful techniques for determining the efficacy of rehabilitation interventions ; however , r and omized clinical trials have some practical and ethical limitations when applied to many research questions important to the field of medical rehabilitation , and alternative methods are needed to fully examine the effectiveness of treatment techniques for individual patients and to document clinical accountability . This paper examines the use of single-system design s and N of 1 research strategies . The advantages and limitations of single-system methods are described , and examples relevant to the documentation of clinical outcomes in medical rehabilitation are presented |
1,864 | 23,979,963 | Conclusion Based on this systematic review , we concluded that the uptake of more advanced statistical methods has been relatively slow , while simpler naïve methods are still routinely employed | Background National regulatory agencies often have to use cost-effectiveness ( CE ) data from multinational r and omized controlled trials ( RCTs ) for national decision making on reimbursement of new drugs .
We need to make the best use of these patient-level data to obtain estimates of country-specific CE .
Several methods , ranging from simple to statistically complex , have existed for years .
We investigated which of these methods are used to estimate CE ratios in economic evaluations performed alongside recent , multinational RCTs that enrolled at least 500 patients . | Background : Daivobet ® is a once-daily treatment of psoriasis vulgaris containing betamethasone dipropionate and calcipotriol in a new ointment vehicle . Objective : To assess the cost-effectiveness of once-daily treatment with Daivobet ( 4 weeks ) followed by calcipotriol ( 4 weeks ) compared to tacalcitol ( 8 weeks ) . Methods : Re source utilization was assessed within a double-blind 8-week clinical trial ( all treatments for psoriasis , adverse events and concomitant dermatological medication ) , estimated from the French societal perspective . Results : Total direct medical costs for psoriasis were comparable ( Daivobet : EUR 107.53 and tacalcitol EUR 113.50 ) despite a higher acquisition cost for Daivobet . The probability of ≧75 % reduction in the Psoriasis Area and Severity Index ( effectiveness criterion ) was 46.6 % with Daivobet and 13.9 % with tacalcitol at 4 weeks , and 44.6 and 23.8 % , respectively , at 8 weeks ( both : p < 0.001 ) . Over 8 weeks , Daivobet was almost twice as cost-effective as tacalcitol ( EUR 241.22 per successful treatment vs. EUR 476.70 ) ; this result was robust to sensitivity assumptions . Conclusion : Daivobet is more effective and less costly than tacalcitol for treating psoriasis BACKGROUND Overall assessment s of cost-effectiveness are now commonplace in informing medical policy decision making . It is often important , however , also to investigate how cost-effectiveness varies between patient subgroups . Yet such analyses are rarely undertaken , because appropriate methods have not been sufficiently developed . METHODS We propose a coherent set of Bayesian methods to extend cost-effectiveness analyses to adjust for baseline covariates , to investigate differences between subgroups , and to allow for differences between centres in a multicentre study using a hierarchical model . These methods consider costs and effects jointly , and allow for the typically skewed distribution of cost data . The results are presented as inferences on the cost-effectiveness plane , and as cost-effectiveness acceptability curves . RESULTS In applying these methods to a r and omised trial of case management of psychotic patients , we show that overall cost-effectiveness can be affected by ignoring the skewness of cost data , but that it may be difficult to gain substantial precision by adjusting for baseline covariates . While analyses of overall cost-effectiveness can mask important subgroup differences , crude differences between centres may provide an unrealistic indication of the true differences between them . CONCLUSIONS The methods developed allow a flexible choice for the distributions used for cost data , and have a wide range of applicability -- to both r and omised trials and observational studies . Experience needs to be gained in applying these methods in practice , and using their results in decision making Few studies have compared preference values for health states obtained in different countries . The present study compared Spanish and United Kingdom ( UK ) time trade-off values for EuroQol-5D health states . The same preference elicitation protocol was followed in both countries . Differences in values for 43 health states rated directly were analyzed using t tests , and regression coefficients generated by r and om effects modeling were compared by aggregating the 2 value sets and using dummy variables to analyze country effect by dimension and level of severity . For the milder health states , Spanish and UK value assignation was similar ; for intermediate health states , Spanish values were both higher and lower than UK values , whereas for health states worse than death , UK values were generally higher than Spanish values . There were statistically significant differences ( P < 0.01 ) in values for 34.9 % of health states rated directly , and some preference reversals between countries . UK raters ascribed greater importance to dimensions of pain/discomfort and anxiety/depression , whereas Spanish raters placed more importance on functional dimensions of mobility and self-care . Further analysis is required to determine how these differences affect cost-effectiveness and cost-utility analyses Background —In the Eplerenone Post-Acute Myocardial Infa rct ion Heart Failure Efficacy and Survival Study ( EPHESUS ) , aldosterone blockade with eplerenone decreased mortality in patients with left ventricular systolic dysfunction and heart failure after acute myocardial infa rct ion . The present study was performed to evaluate the cost-effectiveness of eplerenone compared with placebo in these patients . Methods and Results —A total of 6632 patients with left ventricular systolic dysfunction and heart failure after acute myocardial infa rct ion were r and omized to eplerenone or placebo and followed up for a mean of 16 months . The co primary end points were all-cause mortality and the composite of cardiovascular mortality/cardiovascular hospitalization . The evaluation of re source use included hospitalizations , outpatient services , and medications . Eplerenone was priced at the average wholesale price , $ 3.60 per day . Survival beyond the trial period was estimated from data from the Framingham Heart Study , the Saskatchewan Health data base , and the Worcester Heart Attack Registry . The incremental cost-effectiveness of eplerenone in cost per life-year and quality -adjusted life-year gained compared with placebo was estimated . The number of life-years gained with eplerenone was 0.1014 based on Framingham ( 95 % CI , 0.0306 to 0.1740 ) , 0.0636 with Saskatchewan ( 95 % CI , 0.0229 to 0.1038 ) , and 0.1337 with Worcester ( 95 % CI , 0.0438 to 0.2252 ) data . Cost was $ 1391 higher over the trial period in the eplerenone arm ( 95 % CI , 656 to 2165 ) because of drug cost . The incremental cost-effectiveness ratio was $ 13 718 per life-year gained with Framingham ( 96.7 % under $ 50 000 per life-year gained ) , $ 21 876 with Saskatchewan , and $ 10 402 with Worcester . Conclusions —Eplerenone compared with placebo in the treatment of heart failure after acute myocardial infa rct ion is effective in reducing mortality and is cost-effective in increasing years of life by commonly used criteria The TOwards a Revolution in COPD Health ( TORCH ) study was a 3-yr multicentre trial of 6,112 patients r and omised to salmeterol ( Salm ) , fluticasone propionate ( FP ) , a Salm/FP combination ( SFC ) or placebo ( P ) . Here the cost-effectiveness of treatments evaluated in the TORCH study is assessed . For four regions , 3-yr all-cause hospitalisation , medication and outpatient care costs were calculated . The sample was restricted to the 21 countries ( n = 4,237 ) in which European quality of life five-dimension ( EQ-5D ) data were collected in order to estimate the number of quality -adjusted life years ( QALYs ) . Regression models were fitted to survival , study medication cost , other medication cost and EQ-5D data in order to estimate total cost , number of QALYs and cost per QALY , adjusted for missing data and region . SFC had a trial-wide estimate of cost per QALY of 43,600 US dollars ( USD ) compared with P ( 95 % confidence interval 21,400–123,500 USD ) . Estimates for Salm versus P ( 197,000 USD ) and FP versus P ( 78,000 USD ) were less favourable . The US estimates were greater than those from other regions ; for SFC versus P , the cost per QALY was 77,100 ( 46,200–241,700 ) USD compared to 24,200 ( 15,200–56,100 ) USD in Western Europe . Compared with P , SFC has a lower incremental cost-effectiveness ratio than either FP or Salm used alone , and is , therefore , preferred to these monotherapies on the grounds of cost-effectiveness BACKGROUND Allergic rhinoconjunctivitis is a global health problem . Around 14 million people in Spain , France , Italy , and Austria suffer from grass pollen induced allergic rhinitis . St and ard care only provides symptoms relief , while allergen specific immunotherapy ( SIT ) treats the underlying cause of the disease . Grazax from ALK-Abelló is a new , tablet-based , effective route of SIT for home treatment . The objective was to assess the cost-effectiveness of Grazax in four Southern European countries . METHODS A prospect i ve pharmacoeconomic analyses was carried out alongside a multinational , clinical trial measuring the efficacy of Grazax . Pooled data on re source use and health outcomes were collected . A societal perspective was adopted , and the analysis had a nine-year time horizon . The primary outcome measure was quality adjusted life years ( QALYs ) . RESULTS Grazax was superior to st and ard care for all efficacy endpoints , including QALYs gained , and result ed in significantly less use of rescue medication and fewer hours missed from work . Grazax was cost-effective for all countries for an annual price in the range of 1500 euros - 1900 euros . The result was improved by inclusion of future costs of asthma and exclusion of Spanish trial centers which experienced an exceptionally low pollen season . CONCLUSION The analysis illustrates that allergen SIT with Grazax for grass pollen induced rhinoconjunctivitis is a cost-effective intervention in Southern Europe OBJECTIVES We sought to evaluate the long-term cost-effectiveness of clopidogrel for up to one year after an acute coronary syndrome ( ACS ) without ST-segment elevation . BACKGROUND The efficacy of platelet inhibition with clopidogrel for up to one year after ACS was demonstrated in the Clopidogrel in Unstable angina to prevent Recurrent Events ( CURE ) trial , a r and omized trial of 12,562 patients in 28 countries that was conducted between 1998 and 2000 . Patients were given clopidogrel ( 300-mg load followed by 75 mg/day ) versus placebo , both in addition to aspirin , for a mean of nine months . METHODS We used patient-level clinical outcomes and re source use from the CURE trial and estimates of life expectancy gains as a result of the prevention of the clinical events of death , stroke , and myocardial infa rct ion on the basis of data from external sources . RESULTS Excluding clopidogrel costs , average costs of hospitalizations alone were 325 dollars less for the clopidogrel arm ( 95 % confidence interval -722 dollars to 45 dollars ) using diagnosis-related group-based Medicare reimbursement rates . When including clopidogrel costs ( 766 dollars greater for the clopidogrel arm ) , average total costs were 442 dollars higher for the clopidogrel arm ( 95 % confidence interval 62 dollars to 820 dollars ) . The incremental cost-effectiveness ratio ( ICER ) on the basis of the Framingham Heart Study was 6,318 dollars per life-year gained ( LYG ) with clopidogrel , with 94 % of bootstrap-derived ICER estimates < 50,000 dollars/LYG ; based on Saskatchewan , the ICER was 6,475 dollars/LYG with 98 % of estimates < 50,000 dollars . CONCLUSIONS Platelet inhibition with clopidogrel in patients for up to one year after presentation with an acute coronary syndrome is both effective and cost-effective Abstract : Background : Everolimus decreases acute rejection and cardiac allograft vasculopathy after heart transplantation . We compared within‐trial costs and re source use over 1 yr of follow‐up in de novo heart transplant patients r and omized to everolimus 1.5 mg/d ( n = 209 ) , everolimus 3.0 mg/d ( n = 211 ) , or azathioprine ( n = 214 ) OBJECTIVES We used a U.S. model of health care costs to examine the cost effectiveness of enoxaparin compared with unfractionated heparin ( UFH ) as adjunctive therapy for fibrinolysis in patients with ST-segment elevation myocardial infa rct ion ( STEMI ) . BACKGROUND The ExTRACT-TIMI 25 ( Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infa rct ion Treatment-Thrombolysis In Myocardial Infa rct ion 25 ) study , a large , r and omized , multinational trial , demonstrated a reduction in death or nonfatal myocardial infa rct ion when enoxaparin was used instead of UFH as adjunctive therapy for fibrinolysis in patients with STEMI . METHODS We used patient-level clinical outcomes and re source use from the ExTRACT-TIMI 25 trial and estimates of life expectancy gains as a result of the prevention of the clinical events on the basis of the Framingham Heart Study . RESULTS Index hospitalization costs trended lower by $ 126 in the enoxaparin group ( 95 % confidence interval [ CI ] : -$295 to $ 49 ) . Thirty-day costs trended higher by $ 102 for enoxaparin ( 95 % CI : $ 108 to $ 314 ) . Patients receiving enoxaparin gained an average of 0.12 life-years relative to patients given UFH . Estimated total lifetime costs were $ 1,207 higher in the enoxaparin group ( 95 % CI : $ 491 to $ 1,923 ) . The incremental cost-effectiveness ratio of enoxaparin compared with UFH was $ 5,700 per life-year gained , with 99.9 % of bootstrap-derived estimates < $ 50,000 per life-year gained . Using a probabilistic sensitivity analysis , there is a 90 % probability that enoxaparin is cost effective for lifetime , provided that the willingness-to-pay value exceeds $ 50,000 . CONCLUSIONS Based on a U.S. model of health care economics , the strategy of using enoxaparin instead of UFH as adjunctive therapy for fibrinolysis in patients with STEMI is cost effective according to commonly used benchmarks Abstract Background : The positive results of a r and omised clinical trial of rivastigmine in patients with dementia associated with Parkinson ’s disease have been published recently . Patient-level healthcare utilisation data were also collected , and this report is the economic evaluation based on these data . Objective : To determine the cost effectiveness of rivastigmine 3–12 mg/day in patients in whom mild to moderate dementia developed at least 2 years after they received a clinical diagnosis of Parkinson ’s disease . Methods : A cost-effectiveness analysis was performed by applying Canadian and UK cost weights ( year 2004 values ) to healthcare utilisation data collected prospect ively during a r and omised , double-blind , multinational , 24-week trial of rivastigmine 3.12 mg/day ( n = 362 ) versus placebo ( n = 179 ) . Patients were ≥50 years of age , had a Mini-Mental State Examination ( MMSE ) score of between 20 and 24 and had contact with a responsible caregiver at least 3 days a week . Quality -adjusted survival time , transformed from MMSE scores , was the measure of effectiveness . Caregiver costs included paid and unpaid time , and direct costs included concomitant medications , outpatient care , hospitalisations , long-term care and study medications . Analysis was conducted from a societal perspective with a time horizon of 24 weeks . Results : Consistent with the improvement in clinical outcomes , there was an observed increase in quality -adjusted survival time in the rivastigmine arm of 2.81 quality -adjusted life-days ( two-sided p-value 0.13 [ 90 % CI −0.243 , 5.86 ] ) . Using Canadian price weights , there was an observed increase in cost in the rivastigmine arm of $ Can55.76 ( two-sided p-value 0.98 [ 90 % CI −3431 , 3543 ] ) , with a result ing incremental cost-effectiveness ratio of $ Can7429 per QALY . Using UK price weights , there was an observed decrease in cost in the rivastigmine arm of £ 26.18 ( two-sided p-value 0.99 [ 90 % CI −2407 , 2355 ] ) . Conclusion : Although no between-treatment differences in cost were seen , the small sample size , highly variable cost distributions and short time horizon prevent us from making strong conclusions with regard to the effect of rivastigmine on total costs and , by inference , on cost effectiveness Abstract Objective : To compare the healthcare costs and effects of budesonide/formoterol in a single inhaler with those of budesonide and formoterol monotherapies , and placebo , in a multinational study in patients with chronic obstructive pulmonary disease ( COPD ) , National Heart , Lung and Blood Institute (NHLBI)/WHO Global Initiative for Chronic Obstructive Lung Disease ( GOLD ) stages III or IV . Previous analysis of the clinical data from the study had shown that budesonide/formoterol was associated with better lung function and improved health-related QOL compared with the monocomponents or placebo and lower frequency of exacerbations compared with formoterol and placebo . Method : Patients ( n = 1022 ) were r and omised to twice-daily treatment with two inhalations of budesonide/formoterol ( 160μg/4.5μg ) in a single inhaler , budesonide 200μg , formoterol 4.5μg or placebo for 12 months . Data on medication and healthcare use were combined with Swedish unit cost data to estimate the total annual healthcare cost per patient from the Swedish healthcare payer perspective . Costs were valued in Swedish kronor ( SEK ) [ 2001 values ] and converted to euros ( SEK1 = € 0.11 , 25th April 2003 ) . Results : This evaluation estimated the total annual healthcare costs per patient to be numerically lower for budesonide/formoterol ( € 2518 ) than for budesonide ( € 3194 ) , formoterol ( € 3653 ) or placebo ( € 3213 ) . Cost-effectiveness acceptability curves suggest that budesonide/formoterol may be cost effective compared with formoterol , even if the decision maker is not willing to pay anything for the additional clinical effects , and that budesonide/formoterol is cost effective compared with placebo if a decision maker is willing to pay about € 2 per day , per avoided exacerbation . Conclusion : This economic analysis suggests that the clinical benefits of using budesonide/formoterol in a single inhaler are achieved at a numerically lower total healthcare cost than either monocomponent or placebo . Budesonide/formoterol in patients with severe COPD ( GOLD stages III or IV ) may be cost effective , from the healthcare provider perspective , compared with either monocomponent Health care cost-effectiveness analysis ( CEA ) often uses individual patient data ( IPD ) from multinational r and omized controlled trials . Although design ed to account for between-patient sampling variability in the clinical and economic data , st and ard analytical approaches to CEA ignore the presence of between-location variability in the study results . This is a restrictive limitation given that countries often differ in factors that could affect the results of CEAs , such as the availability of health care re sources , their unit costs , clinical practice , and patient case mix . The authors advocate the use of Bayesian bivariate hierarchical modeling to analyze multinational cost-effectiveness data . This analytical framework explicitly recognizes that patient-level costs and outcomes are nested within countries . Using real-life data , the authors illustrate how the proposed methods can be applied to obtain ( a ) more appropriate estimates of overall cost-effectiveness and associated measure of sampling uncertainty compared to st and ard CEA and ( b ) country-specific cost-effectiveness estimates that can be used to assess the between-location variability of the study results while controlling for differences in country-specific and patients pecific characteristics . It is demonstrated that results from st and ard CEA using IPD from multinational trials display a large degree of variability across the 17 countries included in the analysis , producing potentially misleading results . In contrast , ` ` shrinkage estimates ' ' obtained from the modeling approach proposed here facilitate the appropriate quantification of country-specific cost-effectiveness estimates while weighting the results based on the level of information available within each country . The authors suggest that the methods presented here represent a general framework for the analysis of economic data collected from different locations BACKGROUND In a multinational clinical trial , valsartan was statistically not inferior to captopril in reducing mortality and cardiovascular morbidity after myocardial infa rct ion ( MI ) in patients with signs of heart failure and /or left ventricular dysfunction . We conducted a prospect i ve economic evaluation to compare within-trial re source use , costs , and quality of life in patients receiving valsartan , captopril , or both after MI . METHODS We assigned country-specific unit costs to re source use data for 14703 patients and measured health-related quality of life in a subset of 4524 patients . We used the nonparametric bootstrap method to compare rates of re source use and costs , and a piecewise linear mixed-effects regression analysis to compare longitudinal measures of quality of life . RESULTS There were no significant differences in rates of re source use between the valsartan and captopril groups . During an average follow-up of 2 years , total costs for patients receiving valsartan were significantly higher than for patients receiving captopril ( USD 14103 vs USD 13038 ; 95 % CI USD 369-USD 1875 ) . The cost differential was caused primarily by the cost of the study medications ( USD 1056 for valsartan vs USD 165 for captopril ; 95 % CI USD 867 to USD 912 ) . Quality of life did not differ significantly between groups . CONCLUSIONS For most patients at high risk after MI , the availability of generic captopril confers a cost advantage over valsartan because of lower medication costs . The difference will be smaller or nonexistent in setting s where br and -name ACE inhibitors are prescribed BACKGROUND We compared cost-effectiveness of pravastatin in a placebo-controlled trial in 5500 younger ( 31 - 64 years ) and 3514 older patients ( 65 - 74 years ) with previous acute coronary syndromes . METHODS Hospitalizations and long-term medication within the 6 years of the trial were estimated in all patients . Drug dosage , nursing home , and ambulatory care costs were estimated from sub studies . Incremental costs per life saved of pravastatin relative to placebo were estimated from treatment effects and re source use . RESULTS Over 6 years , pravastatin reduced all-cause mortality by 4.3 % in the older patients and by 2.3 % in the younger patients . Older patients assigned pravastatin had marginally lower cost of pravastatin and other medication over 6 years ( A dollar 4442 vs A dollar 4637 ) , but greater cost offsets ( A dollar 2061 vs A dollar 897 ) from lower rates of hospitalizations . The incremental cost per life saved with pravastatin was A dollar 55500 in the old and A dollar 167200 in the young . Assuming no treatment effect beyond the study period , the life expectancy to age 82 years of additional survivors was 9.1 years in the older and 17.3 years in the younger . Estimated additional life-years saved from pravastatin therapy were 0.39 years for older and 0.40 years for younger patients . Incremental costs per life-year saved were A dollar 7581 in the older and A dollar 14944 in the younger , if discounted at 5 % per annum . CONCLUSIONS Pravastatin therapy was more cost-effective among older than younger patients , because of their higher baseline risk and greater cost offsets , despite their shorter life expectancy The growing number of multinational clinical trials in which patient-level health care re source data are collected have raised the issue of which is the best approach for making inference for individual countries with respect to the between-treatment difference in mean cost . We describe and discuss the relative merits of three approaches . The first uses the r and om effects pooled estimate from all countries to estimate the difference for any particular country . The second approach estimates the difference using only the data from the specific country in question . Using empirical Bayes estimation a third approach estimates the country-specific difference using a variance-weighted linear sum of the estimates provided by the other two approaches . The approaches are illustrated and compared using the data from the ASSENT-3 trial Clinical trials of cost-effectiveness are often conducted in more than one country . The two most common ways of dealing with the multinational nature of the data are either to calculate a pooled estimate or to stratify results by country . Since the between-country heterogeneity in costs is potentially substantial , pooled estimates may be difficult to interpret for any one country . Policy decisions are often made at a national level , and so country-specific results are important . However , country-specific analyses will be based on fewer patients and will often fail to provide adequate precision for statistical analyses . Shrinkage estimation is a compromise between these two methods and has been used successfully in other fields . These estimates are country-specific yet less variable than those derived through a subgroup approach . Univariate and multivariate shrinkage estimators for costs and effects are proposed , then compared with one another and to the traditional methods in a simulation study . The methods are illustrated using data from a multinational trial evaluating the cost-effectiveness of three thrombolytic drug regimens in patients with acute myocardial infa rct ion Abstract Rationale : Roflumilast is an oral , once-daily phosphodiesterase IV ( PDE4 ) inhibitor under investigation for chronic obstructive pulmonary disease ( COPD ) . This study investigated the cost effectiveness of roflumilast in patients with severe to very severe COPD from the perspective of the UK society and UK NHS . Methods : The analysis was conducted alongside a 1-year , r and omised , double-blind , placebo-controlled , multinational trial . The trial included 1514 COPD patients aged ≥40 years with a post-bronchodilator forced expiratory volume in 1 second ( FEV1 ) % predicted = 50 % who were r and omised to receive either roflumilast 500μg once daily ( n = 761 ) or placebo ( n = 753 ) . Patients in both treatment groups were allowed to receive active treatment with a short-acting bronchodilator ( salbutamol or anticholinergic ) as needed . About 62 % of patients in both groups were using an inhaled corticosteroid at trial entry . They were allowed to continue this on a stable dosage . Direct healthcare and productivity costs were calculated . Re source utilisation was recorded at every scheduled visit in health economics case report forms ( HECRFs ) . Trial-wide re source use was combined with UK unit cost ( 2004 values ) . Roflumilast was assumed to cost € 1 per day . Incremental costs were related to the differences in the number of moderate to severe exacerbations and the net proportion of patients with an improvement of at least 4 units on the total score of the St George ’s Respiratory Question naire ( SGRQ ) . An intention-to-treat analysis was conducted . Costs and health outcomes that were missing after withdrawal of patients from the trial were imputed using multiple imputation with the propensity score method . Various sensitivity analyses were conducted to test the robustness of the data . Results : In the total group , annual COPD -related costs from a societal perspective were € 1637 in the roflumilast group and € 1401 in the placebo group . From an NHS perspective , this was € 1418 and € 1242 , respectively . The rate of moderate to severe COPD exacerbations per patient was low , and no statistically significant difference existed between roflumilast ( 0.96 ) and placebo ( 1.06 ) . The net proportion of patients with a relevant improvement on SGRQ total score was higher in the roflumilast group ( 0.19 ) than in the placebo group ( 0.14 ) , but the difference was not statistically significant . From a societal perspective , COPD -related costs were € 2356 per exacerbation avoided and € 4712 per net additional patient with a relevant improvement on the SGRQ . The probability that roflumilast was cost effective exceeded 70 % at a willingness to pay of € 5000 to avoid an exacerbation . In a subgroup of patients with very severe COPD ( n = 223 ) , the placebo group had a high exacerbation rate ( 1.7 per patient per year ) whereas roflumilast recipients showed 35 % fewer exacerbations ( 1.1 per patient per year ) . This result ed in roflumilast dominating placebo . In a subgroup of patients with high healthcare utilisation prior to the study ( n = 549 ) roflumilast recipients showed 19 % fewer exacerbations than those receiving placebo , which translated into an ICER of € 804 per exacerbation avoided . Conclusion : Roflumilast increased the overall treatment costs of COPD , although the increase was partly offset by reductions in other forms of healthcare use . Roflumilast has the potential to be cost saving in patients with very severe COPD , due to a statistically significant reduction of exacerbations In a recent multinational r and omized clinical trial , 1356 patients from 14 countries were r and omized between two arms . The primary measure of effectiveness was 30-day survival . Health care utilization was collected on all patients and was combined with a single country 's price weights to provide patient-level cost data . The purpose of this paper is to report the results of the cost-effectiveness analysis for the country that provided the cost weights , so as to provide a case study for illustrating recently proposed method ologies that account for skewed cost data , the between-country variation in treatment effects , possible interactions between treatment and baseline covariates , and the difficulty of estimated adjusted risk differences . A hierarchal model is used to account for the two sources of variation ( between country and between patients , within a country ) . The model , which uses gamma distributions for cost data and recent methods for estimating adjusted risk differences , provides overall and country-specific estimates of treatment effects . Model estimation is facilitated by Markov chain Monte Carlo methods using the WinBUGS software . In addition , the theory of expected value of information is used to determine if the data provided by the trial are sufficient for decision making Cost-effectiveness analysis ( CEA ) in health care is increasingly conducted alongside multicentre and multinational r and omised controlled clinical trials ( RCTs ) . The increased use of stochastic CEA is design ed to account for between-patient sampling variability in cost-effectiveness data assuming that observations are independently distributed . However , between-location variability in cost-effectiveness may result if there is a hierarchical structure in the data ; that is , if there is correlation in costs and outcomes between patients recruited in particular locations . This may be expected in multi-location trials given that centres and countries often differ in factors such as clinical practice , patient case-mix and the unit costs of delivering health care . A failure to acknowledge this feature may lead to misleading conclusions in a trial-based economic study . Multilevel modelling ( MLM ) is an analytical framework that can be used to h and le hierarchical cost-effectiveness data . Using data from a recently conducted economic analysis , this paper shows how multilevel modelling can be used to obtain ( a ) more appropriate estimates of the population average incremental cost-effectiveness and associated st and ard errors compared to st and ard stochastic CEA ; and ( b ) location-specific estimates of incremental cost-effectiveness which can be used to explore appropriately the variability between centres/countries of the cost-effectiveness results Background : Most cost-effectiveness analyses conducted alongside multinational r and omized clinical trials ( RCT ) are carried out applying the unit costs from the country of interest to trial-wide re source use items with the objective of estimating total healthcare costs by treatment group . However , this approach could confound ‘ price effects ’ with ‘ country effects ’ . An alternative approach is to use multilevel modelling techniques to analyse healthcare re source use ( HCRU ) from the trial , and obtain country-specific total costs by applying country-specific unit costs to corresponding shrinkage estimates of differential HCRU . Methods : To illustrate the feasibility of this approach , we analysed data from twin multinational RCTs , which enrolled approximately 2000 individuals into three treatment arms for the management of patients with chronic respiratory disease . The models were implemented using Bayesian multilevel models , to reflect the hierarchical structure of the data while controlling for co-variates at the patient and country level . Results : This analysis showed that directly modelling the level of HCRU is a promising approach to facilitate cost-effectiveness analyses conducted alongside multinational RCTs , offering several advantages compared with the modelling of direct costs . Conclusions : It is argued that modelling the level of HCRU within the Bayesian framework avoids confounding the price effects with the country effects and facilitates the estimation of costs for several countries represented in the trial |
1,865 | 30,496,896 | There was variable evidence of effect on the blood flow perfusion rate .
This systematic review concludes that ESWT has the potential to improve healing in DFUs , although there is , as yet , insufficient evidence to justify its use in routine clinical practice . | BACKGROUND Diabetes mellitus is one of the most common chronic diseases worldwide .
Diabetic foot ulcers ( DFUs ) occur in over 10 % of diabetic patients and are associated with high morbidity .
Clinical trials have shown benefit from extracorporeal shockwave therapy ( ESWT ) in a DFU healing .
This systematic review aims to assess the currently available evidence examining the efficacy of ESWT on healing of DFU . | Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background Diabetes is becoming one of the most common chronic diseases , and ulcers are its most serious complication . Beginning with neuropathy , the subsequent foot wounds frequently lead to lower extremity amputation , even in the absence of critical limb ischemia . In recent years , some research ers have studied external shock wave therapy ( ESWT ) as a new approach to soft tissue wound healing . The rationale of this study was to evaluate if ESWT is effective in the management of neuropathic diabetic foot ulcers . Methods We design ed a r and omized , prospect i ve , controlled study in which we recruited 30 patients affected by neuropathic diabetic foot ulcers and then divided them into two groups based on different management strategies . One group was treated with st and ard care and shock wave therapy . The other group was treated with only st and ard care . The healing of the ulcers was evaluated over 20 weeks by the rate of re-epithelization . Results After 20 weeks of treatment , 53.33 % of the ESWT-treated patients had complete wound closure compared with 33.33 % of the control patients , and the healing times were 60.8 and 82.2 days , respectively ( p < 0.001 ) . Significant differences in the index of the re-epithelization were observed between the two groups , with values of 2.97 mm2/die in the ESWT-group and 1.30 mm2/die in the control group ( p < 0.001 ) . Conclusion Therefore , ESWT may be a useful adjunct in the management of diabetic foot ulceration . Trial registration Current Controlled Trials IS RCT OBJECTIVE This study was conducted to evaluate the efficacy of extracorporeal shock wave therapy ( ESWT ) on the healing rate , wound surface area and wound bed preparation in chronic diabetic foot ulcers ( DFU ) . METHODS Thirty eight patients with 45 chronic DFU were r and omly assigned into ; the ESWT-group ( 19 patients /24 ulcers ) and the control-group ( 19 patients /21 ulcers ) . Blinded therapist measured wound surface area ( WSA ) , the percentage of reduction in the WSA , rate of healing and wound bed preparation at baseline , after the end of the interventions ( W8 ) , and at 20-week follow-up ( W20 ) . The ESWT group received shock wave therapy twice per week for a total of eight treatments . Each ulcer was received ESWT at a frequency of 100 pulse/cm(2 ) , and energy flux density of 0.11mJ/cm(2 ) . All patients received st and ardized wound care consisting of debridement , blood-glucose control agents , and footwear modification for pressure reduction . RESULTS The overall clinical results showed completely healed ulcers in 33.3 % and 54 % in ESWT-groups and 14.28 % and 28.5 % in the control group after intervention ( W8 ) , and at follow-up ( W20 ) respectively . The average healing time was significantly lower ( 64.5 ± 8.06 days vs 81.17 ± 4.35 days , p<0.05 ) in the ESWT-group compared with the control group . CONCLUSION ESWT-treated ulcers had a significant reduction in wound size and median time required for ulcer healing , with no adverse reactions . So , the ESWT is advocated as an adjunctive therapy in chronic diabetic wound BACKGROUND This prospect i ve study compared extracorporeal shockwave treatment ( ESWT ) with hyperbaric oxygen therapy ( HBO ) in chronic diabetic foot ulcers . PATIENTS AND METHODS Seventy-two patients with 72 chronic diabetic foot ulcers were r and omly divided into two groups of similar demographics with 34 patients with 36 ulcers in the ESWT group and 36 patients with 36 ulcers in the HBO group . Patients in the ESWT group received 300 + 100/cm(2 ) impulses of shockwave at 0.11 mJ/cm(2 ) energy flux density every 2 wk for 6 wk , whereas patients in the HBO group received HBO daily for 20 treatments . The evaluations included clinical assessment of the ulcers with photo-documentation , blood flow perfusion scan , bacteriological examination , histological study , and immunohistochemical analysis . RESULTS The overall results showed completely healed in 31 % , improved in 58 % , and unchanged in 11 % for the ESWT group and 22 % completely healed , 50 % improved , and 28 % unchanged for the HBO group . The ESWT group showed significantly better clinical results and local blood flow perfusion , higher cell concentration , and activity than the HBO group . On immunohistochemical analysis , the ESWT group demonstrated significant increases in endothelial nitric oxide synthase , vessel endothelial growth factor , and proliferation cell nuclear antigen expressions and a decrease in transference-mediated digoxigenin-deoxy-UTP nick end-labeling expression than the HBO group . CONCLUSIONS ESWT appears to be more effective than HBO in chronic diabetic foot ulcers BACKGROUND Intermittent claudication is the most common symptom of peripheral arterial disease . Previous research has suggested that extracorporeal shockwave therapy ( ESWT ) may induce angiogenesis in treated tissue . The objective of this feasibility pilot trial was to assess the safety , tolerability , and efficacy of ESWT as a novel treatment . METHODS Patients with unilateral claudication were r and omized to receive ESWT or sham treatment to the calf muscle three times per week for 3 weeks . Primary outcomes were pain-free walking distance ( PFWD ) and maximum walking distance ( MWD ) . Secondary outcomes included safety and tolerability of ESWT treatment , ankle-brachial index before and after exercise , and quality of life assessed using generic ( 36-Item Short Form Health Survey , EuroQol-5 Dimension 3-Level ) and disease-specific ( Vascular Quality of Life ) instruments . Participants were assessed at baseline and 4 , 8 , and 12 weeks after treatment . Feasibility outcomes included recruitment and attendance rates for treatment and follow-up . RESULTS Thirty patients were recruited in total . Statistically significant ( P < .05 ) improvements at all time points were observed in the active treatment group for both MWD and PFWD compared with the sham treatment group . PFWD improved by 276 % in the active group and MWD improved by 167 % in the active group at 12 weeks after treatment . There were no immediate or delayed treatment safety concerns or documented adverse effects of treatment with ESWT in this trial . CONCLUSIONS ESWT is safe and well tolerated when it is applied to the calf and demonstrated significant improvements in walking distances . Current conservative management of intermittent claudication includes supervised exercise . The early results with ESWT as an alternative , noninvasive treatment option show great potential . The mechanism of action , durability of the clinical effect , and cost-effectiveness of ESWT for claudication require further investigation Objective : The Society for Vascular Surgery Wound , Ischemia , and foot Infection ( WIfI ) threatened limb classification has been shown to correlate well with risk of major amputation and time to wound healing in heterogeneous diabetic and nondiabetic population s. Major amputation continues to plague the most severe stage 4 WIfI patients , with 1‐year amputation rates of 20 % to 64 % . Our aim was to determine the association between WIfI stage and wound healing and major amputation among patients with diabetic foot ulcers ( DFUs ) treated in a multidisciplinary setting . Methods : All patients presenting to our multidisciplinary DFU clinic from July 2012 to December 2015 were enrolled in a prospect i ve data base . Wound healing and major amputation were compared for patients stratified by WIfI classification . Results : There were 217 DFU patients with 439 wounds ( mean age , 58.3 ± 0.8 years ; 58 % male , 63 % black ) enrolled , including 28 % WIfI stage 1 , 11 % stage 2 , 33 % stage 3 , and 28 % stage 4 . Peripheral arterial disease and dialysis were more common in patients with advanced ( stage 3 or 4 ) wounds ( P ≤ .05 ) . Demographics of the patients , socioeconomic status , and comorbidities were otherwise similar between groups . There was a significant increase in the number of active wounds per limb at presentation with increasing WIfI stage ( stage 1 , 1.1 ± 0.1 ; stage 4 , 1.4 ± 0.1 ; P = .03 ) . Mean wound area ( stage 1 , 2.6 ± 0.6 cm2 ; stage 4 , 15.3 ± 2.8 cm2 ) and depth ( stage 1 , 0.2 ± 0.0 cm ; stage 4 , 0.8 ± 0.1 cm ) also increased progressively with increasing wound stage ( P < .001 ) . Minor amputations ( stage 1 , 18 % ; stage 4 , 56 % ) and revascularizations ( stage 1 , 6 % ; stage 4 , 55 % ) were more common with increasing WIfI stage ( P < .001 ) . On Kaplan‐Meier analysis , WIfI classification was predictive of wound healing ( P < .001 ) but not of major amputation ( P = .99 ) . For stage 4 wounds , the mean wound healing time was 190 ± 17 days , and risk of major amputation at 1 year was 5.7 % ± 3.2 % . Conclusions : Among patients with DFU , the WIfI classification system correlated well with wound healing but was not associated with risk of major amputation at 1 year . Although further prospect i ve research is warranted , our results suggest that use of a multidisciplinary approach for DFUs may augment healing time and reduce amputation risk compared with previously published historical controls of st and ard wound care among patients with advanced stage 4 disease OBJECTIVE To investigate the efficacy of extracorporeal shockwave therapy ( ESWT ) on healing chronic diabetic foot ulcers ( DFU ) . METHOD Patients with chronic DFUs were r and omised ( 1:1 ) to receive a series of six ESWT treatments over 3 weeks in combination with st and ard care or st and ard care alone . ESWT was performed on DFUs using 250 shocks/cm2 and 500 shocks on arterial beds supplying the ulcer location . RESULTS We recruited 23 patients , 11 in the intervention group and 12 in the control . Transcutaneous oxygen tension was significantly increased in patients treated with ESWT compared with those receiving st and ard care alone at 3 weeks ( p=0.044 ) . Ulcer area reduction was 34.5 % in the intervention group versus 5.6 % in the control group at 7 weeks ( p=0.387 ) . Within-group analysis revealed a significant reduction of ulcer area in the intervention group ( p<0.01 ) , while healing was not demonstrated in the control group ( p>0.05 ) ( data tested for trend ) . CONCLUSION This r and omised study indicates a potential beneficial effect of ESWT on ulcer healing as well as tissue oxygenation . Owing to weaknesses of the study and the fact that ulcer healing was not significantly improved in the intervention group compared with the control group , a larger r and omised trial with blinded design is suggested AIM To identify any significant differences in physiological test results between healing and non healing amputation sites . METHODS A single center prospect i ve non-experimental study design was conducted on fifty subjects living with type 2 diabetes and requiring a forefoot or toe amputation . Subjects underwent non-invasive physiological testing preoperatively . These included assessment of pedal pulses , preoperative arterial spectral waveforms at the ankle , absolute toe pressures , toe-brachial pressure index and ankle-brachial pressure index . After 6 weeks , patients were examined to assess whether the amputation site was completely healed , was healing , had developed complications , or did not heal . RESULTS There was no significant difference in ABPI between the healed/healing and the non-healing groups . Mean TBI ( p=0.031 ) and toe pressure readings ( p=0.014 ) were significantly higher in the healed/healing group compared to the non healing group . A significant difference was also found in ankle spectral waveforms between the two groups ( p=0.028 ) . CONCLUSIONS TBIs , toe pressures and spectral waveforms at the ankle are better predictors of likelihood of healing and non-healing after minor amputation than ABPIs . ABPI alone is a poor indicator of the likelihood of healing of minor amputations and should not be relied on to determine need for revascularization procedures before minor amputation |
1,866 | 25,550,190 | Adverse effects related to oral iron treatment included nausea , diarrhoea and constipation ; most were mild .
Thus , little evidence was found to support the use of one preparation or regimen over another .
Subgroup analyses did not reveal consistent results ; therefore we were unable to determine whether iron is useful in specific clinical situations , or whether iron therapy might be useful for people who are receiving erythropoietin .
• Very low- quality evidence suggests that oral iron might decrease the proportion of people who require blood transfusion , and no evidence indicates that it decreases mortality . | BACKGROUND Anaemia affects about a quarter of the world 's population .
An estimated 50 % of anaemic people have anaemia due to iron deficiency .
OBJECTIVES To assess the safety and efficacy of iron therapies for the treatment of adults with anaemia who are not pregnant or lactating and do not have chronic kidney disease . | PURPOSE To evaluate the safety and efficacy of intravenous ( IV ) sodium ferric gluconate complex ( FG ) , oral ferrous sulfate , or no iron to increase hemoglobin ( Hb ) in anemic cancer patients receiving chemotherapy and epoetin alfa . PATIENTS AND METHODS In this open-label , multicenter trial , 187 patients with chemotherapy-related anemia ( Hb < 11 g/dl ; serum ferritin > or = 100 ng/ml or transferrin saturation > or = 15 % ) scheduled to receive chemotherapy and epoetin alfa ( 40,000 U subcutaneously weekly ) were r and omized to 8 weeks of 125 mg of IV FG weekly , 325 mg of oral ferrous sulfate three times daily , or no iron . The primary outcome was a change in Hb from baseline to endpoint , first whole-blood or red blood cell transfusion , or study withdrawal . RESULTS One hundred twenty-nine patients were evaluable for efficacy ( FG , n = 41 ; oral iron , n = 44 ; no iron , n = 44 ) . Mean increase in Hb was 2.4 g/dl ( 95 % confidence interval [ CI ] , 2.1 - 2.7 ) for FG ( p = .0092 vs. oral iron ; p = .0044 vs. no iron ) , 1.6 g/dl ( 95 % CI , 1.1 - 2.1 ) for oral iron ( p = .7695 vs. no iron ) , and 1.5 g/dl ( 95 % CI , 1.1 - 1.9 ) for no iron . Hb response ( increase > or = 2 g/dl ) was 73 % for FG ( p = .0099 vs. oral iron ; p = .0029 vs. no iron ) , 46 % for oral iron ( p = .6687 vs. no iron ) , and 41 % for no iron . FG was well tolerated . CONCLUSION For cancer patients with chemotherapy-related anemia receiving epoetin alfa , FG produces a significantly greater increase in Hb and Hb response compared with oral iron or no iron , supporting more aggressive treatment with IV iron supplementation for these patients Aims Therapy with i.v . iron in patients with chronic heart failure ( CHF ) and iron deficiency ( ID ) improves symptoms , functional capacity , and quality of life . We sought to investigate whether these beneficial outcomes are independent of anaemia . Methods and results FAIR-HF r and omized 459 patients with CHF [ NYHA class II or III , LVEF ≤40 % ( NYHA II ) or ≤45 % ( NYHA III ) ] and ID to i.v . iron as ferric carboxymaltose ( FCM ) or placebo in a 2:1 ratio . We analysed the efficacy and safety according to the presence or absence of anaemia ( haemoglobin ≤120 g/L ) at baseline . Of 459 patients , 232 had anaemia at baseline ( 51 % ) . The effect of FCM on the primary endpoints of self-reported Patient Global Assessment ( PGA ) and NYHA class at week 24 was similar in patients with and without anaemia [ odds ratio ( OR ) for improvement , 2.48 vs. 2.60 , P = 0.97 for PGA and 1.90 vs. 3.39 , P = 0.51 for NYHA ) . Results were also similar for the secondary endpoints , including PGA and NYHA at weeks 4 and 12 , 6 min walk test distance , Kansas City Cardiomyopathy Question naire overall score , and European Quality of Life-5 Dimensions Visual Analogue Scale at most time points . Regarding safety , no differences were noticed in the rates of death or first hospitalization between FCM and placebo both in anaemic and in non-anaemic patients . Conclusions Treatment of ID with FCM in patients with CHF is equally efficacious and shows a similar favourable safety profile irrespective of anaemia . Iron status should be assessed in symptomatic CHF patients both with and without anaemia and treatment of ID should be considered BACKGROUND Iron deficiency may impair aerobic performance . This study aim ed to determine whether treatment with intravenous iron ( ferric carboxymaltose ) would improve symptoms in patients who had heart failure , reduced left ventricular ejection fraction , and iron deficiency , either with or without anemia . METHODS We enrolled 459 patients with chronic heart failure of New York Heart Association ( NYHA ) functional class II or III , a left ventricular ejection fraction of 40 % or less ( for patients with NYHA class II ) or 45 % or less ( for NYHA class III ) , iron deficiency ( ferritin level < 100 microg per liter or between 100 and 299 microg per liter , if the transferrin saturation was < 20 % ) , and a hemoglobin level of 95 to 135 g per liter . Patients were r and omly assigned , in a 2:1 ratio , to receive 200 mg of intravenous iron ( ferric carboxymaltose ) or saline ( placebo ) . The primary end points were the self-reported Patient Global Assessment and NYHA functional class , both at week 24 . Secondary end points included the distance walked in 6 minutes and the health-related quality of life . RESULTS Among the patients receiving ferric carboxymaltose , 50 % reported being much or moderately improved , as compared with 28 % of patients receiving placebo , according to the Patient Global Assessment ( odds ratio for improvement , 2.51 ; 95 % confidence interval [ CI ] , 1.75 to 3.61 ) . Among the patients assigned to ferric carboxymaltose , 47 % had an NYHA functional class I or II at week 24 , as compared with 30 % of patients assigned to placebo ( odds ratio for improvement by one class , 2.40 ; 95 % CI , 1.55 to 3.71 ) . Results were similar in patients with anemia and those without anemia . Significant improvements were seen with ferric carboxymaltose in the distance on the 6-minute walk test and quality -of-life assessment s. The rates of death , adverse events , and serious adverse events were similar in the two study groups . CONCLUSIONS Treatment with intravenous ferric carboxymaltose in patients with chronic heart failure and iron deficiency , with or without anemia , improves symptoms , functional capacity , and quality of life ; the side-effect profile is acceptable . ( Clinical Trials.gov number , NCT00520780 ) OBJECTIVES Anaemia is a frequent complication after cardiopulmonary bypass surgery . Iron therapy has been variably employed by medical centres over the years . In our study we test the clinical effectiveness of intravenous and oral iron supplementation in correcting anaemia , and its impact on blood transfusion requirements , in patients undergoing cardiopulmonary bypass surgery . METHODS A double-blind , r and omized , placebo-controlled clinical trial with three parallel groups of patients . Group I ( n = 54 ) : intravenous iron(III)-hydroxide sucrose complex , three doses of 100 mg/24 h during pre- and postoperative hospitalization and 1 pill/24 h of oral placebo in the same period and during 1 month after discharge . Group II ( n = 53 ) : oral ferrous fumarate iron 1 pill/24 h pre- and postoperatively and during 1 month after discharge , and intravenous placebo while hospitalized . Group III ( n = 52 ) : oral and intravenous placebo pre- and postoperatively , following the same protocol . Data were collected preoperatively , at theatre , at intensive care unit admission , before hospital discharge and 1 month later . RESULTS ( 1 ) Baseline clinical and demographic characteristics and surgical procedures were similar in the three groups ; ( 2 ) no inter-group differences were found in haemoglobin and haematocrit during the postoperative period ; ( 3 ) the intravenous iron group showed higher serum ferritin levels at hospital discharge ( 1321 ± 495 ng/ml ; P < 0.001 ) and 1 month later ( 610 ± 387 ; P < 0.001 ) compared with the other groups and ( 4 ) we did not observe statistical differences in blood transfusion requirements between the three groups . CONCLUSIONS The use of intravenous or oral iron supplementation proved ineffective in correcting anaemia after cardiopulmonary bypass and did not reduce blood transfusion requirements . [ Current Controlled Trials number : NCT01078818 ( oral and intravenous iron in patients postoperative cardiovascular surgery under EC ) ] To determine if high doses of oral iron could shorten the duration of therapy necessary to treat Fe deficiency anemia , high-dose Fe 600 mg three times per day ( given as nontoxic carbonyl Fe ) was compared with st and ard ferrous sulfate 60 mg Fe++ three times per day in a r and omized , double-blind , 3-wk trial involving 36 female blood donors with mild Fe deficiency anemia . In animal studies , both forms of Fe have similar bioavailability when administered in equal amounts . High-dose carbonyl Fe was well tolerated with gastrointestinal side effects similar those observed with st and ard FeSO4 therapy . The 10-fold larger amount of Fe result ed in a mean 1.5-fold increase in estimated Fe absorption . Both regimens corrected anemia but neither replenished storage Fe . These results suggest that the principal advantage to the use of carbonyl Fe would derive from its safety rather than from the large doses that can be given OBJECTIVE Sub clinical hypothyroidism is a health state that is associated with hypercholesterolemia , infertility , iron-deficiency anemia , and poor obstetric outcome . This article summarizes the results of a prospect i ve clinical investigation of whether treatment of sub clinical hypothyroidism and iron-deficiency anemia with a combination of levothyroxine plus iron salt would be superior to each treatment alone . METHODS In a r and omized , double-blind , active-controlled trial , 60 patients with sub clinical hypothyroidism and iron-deficiency anemia received iron salt+placebo ( 20 patients ) , levothyroxine+placebo ( 20 patients ) , or levothyroxine+iron salt ( 20 patients ) for 3 months . Change from baseline ( before ) to end of study ( after ) in hemoglobin , ferritin , and thyroid-stimulating hormone levels were compared among groups . RESULTS The increase from baseline in hemoglobin and ferritin in the levothyroxine+iron group was superior to the other groups , in which a decrease in thyroid-stimulating hormone in the 2 groups that received levothyroxine was superior to the group treated with iron salt . CONCLUSION Sub clinical hypothyroidism was investigated in iron-deficient patients with no acceptable response to iron salt alone . A combination of levothyroxine and iron salt is better than each one alone Background : The aim of this study was to compare the efficacy , safety and achievement of the target hemoglobin level ( Hb ≥10 g/dl ) in patients with preoperative anemia due to menorrhagia who received intravenous iron sucrose compared with oral iron protein succinylate for anemia management . Methods : Seventy-six patients with Hb levels < 9.0 g/dl who were scheduled to undergo surgical treatment were r and omized to receive either intravenous iron sucrose ( based on the calculated total iron deficit divided into 2 ampoule infusions intravenously 3 times a week , beginning 3 weeks before surgery ) or oral iron ( 80 mg/day of oral iron protein succinylate daily ) . Results : The intravenous iron group had higher increases in Hb ( 3.0 vs. 0.8 g/dl ; p < 0.0001 ) and ferritin levels ( 170.1 vs. 4.1 μg/l ; p < 0.0001 ) than the oral iron group . Achieving the target Hb was also higher in the intravenous iron group than in the oral iron group ( 76.7 vs. 11.5 % ; p < 0.0001 ) . There were tolerable adverse events in both groups . Conclusion : Preoperative intravenous iron sucrose administration is more effective than oral iron and is as safe as oral iron therapy in the correction of preoperative anemia due to menorrhagia 8612 Background : Patients ( pts ) with cancer receiving chemotherapy often have chemotherapy-induced anemia ( CIA ) and reduced quality of life . Darbepoetin alfa ( DA ) is an erythropoiesis-stimulating agent ( ESA ) that can effectively treat CIA when administered once every 3 weeks ( Q3W ) . In patients with CIA , limited data in the literature suggest that administration of intravenous ( IV ) iron with ESA therapy may increase clinical response . METHODS This r and omized , multicenter , open-label , 16-week study evaluated the safety and efficacy of DA 500 mcg administered Q3W using the SureClick injection device in pts with CIA ( Hb < 11 g/dL ) who received either IV iron or st and ard practice for iron administration ( oral iron or no iron ) . The dose of IV iron was 200 mcg administered either Q3W with DA Q3W or , if required , as 2 doses ( 200 mcg total ) within a 3-week period . Pts who received ≥ 1 dose of DA and who completed the 16-week study period by October 19 , 2005 are included in this interim analysis ( planned sample size = 400 pts ) . Accrual will have finished by conference time . R and omization was stratified by tumor type and baseline ( BL ) Hb ( < 10 or ≥ 10 g/dL ) . The incidence of adverse events and serious adverse events , in particular embolic/thrombotic events , was summarized . Efficacy endpoints were estimated using the crude % of pts ( 95 % CI ) . Hb values within 28 days of a transfusion were not included in any efficacy analysis . RESULTS Of the 114 pts included in this interim analysis , 65 % were women , 99 % were Caucasian , the mean ( SD ) age was 60 years ( 12 ) , and 26 % had lung or gynecological tumors ; study endpoints are shown in the table . CONCLUSIONS Based on the interim results , the safety profile for pts receiving DA 500 mcg Q3W with IV iron appears to be comparable to pts receiving DA 500 mcg Q3W with oral iron or no iron . The % pts who achieved the target Hb ( ≥ 11 g/dL ) appeared higher , and the % pts who required transfusions appeared lower , in the group receiving IV iron . [ Table : see text ] [ Table : see text ] Several intravenous iron complexes are available for the treatment of iron deficiency anemia ( IDA ) . Iron dextran ( DEX ) is associated with an elevated risk of potentially serious anaphylactic reactions , whereas others must be administered in several small infusions to avoid labile iron reactions . Ferric carboxymaltose ( FCM ) is a nondextran intravenous iron which can be administered in high single doses . A r and omized , open label , and multicenter comparison of FCM to DEX in adults with IDA and baseline hemoglobin of ≤11.0 g/dL was conducted . A total of 160 patients were in the safety population ( FCM n = 82 ; DEX n = 78 ) . Adverse events , including immune system disorders ( 0 % in FCM versus 10.3 % in DEX , P = 0.003 ) and skin disorders ( 7.3 % in FCM versus 24.4 % in DEX , P = 0.004 ) , were less frequently observed in the FCM group . A greater portion of patients in the FCM group experienced a transient , asymptomatic decrease in phosphate compared to patients in the DEX group ( 8.5 % in FCM versus 0 % in DEX , P = 0.014 ) . In the FCM arm , the change in hemoglobin from baseline to the highest observed level was 2.8 g/dL , whereas the DEX arm displayed a change of 2.4 g/dL ( P = 0.20 ) . Treatment of IDA with FCM result ed in fewer hypersensitivity-related reactions than DEX Despite efforts to improve iron supplements for iron deficiency anemia , there is no consensus on products that balance efficacy , safety and tolerability , and cost . Ferrous products are effective , but they are associated with more gastrointestinal side effects than ferric products . Ferric products tend to have lower absorption . We present results from a 12-week study that ran domized 72 people with uncomplicated iron deficiency anemia to receive a ferrous iron supplement ( Ferall , a combination of ferrous fumarate with ascorbic acid , folic acid , and cyanocobalamin ) or a ferric iron polysaccharide complex ( Niferex , ferro-glycine sulfate ) plus ascorbic acid . The ferrous product was significantly more effective , the primary and secondary endpoints including changes in levels of hemoglobin and serum ferritin . There was a slightly higher frequency of gastrointestinal side effects in patients taking the ferrous product , but both supplements were well tolerated . No participant withdrew from the study because of side effects . We concluded that the ferrous product is safe and effective for use in uncomplicated iron deficiency anemia . The lack of direct comparison between single-agent ferrous fumarate and the combination ferrous product limited interpretation of results in terms of possible effects due to other components , such as ascorbic acid After total hip and knee replacement arthroplasty , patients may become anaemic and may be prescribed oral iron . There is , however , no published evidence that this is of benefit when used postoperatively . We treated 72 patients who were anaemic after primary total hip and knee arthroplasty by r and omly allocating them to receive six weeks of either oral ferrous sulphate ( 35 patients ) or a placebo ( 37 patients ) . Both groups of patients were similar in all aspects except for the treatment given . There was no statistically significant difference in the change of haemoglobin levels between the two groups . We therefore believe that the prescription of iron to all anaemic patients post-operatively should be avoided . The level of serum ferritin should be monitored at preoperative assessment Introduction The correction of iron-deficiency anaemia is relatively simple . However , until the cause of the anaemia has been established and treated , the patient must continue ' taking iron preparations ( Avery 1980 ) . It was , therefore , considered useful to assess the efficacy of a new once-a-day iron tablet , Ferrocontin Continusf tablets , compared to a st and ard preparation , Fersamal ' " tablets . If the once-aday Ferrocontin Continus tablets were shown to be equally or more efficacious than the three-times-a-day Fersamal tablets , then Ferrocontin Continus tablets would represent a considerable benefit to the patient PURPOSE Functional iron deficiency may impair response to erythropoiesis-stimulating agents ( ESAs ) in iron-replete patients with chemotherapy-associated anemia ( CAA ) . This study evaluated whether coadministration of parenteral iron improves ESA efficacy in patients with CAA . PATIENTS AND METHODS This prospect i ve , multicenter , r and omized trial enrolled 502 patients with hemoglobin ( Hb ) less than 11 g/dL who were undergoing chemotherapy for nonmyeloid malignancies . All patients received darbepoetin alfa once every 3 weeks and were r and omly assigned to receive either ferric gluconate 187.5 mg intravenously ( IV ) every 3 weeks , oral daily ferrous sulfate 325 mg , or oral placebo for 16 weeks . RESULTS There was no difference in the erythropoietic response rate ( ie , proportion of patients achieving Hb ≥ 12 g/dL or Hb increase ≥ 2 g/dL from baseline ) : 69.5 % ( 95 % CI , 61.9 % to 76.5 % ) of IV iron-treated patients achieved an erythropoietic response compared with 66.9 % ( 95 % CI , 59.1 % to 74.0 % ) who received oral iron and 65.0 % ( 95 % CI , 57.2 % to 72.3 % ) who received oral placebo ( P = .75 ) . There were also no differences in the proportion of patients requiring red cell transfusions , changes in quality of life , or the dose of darbepoetin administered . Adverse events ( AEs ) tended to be more common in the IV iron arm : grade 3 or higher AEs occurred in 54 % ( 95 % CI , 46 % to 61 % ) of patients receiving IV iron compared with 44 % ( 95 % CI , 36 % to 52 % ) who received oral iron and 46 % ( 95 % CI , 38 % to 54 % ) who received oral placebo ( P = .16 ) . CONCLUSION In patients with CAA , addition of IV ferric gluconate to darbepoetin failed to provide additional benefit compared with oral iron or oral placebo OBJECTIVES : Anemia is a frequent complication in patients with inflammatory bowel disease ( IBD ) . The optimal route for iron supplementation to replenish iron stores has not been determined so far . We therefore evaluated the efficacy and safety of intravenous iron sucrose as compared with oral iron sulfate for the treatment of iron deficiency anemia ( IDA ) in patients with IBD . METHODS : A r and omized , prospect i ve , open-label , multicenter study was performed in 46 patients with anemia and transferrin saturation ≤20 % and /or serum ferritin concentrations ≤20 μg/L. The intravenous group received a single dose of iron sucrose of 7 mg iron/kg body weight , followed by five 200 mg infusions for the following 5 wks . The oral group received iron sulfate 100–200 mg per day for 6 wks . RESULTS : While a comparable increase in hemoglobin was observed for both administration routes ( median increase 0.25 g/L in the intravenous group vs 0.21 g/L in the oral group ) , only iron sucrose led to a rise in serum ferritin concentrations . Intractable gastrointestinal adverse events caused permanent study drug discontinuation in five patients ( 20.8 % ) receiving iron sulfate , whereas only one patient ( 4.5 % ) had to be withdrawn because of side effects due to iron sucrose . CONCLUSIONS : Although being equal in short-term efficacy and overall tolerability our results suggest a better gastrointestinal tolerability for iron sucrose . Larger trials are m and atory to prove a possible advantage of iron sucrose in short- and long-term efficacy as well as in tolerability over iron sulfate in the management of IDA in IBD OBJECTIVE The aim of this study was to ascertain whether high-dose intravenous ( IV ) iron sucrose could improve symptoms and change brain iron concentrations in idiopathic RLS . METHODS The study was a r and omized , parallel-group double-blind study of 1000 mg iron sucrose given IV versus placebo . Primary measures of the clinical status were global rating scale ( GRS ) and periodic leg movements of sleep ( PLMS ) . Primary measures of brain iron status were CSF ferritin and MRI-determined iron in the substantia nigra . RESULTS At the time of the interim analysis there were 7 placebo and 11 iron-treated subjects . At 2-weeks post-treatment , iron treatment result ed in a small but significant increase in CSF ferritin and a decrease in RLS severity ( GRS ) but did not change PLMS or MRI iron index . None of the secondary outcomes changed with treatment . There was no single case of clear treatment benefit in any of the patients . This interim analysis revealed an effect size that was too small to allow for adequate power to find significant differences with the planed 36-subject enrollment for either the primary objective outcome of PLMS or any of the secondary outcomes . The study was stopped at this planned break-point given the lack of both adequate power and any indication for clinical ly significant benefit . CONCLUSIONS High-dose IV iron failed to demonstrate the robust changes reported in three prior open-label studies . Differences in iron formulation , dosing regiment , and peripheral iron status may explain some of the discrepancies between this and previous IV iron treatment studies Although oral iron is the initial treatment approach for iron deficiency anemia ( IDA ) , some patients fail to respond to or can not tolerate oral iron . This double‐blind safety and efficacy study of the intravenous ( IV ) iron , ferumoxytol , r and omized patients with a history of unsatisfactory oral iron therapy , or in whom oral iron could not be used , to ferumoxytol ( n = 609 ) or placebo ( n = 203 ) . The proportion of patients achieving the primary endpoint ( hemoglobin increase ≥2.0 g/dL at Week 5 ) was 81.1 % with ferumoxytol versus 5.5 % with placebo ( P < 0.0001 ) . The mean increase in hemoglobin from Baseline to Week 5 , a secondary endpoint ( also the alternative preplanned primary efficacy endpoint for other health authorities ) , was 2.7 versus 0.1 g/dL ( P < 0.0001 ) . Achievement of a hemoglobin ≥12 g/dL , time to a hemoglobin increase ≥2.0 g/dL , and improvement in the Functional Assessment of Chronic Illness Therapy Fatigue score also significantly favored ferumoxytol over placebo at Week 5 ( P < 0.0001 ) . Ferumoxytol treatment‐emergent adverse events were mainly mild to moderate . Ferumoxytol was effective and well tolerated in patients with IDA of any underlying cause in whom oral iron was ineffective or could not be used . This trial was registered at www . clinical trials.gov as # NCT01114139 . Am . J. Hematol . 89:7–12 , 2014 . © 2013 Wiley Periodicals , Background Absolute iron deficiency , irrespective of aetiology , remains a major and worldwide cause of morbidity . After correction of the causative lesion , reconstitution of haemoglobin level and body iron stores is traditionally achieved with oral administration of ferrous salts . The latter have significant gastrointestinal tract side-effects that , in the short-term , may impair compliance . With protracted administration these products can cause lipid peroxidation which , in turn , may accelerate atherogenesis . An alternative formulation is an iron polymaltose complex where animal data supported a promoting effect of glycerophosphate . Setting and Trial Design This was a single-centre , open , r and omised , multidose four treatment parallel group study . A st and ard dose of ferric polymaltose complex with two differing levels of glycerophosphate was compared with an equivalent amount of iron supplied as ferrous sulphate in anaemic volunteer blood donors . The endpoints were rate of haemoglobin rise and re-expansion of body iron stores reflected in blood ferritin concentration , as well as percentage saturation of transferrin . Secondary observations were changes in the proportion of hypochromic red cells during the course of treatment , erythropoietin levels and tolerability of the two formulations . Results Outcome in the rat model suggested that the utilisation of iron from polymaltose might be enhanced by glycerophosphate . However , in donors this difference was not evident and , accordingly , the data from the three polymaltose groups combined and compared to those receiving ferrous sulphate . The rate at which haemoglobin level improved , red cell indices returned to normal , and the number of hypochromic and microcytic red cells fell was not significantly different between the groups . Similarly the serum iron , percentage saturation of transferrin and red cell ferritin were comparable . In contrast the serum ferritin levels were higher for those receiving ferrous sulphate . Additionally , side-effects were significantly more frequently encountered with the latter preparation . Conclusion These data demonstrate that the addition of glycerophosphate , observed to be beneficial in rats , did not occur in humans . Secondly , in the blood donors , equivalent amounts of iron provided as the polymaltose , with or without glycerophosphate or ferrous sulphate , corrected haemoglobin concentration and morphologically abnormal erythropoiesis at comparable rates . Similarly iron stores are replenished to an equivalent extent as seen in the matching percentage saturation of transferrin and red cell ferritin levels . Interestingly , there is a discrepancy in the serum ferritin which is higher with the salt and this may reflect oxidative stress . Thirdly , corresponding efficacy can be achieved with better patient tolerance for the complex . Finally it is postulated that the iron polymaltose complex formulation more closely approximates the way in which enterocytes h and le dietary iron and thus physiologic regulatory mechanisms would be expected to reciprocally slow down absorption as stores exp and . Logically , therefore and , if confirmed , the latter finding suggests that this formulation may have a potential role in longer-term supplementation programmes OBJECTIVE To compare the incidence of repeated red blood cell ( RBC ) transfusion in anemic gynecologic cancer patients receiving platinum-based chemotherapy comparing intravenous and oral iron . MATERIAL S AND METHODS Forty-four anemic gynecologic cancer patients ( hemoglobin level below 10 mg/dl ) who required RBC transfusion were stratified and r and omized according to baseline hemoglobin levels and chemotherapy regimen . Study group received 200 mg of intravenous iron sucrose and control group received oral ferrous sulphate 600 mg/day . RBC transfusion requirement in the consecutive cycle of chemotherapy was the primary outcome . Quality of life was evaluated by vali date d Thai version of the Functional Assessment of Cancer Therapy-Anemia ( FACT-An ) . RESULTS In a total of the 44 patients , there were 22 patients in each group . Five patients ( 22.7 % ) in the study group and 14 patients ( 63.6 % ) in the control group required RBC transfusion in consecutive cycle of chemotherapy ( p=0.01 ) . No significant difference in baseline hemoglobin and hematocrit levels was demonstrated in both groups . Significantly higher mean hemoglobin and hematocrit levels after treatment were reported in the study group ( 10.0+/-0.8 g/dl and 30.5+/-2.4 % ) than the control group ( 9.5+/-0.9 g/dl and 28.4+/-2.7 % ) . No significant change of total FACT-An scores was noted between before and after treatment in both groups . No serious adverse events were reported and there was no significant difference among adverse events between both groups . CONCLUSION Intravenous iron is an alternative treatment for anemic gynecologic cancer patients receiving platinum-based chemotherapy and reduces the incidence of RBC transfusion without serious adverse events Background and Aims Secondary thrombocytosis is a clinical feature of unknown significance . In inflammatory bowel disease ( IBD ) , thrombocytosis is considered a marker of active disease ; however , iron deficiency itself may trigger platelet generation . In this study we tested the effect of iron therapy on platelet counts in patients with IBD-associated anemia . Methods Platelet counts were analyzed before and after iron therapy from four prospect i ve clinical trials . Further , changes in hemoglobin , transferrin saturation , ferritin , C-reactive protein , and leukocyte counts , before and after iron therapy were compared . In a subgroup the effect of erythropoietin treatment was tested . The results were confirmed in a large independent cohort ( FERGIcor ) . Results A total of 308 patient records were available for the initial analysis . A dose-depended drop in platelet counts ( mean 425 G/L to 320 G/L ; p<0.001 ) was found regardless of the type of iron preparation ( iron sulphate , iron sucrose , or ferric carboxymaltose ) . Concomitant erythropoietin therapy as well as parameters of inflammation ( leukocyte counts , C-reactive protein ) had no effect on the change in platelet counts . This effect of iron therapy on platelets was confirmed in the FERGIcor study cohort ( n=448 , mean platelet counts before iron therapy : 383 G/L , after : 310 G/L , p<0.001 ) . Conclusion Iron therapy normalizes elevated platelet counts in patients with IBD-associated anemia . Thus , iron deficiency is an important pathogenetic mechanism of secondary thrombocytosis in IBD Objective . Iron therapy may reinforce intestinal inflammation by catalysing production of reactive oxygen species . The effects of oral ferrous fumarate and intravenous iron sucrose on clinical disease activity and plasma redox status were investigated in patients with inflammatory bowel disease ( IBD ) . Material and methods . Nineteen patients with iron deficiency anaemia and Crohn 's disease ( 11 ) or ulcerative colitis ( 8) were included in a crossover study . The patients were r and omly assigned to start treatment with ferrous fumarate ( Neo-fer ® ) 120 mg orally once daily or iron sucrose ( Venofer ® ) 200 mg intravenously 3 times during a period of 14 days . Clinical disease activity assessment and blood and faecal analysis were performed on days 1 and 15 . Results . Following oral ferrous fumarate clinical disease activity ( p=0.037 ) , general well-being score ( i.e. patients felt worse ) ( p=0.027 ) and abdominal pain score ( p=0.027 ) increased , while no changes were seen following iron sucrose treatment . C-reactive protein ( CRP ) and faecal calprotectin were unchanged after both treatments . As compared with iron sucrose , ferrous fumarate increased Crohn 's disease activity index ( CDAI ) scores of general well-being ( p=0.049 ) , whereas alterations in clinical disease activity ( p=0.14 ) and abdominal pain score ( p=0.20 ) did not differ . Ferrous fumarate did not significantly alter plasma malondialdehyde ( MDA ) or plasma antioxidants . Iron sucrose increased plasma MDA ( p=0.004 ) and decreased plasma vitamin C ( p=0.017 ) and betacarotene ( p=0.008 ) . Conclusions . Oral ferrous fumarate , but not intravenous iron sucrose , increased clinical disease activity in IBD patients . Intravenous iron sucrose increased intravascular oxidative stress Background Around one third to one half of patients with hip fractures require red-cell pack transfusion . The increasing incidence of hip fracture has also raised the need for this scarce re source . Additionally , red-cell pack transfusions are not without complications which may involve excessive morbidity and mortality . This makes it necessary to develop blood-saving strategies . Our objective was to assess safety , efficacy , and cost-effictveness of combined treatment of i.v . ferric carboxymaltose and erythropoietin ( EPOFE arm ) versus i.v . ferric carboxymaltose ( FE arm ) versus a placebo ( PLACEBO arm ) in reducing the percentage of patients who receive blood transfusions , as well as mortality in the perioperative period of hip fracture intervention . Methods / Design Multicentric , phase III , r and omized , controlled , double blinded , parallel groups clinical trial . Patients > 65 years admitted to hospital with a hip fracture will be eligible to participate . Patients will be treated with either a single dosage of i.v . ferric carboxymaltose of 1 g and subcutaneous erythropoietin ( 40.000 IU ) , or i.v . ferric carboxymaltose and subcutaneous placebo , or i.v . placebo and subcutaneous placebo . Follow-up will be performed until 60 days after discharge , assessing transfusion needs , morbidity , mortality , safety , costs , and health-related quality of life . Intention to treat , as well as per protocol , and incremental cost-effectiveness analysis will be performed . The number of recruited patients per arm is set at 102 , a total of 306 patients . Discussion We think that this trial will contribute to the knowledge about the safety and efficacy of ferric carboxymaltose with/without erythropoietin in preventing red-cell pack transfusions in patients with hip fracture . Clinical Trials.gov identifier : NCT01154491 Side-effects of iron supplementation lead to poor compliance . A weekly-dose schedule of iron supplementation rather than a daily-dose regimen has been suggested to produce fewer side-effects , thereby achieving a higher compliance . This study compared side-effects of iron supplementation and their impact on compliance among pregnant women in Bangladesh . These women were assigned to receive either weekly doses of 2 x 60 mg iron ( one tablet each Friday morning and evening ) or a daily dose of 1 x 60 mg iron . Fifty antenatal care centres were r and omly assigned to prescribe either a weekly- or a daily-supplementation regimen ( 86 women in each group ) . Side-effects were assessed by recall after one month of supplementation and used for predicting compliance in the second and third months of supplementation . Compliance was monitored using a pill bottle equipped with an electronic counting device that recorded date and time whenever the pill bottle was opened . Of five gastrointestinal side-effects ( heartburn , nausea , vomiting , diarrhoea , or constipation ) assessed , vomiting occurred more frequently in the weekly group ( 21 % ) than in the daily group ( 11 % , p<0.05 ) . Compliance ( ratio between observed and recommended tablet intake ) was significantly higher in the weekly-supplementation regimen ( 93 % ) than in the daily-supplementation regimen ( 61 % , p<0.05 ) . Overall , gastrointestinal side-effects were not significantly associated with compliance . However , the presence of nausea and /or vomiting reduced compliance in both the regimens-but only among women from the lower socioeconomic group . In conclusion , weekly supplementation of iron in pregnancy had a higher compliance compared to daily supplementation of iron despite a higher frequency of side-effects . The findings support the view that gastrointestinal side-effects generally have a limited influence on compliance , at least in the dose ranges studied . Efforts to further reduce side-effects of iron supplementation may not be a successful strategy for improving compliance and effectiveness of antenatal iron supplementation We r and omised 120 patients who were undergoing either primary total hip or knee arthroplasty to receive either ferrous sulphate or a placebo for three weeks after surgery . The level of haemoglobin and absolute reticulocyte count were measured at one and five days , and three and six weeks after operation . Ninety-nine patients ( ferrous sulphate 50 , placebo 49 ) completed the study . The two groups differed only in the treatment administered . Recovery of level of haemoglobin was similar at five days and three weeks and returned to 85 % of the pre-operative level , irrespective of the treatment group . A small , albeit greater recovery in the level of haemoglobin was identified at six weeks in the ferrous sulphate group in both men ( ferrous sulphate 5 % , placebo 1.5 % ) and women ( ferrous sulphate 6 % , placebo 3 % ) . The clinical significance of this is question able and may be outweighed by the high incidence of reported side effects of oral iron and the cost of the medication . Administration of iron supplements after elective total hip or total knee arthroplasty does not appear to be worthwhile Background . Iron deficiency anemia ( IDA ) is a common hematological complication with potentially serious clinical consequences that may require intravenous iron therapy . Ferric carboxymaltose ( FCM ) is a stable , nondextran iron formulation administered intravenously in large single doses to treat IDA . Objective . Two open-label , r and omized , placebo-controlled trials evaluated safety of multiple or single 750 mg FCM doses compared to st and ard medical care ( SMC ) in IDA patients . Secondary endpoints were improvements in hemoglobin and iron indices . Design and Patients . Adults with hemoglobin ≤12 g/dL , ferritin ≤100 or ≤300 ng/mL with transferrin saturation ≤30 % were r and omized to receive single ( n = 366 ) or weekly ( n = 343 ) FCM or SMC ( n = 360 and n = 366 ) . Results . Significantly greater ( P ≤ 0.001 ) increases in hemoglobin and iron indices occurred in FCM groups versus SMC . In the multidose study , up to two infusions of FCM were needed to reach target iron levels versus 3–5 of intravenous iron comparators . FCM and SMC groups had similar incidences and types of adverse events and serious adverse events . Transient hypophosphatemia not associated with adverse events or clinical sequelae occurred in the FCM groups . Conclusion . Intravenous FCM is safe , well tolerated , and associated with improvements in hemoglobin and iron indices comparable to SMC when administered in single doses of up to 750 mg at a rate of 100 mg/min . Fewer FCM infusions were required to reach target iron levels compared to other intravenous iron preparations Aims Patients with chronic heart failure ( CHF ) show impaired health-related quality of life ( HRQoL ) , an important target for therapeutic intervention . Impaired iron homeostasis may be one mechanism underlying the poor physical condition of CHF patients . This detailed sub analysis of the previously published FAIR-HF study evaluated baseline HRQoL in iron-deficient patients with CHF and the effect of intravenous ferric carboxymaltose ( FCM ) on HRQoL. Methods and results FAIR-HF r and omized 459 patients with reduced left ventricular ejection fraction and iron deficiency , with or without anaemia , to FCM or placebo ( 2:1 ) . Health-related quality of life was assessed at baseline and after 4 , 12 , and 24 weeks of therapy using the generic EQ-5D question naire and disease-specific Kansas City Cardiomyopathy Question naire ( KCCQ ) . Baseline mean Visual Analogue Scale ( VAS ) score was 54.3 ± 16.4 and KCCQ overall summary score was 52.4 ± 18.8 . Ferric carboxymaltose significantly improved VAS and KCCQ ( mean differences from baseline in KCCQ overall , clinical and total symptom scores , P < 0.001 vs. placebo ) at all time points . At Week 24 , significant improvement vs. placebo was observed in four of the five EQ-5D dimensions : mobility ( P= 0.004 ) , self-care ( P < 0.001 ) , pain/discomfort ( P= 0.006 ) , anxiety/depression ( P= 0.012 ) , and usual activity ( P= 0.035 ) . Ferric carboxymaltose improved all KCCQ domain mean scores from Week 4 onward ( P≤ 0.05 ) , except for self-efficacy and social limitation . Effects were present in both anaemic and non-anaemic patients . Conclusions HRQoL is impaired in iron-deficient patients with CHF . Intravenous FCM significantly improved HRQoL after 4 weeks , and throughout the remaining study period . The positive effects of FCM were independent of anaemia status This r and omized study assessed if intravenous iron improves hemoglobin ( Hb ) response and permits decreased epoetin dose in anemic ( Hb 9–11 g/dl ) , transfusion-independent patients with stainable iron in the bone marrow and lymphoproliferative malignancies not receiving chemotherapy . Patients ( n=67 ) were r and omized to subcutaneous epoetin beta 30 000 IU once weekly for 16 weeks with or without concomitant intravenous iron supplementation . There was a significantly ( P<0.05 ) greater increase in mean Hb from week 8 onwards in the iron group and the percentage of patients with Hb increase ⩾2 g/dl was significantly higher in the iron group ( 93 % ) than in the no-iron group ( 53 % ) ( per- protocol population ; P=0.001 ) . Higher serum ferritin and transferrin saturation in the iron group indicated that iron availability accounted for the Hb response difference . The mean weekly patient epoetin dose was significantly lower after 13 weeks of therapy ( P=0.029 ) and after 15 weeks approximately 10 000 IU ( > 25 % ) lower in the iron group , as was the total epoetin dose ( P=0.051 ) . In conclusion , the Hb increase and response rate were significantly greater with the addition of intravenous iron to epoetin treatment in iron-replete patients and a lower dose of epoetin was required BACKGROUND AIMS : Anemia is a common complication of inflammatory bowel diseases ( IBD ) This multicenter study tested the noninferiority and safety of a new intravenous iron preparation , ferric carboxymaltose ( FeCarb ) , in comparison with oral ferrous sulfate ( FeSulf ) in reducing iron deficiency anemia ( IDA ) in IBD . METHODS : Two hundred patients were r and omized in a 2:1 ratio ( 137 FeCarb:63 FeSulf ) to receive FeCarb ( maximum 1,000 mg iron per infusion ) at 1-wk intervals until the patients ' calculated total iron deficit was reached or FeSulf ( 100 mg b.i.d . ) for 12 wk . The primary end point was change in hemoglobin ( Hb ) from baseline to week 12 . RESULTS : The median Hb improved from 8.7 to 12.3 g/dL in the FeCarb group and from 9.1 to 12.1 g/dL in the FeSulf group , demonstrating noninferiority ( P = 0.6967 ) . Response ( defined as Hb increase of > 2.0 g/dL ) was higher for FeCarb at week 2 ( P = 0.0051 ) and week 4 ( P = 0.0346 ) . Median ferritin increased from 5.0 to 323.5 μg/L at week 2 , followed by a continuous decrease in the FeCarb group ( 43.5 μg/L at week 12 ) . In the FeSulf group , a moderate increase from 6.5 to 28.5 μg/L at week 12 was observed . Treatment-related adverse events ( AEs ) occurred in 28.5 % of the FeCarb and 22.2 % of the FeSulf groups , with discontinuation of study medication due to AEs in 1.5 % and 7.9 % , respectively . CONCLUSIONS : FeCarb is effective and safe in IBD-associated anemia . It is noninferior to FeSulf in terms of Hb change over 12 wk , and provides a fast Hb increase and a sufficient refill of iron stores OBJECTIVES : Anemia is a common complication of inflammatory bowel disease ( IBD ) and iron deficiency ( ID ) is its predominant cause . Therefore , oral and intravenous iron replacements are widely used . This study was performed to evaluate the frequency and timing of anemia and ID recurrence after a successful treatment cycle . METHODS : Medical records of patients who had received iron sucrose with or without erythropoietin ( EPO ) in one of three prospect i ve clinical trials that had been conducted at our center ( Ann Intern Med 1997 , Digestion 1999 , and Am J Gastroenterol 2001 ) were analyzed for a 5-year follow-up period . The risk for recurrence of anemia ( hemoglobin (Hb)<12/13 g per 100 ml ) and ID ( ferritin < 30 μg/l ) was evaluated by Kaplan – Meier analysis using the log-rank test . RESULTS : Eighty-eight patients were available for analysis . Patients had received a mean iron dose of 2,500 mg ( range 600–3,600 mg ) ; 33 ( 37.1 % ) patients had also received EPO . Anemia recurred in a median of 10 months ( 95 % confidence interval ( CI ) 8–12 ) and ID recurred within 19 months ( 95 % CI 11–28 ) . The iron dose had no influence on recurrence of ID or anemia . ID ( but not anemia ) recurred faster in patients with a post-treatment ferritin level < 100 μg/l ( median 4 months , 95 % CI 1–7 ) than in patients with ferritin level between 100 and 400 μg/l ( median 11 months , 95 % CI 6–16 ) and > 400 μg/l ( median 49 months , 95 % CI 32–66 ; P<0.001 ) . CONCLUSIONS : IBD-associated ID and anemia recur surprisingly fast , indicating that maintenance treatment may be needed in a portion of the patient population . Recurrence of ID ( but not anemia ) can be delayed by aim ing for high post-treatment ferritin levels BACKGROUND Previous studies on patients with hip fractures and in patients with colorectal cancer have documented that perioperative transfusion is associated with a significant increase in postoperative infection rate . Therefore , we sought to investigate the incidence of preoperative and postoperative anemia in noncardiac surgical patients and to determine if transfusion is an independent risk factor for infection and adverse outcome postoperatively . METHODS Prospect i ve data from the National Veterans Administration Surgical Quality Improvement Program ( NSQIP ) was collected on 6301 noncardiac surgical patients at the Veterans Affairs Maryl and Healthcare System from 1995 to 2000 . RESULTS The mean age of the study cohort was 61 + /- 13 . Descriptive data revealed 95 % were male , 44 % used tobacco , 19 % were diabetic , 9 % had COPD , 9 % used alcohol , 3 % used steroids , 1.7 % had a diagnosis of cancer , and 1.2 % had ascites . Preoperative anemia ( hematocrit less than 36 ) was found in 33.9 % and postoperative anemia was found in 84.1 % of the study cohort . In the postoperative period , 32.5 % of patients had a hematocrit of 26 - 30 , and 26.5 % had a hematocrit of 21 - 25 . Mean units of blood transfused in the perioperative period ranged from 0.1 + /- 0.9 in patients without anemia to 2.7 + /- 2.9 in those with anemia . Incidence of pneumonia increased from 2.6 to 5 % with increasing degree of anemia . Multiple logistic regression analysis documented that low preoperative hematocrit , low postoperative hematocrit , and increased blood transfusion rates were associated with increased mortality ( P < 0.01 ) , increased postoperative pneumonia ( P < or = 0.05 ) , and increased hospital length of stay ( P < 0.05 ) . CONCLUSION There is a high incidence of preoperative and postoperative anemia in surgical patients , with a coincident increase in blood utilization . These factors are associated with increased risk for perioperative infection and adverse outcome ( mortality ) in surgical patients . Consideration should be given to preoperative diagnosis and correction of anemia with iron , vitamin B12 , folate supplementation , or administration of recombinant human erythropoietin BACKGROUND & AIMS Iron-deficiency anemia is the most common systemic complication of inflammatory bowel diseases ( IBD ) . Iron-deficiency anemia recurs frequently and rapidly after iron-replacement therapy in patients with IBD . We performed a r and omized , placebo-controlled trial to determine if administration of ferric carboxymaltose ( FCM ) prevents anemia in patients with IBD and low levels of serum ferritin . METHODS We performed a single-blind , multicenter study of nonanemic patients who had completed the FERGIcor study . Serum levels of ferritin were assessed every second month , and patients were given FCM ( total iron dose , 1181 ± 662 mg ; n = 105 ) or placebo ( n = 99 ) when levels decreased to less than 100 μg/L. The primary end point was time to recurrence of anemia within 8 months . Secondary end points included changes of quality of life , disease activity , results from laboratory tests , and adverse events . RESULTS Anemia recurred in 26.7 % of subjects given FCM and in 39.4 % given placebo . The time to anemia recurrence was longer in the FCM group ( hazard ratio , 0.62 ; 95 % confidence interval , 0.38 - 1.00 ; P = .049 ) . Markers of body levels of iron increased or remained at normal levels in subjects given FCM ( ferritin increased by 30.3 μg/L , transferrin saturation increased by 0.6 % ) but decreased in the group given placebo ( ferritin decreased by 36.1 μg/L , transferrin saturation decreased by 4.0 % ) . Changes in quality of life and disease activity were comparable between groups . Adverse events were reported in 59.0 % of the FCM group and 50.5 % of the placebo group , and serious adverse events were reported in 6.7 % and 8.1 % , respectively . CONCLUSIONS FCM prevents recurrence of anemia in patients with IBD , compared with placebo . Nevertheless , the high rate of anemia recurrence warrants optimization of the frequency and requirements for FCM treatment Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . PURPOSE Recombinant human erythropoietin ( rHuEPO ) is the st and ard of care for patients with chemotherapy-related anemia . Intravenous ( IV ) iron improves hemoglobin ( Hb ) response and decreases dosage requirements in patients with anemia of kidney disease , but its effect has not been studied in r and omized trials in cancer patients . METHODS This prospect i ve , multicenter , open-label , r and omized trial enrolled 157 patients with chemotherapy-related anemia ( Hb < or= 105 g/L , serum ferritin < or= 450 pmol/L or < or= 675 pmol/L with transferrin saturation < or= 19 % ) receiving subcutaneously rHuEPO 40000 U once weekly to : ( 1 ) . no-iron ; ( 2 ) . oral iron 325 mg twice daily ; ( 3 ) iron dextran repeated 100 mg IV bolus ; or ( 4 ) iron dextran total dose infusion ( TDI ) . Hb and quality of life ( QOL ) were measured at baseline and throughout . RESULTS All groups showed Hb ( P < .0001 ) increases from baseline . Mean Hb increases for both IV iron groups were greater ( P < .02 ) than for no-iron and oral iron groups . The percentage of patients with hematopoietic responses was higher ( P < .01 ) in both IV iron groups ( each case 68 % ) compared with no-iron ( 25 % ) and oral iron ( 36 % ) groups . IV iron groups showed increases in energy , activity , and overall QOL from baseline , compared with a decrease in energy and activity for no-iron group and no change in activity or overall QOL for oral iron group . CONCLUSION rHuEPO increases Hb levels and improves QOL in patients with chemotherapy-related anemia . Magnitude of Hb increase and QOL improvement is significantly greater if IV iron is added BACKGROUND Preoperative treatment with rHuEPO ( epoetin alfa : EPREX , Janssen-Cilag ; or PROCRIT , Ortho Biotech ) in conjunction with iron supplementation increases the erythropoietic response in elective orthopedic surgery patients , but it is not known whether the magnitude of this response is dependent on the route of iron administration . STUDY DESIGN AND METHODS Non-iron-deficient patients undergoing elective orthopedic surgery ( N = 110 ) with baseline Hb > or = 10 to < or = 13 g per dL were r and omly assigned to receive either epoetin alfa ( 600 IU/kg ) plus IV iron ( n = 29 ) or oral iron ( n = 29 ) or placebo plus IV iron ( n = 25 ) or oral iron ( n = 27 ) in this 14-day study . RBC production , Hb , Hct , reticulocytes , iron status , and adverse events were monitored throughout the study . RESULTS Epoetin alfa treatment plus either oral or IV iron supplementation significantly increased total RBC production , Hb , Hct , and reticulocytes over the values seen with the respective placebo treatments ( p = 0.0001 ) . There were no differences between the epoetin alfa treatment groups . Placebo treatment plus oral or IV iron supplementation was not associated with increases in hematologic values . There were no differences in the incidence of adverse events among the treatment groups . CONCLUSION There was a comparable erythropoietic response to epoetin alfa , irrespective of the route of iron administration . The route of iron administration , therefore , does not modulate the erythropoietic response to epoetin alfa in patients who are not iron deficient . Safety and convenience benefits may be gained by adopting oral iron supplementation in this patient subset A single-blind , crossover comparative study was carried out in 40 patients with iron deficiency anaemia to assess the clinical efficacy and tolerance of once daily treatment with a controlled-release preparation of ferrous glycine sulphate ( ' Ferrocontin ' Continus ) and ferrous fumarate . Patients were allocated at r and om to receive 1 tablet ( equivalent to 100 mg elemental iron ) daily of one or other preparation for 4 weeks and were then crossed over to the alternative preparation for a further 4 weeks . The results showed that the significant increases in haemoglobin , packed cell volume and mean corpuscular volume were similar with both preparations . Seventeen patients reported gastro-intestinal side-effects on one or both preparations and the incidence was slightly less in patients whilst receiving the ferrous glycine sulphate preparation . In 3 patients , side-effects were sufficiently severe whilst taking ferrous fumarate to warrant interruption of treatment in 2 and withdrawal from the study in the other Purpose To determine if early recovery from severe postoperative anemia is accelerated byiv iron therapy alone or in combination with recombinant erythropoietin ( EPO ) . Methods In this double-blinded , placebo-controlled r and omized study , consenting adult patients without preoperative anemia whose hemoglobin concentration ( Hb ) was 70 to 90 g·L-1 on the first day after cardiac or orthopedic surgery ( POD 1 ) were assigned to one of three groups : control , iv iron alone ( 200 mg of iron sucrose on POD 1 , 2 , and 3 ) or in combination with EPO ( 600 U·kg-1 on POD 1 and 3 ) . The primary outcome was increase in Hb ( adjusted for red blood cell transfusions ) from POD 1 to 7 . Analysis was by intention-to-treat in patients for whom the primary outcome was available . Group effect was analyzed by the ANOVA test , and between-group differences were specified with a Duncan multiple-range test . Results The primary outcome was available in 31 of 38 r and omized patients . The average POD 1 Hb was 84 ± 4 g·L-1 . There were no between-group differences in outcomes except for higher reticulocyte counts on POD-7 in the combination group . The average adjusted one-week increases in Hb were 7 ± 8 g·L-1 in the control group ( n = 10 ) , 9 ± 9 g·L-1 in theiv iron group ( n = 11 ) , and 10 ± 14 g·L-1 in the combination group ( n = 10 ) . The average adjusted six-week increases in Hb were 37 ± 14 g·L-1 in the control group , 40 ± 7 g·L-1 in theiv iron group , and 45 ± 12 g·L-1 in the combination group . Conclusion Early postoperative treatment withiv iron alone or in combination with EPO does not appear to accelerate early recovery from postoperative anemia . RésuméObjectifVérifier si la récupération précoce ďune sévère anémie postopératoire est accélérée par le fer iv seul ou en combinaison avec de ľérythropoÏétine recombinante (EPO).MéthodePour ľétude à double insu , r and omisée et contrôlée contre placebo , des adultes sans anémie préopératoire , chez qui la concentration ďhémoglobine ( Hb ) était de 70 à 90 g·L-1 au premier jour post-opération cardiaque ou orthopédique ( JPO 1 ) , ont été assignés à ľun des trois groupes : témoin , fer iv seul ( 200 mg de sucrose ferreux aux JPO 1 , 2 et 3 ) ou en combinaison avec de ľEPO ( 600 U·kg-1 aux JPO POD 1 et 3 ) . Le résultat principal était une hausse de ľHb ( ajustée pour les transfusions de culots globulaires ) des JPO 1 à 7 . Ľévaluation , pour les patients ayant atteint ce résultat , utilisait ľanalyse par intention de traiter . Ľeffet de groupe a été analysé par le test ANOVA test et les différences intergroupes ont été précisées avec le test à gamme multiple de Duncan . RésultatsLe résultat principal était atteint chez 31 des 38 patients r and omisés . La moyenne de ľHb au JPO 1 a été de 84 ± 4 g·L-1 . Il n’y a pas eu de différence de résultat intergroupe sauf pour une numération plus élevée des réticulocytes au JPO 7 dans le groupe ďEPO . Les hausses moyennes ďHb ajustées sur une semaine ont été de 7 ± 8 g·L-1dans le groupe témoin ( n = 10 ) , 9 ± 9 g·L-1 avec le fer iv ( n = 11 ) et 10 ± 14 g·L-1 avec ľEPO ( n = 10 ) . Les hausses moyennes ďHb ajustées sur six semaines ont été de 37 ± 14 g·L-1 chez les témoins , 40 ± 7 g·L-1 avec le fer iv et 45 ± 12 g·L-1 avec ľEPO . Conclusion Le traitement postopératoire précoce avec du fer iv seul ou en combinaison avec ľEPO ne semble pas hâter la récupération de ľanémie postopératoire Background : Oral iron therapy is often used after orthopaedic surgery to improve haemoglobin levels . The aim of the present trial was to determine if administration of oral iron after orthopaedic surgery results in a better improvement of haemoglobin levels than a control treatment BACKGROUND The main objective of this study was to determine the efficacy of intravenous ( IV ) iron sucrose therapy reducing transfusion requirements in elderly patients undergoing hip fracture surgery . STUDY DESIGN AND METHODS This study was a prospect i ve r and omized controlled trial involving 200 patients undergoing hip fracture surgery . Group A ( 100 patients ) received st and ard treatment , while Group B ( 100 patients ) received iron sucrose ( 600 mg IV ) . The primary endpoint was the number of patients that were transfused postoperatively . The secondary endpoints were the rate of red blood cell units used , hematimetric variables of blood tests , mortality , infection rates , length of hospital stay , and appearance of side effects . RESULTS Differences in the percentage of patients requiring transfusion ( Group A 41.3 % vs. Group B 33.3 % ) and in the number of concentrates transfused ( 0.87±1.21 for Group A vs. 0.76±1.16 for Group B ) were not significant for the patient group as a whole , but were significant for patients with intracapsular fractures ( 45.7 % required transfusion in Group A vs. 14.3 % in Group B ; p<0.005 ) and in patients with a baseline hemoglobin ( Hb ) level of 12 g/dL or more ( 35.2 % required transfusions in Group A vs. 19 % in Group B ; p<0.05 ) . CONCLUSIONS Transfusion requirements in patients with intracapsular fracture or baseline Hb level of 12 g/dL or more appear to be reduced by IV iron sucrose therapy , but there was no difference in morbidity , mortality , or length of hospital stay . The treatment is safe and hastens recovery from blood loss BACKGROUND Anemia in heart failure patients and has been associated with increased morbi-mortality . Previous studies have treated anemia in heart failure patients with either erythropoietin alone or combination of erythropoietin and intravenous ( i.v . ) iron . However , the effect of i.v . or oral ( p.o . ) iron supplementation alone in heart failure patients with anemia was virtually unknown . AIM To compare , in a double-blind design , the effects of i.v . iron versus p.o . iron in anemic heart failure patients . METHODS IRON-HF study was a multicenter , investigator initiated , r and omized , double-blind , placebo controlled trial that enrolled anemic heart failure patients with preserved renal function , low transferrin saturation ( TSat ) and low-to-moderately elevated ferritin levels . Interventions were Iron Sucrose i.v . 200 mg , once a week , for 5 weeks , ferrous sulfate 200 mg p.o . TID , for 8 weeks , or placebo . Primary endpoint was variation of peak oxygen consumption ( peak VO2 ) assessed by ergospirometry over 3 month follow-up . RESULTS Eighteen patients had full follow-up data . There was an increment of 3.5 ml/kg/min in peak VO2 in the i.v . iron group . There was no increment in peak VO2 in the p.o . iron group . Patients ' ferritin and TSat increased significantly in both treated groups . Hemoglobin increased similarly in all groups . CONCLUSION I.v . iron seems to be superior in improving functional capacity of heart failure patients . However , correction of anemia seems to be at least similar between p.o . iron and i.v . iron supplementation BACKGROUND The objective was to evaluate efficacy and safety of rapid , large-dose intravenous ( IV ) administration of ferric carboxymaltose compared to oral iron in correcting iron deficiency anemia due to heavy uterine bleeding . STUDY DESIGN AND METHODS In a r and omized , controlled trial , 477 women with anemia , iron deficiency , and heavy uterine bleeding were assigned to receive either IV ferric carboxymaltose ( < or=1000 mg over 15 min , repeated weekly to achieve a total calculated replacement dose ) or 325 mg of ferrous sulfate ( 65 mg elemental iron ) prescribed orally thrice daily for 6 weeks . RESULTS Compared to those assigned to ferrous sulfate , more patients assigned to ferric carboxymaltose responded with a hemoglobin ( Hb ) increase of 2.0 g/dL or more ( 82 % vs. 62 % , 95 % confidence interval for treatment difference 12.2 - 28.3 , p < 0.001 ) , more achieved a 3.0 g/dL or more increase ( 53 % vs. 36 % , p < 0.001 ) , and more achieved correction ( Hb > or= 12 g/dL ) of anemia ( 73 % vs. 50 % , p < 0.001 ) . Patients treated with ferric carboxymaltose compared to those prescribed ferrous sulfate reported greater gains in vitality and physical function and experienced greater improvement in symptoms of fatigue ( p < 0.05 ) . There were no serious adverse drug events . CONCLUSIONS In patients with iron deficiency anemia due to heavy uterine bleeding , rapid IV administration of large doses of a new iron agent , ferric carboxymaltose , is more effective than oral iron therapy in correcting anemia , replenishing iron stores , and improving quality of life BACKGROUND Anemia is a common finding in heart failure ( HF ) patients and has been associated with increased morbidity and mortality . It is generally denominated as anemia of chronic disease ( ACD ) , but the association with true ferropenic anemia is common . Many studies have investigated the effects of treating anemia in HF patients with either erythropoietin alone or combination of erythropoietin and intravenous iron . However , the effect of iron supplementation alone in HF patients with ACD , ferropenic anemia , or both is unknown . METHODS AND RESULTS IRON-HF study is a multicenter , investigator initiated , r and omized , double-blind , placebo controlled trial that will enroll anemic HF patients with relatively preserved renal function , low transferrin saturation , low iron levels , and low to moderately elevated ferritin levels . Interventions are iron sucrose intravenously 200 mg once per week for 5 weeks , ferrous sulfate 200 mg by mouth 3 times per day for 8 weeks , or placebo . The primary objective is to assess the impact of iron supplementation ( intravenously or by mouth ) compared with placebo in HF patients with anemia from deficient iron availability . The primary end point is variation of peak oxygen consumption assessed by ergospirometry over 3-month follow-up . Secondary end points include functional class , brain natriuretic peptide levels , quality of life scores , left ventricular ejection fraction , adverse events , HF hospitalization , and death . CONCLUSIONS The results of IRON-HF should help to clarify the potential clinical impact of mild to moderate anemia correction in HF patients Iron deficiency may exacerbate symptoms in the Restless Legs Syndrome ( RLS ) . We investigated the effect of intravenous iron sucrose or placebo on symptoms in patients with RLS and mild to moderate iron deficit . Sixty patients with primary RLS ( seven males , age 46 ( 9 ) years , S-ferritin < or = 45 microg/L ) recruited from a cohort of 231 patients were r and omly assigned in a 12-months double-blind , multi-centre study of iron sucrose 1000 mg ( n = 29 ) or saline ( n = 31 ) . The primary efficacy variable was the RLS severity scale ( IRLS ) score at week 11 . Median IRLS score decreased from 24 to 7 ( week 11 ) after iron sucrose and from 26 to 17 after placebo ( P = 0.123 , N.S. for between treatment comparison ) . The corresponding scores at week 7 were 12 and 20 in the two groups ( P = 0.017 ) . Drop out rate because of lack of efficacy at 12 months was 19/31 after placebo and 5/29 patients after iron sucrose ( Kaplan-Meier estimate , log rank test P = 0.0006 ) suggesting an iron induced superior long term RLS symptom control . Iron sucrose was well tolerated . This study showed a lack of superiority of iron sucrose at 11 weeks but found evidence that iron sucrose reduced RLS symptoms both in the acute phase ( 7 weeks ) and during long-term follow up in patients with variable degree of iron deficiency . Further studies on target patient groups , dosing and dosing intervals are warranted before iron sucrose could be considered for treatment of iron deficient patients with RLS PURPOSE To determine long-term survival and potential cure with salvage chemotherapy with paclitaxel plus gemcitabine after progression after both cisplatin combination chemotherapy and subsequent high-dose chemotherapy with t and em transplantation . PATIENTS AND METHODS One hundred eighty-four patients received salvage high-dose chemotherapy at Indiana University ( Indianapolis , IN ) from February 1996 to December 2004 . After further evidence of progressive disease , 32 patients were subsequently treated with paclitaxel 100 mg/n2 over 1 hour plus gemcitabine 1,000 mg/m2 over 30 minutes , days 1 , 8 , and 15 every 4 weeks for a maximum of six courses . This is a retrospective review of this patient population . Patients were evaluated for response , duration of response , and survival . Patients were ineligible if they received prior paclitaxel or gemcitabine . RESULTS Ten ( 31 % ) of 32 patients achieved objective response , including four partial remissions ( 2- to 6-month duration ) and six complete responses ( CRs ) . Four of these six CRs ( 12.5 % of total patient population ) are continuously disease free ( NED ) with paclitaxel plus gemcitabine alone ( no postchemotherapy surgery ) at more than 20 , 40 , 44 , and 57 months from start of paclitaxel plus gemcitabine , respectively . One additional CR is currently NED more than 63 months after paclitaxel plus gemcitabine with two subsequent resections of carcinoma . CONCLUSION Long-term disease-free survival is possible with paclitaxel plus gemcitabine in this patient population that progressed after high-dose chemotherapy , and had not received prior paclitaxel or gemcitabine OBJECTIVE The incidence of anemia in the cervical cancer patients treated with concurrent chemoradiotherapy is estimated to be more than 50 % . Transfusion has been the mainstay of hematologic support with its inherent hazards including infection and transfusion reaction . The aim of this study was to examine the impact of intravenously administered iron sucrose on the prevention of anemia in the cervical cancer patients undergoing concurrent chemoradiotherapy . METHODS From Oct. 2003 to Dec. 2005 , 75 patients were treated with platinum-based concurrent chemoradiotherapy . Thirty patients received 200 mg of iron sucrose intravenously ( study group ) and 45 patients did not receive it ( control group ) . RESULTS In the study group , only 12 ( 40.0 % ) patients required blood transfusions , whereas 29 ( 64.0 % ) patients in the control group needed blood transfusions ( P=0.04 ) . Mean transfusion units were 1.87 units in the study group and 3.58 units in the control group ( P=0.04 ) . CONCLUSION This study showed that intravenous supply of iron sucrose could decrease transfusion requirement and increase serum hemoglobin level in patients with cervical carcinoma undergoing concurrent chemoradiotherapy . Therefore , intravenously administered iron sucrose would be effective in the prevention of anemia of cervical cancer patients receiving concurrent chemoradiotherapy OBJECTIVE To evaluate the use of oral iron replacement therapy as an effective treatment for acute surgically induced anemia . DESIGN Double-blind , placebo-controlled , r and omized clinical trial . SETTING Perioperative acute care hospital and a surgery clinic for a single cardiothoracic physician group . PATIENTS One hundred twenty-eight men and postmenopausal women , 50 years of age or older , admitted for elective coronary artery bypass surgery over a consecutive 8-month period . OUTCOME MEASURES Before surgery : serum iron , serum ferritin , hemoglobin and hematocrit . Six days after surgery : hemoglobin and hematocrit . Mean of 59 days after surgery : serum iron , serum ferritin , hemoglobin and hematocrit . INTERVENTION Patients were r and omized to one of four groups : control group ; placebo group ; low-dose group , 50 mg elemental iron + 60 mg ascorbic acid in a multi-vitamin daily ; and usual-dose group , 200 mg elemental iron daily . RESULTS One hundred twenty-one subjects completed the study : 100 men ( 82.6 % ) mean age 64.5 years and 21 women ( 17.4 % ) , mean age 65.7 years . There were no statistically significant age or gender differences among groups . Statistical analysis revealed , except for side effects , no differences between or among groups for any variable measured during the last two time intervals . The mean hemoglobin and hematocrit of the entire sample at 6 days was 9.5 + /- 1.2 gm/dl and 28 % + /- 2.3 % , respectively . At a mean of 59 days later these values increased equally for all groups to a mean for the cohort of 13.6 + /- 1 gm/dl for hemoglobin and 40.6 % + /- 3 for hematocrit . Serum iron and ferritin were within the normal range . The 200 mg group experienced significantly more side effects ( p < 0.01 ) . CONCLUSION Thus the use of oral iron supplements for the treatment of acute blood loss anemia after uncomplicated coronary artery bypass surgery did not assist in restoring red blood cell mass or help maintain total body iron stores INTRODUCTION Allogeneic blood transfusion confers a risk to the recipient . Recent trials in colorectal surgery have shown that the most significant factors predicting blood transfusion are pre-operative haemoglobin , operative blood loss and presence of a transfusion protocol . We report a r and omised , controlled trial of oral ferrous sulphate 200 mg TDS for 2 weeks ' pre-operatively versus no iron therapy . PATIENTS AND METHODS Patients diagnosed with colorectal cancer were recruited from out-patient clinic and haematological parameters assessed . R and omisation was co-ordinated via a telephone r and omisation centre . RESULTS Of the 49 patients recruited , 45 underwent colorectal resection . There were no differences between those patients not receiving iron ( n = 23 ) and the iron-supplemented group ( n = 22 ) for haemoglobin at recruitment , operative blood loss , operation duration or length of hospital stay . At admission to hospital , the iron-supplemented group had a higher haemoglobin than the non-iron treated group ( mean haemoglobin concentration 13.1 g/dl [ range , 9.6 - 17 g/dl ] versus 11.8 g/dl [ range , 7.8 - 14.7 g/dl ] ; P = 0.040 ; 95 % CI 0.26 - 0.97 ) and were less likely to require operative blood transfusion ( mean 0 U [ range , 0 - 4 U ] versus 2 U [ range , 0 - 11 U ] transfused ; P = 0.031 ; 95 % CI 0.13 - 2.59 ) . This represented a cost reduction of 66 % ( 47 U of blood = pound4700 versus oral FeSO(4 ) at pound30 + 15 U blood at pound1500 ) . At admission , ferritin in the iron-treated group had risen significantly from 40 microg/l ( range , 15 - 222 microg/l ) to 73 microg/l ( range , 27 - 386 microg/l ; P = 0.0036 ; 95 % CI 46.53 - 10.57 ) . CONCLUSIONS Oral ferrous sulphate given pre-operatively in patients undergoing colorectal surgery offers a simple , inexpensive method of reducing blood transfusions BACKGROUND Anemia as a consequence of surgery is often treated with iron therapy . The evidence base for this practice is limited . To determine if oral iron therapy is beneficial for the treatment of anemia after surgery for the treatment of a hip fracture , we undertook a prospect i ve , r and omized controlled trial . METHODS Three hundred patients with a hemoglobin level of < 110 g/L after treatment for a hip fracture were r and omized to receive either a twenty-eight-day course of ferrous sulfate therapy or no iron therapy . Hemoglobin levels were measured at six weeks after surgery . The length of the hospital stay and the mortality rate at one year were compared between groups . RESULTS The mean rise in hemoglobin levels six weeks after discharge from the hospital was 21 g/L in the iron group , compared with 18 g/L in the no-iron group ( p = 0.07 ) . There was no significant difference between the two groups with regard to the length of hospital stay or the mortality rate . Seventeen percent of the patients who were allocated to iron therapy reported adverse effects of the medication . CONCLUSIONS The present study demonstrated that iron therapy had no clinical ly relevant benefit when used to treat anemia associated with a hip fracture In cancer patients mild-moderate non-chemotherapy-induced iron deficiency anemia ( IDA ) is usually treated with oral iron salts , mostly ferrous sulfate . In this study , we compare efficacy and toxicity of oral ferrous bisglycinate chelate and ferrous sulfate in cancer patients with mild IDA . Twenty-four patients operated on for solid tumors ( 10 breast , 12 colorectal , 2 gastric ) , aged 61±10 years ( range 45 - 75 ) , with non-chemotherapy-induced hemoglobin ( Hb ) values between 10 and 12 g/dL and ferritin lower than 30 ng/mL were r and omized to receive oral ferrous bisglycinate chelate , 28 mg per day for 20 days , and then 14 mg per day for 40 days ( 12 patients ) ( A group ) or oral ferrous sulphate , 105 mg per day for 60 days ( 12 patients ) ( B group ) . Values of hemoglobin and ferritin obtained at diagnosis , 1 and 2 months from the beginning of treatment were compared . Adverse events ( AEs ) related to the two treatments were recorded . In the 12 patients treated with ferrous bisglycinate chelate , basal hemoglobin and ferritin values ( mean±SD ) were 11.6±0.8 g/dL and 16.1±8.0 ng/mL. After 2 months of treatment , they were 13.0±1.4 g/dL and 33.8±22.0 ng/mL , respectively ( P=0.0003 and P=0.020 ) . In the group treated with ferrous sulphate , hemoglobin and ferritin mean values were 11.3±0.6 g/dL and 19.0±6.4 ng/mL basally , and 12.7±0.70 g/dL and 40.8±28.1 ng/mL ( P<0.0001 and P=0.017 ) after 2 months of treatment . AEs occurred in six cases . In all these six cases , two ( 17 % ) treated with ferrous bisglycinate chelate and four ( 33 % ) with ferrous sulphate , toxicity was grade 1 . In conclusion , these data suggest that ferrous bisglycinate chelate has similar efficacy and likely lower GI toxicity than ferrous sulphate given at the conventional dose of 105 mg per day for the same time OBJECTIVE To determine if column agglutination technology ( CAT ) for titration of anti-D and anti-c concentrations produces comparable results to those obtained by continuous flow analyser ( CFA ) . BACKGROUND Anti-D and anti-c are the two commonest antibodies that contribute to serious haemolytic disease of the foetus and neonate ( HDFN ) . Current practice in the UK is to monitor these antibodies by CFA quantification , which is considered more reproducible and less subjective than manual titration by tube IAT ( indirect antiglobulin test ) . CAT is widely used in transfusion laboratory practice and provides a more objective endpoint than tube technique . MATERIAL S AND METHODS Antenatal sample s were ( i ) quantified using CFA and ( ii ) titrated using CAT with the reaction strength recorded by a card reader and expressed as a titre score ( TS ) . RESULTS The TS rose in accordance with levels measured by quantification and was able to distinguish antibody levels above and below the threshold of clinical significance . CONCLUSION CAT titre scores provided a simple and reproducible method to monitor anti-D and anti-c levels . The method was sensitive to a wide range of antibody levels as determined by quantification . This technique may have the potential to replace CFA quantification by identifying those cases that require closer monitoring for potential HDFN Objective . Patients with inflammatory bowel disease ( IBD ) often have low iron stores or anaemia . There is controversy about whether iron should be supplemented orally or intravenously ( i.v . ) . The purpose of this study was to investigate whether treatment with intravenous iron is superior to treatment with oral iron . The primary end-points were response and remaining anaemia at the end of treatment ( EOT ) . Material and methods . Ninety-one patients with IBD and anaemia ( B-Hb < 115 g/L ) were r and omized to oral iron sulphate ( n=46 ) or intravenous iron sucrose ( n=45 ) treatment for 20 weeks . Results . Forty-three patients in the intravenous iron group completed the study compared to 35 patients in the oral iron group ( p=0.0009 ) . Only 22 patients ( 48 % ) tolerated the prescribed oral dose , and 52 % reduced the dose or withdrew from treatment because of poor tolerance . At EOT , 47 % patients in the oral iron group increased their B-Hb by ≥20 g/L , compared with 66 % in the intravenous iron group ( p=0.07 ) . In the oral iron group , 41 % still had anaemia versus 16 % of the patients in the intravenous iron group ( p=0.007 ) , and 22 % versus 42 % reached their reference B-Hb level ( p=0.04 ) . Treatment with intravenous iron sucrose improved iron stores faster and more effectively than oral iron ( p=0.002 ) . Under treatment with intravenous iron , 74 % of the patients had no anaemia and normal S-ferritin levels ( > 25 µg/L ) at EOT compared with 48 % of patients receiving oral iron ( p=0.013 ) . Conclusions . Treatment with intravenous iron sucrose is effective , safe , well tolerated and superior to oral iron in correcting haemoglobin and iron stores in patients with IBD BACKGROUND & AIMS Iron deficiency anemia ( IDA ) is common in chronic diseases and intravenous iron is an effective and recommended treatment . However , dose calculations and inconvenient administration may affect compliance and efficacy . We compared the efficacy and safety of a novel fixed-dose ferric carboxymaltose regimen ( FCM ) with individually calculated iron sucrose ( IS ) doses in patients with inflammatory bowel disease ( IBD ) and IDA . METHODS This r and omized , controlled , open-label , multicenter study included 485 patients with IDA ( ferritin < 100 μg/L , hemoglobin [ Hb ] 7 - 12 g/dL [ female ] or 7 - 13 g/dL [ male ] ) and mild-to-moderate or quiescent IBD at 88 hospitals and clinics in 14 countries . Patients received either FCM in a maximum of 3 infusions of 1000 or 500 mg iron , or Ganzoni-calculated IS dosages in up to 11 infusions of 200 mg iron . Primary end point was Hb response ( Hb increase ≥ 2 g/dL ) ; secondary end points included anemia resolution and iron status normalization by week 12 . RESULTS The results of 240 FCM-treated and 235 IS-treated patients were analyzed . More patients with FCM than IS achieved Hb response ( 150 [ 65.8 % ] vs 118 [ 53.6 % ] ; 12.2 % difference , P = .004 ) or Hb normalization ( 166 [ 72.8 % ] vs 136 [ 61.8 % ] ; 11.0 % difference , P = .015 ) . Both treatments improved quality of life scores by week 12 . Study drugs were well tolerated and drug-related adverse events were in line with drug-specific clinical experience . Deviations from scheduled total iron dosages were more frequent in the IS group . CONCLUSIONS The simpler FCM-based dosing regimen showed better efficacy and compliance , as well as a good safety profile , compared with the Ganzoni-calculated IS dose regimen Advanced-stage cancer patients often suffer from anemia that closely resembles the anemia of chronic inflammatory diseases characterized by specific changes in iron homeostasis and absorption . i.v . iron improves the efficacy of recombinant human erythropoietin ( rHuEPO ) in anemic cancer patients undergoing chemotherapy . We report the results of an open-label , r and omized , prospect i ve trial aim ed at testing the efficacy and safety of treatment with oral lactoferrin versus i.v . iron , both combined with rHuEPO , for the treatment of anemia in a population of 148 advanced cancer patients undergoing chemotherapy . All patients received s.c . rHuEPO-beta , 30,000 UI once weekly for 12 weeks , and were r and omly assigned to ferric gluconate ( 125 mg i.v . weekly ) or lactoferrin ( 200 mg/day ) . Both arms showed a significant hemoglobin increase . No difference in the mean hemoglobin increase or the hematopoietic response , time to hematopoietic response , or mean change in serum iron , C-reactive protein , or erythrocyte sedimentation rate were observed between arms . In contrast , ferritin decreased in the lactoferrin arm whereas it increased in the i.v . iron arm . In conclusion , these results show similar efficacy for oral lactoferrin and for i.v . iron , combined with rHuEPO , for the treatment of anemia in advanced cancer patients undergoing chemotherapy OBJECTIVES The aim of this study was to examine whether intravenous iron III-hydroxide sucrose complex ( IHSC ) used alone was sufficient to provide rapid correction of anemia after cardiac surgery and whether additional stimulation of erythropoiesis is possible by means of a single low dose of recombinant-human erythropoietin ( r-HuEPO ) administration . DESIGN Prospect i ve , r and omized , double-blind study . SETTING The study was conducted in a university hospital . PARTICIPANTS One hundred twenty American Society of Anesthesiologists II or III patients , who underwent elective cardiac surgery using cardiopulmonary bypass and in whom postpump hemoglobin ranged between 7 and 10 g/dL. INTERVENTIONS Patients were divided into 3 groups : group I = control ; group II received postoperative intravenous iron supplementation with an iron III-hydroxide sucrose complex ( IHSC ) ; and group III received IV iron and a single dose of r-HuEPO ( 300 U/kg ) . MEASUREMENTS AND RESULTS No significant difference in transfusion needs was observed among the 3 groups ( 22 % , 25 % , and 17 % of patients transfused in groups I , II , and III , respectively ) . Hemoglobin levels , reticulocyte counts , and serum ferritin levels were evaluated at different time intervals ( until day 30 postoperatively ) . No side effects because of iron administration were noted in the study . Reticulocyte counts increased rapidly at day 5 ( 2.24 % + /- 1.11 % , 1.99 % + /- 1.44 % , and 3.84 % + /- 2.02 % in groups I , II , and III , respectively ) and decreased after day 15 in the 3 groups . Ferritin levels increased significantly at day 5 in the 2 treated groups ( 899.33 + /- 321.55 ng/mL in group II , 845.75 + /- 289.96 ng/mL in group III v 463.15 + /- 227.74 ng/mL in group I ) . In group I , ferritin levels , after a slight elevation on day 5 , decreased at day 15 to lower than baseline levels . No significant difference in hemoglobin increase was noted among the 3 groups . CONCLUSION Postoperative intravenous iron supplementation alone or in combination with a single dose of r-HuEPO ( 300 U/kg ) is not effective in correcting anemia after cardiac surgery OBJECTIVES There is evidence of iron deficiency ( ID ) in patients treated with lipoprotein apheresis . Aim of this study was to assess ID in apheresis patients and to study its management comparing safety and efficacy of two approved intravenous ( i.v . ) iron formulations . METHODS Inclusion criteria were defined as a ) serum ferritin < 300 μg/l and transferrin saturation < 20 % , b ) ferritin < 100 μg/l . Both iron deficient alone and ID anemic ( IDA ) patients were included . Other causes for anemia were ruled out by thorough history-taking and examination/blood tests . Patients were treated with six different lipoprotein apheresis methods : DALI , Liposorber D , TheraSorb LDL , HELP , MONET and Lipidfiltration . 50 patients were r and omized to either ferric carboxymaltose ( FCM , 500 - 1000 mg as single shot infusion over 20 min ) or ferric gluconate ( FG , 62.5 mg once weekly ) . RESULTS 50 of 67 patients of our Lipoprotein Apheresis Center showed iron deficiency . Both i.v . iron formulations studied were equally safe ( no serious adverse events ( SAEs ) , 6 patients /group showed adverse events ( AEs ) ) and both effective ( clinical ly and with respect to laboratory data ) in lipoprotein apheresis patients , however FCM led to a more rapid and steeper rise of iron parameters . CONCLUSIONS ID and IDA are common findings in lipoprotein apheresis patients . The pathogenesis remains yet poorly understood and is probably multifactorial . Differential diagnosis of ID/IDA is as essential as differential therapy . H and led with care , older i.v . iron preparations like FG appear to be safe and effective in lipoprotein apheresis patients . However , novel formulations like FCM can be administered rapidly at higher doses due to high complex stability , allowing faster filling of iron stores . Newer laboratory parameters ( Reticulocyte-He , low/medium/high fluorescence reticulocytes ( LFR/MFR/HFR ) ) assessing iron status may be helpful in early detection of ID and in monitoring iron replacement therapy OBJECTIVE To assess the efficacy of oral iron therapy in the recovery of patients ' hemoglobin levels after major surgery . DESIGN R and omized controlled trial . SETTING Private orthopedic practice confined to one large community hospital . PATIENTS One hundred seventy consecutive elderly patients undergoing hip surgery ; 75 failed to meet entry hematologic or medical criteria ; 95 were r and omized , with 16 withdrawn because of complications . INTERVENTION Thirty-seven patients received ferrous sulfate orally four times a day for the duration of their hospitalization . Forty-two patients who received no iron supplement served as the control group . MAIN OUTCOME MEASURES Changes in hemoglobin levels and reticulocyte counts over the 2- to 3-week follow-up period . RESULTS There was no significant difference in mean hemoglobin levels between the treatment and control groups ( 95 % confidence interval [ CI ] for difference of -6.6 to 5.4 g/L ) . Corrected reticulocyte fractions increased equally in both groups ( 95 % CI for difference of -9 x 10(3 ) to 2 x 10(-3 ) . The study was design ed to detect a difference in mean hemoglobin levels of 8.5 g/L or greater or a difference in mean reticulocyte fraction of 10 x 10(-3 ) between the two groups with a power of 0.80 at the .05 ( two-sided ) level of significance . CONCLUSION The administration of oral iron supplements to elderly , healthy orthopedic patients postoperatively did not hasten the recovery of hemoglobin levels , provided adequate tissue iron stores were present The objective of the study is to evaluate the bioavailability , efficacy and safety of a new modified-release ( MR ) formulation of carbonyl iron ( 45 mg ) relative to a commercially available conventional formulation of ferrous fumarate ( 300 mg ) in adult Indian patients with clinical and laboratory diagnosis of nutritional iron deficiency anaemia . This prospect i ve , comparative , r and omised , double-blind study was carried out among 60 patients received a single daily dose of either MR carbonyl iron or ferrous fumarate for 12 weeks . The effect of therapy on haematological parameters and iron status and estimation of bioavailability were the main efficacy outcomes . There was a significant ( p<0.05 ) increase in mean haemoglobin levels , reticulocyte counts , haematocrit and mean corpuscular volume in MR carbonyl iron group compared to ferrous fumarate group . There was also an increase in mean serum iron and ferritin levels and a corresponding decrease in total iron binding capacity in MR carbonyl iron group compared to ferrous fumarate group at the end of 12 weeks therapy . The estimated overall bioavailability of MR carbonyl iron was about 147 % that of ferrous fumarate . Both the formulations were equally well-tolerated and adverse events were mainly gastrointestinal in nature . The prevalence of adverse events was slightly more in the ferrous fumarate group . It can be concluded that the MR formulation of carbonyl iron was more efficacious than ferrous fumarate in correcting haematologic abnormalities and improving iron status in patients with nutritional iron deficiency anaemia . In conditions where efficacy is an important consideration , the higher bioavailability of MR carbonyl iron may make it the treatment of choice for nutritional iron deficiency anaemia A prospect i ve , controlled , double-blind , double-dummy , multicenter clinical trial was made to assess the efficacy and tolerability of iron-protein-succinylate ( ITF 282 ) in comparison with a well known iron preparation in the treatment of iron deficiency or iron deficient anemia . One thous and and ninety-five patients affected with iron deficiency or overt iron deficient anemia were r and omized to receive either two ITF 282 tablets/day ( 60 mg iron each ) or a commercially available ferrous sulphate controlled release tablet ( one tablet containing 105 mg iron/day ) . Five hundred and forty-nine patients received ITF 282 ; 546 patients were treated with ferrous sulphate . Both treatments lasted 60 days . The treatment outcome was checked by evaluating special hematology , symptomatology , safety hematology and hematochemistry . After two months of treatment , the normalization of the main hematologic parameters in both groups was detected . Although in the first month the reference treatment appears to provide somewhat faster results , at the end of the observation , the values of hematocrit , hemoglobin and ferritin were greater in the ITF 282 group , indicating a more progressive and steady therapeutic effect . The overall clinical rating was significantly in favor of ITF 282 , with 78.9 % of favorable results vs 67.6 % . By dividing the patient population according to pathological conditions ( iron deficiency or overt anemia ) , or according to the etiopathogenesis of the iron deficiency ( increased requirement , or increased loss in adults and in the elderly ) , separate analyses on the treatment outcome were made ( and have been included ) . The general tolerability , although favorable with both treatments , was significantly more favorable with ITF 282 . With this medication , 63 patients ( 11.5 % ) complained of 69 adverse reactions ( 25 heartburn , 19 constipation , 25 abdominal pain ) vs 141 events reported by 127 patients ( 26.3 % ) with the reference medication ( 33 heartburn , 31 epigastric pain , 23 constipation , 32 abdominal pain , 8 skin rash , 14 nausea ) . These observations confirm that , although the most modern preparations of ferrous sulphate exhibit a relatively low frequency of adverse events of limited clinical concern , it is nevertheless possible to decrease both the prevalence and the duration of such events without prejudice for the clinical efficacy , with the use of more " physiological " preparations in which the iron is reversibly bound to a protein carrier , thus effectively removing one of the main obstacles to the correct compliance with treatments that must be administered for prolonged periods of time Levels of hepcidin , a major regulator of iron homeostasis , may identify patients with iron deficiency anemia ( IDA ) who will not respond to oral iron therapy . In this study , IDA patients underwent a 14‐day trial ( run‐in ) course of ferrous sulfate therapy . Nonresponders ( Hgb increase < 1 g/dL with 67 % compliance rate ) were r and omized to IV ferric carboxymaltose ( FCM ; two injections of 750 mg ) or further oral iron for 14 days . Screening hepcidin levels were 38.4 versus 11.3 ng/mL , P = 0.0002 in nonresponders versus responders to a trial of oral iron . Hepcidin of > 20 ng/mL , showed sensitivity of 41.3 % , specificity of 84.4 % , and positive predictive value of 81.6 % for predicting nonresponsiveness to oral iron . PPVs for ferritin > 30 ng/mL or transferrin saturation (TSAT)>15 % were 59.2 and 55 % , respectively . Negative predictive values for hepcidin , ferritin , and TSAT were 46.3 , 22.7 , and 19.7 , respectively . FCM versus oral iron showed Hgb increases of ≥1 gm/dL in 65.3 % versus 20.8 % ( P < 0.0001 ) and Hgb increases of 1.7 ± 1.3 versus 0.6 ± 0.9 g/dL ( P = 0.0025 ) , respectively . We conclude that hepcidin predicts nonresponsiveness to oral iron in patients with IDA and is superior to TSAT or ferritin for this purpose . Nonresponse to oral iron therapy does not rule out IDA , since two‐thirds of patients subsequently responded to intravenous iron . Am . J. Hematol . 88:97–101 , 2013 . © 2012 Wiley Periodicals , Forty patients suffering from iron deficiency anemia were r and omly assigned to receive iron succinylprotein complex ( containing 80 mg of elemental iron daily ) or iron gluconate complex ( containing 125 mg of elemental iron daily ) for two months . Improvement , as measured by hematological variables , was noted in both groups , iron succinylprotein complex being superior to iron gluconate complex on some measures . Side effects were reported by two of the 20 patients treated with iron succinylprotein complex and by ten of the 20 patients treated with iron gluconate complex An investigation has been carried out to study the efficacy of iron-poly ( sorbitol-gluconic acid ) complex ( Ferastral ) in the treatment of iron deficiency anaemia . Ferastral was given by the intramuscular route every second or third day in a dose of 500 mg , divided in two injections . These were compared with the results of a group treated with iron-dextran given by Total Dose Infusion ( TDI ) . A total of 38 patients were treated with either Ferastral or iron-dextran by TDI , respectively , given according to r and om allocation . The total dose of iron given in both groups was 1 500 mg of elemental iron . The parameters investigated were haematocrit and haemoglobin . Side-effects were also recorded . The results in the group treated with Ferastral where the mean initial haemoglobin value was 9.5 g/100 ml showed a mean haemoglobin increase to 13.2 g/100 ml after eight weeks . Initial haemoglobin values and haemoglobin increase for iron-dextran by TDI were quite similar . Three patients in the Ferastral group had transient discolouration at the site of injection and one patient in the iron-dextran TDI-group had a serious allergic reaction Abstract : 49 female blood donors with iron‐deficiency anemia were treated with equal doses of iron either as carbonyl iron or ferrous sulfate in a r and omized , double‐blind fashion . The prevalence of side‐effects was similar in the two groups . Mean values for hemoglobin concentration , mean corpuscular volume , corrected reticulocyte count , platelet count , serum iron , total iron‐binding capacity , transferrin saturation or erythrocyte proto‐porphyrin did not differ significantly between the two groups throughout the study . After 16 weeks of therapy , the mean increase in hemoglobin iron was similar in both groups ( p = 0.2 ) . Estimates of net changes in total body iron suggested that the overall bioavailability of carbonyl iron was high , about 70 % that of ferrous sulfate BACKGROUND Preoperative anaemia is associated with adverse outcomes after cardiac surgery but outcomes after non-cardiac surgery are not well established . We aim ed to assess the effect of preoperative anaemia on 30-day postoperative morbidity and mortality in patients undergoing major non-cardiac surgery . METHODS We analysed data for patients undergoing major non-cardiac surgery in 2008 from The American College of Surgeons ' National Surgical Quality Improvement Program data base ( a prospect i ve vali date d outcomes registry from 211 hospitals worldwide in 2008 ) . We obtained anonymised data for 30-day mortality and morbidity ( cardiac , respiratory , CNS , urinary tract , wound , sepsis , and venous thromboembolism outcomes ) , demographics , and preoperative and perioperative risk factors . We used multivariate logistic regression to assess the adjusted and modified ( nine predefined risk factor subgroups ) effect of anaemia , which was defined as mild ( haematocrit concentration > 29-<39 % in men and > 29-<36 % in women ) or moderate-to-severe ( ≤29 % in men and women ) on postoperative outcomes . FINDINGS We obtained data for 227,425 patients , of whom 69,229 ( 30·44 % ) had preoperative anaemia . After adjustment , postoperative mortality at 30 days was higher in patients with anaemia than in those without anaemia ( odds ratio [ OR ] 1·42 , 95 % CI 1·31 - 1·54 ) ; this difference was consistent in mild anaemia ( 1·41 , 1·30 - 1·53 ) and moderate-to-severe anaemia ( 1·44 , 1·29 - 1·60 ) . Composite postoperative morbidity at 30 days was also higher in patients with anaemia than in those without anaemia ( adjusted OR 1·35 , 1·30 - 1·40 ) , again consistent in patients with mild anaemia ( 1·31 , 1·26 - 1·36 ) and moderate-to-severe anaemia ( 1·56 , 1·47 - 1·66 ) . When compared with patients without anaemia or a defined risk factor , patients with anaemia and most risk factors had a higher adjusted OR for 30-day mortality and morbidity than did patients with either anaemia or the risk factor alone . INTERPRETATION Preoperative anaemia , even to a mild degree , is independently associated with an increased risk of 30-day morbidity and mortality in patients undergoing major non-cardiac surgery . FUNDING Vifor Pharma Oral iron is a st and ard treatment of iron deficient anemia despite high rates of intolerance and nonadherence and may not replenish iron stores rapidly enough to meet ongoing losses [ 1 ] . Intravenous ( IV ) iron has advantages but remains underutilized . Whereas most formulations of IV iron require multiple doses for replacement , low molecular weight iron dextran ( LMW ID ) may be administered as a total dose infusion , typically over a 4to 6-hr period [ 2,3 ] . A 4-hr infusion for doses up to 4 g was st and ard in our practice until 2 years ago . However , clinical studies suggest that 1 g of IV iron is an adequate dose for many patients [ 3–5 ] , and it became apparent that we were frequently infusing doses of at least 1 g in 1 hr without evidence of significant adverse events [ 3 ] . Now , our clinical practice routinely infuses 1 g of LMW ID in 250 mL normal saline over 1 hr without premedication as our st and ard practice . We summarize our experience with the safety and efficacy of this method of administering IV iron in unselected patients with iron deficiency . From July 11 , 2008 to February 25 , 2010 , a total of 396 consecutive iron deficient patients received 1 g LMW ID infusions . The mean age was 50.7 years ( range 14 to 90 ) , 84.1 % were women , 75.1 % were white , and 14.4 % had multiple documented drug allergies at baseline . The most common diagnoses were heavy uterine bleeding among women ( 43.5 % ) and gastrointestinal bleeding among men ( 33.3 % ) . The majority ( 78.9 % ) included in this study had baseline transferrin saturation ( TSAT ) 20 % ( mean : 11.5 ± 8.7 % ) and serum ferritin 100 ng/mL ( median : 11.0 ng/mL , range : 2 ) drug allergies and an increased likelihood of an AE [ odds ratio ( OR ) 5 3.40 ; 95 % CI : 1.09–10.63 ; P 5 0.036 ] when controlling for race , gender , and relative dose [ estimated body surface area ( BSA ) ] ( Figure 2 ; Supplemental Table II , available online ) . However , this finding should be interpreted with caution due to the very low absolute incidence rate . Other variables , including baseline iron status and age , were not associated with the incidence of observed AEs . Premedication with 125 mg of IV methylprednisolone was administered to only 10 patients with a history of multiple drug allergies ( 4 ) , asthma , active inflammatory bowel disease , and /or a previous reaction to IV iron . Three received granisetron premedication due to anticipatory nausea ( n 5 2 ) or nausea with prior IV iron therapy ( n 5 1 ) . All premedicated patients subsequently received the infusion without AEs . No patient received premedication with antihistamines . Clinical ly significant hypophosphatemia , defined as a serum phosphate level 20 % and /or serum ferritin > 100 ng/mL. There was no significant difference in magnitude of Hb response between these two subsets ( mean difference in Hb increase between patients with TSAT 20 % and serum ferritin 100 ng/mL and the others was 0.3 g/dL ; 95 % CI:20.0 to 0.5 g/dL ; P 5 0.08 ) . When baseline TSAT 20 % and serum ferritin 100 ng/mL , 54 % of infusions led to an increase in Hb of at least 1 g/dL , while 37 % of infusions when TSAT > 20 % or serum ferritin > 100 ng/mL achieved an increase in Hb of at least 1 g/dL ( Supplemental Table IV , available online ) . A total of 31 infusions in 43 women with pregnancy-related anemia ( second and third trimester , or postpartum ) , for whom follow-up data were available , were included in the efficacy analysis . In this subgroup , the mean change in Hb from baseline was 1.2 g/dL ( 95 % CI : 0.79–1.65 g/dL ; P 2 g/dL. Four of the patients with pregnancy-related anemia reported AEs . One resolved with a decreased rate and temporary interruption of the infusion and three received treatment with IV methylprednisolone . Although oral iron is a convenient and inexpensive therapy for iron deficient anemia , it has several important limitations . Even in patients who are not inflamed , and therefore have no problems with absorption , effective treatment requires a long course to correct anemia and completely replenish stores . Significant nonadherence and intolerance abound . While any of the available IV irons can infrequently cause acute reactions , the incidence and severity of these reactions are far less than perceived [ 6 ] . Whereas LMW ID , iron sucrose , ferric gluconate , and ferumoxytol can be administered safely and effectively , only LMW ID can be used to provide total dose repletion in a single setting ( a method of administration approved in Europe but not the United States ) . This method of administration has typically been 2–6 hr in published reports . In some studies , doses of 3 g ( and up to 4.5 g ) were infused . Numerous clinical studies suggest that 1 g is an adequate dose for the majority of patients , and several support the use of 1 g/hr , providing a rationale for administering 1 g over 1 hr in this study [ 3,7–11 ] . No prospect i ve study has shown benefit of premedication with antihistamines , yet they are often administered empirically . A study of 135 iron deficient patients who received antihistamines before the administration of IV iron reported that the most frequent AE observed was sedation due to the antihistamine [ 1 ] . Antihistamines have been associated with flushing , hypotension , supraventricular tachycardia and somnolence , all of which may be misinterpreted as iron-related reactions . In contradistinction to the AEs just described , there is a syndrome occurring in 1:200 patients described by Fishbane , consisting of arthralgia and myalgia of the chest or flank , usually This study evaluated efficacy and safety of darbepoetin alfa administered every 3 weeks ( Q3W ) at fixed doses of 300 or 500 μg with or without intravenous ( IV ) iron in treating anemia in patients receiving multicycle chemotherapy . This Phase 2 , double‐blind , 2 × 2 factorial study r and omized patients to one of four treatment arms ; darbepoetin alfa 300 μg ( n = 62 ) , darbepoetin alfa 300 μg plus IV iron ( n = 60 ) , darbepoetin alfa 500 μg ( n = 60 ) , or darbepoetin alfa 500 μg plus IV iron ( n = 60 ) . Patients had nonmyeloid malignancies , hemoglobin levels ≤10 g dL−1 , and no iron deficiency . Primary endpoint was achievement of target hemoglobin ( ≥11 g dL−1 ) . Secondary endpoints included incidence of transfusions and change in Functional Assessment of Cancer Therapy Fatigue ( FACT‐F ) score from baseline to end of study . Safety was evaluated by incidence of adverse events . No evidence of a statistically significant interaction between darbepoetin alfa dose received and IV iron usage was observed , therefore , results are provided separately comparing darbepoetin alfa doses and comparing IV iron usage groups . Similar proportions of patients receiving darbepoetin alfa 300 or 500 μg achieved target hemoglobin ( 75 and 78 % , respectively ) ; Kaplan – Meier median time to target hemoglobin was 10 and 8 weeks , respectively . More patients receiving IV iron ( 82 % ) than not receiving IV iron ( 72 % ) achieved hemoglobin target . Adverse events profiles were similar for darbepoetin alfa treatment groups . Transient anaphylactoid reactions were reported in two patients receiving IV iron . Darbepoetin alfa at 300 μg Q3W and 500 μg Q3W showed similar benefit , while added IV iron improved treatment response in these patients . Am . J. Hematol . , 2010 . © 2010 Wiley‐Liss , A prospect i ve r and omised controlled trial was performed to establish the effect of oral iron supplementation on haemoglobin level at 4 weeks post-operative in elderly patients with fractured neck of femur undergoing surgical treatment . We single blindly r and omised 68 patients into two groups . Thirty-four patients in the treatment group were compared with 32 in the control group . The treatment group received 200 mg of oral iron tablets 3 times a day for 4 weeks in the post-operative period compared to nothing for the control group . The groups were comparable in all other aspects . The iron treatment result ed in significantly increased haemoglobin value at 4 weeks ; 0.76 g% higher than the control group ( 95 % CI of + 0.01 to + 1.51 ) which is statistically significant ( P<0.05 ) . There was no major complication . We recommend oral iron supplementation in elderly anaemic patients with hip fracture in the post-operative period OBJECTIVES We tested the hypothesis that intravenous iron improves exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure ( CHF ) and iron deficiency . BACKGROUND Anemia is common in heart failure . Iron metabolism is disturbed , and administration of iron might improve both symptoms and exercise tolerance . METHODS We r and omized 35 patients with CHF ( age 64 + /- 13 years , peak oxygen consumption [ pVO2 ] 14.0 + /- 2.7 ml/kg/min ) to 16 weeks of intravenous iron ( 200 mg weekly until ferritin > 500 ng/ml , 200 mg monthly thereafter ) or no treatment in a 2:1 ratio . Ferritin was required to be < 100 ng/ml or ferritin 100 to 300 ng/ml with transferrin saturation < 20 % . Patients were stratified according to hemoglobin levels ( < 12.5 g/dl [ anemic group ] vs. 12.5 to 14.5 g/dl [ nonanemic group ] ) . The observer-blinded primary end point was the change in absolute pVO2 . RESULTS The difference ( 95 % confidence interval [ CI ] ) in the mean changes from baseline to end of study between the iron and control groups was 273 ( 151 to 396 ) ng/ml for ferritin ( p < 0.0001 ) , 0.1 ( -0.8 to 0.9 ) g/dl for hemoglobin ( p = 0.9 ) , 96 ( -12 to 205 ) ml/min for absolute pVO2 ( p = 0.08 ) , 2.2 ( 0.5 to 4.0 ) ml/kg/min for pVO2/kg ( p = 0.01 ) , 60 ( -6 to 126 ) s for treadmill exercise duration ( p = 0.08 ) , -0.6 ( -0.9 to -0.2 ) for New York Heart Association ( NYHA ) functional class ( p = 0.007 ) , and 1.7 ( 0.7 to 2.6 ) for patient global assessment ( p = 0.002 ) . In anemic patients ( n = 18 ) , the difference ( 95 % CI ) was 204 ( 31 to 378 ) ml/min for absolute pVO2 ( p = 0.02 ) , and 3.9 ( 1.1 to 6.8 ) ml/kg/min for pVO2/kg ( p = 0.01 ) . In nonanemic patients , NYHA functional class improved ( p = 0.06 ) . Adverse events were similar . CONCLUSIONS Intravenous iron loading improved exercise capacity and symptoms in patients with CHF and evidence of abnormal iron metabolism . Benefits were more evident in anemic patients . ( Effect of Intravenous Ferrous Sucrose on Exercise Capacity in Chronic Heart Failure ; http://www . clinical trials.gov/ct/show/NCT00125996 ; NCT00125996 ) BACKGROUND Critical illness is characterized by hypoferremia , iron-deficient erythropoiesis ( IDE ) , and anemia . The relative risks and benefits of iron supplementation in this setting are unknown . METHODS Anemic , critically ill surgical patients with an expected intensive care unit length of stay ( ULOS ) > or= 5 days were r and omized to either enteral iron supplementation ( ferrous sulfate 325 mg three times daily ) or placebo until hospital discharge . Outcomes included hematocrit , iron markers ( i.e. , serum concentrations of iron , ferritin , and erythrocyte zinc protoporphyrin [ eZPP ] ) , red blood cell ( RBC ) transfusion , transfusion rate ( mL RBC/ study day ) , nosocomial infection , antibiotic days , study length of stay ( LOS ) , ULOS , and death . Iron-deficient erythropoiesis was defined as an elevated eZPP concentration . RESULTS Two hundred patients were r and omized ; 97 received iron , and 103 received placebo . Socio-demographics , baseline acuity , hematocrit , and iron markers were similar in the two groups . No differences were observed between the iron and placebo groups with respect to either hematocrit or iron markers following up to 28 days . However , patients treated with iron were significantly less likely to receive an RBC transfusion ( 29.9 % vs. 44.7 % , respectively ; p = 0.03 ) and had a significantly lower transfusion rate ( 22.0 mL/day vs. 29.9 mL/day ; p = 0.03 ) . Subgroup analysis revealed that these differences were observed in patients with baseline IDE only . Iron and placebo groups did not differ with respect to incidence of infection ( 46.8 % vs. 48.9 % ; p = 0.98 ) , antibiotic days ( 14 vs. 16 ; p = 0.45 ) , LOS ( 14 vs. 16 days ; p = 0.24 ) , ULOS ( 12 vs. 14 days ; p = 0.69 ) , or mortality rate ( 9.4 % vs. 9.9 % ; p = 0.62 ) . CONCLUSIONS Enteral iron supplementation of anemic , critically ill surgical patients does not increase the risk of infection and may benefit those with baseline IDE by decreasing the risk of RBC transfusion . A trial comparing enteral and parenteral iron supplementation in this setting is warranted ( Clinical Trials.gov number , NCT00450177 ) PURPOSE The concomitant use of intravenous ( IV ) iron as a supplement to erythropoiesis-stimulating agents in patients with chemotherapy-induced anemia is controversial . This study was design ed to evaluate the efficacy and safety of darbepoetin alpha given with IV iron versus with local st and ard practice ( oral iron or no iron ) . PATIENTS AND METHODS In this multicenter , r and omized , open-label , phase III study , 396 patients with nonmyeloid malignancies and hemoglobin ( Hb ) less than 11 g/dL received darbepoetin alpha 500 microg with ( n = 200 ) or without ( n = 196 ) IV iron once every 3 weeks ( Q3W ) for 16 weeks . RESULTS The hematopoietic response rate ( proportion of patients achieving Hb > or= 12 g/dL or Hb increase of > or= 2 g/dL from baseline ) was significantly higher in the IV iron group : 86 % versus 73 % in the st and ard practice group ( difference of 13 % [ 95 % CI , 3 % to 23 % ] ; P = .011 ) . Fewer RBC transfusions ( week 5 to the end of the treatment period ) occurred in the IV iron group : 9 % versus 20 % in the st and ard practice group ( difference of -11 % [ 95 % CI , -18 % to -3 % ] ; P = .005 ) . Both treatments were well tolerated with no notable differences in adverse events . Serious adverse events related to iron occurred in 3 % of patients in the IV iron group and were mostly gastrointestinal in nature . CONCLUSION Addition of IV iron to darbepoetin alpha Q3W in patients with chemotherapy-induced anemia was well tolerated , result ing in an improved hematopoietic response rate and lower incidence of transfusions compared with darbepoetin alpha alone PURPOSE Unresponsiveness to erythropoiesis-stimulating agents , occurring in 30 % to 50 % of patients , is a major limitation to the treatment of chemotherapy-related anemia . We have prospect ively evaluated whether intravenous iron can increase the proportion of patients with chemotherapy-related anemia who respond to darbepoetin . PATIENTS AND METHODS Between December 2004 and February 2006 , 149 patients with lung , gynecologic , breast , and colorectal cancers and > or= 12 weeks of planned chemotherapy were enrolled from 33 institutions . Patients were required to have hemoglobin < or= 11 g/L and no absolute or functional iron deficiency . All patients received darbepoetin 150 microg subcutaneously once weekly for 12 weeks and were r and omly assigned to sodium ferric gluconate 125 mg intravenously ( IV ) weekly for the first 6 weeks ( n = 73 ) or no iron ( n = 76 ) . Primary end point of the study was the percentage of patients achieving hematopoietic response ( hemoglobin > or= 12 g/dL or > or= 2 g/dL increase ) . RESULTS Hematopoietic response by intention-to-treat analysis was 76.7 % ( 95%CI , 65.4 % to 85.8 % ) in the darbepoetin/iron group and 61.8 % ( 95%CI , 50.0 % to 72.7 % ) in the darbepoetin group ( P = .0495 ) . Among patients fulfilling eligibility criteria and having received at least four darbepoetin administrations , hematopoietic responses in the darbepoetin/iron group ( n = 53 ) and in the darbepoetin-only group ( n = 50 ) were 92.5 % ( 95 % CI , 81.8 % to 97.9 % ) and 70 % ( 95 % CI , 55.4 % to 82.1 % ) , respectively ( P = .0033 ) . Increase of hemoglobin during treatment period showed a time profile favoring darbepoetin/iron with statistically significant effect from week 5 on . The safety profile was comparable in the two arms . CONCLUSION In patients with chemotherapy-related anemia and no iron deficiency , IV iron supplementation significantly reduces treatment failures to darbepoetin without additional toxicity |
1,867 | 28,595,509 | There is consistent evidence that rehabilitation improves function , mobility , ataxia , and balance in genetic degenerative ataxia | Background .
Treatment of genetic degenerative ataxia is currently based on symptom management and maintenance of function .
However , utilization of rehabilitation is limited due to a lack of evidence supporting its efficacy .
This systematic review evaluated rehabilitation interventions for individuals with genetic degenerative ataxia .
In addition , long-term outcomes from rehabilitation and optimal duration and intensity of rehabilitation were examined . | Objectives : The cerebellum is known to play a strong functional role in both motor control and motor learning . Hence , the benefit of physiotherapeutic training remains controversial for patients with cerebellar degeneration . In this study , we examined the effectiveness of a 4-week intensive coordinative training for 16 patients with progressive ataxia due to cerebellar degeneration ( n = 10 ) or degeneration of afferent pathways ( n = 6 ) . Methods : Effects were assessed by clinical ataxia rating scales , individual goal attainment scores , and quantitative movement analysis . Four assessment s were performed : 8 weeks before , immediately before , directly after , and 8 weeks after training . To control for variability in disease progression , we used an intraindividual control design , where performance changes with and without training were compared . Results : Significant improvements in motor performance and reduction of ataxia symptoms were observed in clinical scores after training and were sustained at follow-up assessment . Patients with predominant cerebellar ataxia revealed more distinct improvement than patients with afferent ataxia in several aspects of gait like velocity , lateral sway , and intralimb coordination . Consistently , in patients with cerebellar but without afferent ataxia , the regulation of balance in static and dynamic balance tasks improved significantly . Conclusion : In patients with cerebellar ataxia , coordinative training improves motor performance and reduces ataxia symptoms , enabling them to achieve personally meaningful goals in everyday life . Training effects were more distinct for patients whose afferent pathways were not affected . For both groups , continuous training seems crucial for stabilizing improvements and should become st and ard of care . Level of evidence : This study provides Class III evidence that coordinative training improves motor performance and reduces ataxia symptoms in patients with progressive cerebellar ataxia Occupational therapy ( OT ) is a profession concerned with promoting health and well-being through occupation , by enabling h and icapped people to participate in the activities of everyday life . OT is part of the clinical rehabilitation of progressive genetic neurodegenerative diseases such as spinocerebellar ataxias ; however , its effects have never been determined in these diseases . Our aim was to investigate the effect of OT on both physical disabilities and depressive symptoms of spinocerebellar ataxia type 3 ( SCA3 ) patients . Genomically diagnosed SCA3 patients older than 18 years were invited to participate in the study . Disability , as evaluated by functional independence measurement and Barthel incapacitation score , Hamilton Rating Scale for Depression , and World Health Organization Quality of Life question naire ( WHOQOL-BREF ) , was determined at baseline and after 3 and 6 months of treatment . Twenty-six patients agreed to participate in the study . All were treated because OT prevents blinding of a control group . Fifteen sessions of rehabilitative OT were applied over a period of 6 months . Difficult access to food , clothing , personal hygiene , and leisure were some of the main disabilities focused by these patients . After this treatment , disability scores and quality of life were stable , and the Hamilton scores for depression improved . Since no medication was started up to 6 months before or during OT , this improvement was related to our intervention . No association was found between these endpoints and a CAG tract of the MJD1 gene ( CAGn ) , age , age of onset , or neurological scores at baseline ( Spearman test ) . Although the possibly temporary stabilization of the downhill disabilities as an effect of OT remains to be established , its clear effect on depressive symptoms confirms the recommendation of OT to any patient with SCA3 or spinocerebellar ataxia Locomotor adaptability ranges from the simple and fast-acting to the complex and long-lasting and is a requirement for successful mobility in an unpredictable environment . Several neural structures , including the spinal cord , brainstem , cerebellum , and motor cortex , have been implicated in the control of various types of locomotor adaptation . However , it is not known which structures control which types of adaptation and the specific mechanisms by which the appropriate adjustments are made . Here , we used a splitbelt treadmill to test cerebellar contributions to two different forms of locomotor adaptation in humans . We found that cerebellar damage does not impair the ability to make reactive feedback-driven motor adaptations , but significantly disrupts predictive feedforward motor adaptations during splitbelt treadmill locomotion . Our results speak to two important aspects of locomotor control . First , we have demonstrated that different levels of locomotor adaptability are clearly dissociable . Second , the cerebellum seems to play an essential role in predictive but not reactive locomotor adjustments . We postulate that reactive adjustments may instead be predominantly controlled by lower neural centers , such as the spinal cord or brainstem Objective : To investigate the feasibility of a r and omized controlled trial of a home-based balance intervention for people with cerebellar ataxia . Design : A r and omized controlled trial design . Setting : Intervention and assessment took place in the home environment . Participants : A total of 12 people with spinocerebellar ataxia type 6 were r and omized into a therapy or control group . Both groups received identical assessment s at baseline , four and eight weeks . Interventions : Therapy group participants undertook balance exercises in front of optokinetic stimuli during weeks 4–8 , while control group participants received no intervention . Main measures : Test – retest reliability was analysed from outcome measures collected twice at baseline and four weeks later . Feasibility issues were evaluated using daily diaries and end trial exit interviews . Results : The home-based training intervention with opto-kinetic stimuli was feasible for people with pure ataxia , with one drop-out . Test – retest reliability is strong ( intraclass correlation coefficient > 0.7 ) for selected outcome measures evaluating balance at impairment and activity levels . Some measures reveal trends towards improvement for those in the therapy group . Sample size estimations indicate that Bal-SARA scores could detect a clinical ly significant change of 0.8 points in this functional balance score if 80 people per group were analysed in future trials . Conclusions : Home-based targeted training of functional balance for people with pure cerebellar ataxia is feasible and the outcome measures employed are reliable Balance and gait problems in patients with cerebellar degeneration lead to reduced mobility , loss of independence , and frequent falls . It is currently unclear , however , whether balance and gait capacities can be improved by training in this group of patients . Therefore , the aim of this study was to examine the effects of gait adaptability training on obstacle avoidance and dynamic stability during adaptive gait . Ten patients with degenerative cerebellar ataxia received 10 protocol ized gait adaptability training sessions of 1 h each during 5 weeks . Training was performed on a treadmill with visual stepping targets and obstacles projected on the belt 's surface . As the primary outcome , we used an obstacle avoidance task while walking on a treadmill . We determined avoidance success rates , as well as dynamic stability during the avoidance manoeuvre . Clinical ratings included the scale for the assessment of ataxia ( SARA ) , 10 m walking test , timed up- and -go test , berg balance scale , and the obstacle subtask of the emory functional ambulation profile ( EFAP ) . Following the intervention , success rates on the obstacle avoidance task had significantly improved compared to pre-intervention . For successful avoidance , participants allowed themselves smaller stability margins in the sagittal plane in the ( shortened ) pre-crossing step . However , in the subsequent steps they returned to baseline stability values more effectively than before training . SARA scores and the EFAP obstacle subtask improved significantly as well . This pilot study provides preliminary evidence of a beneficial effect of gait adaptability training on obstacle avoidance capacity and dynamic stability in patients with cerebellar degeneration Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists Objective . To investigate short- and long-term effects of intensive rehabilitation on ataxia , gait , and activities of daily living ( ADLs ) in patients with degenerative cerebellar disease . Methods . A total of 42 patients with pure cerebellar degeneration were r and omly assigned to the immediate group or the delayed-entry control group . The immediate group received 2 hours of inpatient physical and occupational therapy , focusing on coordination , balance , and ADLs , on weekdays and 1 hour on weekends for 4 weeks . The control group received the same intervention after a 4-week delay . Short-term outcome was compared between the immediate and control groups . Long-term evaluation was done in both groups at 4 , 12 , and 24 weeks after the intervention . Outcome measures included the assessment and rating of ataxia , Functional Independence Measure , gait speed , cadence , functional ambulation category , and number of falls . Results . The immediate group showed significantly greater functional gains in ataxia , gait speed , and ADLs than the control group . Improvement of truncal ataxia was more prominent than limb ataxia . The gains in ataxia and gait were sustained at 12 weeks and 24 weeks , respectively . At least 1 measure was better than at baseline at 24 weeks in 22 patients . Conclusions . Short-term benefit of intensive rehabilitation was evident in patients with degenerative cerebellar diseases . Although functional status tended to decline to the baseline level within 24 weeks , gains were maintained in more than half of the participants Exercise therapy ( ET ) can be beneficial in disabled multiple sclerosis ( MS ) patients . Intermittent transcranial magnetic theta burst stimulation ( iTBS ) induces long-term excitability changes of the cerebral cortex and may ameliorate spasticity in MS . We investigated whether the combination of iTBS and a program of ET can improve motor disability in MS patients . In a double-blind , sham-controlled trial , 30 participants were r and omized to three different interventions : iTBS plus ET , sham stimulation plus ET , and iTBS alone . Before and after 2 weeks of treatment , measures of spasticity through the modified Ashworth scale ( MAS ) and the 88 items Multiple Sclerosis Spasticity Score question naire ( MSSS-88 ) , fatigue through the Fatigue Severity Scale ( FSS ) , daily living activities ( ADL ) through the Barthel index and health-related quality of life ( HRQoL ) through the 54 items Multiple Sclerosis Quality of life inventory ( MSQoL-54 ) were collected . iTBS plus ET reduced MAS , MSSS-88 , FSS scores , while in the Barthel index and MSQoL-54 , physical composite scores were increased . iTBS alone caused a reduction of the MAS score , while none of the measured scales showed significant changes after sham iTBS plus ET . iTBS associated with ET is a promising tool for motor rehabilitation of MS patients Friedreich ’s ataxia results in morbidity because of many factors ; progressive equinovarus deformity is one of these . We studied the risk factors and incidence of this deformity . We sought to assess whether surgical management of fixed equinovarus deformity leads to functional improvement . Thirty-six patients with Friedrich ’s ataxia were assessed for this deformity . These patients were treated by splinting , botulinum toxin Type A injection , and surgery , as indicated by the severity , followed by an ongoing rehabilitation program . The effect of surgery was assessed using subscales of the Barthel index and functional independence measure . Severe foot deformities in which either surgery or botulinum toxin injection was recommended correlated with current age , years since disease onset , and years that the patient required a wheelchair for mobility , but not with the GAA repeat size or age at disease onset . Function and mobility were improved after surgery compared with a similar period before surgery . Three of seven patients who had surgery had significant complications . Aggressive management of foot deformities should be considered , and active measures to prevent permanent foot deformities should be pursued to maximize quality of life and independence of patients with Friedreich ’s ataxia . Level of Evidence : Therapeutic study , Level IV ( case series-no , or historical control group Few clinical studies have evaluated physiotherapeutic interventions for patients with degenerative cerebellar disease . In particular , evidence for long-term effects and transfer to activities of daily life is rare . We have recently shown that coordinative training leads to short-term improvements in motor performance . To evaluate long-term benefits and translation to real world function , we here assessed motor performance and achievements in activities of daily life 1 year after a 4 week intensive coordinative training , which was followed by a home training program . Effects were assessed by clinical rating scales , a goal attainment score and quantitative movement analysis . Despite gradual decline of motor performance and gradual increase of ataxia symptoms due to progression of disease after 1 year , improvements in motor performance and achievements in activities of daily life persisted . Thus , also in patients with degenerative cerebellar disease , continuous coordinative training leads to long-term improvements , which translate to real world function Recent research indicates that physiotherapy can improve motor performance of patients with cerebellar degeneration . Given the known contributions of the cerebellum to motor learning , it remains unclear whether such observable changes in performance are mediated by the cerebellum or cerebral brain areas involved in motor control and learning . The current study addressed this question by assessing the increase in gray matter volume due to sensorimotor training in cerebellar patients using voxel-based morphometry . Nineteen human subjects with pure cerebellar degeneration and matched healthy controls were trained for 2 weeks on a balance task . Postural and clinical assessment s along with structural magnetic resonance imaging were performed pretraining and post-training . The main findings were as follows . First , training enhanced balance performance in cerebellar patients . Second , in contrast to controls patients revealed significantly more post-training gray matter volume in the dorsal premotor cortex . Third , training-related increase in gray matter volume was observed within the cerebellum and was more pronounced in controls than in patients . However , statistically cerebellar changes were at the trend level and thus require additional , independent confirmation . We conclude that sensorimotor training of patients with cerebellar neurodegeneration induces gray matter changes primarily within nonaffected neocortical regions of the cerebellar-cortical loop . Residual function of the cerebellum appears to be exploited suggesting either a recovery from degeneration or intact processes of cerebellar plasticity in the remaining healthy tissue OBJECTIVES To compare the reciprocal control of agonist and antagonist muscles in individuals with and without spinocerebellar ataxia ( SCA ) and to evaluate the effect of a 4-week leg cycling regimen on functional coordination and reciprocal control of agonist and antagonist muscles in patients with SCA . DESIGN R and omized controlled trial with repeated measures . SETTING Research laboratory in a general hospital . PARTICIPANTS Individuals with SCA ( n=20 ) and without SCA ( n=20 ) . INTERVENTIONS A single 15-minute session of leg cycling and a 4-week cycling regimen . MAIN OUTCOME MEASURES Individuals with SCA ( n=20 ) and without SCA ( n=20 ) underwent disynaptic reciprocal inhibition and D1 inhibition tests of the soleus muscles before and after a single 15-minute cycling session . Individuals with SCA were r and omly assigned to either participate in 4 weeks of cycling training ( n=10 ) or to receive no training ( n=10 ) . The disynaptic reciprocal inhibition and D1 inhibition and International Cooperative Ataxia Rating Scale ( ICARS ) scores were evaluated in both groups after 4 weeks . RESULTS Individuals with SCA showed abnormally strong resting values of disynaptic reciprocal inhibition and D1 inhibition ( P<.001 ) and impaired inhibition modulation capacity after a single 15-minute session of cycling ( P<.001 ) . The inhibition modulation capacity was restored ( P<.001 ) , and the ICARS scores improved significantly ( pre : 13.5±9.81 , post : 11.3±8.74 ; P=.046 ) after 4 weeks of cycling training . CONCLUSIONS A 4-week cycling regimen can normalize the modulation of reciprocal inhibition and functional performance in individuals with SCA . These findings are applicable to the coordination training of patients |
1,868 | 23,879,694 | Conclusions Enhanced consent forms and extended discussion s were most effective in improving participant underst and ing .
Interventions of all categories had no negative impact on participant satisfaction or study accrual . | Background Obtaining informed consent is a cornerstone of biomedical research , yet participants comprehension of presented information is often low .
The most effective interventions to improve underst and ing rates have not been identified .
Purpose To systematic ally analyze the r and om controlled trials testing interventions to research informed consent process . | We investigated whether a short course in communication skills for physicians would improve the quality of informed consent in a r and omized clinical adjuvant trial on breast cancer . In this prospect i ve , case-controlled intervention study , physicians and research nurses who introduced the cancer treatment trial to patients at three of the participating hospitals first attended a one-day communication skills course . The quality of informed consent was then evaluated by addressing a st and ardized question naire , QuIC , to trial patients at the three intervention hospitals and at control hospitals . Response rate was 90.0 % ( n = 288 ) . Of the patients treated by the intervention group , 73 % were very satisfied with the information received compared with 56 % of those of the control group ( p = 0.003 ) . The patients of the intervention group considered the time given for making their decision sufficient more often than those of the controls ( 98 % vs. 90 % , p=0.004 ) . The patients of the intervention group recalled more often than those of the controls that the physician had also offered other therapeutic options than the trial treatment ( 91 % vs. 97 % , p=0.032 ) . They also understood the main aim of the study better than the patients of the controls ( 89 % vs. 78 % , p=0.030 ) . In conclusion , a short communication skills course for the trial physicians and nurses improved the quality of informed consent and patient satisfaction in the trial OBJECTIVES : To study whether linguistic analysis and changes in information leaflets can improve readability and underst and ing . DESIGN : R and omised , controlled study . Two information leaflets concerned with trials of drugs for conditions/diseases which are commonly known were modified , and the original was tested against the revised version . SETTING : Denmark . PARTICIPANTS : 235 persons in the relevant age groups . MAIN MEASURES : Readability and underst and ing of contents . RESULTS : Both readability and underst and ing of contents was improved : readability with regard to both information leaflets and underst and ing with regard to one of the leaflets . CONCLUSION : The results show that both readability and underst and ing can be improved by increased attention to the linguistic features of the information AIMS International guidelines on ethics in biomedical research require that the informed consent of all enrolled participants is obtained . A written document describing the research , the informed consent ( IC ) document , must be given to all participants by the investigator . Most IC documents are long , containing much information . The aim of the present study was to determine whether the modification of the IC document by a working group or systematic improvement in its lexicosyntactic readability can improve comprehension of the written information given to patients participating in biomedical research . METHODS One hundred and fifty-nine patients were r and omized to read one of the three versions of the IC document : unchanged document , document modified using systematic improvement of lexicosyntactic readability and document modified by a working group . RESULTS Neither the improvement in the lexicosyntactic readability , nor the intervention of the working group significantly improved the score of objective comprehension for the subjects included in this study : it was 66.6 ( 95 % confidence interval 64.0 , 69.2 ) for the control group , 68.8 ( 66.2 , 71.4 ) for the group with the document improved for lexicosyntactic readability and 69.2 ( 66.0 , 72.4 ) for the group who read the document improved by the working group ( P= 0.38 ) . CONCLUSIONS We failed to show that improving IC document comprehension through a lexicosyntactic approach or by a working group leads to better comprehension Background Studies on different methods to supplement the traditional informed consent process have generated conflicting results . This study was design ed to evaluate whether participants who received group counseling prior to administration of informed consent understood the key components of the study and the consent better than those who received individual counseling , based on the hypothesis that group counseling would foster discussion among potential participants and enhance their underst and ing of the informed consent . Methods Parents of children participating in a trial of nutritional supplementation were r and omized to receive either group counseling or individual counseling prior to administration of the informed consent . To assess the participant 's comprehension , a structured question naire was administered approximately 48 - 72 hours afterwards by interviewers who were blinded to the allocation group of the respondents . Results A total of 128 parents were recruited and follow up was established with 118 ( 90.2 % ) for the study . All respondents were aware of their child 's participation in a research study and the details of sample collection . However , their underst and ing of study purpose , r and omization and withdrawal was poor . There was no difference in comprehension of key elements of the informed consent between the intervention and control arm . Conclusions The results suggest that the group counseling might not influence the overall comprehension of the informed consent process . Further research is required to devise better ways of improving participants ' underst and ing of r and omization in clinical trials . Trial Registration Clinical Trial Registry - India ( CTRI ) : To determine subjects ' perception of the purpose of informed consent , 113 subjects were recruited from a dose-controlled clinical trial of didanosine ( ddI ) . Subjects were surveyed regarding how they made decisions regarding their medical care in general , about how they obtained information about this trial in particular , and several aspects of the informed consent procedure . Subjects were then r and omly allocated to receive information about the trial by either a written only format or a written and verbal format 1 week before commencement of the trial . An eight-item instrument assessed knowledge of ddI prior to and subsequent to receiving information . Most subjects obtained information about HIV-related issues from their specialist ( 70 % ) or general ( 51 % ) medical practitioner . A large proportion of subjects ( 88 % ) reported that they believed their specialist medical practitioner always acted in their best interest . The majority of subjects ( 79 % ) believed that subjects should be allowed the choice between participating in the clinical trial and receiving the drug outside the trial mechanism . Of the subjects , 96 % believed that informed consent was necessary in clinical trials ; however , their opinions of the purpose of informed consent varied widely . Although they signed the informed consent , 44 % of the subjects stated that they did not underst and ' all ' of the information that was provided . We found that the provision of information by written mode alone , or written and verbal modes were both associated with significant increases in knowledge levels and that there was a significant interaction in the degree of change between the two methods , with the written plus verbal method showing the most improvement over time . There was an interaction between degree of improvement in knowledge of didanosine in subjects who received written information versus those who received written and verbal knowledge and time ( pre- versus post-consent ) and a significant main effect for time . All subjects were relatively well-informed about the drug and stated that specialist and general medical practitioners were their major source of knowledge for all aspects of their HIV health care Obtaining informed consent for clinical investigations represents a major legal , ethical , and moral consideration in human experimentation . Mechanisms for informing the patient vary widely , and usually no system exists to confirm the degree of information retained by the patient . A Veterans Administration Cooperative Study , begun in 1975 , has used a videotape information package in addition to a st and ard written consent form to ensure uniformity . Each presentation was followed by a question naire to assess the amount of material learned before attempting r and omization . Repeated showings were occasionally necessary and did not affect the rate of r and omization . A videotape presentation , especially in cooperative studies , ensures uniformity , makes allowance for varying educational levels of patients , and provides documentation of the degree of informed consent IN THE EARLY 1890S , DR WILLIAM HALSTED DEVELOPED radical mastectomy for breast cancer . Surgeons performed the Halsted procedure for more than 80 years even though there was little systematic evidence for its success . Then a new breed of scholars subjected the procedure to formal methods of evaluation unknown to Halsted . The methods —r and omized controlled trials ( RCTs ) principal among them — led to a surprise : radical mastectomy had no advantage over simpler forms of treatment . This is but 1 example of the hard-won victory of evidence over belief in medicine . The pioneers of the formal evaluation of medical practice s raised questions that traditional practitioners did not welcome . But in time , formal evaluation prevailed . The pioneers developed a hierarchy of evidentiary rigor relating the design of a study to the confidence that could be placed in the findings , from the lowly , nearly valueless anecdote to the royalty of evidence , the RCT . Concurrently , a similar story of hard-won learning unfolded in the so-called quality movement . Scholars illuminated the scale and types of defects in the processes of care and the outcomes , including high rates of unscientific care , inappropriate care , geographic variations in practice , latent disagreements among specialists , and oftenunrecognized medical injury to patients . Like the pioneers of evidence -based medicine , students of medical quality were at first largely ignored , but no longer . In 1999 and 2001 , the Institute of Medicine published 2 l and mark reports on the evidence for quality failures and called urgently for re design of care systems to achieve improvements . The story could end here happily with 2 great streams of endeavor merging into a framework for conjoint action : improving clinical evidence and improving the process of care . Instead , the 2 endeavors are often in unhappy tension . Neither disputes that progress toward health care ’s main goal , the relief of illness and pain , requires research of many kinds : basic , clinical , systems , epidemiologic . The disagreement centers on epistemology — ways to get at “ truth ” and how those ways should vary depending on the knowledge sought . Individuals most involved in day-to-day improvement work fear that if “ evidence ” is too narrowly defined and the approach to gathering evidence too severely constrained , progress may be the victim . For example , the RCT is a powerful , perhaps unequaled , research design to explore the efficacy of conceptually neat components of clinical practice —tests , drugs , and procedures . For other crucially important learning purpose s , however , it serves less well . Recent controversies about the evaluation of rapid response teams provide a case in point . These controversies show the importance of adjusting research methods to fit research questions . Although only 10 % to 15 % of in patients resuscitated outside intensive care units survive to hospital discharge , early warning signs are present in a large percentage of patients who ultimately experience cardiac arrest . Rapid response team systems bring expert clinicians to the bedsides of deteriorating patients before arrest occurs . In the mid 1990s , based largely on reports from Australian investigators , the Institute for Healthcare Improvement and others began introducing the concept to willing hospitals . Local experience strongly suggested that these systems often , although not always , were associated with improved outcomes , including reduced anxiety among nursing staff ; increased interdisciplinary teamwork ; decreased cardiac arrests outside of intensive care units ; and , in some cases , declines in mortality . The evidence base took a turn in June 2005 with the publication of the Medical Early Response Intervention and Therapy ( MERIT ) Study , a cluster r and omized prospect i ve trial that cl aim ed to find no beneficial effect of these teams on several primary outcomes . Controversy has continued since then regarding the scientific evidence for rapid response systems . In fact , the MERIT trial was not negative ; it was inconclusive . The study team encountered an array of serious problems in execution , common in social science . For example , although the study ’s power calculation assumed a baseline rate of 30 events per 1000 admissions , the actual rate proved to be fewer than 7 events per 1000 admissions ; thus , the study was ef fect ively underpowered by 500 % . Crosscontamination abounded ; some control hospitals implemented rapid response protocol s , and several study Recruitment to cancer clinical trials needs to be improved , as does patient knowledge and underst and ing about clinical trials , in order for patients to make an informed choice about whether or not to take part . Audiovisual patient information ( AVPI ) has been shown to improve knowledge and underst and ing in various areas of practice , but there is limited information about its effect in the cancer clinical trial setting , particularly in relation to consent rates . In this study , 173 patients were r and omised to receive either the AVPI , in addition to the st and ard trial-specific written information , or the written information alone . There was no difference in clinical trial recruitment rates between the two groups with similar study entry rates : 72.1 % in the AVPI group and 75.9 % in the st and ard information group . The estimated odds ratio for refusal ( intervention/no intervention ) was 1.19 ( 95 % CI 0.55–2.58 , P=0.661 ) . Knowledge scores increased more in the AVPI group compared to the st and ard group ( P=0.0072 ) . The change in anxiety score between the arms was also statistically significant ( P=0.011 ) with anxiety improving in the intervention arm more than in the no intervention arm . Audiovisual patient information was shown to be a useful tool in improving patient knowledge and anxiety , but further work is necessary in relation to its effect on clinical trial recruitment rates Procedures must be developed to ensure that valid informed consent is obtained from participants in HIV vaccine efficacy trials . A prototype informed consent process was evaluated among 4,892 persons at high risk for HIV infection in the HIV Network for Prevention Trials Vaccine Preparedness Study ( VPS ) , a prospect i ve cohort study of HIV seroincidence in eight U.S. metropolitan areas . Twenty percent of VPS participants were selected at r and om to undergo the prototype informed consent process at VPS month 3 . Participants ' knowledge of 10 key HIV vaccine trial concepts and willingness to participate in HIV vaccine efficacy trials were assessed and compared at baseline and semiannually thereafter for 18 months . Knowledge of HIV vaccine trial concepts was low at baseline . Participation in the prototype process was associated with substantial and sustained increases in knowledge ( relative risks for the 10 items , 1.04–2.26 ) , which were of similar magnitude across HIV risk groups , race/ethnicity , and educational levels . It is recommended that the prototype informed consent process be adopted for future HIV vaccine efficacy trials as well as for clinical trials in other research areas Methods of obtaining informed consent have evolved differently in Western countries without substantive information on the impact of these different practice s on the patients . A r and omised study was performed to compare two commonly adopted methods of seeking consent to r and omised treatment : an individual approach at the discretion of each doctor and a uniform policy of total disclosure of all relevant information . The impact of both consent procedures on the patient 's underst and ing and anxiety levels and on the doctor-patient relationship was assessed by means of a question naire given soon after the consent interview . Fifty seven patients were assigned at r and om to two groups : to 29 patients an individual approach to seeking consent was adopted and to 28 patients all relevant information was given . Seven patients refused consent to r and omised treatment , with slightly more refusals by patients in the total disclosure group ( 5 v 2 , p = 0.25 ) . The main effects of total disclosure of all information compared with an individual approach to seeking consent were : a better underst and ing of treatment and side effects and of research aspects of the treatments ; less willingness to agree to r and omised treatment ; and increased anxiety . No significant differences were found in patients ' perceptions of the doctor-patient relationship . A repeat question naire given three to four weeks later no longer showed significant differences between the two groups OBJECTIVE To assess the efficacy , with respect to participant underst and ing of information , of a computer-based approach to communication about complex , technical issues that commonly arise when seeking informed consent for clinical research trials . DESIGN , SETTING AND PARTICIPANTS An open , r and omised controlled study of 60 patients with diabetes mellitus , aged 27 - 70 years , recruited between August 2006 and October 2007 from the Department of Diabetes and Endocrinology at the Alfred Hospital and Baker IDI Heart and Diabetes Institute , Melbourne . INTERVENTION Participants were asked to read information about a mock study via a computer-based presentation ( n = 30 ) or a conventional paper-based information statement ( n = 30 ) . The computer-based presentation contained visual aids , including diagrams , video , hyperlinks and quiz pages . MAIN OUTCOME MEASURES Underst and ing of information as assessed by quantitative and qualitative means . RESULTS Assessment scores used to measure level of underst and ing were significantly higher in the group that completed the computer-based task than the group that completed the paper-based task ( 82 % v 73 % ; P = 0.005 ) . More participants in the group that completed the computer-based task expressed interest in taking part in the mock study ( 23 v 17 participants ; P = 0.01 ) . Most participants from both groups preferred the idea of a computer-based presentation to the paper-based statement ( 21 in the computer-based task group , 18 in the paper-based task group ) . CONCLUSIONS A computer-based method of providing information may help overcome existing deficiencies in communication about clinical research , and may reduce costs and improve efficiency in recruiting participants for clinical trials OBJECTIVE The objective of this study was to evaluate alternative procedures for improving the underst and ing of research consent disclosures by persons who have mental illness . METHODS Three groups participated in the study : persons with schizophrenia ( N=79 ) , persons with depression ( N=82 ) , and a healthy control group ( N=80 ) . The participants were guided through an informed consent process in which two factors were manipulated . One was the structure of the disclosure form ; either a typical disclosure form involving st and ard dense text was used , or a graphically enhanced form was used . The other was the interpersonal process : the presence or absence of a third-party facilitator , with iterative feedback given to participants for whom a facilitator was not present . Participants ' underst and ing of the disclosure was assessed with the use of recall tests that involved paraphrasing and recognition tests that involved multiple choice . RESULTS The mean underst and ing scores did not differ significantly between the depression and control groups , and the mean scores of the schizophrenia group were significantly lower than those of the other two groups . Neither the graphically enhanced consent disclosure form nor the presence of a third-party facilitator was associated with improved underst and ing . The use of iterative feedback was associated with improvement in comprehension scores in all groups . CONCLUSIONS The use of a feedback procedure in the consent disclosure process during the recruitment of persons who are mentally ill may be a valuable safeguard for ensuring adequate underst and ing and appropriate participation in research There is a paucity of information regarding the optimal method of presenting risk/benefit information to parents of pediatric research subjects . This study , therefore , was design ed to examine the effect of different message formats on parents ' underst and ing of research risks and benefits . An Internet-administered survey was completed by 4,685 parents who were r and omized to receive risk/benefit information about a study of pediatric postoperative pain control presented in different message formats ( text , tables , and pictographs ) . Survey questions assessed participants ' gist and verbatim underst and ing of the information and their perceptions of the risks and benefits . Pictographs were associated with significantly ( p < .05 ) greater likelihood of adequate gist and verbatim underst and ing compared with text and tables regardless of the participants ' numeracy . Parents who received the information in pictograph format perceived the risks to be lower and the benefits to be higher compared with the other formats ( p < .001 ) . Furthermore , compared with text and tables , pictographs were perceived as more “ effective , ” “ helpful , ” and “ trustworthy ” in presenting risk/benefit information . These results underscore the difficulties associated with presenting risk/benefit information for clinical research but suggest a simple method for enhancing parents ' informed underst and ing of the relevant statistics PURPOSE Here we report the results of a r and omized study undertaken to test the efficacy of a supplementary , telephone-based nursing intervention in increasing patients ' awareness and underst and ing of the clinical trials in which they are asked to participate . METHODS During a 12-month period , 180 cancer patients who were approached to participate in a phase II or III clinical trial were r and omized to undergo either of the following : ( 1 ) st and ard informed consent procedures based on verbal explanations from the treating physician plus written information ( controls ) ; or ( 2 ) st and ard informed consent procedures plus a supplementary , telephone-based contact with an oncology nurse ( intervention ) . For purpose s of evaluation , face-to-face interviews were conducted with all patients approximately 1 week after the informed consent process had been completed . RESULTS The two groups were comparable with regard to sociodemographic and clinical variables . Both groups had a high level of awareness of the diagnosis and of the nature and objectives of the proposed treatments . The intervention group was significantly ( P < .01 ) better informed about the following : ( 1 ) the risks and side effects of treatment ; ( 2 ) the clinical trial context of the treatment ; ( 3 ) the objectives of the clinical trial ; ( 4 ) where relevant , the use of r and omization in allocating treatment ; ( 5 ) the availability of alternative treatments ; ( 6 ) the voluntary nature of participation ; and ( 7 ) the right to withdraw from the clinical trial . The intervention did not have any significant effect on patients ' anxiety levels or on rates of clinical trial participation . Patients reported high levels of satisfaction with the intervention . CONCLUSION The use of a supplementary , telephone-based nursing intervention is a feasible and effective means to increase cancer patients ' awareness and underst and ing of the salient issues that surround the clinical trials in which they are asked to participate BACKGROUND . Valid consent for research requires comprehensive and underst and able information to be disclosed to participants . The way that information is shared varies , but regulatory bodies usually determine style . Some reports have suggested that although information may be all-inclusive , it does little to support underst and ing . OBJECTIVE . To explore the impact of various information-sharing approaches on parents ' underst and ing of a research study and the validity of their consent . METHODS . This was a r and omized , controlled trial . Parents of immature but well infants admitted to a large tertiary NICU in Edinburgh , Scotl and , were r and omly assigned within 72 hours of their infant 's admission to receive 1 of 2 information leaflets , with or without a st and ardized verbal explanation , for a hypothetical intensive care research study . The leaflets differed in length and in the amount of detail in which the study process , risks , benefits , and patient rights were described . A question naire was used to elicit underst and ing about the purpose of the research , design of the study , procedures involved , and the consent process . RESULTS . Forty-one parents participated in the study . Those who received the longer leaflet without verbal explanation gained only limited underst and ing of the purpose of the research . The procedures involved in the study were understood better by those who received the shorter leaflet . Issues relating to consent and study design were readily understood in all groups . Irrespective of documentation style , verbal explanation significantly improved underst and ing . Differences in underst and ing had little effect on whether a parent would enroll his or her infant into the study . CONCLUSIONS . Verbal explanation significantly enhances underst and ing of the research process for participants regardless of the style of written documentation . However , shorter written information may lead to better underst and ing than lengthy , more complex documentation BACKGROUND The purpose of this study was to systematic ally compare two audiotape formats for the delivery of information relevant to informed consent to participate in a clinical trial in breast oncology , and to establish the feasibility of adding a consultation recording protocol to a clinical treatment trial . METHOD Participants were 69 women with newly diagnosed breast cancer and 21 oncologists from 5 Canadian cancer centers . Patients were block r and omized to one of three groups : 1 . st and ardized audiotape ; 2 . consultation audiotape ; or 3 . both audiotapes . Patients received their tapes immediately following the clinical trial consultation . Patient outcomes included perception of being informed about clinical trials , knowledge of information relevant to providing informed consent to a clinical trial , and satisfaction with communication during the consultation . RESULTS The consultation audiotapes contained less trial-related information than the st and ardized audiotape but there were no differences in clinical trial knowledge or perception of being informed across the intervention groups . Patients expressed a marginally significant preference for consultation audiotapes over st and ardized audiotapes . CONCLUSIONS Patients tended to prefer receiving an audiotape of their own consultation over a st and ardized audiotape . The majority of oncologists considered the audiotape intervention feasible but were less enthusiastic about being involved in a larger study given the accrual challenges that arose when trying to " piggy-back " one r and omized controlled trial on an existing clinical trial Growing recognition of the inadequacy of traditional methods of providing informed consent , especially for individuals vulnerable to impaired decisional capacity , has spurred recent interest in how to assess and improve components of consent-related decision making . In this preliminary study , we aim ed to compare different methods of interactive question ing during presentation of research consent information among patients with schizophrenia . Patients were r and omized to receive either st and ard administration ( SA ) of a consent form or one of two interactive question ing methods : Corrective Feedback ( CF ) , in which the correct answer was provided following the participant 's response , or Errorless Learning ( EL ) , in which correct answers were provided just prior to the question . The MacArthur Competence Assessment Tool for Clinical Research ( MacCAT-CR ) was used to measure underst and ing , appreciation , reasoning , and expression of a choice following presentation of the consent form . There was no significant effect of condition ( SA vs. EL vs. CF ) on any of the components of decisional capacity . Underst and ing scores measured during the consent process were higher than those measured afterward , but the two scores were highly correlated . Thus , the results of this r and omized study suggest that interactive question ing neither helped nor harmed underst and ing , appreciation , or reasoning among patients with schizophrenia . Other considerations , however , may favor use of such methods in the consenting process OBJECTIVE The objective of this study was to assess a modified consent procedure allowed under federal regulations and developed for studies , particularly clinical trials , that are judged by the Institutional Review Board to reduce or have no effect on patient risk . STUDY DESIGN This was a r and omized trial of a conventional consent procedure that required parental signature to give consent ( opting in ) after a comprehensive disclosure of the rights of participants in research versus a modified consent procedure that required parental signature to refuse consent ( opting out ) after specific disclosures appropriate when risk is not increased . Consent was sought for a trial of primary follow-up care for disadvantaged infants at high risk , a trial judged by our Institutional Review Board to increase access to care for both groups . A blinded assessor interviewed mothers within 24 hours of the consent decision . RESULTS Among the 44 mothers interviewed , the modified consent group scored higher than the conventional consent group in recall and underst and ing of study purpose and methods ( 47 % vs 30 % ; p < 0.02 ) . Other comparisons provided no evidence that the modified consent procedure was less desirable . Virtually all mothers reported satisfaction . CONCLUSIONS The modified approach may improve communication and facilitate studies judged by the Institutional Review Board to be risk-neutral or risk-reducing . Further evaluation of a modified consent procedure for such studies is warranted Individuals with schizophrenia may show impaired capacity to make decisions about participating in research , yet these patients also show considerable heterogeneity in decisional abilities . Problems with procedures contribute to patients ' difficulties in underst and ing consent forms . Few studies have focused on improving comprehension of research consent in older patients with psychotic disorders . In this study , 80 middle-aged and elderly out patients with schizophrenia or related psychotic disorders and 19 normal comparison subjects were r and omized to receive a routine consent ( RC ) or enhanced consent ( EC ) procedure . The EC procedure consisted of a computerized slide show incorporating more structure and review of important information . A comprehension test was administered after the consent procedure ; subjects were given up to three trials of the post-test to answer all of the questions correctly . Overall , the normal comparison subjects obtained a higher score on the post-consent comprehension test than the patients . Within each of these two groups , those who received EC had better comprehension than those who received RC . Interestingly , EC patients did not differ significantly from RC normal comparison subjects in their post-test scores . Among the patients , comprehension test scores correlated with level of education and cognitive performance OBJECTIVE This study evaluated a brief educational video design ed to enhance the informed consent process for people with serious mental and medical illnesses who are considering participating in treatment research . METHOD Individuals with schizophrenia who were being recruited for ongoing clinical trials , medical patients without self-reported psychiatric comorbidity , and university undergraduates were r and omly assigned to view either a highly structured instructional videotape about the consent process in treatment research or a control videotape that presented only general information about bioethical issues in human research . Knowledge about informed consent was measured before and after viewing . RESULTS Viewing the experimental videotape result ed in larger gains in knowledge about informed consent . St and ardized effect sizes were large in all groups . CONCLUSIONS The videotape was thus an effective teaching tool across diverse population s , ranging from individuals with severe chronic mental illness to university undergraduates Research participants often fail to recall substantial amounts of informed consent information after delays of only a few days . Numerous interventions have proven effective at improving consent recall ; however , virtually all have focused on compensating for potential cognitive deficits and have ignored motivational factors . In this pilot study , the authors r and omly assigned 31 drug court clients participating in a clinical research trial to a control group that received a st and ard informed consent procedure or to a group that received the same procedure plus incentives for correctly recalling consent information . The incentive group was told they would receive $ 5 for each of the 15 consent items they could answer correctly 1 week later . At the follow-up , the incentive group recalled a significantly greater percentage of consent information overall than the control group ( 65 % vs. 42 % , p<.01 ) . Findings from this study have important implication s for the ethical conduct of human subject research . The incentivized consent procedure may be useful for improving consent recall in research studies , particularly those involving potentially serious side effects . The results also provide an important " proof of concept " regarding the utility of motivational procedures for improving recall of consent information Writing an informed consent form ( ICF ) for biomedical research is a difficult task . We conducted a multicenter single‐blind r and omized controlled trial to identify whether a working group or the systematic improvement in lexico‐syntactic readability or an association of the two could increase the comprehension of the written information given to healthy volunteers enrolled in biomedical research . Participants were r and omized to read one of four versions of the ICF : unchanged ICF ( A ) , ICF with systematic lexico‐syntactic readability improvement ( B ) , ICF modified by a working group ( C ) , and ICF modified by the working group followed by systematic lexico‐syntactic improvement ( D ) . The primary end‐point was the objective comprehension score at day 0 for each study group . The scores of objective comprehension at day 0 were statistically different between the four study groups ( anovaP = 0.020 ) . The pairwise analysis showed an improvement in the working group vs. the unchanged group ( P = 0.003 ) , and a tendency to improvement in the group who read the ICF modified using lexico‐syntactic readability and in the group who read the ICF modified using the two methods ( P = 0.020 and 0.027 respectively ) . We conducted a two‐way anova to identify some characteristics of the population which could explain this score . There was a significant interaction between the type of informed consent document ( ICD ) and the gender . Improving the ICD in phase I biomedical research leads to better comprehension , whether the method used is systematic lexico‐syntactic improvement or a review by a working group . The improvement is specifically observed in men compared with women . Conversely , while both methods diverge in their effect on lexico‐syntactic readability , their association is not m and atory . We suggest that in all phase I clinical trials , the ICF be improved by either method A simplified version of the prototype HIV vaccine material was developed through ( a ) reducing reading grade level , ( b ) restructuring of the organization and categorization of the material , ( c ) adding pictures design ed to emphasize key concepts , and ( d ) obtaining feedback on the simplified version through focus groups with the target population . Low-income women at risk for HIV ( N = 141 ) recruited from a primary care clinic were r and omly assigned to be presented the st and ard or the simplified version . There were no significant differences between the groups in terms of education or Vocabulary , Block Design , and Passage Comprehension scores . Women who received the simplified version had significantly higher comprehension scores immediately following presentation of the material than did women who received the st and ard version and were also significantly more likely to recall study benefits and risks . These findings were maintained at 3-month follow-up . Implication s for informed consent are discussed OBJECTIVE Patients are commonly presented with complex documents that they have difficulty underst and ing . The objective of this study was to design and evaluate an animated computer agent to explain research consent forms to potential research participants . METHODS Subjects were invited to participate in a simulated consent process for a study involving a genetic repository . Explanation of the research consent form by the computer agent was compared to explanation by a human and a self- study condition in a r and omized trial . Responses were compared according to level of health literacy . RESULTS Participants were most satisfied with the consent process and most likely to sign the consent form when it was explained by the computer agent , regardless of health literacy level . Participants with adequate health literacy demonstrated the highest level of comprehension with the computer agent-based explanation compared to the other two conditions . However , participants with limited health literacy showed poor comprehension levels in all three conditions . Participants with limited health literacy reported several reasons , such as lack of time constraints , ability to re-ask questions , and lack of bias , for preferring the computer agent-based explanation over a human-based one . CONCLUSION Animated computer agents can perform as well as or better than humans in the administration of informed consent . PRACTICE IMPLICATION S Animated computer agents represent a viable method for explaining health documents to patients We evaluate the impact of a videotape specially produced to supplement written information about preventive HIV vaccine trials . One hundred eighty-six injection drug users were r and omly assigned to an education session in which either : ( a ) a pamphlet was review ed before a brief discussion period or ( b ) the videotape was watched prior to review ing the pamphlet and participating in the discussion . The relationship among retention of information , trust in government , and willingness to participate in a vaccine trial was tested before the presentation of information , immediately after , and 1 month later . Results indicate that both methods produced significant increases in knowledge immediately after information presentation , but only the video-supplemented group retained the information 1 month later . Subjects receiving the video supplement also showed a significant increase in trust at the first posttest period , but this increase was not maintained 1 month later . Regardless of group assignment or evaluation point , willingness to participate was not associated with knowledge but was associated with trust in government The study objective was to assess the relative effects of 2 approaches to teaching about a clinical trial , in terms of patients ' satisfaction , information underst and ing , and whether or not they would enter such a trial . One hundred patients receiving radiation therapy for a variety of cancer diagnoses were r and omized to receive information about a hypothetical trial , either by audio tape or interactive computer program . A day later , information underst and ing was assessed . One week later , method satisfaction and whether respondents would enter such a trial were assessed . There were no differences in underst and ing or satisfaction . Members of the computer program group tended to report a more positive attitude towards trial entry ( chi 2 = 4.0 ; 1 df ; P = 0.05 ) . Overall , refusers tended to be women with higher underst and ing scores . The results suggest that teaching with interactive components might not adversely affect trial accrual . Further work involving an actual trial entry decision is merited ; the sex of the respondent should be controlled in design ing this future work Federal research regulations require investigators to inform research subjects of " significant new findings developed during the course of the research which may relate to the subject 's willingness to continue participation."1 However , the determination of what is , and what is not , relevant to disclose is open to interpretation and potential ethical conflict . The recently reported results of a multi-center r and omized Phase III trial ( in which the author of this commentary was the principal investigator ) examining " maintenance/consolidation therapy " of advanced ovarian cancer provide a poignant example of the complexity of this fundamental issue . The study objective was to evaluate the effect of a patient information video during the informed consent process of a perinatal trial . Ninety women , between 19 and 33 weeks gestation , were r and omised to receive written information about this perinatal trial and watch an information video or to receive written information only . Participants completed a question naire immediately after entry and 2 - 4 weeks later assessing knowledge of ; feelings about the worth of ; and willingness for future participation in the perinatal trial . When initially asked , more women who watched the video thought they would consent to the study ( chi 2 = 6.3 ; df = 1 ; P = 0.01 ) . No differences in knowledge about the perinatal trial were found initially , but 2 - 4 weeks later more knowledge had been retained by women who had watched the video ( chi 2 = 6.7 ; df = 1 ; P = 0.01 ) . These results suggest that a patient information video combined with an information sheet may result in greater participation in a research trial and may increase women 's knowledge of a specific health problem and related research trial To improve the patient education process in clinical research , three information material s describing general aspects of design and conduct of r and omized clinical trials were developed . The material s varied in length , reading ability level , and reader appeal . Their influence on knowledge about and attitude toward r and omized clinical trials was assessed in a r and omized , parallel group , evaluator-blinded trial among 415 out patients . The patients were r and omized to the following groups : control ( no intervention ) , leaflet , brochure , or booklet . Knowledge was assessed by a 17-item multiple-choice question naire and attitude was assessed by a 32-item Likert question naire at entry and 2 weeks after the intervention . The interventions and the question naires were pilot tested and power calculations were performed . At entry , the mean knowledge score was 7.9 points . At follow-up , the knowledge scores increased by 0.5 for the control , 1.0 for the leaflet , 1.6 for the brochure , and 1.4 for the booklet . The brochure and the booklet improved the knowledge score significantly compared with the control . The general attitude was positive at entry ( mean 71.5 points ) . Only the booklet significantly increased the total attitude score ( 4.8 points ) and the r and omized clinical trials attitude subscale score ( 1.8 points ) . In conclusion , written information significantly improved out patients ' knowledge about and attitude toward r and omized clinical trials . Detailed rather than brief information was more effective . Control Clin Trials 2000;21:223 - If evidence -based medicine is the backbone of modern medical practice , clinical trial results are the vertebrae . Appropriately design ed r and omized clinical trials provide valid assessment s of the safety and efficacy of treatments , diagnostics , and preventive therapies . Thus , trial results can influence mainstream medicine and change medical practice . ' Yet an impediment to clinical research is the low number of individuals who enroll in clinical trials . One barrier to enrollment is negative public perceptions about research with humans , e.g. , the Nazi experiments during World War II and the U.S. Public Health Service 's syphilis study in Tuskegee , Alabama , that damaged the reputation of human subjects research among a substantial segment of the population . ' These negative perceptions about human subjects research have been reinforced by recent disclosures of ethical lapses in clinical research .3 Other barriers to enrollment include the public 's lack of underst and ing about the methods and purpose s of clinical research and about the modern institutional safeguards that have been incorporated into the research process to protect participants .4 Accusations of alleged abuses are well-publicized , but the diligent work OBJECTIVE The objective of this study was to evaluate the feasibility , acceptability , and preliminary efficacy of two enhanced consent procedures provided to patients with Alzheimer disease or mild cognitive impairment that used either a PowerPoint presentation or an enhanced printed consent form . METHODS Patients r and omly assigned to an enhanced written consent procedure or slideshow presentation were assessed with the MacArthur Competence Assessment Tool for Clinical Research . RESULTS Verbal reexplanation was associated with improved underst and ing in both conditions . Level of underst and ing did not significantly differ between the two consent groups , but administration time for slideshow presentation was less than that for an enhanced written consent procedure . CONCLUSION Enhanced consent procedures are feasible and useful for consent to research among patients with mild cognitive impairment or mild Alzheimer disease A r and omized trial comparing the amount of knowledge orally recalled from four different presentations of the same consent information was conducted in a non-clinic sample of 233 low-income parents who displayed a range of reading comprehension skill . The study simulated recruitment of children into one of two actual studies underway at another location : one involved high risk to participants , the other did not . Use of a non-clinic sample controlled for prior knowledge of the conditions , and avoiding discussion of the information further assured that differences in recalled information could be attributed more confidently to the format itself . The formats included the original written forms , enhanced print ( simpler language , topic headings , pictures ) , narrated videotapes , and self-paced PowerPoint presentations via laptop computer with bulleted print information , pictures , and narration . No format-related differences in recalled information were found in the full sample but for the 124 individuals with reading comprehension scores at or below the 8th grade level , the enhanced print version tended to be more effective than either the original form or the video . Across all formats , more information was recalled about the low-risk study . The findings emphasize the necessity for clinicians and research ers to verify underst and ing of consent information , especially when there is risk of reduced literacy skill . Reliance on video to convey information in preference to well-done print media appeared question able Background The informed consent process for research warrants improvement but approaches design ed to enhance informed consent need testing in the context of actual clinical research . Purpose Test the cumulative effect of a retrospective quality assurance question naire intended to enhance awareness in the person obtaining informed consent on the quality of the informed consent in clinical trials . Methods In the Veterans Affairs Cooperative Study ` Enhancing the Quality of Informed Consent- Self Monitoring ' , 30 study sites are r and omly assigned from five clinical trials to either use a new quality assurance question naire after each informed consent encounter or the st and ard process of obtaining informed consent . The quality of informed consent is evaluated using independent telephone interviews of 836 subjects who had given consent to participate in the clinical trials and the authors ' study . The main outcome measures are two previously vali date d scores derived from an independent telephone interview , measuring the overall quality of consent as well as the degree of ` therapeutic misapprehension ' . Patients and assessors are blind to the study arm assignment . Results Subjects report complete ( 93 % ) or some ( 6 % ) satisfaction with the consent process of the ` parent ' clinical trial , and 91 % recognize no consequences to non-participation . Concerning the ` primary purpose ' of the parent trial , 67 % indicate underst and ing of the research purpose , 41 % that the research is to benefit others , while 14 % think the research is directed to their own benefit ; 60 % report no risk to participation and 65 % report at least one expects direct benefit . Interviewers assess 77 % of subjects as showing full appreciation of the ` voluntariness ' of participation . The quality assurance question naire do not provide an appreciable effect on the quality of informed consent . Using mixed model methods to account for the group r and omization , near zero , non-significant effects have been found for the overall assessment score ( -0.034 on a 0—10 point scale , st and ard error 0.099 , P = 0.73 ) and for the score measuring ` therapeutic misconception ' ( -0.005 on a 0—5 point scale , st and ard error 0.137 , P = 0.97 ) . Permutation methods yield similar results . Confidence intervals are narrow enough to exclude any clinical ly important effect . Limitations The intervention may work in a more homogeneous patient population , or one that is not sample d. The outcome measurement relies on a short , anonymous , telephone interview ( to minimize burden and eliminate bias ) , but a longer , face-to-face interview may be more sensitive to differences . A ` checklist ' tied directly to the outcome measures may show an effect . Clinical Trials 2007 ; 4 : 638—649 . http://ctj.sagepub.com Conclusions Despite prior beliefs , a st and ardized quality assurance tool do not enhance informed consent in actual clinical trials . Future research is needed to rigorously evaluate proposed methods to enhance informed consent prior to widespread introduction |
1,869 | 25,052,536 | There was reasonably strong evidence for the cost-effectiveness of the use of women ’s groups , home-based newborn care using community health workers and traditional birth attendants , adding services to routine antenatal care , a facility-based quality improvement initiative to enhance compliance with care st and ards , and the promotion of breastfeeding in maternity hospitals . | Background Each year almost 3 million newborns die within the first 28 days of life , 2.6 million babies are stillborn , and 287,000 women die from complications of pregnancy and childbirth worldwide .
Effective and cost-effective interventions and behaviours for mothers and newborns exist , but their coverage remains inadequate in low- and middle-income countries , where the vast majority of deaths occur . | Background Maternal , perinatal and neonatal mortality remains high in low-income countries . We evaluated community and facility-based interventions to reduce deaths in three districts of Malawi . Methods We evaluated a rural participatory women ’s group community intervention ( CI ) and a quality improvement intervention at health centres ( FI ) via a two-by-two factorial cluster r and omized controlled trial . Consenting pregnant women were followed-up to 2 months after birth using key informants . Primary outcomes were maternal , perinatal and neonatal mortality . Clusters were health centre catchment areas assigned using stratified computer-generated r and omization . Following exclusions , including non-birthing facilities , 61 clusters were analysed : control ( 17 clusters , 4912 births ) , FI ( 15 , 5335 ) , CI ( 15 , 5080 ) and FI + CI ( 14 , 5249 ) . This trial was registered as International St and ard R and omised Controlled Trial [ IS RCT N18073903 ] . Outcomes for 14 576 and 20 576 births were recorded during baseline ( June 2007–September 2008 ) and intervention ( October 2008–December 2010 ) periods . Results For control , FI , CI and FI + CI clusters neonatal mortality rates were 34.0 , 28.3 , 29.9 and 27.0 neonatal deaths per 1000 live births and perinatal mortality rates were 56.2 , 55.1 , 48.0 and 48.4 per 1000 births , during the intervention period . Adjusting for clustering and stratification , the neonatal mortality rate was 22 % lower in FI + CI than control clusters ( OR = 0.78 , 95 % CI 0.60–1.01 ) , and the perinatal mortality rate was 16 % lower in CI clusters ( OR = 0.84 , 95 % CI 0.72–0.97 ) . We did not observe any intervention effects on maternal mortality . Conclusions Despite implementation problems , a combined community and facility approach using participatory women ’s groups and quality improvement at health centres reduced newborn mortality in rural Malawi BACKGROUND Women 's groups and health education by peer counsellors can improve the health of mothers and children . We assessed their effects on mortality and breastfeeding rates in rural Malawi . METHODS We did a 2 × 2 factorial , cluster-r and omised trial in 185,888 people in Mchinji district . 48 equal-sized clusters were r and omly allocated to four groups with a computer-generated number sequence . 24 facilitators guided groups through a community action cycle to tackle maternal and child health problems . 72 trained volunteer peer counsellors made home visits at five timepoints during pregnancy and after birth to support breastfeeding and infant care . Primary outcomes for the women 's group intervention were maternal , perinatal , neonatal , and infant mortality rates ( MMR , PMR , NMR , and IMR , respectively ) ; and for the peer counselling were IMR and exclusive breastfeeding ( EBF ) rates . Analysis was by intention to treat . The trial is registered as IS RCT N06477126 . FINDINGS We monitored outcomes of 26,262 births between 2005 and 2009 . In a factorial model adjusted only for clustering and the volunteer peer counselling intervention , in women 's group areas , for years 2 and 3 , we noted non-significant decreases in NMR ( odds ratio 0.93 , 0.64 - 1.35 ) and MMR ( 0.54 , 0.28 - 1.04 ) . After adjustment for parity , socioeconomic quintile , and baseline measures , effects were larger for NMR ( 0.85 , 0.59 - 1.22 ) and MMR ( 0.48 , 0.26 - 0.91 ) . Because of the interaction between the two interventions , a stratified analysis was done . For women 's groups , in adjusted analyses , MMR fell by 74 % ( 0.26 , 0.10 - 0.70 ) , and NMR by 41 % ( 0.59 , 0.40 - 0.86 ) in areas with no peer counsellors , but there was no effect in areas with counsellors ( 1.09 , 0.40 - 2.98 , and 1.38 , 0.75 - 2.54 ) . Factorial analysis for the peer counselling intervention for years 1 - 3 showed a fall in IMR of 18 % ( 0.82 , 0.67 - 1.00 ) and an improvement in EBF rates ( 2.42 , 1.48 - 3.96 ) . The results of the stratified , adjusted analysis showed a 36 % reduction in IMR ( 0.64 , 0.48 - 0.85 ) but no effect on EBF ( 1.18 , 0.63 - 2.25 ) in areas without women 's groups , and in areas with women 's groups there was no effect on IMR ( 1.05 , 0.82 - 1.36 ) and an increase in EBF ( 5.02 , 2.67 - 9.44 ) . The cost of women 's groups was US$ 114 per year of life lost ( YLL ) averted and that of peer counsellors was $ 33 per YLL averted , using stratified data from single intervention comparisons . INTERPRETATION Community mobilisation through women 's groups and volunteer peer counsellor health education are methods to improve maternal and child health outcomes in poor rural population s in Africa . FUNDING Saving Newborn Lives , UK Department for International Development , and Wellcome Trust In this article we examine the cost-effectiveness of the Smiling Sun multichannel media campaign , which was undertaken in Bangladesh from 2001 to 2003 and involved a nationally broadcast television serial drama supported by radio , television , newspaper , and billboard advertisements and local promotion activities . The goal was to encourage the use of a package of family health services at NGO ( nongovernmental organization ) Service Delivery Program ( NSDP ) providers . This analysis relates the costs of the Smiling Sun campaign at the national and local level to measures of change in the use of health services , namely , antenatal care and childhood immunizations . Effectiveness is measured using data from cross-sectional surveys conducted in 2001 and 2003 in NSDP catchment areas in rural Bangladesh . The statistical approach , bivariate probit estimation , controls for nonr and om exposure to the program 's media messages , advertisements , and signs . Using national-level data , we find that the Smiling Sun campaign was both effective and cost-effective , inducing higher levels of service utilization for only $ 0.05 per additional antenatal care ( ANC ) user and only $ 0.30 and $ 0.36 for each additional child vaccinated for measles and DPT3 , respectively . With respect to local promotion activities , the cost per attributable behavior change was considerably higher — nearly $ 8 per new ANC user , $ 37 per new DPT3 vaccination , and $ 32 per new measles vaccination OBJECTIVE To evaluate and compare the cost-effectiveness of two strategies for neonatal care in Sylhet division , Bangladesh . METHODS In a cluster-r and omized controlled trial , two strategies for neonatal care -- known as home care and community care -- were compared with existing services . For each study arm , economic costs were estimated from a societal perspective , inclusive of programme costs , provider costs and household out-of-pocket payments on care-seeking . Neonatal mortality in each study arm was determined through household surveys . The incremental cost-effectiveness of each strategy --compared with that of the pre-existing levels of maternal and neonatal care -- was then estimated . The levels of uncertainty in our estimates were quantified through probabilistic sensitivity analysis . FINDINGS The incremental programme costs of implementing the home-care package were 2939 ( 95 % confidence interval , CI : 1833 - 7616 ) United States dollars ( US$ ) per neonatal death averted and US$ 103.49 ( 95 % CI : 64.72 - 265.93 ) per disability-adjusted life year ( DALY ) averted . The corresponding total societal costs were US$ 2971 ( 95 % CI : 1844 - 7628 ) and US$ 104.62 ( 95 % CI : 65.15 - 266.60 ) , respectively . The home-care package was cost-effective -- with 95 % certainty -- if healthy life years were valued above US$ 214 per DALY averted . In contrast , implementation of the community-care strategy led to no reduction in neonatal mortality and did not appear to be cost-effective . CONCLUSION The home-care package represents a highly cost-effective intervention strategy that should be considered for replication and scale-up in Bangladesh and similar setting s elsewhere OBJECTIVE To assess the cost-effectiveness of an ambulance service within a comprehensive hospital/community-based program aim ed at improving access and quality of reproductive health in poor-re sources setting s. METHODS Obstetrical cases referred to the hospital with the ambulance during a 3-month period were prospect ively recorded . Clinical indications were used to determine the effectiveness of the referral ; the direct costs of the service were calculated . Overall effectiveness was then measured against WHO thresholds . RESULTS Ninety-two obstetrical referrals were recorded . Eleven ( 12 % ) were considered effective , corresponding to 611.7 years saved . Cost per year saved was 15.82 US dollars which about half of WHO 's 30 US dollar benchmark defining very attractive interventions . Sensitivity analyses on the costs of the ambulance and the rate of effective referrals emphasized the robustness of the result . CONCLUSIONS The cost-effectiveness profile of an ambulance service within a series of interventions aim ed at improving reproductive health in remote setting s is very attractive We did a cost-effectiveness analysis alongside a cluster-r and omised controlled trial of a participatory intervention with women 's groups to improve birth outcomes in rural Nepal . The average provider cost of the women 's group intervention was US0.75 dollars per person per year ( 0.90 dollars with health-service strengthening ) in a population of 86,704 . The incremental cost per life-year saved ( LYS ) was 211 dollars ( 251 dollars ) , and expansion could rationalise on start-up costs and technical assistance , reducing the cost per LYS to 138 dollars ( 179 dollars ) . Sensitivity analysis showed a variation from 83 dollars to 263 dollars per LYS for most variables . This intervention could provide a cost-effective way of reducing neonatal deaths IMPORTANCE Community-based interventions can reduce neonatal mortality when health systems are weak . Population coverage of target groups may be an important determinant of their effect on behavior and mortality . A women 's group trial at coverage of 1 group per 1414 population in rural Bangladesh showed no effect on neonatal mortality , despite a similar intervention having a significant effect on neonatal and maternal death in comparable setting s. OBJECTIVE To assess the effect of a participatory women 's group intervention with higher population coverage on neonatal mortality in Bangladesh . DESIGN A cluster r and omized controlled trial in 9 intervention and 9 control clusters . SETTING Rural Bangladesh . PARTICIPANTS Women permanently residing in 18 unions in 3 districts and accounting for 19 301 births during the final 24 months of the intervention . INTERVENTIONS Women 's groups at a coverage of 1 per 309 population that proceed through a participatory learning and action cycle in which they prioritize issues that affected maternal and neonatal health and design and implement strategies to address these issues . MAIN OUTCOMES AND MEASURES Neonatal mortality rate . RESULTS Analysis included 19 301 births during the final 24 months of the intervention . More than one-third of newly pregnant women joined the groups . The neonatal mortality rate was significantly lower in the intervention arm ( 21.3 neonatal deaths per 1000 live births vs 30.1 per 1000 in control areas ) , a reduction in neonatal mortality of 38 % ( risk ratio , 0.62 [ 95 % CI , 0.43 - 0.89 ] ) when adjusted for socioeconomic factors . The cost-effectiveness was US $ 220 to $ 393 per year of life lost averted . Cause-specific mortality rates suggest reduced deaths due to infections and those associated with prematurity/low birth weight . Improvements were seen in hygienic home delivery practice s , newborn thermal care , and breastfeeding practice s. CONCLUSIONS AND RELEVANCE Women 's group community mobilization , delivered at adequate population coverage , is a highly cost-effective approach to improve newborn survival and health behavior indicators in rural Bangladesh . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N01805825 BACKGROUND Community mobilisation through participatory women 's groups might improve birth outcomes in poor rural communities . We therefore assessed this approach in a largely tribal and rural population in three districts in eastern India . METHODS From 36 clusters in Jharkh and and Orissa , with an estimated population of 228 186 , we assigned 18 clusters to intervention or control using stratified r and omisation . Women were eligible to participate if they were aged 15 - 49 years , residing in the project area , and had given birth during the study . In intervention clusters , a facilitator convened 13 groups every month to support participatory action and learning for women , and facilitated the development and implementation of strategies to address maternal and newborn health problems . The primary outcomes were reductions in neonatal mortality rate ( NMR ) and maternal depression scores . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N21817853 . FINDINGS After baseline surveillance of 4692 births , we monitored outcomes for 19 030 births during 3 years ( 2005 - 08 ) . NMRs per 1000 were 55.6 , 37.1 , and 36.3 during the first , second , and third years , respectively , in intervention clusters , and 53.4 , 59.6 , and 64.3 , respectively , in control clusters . NMR was 32 % lower in intervention clusters adjusted for clustering , stratification , and baseline differences ( odds ratio 0.68 , 95 % CI 0.59 - 0.78 ) during the 3 years , and 45 % lower in years 2 and 3 ( 0.55 , 0.46 - 0.66 ) . Although we did not note a significant effect on maternal depression overall , reduction in moderate depression was 57 % in year 3 ( 0.43 , 0.23 - 0.80 ) . INTERPRETATION This intervention could be used with or as a potential alternative to health-worker-led interventions , and presents new opportunities for policy makers to improve maternal and newborn health outcomes in poor population s. FUNDING Health Foundation , UK Department for International Development , Wellcome Trust , and the Big Lottery Fund ( UK ) Background The Lufwanyama Neonatal Survival Project ( “ LUNESP ” ) was a cluster r and omized , controlled trial that showed that training traditional birth attendants ( TBAs ) to perform interventions targeting birth asphyxia , hypothermia , and neonatal sepsis reduced all-cause neonatal mortality by 45 % . This companion analysis was undertaken to analyze intervention costs and cost-effectiveness , and factors that might improve cost-effectiveness . Methods and Findings We calculated LUNESP 's financial and economic costs and the economic cost of implementation for a forecasted ten-year program ( 2011–2020 ) . In each case , we calculated the incremental cost per death avoided and disability-adjusted life years ( DALYs ) averted in real 2011 US dollars . The forecasted 10-year program analysis included a base case as well as ‘ conservative ’ and ‘ optimistic ’ scenarios . Uncertainty was characterized using one-way sensitivity analyses and a multivariate probabilistic sensitivity analysis . The estimated financial and economic costs of LUNESP were $ 118,574 and $ 127,756 , respectively , or $ 49,469 and $ 53,550 per year . Fixed costs accounted for nearly 90 % of total costs . For the 10-year program , discounted total and annual program costs were $ 256,455 and $ 26,834 respectively ; for the base case , optimistic , and conservative scenarios , the estimated cost per death avoided was $ 1,866 , $ 591 , and $ 3,024 , and cost per DALY averted was $ 74 , $ 24 , and $ 120 , respectively . Outcomes were robust to variations in local costs , but sensitive to variations in intervention effect size , number of births attended by TBAs , and the extent of foreign consultants ' participation . Conclusions Based on established guidelines , the strategy of using trained TBAs to reduce neonatal mortality was ‘ highly cost effective ’ . We strongly recommend consideration of this approach for other remote rural population s with limited access to health care Background and Aims Little is known about the extent and nature of publication bias in economic evaluations . Our objective was to determine whether economic evaluations are subject to publication bias by considering whether economic data are as likely to be reported , and reported as promptly , as effectiveness data . Methods Trials that intended to conduct an economic analysis and ended before 2008 were identified in the International St and ard R and omised Controlled Trial Number ( IS RCT N ) register ; a r and om sample of 100 trials was retrieved . Fifty comparator trials were r and omly drawn from those not identified as intending to conduct an economic study . The trial start and end date s , estimated sample size and funder type were extracted . For trials planning economic evaluations , effectiveness and economic publications were sought ; publication date s and journal impact factors were extracted . Effectiveness abstract s were assessed for whether they reached a firm conclusion that one intervention was most effective . Primary investigators were contacted about reasons for non-publication of results , or reasons for differential publication strategies for effectiveness and economic results . Results Trials planning an economic study were more likely to be funded by government ( p = 0.01 ) and larger ( p = 0.003 ) than other trials . The trials planning an economic evaluation had a mean of 6.5 ( range 2.7–13.2 ) years since the trial end in which to publish their results . Effectiveness results were reported by 70 % , while only 43 % published economic evaluations ( p < 0.001 ) . Reasons for non-publication of economic results included the intervention being ineffective , and staffing issues . Funding source , time since trial end and length of study were not associated with a higher probability of publishing the economic evaluation . However , studies that were small or of unknown size were significantly less likely to publish economic evaluations than large studies ( p < 0.001 ) . The authors ’ confidence in labelling one intervention clearly most effective did not affect the probability of publication . The mean time to publication was 0.7 years longer for cost-effectiveness data than for effectiveness data where both were published ( p = 0.001 ) . The median journal impact factor was 1.6 points higher for effectiveness publications than for the corresponding economic publications ( p = 0.01 ) . Reasons for publishing in different journals included editorial decision making and the additional time that economic evaluation takes to conduct . Conclusions Trials that intend to conduct an economic analysis are less likely to report economic data than effectiveness data . Where economic results do appear , they are published later , and in journals with lower impact factors . These results suggest that economic output may be more susceptible than effectiveness data to publication bias . Funders , grant review ers and trialists themselves should ensure economic evaluations are prioritized and adequately staffed to avoid potential problems with bias |
1,870 | 12,668,908 | ‘ Early ’ cohorts were important in defining the major risk factors for CHD , particularly smoking , cholesterol , blood pressure , physical activity and body mass index .
Conclusions The current and proposed prospect i ve UK cohorts have sufficient power potentially to determine the importance of many traditional and newer CHD risk factors on cardiovascular risk in men , women and even ethnic minorities . | Background Prospect i ve cohort studies have made enormous contributions to our underst and ing of coronary heart disease ( CHD ) epidemiology in the UK .
However , identification of cohorts and dissemination of key characteristics and results can be haphazard , and it is difficult to identify studies which are at the planning stage . | STUDY OBJECTIVE --To examine the effect on mortality of stopping smoking after myocardial infa rct ion and the psychosocial factors that influence the decision to stop . DESIGN -- Analysis of smokers in a large prospect i ve study . Self completed question naires provided information on psychosocial factors . SETTING --Coronary care units at six English hospitals participating in a multicentre clinical trial . SUBJECTS -- These comprised consenting myocardial infa rct ion survivors who had been identified as smokers and who completed question naires within seven days of infa rct at six hospitals participating in the Anglo-Sc and inavian study of early thrombolysis . The 532 patients identified have been followed for over five and a half years . The main outcome measure was five year all cause mortality . MAIN RESULTS --Smokers who stopped within one month showed significantly reduced mortality compared with those who persisted , adjusting for other prognostic indicators ( odds ratio 0.56 , 95 % confidence interval 0.33 , 0.98 ) . Overall , 74 % stopped smoking . Being married , low life stress levels before infa rct , and higher social class were associated with stopping smoking but the differentials were small . Of the clinical variables , a final diagnosis of definite myocardial infa rct ion was associated with stopping smoking . All associations remained after multiple logistic regression . CONCLUSION --Smoking cessation can halve the smokers ' odds of dying after myocardial infa rct ion and psychosocial factors play a small but important role in the important decision to stop smoking . Health professionals should continue to stress the importance of stopping smoking to all patients as there is little evidence to support specific directing of advice to relatively " stress or " socially isolated " groups STUDY OBJECTIVE : To determine the relationship between obesity and subsequent incidence of ischaemic heart disease ( IHD ) . DESIGN : Prospect i ve cohort survey . SETTING : Study of three occupational groups , with follow up examinations . SUBJECTS : 3500 people recruited between 1972 and 1978 ( 80 % response rate ) , and followed up between 1978 and 1984 . This report is based on subgroup of 1511 white men aged 40 - 64 at entry . MEASUREMENTS AND MAIN RESULTS : Information was obtained on smoking and family history of IHD . Blood pressure , weight , height , skinfold thickness at four sites , fibrinogen , factor VII activity and cholesterol were measured during follow up . Body mass index ( BMI ) was used as an index of obesity . BMI was found to be more strongly correlated with IHD than any of the skinfold measurements , none of which was significantly associated with IHD when BMI was allowed for . Increase in BMI by 1 SD ( approximately 8 kg ) was associated with a 44 % increase in the risk of IHD . Of the four skinfolds , subscapular was the most closely associated with risk , confirming the relevance of central obesity . The association between obesity and IHD remained when possible mechanisms for its effects were taken into account , and its strength may increase with time : for 1 SD increase in BMI , risk of events within 5 years was increased by 28 % , while risk of events after longer than 5 years was increased by 65 % . CONCLUSIONS : Preventive strategies for IHD should include avoidance of obesity In the British United Provident Association ( BUPA ) study , a prospect i ve observational study of 21,520 men , the serum albumin of 877 men who died during 10 years of follow-up was compared with that of 877 controls , each matched to a case by age ( within 1 year ) and date of attendance ( within 3 months ) . There was little overall difference ( mean case-control difference = -0.11 milligram , P > 0.2 ) despite the fact that other studies have reported a long-term association between low serum albumin and increased mortality . Cause-specific mortality data showed no association of low albumin with ischaemic heart disease or other circulatory diseases . An inverse association with cancer was confined to the first few years of follow-up and so attributable to pre- clinical cancer lowering both serum albumin itself and serum cholesterol , with which albumin was associated . There was an association of chronic respiratory , neurological , renal , liver and gut diseases with low serum albumin ( case-control difference = -1.19 milligram , P < 0.001 ) consistent with the effect of pre- clinical disease lowering serum albumin . Other causes of death showed no association with albumin . Our data do not support a cause and effect association of low serum albumin and mortality BACKGROUND Previous studies on diet and coronary heart disease ( CHD ) focused primarily on individual nutrients or foods . OBJECTIVE We examined whether overall dietary patterns derived from a food-frequency question naire ( FFQ ) predict risk of CHD in men . DESIGN This was a prospect i ve cohort study of 44875 men aged 40 - 75 y without diagnosed cardiovascular disease or cancer at baseline in 1986 . RESULTS During 8 y of follow-up , we documented 1089 cases of CHD ( nonfatal myocardial infa rct ion and fatal CHD ) . Using factor analysis , we identified 2 major dietary patterns using dietary data collected through a 131-item FFQ . The first factor , which we labeled the " prudent pattern , " was characterized by higher intake of vegetables , fruit , legumes , whole grains , fish , and poultry , whereas the second factor , the " Western pattern , " was characterized by higher intake of red meat , processed meat , refined grains , sweets and dessert , French fries , and high-fat dairy products . After adjustment for age and CHD risk factors , the relative risks from the lowest to highest quintiles of the prudent pattern score were 1.0 , 0 . 87 , 0.79 , 0.75 , and 0.70 ( 95 % CI : 0.56 , 0.86 ; P : for trend = 0.0009 ) . In contrast , the relative risks across increasing quintiles of the Western pattern score were 1.0 , 1.21 , 1.36 , 1.40 , and 1.64 ( 95 % CI : 1.24 , 2.17 ; P : for trend < 0.0001 ) . These associations persisted in subgroup analyses according to cigarette smoking , body mass index , and parental history of myocardial infa rct ion . CONCLUSIONS These data suggest that major dietary patterns derived from the FFQ predict risk of CHD , independent of other lifestyle variables Editorial by Jackson Current guidelines for prescribing lipid lowering drugs are based on an individual 's risk of coronary heart disease rather than on the reduction in risk that treatment may bring . We report a strategy for making treatment decisions that combines computer assisted calculation of absolute risk with an estimate of benefit to the patient from treatment . During a period of 14 months , 17 r and omly selected general practice s ( 63 practitioners ) in north Staffordshire were asked to send to the department of clinical biochemistry their requests for coronary heart disease risk assessment on patients being considered for lipid lowering drug treatment . Coronary risk factors in patients being considered for lipid lowering drugs . Values are means ( SD ) We used the Framingham statistical model to estimate a patient 's absolute risk of coronary heart disease over five years . The reduction in risk that treatment would bring over the next five years was calculated from the product of the absolute five OBJECTIVE : To investigate the associations of individual and area-based socioeconomic indicators with cardiovascular disease risk factors and mortality . DESIGN : Prospect i ve study . SETTING : The towns of Renfrew and Paisley in the west of Scotl and . PARTICIPANTS : 6961 men and 7991 women included in a population -based cardiovascular disease screening study between 1972 and 1976 . MAIN OUTCOME MEASURES : Cardiovascular disease risk factors and cardiorespiratory morbidity at the time of screening : 15 year mortality from all causes and cardiovascular disease . RESULTS : Both the area-based deprivation indicator and individual social class were associated with generally less favourable profiles of cardiovascular disease risk factors at the time of the baseline screening examinations . The exception was plasma cholesterol concentration , which was lower for men and women in manual social class groups . Independent contributions of area-based deprivation and individual social class were generally seen with respect to risk factors and morbidity . All cause and cardiovascular disease mortality rates were both inversely associated with socioeconomic position whether indexed by area-based deprivation or social class . The area-based and individual socioeconomic indicators made independent contributions to mortality risk . CONCLUSIONS : Individually assigned and area-based socioeconomic indicators make independent contributions to several important health outcomes . The degree of inequalities in health that exist will not be demonstrated in studies using only one category of indicator . Similarly , adjustment for confounding by socioeconomic position in aetiological epidemiological studies will be inadequate if only one level of indicator is used . Policies aim ed at reducing socioeconomic differentials in health should pay attention to the characteristics of the areas in which people live as well as the characteristics of the people who live in these areas Abstract Objective : To investigate the association between birth weight of offspring and mortality among fathers and mothers in the west of Scotl and . Design : Prospect i ve observational study . Participants : 794 married couples in Renfrew district of the west of Scotl and . Main outcome measures : Mortality from all causes and from cardiovascular disease over 15 year follow up . Results : Women who had heavier babies were taller , had higher body mass index and better lung function , and were less likely to be smokers than mothers of lighter babies . Fathers of heavier babies were taller and less likely to be smokers than fathers of lighter babies . Mortality was inversely related to offspring 's birth weight for both mothers ( relative rate for a 1 kg lower birth weight 1.82 ( 95 % confidence interval 1.23 to 2.70 ) ) and fathers ( relative rate 1.35 ( 1.03 to 1.79 ) ) . For mortality from cardiovascular disease , inverse associations were seen for mothers ( 2.00 ( 1.18 to 3.33 ) ) and fathers ( 1.52 ( 1.03 to 2.17 ) ) . Adjustment for blood pressure , plasma cholesterol , body mass index , height , social class , area based deprivation category , smoking , lung function , angina , bronchitis , and electrocardiographic evidence of ischaemia had little effect on these risk estimates , although levels of statistical significance were reduced . Conclusions : Birth weight of offspring was related inversely to mortality , from all causes and cardiovascular disease , in this cohort . The strength of this association was greater than would have been expected by the degree of concordance of birth weights across generations , but an extensive range of potential confounding factors could not account for the association . Mortality is therefore influenced by a factor related to birth weight that is transmissible across generations . Key messages Low birth weight is associated with increased mortality from cardiovascular disease in later life , and birth weight is associated across generations so that both maternal and paternal birth weights are associated with the offspring 's birth weight In this observational study we found that lower birth weight of offspring was associated with higher parental mortality from all causes and from cardiovascular disease This elevated mortality could not be explained by a range of social , environmental , behavioural , and physiological risk factors The strength of the association was greater than would have been expected by the degree of concordance of birth weights across generations We conclude that mortality is influenced by a factor that is related to birth weight and is transmissible across In prospect i ve studies , disease rates during follow-up are typically analyzed with respect to the values of factors measured during an initial baseline survey . However , because of " regression dilution , " this generally tends to underestimate the real associations of disease rates with the " usual " levels of such risk factors during some particular exposure period . The " regression dilution ratio " describes the ratio of the steepness of the uncorrected association to that of the real association . To assess the relevance of the usual value of a risk factor during particular exposure periods ( e.g. , first , second , and third decades ) to disease risks , regression dilution ratios can be derived by relating baseline measurements of the risk factor to replicate measurements from a reasonably representative sample of study participants after an interval equivalent to about the midpoint of each exposure period ( e.g. , at 5 , 15 , and 25 years , respectively ) . This report illustrates the impact of this time interval on the magnitude of the regression dilution ratios for blood pressure and blood cholesterol . The analyses were based on biennial re measurements over 30 years for participants in the Framingham Study ( Framingham , Massachusetts ) and a 26-year resurvey for a sample of men in the Whitehall Study ( London , Engl and ) . They show that uncorrected associations of disease risk with baseline measurements underestimate the strength of the real associations with usual levels of these risk factors during the first decade of exposure by about one-third , the second decade by about one-half , and the third decade by about two-thirds . Hence , to correct appropriately for regression dilution , replicate measurements of such risk factors may be required at varying intervals after baseline for at least a sample of participants Abstract Objective : To determine the association between adverse psychosocial characteristics at work and risk of coronary heart disease among male and female civil servants . Design : Prospect i ve cohort study ( Whitehall II study ) . At the baseline examination ( 1985 - 8 ) and twice during follow up a self report question naire provided information on psychosocial factors of the work environment and coronary heart disease . Independent assessment s of the work environment were obtained from personnel managers at baseline . Mean length of follow up was 5.3 years . Setting : London based office staff in 20 civil service departments . Subjects : 10 308 civil servants aged 35 - 55 were examined-6895 men ( 67 % ) and 3413 women ( 33 % ) . Main outcome measures : New cases of angina ( Rose question naire ) , severe pain across the chest , diagnosed ischaemic heart disease , and any coronary event . Results : Men and women with low job control , either self reported or independently assessed , had a higher risk of newly reported coronary heart disease during follow up . Job control assessed on two occasions three years apart , although intercorrelated , had cumulative effects on newly reported disease . Subjects with low job control on both occasions had an odds ratio for any subsequent coronary event of 1.93 ( 95 % confidence interval 1.34 to 2.77 ) compared with subjects with high job control at both occasions . This association could not be explained by employment grade , negative affectivity , or classic coronary risk factors . Job dem and s and social support at work were not related to the risk of coronary heart disease . Conclusions : Low control in the work environment is associated with an increased risk of future coronary heart disease among men and women employed in government offices . The cumulative effect of low job control assessed on two occasions indicates that giving employees more variety in tasks and a stronger say in decisions about work may decrease the risk of coronary heart disease . Key messages Low job control in the work environment contributes to the development of coronary heart disease among British male and female civil servants The risk of heart disease is associated with both objective low job control and perceived low job control . Increase in job control over time decreases the risk of coronary heart disease . This suggests that policies giving people a stronger say in decisions about their work or providing them with more variety in work tasks may contribute to better cardiovascular Plasma levels of fibrin D-dimer , tissue plasminogen activator ( tPA ) and plasminogen activator inhibitor ( PAI ) have been associated with ischaemic heart disease ( IHD ) . However their associations with incident IHD in sample s of the general population are not established . D-dimer antigen , tPA antigen and PAI activity were measured in stored , fasting plasma sample s from 1,998 men aged 45 - 65 examined between 1984 and 1988 , during the first re-examination of the Caerphilly Study cohort . These variables were related to major IHD events ( myocardial infa rct ion or IHD death ) which occurred in 129 men during a follow-up period which averaged 61 months . Mean fibrin D-dimer was higher in men who developed IHD events ( 90 vs. 71 ng/ml ; age-adjusted logarithmic mean difference 0.21 ; 95 % CI 0.11 , 0.30 ; p < 0.0001 ) . This association remained after adjusting for baseline IHD and for other risk factors including fibrinogen : the adjusted relative odds of IHD in the highest fifth of D-dimer were 3.5 ( 95 % CI 1.8 , 6.9 ; p = 0.0003 ) . Mean tPA antigen was also higher in men who developed IHD ( 12.6 vs. 11.6 ng/ml ; mean difference 0.9 ; 95 % CI 0.2 , 1.7 ; p = 0.02 ) ; however this difference largely disappeared after adjusting for other risk factors . PAI activity was not associated with risk of IHD Abstract Objective : To investigate the association between social circumstances in childhood and mortality from various causes of death in adulthood . Design : Prospect i ve observational study . Setting : 27 workplaces in the west of Scotl and . Subjects : 5645 men aged 35–64 years at the time of examination . Main outcome measures : Death from various causes . Results : Men whose fathers had manual occupations when they were children were more likely as adults to have manual jobs and be living in deprived areas . Gradients in mortality from coronary heart disease , stroke , lung cancer , stomach cancer , and respiratory disease were seen ( all P<0.05 ) , generally increasing from men whose fathers had professional and managerial occupations ( social class I and II ) to those whose fathers had semiskilled and unskilled manual occupations ( social class IV and V ) . Relative rates of mortality adjusted for age for men with fathers in manual versus non-manual occupations were 1.52 ( 95 % confidence interval 1.24 to 1.87 ) for coronary heart disease , 1.83 ( 1.13 to 2.94 ) for stroke , 1.65 ( 1.12 to 2.43 ) for lung cancer , 2.06 ( 0.93 to 4.57 ) for stomach cancer , and 2.01 ( 1.17 to 3.48 ) for respiratory disease . Mortality from other cancers and accidental and violent death showed no association with fathers ' social class . Adjustment for adult socioeconomic circumstances and risk factors did not alter results for mortality from stroke and stomach cancer , attenuated the increased risk of coronary heart disease and respiratory disease , and essentially eliminated the association with lung cancer . Conclusions : Adverse socioeconomic circumstances in childhood have a specific influence on mortality from stroke and stomach cancer in adulthood , which is not due to the continuity of social disadvantage throughout life . Deprivation in childhood influences risk of mortality from coronary heart disease and respiratory disease in adulthood , although an additive influence of adulthood circumstances is seen in these cases . Mortality from lung cancer , other cancer , and accidents and violence is predominantly influenced by risk factors that are related to social circumstances in adulthood . Key messages Adverse socioeconomic conditions in childhood are associated with mortality in later life Mortality from stroke and stomach cancer is particularly dependent on social circumstances in childhood Mortality from coronary heart disease and respiratory disease is dependent on social circumstances in both adulthood and childhood Mortality from accidents and violence and from lung cancer is mainly dependent on factors acting in adulthood The increases in child poverty seen in Britain and elsewhere over the past 20 years may herald unfavourable future trends in adult Background : Several studies have shown that an elevated heart rate is associated with an increased risk of ischaemic heart disease . The aim of this study was to examine the relationship between heart rate , blood pressure , blood lipids and other cardiovascular risk factors in middle-aged men . Methods : A total of 7735 men , aged 40–59 years at screening , were selected at r and om from one of the general practice s in each of the 24 towns participating in the cross-sectional ( screening ) phase of the British Regional Heart Study . Blood pressure and levels of blood lipids ( serum total cholesterol , high-density-lipoprotein ( HDL ) cholesterol and triglycerides ) and blood glucose were measured . Results : All men with pre-existing evidence of ischaemic heart disease and those on regular antihypertensive treatment were excluded from the analysis . In the remaining 5597 men , heart rate showed a strong positive correlation with cigarette smoking and body-mass index and decreased significantly at higher levels of physical activity and FEV1 ( forced expiratory volume in 1 s ) . These associations remained significant after adjustment for each other . Age , alcohol intake and social class were not independently associated with heart rate . There was a significant positive association between heart rate and systolic and diastolic blood pressures , levels of blood cholesterol , triglycerides and blood glucose and a significant inverse association between heart rate and HDL-cholesterol levels , even after adjusting for the above confounding factors . After further adjustment for each of the other physiological variables , heart rate remained independently associated with diastolic and systolic blood pressures and levels of triglycerides and blood glucose . The relationship between heart rate and levels of total cholesterol and HDL cholesterol appeared to be secondary to its association with triglyceride levels . The association between body-mass index and heart rate diminished after further adjustments for systolic blood pressure , suggesting that the primary effect of body weight is on blood pressure rather than on heart rate . Conclusion : Our findings indicate that elevated heart rate is associated with hypertension and with an atherogenic lipoprotein profile and support the suggestion that disturbance of the autonomic nervous system may underlie these associations Two‐hundred and four men with a defined degree of impaired glucose tolerance derived from the Whitehall Survey and its pilot study were enrolled in a therapeutic trial and followed for ten years . For the first five years of the trial approximately half the group received 50 mg phenformin daily and the other half an identical placebo . For the whole ten years of the trial approximately half the group were recommended a diet in which carbohydrate intake was limited to 120 g/day , while the other half was recommended a qualitative limitation of sugar intake . 60 men ( 29.4 % ) worsened to diabetes during the follow‐up period . The major independent predictor of worsening was the baseline blood glucose level ( glucose tolerance ) . High baseline plasma triglyceride levels and low baseline systolic blood pressure levels were also independent predictors of worsening , though of lower significance ( AIMS To use the ten year follow-up of the Caerphilly and Speedwell studies to assess the contributions of fibrinogen and viscosity to the prediction of risk of ischaemic heart disease . METHODS AND RESULTS Caerphilly and Speedwell are prospect i ve studies based on representative sample s of middle-aged males . Ischaemic heart disease morbidity and mortality were defined using hospital notes , repeat electro-cardiographs and death certificates . There were 603 incident events among the 4860 men . Age-adjusted relative odds of ischaemic heart disease increased to 3.3 and 3.4 in the 20 % of men with the highest levels of fibrinogen and viscosity , respectively . After st and ardizing for the major cardiovascular risk factors , these relative odds were 2.2 ( 95 % confidence interval 1.6 to 3.1 ) for fibrinogen and 2.3 ( 95 % confidence interval 1.7 to 3.2 ) for viscosity . When fibrinogen and viscosity were entered jointly , both remained significant ( P < 0.01 ) predictors . Incidence of ischaemic heart disease increased with increasing fibrinogen at every level of viscosity , and vice versa . Interactions with lipids were also examined . There was no support for the suggestion that risk is independent of cholesterol level when fibrinogen is low . CONCLUSIONS Fibrinogen and viscosity are powerful , long term and independent predictors of the risk of ischaemic heart disease Risk factors for major ischaemic heart disease ( acute myocardial infa rct ion or sudden death ) have been investigated in a prospect i ve study of 7735 men aged 40 - 59 years drawn from general practice s in 24 British towns . After a mean follow-up of 4.2 years , there have been 202 cases of major ischaemic heart disease . Univariate estimates of the risk of ischaemic heart disease show that serum total cholesterol , HDL-cholesterol and triglyceride concentrations , systolic and diastolic blood pressures , cigarette smoking , and body mass index are all associated with increased risk of ischaemic heart disease . Evidence of ischaemic heart disease at initial examination is also strongly associated with increased risk of subsequent ischaemic heart disease . All these factors were then considered simultaneously using multiple logistic models . Definite myocardial infa rct ion on electrocardiogram and recall of a doctor diagnosis of ischaemic heart disease remained predictive of subsequent major ischaemic heart disease , after allowance for all other risk factors . Serum total cholesterol , blood pressure , and cigarette smoking each remained as highly significant independent risk factors whereas overweight , above average levels of HDL-cholesterol and serum triglyceride were not predictive of risk after allowance for the above factors . Men with and without pre-existing ischaemic heart disease were examined separately in the same way ( using multiple logistic models ) . The strength of association between the principal risk factors and subsequent major ischaemic heart disease was reduced in the men with pre-existing ischaemic heart disease , only age and serum total cholesterol remaining highly significant . Overall the levels of the major risk factors commonly encountered in British men have a marked effect on the risk of ischaemic heart disease . Modification of these risk factors in the general population constitutes an important national priority BACKGROUND In patients with unstable coronary artery disease , there is a relation between the short-term risk of death and blood levels of troponin T ( a marker of myocardial damage ) and C-reactive protein and fibrinogen ( markers of inflammation ) . Using information obtained during an extension of the follow-up period in the Fragmin during Instability in Coronary Artery Disease trial , we evaluated the usefulness of troponin T , C-reactive protein , and fibrinogen levels and other indicators of risk as predictors of the long-term risk of death from cardiac causes . METHODS Levels of C-reactive protein and fibrinogen at enrollment and the maximal level of troponin T during the first 24 hours after enrollment were analyzed in 917 patients included in a clinical trial of low-molecular-weight heparin in unstable coronary artery disease . The patients were followed for a mean of 37.0 months ( range , 1.6 to 50.6 ) . RESULTS During follow-up , 1.2 percent of the 173 patients with maximal blood troponin T levels of less than 0.06 microg per liter died of cardiac causes , as compared with 8.7 percent of the 367 patients with levels of 0.06 to 0.59 microg per liter and 15.4 percent of the 377 patients with levels of at least 0.60 microg per liter ( P=0.007 and P=0.001 , respectively ) . The rates of death from cardiac causes were 5.7 percent among the 314 patients with blood C-reactive protein levels of less than 2 mg per liter , 7.8 percent among the 294 with levels of 2 to 10 mg per liter , and 16.5 percent among the 309 with levels of more than 10 mg per liter ( P=0.29 and P=0.001 , respectively ) . The rates of death from cardiac causes were 5.4 percent among the 314 patients with blood fibrinogen levels of less than 3.4 g per liter , 12.0 percent among the 300 with levels of 3.4 to 3.9 g per liter , and 12.9 percent among the 303 with levels of at least 4.0 g per liter ( P=0.004 and P=0.69 , respectively ) . In a multivariate analysis , levels of troponin T and C-reactive protein were independent predictors of the risk of death from cardiac causes . CONCLUSIONS In unstable coronary artery disease , elevated levels of troponin T and C-reactive protein are strongly related to the long-term risk of death from cardiac causes . These markers are independent risk factors , and their effects are additive with respect to each other and other clinical indicators of risk STUDY OBJECTIVE : To relate habitual ( cups per day ) tea and coffee consumption to conventional coronary risk factors and subsequent risk of coronary heart disease and death . DESIGN : Cohort study . SETTING : Nationwide r and om population study . PARTICIPANTS : Over 11,000 men and women aged 40 - 59 who took part in the Scottish Heart Health Study lifestyle and risk factor survey in 1984 - 87 . Participants were followed up to the end of 1993 , an average of 7.7 years , for all cause mortality , coronary death , or any major coronary event ( death , non-fatal infa rct ion or coronary artery surgery ) . Cox 's proportional hazards regression model was used to estimate the hazard in consumers of tea and coffee relative to the zero consumption group , both before and after correction for other factors . MAIN RESULTS : Coffee and tea consumption showed a strong inverse relation . For many conventional risk factors , coffee showed a weak , but beneficial , gradient with increasing consumption , whereas increasing tea consumption showed the reverse . Increasing coffee consumption was associated with beneficial effects for mortality and coronary morbidity , whereas tea showed the opposite . Adjusting for age and social class had some effect in reducing associations . Multiple adjustment for other risk factors removed the associations for tea and most of those for coffee although there was a residual benefit of coffee consumption in avoiding heart disease among men . CONCLUSIONS : The epidemiological differences shown in this study occurred despite the pharmacological similarities between tea and coffee . Either they differ more than is realised , or they identify contrasting associated lifestyle and health risks , for which this multiple adjustment was inadequate The Caerphilly and Speedwell studies are based on representative sample s of over 3000 subjects in South Wales and over 2000 in Bristol . They include cross sectional studies of risk factors for prevalent ischaemic heart disease ( IHD ) and of determinants of those risk factors . Prospect i ve studies based on over 2000 men aged 45 - 59 in each area have been set up . In addition to the examination of lipid and thrombosis factors of possible relevance to IHD , the studies also focus on possible dietary , hormonal , and psychological risk factors , both as possible " risk factors " for IHD and also as possible " determinants " of risk factors Data from 9740 Scottish men and women aged 40 - 59 years , selected at r and om in a population survey during 1984 - 86 , were used to compare self-reported smoking habits and biochemical measures of tobacco smoke inhalation in three groups : 625 with diagnosed coronary heart disease ; 1497 undiagnosed , but with suggestive question naire symptoms or electro-cardiographic signs ; and 7618 with no diagnosis or evidence of coronary disease , nor cardiovascular medication . Men and women with a diagnosis of coronary heart disease reported that they had tried to reduce their cigarette consumption or had quit more often than did the two comparison groups , but this effect was considerably greater in men than in women . Men in all groups had a higher cigarette quitting rate , but this may be due to switching to pipes and cigars . However , the biochemical measurement of tobacco smoke inhalation by cotinine showed that those with a coronary diagnosis had the highest overall levels of tobacco smoke inhalation , and the highest level of cotinine per self-reported cigarette , cigar , or ounce ( 30 g ) of pipe tobacco consumed . Self-reporting after a coronary diagnosis is consequently distorted , and an objective measure of smoke inhalation is to be preferred . In both sexes , particularly women , intake of tobacco products remains higher than that in the general population , whether or not it was even higher before they were diagnosed . Those responsible for continuing care of coronary patients need to be aware that health education and compliance are less effective in this group than they should be , both in male patients and , even more so , in women BACKGROUND Ascorbic acid ( vitamin C ) might be protective for several chronic diseases . However , findings from prospect i ve studies that relate ascorbic acid to cardiovascular disease or cancer are not consistent . We aim ed to assess the relation between plasma ascorbic acid and subsequent mortality due to all causes , cardiovascular disease , ischaemic heart disease , and cancer . METHODS We prospect ively examined for 4 years the relation between plasma ascorbic acid concentrations and mortality due to all causes , and to cardiovascular disease , ischaemic heart disease , and cancer in 19 496 men and women aged 45 - 79 years . We recruited individuals by post using age-sex registers of general practice s. Participants completed a health and lifestyle question naire and were examined at a clinic visit . They were followed-up for causes of death for about 4 years . Individuals were divided into sex-specific quintiles of plasma ascorbic acid . We used the Cox proportional hazard model to determine the effect of ascorbic acid and other risk factors on mortality . FINDINGS Plasma ascorbic acid concentration was inversely related to mortality from all-causes , and from cardiovascular disease , and ischaemic heart disease in men and women . Risk of mortality in the top ascorbic acid quintile was about half the risk in the lowest quintile ( p<0.0001 ) . The relation with mortality was continuous through the whole distribution of ascorbic acid concentrations . 20 micromol/L rise in plasma ascorbic acid concentration , equivalent to about 50 g per day increase in fruit and vegetable intake , was associated with about a 20 % reduction in risk of all-cause mortality ( p<0.0001 ) , independent of age , systolic blood pressure , blood cholesterol , cigarette smoking habit , diabetes , and supplement use . Ascorbic acid was inversely related to cancer mortality in men but not women . INTERPRETATION Small increases in fruit and vegetable intake of about one serving daily has encouraging prospect s for possible prevention of disease BACKGROUND The common isoforms of apolipoprotein E ( apoE ) , E2 , E3 , and E4 , are important determinants of plasma lipid concentrations , and the epsilon4 allele is associated with raised risk of coronary heart disease . We investigated whether the effect of smoking on coronary heart disease risk is affected by APOE genotype . METHODS We enrolled 3052 middle-aged men who were free of coronary heart disease for prospect i ve cardiovascular surveillance in the second Northwick Park Heart Study ( NPHSII ) . Smoking habit was ascertained at baseline and yearly by question naire . APOE genotype was identified by PCR and restriction enzyme digestion . Endpoints were fatal coronary heart disease , non-fatal myocardial infa rct ion , and coronary artery surgery and silent myocardial infa rct ion at follow-up . FINDINGS During 18836 person years of surveillance , 96 men had an acute myocardial infa rct ion , 26 needed coronary artery surgery , and 14 had silent myocardial infa rct ions . Compared with never-smokers , risk of coronary heart disease in ex-smokers was 1.34 ( 95 % CI 0.86 - 2.08 ) and in smokers it was 1.94 ( 1.25 - 3.01 ) . This risk was independent of other classic risk factors . In never-smokers , risk was closely similar in men with different genotypes . Risk in men homozygous for the epsilon3 allele was 1.74 ( 1.10 - 2.77 ) in ex-smokers and 1.68 ( 1.01 - 2.83 ) in smokers , whereas in men carrying the epsilon4 allele risk was 0.84 ( 0.40 - 1.75 ) and 3.17 ( 1.82 - 5.50 ) , respectively , with no significant differences in risk in the epsilon2 carriers . For the epsilon3 group , the genotype effect on risk was no longer significant after adjustment for classic risk factors ( including plasma lipids ) . However , even after adjustment , smokers who were carriers of the epsilon4 allele , showed significantly raised risk of coronary heart disease compared with the non-smoking group ( 2.79 , 1.59 - 4.91 , epsilon4-smoking interaction p=0.007 ) . INTERPRETATION Smoking increases the risk of coronary heart disease in men of all genotypes but particularly in men carrying the epsilon4 allele Health services research based on survey data is subject to potentially serious selection bias because observations are typically available only for survey respondents . This study describes a method of assessing and controlling for selection bias in the context of a survey of prescription and over-the-counter drug use by the elderly . A r and om sample of 6,500 Pennsylvania Medicare enrollees was sent a question naire regarding medicine use , insurance coverage , and health status in 1990 . Applying a two-stage , limited dependent variable selection model developed by Heckman to baseline Medicare enrollment and utilization data for both respondents ( 70 % ) and nonrespondents ( 30 % ) allowed us to detect and control for negative and significant nonresponse bias in estimates of prescription drug use . Purchase of over-the-counter medication was free of such bias . The report describes how the Heckman method can be applied in other cases where health services survey sample s are generated from program or organizational files that contain person-level data on all members of the sample frame A total of 6194 female doctors who in 1951 replied to a question naire about their smoking habits were followed up prospect ively for 22 years . During that time 1094 died . Ischaemic heart disease , lung cancer , and chronic obstructive lung disease were all significantly ( p < 0.001 ) related to smoking , though the absolute excess risks were lower than in male doctors smoking equivalent amounts . Female smokers born before the first world war were less likely to describe themselves as inhalers or as having started to smoke while young than were female smokers who were born later . In these respects this younger group resembled male smokers , and as they move into their 60s and 70s their absolute risk of lung disease and relative risk of ischaemic heart disease will probably come to resemble the risks for men smoking the same numbers of cigarettes . These findings show only that cigarette smoking causes lung cancer , chronic obstructive lung disease , and heart disease in women as in men . Whether the proportional increase in mortality from these diseases is as great in women as in men might be estimated directly from new case-control studies on men and women born since 1920 |
1,871 | 29,251,292 | Locus of control for music selection was more often with the investigator rather than the participant .
IMPLICATION S FOR RESEARCH The existing data have been largely generated by nurse scientists , and implication s for nursing practice are many , because music interventions are low-cost , easily accessible , and without known adverse effects . | PROBLEM IDENTIFICATION Despite three decades of studies examining music interventions as a mitigant of chemotherapy-induced nausea and vomiting ( CINV ) , to date , no systematic review of this literature exists . . | BACKGROUND Adjuvant chemotherapy is associated with poor quality of life ( qol ) in breast cancer patients . We tested the effect of listening to music during chemotherapy on quality of life in these patients . MATERIAL / METHODS We tested in a prospect i ve cohort the changes in qol scores as assessed by European Organization for Research and Treatment of Cancer Quality of Life Question naire ( EORTC QLQ-C30 ) , and the influence of listening to non-preferred music at the chemotherapy unit on these parameters in a mixed linear model by repeated measures analysis of variance ( RMANOVA ) . RESULTS For the whole cohort , musical intervention was not associated with a change in any dimension of quality of life . However ; the music effect significantly interacted with patient age ; patients > 45 years old had improved insomnia and appetite loss scores after musical intervention ( F = 6.76 , P = 0.019 and F = 11.22 , P = 0.004 , respectively ) . CONCLUSIONS Our results show that brief , non-preferred music exposure at the time of chemotherapy administration does not improve quality of life in patients with early breast cancer . Nonetheless , there is still a possibility that a subgroup will benefit from this approach as suggested by the interaction of the music effect with patient age The treatment of pain continues to gain in saliency as a component of defining best practice in medical care . Music therapy is an integrative treatment modality that impacts patient outcomes in the treatment of spinal pain . At Mount Sinai Beth Israel , we conducted a mixed- methods study addressing the effects of music therapy interventions on the recovery of patients after spine surgery . The study combined st and ard medical approaches and integrative music therapy . Sixty patients ( 35 female , 25 male ) ranging in age from 40 to 55 years underwent anterior , posterior , or anterior-posterior spinal fusion and were r and omly assigned to either music therapy plus st and ard care ( medical and nursing care with scheduled pharmacologic pain intervention ) or st and ard care only . Measurements for both groups were completed before and after the intervention . Music therapy involved the use of patient-preferred live music that supported tension release/relaxation through incentive-based clinical improvisation , singing , and /or rhythmic drumming or through active visualization supported by live music that encompasses tension resolution . The control and music groups showed significant differences in degree and direction of change in the visual analog scale ( VAS ) pain ratings from before to after intervention ( P = .01 ) . VAS pain levels increased slightly in the control group ( to 5.87 from 5.20 ) but decreased by more than 1 point in the music group ( to 5.09 from 6.20 ) . The control and music therapy groups did not differ in the rate of change in scores on Hospital Anxiety and Depression Scale ( HADS ) Anxiety ( P = .62 ) , HADS Depression ( P = .85 ) , or Tampa Scale for Kinesiophobia ( P = .93 ) . Both groups had slight increases in HADS Anxiety , comparable decreases in HADS Depression , and minimal changes in fear-related movement ( Tampa scale ) Goals of workPrevention of chemotherapy-induced nausea and vomiting ( CINV ) with st and ard antiemetics has been more difficult to achieve in female patients . Data from two phase III trials of the NK1 antagonist aprepitant were assessed for potential effect of gender on treatment response . Patients and methods 1,044 patients receiving cisplatin ( ≥70 mg/m2 ) were r and omly assigned to control regimen [ ondansetron ( O ) 32 mg i.v . and dexamethasone ( D ) 20 mg p.o . on day 1 ; D 8 mg twice daily on days 2–4 ] or aprepitant ( A ) regimen ( A 125 mg p.o . plus O 32 mg and D 12 mg on day 1 ; A 80 mg and D 8 mg once daily on days 2–3 ; and D 8 mg on day 4 ) . The primary endpoint was overall complete response ( no emesis and no rescue therapy over days 1–5 ) . Data were analyzed by a modified intent-to-treat approach . Between-treatment comparisons for each gender were made using logistic regression . Main results Women comprised 42 and 43 % of the aprepitant and control groups , respectively . In the control group , 41 % of women had overall complete response compared with 53 % of men . In the aprepitant group , 66 % of women had overall complete response compared with 69 % of men . Conclusion The addition of aprepitant may negate the adverse prognostic effect of female gender on the prevention of CINV in patients receiving highly emetogenic chemotherapy PURPOSE To examine the effect of patient-selected music intervention during daily weaning trials for patients on prolonged mechanical ventilation . METHODS Using a crossover repeated measures design , patients were r and omized to music vs no music on the first intervention day . Provision of music was alternated for 6 days , result ing in 3 music and 3 no music days . During weaning trials on music days , data were obtained for 30min prior to music listening and continued for 60min while patients listened to selected music ( total 90min ) . On no music days , data were collected for 90min . Outcome measures were heart rate ( HR ) , respiratory rate ( RR ) , oxygen saturation ( SpO2 ) , blood pressure ( BP ) , dyspnea and anxiety assessed with a visual analog scale ( VAS-D , VAS-A ) and weaning duration ( meanh per day on music and non-music days ) . RESULTS Of 31 patients r and omized , 23 completed the 6-day intervention . When comparisons were made between the 3 music and 3 no music days , there were significant decreases in RR and VAS-D and a significant increase in daily weaning duration on music days ( p<0.05 ) . A multivariate mixed-effects model analysis that included patients who completed ≥2 days of the intervention ( n=28 ) demonstrated significant decreases in HR , RR , VAS-A , and VAS-D and a significant increase in daily weaning duration on music days ( p<0.05 ) . CONCLUSIONS Providing patient selected music during daily weaning trials is a simple , low-cost , potentially beneficial intervention for patients on prolonged mechanical ventilation . Further study is indicated to test ability of this intervention to promote weaning success and benefits earlier in the weaning process PURPOSE / OBJECTIVES To test whether use of music as a diversional intervention during high-dose chemotherapy administration would affect perception of nausea and episodes of vomiting . SAMPLE 39 patients undergoing bone marrow transplant . A total of 33 patients were included in the data analysis , with 17 in the control group and 16 in the music intervention group . METHODS Patients were assigned r and omly to a control group ( usual antiemetic protocol ) or the experimental group ( usual antiemetic group plus music intervention during the 48 hours of high-dose cyclophosphamide administered as part of the preparative regimen ) . MAIN RESEARCH VARIABLES Use of a music intervention , perception of nausea , and instances of vomiting . FINDINGS Significant differences were found between group scores on a visual analog scale for nausea and number of episodes of vomiting , demonstrating that the experimental group experienced less nausea and fewer instances of vomiting . CONCLUSION This study found that music is an effective adjunct to a pharmacologic antiemetic regimen for lessening nausea and vomiting , and this study merits further investigation through a larger multi-institutional effort . IMPLICATION S FOR NURSING PRACTICE Using music as a diversional adjunct intervention to antiemetic therapy is helpful in decreasing nausea and vomiting . The intervention can be initiated independently by nurses and individualized for each patient , leading to greater patient comfort and compliance with high-dose chemotherapy Purpose Despite significant advances in antiemetic management , almost 50 % of cancer patients still experience nausea and vomiting during treatment . The goal of antiemetic therapy is complete prevention of treatment-induced nausea and /or vomiting ( TINV ) ; however , realisation of this goal remains elusive , thus supplementary strategies identifying patients at high risk must be employed in the interim . Consequently , we examined TINV incidence and its risk factors , including patient , clinical and pretreatment quality of life (QOL)/psychological factors . Methods Two hundred newly diagnosed cancer patients beginning combined treatment participated in this prospect i ve , longitudinal , observational study . QOL ( including TINV ) , psychological adjustment , and patient/ clinical characteristics were examined at pretreatment , on-treatment ( 8 weeks ± 1 week ) and post-treatment . Results Overall , 62 % of patients experienced TINV , with TIN incidence ( 60 % ) doubling that of TIV ( 27 % ) . Eight independent risk factors predicted 73 % of TIN incidence : high premorbid/anticipatory NV , moderately/highly emetogenic chemotherapy ( M/HEC ) , longer treatment ( > 3 months ) , female gender , surgery prior to adjuvant chemotherapy ± radiotherapy , private health insurance and low emotional functioning ( pretreatment ) . Six independent risk factors predicted 77 % of TIV incidence : premorbid/anticipatory vomiting , M/HEC , female gender , cancer resection and low role functioning ( pretreatment ) . Conclusions TINV still represents a very major concern for patients . Several pretreatment risk factors for the development of TIN and TIV , respectively , were identified . Patients about to undergo cancer treatment , particularly combined treatment involving emetogenic chemotherapy and surgery , should be screened for these factors with a view to modifying st and ard pretreatment/maintenance antiemetic therapy . Furthermore , and consistent with recent research , it is recommended that more comprehensive interventions combining antiemetics with other effective pharmacological ( e.g. anxiolytics ) and non-pharmacological approaches ( e.g. acupuncture , relaxation techniques ) be considered by clinicians in attempts to improve control of TIN and TIV ( and overall QOL ) for their patients . In this way , optimal holistic care will be ensured for cancer patients by clinicians providing conventional oncology treatment PURPOSE Pharmacological therapy is only partially effective in preventing or treating chemotherapy induced nausea and vomiting ( CINV ) . Therefore , exploring the complementary role of non-pharmacological approaches used in addition to pharmacological agents is important . Nevasic uses specially constructed audio signals hypothesized to generate an antiemetic reaction . The aim of this study was to examine the feasibility of conducting a r and omized controlled trial ( RCT ) to evaluate the effectiveness of Nevasic to control CINV . METHODS A mixed methods design incorporating an RCT and focus group interviews . For the RCT , female breast cancer patients were r and omized to receive either Nevasic plus usual care , music plus usual care , or usual care only . Data were analysed using descriptive statistics and linear mixed-effects models . Five focus group interviews were conducted to obtain participants ' views regarding the acceptability of the interventions in the trial . RESULTS 99 participants were recruited to the RCT and 15 participated in focus group interviews . Recruitment targets were achieved . Issues of Nevasic acceptability were highlighted as weaknesses of the program . This study did not detect any evidence for the effectiveness of Nevasic ; however , the results showed statistically significant less use of anti-emetics ( p = 0.003 ) and borderline non-significant improvement in quality of life ( p = 0.06 ) . CONCLUSIONS Conducting a non-pharmacological intervention using such an audio program is feasible , although difficulties and limitations exist with its use . Further studies are required to investigate the effectiveness of Nevasic from perspectives such as anti-emetic use , as well as its overall effect on the levels of nausea and vomiting Goals of workA number of prognostic factors have been identified as risk factors for chemotherapy-induced emesis . This post-hoc analysis addressed whether : ( 1 ) these prognostic factors can identify a low-risk group for whom ondansetron plus dexamethasone alone provide a high level of protection ( ≥80 % no emesis ) ; ( 2 ) the NK1 receptor antagonist aprepitant improves antiemetic outcome regardless of emetic risk . Patients and methods Breast cancer patients in a phase III double-blind , placebo-controlled trial were r and omized to antiemetic regimens including ondansetron and dexamethasone , or aprepitant , ondansetron , and dexamethasone . Multivariate logistic regression models were used to assess the impact on emesis ( but not nausea ) of the regimen with aprepitant , and previously reported risk factors , including age ( < 55 and ≥55 years ) , ethanol use ( 0–4 or ≥5 drinks/week ) , history of pregnancy-related morning sickness , and history of motion sickness , using a modified intent-to-treat approach . Results Treatment with aprepitant ( P < 0.0001 ) , older age ( P = 0.006 ) , ethanol use ( P = 0.0048 ) , and no history of morning sickness ( P = 0.0007 ) were all significantly associated with reduced likelihood of emesis . The proportion of patients with one , two , or three risk factors who remained emesis free was significantly higher with the aprepitant-containing regimen than with the active control ( 70.2–82.8 % vs. 38.6–66.4 % , respectively ) . Conclusions Aprepitant markedly improved control of emesis in patients with one or more risk factors . This analysis did not support using risk factors for modifying the antiemetic approach . A low-risk group with zero risk factors for whom aprepitant provided little benefit was of question able clinical utility , since they comprised less than 3 % of patients The purpose of this pilot study was to evaluate the benefits of a message from a patient 's physician audiotaped over music on reducing anxiety and side effects of patients receiving chemotherapy . A convenience sample of 97 adult patients receiving chemotherapy for the first time was assigned to either an experimental or control group . Before beginning the first chemotherapy treatment , all subjects completed a demographic question naire and the Spielberger State Anxiety Inventory ( SSAI ) . Participants in the experimental group ( n = 47 ) received taped music and a message from their physicians during the next four chemotherapy treatments . Participants in the control group ( n = 50 ) received no intervention from the research ers and underwent their next four chemotherapy treatments as prescribed . After the fourth chemotherapy treatment , the SSAI and a side-effects self- assessment evaluation were completed by all subjects . A paired one-tailed t test found a significant difference between pre- and postintervention scores on the state anxiety scale ( p < 0.001 ) . In addition , anxiety remained the same over time in the control group . There was no significant difference in the severity of side effects experienced between control and experimental groups . These preliminary findings indicate that a simple and cost-effective intervention can decrease a patient 's anxiety when receiving chemotherapy This mixed methods pilot study evaluated the effects of the creative arts therapy ( CAT ) on the quality of life ( QOL ) of children receiving chemotherapy . A 2-group , repeated measures r and omized design compared CAT with a volunteer ’s attention ( n = 16 ) . Statistical analysis of the r and omized controlled phase of the study suggested an improvement in the following areas after the CAT : parent report of child ’s hurt ( P = .03 ) and parent report of child ’s nausea ( P = .0061 ) . A nonr and omized phase , using a different instrument showed improved mood with statistical significance on the Faces Scale ( P < .01 ) , and patients were more excited ( P < .05 ) , happier ( P < .02 ) , and less nervous ( P < .02 ) . Provider focus groups revealed positive experiences . Case studies are included to exemplify the therapeutic process . With heightened interest in complementary therapy for children with cancer , future research with a larger sample size is needed to document the impact of incorporating creative arts into the healing process Mechanical ventilation ( MV ) is a life-saving measure and supportive modality utilized to treat patients experiencing respiratory failure . Patients experience pain , discomfort , and anxiety as a result of being mechanically ventilated . Music listening is a non-pharmacological intervention used to manage these psychophysiological symptoms associated with mechanical ventilation . The purpose of this secondary analysis was to examine music preferences of 107 MV patients enrolled in a r and omized clinical trial that implemented a patient-directed music listening protocol to help manage the psychophysiological symptom of anxiety . Music data presented includes the music genres and instrumentation patients identified as their preferred music . Genres preferred include : classical , jazz , rock , country , and oldies . Instrumentation preferred include : piano , voice , guitar , music with nature sounds , and orchestral music . Analysis of three patients ' preferred music received throughout the course of the study is illustrated to demonstrate the complexity of assessing MV patients and the need for an ongoing assessment process BACKGROUND We examined the efficacy of olanzapine for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy . METHODS In a r and omized , double-blind , phase 3 trial , we compared olanzapine with placebo , in combination with dexamethasone , aprepitant or fosaprepitant , and a 5-hydroxytryptamine type 3-receptor antagonist , in patients with no previous chemotherapy who were receiving cisplatin ( ≥70 mg per square meter of body-surface area ) or cyclophosphamide-doxorubicin . The doses of the three concomitant drugs administered before and after chemotherapy were similar in the two groups . The two groups received either 10 mg of olanzapine orally or matching placebo daily on days 1 through 4 . Nausea prevention was the primary end point ; a complete response ( no emesis and no use of rescue medication ) was a secondary end point . RESULTS In the analysis , we included 380 patients who could be evaluated ( 192 assigned to olanzapine , and 188 to placebo ) . The proportion of patients with no chemotherapy-induced nausea was significantly greater with olanzapine than with placebo in the first 24 hours after chemotherapy ( 74 % vs. 45 % , P=0.002 ) , the period from 25 to 120 hours after chemotherapy ( 42 % vs. 25 % , P=0.002 ) , and the overall 120-hour period ( 37 % vs. 22 % , P=0.002 ) . The complete-response rate was also significantly increased with olanzapine during the three periods : 86 % versus 65 % ( P<0.001 ) , 67 % versus 52 % ( P=0.007 ) , and 64 % versus 41 % ( P<0.001 ) , respectively . Although there were no grade 5 toxic effects , some patients receiving olanzapine had increased sedation ( severe in 5 % ) on day 2 . CONCLUSIONS Olanzapine , as compared with placebo , significantly improved nausea prevention , as well as the complete-response rate , among previously untreated patients who were receiving highly emetogenic chemotherapy . ( Funded by the National Cancer Institute ; Clinical Trials.gov number , NCT02116530 . ) |
1,872 | 24,711,559 | Overall , the number of statistically significant findings were limited and PROMs ' intervention effect sizes were predominantly small-to-moderate .
The routine use of PROMs increases the frequency of discussion of patient outcomes during consultations .
In some studies , PROMs are associated with improved symptom control , increased supportive care measures , and patient satisfaction . | PURPOSE The systematic use of patient-reported outcome measures ( PROMs ) has been advocated as an effective way to st and ardize cancer practice .
Yet , the question of whether PROMs can lead to actual improvements in the quality of patient care remains under debate .
This review examined whether inclusion of PROM in routine clinical practice is associated with improvements in patient outcomes , processes of care , and health service outcomes during active anticancer treatment . | Background : Despite thous and s of papers , the value of quality of life ( QoL ) in curing disease remains uncertain . Until now , we lacked tools for the diagnosis and specific treatment of diseased QoL. We approached this problem stepwise by theory building , modelling , an exploratory trial and now a definitive r and omised controlled trial ( RCT ) in breast cancer , whose results we report here . Methods : In all , 200 representative Bavarian primary breast cancer patients were recruited by five hospitals and treated by 146 care professionals . Patients were r and omised to either ( 1 ) a novel care pathway including diagnosis of ‘ diseased ’ QoL ( any QoL measure below 50 points ) using a QoL profile and expert report sent to the patient 's coordinating practitioner , who arranged QoL therapy consisting of up to five st and ardised treatments for specific QoL defects or ( 2 ) st and ard postoperative care adhering to the German national guideline for breast cancer . The primary end point was the proportion of patients in each group with diseased QoL 6 months after surgery . Patients were blinded to their allocated group . Results : At 0 and 3 months after surgery , diseased QoL was diagnosed in 70 % of patients . The QoL pathway reduced rates of diseased QoL to 56 % at 6 months , especially in emotion and coping , compared with 71 % in controls ( P=0.048 ) . Relative risk reduction was 21 % ( 95 % confidence interval ( CI ) : 0–37 ) , absolute risk reduction 15 % ( 95 % CI : 0.3–29 ) , number needed to treat (NNT)=7 ( 95 % CI : 3–37 ) . When QoL therapy finished after successful treatment , diseased QoL often returned again , indicating good responsiveness of the QoL pathway . Conclusion : A three-component outcome system including clinician-derived objective , patient-reported subjective end points and qualitative analysis of clinical relevance was developed in the last 10 years for cancer as a complex intervention . A separate QoL pathway was implemented for the diagnosis and treatment of diseased QoL and its effectiveness tested in a community-based , pragmatic , definitive RCT . While the pathway was active , it was effective with an NNT of 7 PURPOSE To examine the effect of weekly completion of a patient-held quality -of-life ( QOL ) diary in routine oncology practice for palliative care patients . PATIENTS AND METHODS In a pragmatic r and omized controlled trial , 115 patients with inoperable lung cancer were r and omly assigned to receive either st and ard care or a structured QOL diary ( European Organisation for Research and Treatment of Cancer Quality of Life Question naire C30 and the related lung cancer module LC13 ) that they completed at home each week for 16 weeks . Patients were encouraged to share the QOL information with health professionals involved in their care . Changes in QOL over time ( measured by the Functional Assessment of Cancer Therapy-Lung question naire and the Palliative Care Quality of Life Index ) , discussion of patient problems , and satisfaction with communication and general care were assessed at baseline and at 2 and 4 months after baseline . RESULTS Analysis of QOL indicated a small but consistent difference between patients in the diary group and the st and ard care group . The diary group had a poorer QOL in many domains . Two different QOL summary scores ( total and overall QOL ) indicated a statistically significant between-group difference . No effects were found in relation to satisfaction with care , communication , or the discussion of patient problems . CONCLUSION The regular completion of a QOL question naire without appropriate feedback to health care professionals and without the provision of appropriate support may have a negative impact on inoperable lung cancer patients . Further research should focus on identifying features such as feedback loops that are required for the successful and meaningful use of QOL question naires in routine patient care 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 PURPOSE Although psychosocial intervention can reduce psychosocial distress following breast cancer , many women who are experiencing problems are not identified and offered additional help . This trial assessed effects on quality of life of psychologic distress screening among newly diagnosed , nonmetastatic breast cancer patients . PATIENTS AND METHODS From 1990 to 1992 , all eligible patients in one regional breast cancer center were identified and offered study participation . Women in both control and experimental groups received brief psychosocial intervention from a social worker at initial treatment . The experimental group also had monthly telephone screening of distress levels using a brief , vali date d instrument , with additional psychosocial intervention offered only to those with high distress at screening . RESULTS Among 282 eligible patients , 89 % were r and omized and completed the study . Participants ' psychologic distress levels decreased over the study period ( P = .0001 ) . However , no between-group differences were observed . Mean distress scores among control and experimental women at 0- , 3- , and 12-month interviews were 20.7 and 20.4 , 15.5 and 15.0 , and 14.6 and 13.5 , respectively . No between-group differences were observed with respect to physical health , functional status , social and leisure activities , return to work , or marital satisfaction . CONCLUSION Our results indicate that , among patients who receive a minimal psychosocial intervention as part of their initial cancer care , a distress screening program does not improve quality of life . Minimal psychosocial intervention at initial treatment may be effective in reducing distress , thus making it difficult to obtain additional benefit from a screening program PURPOSE Although patient-reported cancer symptoms and quality -of-life issues ( SQLIs ) have been promoted as essential to a comprehensive assessment , efficient and efficacious methods have not been widely tested in clinical setting s. The purpose of this trial was to determine the effect of the Electronic Self-Report Assessment -Cancer ( ESRA-C ) on the likelihood of SQLIs discussed between clinicians and patients with cancer in ambulatory clinic visits . Secondary objectives included comparison of visit duration between groups and usefulness of the ESRA-C as reported by clinicians . PATIENTS AND METHODS This r and omized controlled trial was conducted in 660 patients with various cancer diagnoses and stages at two institutions of a comprehensive cancer center . Patient-reported SQLIs were automatically displayed on a graphical summary and provided to the clinical team before an on-treatment visit ( n = 327 ) ; in the control group , no summary was provided ( n = 333 ) . SQLIs were scored for level of severity or distress . One on-treatment clinic visit was audio recorded for each participant and then scored for discussion of each SQLI . We hypothesized that problematic SQLIs would be discussed more often when the intervention was delivered to the clinicians . RESULTS The likelihood of SQLIs being discussed differed by r and omized group and depended on whether an SQLI was first reported as problematic ( P = .032 ) . Clinic visits were similar with regard to duration between groups , and clinicians reported the summary as useful . CONCLUSION The ESRA-C is the first electronic self-report application to increase discussion of SQLIs in a US r and omized clinical trial Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objectives To evaluate the impact of a mobile phone-based , remote monitoring , advanced symptom management system ( ASyMS © ) on the incidence , severity and distress of six chemotherapy-related symptoms ( nausea , vomiting , fatigue , mucositis , h and –foot syndrome and diarrhoea ) in patients with lung , breast or colorectal cancer . Design A two group ( intervention and control ) by five time points ( baseline , pre-cycle 2 , pre-cycle 3 , pre-cycle 4 and pre-cycle 5 ) r and omised controlled trial . Setting Seven clinical sites in the UK ; five specialist cancer centres and two local district hospitals . Participants One hundred and twelve people with breast , lung or colorectal cancer receiving outpatient chemotherapy . Interventions A mobile phone-based , remote monitoring , advanced symptom management system (ASyMS © ).Main outcome measures Chemotherapy-related morbidity of six common chemotherapy-related symptoms ( nausea , vomiting , fatigue , mucositis , h and –foot syndrome and diarrhoea ) . Results There were significantly higher reports of fatigue in the control group compared to the intervention group ( odds ratio = 2.29 , 95%CI = 1.04 to 5.05 , P = 0.040 ) and reports of h and –foot syndrome were on average lower in the control group ( odds ratio control/intervention = 0.39 , 95%CI = 0.17 to 0.92 , P = 0.031 ) . Conclusion The study demonstrates that ASyMS © can support the management of symptoms in patients with lung , breast and colorectal cancer receiving chemotherapy The potential benefits of health-related quality of life ( HRQL ) assessment in oncology clinical practice include better detection of problems , enhanced disease and treatment monitoring and improved care . However , few empirical studies have investigated the effects of incorporating such assessment s into routine clinical care . Recent r and omized studies have reported improved detection of and communication about patients ' concerns , but few have found effects on patient HRQL or satisfaction . This study examined whether offering interpretive assistance of HRQL results would improve these patient outcomes . Two hundred and thirteen participants with metastatic breast , lung or colorectal cancer were r and omly assigned to one of three conditions : usual care ; HRQL assessment or HRQL assessment followed by a structured interview and discussion . Interviews about patients ' assessment responses were conducted by a research nurse , who then presented HRQL information to the treating nurse . HRQL and treatment satisfaction outcomes were assessed at 3 and 6 months . No significant differences were found between study conditions in HRQL or satisfaction . Results suggest that routine HRQL assessment , even with description of results , is insufficient to improve patient HRQL and satisfaction . It is suggested that positive effects may require supplementing assessment results with specific suggestions for clinical management changes OBJECTIVE To examine the effects of a computer-assisted , interactive tailored patient assessment ( ITPA ) tool in oncology practice on : documented patient care , symptom distress , and patients ' need for symptom management support during treatment and rehabilitation . DESIGN AND METHODS For this repeated measures clinical trial at a university hospital in Norway , 145 patients starting treatment for leukemia or lymphoma were r and omly assigned to either an intervention ( n=75 ) or control group ( n=70 ) . Both groups used the ITPA for symptom assessment s prior to inpatient and outpatient visits for up to one year . The assessment summary , which displayed patients ' self-reported symptoms , problems , and distress in rank-order of the patient 's need for support , was provided to physicians and nurses in the intervention group only but not in the control group . RESULTS Significantly more symptoms were addressed in the intervention group patient charts versus those of the control group . Symptom distress in the intervention group decreased significantly over time in 11 ( 58 % ) of 19 symptom/problem categories versus 2 ( 10 % ) for the control group . Need for symptom management support over time also decreased significantly more for the intervention group than the control group in 13 ( 68 % ) symptom categories . CONCLUSION This is the first study to show that an ITPA used in an interdisciplinary oncology practice can significantly improve patient-centered care and patient outcomes , including reduced symptom distress and reduced need for symptom management support BACKGROUND Menopausal symptoms ( e.g. , hot flashes , vaginal dryness , and stress urinary incontinence ) are very common in breast cancer survivors and can not be managed with st and ard estrogen replacement therapy ( ERT ) in these patients . The purpose of this study was to test the efficacy of a comprehensive menopausal assessment ( CMA ) intervention program in achieving relief of symptoms , the improvement in quality of life ( QOL ) , and sexual functioning in breast cancer survivors . METHODS Using a two-group , r and omized controlled design , we assigned 76 postmenopausal breast cancer survivors with at least one severe target symptom either to the intervention group or to a usual-care group . Seventy-two women were evaluable at the end of the study period . The CMA intervention , delivered by a nurse practitioner , focused on symptom assessment , education , counseling and , as appropriate , specific pharmacologic and behavioral interventions for each of the three target symptoms . Psychosocial symptoms were assessed with the use of a self-report screening instrument , and distressed women were referred for counseling if needed . The intervention took place over a 4-month period . Outcomes measured were scores on a composite menopausal symptom scale , the R AND Short Form Health Survey Vitality Scale , and the Cancer Rehabilitation Evaluation System ( CARES ) Sexual Functioning Scale at baseline and at 4-month follow-up . All statistical tests were two-sided and were performed at the alpha = . 05 significance level . RESULTS Patients receiving the intervention demonstrated statistically significant improvement ( P = .0004 ) in menopausal symptoms but no significant change in vitality ( P = .77 ) . Sexual functioning was statistically significantly improved ( P = .04 ) in the treatment group compared with the usual-care group . CONCLUSIONS A clinical assessment and intervention program for menopausal symptom management in breast cancer survivors is feasible and acceptable to patients , leading to reduction in symptoms and improvement in sexual functioning . Measurable improvement in a general QOL measure was not demonstrated This r and omized controlled trial investigated the effect of reporting physical symptoms by using a systematic symptom monitoring instrument , the Symptom Monitor , on symptom prevalence and severity among patients with cancer in the palliative phase . The overall objective was to achieve symptom relief through systematic and regular symptom reporting by patients themselves . One hundred forty-six patients with cancer in the palliative phase were r and omized to either the intervention group ( n = 69 with Symptom Monitor ) or the control group ( n = 77 without Symptom Monitor ) . Ten physical symptoms with regard to prevalence and severity were monitored . After 2 months , the prevalence of symptoms was lower in the intervention group compared to the control group ( prevalent differences 2.1 - 24.3 % ) for 9 out of 10 symptoms ( except coughing ) . The intervention group scored a statistically significantly lower prevalence in constipation and vomiting ( prevalence differences 24.3 % and 18.0 % , respectively ) . In four symptoms ( fatigue , lack of appetite , shortness of breath , and nausea ) , the intervention group had a lower , although not statistically significant , severity score ( median differences 0.5 - 1 ) . In four symptoms ( pain , coughing , sleeplessness , and diarrhea ) , the severity score was the same in both groups ( medians 2 - 4 ) . In two symptoms ( constipation and vomiting ) , the severity score was lower in the control group ( median differences -1 and -2 ) . A comparison between the study groups on improved , deteriorated , or steady-state cases showed that the severity score had deteriorated less for 8 out of 10 symptoms in a larger proportion of patients in the intervention group . Although statistical significance was not reached , the prevalence as well as severity of symptoms in the palliative phase of cancer can be influenced by using the Symptom Monitor PURPOSE Patients with cancer experience considerable symptom burden , psychological morbidity , and unmet psychosocial needs . Research suggests that feedback of patient-reported outcomes to clinicians or caseworkers , alongside management strategies , may result in improved patient functioning . Two intervention models were developed to test this effect in a r and omized , controlled trial against usual care ( UC ) : a telephone caseworker ( TCW ) model and an oncologist/general practitioner ( O/GP ) model . Primary end points included anxiety , depression , physical/emotional functioning , and unmet supportive care needs . PATIENTS AND METHODS Participants with nonlocalized breast or colorectal cancers were surveyed by computer-assisted telephone interview ( CATI ) at three time points : baseline , 3 months , and 6 months . Data collected from participant CATIs in the supportive care models were used to generate feedback to either each participant 's design ated TCW , or their nominated O/GPs . Data obtained from participants in the UC model were used only to assess the impact of supportive care models . In total , 356 participants consented to study participation , completed the baseline CATI , and were r and omly assigned to the UC , TCW , or O/GP groups . RESULTS No overall intervention effect was observed . Physical functioning was significantly improved at the third CATI for participants in the TCW model ( P = .01 ) , and there was a trend toward fewer participants with unmet needs ( P = .07 ) . TCW group participants also were more likely to have the following : identified issues of need discussed ( P < .0001 ) ; referrals made ( P < .0001 ) ; and strong agreement that the intervention improved communication with their health care team ( P = .0005 ) . CONCLUSION The TCW model holds some promise ; however , additional work in at-risk population s is required before we recommend implementation Purpose The aims of this study were to investigate the impact of individual health-related quality of life ( HRQL ) evaluation on the attention towards symptom control and psychosocial function in advanced cancer patients . Methods Patients with advanced lung cancer or mesothelioma who attended a pulmonary oncology outpatient clinic were r and omized to either of two strategies for HRQL assessment . The experimental group ( EG ) answered the EORTC QLQ-C30 + LC13 question naire using a digital table interface , with outprint of aggregated scale scores presented to the consulting physician as a support for evaluation . The control group ( CG ) answered a paper version of the same question naire , which was stored for later analysis . Consultations were audio-recorded . Outcome measures were a quantitative content analysis of audio-recorded consultations and medical and psychosocial interventions abstract ed from clinical records . Results One hundred seventy-one patients were r and omized and participated in the study . Issues regarding emotional function were more frequently discussed during consultations in the EG ( p < 0.05 ) . Similarly , interventions directed to emotional and social concerns were more frequent in the EG ( p = 0.013 and p = 0.0036 , respectively ) . HRQL measures over time were similar across the groups . Conclusion Individual HRQL assessment increased the attention to psychosocial functioning in patients with chest malignancies PURPOSE Regularly collecting patient-reported outcomes ( PROs ) of health-related quality of life with feedback to oncologists may assist in eliciting and monitoring patients ' problems during cancer treatment . This study examined how PRO feedback had an impact on patient-physician communication over time to gain a better underst and ing of how it may influence patient care . PATIENTS AND METHODS Exploratory analyses were performed on a data set from a previous study . Patients were r and omly assigned to intervention ( regular completion of European Organisation for Research and Treatment of Cancer Quality of Life Question naire-Core 30 and Hospital Anxiety and Depression Scale with feedback to oncologists ) , attention-control ( completion of same question naires without feedback ) , and control ( st and ard care ) arms . The content of consultation audio recordings between 28 oncologists and 198 patients over four consecutive visits ( 792 consultations ) was analyzed . Mixed-effects models and multivariate regressions were used to examine the longitudinal impact of the intervention on patient-physician communication , dynamics of patient-physician interaction , and the association between PROs and the content of clinic discussion . RESULTS Patients in the intervention arm discussed more symptoms over time compared with patients in the attention-control ( P = .008 ) and control ( P = .04 ) arms . No study arm effect was observed for function discussion s. Discussion topics were predominantly raised by patients /relatives , regardless of arm allocation . Clinic discussion s were associated with severity of patient-reported symptoms but not with patient-reported functional concerns . CONCLUSION A positive longitudinal impact of the intervention on symptom discussion was observed , but not for function discussion , suggesting that potentially serious problems may remain unaddressed . Training oncologists in responding to patient-reported functional concerns may increase the impact of this intervention INTRODUCTION AND AIM In a r and omised trial investigating the effects of regular use of health-related quality of life ( HRQOL ) in oncology practice , we previously reported an improvement in communication ( objective analysis of recorded encounters ) and patient well-being . The secondary aims of the trial were to measure any impact on patient satisfaction and patients ' perspectives on continuity and coordination of their care . METHODS In a prospect i ve trial involving 28 oncologists , 286 cancer patients were r and omised to : ( 1 ) intervention arm : regular touch-screen completion of HRQOL with feedback to physicians ; ( 2 ) attention-control arm : completion of HRQOL without feedback ; and ( 3 ) control arm : no HRQOL assessment . Secondary outcomes were patients ' experience of continuity of care ( Medical Care Question naire , MCQ ) including ' Communication ' , ' Coordination ' and ' Preferences to see usual doctor ' subscales , patients ' satisfaction , and patients ' and physicians ' evaluation of the intervention . Analysis employed mixed-effects modelling , multiple regression and descriptive statistics . RESULTS Patients in the intervention arm rated their continuity of care as better than the control group for ' Communication ' subscale ( p=0.03 ) . No significant effects were found for ' Coordination ' or ' Preferences to see usual doctor ' . Patients ' evaluation of the intervention was positive . More patients in the intervention group rated the HRQOL assessment as useful compared to the attention-control group ( 86 % versus 29 % ) , and reported their doctors considered daily activities , emotions and quality of life . CONCLUSION Regular use of HRQOL measures in oncology practice brought changes to doctor-patient communication of sufficient magnitude and importance to be reported by patients . HRQOL data may improve care through facilitating rapport and building inter-personal relationships PURPOSE To determine whether making patient-reported cancer needs , quality -of-life ( QOL ) , and psychosocial information available to the health care team , allowing coordinated specifically targeted psychosocial interventions , result ed in reduced cancer needs , improved QOL , and increased satisfaction with care received . METHODS Self-reported cancer needs , QOL , and psychosocial information was collected from 450 people with cancer , using st and ardized question naires via a touch-screen computer . For a r and omly chosen two thirds , this information was made available to the health care team who coordinated targeted psychosocial interventions . Information from the remaining one third was not seen . Patients were assessed 2 and 6 months after r and omization for changes in their cancer needs , QOL , and psychosocial functioning and satisfaction with overall care received . RESULTS There were no significant differences between the two arms with respect to changes in cancer needs , QOL , or psychosocial functioning between the baseline and follow-up assessment s , nor with respect to satisfaction with care . However , for the subgroup of patients who were moderately or severely depressed at baseline , there was a significant reduction in depression for the intervention arm relative to the control arm at the 6-month assessment ( P = .001 ) . CONCLUSION Making patient-reported cancer needs , QOL , and psychosocial data available to the health care team at a single consultation together with coordinated psychosocial interventions does not seem to reduce cancer needs nor improve QOL , psychosocial functioning , or satisfaction with the care received . However , identification of patients with moderate or severe levels of depression may be valuable in reducing subsequent levels of depression PURPOSE Distress has been recognized as the sixth vital sign in cancer care and several guidelines recommend routine screening . Despite this , screening for distress is rarely conducted and infrequently evaluated . METHODS A program of routine online screening for distress was implemented for new patients with breast and lung cancer . Patients were r and omly assigned to one of three conditions : ( 1 ) minimal screening : the distress thermometer ( DT ) only plus usual care ; ( 2 ) full screening : DT , problem checklist , Psychological Screen for Cancer part C measuring anxiety and depression , a personalized report summarizing concerns and the report on the medical file ; or ( 3 ) triage : full screening plus optional personalized phone triage with referral to re sources . Patients in all conditions received an information packet and were reassessed 3 months later with the full screening battery . RESULTS Five hundred eighty-five patients with breast cancer and 549 patients with lung cancer were assessed at baseline ( 89 % of all patients ) , and 75.5 % retained for follow-up . High prevalence of baseline distress was found across patients . Twenty percent fewer patients with lung cancer in triage continued to have high distress at follow-up compared to those in the other two groups , and patients with breast cancer in the full screening and triage conditions showed lower distress at follow-up than those in minimal screening . The best predictor of decreased anxiety and depression in full screening and triage conditions was receiving a referral to psychosocial services . CONCLUSION Routine online screening is feasible in a large cancer center and may help to reduce future distress levels , particularly when coupled with uptake of appropriate re sources PURPOSE To examine the effects on process of care and patient well-being , of the regular collection and use of health-related quality -of-life ( HRQL ) data in oncology practice . PATIENTS AND METHODS In a prospect i ve study with repeated measures involving 28 oncologists , 286 cancer patients were r and omly assigned to either the intervention group ( regular completion of European Organization for Research and Treatment of Cancer-Core Quality of Life Question naire version 3.0 , and Hospital Anxiety and Depression Scale on touch-screen computers in clinic and feedback of results to physicians ) ; attention-control group ( completion of question naires , but no feedback ) ; or control group ( no HRQL measurement in clinic before encounters ) . Primary outcomes were patient HRQL over time , measured by the Functional Assessment of Cancer Therapy-General question naire , physician-patient communication , and clinical management , measured by content analysis of tape-recorded encounters . Analysis employed mixed-effects modeling and multiple regression . RESULTS Patients in the intervention and attention-control groups had better HRQL than the control group ( P = .006 and P = .01 , respectively ) , but the intervention and attention-control groups were not significantly different ( P = .80 ) . A positive effect on emotional well-being was associated with feedback of data ( P = .008 ) , but not with instrument completion ( P = .12 ) . A larger proportion of intervention patients showed clinical ly meaningful improvement in HRQL . More frequent discussion of chronic nonspecific symptoms ( P = .03 ) was found in the intervention group , without prolonging encounters . There was no detectable effect on patient management ( P = .60 ) . In the intervention patients , HRQL improvement was associated with explicit use of HRQL data ( P = .016 ) , discussion of pain , and role function ( P = .046 ) . CONCLUSION Routine assessment of cancer patients ' HRQL had an impact on physician-patient communication and result ed in benefits for some patients , who had better HRQL and emotional functioning PURPOSE : To determine the effectiveness of a clinical - practice intervention in improving the control of pain in out patients with cancer . METHOD : Between July 5 and September 30 , 1995 , a r and omized , controlled trial of 510 cancer out patients and 13 oncologists was conducted at 23 clinics in Indiana . All the patients completed assessment s of their pain , their pain regimens , and the degrees of relief received ; they were surveyed again by mail four weeks after their clinic visits . The intervention group 's clinical charts contained a summary of the completed pain scales ; the oncologists who treated these patients were instructed to review the summary sheet prior to an evaluation . This summary was not available for the oncologists treating the patients in the control group . Each patient 's pain management index ( PMI ) was calculated : the patient 's pain medication level was rated on a scale of 0 to 3 ; the patients 's pain level was rated on a scale of 0 to 3 and then subtracted from the first rating . A negative PMI was interpreted as representing insufficient treatment . Data were analyzed with several statistical tests . RESULTS : In all , only 320 patients who reported cancer-related pain were used in the analysis : 160 to 260 in the control group and 160 of 250 in the intervention group . The groups were similar with respect to demographics , cancer sites , and performance status . A significant difference ( p = .0162 ) in the physicians ' prescription patterns was found . In the control group , prescriptions for 86 % of the patients did not change , with no decrease in analgesic prescriptions ; for 14 % of the patients analgesic prescriptions increased . In the intervention group , analgesic prescriptions changed for 25 % of the patients , decreasing for 5 % and increasing for 20 % . A decrease in the incidence of pain described as more than life 's usual aches and pains was found for the intervention group ( p = .05 ) . No significant difference was found between the groups for the patients undertreated for pain , as measured by PMIs . CONCLUSION : Although analgesic regimens were altered significantly when the physicians understood more about the patient 's pain , cancer pain management remains a complex problem . Future studies should focus on the long-term systematic incorporation of simple pain- assessment tools into daily outpatient oncology practice s as well as on innovative ways to address other aspects of managing cancer pain The current study evaluated the efficacy of incorporating st and ardized health‐related quality of life ( HRQL ) assessment s as a routine part of the outpatient chemotherapy treatment of cancer patients in a community hospital in terms of : 1 ) facilitating nurse‐patient communication , 2 ) increasing nurses ' awareness of patients ' HRQL , 3 ) patient management , 4 ) patients ' satisfaction , and 5 ) patients ' HRQL CONTEXT There has been increasing interest in the use of health-related quality -of-life ( HRQL ) assessment s in daily clinical practice , yet few empirical studies have been conducted to evaluate the usefulness of such assessment s. OBJECTIVE To evaluate the efficacy of st and ardized HRQL assessment s in facilitating patient-physician communication and increasing physicians ' awareness of their patients ' HRQL-related problems . DESIGN Prospect i ve , r and omized crossover trial . SETTING Outpatient clinic of a cancer hospital in the Netherl and s. PARTICIPANTS Ten physicians and 214 patients ( 76 % women ; mean age , 57 years ) undergoing palliative chemotherapy who were invited to participate between June 1996 and June 1998 . INTERVENTION At 3 successive outpatient visits , patients completed an HRQL question naire ( European Organization for Research and Treatment of Cancer Quality of Life Question naire-Core 30 ) . The responses were computer scored and transformed into a graphic summary . Physicians and patients received a copy of the summary before the consultation . MAIN OUTCOME MEASURES Audiotapes of the consultations were content analyzed to evaluate patient-physician communication . Physicians ' awareness of their patients ' health problems was assessed by comparing physicians ' and patients ' ratings on the Dartmouth Primary Care Cooperative Information Functional Health Assessment ( COOP ) and the World Organisation Project of National Colleges and Academics ( WONCA ) charts . RESULTS The HRQL-related issues were discussed significantly more frequently in the intervention than in the control group ( mean [ SD ] communication composite scores : 4.5 [ 2.3 ] vs 3.7 [ 1.9 ] , respectively ( P = .01 ) . Physicians in the intervention group identified a greater percentage of patients with moderate-to-severe health problems in several HRQL domains than did those in the control group . All physicians and 87 % of the patients believed that the intervention facilitated communication and expressed interest in its continued use . CONCLUSION Incorporating st and ardized HRQL assessment s in daily clinical oncology practice facilitates the discussion of HRQL issues and can heighten physicians ' awareness of their patients ' HRQL PURPOSE / OBJECTIVES To test the efficacy of structured symptom assessment on level and rate of change in symptom distress over time . DESIGN Prospect i ve six-month r and omized control trial . SETTING Outpatient oncology offices and clinics in California . SAMPLE 48 subjects newly diagnosed with advanced lung cancer , predominantly non-small cell . Most subjects received chemotherapy , 50 % were women , and their average age was 62 years . 190 observations were analyzed . METHODS Subjects were assigned r and omly to structured assessment or usual care . Both groups completed the Symptom Distress Scale ( SDS ) monthly . After bivariate screening of potential predictors , a multivariate regression model for level and rate of change in SDS scores was created . MAIN RESEARCH VARIABLES Symptom distress , functional status , and emotional distress . FINDINGS Fatigue was the most common severely distressing symptom . In a multivariate model , chemotherapy and systematic assessment were associated with less symptom distress over time . Higher scores in depression and more functional limitations were related to higher levels of overall distress . Weight loss had a small impact . CONCLUSIONS Systematic use of structured symptom assessment forestalled increased symptom distress over time . Chemotherapy lessened symptom distress , but the impact diminished with time . Subjects with more depression and greater functional limitations had greater symptom distress . IMPLICATION S FOR NURSING PRACTICE During the course of advanced lung cancer , systematic ongoing nursing assessment of symptoms may be the first step in enhancing interventions to decrease distress . Patients at highest risk for symptom distress are those who experience emotional distress and functional limitations The purpose of this paper was to determine if providing patient specific Quality of Life ( QL ) information to clinic staff before a clinic appointment improved patient care in a lung cancer outpatient clinic . Patients were sequentially assigned to either a usual care control group or the experimental group , which completed a computerized version of the European Organization for Research and Treatment of Cancer ( EORTC ) QLQ-C30 question naire in order to provide the clinic staff with QL information prior to the clinic appointment . The control group completed the EORTC QLQ-C30 paper version after the clinic appointment . Outcome measures were patient satisfaction , the degree to which issues identified on the QL question naire were addressed in the appointment , and a chart audit , which measured charting of QL issues and actions taken by the clincian relating to QL . In the experimental group , more QL issues identified by the patient on the EORTC QLQ-C30 were addressed during the clinic appointment than in the control group . As well , marginally more categories were charted and a trend towards more actions being taken was seen in the experimental group . Patients reported being equally and highly satisfied with the treatment in both groups . The clinical implication is that the computerized administration of the EORTC QLQ-C30 question naire and providing staff with a report highlighting patient-specific QL deficits is a simple , time-effective and acceptable means of improving patient-provider communication in a busy outpatient clinic . Large trials study ing its effectiveness in different patient population s and regions would further eluci date the nature of this effect and potentially improve the overall quality of care that patients receive PURPOSE Patients receiving cancer-related thoracotomy are highly symptomatic in the first weeks after surgery . This study examined whether at-home symptom monitoring plus feedback to clinicians about severe symptoms contributes to more effective postoperative symptom control . PATIENTS AND METHODS We enrolled 100 patients receiving thoracotomy for lung cancer or lung metastasis in a two-arm r and omized controlled trial ; 79 patients completed the study . After hospital discharge , patients rated symptoms twice weekly for 4 weeks via automated telephone calls . For intervention group patients , an e-mail alert was forwarded to the patient 's clinical team for response if any of a subset of symptoms ( pain , disturbed sleep , distress , shortness of breath , or constipation ) reached a predetermined severity threshold . No alerts were generated for controls . Group differences in symptom threshold events were examined by generalized estimating equation modeling . RESULTS The intervention group experienced greater reduction in symptom threshold events than did controls ( 19 % v 8 % , respectively ) and a more rapid decline in symptom threshold events . The difference in average reduction in symptom interference between groups was -0.36 ( SE , 0.078 ; P = .02 ) . Clinicians responded to 84 % of e-mail alerts . Both groups reported equally high satisfaction with the automated system and with postoperative symptom control . CONCLUSION Frequent symptom monitoring with alerts to clinicians when symptoms became moderate or severe reduced symptom severity during the 4 weeks after thoracic surgery . Methods of automated symptom monitoring and triage may improve symptom control after major cancer surgery . These results should be confirmed in a larger study |
1,873 | 28,191,679 | Moreover , the survival rate was higher for RBBs inserted in the anterior area of the oral cavity compared with posterior RBBs .
Despite the high survival rate of RBBs after 5 and 10 years , technical complications like de-bonding and minor chipping were frequent .
RBBs with zirconia framework and RBBs with one retainer tooth showed the highest survival rate | OBJECTIVES The objective of this systematic review was to assess the 5-year and 10-year survival of resin-bonded fixed dental prostheses ( RBBs ) and to describe the incidence of technical and biological complications . | OBJECTIVES All-ceramic resin-bonded fixed partial dentures ( RBFPDs ) were introduced as a conservative treatment approach 15 years ago . The purpose of this prospect i ve study was to evaluate the long-term clinical survival of RBFPDs made with a conventional two-retainer design or a cantilever single-retainer design . METHOD AND MATERIAL S A total of 37 anterior RBFPDs were made from the glass-infiltrated alumina ceramic In-Ceram . Sixteen RBFPDs with a conventional two-retainer design were inserted in 14 patients , and 21 RBFPDs with a cantilever single-retainer design were inserted in 16 patients . Panavia or Panavia 21 were used as luting agents either after silica-coating and silanation or after air-abrasion only . Patients were recalled every year for a clinical examination to evaluate the restorations with regard to function and possible failures . The mean observation time in the two-retainer group was 75.8 months , and in the single-retainer group it was 51.7 months . RESULTS No restoration debonded . In the two-retainer group , one restoration was lost because it fractured after 3 months at both connectors and one restoration was removed alio loco accidentally . Also in this group , four RBFPDs fractured within 15 months after insertion at one connector , but the pontic remained in situ as a cantilever RBFPD for several years . In the single-retainer group , only one FPD fractured and was lost 48 months after insertion . The 5-year survival rate was 73.9 % in the two-retainer group and 92.3 % in the single-retainer group . When unilateral fracture of a FPD was taken as criterion for failure , the five-year survival rate decreased to 67.3 % in the two-retainer group . CONCLUSIONS Cantilever all-ceramic resin-bonded fixed partial dentures made from high-strength oxide ceramics present a promising treatment alternative to two-retainer RBFPDs in the anterior region OBJECTIVES The purpose of this clinical study was to evaluate the long-term outcome of 3-unit anterior fixed partial dentures ( FPDs ) made of fiber-reinforced resin composite ( FRC ) , and to identify design factors influencing the survival rate . METHODS 52 patients ( 26 females , 26 males ) received 60 indirectly made FRC FPDs , using pre-impregnated unidirectional glass fibers , requiring manual wetting , as framework material . FPDs were surface ( n=48 ) or hybrid ( n=12 ) retained and mainly located in the upper jaw . Hybrid FPDs had a combination of retainers ; i.e. crown at one and surface retention at the other abutment tooth . Surface FPDs were either purely adhesively retained ( n=29 ) or with additional mechanical retention ( n=19 ) . Follow-up period was at minimum 5 years , with check-ups every 1 - 2 years . Six operators were involved , in three centers in the Netherl and s , Finl and and Sweden . Survival rates , including repairable defects of FPDs , and success rates were determined . RESULTS Kaplan-Meier survival rate at 5 years was 64 % ( SE 7 % ) . For the level of success , values were 45 % ( SE 7 % ) and the estimated median survival time 58 ( SE 10.1 ) months . For surface FPDs , additional mechanical retention did not improve survival significantly . There was a trend towards better survival of surface FPDs over hybrid FPDs , but differences were not significant . Main failure modes were fracture of the FPD and delamination of veneering composite . SIGNIFICANCE A success rate of 45 % and a survival rate of 64 % after 5 years was found . Fracture of the framework and delamination are the most prevalent failure modes , especially for surface FPDs OBJECTIVES This prospect i ve clinical study evaluated the performance of indirect , anterior , surface-retained , fibre-reinforced-composite restorations ( ISFRCR ) . METHODS Between June-2003 and January-2011 , a total of 134 patients ( 83 females , 51 males , 16 - 68 years old ) received 175 ISFRCRs ( local ethical registration number : 14/9/4 ) . All restorations were made indirectly on a plaster model using unidirectional E-glass fibres ( everStick C&B , StickTech ) in combination with a laboratory resin composite ( Dialogue , Schütz Dental ) and cemented according to the instructions of 4 resin cements [ ( RelyX ARC , 3M-ESPE , n=61 ) , Bifix DC , VOCO , n=45 ) , Variolink II ( Ivoclar Vivadent , n=32 ) and Multilink ( Ivoclar Vivadent , n=37 ) ] . After baseline recordings , patients were followed at 6 months and thereafter annually up to 7.5 years . The evaluation protocol involved technical ( chipping , debonding or fracture of tooth/restoration ) and biological failures ( caries ) . RESULTS Mean observation period was 58 months . Altogether , 13 failures were observed [ survival rate : 97.7 % ] ( Kaplan-Meier ) . One catastrophic fracture [ ( cement : RelyX ARC ) , eight partial debonding ( cement : Bifix DC ( 5 ) , Multilink ( 1 ) , RelyX ARC ( 1 ) , Variolink II ( 1 ) ] and four delaminations of veneering composite [ ( cement : Bifix DC ( 2 ) , RelyX ARC ( 1 ) , Multilink ( 1 ) ] were observed . Except one replacement , all defective restorations were repaired or recemented . Annual failure rate of ISFRCRs was 1.73 % . The survival rates with the four resin cements did not show significant differences ( RelyX ARC : 98.3 % ; Bifix DC : 93.5 % ; Variolink 2 : 100 % ; Multilink : 100 % ) ( p=0.114 ) . Secondary caries did not occur in any of the teeth . CONCLUSION The 3-unit anterior indirect surface-retained resin-bonded FRC FDPs showed similar clinical survival rate when cemented with the resin cements tested . Experienced failures in general were due to debonding of the restoration or delamination of the veneering composite . CLINICAL SIGNIFICANCE 3-unit surface retained resin-bonded FRC FDPs could be considered minimal invasive and cost-effective alternatives to conventional tooth- or implant-borne FDPs . Failures were mainly repairable in the form of chipping or debonding depending on the resin cement type PURPOSE To retrospectively evaluate the 6-year survival rates and technical/ biologic complication rates of single-retainer glass-ceramic resin-bonded fixed dental prostheses ( RBFDPs ) . MATERIAL S AND METHODS Forty patients with 49 anterior/posterior glass-ceramic RBFDPs were included . The RBFDPs replaced 11 maxillary/m and ibular central incisors , 18 lateral incisors , 18 premolars , and 2 molars . Patients willing to participate were clinical ly and radiologically examined . The technical outcome was assessed with modified United States Public Health Service criteria . Fracture and /or chipping of the restoration , occlusal wear , marginal adaptation , marginal discoloration , shape , surface texture , and esthetic integration were recorded . Tooth vitality and postoperative sensitivity were tested . The following biologic parameters were assessed at test and control teeth : probing pocket depth , gingival recession , attachment loss , bleeding on probing , furcation involvement , and periodontal mobility . Statistical analysis was performed with exact 95 % confidence intervals to relative frequencies and the paired t test . RESULTS Twenty-eight patients with 35 RBFDPs participated . The mean follow-up of the RBFDPs was 6 years . Twelve patients with 14 RBFDPs were not willing to participate or not available . No catastrophic failures occurred . The 6-year survival rate of the examined RBFDPs was 100 % . No debonding was recorded . Chipping of the ceramic was found in 5.7 % of the RBFDPs . Biologic outcomes were similar at test and control teeth . CONCLUSION Glass-ceramic RBFDPs exhibited promising clinical outcomes in both anterior and posterior regions Previous clinical observations have revealed that resin-bonded bridges for posterior tooth replacements are less retentive than anterior resin-bonded bridges . Improved bonding procedures and preparation design s , however , may have a positive effect on the functional durability of these restorations . The present study reports the final analysis of a r and omized controlled clinical trial in which different design s of posterior resin-bonded bridges were evaluated for a period of at least 5 years . The operational hypothesis was that the bonding system and the preparation design used in posterior resin-bonded bridges have an influence on the survival and clinical functioning of these restorations . Survival in this study was defined at two levels : ( 1 ) ' complete ' survival ( survival without any debonding ) , and ( 2 ) ' functional ' survival ( survival including loss of retention on one occasion and successful rebonding of the original RBB without further debonding ) . With regard to ' complete ' survival , no significant differences were found between the bonding systems used for adherence of the restorations to abutment teeth ( etching/Clearfil F2 , s and blasting/Panavia EX , and silica-coating/Microfill Pontic C ) . The variable ' preparation form ' ( conventional preparation form vs. modified preparation form ) for complete survival was statistically in favor of the modified preparation form ( 62 % vs. 46 % ) , but did not influence the functional survival . With regard to ' functional ' survival , the combination of silica coating and Microfill Pontic C was more retentive than the other bonding systems ( 90 % survival vs. 72 % and 75 % , p < 0.01 ) . Factor location was found to be highly significant for both survival levels [ Cox 's PH model , p = 0.0002 ( Cox , 1972 ) ] : The five-year ' complete ' survival rates were 65 % for maxillary restorations and 40 % for m and ibular restorations , while the five-year ' functional ' survival rates were 89 % and 68 % , respectively . It is concluded that preparation of grooves in abutment teeth for posterior resin-bonded bridges is beneficial to their chance of survival . Resin-bonded bridges placed in the maxilla have a better prognosis than those made in the m and ible . The bonding systems used in this study appear to have no influence on the chance of failure . In rebonded posterior resin-bonded bridges , the bonding system silica-coating/Microfill Pontic C was more retentive than the other systems tested |
1,874 | 17,943,756 | No differences were detected in postabortal infection rates with routine prophylaxis or control .
However , compliance with antibiotic treatment was also low .
There is not enough evidence to evaluate a policy of routine antibiotic prophylaxis to women with incomplete abortion | BACKGROUND Unsafe abortions result not only in costs for acute care but may also be responsible for longer-term complications such as pelvic inflammatory disease , damage to reproductive organs , and secondary infertility .
If effective , antibiotic prophylaxis at the time of the procedure can potentially prevent these adverse consequences .
OBJECTIVES The value of routine antibiotics before surgical evacuation of the uterus in women with incomplete abortion is controversial .
In some health centres antibiotic prophylaxis is advised ; in others antibiotics are only prescribed when there are signs of infection .
The objective of this review is to evaluate the effectiveness of routine antibiotic prophylaxis to women with incomplete abortion . | OBJECTIVE To describe the epidemiology of incomplete abortion ( spontaneous miscarriage and illegally induced ) in South Africa . DESIGN Multicentre , prospect i ve , descriptive study . SETTING Fifty-six public hospitals in nine provinces ( a stratified , r and om sample of all hospitals treating gynaecological emergencies ) . PATIENTS All women of gestation under 22 weeks who presented with incomplete abortion during the 2-week study period . MAIN OUTCOME MEASURES Incidence of , morbidity associated with and mortality from incomplete abortion . MAIN RESULTS An estimated 44686 ( 95 % CI 35633 - 53709 ) women per year were admitted to South Africa 's public hospitals with incomplete abortion . An estimated 425 ( 95 % CI 78 - 735 ) women die in public hospitals from complications of abortion . Fifteen per cent ( 95 % CI 13 - 18 ) of patients have severe morbidity while a further 19 % ( 95 % CI 16 - 22 ) have moderate morbidity , as assessed by categories design ed for the study which largely reflect infection . There were marked inter-provincial differences and inter-age group differences in trimester of presentation and proportion of patients with appreciable morbidity . CONCLUSIONS Incomplete abortions and , in particular , unsafe abortions are an important cause of mortality and morbidity in South Africa . The methods used in this study underestimate the true incidence for reasons that are discussed . A high priority should be given to the prevention of unsafe abortion A r and omised controlled trial involving 140 non-septic incomplete abortions was performed to determine the efficacy of prophylactic tetracycline as practice d in these cases in Harare Central Hospital . The treatment group ( 62 ) received tetracycline ( 500 mg four times daily ) for a week . The remainder acted as controls . No significant difference in sepsis rate between treatment and control groups was noted . The high sepsis recorded in the treatment group was thought to be due to poor compliance . A new prophylaxis regimen has been suggested In a double‐blind controlled trial the effect of prophylactic metronidazole on postabortal infection in women with a history of pelvic inflammatory disease ( PID ) was assessed . One hundred and thirty‐five women were eligible for r and omization , of whom 17 were excluded . The regimen consisted of oral metronidazole 400 mg 1 h before the abortion and again 4 and 8 h after , or else placebo . In the placebo group the rate of postabortal PID was 13.0 % ( 7/54 ) and in the metronidazole group 10.9 % ( 7/64 ) , a nonsignificant difference ( p>0.7 ) . Women in gestational weeks 11−12 had a significantly increased rate of postabortal PID compared with women in weeks 6–10 ( p<0.005 ) , but this rate was not influenced by the treatment ( p>0.2 ) . Women with parity 1 had a significantly increased rate of postabortal PID compared with women with parity 0 ( p<0.05 ) , but again the treatment did not influence this rate significantly ( p>0.2 ) . The number of hospital days for women in the metronidazole group did not differ significantly from that in the placebo group ( p<0.1 ) . The amount of metronidazole administered for prophylactic and postabortal treatment was significantly greater in the metronidazole group ( p<0.001 ) . The amounts of other antibiotics prescribed showed non‐significant differences between the two groups ( all p‐values > 0.3 ) This r and omised controlled trial of 357 patients who had had an incomplete abortion compared suction curettage with conventional curettage for evacuation of the uterus . The 179 patients undergoing suction curettage had a significantly lower intra-operative blood loss ( P < 0.0001 ) and a significantly higher mean haemoglobin level at follow-up compared with the 178 patients who had conventional curettage . Suction curettage was a faster procedure and less painful . No difference was found between the two groups with regard to the incidence of post-abortal sepsis , or the re-evacuation rate . No problems were encountered with the use of suction curettage in the presence of uterine sepsis . In an era where blood transfusions should be kept to an absolute minimum , suction curettage will help to save blood in several ways In 1994 , a national hospital-based study was undertaken of cases of incomplete abortion presenting to public hospitals in South Africa . Data were collected for all women admitted to a r and om sample of hospitals with incomplete abortion during a two-week period . The WHO protocol for such studies was used as a basis for developing the methods to describe the epidemiology of incomplete abortion and hospital management of cases . Attempts were made to estimate the proportion of cases that might have been induced . This report focuses on method ological issues arising from the study that have implication s for future research . The findings demonstrate that only a small proportion of the women acknowledged having had an induced abortion and that only a few of those who did showed evidence of interference with pregnancy . Clinical opinion of sepsis and the likelihood of induction were found to be highly unreliable . These findings considerably reduce the usefulness of the WHO- protocol method of estimating the likely origin of incomplete abortions . Results presented in terms of three partially overlapping descriptive categories are judged to better reflect the limitations of the data collected The responses to therapy with either clindamycin alone or penicillin plus chloramphenicol in 77 patients with septic abortions were compared in a r and omized , double-blind study . Although fever index and duration of hospitalization were similar for both groups of patients , significantly more patients in the group that received clindamycin developed major complications ( P less than 0.05 ) . This is believed to result from clindamycin 's lack of activity against aerobic gram-negative bacilli . Aggressive management that included early uterine evacuation and broad-spectrum antibiotics effective against both aerobic and anaerobic bacteria was the key to reduced morbidity and mortality rates in treatment of septic abortion . For patients treated with clindamycin , early uterine evacuation appeared more important than antibiotic therapy ( P less than 0.005 ) . Bacteremia was documented in a total of 29 patients ( 38 % ) . Bacteremia was polymicrobial in eight patients ( 28 % ) and involved anaerobes exclusively in 18 ( 62 % ) , aerobes exclusively in nine ( 31 % ) , and both aerobes and anaerobes in two ( 7 % ) . The organisms most frequently isolated were Bacteroides ( other than Bacteroides fragilis ) , Peptostreptococcus , and Escherichia coli Opinion is divided as to the advisability of routine use of prophylactic antibiotics for curettage abortion . Six studies , including three r and omized clinical trials , suggest that prophylaxis reduces infectious morbidity associated with curettage abortions by about one half . Three other studies , two involving prophylaxis for instillation abortions and one involving a vaginal antiseptic for curettage abortion , support the hypothesis that antimicrobial prophylaxis reduces morbidity . Tetracyclines are commonly used for this purpose . The cost of routine prophylaxis even with an expensive tetracycline would appear to be offset by the savings in direct and indirect costs . Prophylaxis may help prevent both short-term morbidity and potential late sequelae , such as ectopic pregnancy and infertility Objective To determine the prevalence of bacterial vaginosis in women undergoing first trimester suction termination of pregnancy and to evaluate the efficacy of metronidazole in reducing the risk of post abortal pelvic infection in women with bacterial vaginosis OBJECTIVE To estimate prospect ively whether reducing oral doxycycline prophylaxis from 7 to 3 days increases the incidence of endometritis after elective first-trimester vacuum abortion . METHODS We r and omized 800 women requesting first-trimester abortion to two study groups : 1 ) 100 mg of doxycycline administered orally twice a day for 7 days or 2 ) 100 mg of doxycycline orally twice a day for 3 days followed by an oral placebo twice daily for the last 4 days . Doxycycline was prescribed immediately after surgery . RESULTS There were no statistically significant differences in age , race , gravidity , parity , number of previous abortions , current gestational age , and history of previous pelvic infection , chlamydia , or intrauterine device use . Women in the doxycycline plus placebo group were more likely to have had a history of gonorrhea ( 3.3 % versus 0.8 % , P = .42 ) or chlamydia ( 7.0 % versus 4.3 % , P = .18 ) . The 66.3 % of enrollees returning for 2-week examinations were distributed similarly between study groups and were similarly compliant in self-reported pill taking ( mean 97.5 % ) . The study groups did not differ in the incidence of postoperative symptoms or examination findings suggesting infection . One patient in the doxycycline-only group developed endometritis and was treated as an outpatient . CONCLUSION Shortening oral doxycycline prophylaxis from 7 to 3 days had no adverse effect on the incidence of postabortion infection Objective To investigate the incidence of post‐operative infection after first trimester abortion in women treated with a long‐acting cephalosporin ( ceftriaxone ) compared with low risk patients receiving no treatment and with high risk patients receiving our st and ard treatment of ampicillin/pivampicillin and metronidazole complications . Three patients had haemoptysis and two slight epistaxis . Three patients vomited , including the one in whom the procedure was ab and oned . There were 39 visible tumours . In 29 out of the 38 of these that were examined the histological opinion was definitive . Failure to make a positive diagnosis was associated with necrotic tumour tissue , previous radiotherapy , or a difficult biopsy . Where the appearance was of extrinsic compression a positive diagnosis was possible in only two out of 11 cases . In 11 cases examination showed non-malignant disease The efficacy of prophylactic antibiotic therapy in induced first-trimester abortions was investigated in a double-blind study . Of the 493 women in the study , 254 received doses of 2 million IU of penicillin G intramuscularly one-half hour before and 3 hours after the procedure , followed by 350 mg of pivampicillin three times daily for 4 days , and 239 women received corresponding doses of placebo . The incidence of pelvic infectious complications was 5.5 % in the treated group and 10.9 % in the control group ( p = 0.05 ) . The difference could be attributed to a selective prophylactic effect in women who had earlier suffered from pelvic inflammatory disease ( N = 105 ) . The rate of infection in this group was 22.4 % among those receiving placebo and 2.1 % among those receiving antibiotics ( p = 0.006 ) . Prophylactic administration of antibiotics for first-trimester abortions should be used in women who have earlier had pelvic inflammatory disease A prospect i ve double-blind study was performed to evaluate the effect of prophylactic antibiotic treatment before induced abortion . Eight hundred consecutive women admitted for first-trimester abortion , without signs of genital infection or antibiotic use in the last three weeks , were included in the study . Doxycycline 400 mg or placebo was given as a single oral dose ten to 12 hours before vacuum aspiration . Ninety-one women ( 11.8 % ) returned to the hospital with suspected complications . Thirty-two of these women were diagnosed as having pelvic inflammatory disease , eight of whom ( 2.1 % ) had received doxycycline before the abortion and 24 of whom ( 6.2 % ) had received placebo , a statistically significant difference ( P < .01 ) . A history of pelvic inflammatory disease increased the risk of developing it again after an abortion Objective To evaluate the efficacy of metronidazole to reduce post‐abortion complications among women with bacterial vaginosis Objective To evaluate the effectiveness and efficiency of a tailored multifaceted strategy , delivered by a national clinical effectiveness programme , to implement a guideline on induced abortion The prophylactic use of 300 mg doxycycline at the time of an abortion was evaluated in a r and omized controlled trial . In the group with negative chlamydia screening results , only two ( 0.4 % ) of 502 patients who received prophylactic treatment developed pelvic infection , compared with 15 ( 3.0 % ) of 497 patients who received placebos ( p = 0.001 ) . The same effectiveness was found in women with positive chlamydia screening results . Vomiting was the major side effect of the medication and could limit its use . A simulation of selective prophylaxis in women with negative chlamydia screening results showed that its selective use in patients with a history of gonorrhea or in nulliparous women with multiple sex partners could be nearly two thirds as effective as general prophylaxis A r and omized prospect i ve double-blind study was conducted to determine the efficacy of prophylactic antibiotics as compared with placebo in 198 women undergoing secondtrimester intraamniotic injection abortions . Patients received either sodium cephalothin or placebo intravenously before the procedure and for up to 8 additional doses . In 11 patients postabortion endometritis developed ; 2 had received the antibiotic and 9 had received a placebo ( P<.05 ) . Prophylactic cephalothin decreases the incidence of endometritis in patients undergoing midtrimester injection abortion . An injection-abortion interval greater than 24 hours appears to identify patients at increased risk for the development of postabortion endometritis Objective To determine whether prophylactic doxycycline at suction curettage for incomplete abortion decreases the rate of postoperative pelvic infection . Methods We r and omized 240 patients to receive intravenous doxycycline or placebo at curettage . Cervical specimens for gonorrhea and chlamydia were obtained preoperatively . Two weeks post-procedure , we evaluated all patients for infectious morbidity and repeated gonorrhea and chlamydia cultures . Statistical analysis used Mann-Whitney U test , McNemar test , or Fisher exact test , as appropriate . Results There were no statistically significant differences in age , parity , gestational age , history of sexually transmitted disease , pelvic inflammatory disease , or multiple sex partners between the doxycycline and placebo groups . Preoperative gonorrhea or chlamydia isolates were positive in five ( 4.2 % ) and six ( 5 % ) of 120 doxycycline patients and four ( 3.3 % ) and eight ( 6.6 % ) of 120 controls ( not significant ) . All preoperative gonorrhea isolates remained positive postoperatively . Seven ( 5.8 % ) controls had positive postoperative chlamydia isolates , as did one ( 0.8 % ) in the doxycycline group ( P = .06 ) . We diagnosed eight ( 6.6 % ) of 120 doxycycline patients and seven ( 5.8 % ) of 120 controls with infectious morbidity ( not significant ) . Conclusion In our population of patients with incomplete abortion , the prevalence of gonorrhea and chlamydia was low , and prophylactic doxycycline did not decrease the rate of postoperative febrile morbidity |
1,875 | 31,725,647 | The general heterogeneity was not found among included trials .
But predictive intervals ( PrIs ) were conspicuously wider than confidential intervals ( CIs ) of all pairwise comparisons , indicating that heterogeneity may exist between studies .
Complementary therapy showed the greatest probability ( 42.7 % ) to be the best intervention .
Based on the limited evidence of available trials , complementary therapy seemed to be slightly more effective than remaining treatment modalities for pain reduction in TMD patients with masticatory muscle pain . | BACKGROUND Numerous treatment modalities have been attempted for masticatory muscle pain in patients with temporom and ibular disorders ( TMD ) .
To compare the treatment efficacy of more than 2 competing treatments , a network meta- analysis ( NMA ) was conducted . | ABSTRACT Forty-five patients with a primary diagnosis of muscular MD were evaluated and treated in a university based facial pain center . The patients were equally and r and omly assigned to one of three treatment groups . Group 1 patients were treated with traditional therapies appropriate for the particular patient . Group two patients used similar therapies that were appropriate for the patient but also had an oral vertical exercise device integrated into their therapy . Patients in the third group were instructed in home care , educated about TMD , and instructed in the use of the oral exercise device . Results indicated that all three groups demonstrated significant overall patient clinical and subjective improvement . The three groups did not differ significantly from each other in degree of patient improvement A study of the effectiveness of physical therapy for patients with myofacial pain dysfunction syndrome was performed . Clinical evaluation of 120 patients revealed marked male preponderance , distribution according to age showed a great prevalence of the third decade , and most common chief complaints were pain and muscle tenderness . Patients were classified r and omly into three equal groups treated by muscle relaxant drugs , shortwave diathermy , and ultrasonic therapy , respectively . Regular follow-up was carried out for 6 to 12 months to assess patients ' responses to different forms of treatment . Evaluation revealed marked relief of symptoms by the use of physical therapy , and the best results were obtained by the use of ultrasonic therapy Objective The aim of the present study was to evaluate the effects of upper thoracic manipulation on pain in subjects with temporom and ibular disorder . Design Thirty-two women with a diagnosis of temporom and ibular disorder were r and omly allocated to an experimental group ( n = 16 ) , su bmi tted to upper thoracic manipulation , and a placebo group ( n = 16 ) , su bmi tted to a procedure in the thoracic region with no therapeutic effect . All volunteers underwent an evaluation of pain in the masticatory muscles and the temporom and ibular joint using an algometer and the visual analog scale before and immediately after the procedure as well as after 48–72 hrs . Two-way repeated- measures analysis of variance was used for the intragroup and intergroup analyses , with the level of significance set to 5 % ( P < 0.05 ) . Cohen d was calculated for the determination of the effect size . Results No significant group-by-time interaction was found ( P > 0.05 ) for algometry in any analysis , and Cohen d revealed no significant effect of the treatment . Moreover , no significant group-by-time interaction was found for facial pain intensity determined using the visual analog scale ( P > 0.05 ) , and Cohen d also revealed no significant effect of the treatment regarding this variable . Conclusions On the basis of the present findings , upper thoracic spinal manipulation does not lead to a reduction in pain in women with temporom and ibular disorder BACKGROUND Temporom and ibular pain has multiple etiologies and a range of therapeutic options . In this pilot study , the authors assessed the feasibility of conducting a larger trial to evaluate chiropractic treatment of temporom and ibular disorders ( TMDs ) . METHODS The authors assigned 80 participants r and omly into one of the following four groups , all of which included a comprehensive self-care program : reversible interocclusal splint therapy ( RIST ) , Activator Method Chiropractic Technique ( AMCT ) ( Activator Methods International , Phoenix ) , sham AMCT and self-care only . They made assessment s at baseline and at month 2 and month 6 , including use of the Research Diagnostic Criteria for Temporom and ibular Disorders . RESULTS The authors screened 721 potential participants and enrolled 80 people ; 52 participants completed the six-month assessment . The adjusted mean change in current pain over six months , as assessed on the 11-point numerical rating scale , was 2.0 ( 95 percent confidence interval , 1.1 - 3.0 ) for RIST , 1.7 ( 0.9 - 2.5 ) for self-care only , 1.5 ( 0.7 - 2.4 ) for AMCT and 1.6 ( 0.7 - 2.5 ) for sham AMCT . The authors also assessed bothersomeness and functionality . CONCLUSIONS The authors found the study design and methodology to be manageable . They gained substantial knowledge to aid in conducting a larger study . AMCT , RIST and self-care should be evaluated in a future comparative effectiveness study . PRACTICAL IMPLICATION S This pilot study was a necessary step to prepare for a larger study that will provide clinicians with information that should be helpful when discussing treatment options for patients with TMD Background Myogenous temporom and ibular disorders ( TMD ) are considered to be a common musculoskeletal condition . No studies exist comparing intra-oral myofascial therapies to education , self-care and exercise ( ESC ) for TMD . This study evaluated short-term differences in pain and mouth opening range between intra-oral myofascial therapy ( IMT ) and an ESC program . Methods Forty-six participants with chronic myogenous TMD ( as assessed according to the Research Diagnostic Criteria Axis 1 procedure ) were consecutively block r and omised into either an IMT group or an ESC group . Each group received two sessions per week ( for five weeks ) of either IMT or short talks on the anatomy , physiology and biomechanics of the jaw plus instruction and supervision of self-care exercises . The sessions were conducted at the first author ’s jaw pain and chiropractic clinic in Sydney , Australia . Primary outcome measures included pain at rest , upon opening and clenching , using an eleven point ordinal self reported pain scale . A secondary outcome measure consisted of maximum voluntary opening range in millimetres . Data were analysed using linear models for means and logistic regression for responder analysis . Results After adjusting for baseline , the IMT group had significantly lower average pain for all primary outcomes at 6 weeks compared to the ESC group ( p < 0.001 ) . These differences were not clinical ly significant but the IMT group had significantly higher odds of a clinical ly significant change ( p < 0.045 ) . There was no significant difference in opening range between the IMT and ESC groups . Both groups achieved statistically significant decreases in all three pain measures at six weeks ( p ≤ 0.05 ) , but only the IMT group achieved clinical ly significant changes of 2 or more points . Conclusion This study showed evidence of superiority of IMT compared to ESC over the short-term but not at clinical ly significant levels . Positive changes over time for both IMT and ESC protocol s were noted . A longer term , multi-centre study is warranted . Trial registration Australian and New Zeal and Clinical Trials Registry ACTRN12610000508077 A r and om sample of U.S. dentists was surveyed with a mailed question naire to determine the number of splints that they fabricated over the preceding year for bruxers , patients with myofascial pain-dysfunction syndrome and patients with TM joint pain . The results indicate that a significant number of dentists treat these disorders with dental splints . Estimates are provided for the dental profession 's yearly splint output for each disorder Abstract The aim of this research was to study if changes in condyle position in temporom and ibular disorders ( TMD ) patients could be a factor that is affected by resilient appliance therapy and if it influences the treatment outcome . The study investigated 48 patients r and omly assigned to a treatment group ( T group = 21 patients , using resilient appliance ) or a control group ( C group = 27 patients , using nonoccluding appliance ) . Changes in the condyle-fossa relationship ( with and without the appliance ) were determined in an MRI examination . Ten weeks after treatment , the treatment outcome was measured . The results showed that with the appliance , change in condyle position occurred in 76 % of the T group and 22 % of the C group ( p<0.001 ) . Sixty-seven percent ( 67 % ) of the T group and 44 % of the C group experienced a successful treatment outcome . Treatment outcome was not related to changes in condyle position in patients with TMD pain OBJECTIVE Studies investigating the efficacy of intraoral myofascial therapies ( IMTs ) for chronic temporom and ibular disorder ( TMD ) are rare . The present study was an expansion of a previously published pilot study that investigated whether chiropractic IMT and the addition of education and self-care were superior to no-treatment or IMT alone for 5 outcome measures -interincisal opening range , jaw pain at rest , jaw pain upon opening , jaw pain upon clenching , and global reporting of change-over the course of 1 year . METHODS Ninety-three participants with myogenous TMD between the ages of 18 and 50 years experiencing chronic jaw pain of longer than 3 months in duration were recruited for the study . Successful applicants were r and omized into 1 of 3 groups : ( 1 ) IMT consisting of 2 treatment interventions per week for 5 weeks , ( 2 ) IMT plus education and " self-care " exercises ( IMTESC ) , and ( 3 ) wait-list control . The main outcome measures were used . Range of motion findings were measured by vernier callipers in millimeters , and pain scores were quantified using an 11-point self-reported grade d chronic pain scale . Global reporting of change was a 7-point self-reported scale , balanced positively and negatively around a zero midpoint . RESULTS There were statistically significant differences in resting , opening and clenching pain , opening scores , and global reporting of change ( P < .05 ) in both treatment groups compared with the controls at 6 months and 1 year . There were also significant differences between the 2 treatment groups at 1 year . CONCLUSIONS The study suggests that both chiropractic IMT and IMTESC were superior to no-treatment of chronic myogenous TMD over the course of 1 year , with IMTESC also being superior to IMT at 1 year AIMS To compare the effectiveness of adding cyclobenzaprine , tizanidine , or placebo to patient education and a self-care management program for patients with myofascial pain and specifically presenting with jaw pain upon awakening . METHODS Forty-five patients with a diagnosis of myofascial pain based on the guidelines of the American Academy of Orofacial Pain participated in this 3-week study . The subjects were r and omly assigned into one of three groups : placebo group , TZA group ( tizanidine 4 mg ) , or CYC group ( cyclobenzaprine 10 mg ) . Patients were evaluated for changes in pain intensity , frequency , and duration by using the modified Severity Symptoms Index and changes in sleep quality with the use of the Pittsburgh Sleep Quality Index . Data were analyzed by ANOVA and post-hoc or nonparametric statistical tests as appropriate . RESULTS All three groups had a reduction in pain symptoms and improvement of sleep quality based on a comparison of pretreatment and treatment scores . However , no significant differences among the groups were observed at the posttreatment evaluation . CONCLUSION The use of tizanidine or cyclobenzaprine in addition to self-care management and patient education was not more effective than placebo for the management of patients with myofascial jaw pain upon awakening Abstract Objective . The aim of this study was to analyze and compare prevalence of signs and frequently occurring symptoms indicative of temporom and ibular disorder ( TMD ) and headaches in 35- , 50- , 65- and 75-year-old men and women in Västerbotten County , Sweden . Material s and methods . From a total target population of 11 324 subjects living in Västerbotten County in the year 2002 , 300 individuals in each age group were r and omly selected . Of these , 998 ( 82 % response rate ) answered and returned a postal question naire and 779 ( 65 % response rate ) individuals accepted a clinical examination . Results . The prevalence of frequent TMD symptoms peaked among 50-year-old women and then declined . Women at this age reported significantly higher prevalence compared to men for all TMD symptoms except temporom and ibular joint locking . In the 65- and 75-year-olds , the prevalence was practically equal between men and women as well as between these ages . Frequent headaches showed the highest prevalence among 35- and 50-year-old women , with a statistically significant difference between men and women of 50 years of age ( p < 0.05 ) . Fifty-year-old women had statistically significantly higher prevalence of muscle pain to palpation ( p < 0.001 ) , temporom and ibular joint sounds ( p < 0.01 ) and impaired maximal jaw opening capacity ( p < 0.01 ) , compared to 50-year-old men . Conclusions . The different symptoms indicative of TMD and headaches showed a similar pattern , with higher prevalence among the 35- and 50-year-old , as compared to the 65- and 75-year-old , participants . The pattern may be related to biological , psychosocial or generation-related factors Summary Dental hygienist‐delivered pain self‐management training was superior to continuous oral contraceptive therapy for women with TMD pain ; focusing on menstrually‐related changes in symptoms did not increase its efficacy . ABSTRACT Mounting evidence supports the importance of hormonal fluctuations in temporom and ibular disorder ( TMD ) pain among women . Stabilizing influential hormones or having a plan and skills for coping with hormonally related increases in TMD pain , therefore , may be beneficial for women with TMD pain . This r and omized clinical trial evaluated the short‐ and long‐term efficacy of 3 interventions for women with TMD pain : ( 1 ) dental hygienist‐delivered pain self‐management training ( SMT ; n = 59 ) ; ( 2 ) the same dental hygienist‐delivered pain self‐management training , but with a focus on menstrual cycle‐related changes in pain and other symptoms ( targeted SMT , or TSMT ; n = 55 ) ; and ( 3 ) continuous oral contraceptive therapy ( 6‐month trial ) aim ed at stabilizing hormones believed to be influential in TMD pain ( COCT ; n = 57 ) . Study participants completed outcome ( pain , activity interference , depression ) and process ( pain beliefs , catastrophizing , coping effectiveness ) measures before r and omization , and 6 and 12 months later . Intent‐to‐treat analyses supported the benefits of the SMT and TSMT interventions relative to COCT . Targeting the self‐management treatment to menstrual cycle‐related symptoms did not increase the treatment ’s efficacy . The benefits of the self‐management interventions relative to COCT for pain and activity interference were statistically significant at 12 months , but not at 6 months , whereas the benefits for the process measures generally were apparent at both time points . COCT was associated with multiple adverse events ( none serious ) . The study provides further support for long‐term benefits of a safe , low‐intensity ( 2 in‐person sessions and 6 brief telephone contacts ) , dental hygienist‐delivered self‐management treatment for TMD pain BACKGROUND The authors conducted a clinical trial to compare the effectiveness of an education program with that of an occlusal splint in treating myofascial pain of the jaw muscles across a short period . METHOD The authors assigned 44 patients r and omly to two treatment groups ; 41 patients completed the study . The first group ( four male , 19 female ; mean [ st and ard deviation { SD } ] age , 31.4 [ 14.0 ] years ) received information regarding the nature of temporom and ibular disorder ( TMD ) and self-care measures , whereas the second group ( five male , 13 female ; mean [ SD ] age , 31.1 [ 8.8 ] years ) received an occlusal splint . One of the authors evaluated each patient every three weeks during a three-month treatment period . Treatment outcomes included pain-free maximal mouth opening , spontaneous muscle pain , pain during chewing and headache . RESULTS After three months , changes in spontaneous muscle pain differed significantly between the education and occlusal splint groups ( P = .034 ; effect size = 0.33 ) . Changes in pain-free maximal mouth opening did not differ significantly between groups ( P = .528 ; effect size = 0.20 ) . Changes of headache and pain on chewing did not differ significantly between groups ( P ≥ .550 , effect size ≤ 0.10 ) . CONCLUSIONS During a short period , education was slightly more effective than an occlusal splint delivered without education in reducing spontaneous muscle pain in patients with TMD . Pain-free mouth opening , headache and pain during chewing were not significantly different between the two treatments The purpose of this study was to compare the short-term effectiveness of home physical therapy ( HPT ) alone with that of manual therapy ( MT ) in conjunction with home physical therapy ( MT-HPT ) performed for four weeks in patients with temporom and ibular disorders ( TMD ) . Forty subjects ( nine males and 31 females ; age , 18 - 72 years ) with TMD were r and omly divided into two groups : HPT ( n = 20 ; five males and 15 females ; mean age , 34.8 ± 12.4 years ) and MT-HPT ( n = 20 ; four males and 16 females ; mean age , 37.0 ± 14.6 years ) . Pain intensity was evaluated at rest and with stress using a visual analogue scale ( VAS ) . Pain-free maximum mouth opening ( MMO ) was also evaluated . Mean change score ( MCS ) in VAS and the smallest detectable difference ( SDD ) in pain-free MMO were measured over time . The results were analysed by MANOVA to evaluate the effects of treatment over time . At baseline , the groups did not differ from each other with respect to VAS scores and pain-free MMO ( p > 0.05 ) . Within each group , VAS with stress decreased ( p < 0.001 ) and pain-free MMO increased ( p < 0.001 ) over time . Between groups , both time*treatment effect and treatment effect were significant for VAS with stress ( p < 0.001 ) ; however , only time*treatment effect was significant for pain-free MMO ( p = 0.009 ) . In the MT-HPT group , MCS for VAS with stress was 91.3 % and SDD for pain-free MMO was 10 mm . Our results suggest that a four-week period of MT-HPT has a clinical ly significant effect on both pain and pain-free maximum mouth opening in patients with TMD BACKGROUND AND OBJECTIVES To test the hypothesis that dry needling is more effective than sham dry needling in relieving myofascial pain of the temporom and ibular muscles . MATERIAL AND METHOD Fifty-two subjects with established myofascial trigger points were r and omized into two groups ; study group ( N : 26 ) and placebo group ( N : 26 ) . Dry needling was applied using acupuncture needles . Sham dry needling was applied to the placebo group . Pain pressure threshold was measured with pressure algometry , pain intensity was rated using a 10-cm visual analog scale ( VAS ) and the unassisted jaw opening without pain measurement was performed . Evaluations were done by a physician blinded to the data . RESULTS Of 52 patients assigned , 50 completed the study . Mean algometric values were significantly higher in the study group when compared to the placebo group ( p values being less than 0.05 ) . There were no differences between the two groups in terms of VAS and unassisted jaw-opening without pain values . CONCLUSION Dry needling appears to be an effective treatment method in relieving the pain and tenderness of myofascial trigger points Abstract The aim of this study was to investigate the reliability between different examiners when using the axis I of the Research Diagnostic Criteria for Temporom and ibular Disorders ( RDC/TMD ) . The hypothesis was that the st and ardized RDC/TMD examination protocol enables calibrated examiners to evaluate all examination items reliably . After calibration training by the RDC/TMD calibration team including the calibration of palpation pressure and the performance of the st and ardized examination protocol , four examiners , blinded to the patients ’ medical histories examined 24 subjects in a r and omized sequence . One experienced examiner was the st and ard ( hierarchical calibration ) . The recorded measurements strictly followed the RDC/TMD . Intraclass correlation coefficients ( ICC ) , bias and precision were calculated to estimate interrater reliability . Acceptable ( 0.75≥ICC>0.4 ) to excellent ( ICC>0.75 ) reliability was found for 20 of the 23 ( 87 % ) examinations . Only sub-retrom and ibular muscle palpation and joint sound vibration recordings on lateral excursion showed poor- results ( ICC≤0.4 ) . The RDC/TMD examination protocol enables calibrated examiners to perform most ( 87 % ) examination items with satisfactory reliability . Therefore multi-site studies based on the RDC/TMD examination protocol may become feasible , keeping in mind the unsatisfactory reliability of 13 % of the items ( clicking during laterotrusion to the ipsilateral side , palpation of the posterior and subm and ibular region ) OBJECTIVE To assess the immediate effects of hamstrings stretching alone or combined with ischemic compression of the masseter muscle on hamstrings extensibility , active mouth opening and pain in athletes with temporom and ibular dysfunction and hamstrings shortening . METHODS Forty-two participants were r and omized to receive the stretching technique ( n = 21 ) or the stretching plus the ischemic compression ( n = 21 ) . Outcome measures were : hamstrings extensibility , active mouth opening , pressure pain thresholds and pain intensity . RESULTS Both interventions improved significantly active mouth opening ( group 1 : 35.7 ± 6.7 to 39.1 ± 7.6 mm , p < 0.001 ; group 2 : 34.0 ± 6.2 to 37.6 ± 5.6 mm , p < 0.001 ) , active knee extension ( group 1 : 33.1 ± 8.5 to 40.8 ± 8.2 ° , p < 0.001 ; group 2 : 28.9 ± 6.5 to 35.5 ± 6.4 ° , p < 0.001 ) and pain . No significant differences were found between interventions . CONCLUSION Hamstrings stretching induced an acute improvement in hamstrings extensibility , active mouth opening and pain . Moreover , the addition of ischemic compression did not induce further improvements on the assessed parameters Objective This study contrasted the effect of hypnosis on self-reported pain and changes in a nociceptive brainstem reflex , the blink reflex ( BR ) , in 39 women with temporom and ibular disorder . Methods The patients were r and omized to hypnosis or control ( nonhypnotic relaxation ) . Pain intensity was assessed 3 times daily on a 0 to 10 numerical rating scale . BRs were elicited by electrical stimulation with a nociceptive-specific electrode and recorded before and after treatment at pain threshold ( Ip ) and supra threshold ( 2 × Ip ) . Results Significant reduction of pain intensity was observed in the hypnosis group from 4.5±2.1 at baseline to 2.9±2.4 after treatment ( P<0.001 ) . The pain reduction was generally unrelated to changes in the BR , with the exception being a lowered ipsilateral R2 BR component at the right side supra threshold ( P=0.034 ) . Conclusions Hypnosis thus seems to reduce complex temporom and ibular disorder pain , most likely because of cortical changes with little , if any , involvement of brainstem reflex pathways Abstract Objectives : Studies investigating the efficacy of intra-oral myofascial therapies ( IMT ) for chronic temporom and ibular disorder ( TMD ) are rare . The objective of this r and omized , controlled pilot study was to compare the effects of IMT and the addition of self-care and education over 6 months on four common TMD outcome measures : inter-incisal opening range , jaw pain at rest , jaw pain upon opening , and jaw pain upon clenching . Participants : Thirty myogenous TMD participants between the ages of 18 and 50 years , experiencing chronic jaw pain of longer than 3-month duration , were recruited for the present study . Intervention : Included patients were r and omized into one of three groups : ( 1 ) IMT consisting of two treatment interventions per week for 5 weeks ; ( 2 ) IMT plus ' self-care ' involving education and exercises ; and ( 3 ) wait list control . Main outcome measures : Range of motion findings were measured in millimetres by vernier callipers and pain scores were quantified using an 11-point self-reported grade d chronic pain scale . Measurements were taken at baseline , 6 weeks post-treatment , and 6 months post-treatment . Results : The results showed statistically significant differences in resting , opening , and clenching pain and opening range scores ( P<0.05 ) in both treatment groups compared to control at 6 months . No significant differences were observed between the two treatment groups during the course of the trial . Conclusions : This study suggests that IMT alone or with the addition of self-care may be of some benefit in the management of chronic TMD over the short-medium term . A larger scale study over a longer term ( 1–2 years ) may be of further value This study investigated the effect of hypnosis in patients with temporom and ibular disorders ( TMD ) with focus on oral function and psychological outcomes . Forty women ( mean age + /- s.d . : 38.6 + /- 10.8 years ) suffering from TMD ( mean duration 11.9 + /- 9.9 years ) were r and omized to four individual 1-hour sessions of either hypnotic intervention or a control condition of simple relaxation . Pain intensity was assessed three times daily on a 0 - 10 Numerical Rating Scale . Additional outcomes were TMD-associated symptoms assessed by the Research Diagnostic Criteria examination form and question naire , psychological symptoms ( Symptom Check List 60 ) , pain coping strategies ( Coping Strategies Question naire ) , sleep difficulties ( Pittsburgh Sleep Quality Index ) and use of analgesics . Data were analyzed with between-groups within-subjects anovas . The hypnosis group significantly reduced the daily NRS pain scores from 4.5 + /- 2.1 at baseline to 2.9 + /- 2.4 after treatment ( P < 0.001 ) compared to the control group where no significant changes were found ( 4.2 + /- 1.4 to 3.9 + /- 1.5 ) ( P = 0.733 ) . Number needed to treat for a 50 % pain reduction was 4.0 . The hypnosis group also increased use of the coping strategy ' reinterpreting pain sensations ' from 5.2 + /- 6.9 to 10.3 + /- 6.8 ( P < 0.001 ) . Both groups exhibited significant reductions in the number of painful muscle palpation sites and pain on palpation ( P < 0.004 ) , in number of awakenings due to pain ( P < 0.006 ) , and in somatization , obsessive compulsive symptoms and anxiety ( P < 0.004 ) . Hypnosis thus appears to effectively reduce some aspects of complex TMD pain Abstract Trigger point injections with different solutions have been studied mainly with regard to the management of myofascial pain ( MFP ) patient management . However , few studies have analyzed their effect in a chronic headache population with associated MFP . The purpose of this study was to assess if trigger point injections using lidocaine associated with corticoid would be better than lidocaine alone , as in comparison with dry-needling in for the management of local pain and associated headache management . Forty-five ( 45 ) myofascial pain patients with headaches that could be reproduced by activating at least one trigger point , were r and omly assigned into one of the three groups : G1 , dry-needling , G2 , 0.25 % lidocaine , at 0.25 % and G3 , 0.25 % lidocaine at 0.25 % associated with corticoid , and were assessed during a 12 week period . Levels of pain intensity , frequency and duration , local post-injection sensitivity , obtainment time and duration of relief , and the use of rescue medication were evaluated . Statistically , all three groups showed favorable results for the evaluated requisites ( p≤0.05 ) , but only for post-injection sensitivity did the association of lidocaine with corticoid present the best results and ingestion of rescue medication The long-term effectiveness of a prefabricated oral appliance ( R ) was compared with a stabilisation appliance ( S ) in patients with myofascial pain . Sixty-five patients diagnosed with myofascial pain at two centres for Stomatognathic Physiology in Sweden and Finl and were included in a r and omised controlled trial using Research Diagnostic Criteria for Temporom and ibular Disorders , with history question naires and clinical examinations performed by blinded examiners at baseline and at 6- and 12-month follow-ups . Patients were r and omly assigned either to the R or the S group . Treatment outcome was measured according to IMMPACT for four chronic pain outcome domains : pain intensity , overall improvement , physical functioning and emotional functioning . Physical functioning was classified for Grade d Chronic Pain severities and assessed by the Jaw Functional Limitation scale . Emotional functioning composed of scores of non-specific physical symptoms and depression . There were no differences between groups at baseline . At both follow-ups , all outcome domains showed significant within-group improvement , without significant differences between groups . At 12 months , 72 % of all patients reported a 30 % reduction in worst pain and 63 % of the patients a 50 % reduction in worst pain . Overall improvement ' better ' to ' symptom-free ' was observed in 81 % in the R and 64 % in the S group at the 12-month follow-up . Grade d Chronic Pain , Functional Limitation of the Jaw , non-specific physical symptoms and depression showed statistically significant reduction at 12-month follow-up . Results support the hypothesis that the effectiveness of the prefabricated appliance is similar to that of the stabilisation appliance in the long-term when treating patients with myofascial pain ABSTRACT Loss of function , muscle inflammation , and pain are some of the signs and symptoms of temporom and ibular dysfunction ( TMD ) . Pharmacological strategies to minimize the clinical manifestation of these disorders often focus on blocking or inhibiting the pain-causing symptom . Re sources such as muscle-relaxants , anxiety-relief drugs , and splint therapy are often used to reduce muscular hyper-activity related to TMD muscle pain . This study compares the effect of a r and omly ordered association of occlusal splint therapy ( S ) , nonsteroid anti-inflammatory with a muscle-relaxant drug ( orphenadrine citrate ) ( O ) , and an anxiety-relief drug ( benzodiazepine ) ( B ) , to ease painful TMD muscle symptoms . Clinical and anamnestic analyses were recorded in accordance with the Helkimo TMD index and applied before and after treatments . Twenty-one group two Helkimo TMD adult female patients were treated , all of whom were subjected to the three r and om therapeutic associations proposed : SBO , BOS , and OSB . The same operator applied the three specific associations over a period of 21 days in the proposed sequence , seven days for each therapy . The results show that all the groups presented the best results in terms of relief from pain after the therapeutic association ( 28.5 % showed a decrease and 47.6 % showed an absence of symptoms ) . No significant difference was observed among association therapeutic protocol Abstract Objectives . The aim of this study was to assess the effect of occlusal splint therapy on the electromyographic amplitude records ( μV ) of masticatory muscles in temporom and ibular disorder ( TMD ) with myofascial pain and to detect a possible existence of a relationship between this effect and the treatment outcome . Material s and methods . Forty patients ( 23 females and 17 males ) having TMD with myofascial pain were included in this study . They were r and omly divided into two equal groups ( 20 of each ) . The first group ( A ) was treated by occlusal splints for 6 months while the second group ( B ) acted as a control . A clinical assessment and surface electromyography ( EMG ) for the masticatory muscles were performed at the beginning of the study , then 6 months later . The collected data were statistically analyzed using paired t-test . The differences were considered significant at p < 0.05 . Results . The results showed that 85 % of group A either completely recovered ( 35 % ) or clinical ly improved ( 50 % ) while only 20 % of group B had a spontaneous improvement . In group A , the means of the electromyographic amplitude records ( μV ) of the monitored muscles have decreased after 6 months . However , the decrease was statistically insignificant ( p > 0.05 ) in the patients ( 15 % ) who had no clinical changes . In group B , the means of the muscles ' records ( μV ) in the left side slightly increased while those of the right side slightly decreased . These changes were statistically insignificant ( p > 0.05 ) . Conclusions . Occlusal splint could eliminate or improve the signs and symptoms of TMD patients with myofascial pain . It reduces the electromyographic amplitude records ( μV ) of the masticatory muscles . The splint therapy outcome has a correlation with the electromyographic amplitude changes of the masticatory muscles |
1,876 | 31,760,593 | According to the results , telemedicine improves the clinical outcomes and results in considerable saving in costs .
Utilizing telemedicine concurrent with the usual care for service delivery is more cost-effective . | Cardiovascular disease is one of the major causes of mortality in the world , with high human and financial burdens on communities .
Telemedicine is a tool for providing services for patients that are difficult to access or in need of immediate care .
The aim of this study was to systematic ally review economic evaluation studies that compared telemedicine with usual care for cardiovascular patients . | Aim To determine the effectiveness and cost-effectiveness of a mobile phone intervention to improve exercise capacity and physical activity behaviour in people with ischaemic heart disease ( IHD ) . Methods and results In this single-blind , parallel , two-arm , r and omized controlled trial adults ( n = 171 ) with IHD were r and omized to receive a mobile phone delivered intervention ( HEART ; n = 85 ) plus usual care , or usual care alone ( n = 86 ) . Adult participants aged 18 years or more , with a diagnosis of IHD , were clinical ly stable as out patients , able to perform exercise , able to underst and and write English , and had access to the Internet . The HEART ( Heart Exercise And Remote Technologies ) intervention involved a personalized , automated package of text messages and a secure website with video messages aim ed at increasing exercise behaviour , delivered over 24 weeks . All participants were able to access usual community-based cardiac rehabilitation , which involves encouragement of physical activity and an offer to join a local cardiac support club . All outcomes were assessed at baseline and 24 weeks and included peak oxygen uptake ( PVO2 ; primary outcome ) , self-reported physical activity , health-related quality of life , self-efficacy and motivation ( secondary outcomes ) . Results showed no differences in PVO2 between the two groups ( difference −0.21 ml kg−1 min−1 , 95 % CI : −1.1 , 0.7 ; p = 0.65 ) at 24 weeks . However significant treatment effects were observed for selected secondary outcomes , including leisure time physical activity ( difference 110.2 min/week , 95 % CI : −0.8 , 221.3 ; p = 0.05 ) and walking ( difference 151.4 min/week , 95 % CI : 27.6 , 275.2 ; p = 0.02 ) . There were also significant improvements in self-efficacy to be active ( difference 6.2 % , 95 % CI : 0.2 , 12.2 ; p = 0.04 ) and the general health domain of the SF36 ( difference 2.1 , 95 % CI : 0.1 , 4.1 ; p = 0.03 ) at 24 weeks . The HEART programme was considered likely to be cost-effective for leisure time activity and walking . Conclusions A mobile phone intervention was not effective at increasing exercise capacity over and above usual care . The intervention was effective and probably cost-effective for increasing physical activity and may have the potential to augment existing cardiac rehabilitation services Background Several heart failure studies have shown promising results for implementing telehealthcare . These studies have led to clinical and political interest in telehealthcare as a way to improve heart failure outcomes and lower costs . However , there is a need for large-scale clinical trials with cost-effectiveness assessment s. Methods / design The present study is known as the TeleCare North Heart Failure Trial in Denmark . We are study ing the health effectiveness and cost-effectiveness of a telehealth ( Telekit ) solution compared with usual care for patients with heart failure . The design is a multicenter , two-arm , parallel-group , nonblinded , superiority r and omized controlled trial . Outpatient healthcare centers will be responsible for recruiting eligible participants ( 600 participants are expected ) for the trial in the geographic area of the North Denmark Region . Participants are qualified for inclusion if they have been diagnosed according to national guidelines and are categorized in New York Heart Association class 2 , 3 , or 4 . Patients must have a permanent residence and be motivated to use telehealth care . The primary outcomes are changes in health-related quality of life ( assessed using the Kansas City Cardiomyopathy Question naire , the EuroQol EQ-5D-5L question naire , and the Short Form Health Survey [ SF-36 ] ) and in the incremental cost-effectiveness ratio measured from baseline to follow-up . The secondary outcomes are changes in mortality and in physiological indicators such as blood pressure , pulse , and weight . Discussion The TeleCare North Heart Failure Trial is intended to improve the international evidence base for the health effectiveness and cost-effectiveness of telehealthcare for patients with heart failure . The expectation is that the results of the trial can be generalized to all municipalities in Denmark and serve as an inspiration for further international research .Trial registration Clinical Trials.gov ( NCT02860013 ) . Registered on 28 July 2016 Aim Although cardiac rehabilitation improves physical fitness after a cardiac event , many eligible patients do not participate in cardiac rehabilitation and the beneficial effects of cardiac rehabilitation are often not maintained over time . Home-based training with telemonitoring guidance could improve participation rates and enhance long-term effectiveness . Methods and results We r and omised 90 low-to-moderate cardiac risk patients entering cardiac rehabilitation to three months of either home-based training with telemonitoring guidance or centre-based training . Although training adherence was similar between groups , satisfaction was higher in the home-based group ( p = 0.02 ) . Physical fitness improved at discharge ( p < 0.01 ) and at one-year follow-up ( p < 0.01 ) in both groups , without differences between groups ( home-based p = 0.31 and centre-based p = 0.87 ) . Physical activity levels did not change during the one-year study period ( centre-based p = 0.38 , home-based p = 0.80 ) . Healthcare costs were statistically non-significantly lower in the home-based group ( € 437 per patient , 95 % confidence interval –562 to 1436 , p = 0.39 ) . From a societal perspective , a statistically non-significant difference of € 3160 per patient in favour of the home-based group was found ( 95 % confidence interval –460 to 6780 , p = 0.09 ) and the probability that it was more cost-effective varied between 97 % and 75 % ( willingness-to-pay of € 0 and € 100,000 per quality -adjusted life-years , respectively ) . Conclusion We found no differences between home-based training with telemonitoring guidance and centre-based training on physical fitness , physical activity level or health-related quality of life . However , home-based training was associated with a higher patient satisfaction and appears to be more cost-effective than centre-based training . We conclude that home-based training with telemonitoring guidance can be used as an alternative to centre-based training for low-to-moderate cardiac risk patients entering cardiac rehabilitation Objectives To compare the costs and cost-effectiveness of managing patients with uncontrolled blood pressure ( BP ) using telemonitoring versus usual care from the perspective of the National Health Service ( NHS ) . Design Within trial post hoc economic evaluation of data from a pragmatic r and omised controlled trial using an intention-to-treat approach . Setting 20 socioeconomically diverse general practice s in Lothian , Scotl and . Participants 401 primary care patients aged 29–95 with uncontrolled daytime ambulatory blood pressure ( ABP ) ( ≥135/85 , but < 210/135 mm Hg ) . Intervention Participants were central ly r and omised to 6 months of a telemonitoring service comprising of self-monitoring of BP transmitted to a secure website for review by the attending nurse/doctor and patient , with optional automated patient decision-support by text/email ( n=200 ) or usual care ( n-201 ) . R and omisation was undertaken with minimisation for age , sex , family practice , use of three or more hypertension drugs and self-monitoring history . Main outcome measures Mean difference in total NHS costs between trial arms and blinded assessment of mean cost per 1 mm Hg systolic BP point reduced . Results Home telemonitoring of BP costs significantly more than usual care ( mean difference per patient £ 115.32 ( 95 % CI £ 83.49 to £ 146.63 ; p<0.001 ) ) . Increased costs were due to telemonitoring service costs , patient training and additional general practitioner and nurse consultations . The mean cost of systolic BP reduction was £ 25.56/mm Hg ( 95 % CI £ 16.06 to £ 46.89 ) per patient . Conclusions Over the 6-month trial period , supported telemonitoring was more effective at reducing BP than usual care but also more expensive . If clinical gains are maintained , these additional costs would be very likely to be compensated for by reductions in the cost of future cardiovascular events . Longer-term modelling of costs and outcomes is required to fully examine the cost-effectiveness implication s. Trial registration International St and ard R and omised Controlled Trials , number IS RCT N72614272 Aims The purpose of this prospect i ve study was to investigate whether internet-based remote monitoring offers a safe , practical , and cost-effective alternative to the in-office follow-up visits of patients with an implantable cardioverter defibrillator ( ICD ) . Methods and results Forty-one patients ( 62 ± 10 years , range 41–76 , 83 % male ) with previously implanted ICD were followed for 9 months . One-hundred and nineteen scheduled and 18 unscheduled data transmissions were performed . There were no device-related adverse events . Over 90 % of the patients found the system easy to use . Physicians reported the system as being ‘ very easy ’ or ‘ easy ’ to use and found the data comparable to traditional device interrogation in 99 % of the cases . They were able to address all unscheduled data transmissions remotely . Compared with the in-office visits , remote monitoring required less time from patients ( 6.9 ± 5.0 vs. 182 ± 148 min , P < 0.001 ) and physicians ( 8.4 ± 4.5 vs. 25.8 ± 17.0 min , P < 0.001 ) to complete the follow-up . Substitution of two routine in-office visits during the study by remote monitoring reduced the overall cost of routine ICD follow-up by 524 € per patient ( 41 % ) . Conclusion Remote monitoring offers a safe , feasible , time-saving , and cost-effective solution to ICD follow-up Objectives To investigate the cost-effectiveness of a telehealth intervention for primary care patients with raised cardiovascular disease ( CVD ) risk . Design A prospect i ve within-trial patient-level economic evaluation conducted alongside a r and omised controlled trial . Setting Patients recruited through primary care , and intervention delivered via telehealth service . Participants Adults with a 10-year CVD risk ≥20 % , as measured by the QRISK2 algorithm , with at least 1 modifiable risk factor . Intervention A series of up to 13 scripted , theory-led telehealth encounters with healthcare advisors , who supported participants to make behaviour change , use online re sources , optimise medication and improve adherence . Participants in the control arm received usual care . Primary and secondary outcome measures Cost-effectiveness measured by net monetary benefit at the end of 12 months of follow-up , calculated from incremental cost and incremental quality -adjusted life years ( QALYs ) . Productivity impacts , participant out-of-pocket expenditure and the clinical outcome were presented in a cost-consequences framework . Results 641 participants were r and omised—325 to receive the telehealth intervention in addition to usual care and 316 to receive only usual care . 18 % of participants had missing data on either costs , utilities or both . Multiple imputation was used for the base case results . The intervention was associated with incremental mean per-patient National Health Service ( NHS ) costs of £ 138 ( 95 % CI 66 to 211 ) and an incremental QALY gain of 0.012 ( 95 % CI −0.001 to 0.026 ) . The incremental cost-effectiveness ratio was £ 10 859 . Net monetary benefit at a cost-effectiveness threshold of £ 20 000 per QALY was £ 116 ( 95 % CI −58 to 291 ) , and the probability that the intervention was cost-effective at this threshold value was 0.77 . Similar results were obtained from a complete case analysis . Conclusions There is evidence to suggest that the Healthlines telehealth intervention was likely to be cost-effective at a threshold of £ 20 000 per QALY . Trial registration number IS RCT N27508731 ; Results . Prospect ively registered 05 July 2012 Background Heart failure patients with implantable defibrillators place a significant burden on health care systems . Remote monitoring allows assessment of device function and heart failure parameters , and may represent a safe , effective , and cost-saving method compared to conventional in-office follow-up . Objective We hypothesized that remote device monitoring represents a cost-effective approach . This paper summarizes the economic evaluation of the Evolution of Management Strategies of Heart Failure Patients With Implantable Defibrillators ( EVOLVO ) study , a multicenter clinical trial aim ed at measuring the benefits of remote monitoring for heart failure patients with implantable defibrillators . Methods Two hundred patients implanted with a wireless transmission – enabled implantable defibrillator were r and omized to receive either remote monitoring or the conventional method of in-person evaluations . Patients were followed for 16 months with a protocol of scheduled in-office and remote follow-ups . The economic evaluation of the intervention was conducted from the perspectives of the health care system and the patient . A cost-utility analysis was performed to measure whether the intervention was cost-effective in terms of cost per quality -adjusted life year ( QALY ) gained . Results Overall , remote monitoring did not show significant annual cost savings for the health care system ( € 1962.78 versus € 2130.01 ; P=.80 ) . There was a significant reduction of the annual cost for the patients in the remote arm in comparison to the st and ard arm ( € 291.36 versus € 381.34 ; P=.01 ) . Cost-utility analysis was performed for 180 patients for whom QALYs were available . The patients in the remote arm gained 0.065 QALYs more than those in the st and ard arm over 16 months , with a cost savings of € 888.10 per patient . Results from the cost-utility analysis of the EVOLVO study show that remote monitoring is a cost-effective and dominant solution . Conclusions Remote management of heart failure patients with implantable defibrillators appears to be cost-effective compared to the conventional method of in-person evaluations . Trial Registration Clinical Trials.gov NCT00873899 ; http:// clinical trials.gov/show/NCT00873899 ( Archived by WebCite at http://www.webcitation.org/6H0BOA29f ) Objectives To investigate the long-term cost-effectiveness ( measured as the ratio of incremental NHS cost to incremental quality -adjusted life years ) of a telehealth intervention for patients with raised cardiovascular disease ( CVD ) risk . Design A cohort simulation model developed as part of the economic evaluation conducted alongside the Healthlines r and omised controlled trial . Setting Patients recruited through primary care , and intervention delivered via telehealth service . Participants Participants with a 10-year CVD risk ≥20 % , as measured by the QRISK2 algorithm , and with at least 1 modifiable risk factor , individually r and omised from 42 general practice s in Engl and . Intervention A telehealth service delivered over a 12-month period . The intervention involved a series of responsive , theory-led encounters between patients and trained health information advisors who provided access to information re sources and supported medication adherence and coordination of care . Primary and secondary outcome measures Cost-effectiveness measured by net monetary benefit over the simulated lifetime of trial participants from a UK National Health Service perspective . Results The probability that the intervention was cost-effective depended on the duration of the effect of the intervention . The intervention was cost-effective with high probability if effects persisted over the lifetime of intervention recipients . The probability of cost-effectiveness was lower for shorter duration s of effect . Conclusions The intervention was likely to be cost-effective under a lifetime perspective . Trial registration number IS RCT N27508731 ; Results Abstract Background : Cardiac rehabilitation can reduce mortality of patients with cardiovascular disease , but a frequently low participation rate in rehabilitation programs has been found globally . The objective of the Teledialog study was to assess the cost-utility ( CU ) of a cardiac telerehabilitation ( CTR ) program . The aim of the intervention was to increase the patients ' participation in the CTR program . At discharge , an individualized 3-month rehabilitation plan was formulated for each patient . At home , the patients measured their own blood pressure , pulse , weight , and steps taken for 3 months . Material s and Methods : The analysis was carried out together with a r and omized controlled trial with 151 patients during 2012–2014 . Costs of the intervention were estimated with a health sector perspective following international guidelines for CU . Quality of life was assessed using the 36-Item Short Form Health Survey . Results : The rehabilitation activities were approximately the same in the two groups , but the number of contacts with the physiotherapist was higher among the intervention group . The mean total cost per patient was € 1,700 higher in the intervention group . The quality -adjusted life-years ( QALYs ) gain was higher in the intervention group , but the difference was not statistically significant . The incremental CU ratio was more than € 400,000 per QALY gained . Conclusions : Even though the rehabilitation activities increased , the program does not appear to be cost-effective . The intervention itself was not costly ( less than € 500 ) , and increasing the number of patients may show reduced costs of the devices and make the CTR more cost-effective . Telerehabilitation can increase participation , but the intervention , in its current form , does not appear to be cost-effective IMPORTANCE Most primary care clinicians lack the skills and re sources to offer effective lifestyle and medication ( L&M ) counseling to reduce coronary heart disease ( CHD ) risk . Thus , effective and feasible CHD prevention programs are needed for typical practice setting s. OBJECTIVE To assess the effectiveness , acceptability , and cost-effectiveness of a combined L&M intervention to reduce CHD risk offered in counselor-delivered and web-based formats . DESIGN , SETTING , AND PARTICIPANTS A comparative effectiveness trial in 5 diverse family medicine practice s in North Carolina . Participants were established patients , aged 35 to 79 years , with no known cardiovascular disease , and at moderate to high risk for CHD ( 10-year Framingham Risk Score [ FRS ] , ≥10 % ) . INTERVENTIONS Participants were r and omized to counselor-delivered or web-based format , each including 4 intensive and 3 maintenance sessions . After r and omization , both formats used a web-based decision aid showing potential CHD risk reduction associated with L&M risk-reducing strategies . Participants chose the risk-reducing strategies they wished to follow . MAIN OUTCOMES AND MEASURES The primary outcome was within-group change in FRS at 4-month follow-up . Other measures included st and ardized assessment s of blood pressure , blood lipid levels , lifestyle behaviors , and medication adherence . Acceptability and cost-effectiveness were also assessed . Outcomes were assessed at 4 and 12 months . RESULTS Of 2274 screened patients , 385 were r and omized ( 192 counselor ; 193 web ) : mean age , 62 years ; 24 % African American ; and mean FRS , 16.9 % . Follow-up at 4 and 12 months included 91 % and 87 % of the r and omized participants , respectively . There was a sustained reduction in FRS at both 4 months ( primary outcome ) and 12 months for both counselor-based ( -2.3 % [ 95 % CI , -3.0 % to -1.6 % ] and -1.9 % [ 95 % CI , -2.8 % to -1.1 % ] , respectively ) and web-based groups ( -1.5 % [ 95 % CI , -2.2 % to -0.9 % ] and -1.7 % [ 95 % CI , -2.6 % to -0.8 % ] respectively ) . At 4 months , the adjusted difference in FRS between groups was -1.0 % ( 95 % CI , -1.8 % to -0.1 % ) ( P = .03 ) , and at 12 months , it was -0.6 % ( 95 % CI , -1.7 % to 0.5 % ) ( P = .30 ) . The 12-month costs from the payer perspective were $ 207 and $ 110 per person for the counselor- and web-based interventions , respectively . CONCLUSIONS AND RELEVANCE Both intervention formats reduced CHD risk through 12-month follow-up . The web format was less expensive . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01245686 BACKGROUND To evaluate the long-term cost-effectiveness of two home-based cardiac rehabilitation ( CR ) interventions ( Healthy Weight ( HW ) and Physical Activity ( PA ) ) for patients with cardiovascular disease ( CVD ) , who had been referred to cardiac rehabilitation ( CR ) but had not attended . The interventions consisted of pedometer-based telephone coaching sessions on weight , nutrition and physical activity ( HW group ) or physical activity only ( PA group ) and were compared to a control group who received information brochures about physical activity . METHODS A cost-effectiveness analysis was conducted using data from two r and omised controlled trials . One trial compared HW to PA ( PANACHE study ) , and the second compared PA to usual care . A Markov model was developed which used one risk factor , body mass index ( BMI ) to determine the CVD risk level and mortality . Patient-level data from the trials were used to determine the transitions to CVD states and healthcare related costs . The model was run for separate cohorts of males and females . Univariate and probabilistic sensitivity analysis were conducted to test the robustness of the results . RESULTS Given a willingness-to-pay threshold of $ 50,000/QALY , in the long run , both the HW and PA interventions are cost-effective compared with usual care . While the HW intervention is more effective , it also costs more than both the PA intervention and the control group due to higher intervention costs . However , the HW intervention is still cost-effective relative to the PA intervention for both men and women . Sensitivity analysis suggests that the results are robust . CONCLUSION The results of this paper provide evidence of the long-term cost-effectiveness of home-based CR interventions for patients who are referred to CR but do not attend . Both the HW and PA interventions can be recommended as cost-effective home-based CR programs , especially for people lacking access to hospital services or who are unable to participate in traditional CR programs Objective To assess whether non- clinical staff can effectively manage people at high risk of cardiovascular disease using digital health technologies . Design Pragmatic , multicentre , r and omised controlled trial . Setting 42 general practice s in three areas of Engl and . Participants Between 3 December 2012 and 23 July 2013 we recruited 641 adults aged 40 to 74 years with a 10 year cardiovascular disease risk of 20 % or more , no previous cardiovascular event , at least one modifiable risk factor ( systolic blood pressure ≥140 mm Hg , body mass index ≥30 , current smoker ) , and access to a telephone , the internet , and email . Participants were individually allocated to intervention ( n=325 ) or control ( n=316 ) groups using automated r and omisation stratified by site , minimised by practice and baseline risk score . Interventions Intervention was the Healthlines service ( alongside usual care ) , comprising regular telephone calls from trained lay health advisors following scripts generated by interactive software . Advisors facilitated self management by supporting participants to use online re sources to reduce risk factors , and sought to optimise drug use , improve treatment adherence , and encourage healthier lifestyles . The control group comprised usual care alone . Main outcome measures The primary outcome was the proportion of participants responding to treatment , defined as maintaining or reducing their cardiovascular risk after 12 months . Outcomes were collected six and 12 months after r and omisation and analysed masked . Participants were not masked . Results 50 % ( 148/295 ) of participants in the intervention group responded to treatment compared with 43 % ( 124/291 ) in the control group ( adjusted odds ratio 1.3 , 95 % confidence interval 1.0 to 1.9 ; number needed to treat=13 ) ; a difference possibly due to chance ( P=0.08 ) . The intervention was associated with reductions in blood pressure ( difference in mean systolic −2.7 mm Hg ( 95 % confidence interval −4.7 to −0.6 mm Hg ) , mean diastolic −2.8 ( −4.0 to −1.6 mm Hg ) ; weight −1.0 kg ( −1.8 to −0.3 kg ) , and body mass index −0.4 ( −0.6 to −0.1 ) but not cholesterol −0.1 ( −0.2 to 0.0 ) , smoking status ( adjusted odds ratio 0.4 , 0.2 to 1.0 ) , or overall cardiovascular risk as a continuous measure ( −0.4 , −1.2 to 0.3 ) ) . The intervention was associated with improvements in diet , physical activity , drug adherence , and satisfaction with access to care , treatment received , and care coordination . One serious related adverse event occurred , when a participant was admitted to hospital with low blood pressure . Conclusions This evidence based telehealth approach was associated with small clinical benefits for a minority of people with high cardiovascular risk , and there was no overall improvement in average risk . The Healthlines service was , however , associated with improvements in some risk behaviours , and in perceptions of support and access to care . Trial registration Current Controlled Trials IS RCT N 27508731 Background Finding innovative and cost-efficient care strategies that induce long-term health benefits in cardiac patients constitutes a big challenge today . The aim of this Telerehab III follow-up study was to assess whether a 6-month additional cardiac telerehabilitation programme could induce long-term health benefits and remain cost-efficient after the tele-intervention ended . Methods and results A total of 126 cardiac patients first completed the multicentre , r and omised controlled telerehabilitation trial ( Telerehab III , time points t0 to t1 ) . They consequently entered the follow-up study ( t1 ) with evaluations 2 years later ( t2 ) . A quantitative analysis of peak aerobic capacity ( VO2 peak , primary endpoint ) , international physical activity question naire self-reported physical activity and HeartQoL quality of life ( secondary endpoints ) was performed . The incremental cost-effectiveness ratio was calculated . Even though a decline in VO2 peak ( 24 ± 8 ml/[min*kg ] at t1 and 22 ± 6 ml/[min*kg ] at t2 ; P ≤ 0.001 ) was observed within the tele-intervention group patients ; overall they did better than the no tele-intervention group ( P = 0.032 ) . Dividing the incremental cost ( −€878/patient ) by the differential incremental quality -adjusted life years ( QALYs ) ( 0.22 QALYs ) yielded an incremental cost-effectiveness ratio of –€3993/QALY . Conclusions A combined telerehabilitation and centre-based programme , followed by transitional telerehabilitation induced persistent health benefits and remained cost-efficient up to 2 years after the end of the intervention . A partial decline of the benefits originally achieved did occur once the tele-intervention ended . Healthcare professionals should reflect on how innovative cost-efficient care models could be implemented in st and ard care . Future research should focus on key behaviour change techniques in technology-based interventions that enable full persistence of long-term behaviour change and health benefits . This study is registered in the IS RCT N registry ( IS RCT N29243064 ) OBJECTIVE To evaluate the cost-effectiveness of a telephonic disease management ( DM ) intervention in heart failure ( HF ) . STUDY DESIGN R and omized controlled trial of telephonic DM among 1069 community-dwelling patients with systolic HF ( SHF ) and diastolic HF performed between 1999 and 2003 . The enrollment period was 18 months per subject . METHODS Bootstrap-re sample d incremental cost-effectiveness ratios ( ICERs ) were computed and compared across groups . Direct medical costs were obtained from a medical record review that collected records from 92 % of patients ; 66 % of records requested were obtained . RESULTS Disease management produced statistically significant survival advantages among all patients ( 17.4 days , P = .04 ) , among patients with New York Heart Association ( NYHA ) class III/IV symptoms ( 47.7 days , P = .02 ) , and among patients with SHF ( 24.2 days , P = .01 ) . Analyses of direct medical and intervention costs showed no cost savings associated with the intervention . For all patients and considering all-cause medical care , the ICER was $ 146 870 per quality -adjusted life-year ( QALY ) gained , while for patients with NYHA class III/IV symptoms and patients with SHF , the ICERs were $ 67 784 and $ 95 721 per QALY gained , respectively . Costs per QALY gained were $ 101 120 for all patients , $ 72 501 for patients with SHF , and $ 41 348 for patients with NYHA class III/IV symptoms . CONCLUSIONS The intervention was effective but costly to implement and did not reduce utilization . It may not be cost-effective in other broadly representative sample s of patients . However , with program cost reductions and proper targeting , this program may produce life-span increases at costs that are less than $ 100 000 per QALY gained Objective To examine the costs and cost effectiveness of telehealth in addition to st and ard support and treatment , compared with st and ard support and treatment . Design Economic evaluation nested in a pragmatic , cluster r and omised controlled trial . Setting Community based telehealth intervention in three local authority areas in Engl and . Participants 3230 people with a long term condition ( heart failure , chronic obstructive pulmonary disease , or diabetes ) were recruited into the Whole Systems Demonstrator telehealth trial between May 2008 and December 2009 . Of participants taking part in the Whole Systems Demonstrator telehealth question naire study examining acceptability , effectiveness , and cost effectiveness , 845 were r and omised to telehealth and 728 to usual care . Interventions Intervention participants received a package of telehealth equipment and monitoring services for 12 months , in addition to the st and ard health and social care services available in their area . Controls received usual health and social care . Main outcome measure Primary outcome for the cost effectiveness analysis was incremental cost per quality adjusted life year ( QALY ) gained . Results We undertook net benefit analyses of costs and outcomes for 965 patients ( 534 receiving telehealth ; 431 usual care ) . The adjusted mean difference in QALY gain between groups at 12 months was 0.012 . Total health and social care costs ( including direct costs of the intervention ) for the three months before 12 month interview were £ 1390 ( € 1610 ; $ 2150 ) and £ 1596 for the usual care and telehealth groups , respectively . Cost effectiveness acceptability curves were generated to examine decision uncertainty in the analysis surrounding the value of the cost effectiveness threshold . The incremental cost per QALY of telehealth when added to usual care was £ 92 000 . With this amount , the probability of cost effectiveness was low ( 11 % at willingness to pay threshold of £ 30 000 ; > 50 % only if the threshold exceeded about £ 90 000 ) . In sensitivity analyses , telehealth costs remained slightly ( non-significantly ) higher than usual care costs , even after assuming that equipment prices fell by 80 % or telehealth services operated at maximum capacity . However , the most optimistic scenario ( combining reduced equipment prices with maximum operating capacity ) eliminated this group difference ( cost effectiveness ratio £ 12 000 per QALY ) . Conclusions The QALY gain by patients using telehealth in addition to usual care was similar to that by patients receiving usual care only , and total costs associated with the telehealth intervention were higher . Telehealth does not seem to be a cost effective addition to st and ard support and treatment . Trial registration IS RCT N43002091 Abstract Aims . The purpose of the present study was to compare the costs of home blood pressure ( BP ) telemonitoring ( HBPM ) with the costs of conventional office BP monitoring . In a r and omized controlled trial , 105 hypertensive patients performed HBPM and 118 patients received usual care with conventional office BP monitoring during 6 months . Costs were quantified from the healthcare perspective . Non-parametric simulations were performed to quantify the uncertainty around the mean estimates and cost-effectiveness acceptability curves were made . Major findings . Systolic and diastolic daytime and night-time ambulatory BP ( ABP ) were reduced in both groups . The uncertainty around the incremental cost effectiveness ratio point estimates was considerable for both systolic and diastolic ABP . For systolic ABP , the difference in cost effectiveness ratio between the two groups was 256 Danish kroner (DKK)/mmHg [ 95 % uncertainty interval , UI −860 to 4544 ] . For diastolic ABP , the difference in cost effectiveness ratio between the two groups was 655 DKK/mmHg [ 95 % UI −674 to 69315 ] . Medication and consultation costs were lowest in the intervention group , but were offset by the cost of the telemonitoring equipment . Conclusions . Cost-effectiveness analysis showed that telemonitoring of home BP was more costly compared with usual monitoring of office BP . The cost-effectiveness result is surrounded with considerable uncertainty . Trial registration : Clinical Trials.gov identifier : NCT282334 Background Notwithst and ing the cardiovascular disease epidemic , current budgetary constraints do not allow for budget expansion of conventional cardiac rehabilitation programmes . Consequently , there is an increasing need for cost-effectiveness studies of alternative strategies such as telerehabilitation . The present study evaluated the cost-effectiveness of a comprehensive cardiac telerehabilitation programme . Design and methods This multi-centre r and omized controlled trial comprised 140 cardiac rehabilitation patients , r and omized ( 1:1 ) to a 24-week telerehabilitation programme in addition to conventional cardiac rehabilitation ( intervention group ) or to conventional cardiac rehabilitation alone ( control group ) . The incremental cost-effectiveness ratio was calculated based on intervention and health care costs ( incremental cost ) , and the differential incremental quality adjusted life years ( QALYs ) gained . Results The total average cost per patient was significantly lower in the intervention group ( € 2156 ± € 126 ) than in the control group ( € 2720 ± € 276 ) ( p = 0.01 ) with an overall incremental cost of € –564.40 . Dividing this incremental cost by the baseline adjusted differential incremental QALYs ( 0.026 QALYs ) yielded an incremental cost-effectiveness ratio of € –21,707/QALY . The number of days lost due to cardiovascular rehospitalizations in the intervention group ( 0.33 ± 0.15 ) was significantly lower than in the control group ( 0.79 ± 0.20 ) ( p = 0.037 ) . Conclusions This paper shows the addition of cardiac telerehabilitation to conventional centre-based cardiac rehabilitation to be more effective and efficient than centre-based cardiac rehabilitation alone . These results are useful for policy makers charged with deciding how limited health care re sources should best be allocated in the era of exploding need |
1,877 | 25,179,793 | Our systematic review provides no evidence supporting an increased risk for stroke associated with sub clinical thyroid dysfunction . | Sub clinical thyroid dysfunction has been associated with coronary heart disease , but the risk of stroke is unclear .
Our aim is to combine the evidence on the association between sub clinical thyroid dysfunction and the risk of stroke in prospect i ve cohort studies . | Sub clinical hypothyroidism ( sHT ) affects 5 - 15 % of the general population ; however , the need of lifelong L-T(4 ) therapy is still controversial . As myocardium is a main target of thyroid hormone action , we investigated whether sHT induces cardiovascular alterations . Twenty sHT patients were r and omly assigned to receive placebo or L-T(4 ) therapy and were followed for 1 yr . Twenty sex- and age-matched normal subjects served as controls . Doppler echocardiography and videodensitometric analysis were performed in all subjects . Myocardium textural parameters were obtained as mean gray levels , which were then used to calculate the cyclic variation index ( CVI ; percent systolic/diastolic change in mean gray levels ) . Patients had a significantly higher isovolumic relaxation time ( 3.1 + /- 0.5 vs. 2.6 + /- 0.6 ; P < 0.03 ) , peak A ( 0.77 + /- 0.16 vs. 0.56 + /- 0.13 m/s ; P < 0.01 ) , and preejection/ejection time ( PEP/ET ) ratio ( 0.72 + /- 0.05 vs. 0.57 + /- 0.06 ; P < 0.03 ) and a lower CVI ( P < 0.0001 ) than controls . CVI was inversely related to TSH level ( P < 0.0001 ) and PEP/ET ratio ( P < 0.01 ) . L-T(4)-treated patients showed a significant reduction of the PEP/ET ratio ( P < 0.05 ) , peak A ( P < 0.05 ) , and isovolumic relaxation time ( P < 0.05 ) along with a normalization of CVI . Conversely , no changes were observed in the placebo-treated group . In conclusion , sHT affects both myocardial structure and contractility . These alterations may be reversed by L-T(4 ) therapy Sub clinical hypothyroidism ( sHT ) is associated with dyslipidemia and enhanced cardiovascular risk . We assessed carotid artery intima-media thickness ( IMT , high-resolution ultrasonography ) and lipoprotein profile in 45 sHT patients ( aged 37 + /- 11 yr ) at baseline and after 6 months of r and omized , placebo-controlled L-T(4 ) replacement . In comparison with 32 age- and sex-matched controls , sHT patients had elevated total and low-density lipoprotein ( LDL ) cholesterol and ApoB levels ( P = 0.002 , P = 0.0007 , and P = 0.01 , respectively ) and higher mean-IMT values ( P < 0.0001 ) . In stepwise regression analysis , mean-IMT was positively related ( r(2 ) = 0.71 , P < 0.0001 ) to age , TSH , and LDL cholesterol . L-T(4 ) replacement significantly reduced both total and LDL cholesterol ( P < 0.0001 for both ) and mean-IMT ( by 11 % , P < 0.0001 ) . The decrement in IMT was directly related to the decrements of both total cholesterol and TSH ( P = 0.02 and P = 0.0001 , respectively ) . We conclude that early carotid artery wall alterations are present in sHT patients . Whether such IMT increase is related to an early atherosclerotic involvement of the arterial wall can not be clearly decided on the basis of the present results . However , the fact that L-T(4 ) replacement therapy was able to improve both the atherogenic lipoprotein profile and intima-media thickening suggests that lipid infiltration of arterial wall may represent a major mechanism underlying IMT increase in sub clinical hypothyroidism BACKGROUND Sub clinical hypothyroidism ( SCH ) is postulated to increase stroke risk via atherogenic changes associated with abnormal thyroid function . However , the direct relationship of SCH with subsequent stroke is poorly studied . METHODS In this nested case-cohort study , we prospect ively evaluated the association between any SCH and severity of SCH in relation to incident ischemic stroke risk among postmenopausal women in the Women 's Health Initiative Observational Study . Trained Women 's Health Initiative staff , masked to thyroid status , adjudicated stroke cases . We assessed thyroid function using baseline blood specimens . Women with normal free thyroxine levels and thyrotropin ( TSH ) levels ≥4.69 mU/L were considered to have SCH . Primary analysis included 639 ischemic stroke cases and 2927 r and omly selected subcohort members with an average of seven years of follow-up . RESULTS The multivariable adjusted hazard ratios ( HR ) from weighted Cox models were 1.06 ( 95 % confidence interval [ CI ] : 0.77 , 1.46 ) and 0.99 ( 95 % CI : 0.67 , 1.47 ) for women with any SCH and with mild SCH ( TSH 4.69 to 6.99 mU/L ) , when compared with women with normal thyroid function . The HR for moderate/severe SCH ( TSH ≥7.00 mU/L ) was modestly elevated ( HR : 1.22 ; 95 % CI : 0.73 , 2.05 ) . CONCLUSIONS We found no evidence to suggest an association between SCH and ischemic stroke among healthy postmenopausal women Background Health technology assessment s of surgical interventions frequently require the inclusion of non-r and omised evidence . Literature search strategies employed to identify this evidence often exclude a method ological component because of uncertainty surrounding the use of appropriate search terms . This can result in the retrieval of a large number of irrelevant records . Method ological filters would help to minimise this , making literature search ing more efficient . Methods An objective approach was employed to develop MEDLINE and EMBASE filters , using a reference st and ard derived from screening the results of an electronic literature search that contained only subject-related terms . C and i date terms for MEDLINE ( N = 37 ) and EMBASE ( N = 35 ) were derived from examination of the records of the reference st and ard . The filters were vali date d on two sets of studies that had been included in previous health technology assessment s. Results The final filters were highly sensitive ( MEDLINE 99.5 % , EMBASE 100 % , MEDLINE / EMBASE combined 100 % ) with precision ranging between 16.7 % – 21.1 % , specificity 35.3 % – 43.5 % , and a reduction in retrievals of over 30 % . Against the validation st and ards , the individual filters retrieved 85.2 % – 100 % of records . In combination , however , the MEDLINE and EMBASE filters retrieved 100 % against both validation st and ards with a reduction in retrieved records of 28.4 % and 30.1 % Conclusion The MEDLINE and EMBASE filters were highly sensitive and substantially reduced the number of records retrieved , indicating that they are useful tools for efficient literature search ing CONTEXT Data regarding the association between sub clinical hypothyroidism and cardiovascular disease outcomes are conflicting among large prospect i ve cohort studies . This might reflect differences in participants ' age , sex , thyroid-stimulating hormone ( TSH ) levels , or preexisting cardiovascular disease . OBJECTIVE To assess the risks of coronary heart disease ( CHD ) and total mortality for adults with sub clinical hypothyroidism . DATA SOURCES AND STUDY SELECTION The data bases of MEDLINE and EMBASE ( 1950 to May 31 , 2010 ) were search ed without language restrictions for prospect i ve cohort studies with baseline thyroid function and subsequent CHD events , CHD mortality , and total mortality . The reference lists of retrieved articles also were search ed . DATA EXTRACTION Individual data on 55,287 participants with 542,494 person-years of follow-up between 1972 and 2007 were supplied from 11 prospect i ve cohorts in the United States , Europe , Australia , Brazil , and Japan . The risk of CHD events was examined in 25,977 participants from 7 cohorts with available data . Euthyroidism was defined as a TSH level of 0.50 to 4.49 mIU/L. Sub clinical hypothyroidism was defined as a TSH level of 4.5 to 19.9 mIU/L with normal thyroxine concentrations . RESULTS Among 55,287 adults , 3450 had sub clinical hypothyroidism ( 6.2 % ) and 51,837 had euthyroidism . During follow-up , 9664 participants died ( 2168 of CHD ) , and 4470 participants had CHD events ( among 7 studies ) . The risk of CHD events and CHD mortality increased with higher TSH concentrations . In age- and sex-adjusted analyses , the hazard ratio ( HR ) for CHD events was 1.00 ( 95 % confidence interval [ CI ] , 0.86 - 1.18 ) for a TSH level of 4.5 to 6.9 mIU/L ( 20.3 vs 20.3/1000 person-years for participants with euthyroidism ) , 1.17 ( 95 % CI , 0.96 - 1.43 ) for a TSH level of 7.0 to 9.9 mIU/L ( 23.8/1000 person-years ) , and 1.89 ( 95 % CI , 1.28 - 2.80 ) for a TSH level of 10 to 19.9 mIU/L ( n = 70 events/235 ; 38.4/1000 person-years ; P < .001 for trend ) . The corresponding HRs for CHD mortality were 1.09 ( 95 % CI , 0.91 - 1.30 ; 5.3 vs 4.9/1000 person-years for participants with euthyroidism ) , 1.42 ( 95 % CI , 1.03 - 1.95 ; 6.9/1000 person-years ) , and 1.58 ( 95 % CI , 1.10 - 2.27 , n = 28 deaths/333 ; 7.7/1000 person-years ; P = .005 for trend ) . Total mortality was not increased among participants with sub clinical hypothyroidism . Results were similar after further adjustment for traditional cardiovascular risk factors . Risks did not significantly differ by age , sex , or preexisting cardiovascular disease . CONCLUSIONS Sub clinical hypothyroidism is associated with an increased risk of CHD events and CHD mortality in those with higher TSH levels , particularly in those with a TSH concentration of 10 mIU/L or greater Sub clinical hypothyroidism ( sHT ) is associated with enhanced cardiovascular risk . To test the hypothesis that patients with sHT are characterized by endothelial dysfunction and impaired nitric oxide ( NO ) availability , in 14 patients [ serum cholesterol , 218 + /- 41 mg/dl ( 5.6 + /- 0.9 mM ) ] and 28 euthyroid subjects , subdivided into groups A and B [ serum cholesterol , 170 + /- 19 mg/dl ( 4.4 + /- 0.5 mM ) and 217 + /- 21 mg/dl ( 5.6 + /- 0.5 mM ) , respectively ] , we studied the forearm blood flow ( strain-gauge plethysmography ) response to intrabrachial acetylcholine , an endothelium-dependent vasodilator , at baseline and during infusion of N(G)-monomethyl-L-arginine ( L-NMMA ) , a NO synthase inhibitor . Response to sodium nitroprusside and minimal forearm vascular resistances were also evaluated . In sHT patients , vasodilation to acetylcholine was reduced , compared with group B ( + 358 + /- 29 % vs. + 503 + /- 19 % , P = 0.0003 ) and group A ( 663 + /- 65 % , P = 0.02 vs. group B and P = 0.0002 vs. sHT ) . L-NMMA blunted the vasodilation to acetylcholine in groups A and B ( 49.1 + /- 6.3 % and 42.7 + /- 5.5 % maximal forearm blood flow reduction , respectively , P < 0.0001 vs. acetylcholine ) , whereas it was ineffective in sHT patients ( 12.8 + /- 2.5 % ) . Response to sodium nitroprusside and minimal vascular resistances were similar . In sHT ( n = 9 ) patients , 6 months of euthyroidism by levothyroxine replacement increased acetylcholine-vasodilation and restored L-NMMA inhibition . Patients with sHT are characterized by endothelial dysfunction result ing from a reduction in NO availability , an alteration partially independent of dyslipidemia and reversed by levothyroxine supplementation CONTEXT Sub clinical hypothyroidism ( SCH ) is defined as raised serum TSH levels with circulating thyroid hormones within the reference range . It is uncertain whether treatment of SCH with L-thyroxine improves cardiovascular ( CV ) risk factors and quality of life . OBJECTIVE The objective of the study was to assess CV risk factors and patient-reported outcomes after treatment . DESIGN This was a r and omized , double-blind , crossover study of L-thyroxine and placebo . SETTING The study was conducted with community-dwelling patients . PATIENTS One hundred patients [ mean age ( sd ) 53.8 ( 12 ) yr , 81 females ] with SCH [ mean TSH 6.6 ( 1.3 ) mIU/liter ] without previously treated thyroid or vascular disease . INTERVENTION Intervention consisted of 100 microg L-thyroxine or placebo daily for 12 wk each . MEASUREMENTS Primary parameters were total cholesterol ( TC ) and endothelial function [ brachial artery flow-mediated dilatation ( FMD ) ] , an early marker of atherosclerosis . Patient-reported outcomes were also assessed . RESULTS L-thyroxine treatment reduced TC ( vs. placebo ) from 231.6 to 220 mg/dl , P < 0.001 ; low-density lipoprotein cholesterol from 142.9 to 131.3 mg/dl , P < 0.05 ; waist to hip ratio from 0.83 to 0.81 , P < 0.006 ; and improved FMD from 4.2 to 5.9 % , P < 0.001 . Multivariate analysis showed that increased serum free T(4 ) level was the most significant variable predicting reduction in TC or improvement in FMD . Furthermore , the symptom of tiredness improved on L-thyroxine therapy , but other patient-reported outcomes were not significantly different after correction for multiple comparisons . CONCLUSION SCH treated by L-thyroxine leads to a significant improvement in CV risk factors and symptoms of tiredness . The CV risk factor reduction is related to the increased level of achieved free T(4 ) concentration BACKGROUND In dialysis patients , the prevalence of thyroid disorders and their impact on specific cardiovascular ( CV ) events and mortality are largely unknown . The aim of the present study was to analyze whether sub clinical thyroid disorders were associated with CV events and mortality . STUDY DESIGN Prospect i ve multicenter cohort study . SETTING & PARTICIPANTS Thyroid status and clinical outcomes were explored in 1,000 diabetic hemodialysis patients from 178 centers in Germany . PREDICTOR Thyroid status , defined by the following cutoff values : euthyroidism ( thyrotropin [ TSH ] , 0.30 - 4.0 mIU/L ; free triiodothyronine [ T3 ] , 2.7 - 7.6 pmol/L ; and free thyroxine [ T4 ] , 11.0 - 24.0 pmol/L ) , sub clinical hyperthyroidism ( TSH<0.3 mIU/L and free T3/free T4 within reference ranges ) , sub clinical hypothyroidism ( TSH , 4.1 - 15.0 mIU/L and free T3/free T4 within reference ranges ) , euthyroid sick syndrome ( free T3<2.7 pmol/L and TSH/free T4 low or within reference ranges ) . OUTCOMES During 4 years ' follow-up , prespecified adjudicated end points were determined : sudden cardiac death , myocardial infa rct ion , stroke , combined CV events , and overall mortality . Short-term effects within the first 12 months were contrasted to long-term effects ( years 2 - 4 ) . MEASUREMENTS TSH , free T3 , and free T4 levels at baseline . RESULTS Euthyroidism was present in 78.1 % of patients ; sub clinical hyperthyroidism , in 13.7 % ; and sub clinical hypothyroidism , in 1.6 % . Euthyroid sick syndrome was exhibited by 5.4 % of patients . The adjusted short-term risk of sudden cardiac death was more than doubled ( HR , 2.03 ; 95 % CI , 0.94 - 4.36 ) in patients with sub clinical hyperthyroidism , and similarly for patients with euthyroid sick syndrome ( HR , 2.74 ; 95 % CI , 0.94 - 7.98 ) compared with patients with euthyroidism . Short-term mortality was increased almost 3-fold for patients with euthyroid sick syndrome ( HR , 2.97 ; 95 % CI , 1.66 - 5.29 ) , but this effect was not seen in the long term . Sub clinical hypothyroidism was not associated with CV events or all-cause mortality . Risks of stroke and myocardial infa rct ion were not affected meaningfully by thyroid disorders . LIMITATIONS Observational study design . CONCLUSIONS Sudden cardiac death may be influenced by sub clinical hyperthyroidism and euthyroid sick syndrome in the short term . Furthermore , euthyroid sick syndrome is associated strongly with mortality in hemodialysis patients . Regular assessment of thyroid status may help estimate the cardiac risk of dialysis patients CONTEXT Despite the equivocal outcomes of r and omized controlled trials , general clinical opinion favors screening and treatment of elderly individuals with sub clinical thyroid disorders . OBJECTIVES To determine whether sub clinical thyroid dysfunction should be treated in old age and the long-term impact of thyroid dysfunction on performance and survival in old age . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve , observational , population -based follow-up study within the Leiden 85-Plus Study of 87 % of a 2-year birth cohort ( 1912 - 1914 ) in the municipality of Leiden , the Netherl and s. A total of 599 participants were followed up from age 85 years through age 89 years ( mean [ SD ] follow-up , 3.7 [ 1.4 ] years ) . MAIN OUTCOME MEASURES Complete thyroid status at baseline ; disability in daily life , depressive symptoms , cognitive function , and mortality from age 85 years through 89 years . RESULTS Plasma levels of thyrotropin and free thyroxine were not associated with disability in daily life , depressive symptoms , and cognitive impairment at baseline or during follow-up . Increasing levels of thyrotropin were associated with a lower mortality rate that remained after adjustments were made for baseline disability and health status . The hazard ratio ( HR ) for mortality per SD increase of 2.71 mIU/L of thyrotropin was 0.77 ( 95 % confidence interval [ CI ] , 0.63 - 0.94 ; P = .009 ) . The HR for mortality per SD increase of 0.21 ng/dL ( 2.67 pmol/L ) of free thyroxine increased 1.16-fold ( 95 % CI , 1.04 - 1.30 ; P = .009 ) . CONCLUSIONS In the general population of the oldest old , elderly individuals with abnormally high levels of thyrotropin do not experience adverse effects and may have a prolonged life span . However , evidence for not treating elderly individuals can only come from a well- design ed , r and omized placebo-controlled clinical trial No consensus exists whether sub clinical thyroid disease should be treated or just observed . Untreated overt thyroid disease is associated with increased risk of cardiovascular disease , and this study was conducted to assess the risk of cardiovascular events in sub clinical thyroid disease . The population -based prospect i ve study was conducted in Denmark . A total of 609 subjects from general practice aged 50 years or above with normal left ventricular function were examined . During a median of 5 years of follow-up , major cardiovascular events were documented . In subjects with abnormal TSH at baseline , information about potential thyroid treatment during follow-up was obtained from case reports and mailings . At baseline , 549 ( 90.7 % ) were euthyroid ( TSH 0.40 - 4.00 mU/l ) , 31 ( 5.1 % ) were sub clinical hypothyroid ( TSH>4.00 mU/l ) , and 25 ( 4.1 % ) were sub clinical hyperthyroid ( TSH<0.40 mU/l ) . 1 overt hyperthyroid and 3 overt hypothyroid participants were excluded from the analyses . At baseline , the levels of NT-proBNP were inversely associated with the levels of TSH ; the lower the levels of TSH , the higher the NT-proBNP concentration . During follow-up , 88 participants died , 81 had a major cardiovascular event , and 28 had a stroke . The incidence of stroke was increased among subjects with sub clinical hyperthyroidism , HR 3.39 ( 95 % CI 1.15 - 10.00 , p=0.027 ) after adjusting for sex , age , and atrial fibrillation . Sub clinical hypothyroidism was not related with any of the outcome measurements . Sub clinical hyperthyroidism seems to be a risk factor of developing major cardiovascular events , especially stroke in older adults from the general population with normal left ventricular function |
1,878 | 23,780,706 | There are very few long-term studies to date examining green or black tea for the primary prevention of CVD . | BACKGROUND There is increasing evidence that both green and black tea are beneficial for cardiovascular disease ( CVD ) prevention .
OBJECTIVES To determine the effects of green and black tea on the primary prevention of CVD . | BACKGROUND Green tea polyphenols ( GTPs ) have significant antioxidant and antiinflammatory activities , and prior short‐term studies suggest that these compounds may improve photoaging skin . OBJECTIVES To evaluate the long‐term effects of oral GTPs on the clinical and histologic characteristics of photoaging skin . MATERIAL S AND METHODS Double‐blind , placebo‐controlled trial of 56 women aged 25 to 75 r and omized to 250 mg GTPs or placebo twice daily for 2 years . A blinded dermatologist scored the appearance of photodamaged facial skin at 0 , 6 , 12 , and 24 months . A blinded dermatopathologist scored the histologic characteristics of sun‐exposed arm skin at 0 and 24 months . RESULTS Clinical assessment of facial skin revealed that the GTP group had significant improvement in overall solar damage at 6 months ( p=.02 ) and significant improvement in erythema and telangiectasias at 12 months ( p=.02 ) . The placebo group did not have significant improvements in these parameters at 6 months or 12 months . There were no statistically significant differences in other photoaging parameters at 6 , 12 , or 24 months in the GTP or placebo groups . Histopathologic analysis of sunexposed arm skin showed no statistically significant difference in photoaging parameters in the GTP group or the placebo group at 24 months . CONCLUSIONS Long‐term supplementation with oral GTPs was not superior to placebo in improving clinical or histologic photoaging parameters after 24 months of use . Funding and material s for this study were provided by Nu Skin , Provo , Utah . Dale Kern is an employee of Nu Skin International Green tea ( GT ) consumption is known to be associated with enhanced cardiovascular and metabolic health . The purpose of this study is to examine the hypothesis that supplementation with GT alters insulin resistance and associated cardiovascular risk factors in obese , hypertensive patients . In a double-blind , placebo-controlled trial , 56 obese , hypertensive subjects were r and omized to receive a daily supplement of 1 capsule that contained either 379 mg of GT extract ( GTE ) or a matching placebo , for 3 months . At baseline and after 3 months of treatment , the anthropometric parameters , blood pressure , plasma lipid levels , glucose levels , creatinine levels , tumor necrosis factor α levels , C-reactive protein levels , total antioxidant status , and insulin levels were assessed . Insulin resistance was evaluated according to the homeostasis model assessment -insulin resistance protocol . After 3 months of supplementation , both systolic and diastolic blood pressures had significantly decreased in the GTE group as compared with the placebo group ( P < .01 ) . Considerable ( P < .01 ) reductions in fasting serum glucose and insulin levels and insulin resistance were observed in the GTE group when compared with the placebo group . Serum tumor necrosis factor α and C-reactive protein were significantly lower , whereas total antioxidant status increased in the GTE group compared with the placebo ( P < .05 ) . Supplementation also contributed to significant ( P < .05 ) decreases in the total and low-density lipoprotein cholesterol and triglycerides , but an increase in high-density lipoprotein cholesterol . In conclusion , daily supplementation with 379 mg of GTE favorably influences blood pressure , insulin resistance , inflammation and oxidative stress , and lipid profile in patients with obesity-related hypertension Epidemiological surveys suggest that a higher intake of tea may be associated with a lower risk of CHD . There is accumulating evidence that postpr and ial lipaemia makes a substantial contribution to the incidence of CHD . Our aim was , therefore , to evaluate the effect of tea catechins ( major ingredients in green tea ) on postpr and ial lipid responses in human subjects after the consumption of test meals . In a r and omized triple-crossover design , nine male subjects with mild or borderline hypertriacylglycerolaemia consumed 10 ( control ) , 224 ( moderate dose ) and 674 mg ( high dose ) of the assigned tea catechins three times each along with a st and ardized light meal consisting of a piece of bread spread with 20 g butter . Plasma lipids were measured in the fasting state and 1 , 2 , 3 , 4 and 6 h after consuming the light meal . Results showed that , compared with the control , moderate and high doses of tea catechins reduced the incremental area under the plasma triacylglycerol curves by 15.1 and 28.7 % , respectively . Next , the rapid elevation of remnant-like particle cholesterol was significantly inhibited by a high dose of tea catechins 2 h after consuming the light meal ( P<0.01 ) . In the range of tea catechin dosages , no significant differences were observed in the postpr and ial responses for plasma total cholesterol or NEFA at any time point . In conclusion , this trial demonstrated that tea catechins attenuated the postpr and ial increase in plasma triacylglycerol levels following a fat load . These results may provide evidence for one of the possible mechanisms involved in lowering the incidence of CVD , and may prove useful in further studies on the beneficial health effects of tea drinking Dietary flavonoid intake has been reported to be inversely associated with the incidence of coronary artery disease . To clarify the possible role of tea flavonoids in the prevention of atherosclerosis , we investigated the effects of tea flavonoids on the susceptibility of low-density lipoprotein ( LDL ) to oxidative modification . In an in vitro study , catechins or theaflavins ( 25 - 400 mumol/L ) were added to plasma and incubated for 3 h at 37 degrees C. Then , the LDL fraction was separated by ultracentrifugation . The oxidizability of LDL was estimated by measuring conjugated diene , thiobarbituric acid-reactive substances ( TBARS ) , and lipid peroxides after cupric sulfate was added . TBARS and lipid peroxides in the supernates were also measured after incubation with macrophages . Catechins significantly ( P < 0.01 by ANOVA ) and dose-dependently prolonged the lag time before initiation of oxidation . Among the catechins , epigallocatechin gallate exerted the most marked effect , prolonging the oxidation lag time more than vitamin E at the same molar concentration . Theaflavins exerted stronger inhibitory effects than catechins . Macrophage-mediated LDL oxidation was also inhibited by adding these tea flavonoids to the plasma sample s. In an in vivo study , 14 healthy volunteers consumed 750 mL black tea/d for 4 wk . After the subjects had consumed tea for 4 wk , the lag time before LDL oxidation was significantly ( P < 0.01 ) prolonged from 54 to 62 min . This minor prolongation occurred despite much lower plasma flavonoids than were used in vitro . No significant change was observed in eight control volunteers . LDL exposed to tea flavonoids in vitro or in vivo reduced oxidizability . We speculate that tea flavonoids may have a role in ameliorating atherosclerosis BACKGROUND Tea has been associated with a reduced risk of cardiovascular disease . One proposed mechanism of this risk reduction involves inhibition of lipoprotein oxidation in vivo by antioxidant polyphenolic compounds derived from tea . However , controlled interventions uniformly failed to show that ingestion of tea can inhibit LDL oxidation ex vivo . The absence of effects in previous studies may be due to the isolation of LDL particles from polyphenolic compounds that are present in the aqueous phase of serum . OBJECTIVE The objective of this study was to examine the acute effects of ingestion of black and green tea on ex vivo Cu(2+)-induced lipoprotein oxidation without prior isolation of lipoproteins from serum . DESIGN The acute effects of 4 hot drinks-green tea and black tea ( each at a dose equivalent to 4 st and ard cups ) , water matched to the teas for caffeine content , and water-were assessed in 20 healthy men by using a Latin-square design . The lag time to lipoprotein diene formation , slope of the propagation phase of the oxidation curve , and area under the oxidation curve were calculated . Urinary concentrations of 4-O-methylgallic acid were used as a marker of uptake and metabolism of polyphenolic compounds from tea . RESULTS Significant increases in urinary 4-O-methylgallic acid for black and green tea ( P < 0 . 0001 ) were observed . Caffeine did not significantly influence lipoprotein oxidation . Compared with the water control , there was a greater lag time for black tea ( 5.4 + /- 2.9 min ; P = 0.05 ) that was of borderline significance and a similar trend for green tea ( 4.4 + /- 2.8 min ; P = 0.17 ) . Slope and area under the oxidation curve were not altered . CONCLUSION Black tea has a mild acute effect on ex vivo lipoprotein oxidation in human serum . 2000;71:-7 Prospect i ve studies suggest that tea may protect against cardiovascular disease . A potential mechanism for such an effect involves inhibition of lipid peroxidation by polyphenolic antioxidants derived from tea . Our objective was to determine whether regular ingestion of tea could inhibit in vivo lipid peroxidation . Two controlled intervention studies assessed the effects of regular ingestion of tea on lipid peroxidation determined by measurement of urinary F(2)-isoprostane excretion . Study 1 : The effects of 1000 mL/d of green tea and black tea were compared with hot water containing caffeine in 13 subjects with elevated blood pressure using a r and omized 3-period ( 7 d each ) crossover design . Study 2 : The effects of 1250 mL/d of black tea were compared with hot water in 22 subjects with mildly raised serum total cholesterol concentrations using a r and omized 2-period ( 4 wk each ) crossover design . F(2)-isoprostane excretion was not altered after regular ingestion of green tea ( 273 + /- 48 pmol/mmol creatinine ) or black tea ( 274 + /- 39 pmol/mmol creatinine ) in comparison with hot water ( 263 + /- 47 pmol/mmol creatinine ; Study 1 ) , or by regular ingestion of black tea ( 334 + /- 71 pmol/mmol creatinine ) in comparison with hot water ( 355 + /- 75 pmol/mmol creatinine ; Study 2 ) . These results do not support the suggestion that polyphenolic antioxidants derived from tea inhibit in vivo lipid peroxidation BACKGROUND Polyphenols can act as acceptors of methyl groups during the metabolism of methionine to homocysteine . This may result in elevations in plasma total homocysteine ( tHcy ) concentrations after ingestion of polyphenol-rich beverages such as tea . OBJECTIVES Our major objective was to determine whether regular , moderate-to-high intakes of black tea alter tHcy concentrations . We also assessed the relation between the degree of O-methylation of tea-derived polyphenols and the change in tHcy with regular ingestion of tea . DESIGN Twenty-two subjects completed a r and omized , controlled crossover study . Subjects consumed 1250 mL black tea/d ( 5 cups each containing 2 g tea leaves in 250 mL boiled water ) and 1250 mL hot water/d for 4 wk each . Fasting tHcy concentrations and 24-h urinary excretion of 4-O-methylgallic acid ( 4OMGA , the major O-methylated metabolite of gallic acid ) were measured at the end of each period . 4OMGA was used as a marker of overall O-methylation of tea-derived polyphenols . RESULTS Black tea did not significantly alter mean ( + /- SEM ) tHcy concentrations ( 9.9 + /- 0.5 and 10.0 + /- 0.5 micro mol/L for the hot water and black tea periods , respectively ) . However , the increased excretion of 4OMGA as a consequence of black tea consumption was positively associated with the change in tHcy from the hot water period to the black tea period ( r = 0.55 , P = 0.008 ) . Subjects in the bottom quartile of increase in 4OMGA excretion had a significant decrease in tHcy ( -0.28 + /- 0.10 micro mol/L ; P = 0.046 ) , and those in the top quartile had a significant increase in tHcy ( 0.78 + /- 0.16 micro mol/L ; P = 0.005 ) . CONCLUSIONS Overall , regular ingestion of black tea did not alter mean tHcy concentrations . However , individual differences in O-methylation of polyphenolic compounds may influence the ultimate effects of black tea on tHcy Despite epidemiological evidence that tea consumption is associated with the reduced risk of coronary heart disease , experimental studies design ed to show that tea affects oxidative stress or blood cholesterol concentration have been unsuccessful . We assessed the effects of black tea consumption on lipid and lipoprotein concentrations in mildly hypercholesterolemic adults . Tea and other beverages were included in a carefully controlled weight-maintaining diet . Five servings/d of tea were compared with a placebo beverage in a blinded r and omized crossover study ( 7 men and 8 women , consuming a controlled diet for 3 wk/treatment ) . The caffeine-free placebo was prepared to match the tea in color and taste . In a third period , caffeine was added to the placebo in an amount equal to that in the tea . Five servings/d of tea reduced total cholesterol 6.5 % , LDL cholesterol 11.1 % , apolipoprotein B 5 % and lipoprotein(a ) 16.4 % compared with the placebo with added caffeine . Compared with the placebo without added caffeine , total cholesterol was reduced 3.8 % and LDL cholesterol was reduced 7.5 % whereas apolipoprotein B , Lp(a ) , HDL cholesterol , apolipoprotein A-I and triglycerides were unchanged . Plasma oxidized LDL , F2-isoprostanes , urinary 8-hydroxy-2'-deoxyguanosine , ex vivo ferric ion reducing capacity and thiobarbituric acid reactive substances in LDL were not affected by tea consumption compared with either placebo . Thus , inclusion of tea in a diet moderately low in fat reduces total and LDL cholesterol by significant amounts and may , therefore , reduce the risk of coronary heart disease . Tea consumption did not affect antioxidant status in this study Tea drinking has been associated with decreased occurrence of cancer and heart disease . One potential mechanism for these findings is the strong antioxidant effect of tea polyphenols . A phase II r and omized controlled tea intervention trial was design ed to study the effect of high consumption ( 4 cups/d ) of decaffeinated green or black tea on oxidative DNA damage as measured by urinary 8-hydroxydeoxyguanosine ( 8-OHdG ) among smokers over a 4-mo period . A total of 143 heavy smokers , aged 18 - 79 y , were r and omized to drink either green or black tea or water . Levels of plasma and urinary catechins and urinary 8-OHdG were measured monthly . A total of 133 of 143 smokers completed the 4-mo intervention . Multiple linear regression models were used to estimate the main effects and interaction effect of green and black tea consumption on creatinine-adjusted urinary 8-OHdG , with or without adjustment for potential confounders . Plasma and urinary levels of catechins rose significantly in the green tea group compared with the other two groups . Assessment of urinary 8-OHdG after adjustment for baseline measurements and other potential confounders revealed a highly significant decrease in urinary 8-OHdG ( -31 % ) after 4 mo of drinking decaffeinated green tea ( P = 0.002 ) . No change in urinary 8-OHdG was seen among smokers assigned to the black tea group . These data suggest that regular green tea drinking might protect smokers from oxidative damages and could reduce cancer risk or other diseases caused by free radicals associated with smoking Objectives Flavonoids may protect against cardiovascular disease . Tea is a major source of dietary flavonoids . Studies indicate black tea improves endothelial function but data on arterial haemodynamics , blood pressure ( BP ) and insulin resistance are equivocal . Inconsistency may be due to flaws in study design or flavonoid doses tested . Further , no study has evaluated the dose – response curve . Our study aim ed to test the effects of various doses of black tea on vascular function , BP and insulin resistance . Methods According to a r and omized , double-blind , controlled , cross-over design , 19 healthy men were assigned to receive either five treatments with a twice daily intake of black tea ( 0 , 100 , 200 , 400 and 800 mg tea flvanoids/day ) in five periods lasting 1 week each . Results Black tea dose dependently increased flow-mediated dilation ( FMD ) from 7.8 % ( control ) to 9.0 , 9.1 , 9.6 and 10.3 % after the different flavonoid doses , respectively ( P = 0.0001 ) . Already 100 mg/day ( less than 1 cup of tea ) increased FMD compared with control ( P = 0.0113 ) . FMD improvement after 800 mg/day was significant compared with control ( P < 0.0001 ) but also to 100 mg/day ( P = 0.0121 ) and 200 mg/day ( P = 0.0275 ) . Black tea intake decreased office systolic ( −2.6 mmHg , P = 0.0007 ) and diastolic ( −2.2 mmHg , P = 0.006 ) BP as well as stiffness index ( P = 0.0159 ) without changes in other parameters studied . Conclusion Our study is the first showing black tea ingestion dose dependently improved FMD and decreased peripheral arterial stiffness in healthy volunteers . Our data suggest that worldwide all tea drinkers could benefit from protective cardiovascular effects exerted by tea The objective of this study was to determine the effect of caffeine level in tea and coffee on acute physiological responses and mood . R and omised full crossover design in subjects after overnight caffeine abstention was studied . In study 1 ( n = 17 ) the caffeine level was manipulated naturalistically by preparing tea and coffee at different strengths ( 1 or 2 cups equivalent ) . Caffeine levels were 37.5 and 75 mg in tea , 75 and 150 mg in coffee , with water and no-drink controls . In study 2 ( n = 15 ) caffeine level alone was manipulated ( water , decaffeinated tea , plus 0 , 25 , 50 , 100 , and 200 mg caffeine ) . Beverage volume and temperature ( 55 degrees C ) were constant . SBP , DBP , heart rate , skin temperature , skin conductance , and mood were monitored over each 3-h study session . In study 1 , tea and coffee produced mild autonomic stimulation and an elevation in mood . There were no effects of tea vs. coffee or caffeine dose , despite a fourfold variation in the latter . Increasing beverage strength was associated with greater increases in DBP and energetic arousal . In study 2 , caffeinated beverages increased SBP , DBP , and skin conductance and lowered heart rate and skin temperature compared to water . Significant dose-response relationships to caffeine were seen only for SBP , heart rate , and skin temperature . There were significant effects of caffeine on energetic arousal but no consistent dose-response effects . Caffeinated beverages acutely stimulate the autonomic nervous system and increase alertness . Although caffeine can exert dose-dependent effects on a number of acute autonomic responses , caffeine level is not an important factor . Factors besides caffeine may contribute to these acute effects Epidemiologic studies suggest that tea consumption decreases the risk for cardiovascular events . However , there has been no clinical report examining the effects of tea consumption on coronary circulation . The purpose of this study was to evaluate the effects of black tea on coronary flow velocity reserve ( CFVR ) using transthoracic Doppler echocardiography ( TTDE ) . This was a double-blind crossover study of 10 healthy male volunteers conducted to compare the effects of black tea and caffeine on coronary circulation . The coronary flow velocity of the left anterior descending coronary artery was measured at baseline and at hyperemia during adenosine triphosphate infusion by TTDE to determine CFVR . The CFVR ratio was defined as the ratio of CFVR after beverage consumption to CFVR before beverage consumption . All data were divided into 2 groups according to beverage type : group T ( black tea ) and group C ( caffeine ) . Two-way analysis of variance showed a significant group effect and interaction in CFVR before and after beverage consumption ( p = 0.001 ) . CFVR significantly increased after tea consumption in group T ( 4.5 + /- 0.9 vs 5.2 + /- 0.9 , p < 0.0001 ) . The CFVR ratio of group T was larger than that of group C ( 1.18 + /- 0.07 vs 1.04 + /- 0.08 , p = 0.002 ) . Acute black tea consumption improves coronary vessel function , as determined by CFVR Background Lactic acid-producing bacteria ( LAB ) probiotics demonstrate immunomodulating and anti-inflammatory effects and the ability to lessen the symptoms of arthritis in both animals and humans . This r and omized , double-blind , placebo-controlled , parallel- design , clinical pilot trial was conducted to evaluate the effects of the LAB probiotic preparation , Bacillus coagulans GBI-30 , 6086 , on symptoms and measures of functional capacity in patients with rheumatoid arthritis ( RA ) in combination with pharmacological anti-arthritic medications . Methods Forty-five adult men and women with symptoms of RA were r and omly assigned to receive Bacillus coagulans GBI-30 , 6086 or placebo once a day in a double-blind fashion for 60 days in addition to their st and ard anti-arthritic medications . Arthritis activity was evaluated by clinical examination , the American College of Rheumatology ( ACR ) criteria , the Stanford Health Assessment Question naire Disability Index ( HAQ-DI ) , and laboratory tests for erythrocyte sedimentation rate ( ESR ) and C-reactive protein ( CRP ) . Results Subjects who received Bacillus coagulans GBI-30 , 6086 experienced borderline statistically significant improvement in the Patient Pain Assessment score ( P = .052 ) and statistically significant improvement in Pain Scale ( P = .046 ) vs placebo . Compared with placebo , Bacillus coagulans GBI-30 , 6086 treatment result ed in greater improvement in patient global assessment and self-assessed disability ; reduction in CRP ; as well as the ability to walk 2 miles , reach , and participate in daily activities . There were no treatment-related adverse events reported throughout this study . Conclusions Results of this pilot study suggest that adjunctive treatment with Bacillus coagulans GBI-30 , 6086 LAB probiotic appeared to be a safe and effective for patients suffering from RA . Because of the low study population size , larger trials are needed to verify these results .Trial registration Rationale Tea has anecdotally been associated with stress relief , but this has seldom been tested scientifically . Objectives To investigate the effects of 6 weeks of black tea consumption , compared with matched placebo , on subjective , cardiovascular , cortisol and platelet responses to acute stress , in a parallel group double-blind r and omised design . Material s and methods Seventy-five healthy nonsmoking men were withdrawn from tea , coffee and caffeinated beverages for a 4-week wash-out phase during which they drank four cups per day of a caffeinated placebo . A pretreatment laboratory test session was carried out , followed by either placebo ( n = 38 ) or active tea treatment ( n = 37 ) for 6 weeks , then , a final test session . Cardiovascular measures were obtained before , during and after two challenging behavioural tasks , while cortisol , platelet and subjective measures were assessed before and after tasks . Results The tasks induced substantial increases in blood pressure , heart rate and subjective stress ratings , but responses did not differ between tea and placebo treatments . Platelet activation ( assessed using flow cytometry ) was lower following tea than placebo treatment in both baseline and post-stress sample s ( P < 0.005 ) . The active tea group also showed lower post-task cortisol levels compared with placebo ( P = 0.032 ) , and a relative increase in subjective relaxation during the post-task recovery period ( P = 0.036 ) . Conclusions Compared with placebo , 6 weeks of tea consumption leads to lower post-stress cortisol and greater subjective relaxation , together with reduced platelet activation . Black tea may have health benefits in part by aiding stress recovery This study was undertaken to investigate the effects of green tea on weight reduction in obese Thais . A r and omized , controlled trial involving 60 obese subjects ( body mass index , BMI > 25 kg/m2 ) was conducted . All subjects consumed a Thai diet containing 3 meals ( 8373.6 kJ/day ) for 12 weeks , prepared by the Nutritional Unit at Srinagarind Hospital . The diet contained 65 % carbohydrates , 15 % protein , and 20 % fat . Body weight , BMI , body composition , resting energy expenditure , and substrate oxidation were measured at baseline , and during weeks 4 , 8 , and 12 of the study . Serum levels of leptin and urine VMA were measured at baseline and during the 12th week . Differences over time and between the treatments ( green tea or placebo ) over time were determined using two-factor ANOVA with repeated measures . In comparing the two groups , differences in weight loss were 2.70 , 5.10 , and 3.3 kg during the 4th , 8th , and 12th weeks of the study , respectively . At the 8th and 12th weeks of the study , body weight loss was significantly different ( P < 0.05 ) . At the 8th week , the difference in resting energy expenditure was 183.38 kJ/day ( P < 0.001 ) , the difference in the respiratory quotient was 0.02 ( P < 0.05 ) , and no significant differences existed in satiety score , food intake , or physical activity . Urine VMA was significantly different in the 12th week of the study ( P < 0.05 ) . We conclude that green tea can reduce body weight in obese Thai subjects by increasing energy expenditure and fat oxidation Results of population studies suggest that black tea can reduce cardiovascular risk . Effects of black-tea polyphenols to reduce platelet aggregability may help to explain any benefits . Given that black tea is often consumed with and after meals , and man spends much of his life in the postpr and ial state , the objective of the present study was to investigate the acute effects of ingestion of black tea on postpr and ial platelet aggregation ex vivo . Twenty healthy participants had platelet aggregation and blood lipids assessed before and 4 h after the ingestion of 50 g dairy fat on two occasions in r and om order , corresponding to black tea or hot water . Black tea or hot water ( one cup ) was consumed immediately following the dairy fat , then after 15 and 30 h. Platelet aggregation ex vivo was assessed in platelet-rich plasma in response to three concentrations of collagen ( 0.2 , 0.6 , 20 microg/ml ) and ADP ( 2 , 4 , 8 microM ) . Urinary concentrations of 4-O-methylgallic acid were used as an indicator that tea polyphenols were absorbed . Serum total cholesterol and triacylglycerol concentrations increased significantly 4 h after ingesting the dairy fat , but there was no significant difference between black tea and hot-water treatments on the cholesterol or triacylglycerol responses . Urinary 4-O-methylgallic acid concentrations were significantly increased following ingestion of black tea ( P=0.0001 ) but not water . Black tea in comparison to hot water did not inhibit collagen or ADP-induced postpr and ial platelet aggregation . The results of this study do not support the suggestion that reduced postpr and ial platelet aggregability contributes to any benefits of black tea on cardiovascular risk AIMS To estimate the potential effectiveness of different " high-risk " and " population " approaches to the primary prevention of cardiovascular disease ( CVD ) in middle-aged British men , after correction for regression dilution bias . METHODS AND RESULTS We used a combination of cohort and r and omised controlled trial evidence to estimate the effectiveness of high-risk strategies , based on the identification of high-risk factors or high absolute risk , and strategies based on population -wide reductions in cholesterol and blood pressure . High-risk strategies were potentially effective but would need to be used widely to have a substantial effect on CVD in the population . Aggressive pharmacological treatment ( using statins , beta-blockers , ACE-inhibitors and aspirin ) in individuals with a 10-year Framingham event risk of > or=30 % ( 6 % of population ) would have reduced major CVD by at most 11 % . This figure increased to 34 % at a > or=20 % treatment threshold ( 26 % of population ) . In contrast , modest downwards shifts in the population distributions of serum total cholesterol and systolic blood pressure led to marked expected reductions in major CVD . Taking regression dilution bias into account , 10 % reductions in long-term mean blood cholesterol and blood pressure could have reduced major CVD by 45 % . CONCLUSIONS If high-risk strategies are to have a major impact on CVD in the population , they need to be more widely used than previously envisaged . Population -wide reduction of major risk factors is needed if CVD is to be substantially reduced Background Evidence suggests that both green tea polyphenols ( GTP ) and Tai Chi ( TC ) exercise may benefit bone health in osteopenic women . However , their safety in this population has never been systematic ally investigated . In particular , there have been hepatotoxicity concerns related to green tea extract . This study was to evaluate the safety of 24 weeks of GTP supplementation combined with TC exercise in postmenopausal osteopenic women , along with effects on quality of life in this population . Methods 171 postmenopausal women with osteopenia were r and omly assigned to 4 treatment arms for 24 weeks : ( 1 ) Placebo ( 500 mg starch/day ) , ( 2 ) GTP ( 500 mg GTP/day ) , ( 3 ) Placebo + TC ( placebo plus TC training at 60 min/session , 3 sessions/week ) , and ( 4 ) GTP + TC ( GTP plus TC training ) . Safety was examined by assessing liver enzymes ( aspartate aminotransferase , alanine aminotransferase ) , alkaline phosphatase , and total bilirubin at baseline and every 4 weeks . Kidney function ( urea nitrogen and creatinine ) , calcium , and inorganic phosphorus were also assessed at the same times . Qualify of life using SF-36 question naire was evaluated at baseline , 12 , and 24 weeks . A mixed model of repeated measures ANOVA was applied for analysis . Results 150 subjects completed the study ( 12 % attrition rate ) . The compliance rates for study agents and TC exercise were 89 % and 83 % , respectively . Neither GTP supplementation nor TC exercise affected liver or kidney function parameters throughout the study . No adverse event due to study treatment was reported by the participants . TC exercise significantly improved the scores for role-emotional and mental health of subjects , while no effect on quality of life was observed due to GTP supplementation . Conclusions GTP at a dose of 500 mg/day and /or TC exercise at 3 hr/week for 24 weeks appear to be safe in postmenopausal osteopenic women , particularly in terms of liver and kidney functions . TC exercise for 24 weeks ( 3 hr/wk ) significantly improved quality of life in terms of role-emotional and mental health in these subjects . Clinical Trials.gov identifier : NCT00625391 Regular consumption of green tea may be cardioprotective . In the present study we investigated the health effects of dietary supplementation with green tea catechins and the potential modifying effect of the catechol-O-methyltransferase ( COMT ) Val/Met genotype . Subjects ( sedentary males , aged 40 - 69 years , with BMI ≥ 28 and ≤ 38 kg/m(2 ) ) were r and omly assigned to consume decaffeinated green tea extract ( DGT ; 530 mg containing about 400 mg total catechins/capsule , twice daily ) and placebo in a complete cross-over design . Ambulatory blood pressure and biomarkers of metabolic function ( cholesterol , TAG , glucose and insulin ) were measured at weeks 0 and 6 . Although a marked increase in the concentration of plasma epigallocatechin gallate ( EGCG ) , urinary epigallocatechin ( EGC ) and urinary 4'-O-methyl EGC was found after DGT treatment , no effect on blood pressure or biomarkers of metabolic function was observed . However , a period × treatment interaction ( P < 0·05 ) was detected for body-weight change . Despite a similar increase in estimated energy intake during intervention period 1 , body weight decreased by 0·64 ( sd 2·2 ) kg and increased by 0·53 ( sd 1·9 ) kg in the DGT and placebo groups , respectively ( P = 0·025 ) , suggesting a protective effect of green tea catechins on weight gain . Additionally , the COMT Val/Met genotype influenced urinary accumulation of EGC and 4'-O-methyl EGC ( P < 0·01 ) . Mean concentrations were lower in individuals homozygous for the high-activity G-allele , possibly reflecting increased metabolic flux and a more rapid conversion to downstream metabolic species , compared with individuals carrying at least one copy of the low-activity A-allele . Additional studies are needed to confirm these findings and further explore the modifying effect of genotype There have been no controlled intervention studies to investigate the effects of green tea on circulating hormone levels , an established breast cancer risk factor . We conducted a double-blind , r and omized , placebo-controlled intervention study to investigate the effect of the main green tea catechin , epigallocatechin gallate ( EGCG ) , taken in a green tea extract , polyphenon E ( PPE ) . Postmenopausal women ( n = 103 ) were r and omized into three arms : placebo , 400-mg EGCG as PPE , or 800-mg EGCG as PPE as capsules per day for 2 months . Urinary tea catechin and serum estrogen , and rogen , lipid , glucose-related markers , adiponectin , and growth factor levels were measured at baseline and at the end of months 1 and 2 of intervention . On the basis of urinary tea catechin concentrations , compliance was excellent . Supplementation with PPE did not produce consistent patterns of changes in estradiol ( E2 ) , estrone ( E1 ) , or testosterone ( T ) levels . Low-density lipoprotein (LDL)-cholesterol decreased significantly in both PPE groups but was unchanged in the placebo group ; the change in LDL-cholesterol differed between the placebo and PPE groups ( P = 0.02 ) . Glucose and insulin levels decreased nonsignificantly in the PPE groups but increased in the placebo group ; statistically significant differences in changes in glucose ( P = 0.008 ) and insulin ( P = 0.01 ) were found . In summary , green tea ( 400- and 800-mg EGCG as PPE ; ∼5–10 cups ) supplementation for 2 months had suggestive beneficial effects on LDL-cholesterol concentrations and glucose-related markers . Cancer Prev Res ; 5(3 ) ; 393–402 . © 2012 AACR OBJECTIVE Previous studies examining the effect of tea drinking on cardiovascular health have produced mixed results due to their observational nature and qualitatively and quantitatively imprecise definitions of active tea components . The objective of this study was to determine if a st and ardized and defined decaffeinated green tea ( Camellia sinensis ) product lowers blood pressure , serum lipids , oxidative stress , and markers of chronic inflammation . METHODS A r and omized , double-blind , placebo-controlled , parallel study on 111 healthy adult volunteers 21 - 70 y old was performed . We administered a st and ardized capsule of Camellia sinensis compounds ( CSC ) twice a day . Before and after 3 wk , blood pressure , serum lipids , serum amyloid-alpha ( a marker of chronic inflammation ) , and serum malondialdehyde ( a marker of oxidative stress ) were measured . RESULTS After 3 wk , CSC lowered systolic and diastolic blood pressures by 5 and 4 mmHg , respectively . After 3 mo , systolic blood pressure remained significantly lower . CSC lowered serum amyloid-alpha by 42 % and lowered malondialdehyde by 11.9 % . In men , there were 10- and 9-mg/dL reductions in total and low-density lipoprotein ( LDL ) cholesterol , respectively . In all subjects with a baseline LDL cholesterol level > 99 mg/dL , there was 9 mg/dL lowering of total and LDL cholesterol . Adverse effects were mild and few and not different from placebo . CONCLUSION CSC was effective for decreasing , in as quickly as 3 wk , blood pressure , LDL cholesterol , oxidative stress , and a marker of chronic inflammation , all independent cardiovascular risk factors 1 . A postpr and ial fall in blood pressure ( BP ) in older men and women increases the risks of falls and impaired cerebral perfusion . Postpr and ial hypotension has been suggested to be greater in hypertensive subjects , particularly in those on antihypertensive medication OBJECTIVE The body fat reducing effect and reduction of risks for cardiovascular disease by a green tea extract ( GTE ) high in catechins was investigated in humans with typical lifestyles . RESEARCH METHODS AND PROCEDURES Japanese women and men with visceral fat-type obesity were recruited for the trial . After a 2-week diet run-in period , a 12-week double-blind parallel multicenter trial was performed , in which the subjects ingested green tea containing 583 mg of catechins ( catechin group ) or 96 mg of catechins ( control group ) per day . R and omization was stratified by gender and body mass index at each medical institution . The subjects were instructed to maintain their usual dietary intake and normal physical activity . RESULTS Data were analyzed using per- protocol sample s of 240 subjects ( catechin group ; n = 123 , control group ; n = 117 ) . Decreases in body weight , body mass index , body fat ratio , body fat mass , waist circumference , hip circumference , visceral fat area , and subcutaneous fat area were found to be greater in the catechin group than in the control group . A greater decrease in systolic blood pressure ( SBP ) was found in the catechin group compared with the control group for subjects whose initial SBP was 130 mm Hg or higher . Low-density lipoprotein ( LDL ) cholesterol was also decreased to a greater extent in the catechin group . No adverse effect was found . DISCUSSION The continuous ingestion of a GTE high in catechins led to a reduction in body fat , SBP , and LDL cholesterol , suggesting that the ingestion of such an extract contributes to a decrease in obesity and cardiovascular disease risks Objective : While most studies have shown an inverse relation between tea consumption and cardiovascular risk , other studies have shown opposite results . Aortic stiffness and wave reflections are markers of cardiovascular disease and prognosticators of cardiovascular risk . Methods : The acute effect of black and green tea on aortic stiffness and wave reflections was assessed in 29 healthy volunteers in a r and omized , single-blind , sham-procedure controlled , cross-over design . In the black tea sub- study , 16 subjects received 6 gm of tea , caffeine ( 175 mg ) , or hot water in 3 different sessions . In the green tea sub- study , 13 subjects received 6 gm of tea , caffeine ( 125 mg ) , or hot water . Carotid-femoral pulse wave velocity and wave reflection indices were measured at baseline and for 3 hours after consumption . Results : Black tea increased pulse wave velocity during the first 90 min ( increase by 0.49 m/sec , P < 0.05 ) , showing a rapid return towards baseline values thereafter ( P = 0.07 for the whole study period ) ; in contrast , green tea had no effect . Both black and green tea increased augmentation index ( by 5.0 % and by 6.6 % , P < 0.01 and P < 0.001 , respectively ) throughout the study . These changes were less than the respective changes produced by caffeine . Both black and green tea had a significant pressor effect . No change in oxidant status was found with both types of tea . Conclusions : Both black and green tea increases acutely wave reflections and only black tea increases aortic stiffness . Tea flavonoids may play a role in the attenuation of the effects of caffeine contained in tea BACKGROUND Epidemiological studies have established an association between dyslipidemias and atherosclerosis . Nutritional therapy is a key point in the prevention strategy for individuals who present with risk factors for atherosclerotic disease . OBJECTIVES To investigate the effects of green tea ( Camellia sinensis ) in patients with dyslipidemias . METHODS The study included 33 patients aged between 21 and 71 years who had a low-fat diet ( 25 - 35 % of total calories and 200 mg of cholesterol per day ) . They were r and omized for two sequential treatments : 250-mg capsules of green tea dry extract or placebo for a total period of 16 weeks ; each patient received green tea ( Camellia sinensis ) for eight weeks and placebo for another eight weeks . RESULTS Baseline lipid values ( mg/dL ) were : HDL-cholesterol 60.7 + /- 7.3 ; total cholesterol 255 + /- 30.9 ; LDL-cholesterol 158.8 + /- 29.0 ; triglycerides 169.0 + /- 61.3 and Apo-B 120.2 + /- 18.9 . Mean lipid variations induced by the use of green tea ( Camellia sinensis ) showed a 3.9 % reduction ( p = 0.006 ) in total cholesterol concentrations and a 4.5 % reduction ( p = 0.026 ) in LDL-cholesterol . The intake of green tea did not significantly influence HDL-cholesterol , triglyceride , and Apo-B levels . Non-significant results were found in the assessment of blood lipids ( total cholesterol and LDL-cholesterol ) with the use of placebo . CONCLUSION A beneficial effect of green tea ( Camellia sinensis ) was demonstrated , with a significant reduction of total cholesterol and LDL-cholesterol levels in eight weeks , in the patients studied It has been reported that green tea consumption reduces the risk of coronary artery disease and cardiac events . Catechin is a major constituent of Japanese green tea and an antioxidant . Lipids and oxidization of low-density lipoprotein cholesterol ( LDL-C ) play important roles in atherosclerosis . Therefore , we evaluated the effect of catechin intake on the lipid profile and plasma oxidized LDL . The study population consisted of 40 healthy adult volunteers ( 10 men , 30 women ) . Catechin was extracted from green tea leaves . The subjects were r and omly divided into two groups , a catechin group ( n = 29 ) and a control group ( n = 11 ) . In the catechin group , catechin ( 500 mg : equivalent to 6 or 7 cups of green tea ) was administered orally . Venous blood sample s were obtained before eating a meal at the start and after 4 weeks without any lifestyle modification . Plasma oxidized LDL assay was performed with a s and wich-type enzyme immunoassay using anti-oxidized phosphatidylcholine monoclonal antibody . The baseline lipid profiles and tea consumptions were similar between the two groups . Plasma oxidized LDL was significantly decreased after catechin administration ( from 9.56 + /- 9.2 to 7.76 + /- 7.7 U/mL , P = 0.005 ) , while plasma LDL-C , triglyceride , and HDL-C concentrations did not change . Catechin decreased the plasma oxidized LDL concentration without significant change in plasma LDL concentration . The mechanism of the beneficial effects of green tea on coronary artery disease might result from a decrease in plasma oxidized LDL Obejective : Firstly , to study the effect of tea and tea polyphenols on cardiovascular risk indicators of the inflammatory system ( IL6 , IL1β and TNF-α , CRP ) , and on haemostasis and endothelial proteins with an acute phase behaviour ( fibrinogen , vWF , PAI-1 , FVIIa and u-PA ) . Secondly , to study the relationship between plasma levels of antioxidants ( α-tocopherol , β-carotene and vitamin C ) and these acute-phase , cardiovascular risk indicators . Design : R and omized study .Subjects : Sixty-four smoking healthy volunteers were recruited by newspaper advertisements ; there were five dropouts . Intervention : Four-week administration of black tea , green tea , green tea polyphenol isolate and mineral water ( 13–16 per group ) . Measures : Plasma levels of the inflammatory markers IL6 , IL1β , TNF-α , CRP , fibrinogen , vWF , PAI-1 , FVIIa and u-PA and of the antioxidants α-tocopherol , β-carotene and vitamin C. Results : Different dosages of tea polyphenols had no effect on inflammation , haemostasis and endothelial markers . There was a significant negative correlation between the levels of the antioxidant β-carotene and the inflammation markers IL6 and fibrinogen ( r=−0.35 and r=−0.37 , respectively , P<0.01 ) in this group of smokers . Remarkably , there was a significant positive correlation between the levels of the antioxidant α-tocopherol and the inflammation marker IL6 ( r=0.28 , P<0.05 ) . Conclusions : Tea drinking had no effect on the levels of the inflammation , haemostasis and endothelial cardiovascular risk factors measured . We did observe a relationship between the antioxidant variables α-tocopherol and β-carotene and inflammation markers in this group of healthy smoking subjects . Sponsorship : This work was supported in part by Unilever Research , Vlaardingen , The Netherl and s. European Journal Of Clinical Nutrition ( 2000 ) 24 , Objectives : To investigate the effect of three different food ingredients tyrosine , green tea extract ( GTE ) and caffeine on resting metabolic rate and haemodynamics , and on ad libitum energy intake ( EI ) and appetite . Methods : Twelve healthy , normal weight men ( age : 23.7±2.6 years , mean±s.d . ) participated in a four-way crossover , r and omized , placebo-controlled , double-blind study . Treatments were administered as tablets of 500 mg GTE , 400 mg tyrosine , 50 mg caffeine , or placebo , and were separated by > 3-day washout . The acute thermogenic response was measured in a ventilated hood system for 4 h following ingestion . Blood pressure , heart rate ( HR ) , and subjective appetite sensations were assessed hourly and ad libitum EI 4 h post-dose . Results : Caffeine induced a thermogenic response of 6 % above baseline value ( 72±25 kJ per 4 h , mean±s.e . ) compared to placebo ( P<0.0001 ) . The thermogenic responses to GTE and tyrosine were not significantly different from placebo . Tyrosine tended to increase 4-h respiratory quotient by 1 % compared to placebo ( 0.01±0.005 , P=0.05 ) . Ad libitum EI was not significantly different between treatments but was reduced by 8 % ( −403±183 kJ ) , 8 % ( −400±335 kJ ) and 3 % ( −151±377 kJ ) compared to placebo after intake of tyrosine , GTE and caffeine , respectively . No significant difference in haemodynamics was observed between treatments . Conclusions : Only caffeine was thermogenic in the given dose and caused no haemodynamic side effects . The sample size was probably too small to detect any appetite suppressant properties of the treatments . Further investigations are required The purpose of this study was to examine the effects of three-week consumption of green tea extract ( GTE ) supplementation on time trial performance and metabolism during cycling in endurance athletes . Nine endurance-trained men participated in this double-blind and placebo-controlled cross-over study . At the end of the supplementation period with GTE ( 159 mg/day total catechins ) or placebo , respectively , subjects cycled at 50 % of the individual maximal power output for 2 hours , followed by a 30-minute time trial . Respiratory gas exchange , fatty acids , 3-beta-hydroxybutyrate , lactate , glucose , interleukin-6 , thiobarbituric acid reactive substances , creatine kinase , and C-reactive protein ( CRP ) were measured 1 hour before , during , and 1 hour after the exercise test . Blood lipids were measured at rest before cycling . There was no significant effect on performance , energy metabolism , or any other measured parameter , except for CRP , which was significantly reduced ( p = 0.045 ) after GTE supplementation compared to placebo . GTE supplementation did not affect time trial performance and energy metabolism in endurance-trained men in the non-fasting state . Further studies with athletes , particularly in the fed state , but with higher GTE doses , are needed to address the question whether green tea may influence energy metabolism and performance in athletes BACKGROUND The effects of black tea consumption on cardiovascular risk factors have been inconsistent in previous r and omized trials , all of which have been limited to a few weeks duration . METHODS We conducted a pilot parallel- design r and omized controlled trial among 31 adults aged 55 years and older with either diabetes or 2 other cardiovascular risk factors but no established clinical cardiovascular disease . Participants were r and omized to drink 3 glasses daily of either a st and ardized black tea preparation or water for 6 months . Cardiovascular risk factors were measured at the beginning and conclusion of the study . RESULTS Three participants dropped out of the study , leaving 14 participants assigned to tea and 14 assigned to water eligible for analyses . We found no statistically significant effects of black tea on cardiovascular biomarkers , including lipids , inflammatory markers , hemoglobin , adhesion molecules , prothrombotic and fibrinolytic parameters , and lipoprotein oxidizability . Assignment to tea did not appreciably influence blood pressure , and heart rate among participants assigned to tea was marginally higher than among control participants at 3 months ( P = .07 ) but not 6 months . CONCLUSIONS In this r and omized trial of black tea intake over 6 months among older adults with known cardiovascular risk factors , black tea did not appreciably influence any traditional or novel biomarkers of cardiovascular risk . Longer r and omized trials are needed to verify the inverse association of tea with risk of cardiovascular disease seen in cohort studies and identify potential c and i date mechanisms for such an association Intake of flavonoids is associated with a reduced cardiovascular risk . Oxidation of LDL is a major step in atherogenesis , and antioxidants may protect LDL from oxidation . Because tea is an important source of flavonoids , which are strong antioxidants , we have assessed in a r and omized , placebo-controlled study the effect of consumption of black and green tea and of intake of isolated green tea polyphenols on LDL oxidation ex vivo and on plasma levels of antioxidants and lipids . Healthy male and female smokers ( aged 34+/-12 years , 13 to 16 per group ) consumed during a 4-week period 6 cups ( 900 mL ) of black or green tea or water per day , or they received as a supplement 3.6 grams of green tea polyphenols per day ( equivalent to the consumption of 18 cups of green tea per day ) . Consumption of black or green tea had no effect on plasma cholesterol and triglycerides , HDL and LDL cholesterol , plasma vitamins C and E , beta-carotene , and uric acid . No differences were found in parameters of LDL oxidation . Intake of green tea polyphenols decreased plasma vitamin E significantly in that group compared with the control group ( -11 % P=.016 ) but had no effect on LDL oxidation ex vivo . We conclude that consumption of black or green tea ( 6 cups per day ) has no effect on plasma lipids and no sparing effect on plasma antioxidant vitamins and that intake of a high dose of isolated green tea polyphenols decreases plasma vitamin E. Although tea polyphenols had a potent antioxidant activity on LDL oxidation in vitro , no effect was found on LDL oxidation ex vivo after consumption of green or black tea or intake of a green tea polyphenol isolate Benifuuki is a tea cultivar with an antiallergic effect stronger than that of Yabukita tea , the most popular green tea cultivar consumed in Japan . The effective compound is (-)-epigallocatechin-3-O-(3-O-methyl)gallate ( EGCG3''Me ) , an O-methylated derivative of EGCG . This study examined the antihypertensive effects of EGCG3''Me and Benifuuki tea . First , it was determined that EGCG3''Me has a significant inhibitory effect on the activity of angiotensin I-converting enzyme ( ACE ) . Second , clinical trials showed that Benifuuki tea suppressed high blood pressure to a greater extent than green tea that did not contain EGCG3''Me after equal amounts of tea catechins were consumed for 8 weeks . The effect of Benifuuki tea on human hypertension is mainly the result of the strong inhibitory effect of EGCG3''Me on ACE activity , its high rate of absorption , and its stability in the blood Background Ingestion of tea flavonoids found in both green and black tea is linked to cardiovascular health benefits such as lowering serum lipids . Evidence for a cholesterol-lowering benefit of green or black tea consumption from human intervention studies is , however , conflicting and active components responsible for the effect have not yet been clearly identified . Aim of the study In a r and omized , double-blind , placebo-controlled , parallel design study the effects of ingesting a purified black tea theaflavins ( TFs ) powder alone or in combination with catechin ( TFs/catechins ) on lowering serum total ( TC ) and LDL-cholesterol ( LDL-c ) were assessed . Methods In total , 102 mildly to moderately hypercholesterolemic ( TC and LDL-c : 5.70 ± 0.74 and 3.97 ± 0.61 mmol/L , respectively ) subjects ( 67 men and 35 women ) were r and omly assigned to consume once daily one capsule of one of the 3 treatments : TFs ( providing 77.5 mg ) , TFs/catechins ( providing 75.0 mg TFs plus 150.0 mg catechins and 195.0 mg of other polyphenols ) , or placebo ( cellulose ) . Results Serum TC and LDL-c concentrations did not differ significantly among the 3 treatments as assessed at 4 , 8 , and 11 weeks using analysis of covariance ( p = 0.1187 and p = 0.1063 , respectively ) . Although changes over time from baseline to week 11 were significant for TC and LDL-c ( p = 0.0311 and p = 0.0269 , respectively ) , this decrease over time was seen in the TFs and placebo groups . Conclusion In this human intervention study , no statistically significant LDL-c lowering effect was seen with either TFs alone or the TFs/catechins combination as compared to placebo . Based on these findings it can not be concluded that tea flavonoids such as theaflavins and catechins are responsible for a putative cholesterol-lowering effect of black tea , at least not with the daily dose applied in the present study Abstract Psychopharmacological studies using caffeinated beverages or caffeine have rarely considered temporal effects on psychological and physiological function or the specific contribution of caffeine , hot water , or beverage type to the observed effects . The effect of 400 ml hot tea , coffee , and water consumption on systolic and diastolic blood pressure ( SBP and DBP ) , heart rate , skin conductance ( a measure of sympathetic nervous system activation ) , skin temperature , salivary cortisol , and mood were monitored in 16 healthy caffeine-withdrawn ( 14 h ) subjects in a complete crossover design . Beverages were ingested with/without 100 mg caffeine and milk ( tea/coffee only ) . Hot beverage ingestion rapidly increased skin conductance and temperature ( + 1.7 ° C ) with peak effects observed only 10–30 min post-consumption . Caffeine in the beverage rapidly augmented skin conductance responses but , in contrast to the effect of hot water , reduced the skin temperature response and increased SBP ( + 2.8 mmHg ) and DBP ( + 2.1 mmHg ) 30–60 min post-consumption . Both caffeine and milk addition to beverages independently improved mood and reduced anxiety 30 and 60 min post-consumption . Milk addition had no other effects apart from attenuating the transient increase in physiological responses associated with the drinking phase . There were no effects of beverage consumption on salivary cortisol or of beverage vehicle on salivary caffeine levels , the latter indicating that caffeine pharmacokinetics was similar in both tea and coffee , and not different from caffeinated water . In keeping with this , the responses to tea and coffee ingestion were similar and largely accounted for by the effects of hot water and caffeine . However , tea potentiated the increase in skin temperature compared to coffee and water indicative of a greater vasodilatory response plausibly related to the presence of flavonoids in tea . We conclude that ingestion of hot caffeinated beverages stimulates physiological processes faster than hitherto described , primarily via the effects of hot water and caffeine , but with beverage type and milk playing important modulatory roles Objective : To assess the effects in humans of regular ingestion of black tea on haemostasis-related variables and cell adhesion molecules . Design : Twenty-two subjects were recruited from the general population to a r and omised-controlled crossover study . Subjects stopped drinking tea , apart from that provided , for the duration of the study . During a 4-week baseline period all subjects drank 5 cups/day ( 250 ml ) of hot water . The effects of 5 cups/day of black tea for 4 weeks were then compared with hot water . Platelet aggregation in response to three doses of collagen and ADP , plasma concentrations of coagulation and fibrinolytic factors ( fibrinogen , factor VII , tPA , PAI-1 ) and plasma concentrations of cell adhesion molecules ( soluble P-selectin , E-selectin , ICAM-1 , VCAM-1 ) were assessed twice , one week apart , at the end of each period . Twenty-four hour urinary concentration of 4-O-methylgallic acid ( 4OMGA ) , assessed once at the end of each period , was used as a marker of black tea polyphenol intake . Results : The 24 h urinary excretion of 4OMGA was increased during regular ingestion of black tea in comparison to hot water ( P<0.0001 ) . Black tea result ed in lower soluble P-selectin ( P=0.01 ) in comparison to hot water , but did not influence other adhesion molecules . Soluble P-selectin was significantly correlated with mean collagen-stimulated platelet aggregation at baseline ( r=0.61 , P=0.003 ) , and during regular ingestion of hot water ( r=0.70 , P<0.0001 ) and black tea ( r=0.51 , P=0.01 ) . However , platelet aggregation was not different between the black tea and hot water periods for collagen- or ADP-stimulated aggregation at any dose . Coagulation and fibrinolytic factors were also not different between periods . Conclusions : The effect of black tea on soluble P-selectin provides a potential mechanism for cardiovascular benefits of regular ingestion of tea . Sponsorship : This study was supported by grants from the Tea Trade Health Research Association and the National Heart Foundation of Australia . European Journal of Clinical Nutrition ( 2001 ) 55 , OBJECTIVES A prospect i ve r and omized controlled clinical trial determined the effect of Mauritian black tea consumption on fasting blood plasma levels of glucose , lipid profiles and antioxidant status in a normal population . METHODS The study group ( 71 % ) consumed 3 x 200 ml of black tea infusate/day for 12 weeks without additives followed by a 3 week wash-out . The control group ( 29 % ) consumed equivalent volume of hot water for same intervention period . RESULTS The tea used had high levels of gallic acid derivatives ( 50 ± 0.4 mg/L ) , flavan-3-ols ( 42 ± 2 mg/L ) , flavonols ( 32 ± 1 mg/L ) and theaflavins ( 90 ± 1 mg/L ) . Daily 9 g supplementation of black tea infusate induced , in a normal population , a highly significant decrease of fasting serum glucose ( 18.4 % ; p<0.001 ) and triglyceride levels ( 35.8 % ; p<0.01 ) , a significant decrease in LDL/HDL plasma cholesterol ratio ( 16.6 % ; p<0.05 ) and a non significant increase in HDL plasma cholesterol levels ( 20.3 % ) , while a highly significant rise in plasma antioxidant propensity ( FRAP : 418 % ; p<0.001 ) was noted . CONCLUSION Black tea consumed within a normal diet contributes to a decrease of independent cardiovascular risk factors and improves the overall antioxidant status in humans A water-soluble extract of a traditional Chinese black tea ( Pu-Ehr ) has been shown to precipitate mixed bile salt micelles in foods . In addition , long-term ingestion of this black tea extract ( BTE ) significantly reduces blood cholesterol levels in rats . We investigated the effects of BTE tablets ( a formula design ed to enhance compliance ) as a dietary supplement in a 3-month double-blind r and omized group comparison study in borderline hypercholesterolemic human subjects ( n = 47 ) . All subjects ingested BTE tablets ( 333 mg ) or placebo 3 times daily before meals for 3 months . In the BTE-treated group , the initial mean blood total ( 6.14 + /- 0.14 mol/L ) and low-density lipoprotein ( LDL ) cholesterol ( 4.32 + /- 0.14 mol/L ) levels decreased with time and were significantly ( P < .01 ) lower ( total cholesterol , 5.62 + /- 0.11 ; LDL cholesterol , 3.81 + /- 0.13 mol/L ) after 3 months of ingestion . Furthermore , the mean body weights ( P < .05 ) and triacylglycerol levels ( P < .01 ) were also significantly reduced after 3 months of BTE intake compared with the baseline levels . Significant improvements in the mean LDL cholesterol , body weight , and triacylglycerol values were not accompanied with undesirable changes in other biochemical parameters measured in the subjects . None of the subjects complained of any adverse effects ( eg , abdominal distension ) . The results indicate that BTE intake elicited a significant antihypercholesterolemic effect and might be useful for improving blood cholesterol levels in subjects at risk for heart disease or obesity BACKGROUND The flavonoid components of tea have been associated in epidemiological studies with a decreased risk of cardiovascular disease . Flavonoids have been shown to have antioxidant and vasodilator effects in vitro ; we therefore postulated that drinking green or black tea attenuates the well-characterized acute pressor response to caffeine and lowers blood pressure during regular consumption . OBJECTIVE To determine whether green and black tea can attenuate the transient pressor effect of caffeine , or lower blood pressure during regular consumption . METHODS In the first study , the acute effects of four hot drinks - green tea and black tea ( at a dose equivalent to four st and ard cups ) , water matched to the teas for caffeine content ( ' caffeine ' ) and water - were assessed in 20 normotensive men using a Latin-Square design ed study . Clinic blood pressure was measured before and 30 and 60 min after each drink had been ingested . In the second study , the effects on blood pressure of regular green and black tea ingestion were examined in 13 subjects with high-normal systolic blood pressure and mild systolic hypertension ( systolic blood pressure in the range 130 - 150 mmHg ) using a three-period crossover study . Five cups per day of green tea , black tea and caffeine ( in hot water and matched to the teas ) were consumed for 7 days each , in r and om order . Twenty-four hour ambulatory blood pressure was measured at the end of each seven-day intervention . Results are presented as means and 95 % confidence intervals ( CI ) . RESULTS An acute pressor response to caffeine was observed . Relative to caffeine , there were further acute increases in systolic and diastolic blood pressure at 30 min among those drinking green tea [ 5.5 mmHg ( 95%CI -1.4 to 12.4 ) and 3.1 mmHg ( 95%CI -0.1 to 6.3 ) , respectively ] and black tea [ 10.7 mmHg ( 95%CI 4.0 to 17.4 ) and 5.1 mmHg ( 95%CI 1.8 to 8.4 ) , respectively ] . The changes in blood pressure at 60 min were not significant The effect on 24-h ambulatory systolic and diastolic blood pressure of regular drinking of green tea [ increases of 1.7 mmHg ( 95%CI -1.6 to 5.0 ) and 0.9 mmHg ( 95%CI -1.3 to 3.1 ) , respectively ] or black tea [ increase of 0.7 mmHg ( 95%CI -2.6 to 4.0 ) and decrease of 0.7 mmHg ( 95%CI -2.9 to 1.5 ) , respectively ] was not significant relative to caffeine . CONCLUSIONS Contrary to our initial hypothesis , tea ingestion caused larger acute increases in blood pressure than caffeine alone . However , any acute effects of tea on blood pressure did not translate into significant alterations in ambulatory blood pressure during regular tea consumption BACKGROUND Tea consumption has been associated with decreased cardiovascular risk , but potential mechanisms of benefit are ill-defined . While epidemiologic studies suggest that drinking multiple cups of tea per day lowers low-density lipoprotein cholesterol ( LDL-C ) , previous trials of tea drinking and administration of green tea extract have failed to show any impact on lipids and lipoproteins in humans . Our objective was to study the impact of a theaflavin-enriched green tea extract on the lipids and lipoproteins of subjects with mild to moderate hypercholesterolemia . METHODS Double-blind , r and omized , placebo-controlled , parallel-group trial set in outpatient clinics in 6 urban hospitals in China . A total of 240 men and women 18 years or older on a low-fat diet with mild to moderate hypercholesterolemia were r and omly assigned to receive a daily capsule containing theaflavin-enriched green tea extract ( 375 mg ) or placebo for 12 weeks . Main outcome measures were mean percentage changes in total cholesterol , LDL-C , high-density lipoprotein cholesterol ( HDL-C ) , and triglyceride levels compared with baseline . RESULTS After 12 weeks , the mean + /- SEM changes from baseline in total cholesterol , LDL-C , HDL-C , and triglyceride levels were -11.3 % + /- 0.9 % ( P = .01 ) , -16.4 % + /- 1.1 % ( P = .01 ) , 2.3 % + /- 2.1 % ( P = .27 ) , and 2.6 % + /- 3.5 % ( P = .47 ) , respectively , in the tea extract group . The mean levels of total cholesterol , LDL-C , HDL-C , and triglycerides did not change significantly in the placebo group . No significant adverse events were observed . CONCLUSION The theaflavin-enriched green tea extract we studied is an effective adjunct to a low-saturated-fat diet to reduce LDL-C in hypercholesterolemic adults and is well tolerated Thirty-one men ( 47 ( SD 14 ) years ) and thirty-four women ( 35 ( SD 13 ) years ) took part in a 4-week r and omized cross-over trial to compare the effect of six mugs of black tea daily v. placebo ( water , caffeine , milk and sugar ) on blood lipids , bowel habit and blood pressure , measured during a run-in period and at the end of weeks 2 , 3 and 4 of the test periods . Compliance was established by adding a known amount of p-aminobenzoic acid ( PABA ) to selected tea bags , and then measuring its excretion in urine . Mean serum cholesterol values during run-in , placebo and on tea drinking were 5.67 ( SD 1.05 ) , 5.76 ( SD 1.11 ) and 5.69 ( SD 1.09 ) mmol/l ( P = 0.16 ) . There were also no significant changes in diet , LDL-cholesterol , HDL-cholesterol , triacylglycerols , and blood pressure in the tea intervention period compared with placebo . Compared with placebo , stool consistency was softened with tea ( P = 0.04 ) , and no other differences were found in bowel habit . Results were unchanged when fifteen ' non-compliers ' , whose PABA excretion indicated that fewer than six tea bags had been used , were excluded from the analysis , and when differences between run-in and tea periods were considered separately for those who were given tea first or second The antioxidant activity of green tea ( GT ) has been extensively studied ; however , the results obtained from dietary intervention studies are controversial . In the present study we investigated the effect of the addition of two cups of GT ( containing approximately 250 mg of total catechins ) to a controlled diet in a group of healthy volunteers with respect to a group following the same controlled diet but not consuming GT . Antioxidant status and lipid profile in plasma , the resistance from oxidative damage to lipid and DNA , and the activity of glutathione peroxidase ( GPX ) in isolated lymphocytes were measured at the beginning and the end of the trial . After 42 days , consumption of GT caused a significant increase in plasma total antioxidant activity [ from 1.79 to 1.98 micromol Trolox equivalent (TE)/ml , P<.001 ] , significant decreases in plasma peroxides level ( from 412 to 288 Carr U , P<.05 ) and induced DNA oxidative damage in lymphocytes ( from 14.2 % to 10.1 % of DNA in tail , P<.05 ) , a moderate although significant decrease in LDL cholesterol ( from 119.9 to 106.6 mg/dL , P<.05 ) with respect to control . The present study suggests the ability of GT , consumed within a balanced controlled diet , to improve overall the antioxidative status and to protect against oxidative damage in humans Background The effects of coffee and green , black and oolong teas and caffeine intake on cardiovascular disease ( CVD ) mortality have not been well defined in Asian countries . Methods To examine the relationship between the consumption of these beverages and risk of mortality from CVD , 76 979 individuals aged 40–79 years free of stroke , coronary heart disease ( CHD ) and cancer at entry were prospect ively followed . The daily consumption of beverages was assessed by question naires . Results 1362 deaths were documented from strokes and 650 deaths from CHD after 1 010 787 person-years of follow-up . Compared with non-drinkers of coffee , the multivariable HR and 95 % CI for those drinking 1–6 cups/week , 1–2 cups/day and ≥3 cups/day were 0.78 ( 0.50 to 1.20 ) , 0.67 ( 0.47 to 0.96 ) and 0.45 ( 0.17 to 0.87 ) for strokes among men ( p=0.009 for trend ) . Compared with non-drinkers of green tea , the multivariable HR for those drinking 1–6 cups/week , 1–2 cups/day , 3–5 cups/day and ≥6 cups/day were 0.34 ( 0.06–1.75 ) , 0.28 ( 0.07–1.11 ) , 0.39 ( 0.18–0.85 ) and 0.42 ( 0.17–0.88 ) for CHD among women ( p=0.038 for trend ) . As for oolong tea , the multivariable HR of those drinking 1–6 cups/week and ≥1 cups/day were 1.00 ( 0.65–1.55 ) and 0.39 ( 0.17–0.88 ) for total CVD among men ( p=0.049 for trend ) . Risk reduction for total CVD across categories of caffeine intake was most prominently observed in the second highest quintile , with a 38 % lower risk among men and 22 % among women . Conclusions Consumption of coffee , green tea and oolong tea and total caffeine intake was associated with a reduced risk of mortality from CVD The aim of this study was to evaluate the combined effects of a 10-week exercise program with ingestion of caffeine and epigallocatechin-3-gallate ( EGCG ) on body composition , cardiovascular fitness , and strength in overweight and obese women . In a double-blind , placebo-controlled approach , overweight and obese women ( n = 27 ) were r and omly assigned to treatment groups with exercise ( an active-supplementing group with exercise ( EX-Act ) and a placebo group with exercise ( EX-PL ) ) or without exercise ( an active-supplementing group without exercise ( NEX-Act ) and a placebo group without exercise ( NEX-PL ) ) . All participants consumed 1 drink per day for 10 weeks ; EX-Act and EX-PL participated in a concurrent endurance and resistance training program . Changes in body composition were assessed using a 4-compartment model . Changes in muscle mass ( MM ) were evaluated using a DXA-derived appendicular lean-soft tissue equation . There was a significant time × treatment interaction for MM ( p = 0.026 ) and total cholesterol ( TC ) ( p = 0.047 ) , and a significant time × training interaction for peak oxygen consumption ( p = 0.046 ) and upper-body and lower-body strength ( p < 0.05 ) . Significant differences between the EX groups and NEX groups for percentage change in MM and peak oxygen consumption , and upper-body and lower-body strength , were revealed . Clinical markers for hepatic and renal function revealed no adverse effects . TC significantly decreased for the active-supplementing groups ( EX-Act , NEX-Act ) . The current study suggests that implementing a caffeine-EGCG-containing drink prior to exercise may improve MM , fitness , and lipid profiles in overweight women Obesity is a major health problem in the developed and developing world . Many " functional " foods and ingredients are advocated for their effects on body composition but few have consistent scientific support for their efficacy . However , an increasing amount of mechanistic and clinical evidence is building for green tea ( GT ) . This experiment was therefore undertaken to study the effects of a high-catechin GT on body composition in a moderately overweight Chinese population . In a r and omized placebo-controlled trial , 182 moderately overweight Chinese subjects , consumed either two servings of a control drink ( C ; 30 mg catechins , 10 mg caffeine/day ) , one serving of the control drink and one serving of an extra high-catechin GT1 ( 458 mg catechins , 104 mg caffeine/day ) , two servings of a high-catechin GT2 ( 468 mg catechins , 126 mg caffeine/day ) or two servings of the extra high-catechin GT3 ( 886 mg catechins , 198 mg caffeine/day ) for 90 days . Data were collected at 0 , 30 , 60 , and 90 days . We observed a decrease in estimated intra-abdominal fat ( IAF ) area of 5.6 cm(2 ) in the GT3 group . In addition , we found decreases of 1.9 cm in waist circumference and 1.2 kg body weight in the GT3 group vs. C ( P < 0.05 ) . We also observed reductions in total body fat ( GT2 , 0.7 kg , P < 0.05 ) and body fat % ( GT1 , 0.6 % , P < 0.05 ) . We conclude that consumption of two servings of an extra high-catechin GT leads to improvements in body composition and reduces abdominal fatness in moderately overweight Chinese subjects SCOPE Evidence for the benefits of green tea catechins on vascular function is inconsistent , with genotype potentially contributing to the heterogeneity in response . Here , the impact of the catechol-O-methyltransferase ( COMT ) genotype on vascular function and blood pressure ( BP ) after green tea extract ingestion are reported . METHODS AND RESULTS Fifty subjects ( n = 25 of the proposed low-activity [ AA ] and of the high-activity [ GG ] COMT rs4680 genotype ) , completed a r and omized , double-blind , crossover study . Peripheral arterial tonometry , digital volume pulse ( DVP ) , and BP were assessed at baseline and 90 min after 1.06 g of green tea extract or placebo . A 5.5 h and subsequent 18.5 h urine collection was performed to assess green tea catechin excretion . A genotype × treatment interaction was observed for DVP reflection index ( p = 0.014 ) , with green tea extract in the AA COMT group attenuating the increase observed with placebo . A tendency for a greater increase in diastolic BP was evident at 90 min after the green tea extract compared to placebo ( p = 0.07 ) . A genotypic effect was observed for urinary methylated epigallocatechin during the first 5.5 h , with the GG COMT group demonstrating a greater concentration ( p = 0.049 ) . CONCLUSION Differences in small vessel tone according to COMT genotype were evident after acute green tea extract |
1,879 | 17,302,669 | For all types of respite , the effects upon caregivers were generally small , with better-controlled studies finding modest benefits only for certain subgroups , although many studies reported high levels of caregiver satisfaction .
No reliable evidence was found that respite care delays entry to residential care or adversely affects frail older people .
The economic evaluations all assessed day care , which tended to be associated with similar or higher costs than usual care . | The proportion of frail elderly people in the industrialized world is increasing .
Respite care is a potentially important way of maintaining the quality of life for these people and their caregivers .
The objective of this systematic review was to determine the effectiveness and cost-effectiveness of different models of community-based respite care for frail older people and their caregivers . | Background : There is no single generally accepted clinical definition of frailty . Previously developed tools to assess frailty that have been shown to be predictive of death or need for entry into an institutional facility have not gained acceptance among practising clinicians . We aim ed to develop a tool that would be both predictive and easy to use . Methods : We developed the 7-point Clinical Frailty Scale and applied it and other established tools that measure frailty to 2305 elderly patients who participated in the second stage of the Canadian Study of Health and Aging ( CSHA ) . We followed this cohort prospect ively ; after 5 years , we determined the ability of the Clinical Frailty Scale to predict death or need for institutional care , and correlated the results with those obtained from other established tools . Results : The CSHA Clinical Frailty Scale was highly correlated ( r = 0.80 ) with the Frailty Index . Each 1-category increment of our scale significantly increased the medium-term risks of death ( 21.2 % within about 70 mo , 95 % confidence interval [ CI ] 12.5%–30.6 % ) and entry into an institution ( 23.9 % , 95 % CI 8.8%–41.2 % ) in multivariable models that adjusted for age , sex and education . Analyses of receiver operating characteristic curves showed that our Clinical Frailty Scale performed better than measures of cognition , function or comorbidity in assessing risk for death ( area under the curve 0.77 for 18-month and 0.70 for 70-month mortality ) . Interpretation : Frailty is a valid and clinical ly important construct that is recognizable by physicians . Clinical judgments about frailty can yield useful predictive information Applicants for a newly opened special unit for dementia sufferers were r and omly allocated to full-time care in the unit or placed on a waiting list and offered periodic respite care in the meantime . All applicants were living in the community at the time of r and om assignment . Both groups were followed up for three months to assess the effects on the dementia sufferers and on their family care-givers . Care-givers initially had a high level of psychological symptoms , which was greatly reduced after admission of the dementia sufferer to full-time care . By contrast , the care-givers of the community care group of sufferers continued to have a high level of symptoms . Dementia sufferers continued to deteriorate with both forms of care , with little difference between the two groups . Admission of dementia sufferers to full-time care in a special unit appears to be of great benefit to the psychological health of their care-givers and has no adverse effects on the dementia sufferers themselves A program for elderly persons with cognitive impairment and their caregivers was evaluated for its effectiveness and efficiency with regard to caregiver burden , sense of coherence , satisfaction , and cost to the health-care system . The program consisted of a weekly 2-hour visit and walk by volunteers . During a 9-month period in 1997 , all eligible referrals were r and omly assigned to receive the service immediately ( experimental group ) or be placed on a waiting list to receive it 6 weeks later ( control group ) . Eleven caregivers/recipients formed the experimental group ; 10 caregivers/recipients formed the control group . All completed question naires at r and omization and at 6-week follow-up . Perceived burden decreased by 8 % only for the caregivers in the experimental group ( F = 6.8 , p = .02 ) . They indicated that they appreciated the respite and support and that the care recipient enjoyed the visit/walk . Although this study was short in duration and small in sample size , improvements were noted in perceived caregiver burden and caregivers expressed satisfaction with the program . The program did not result in additional health and social-service expenditures Family units ( N = 541 ) of impaired elderly persons and caregivers were r and omly assigned to a control group or one of five treatment groups eligible for a variety of respite or educational services . After 12 months of service eligibility , caregivers of elderly persons remaining in the community reported lower levels of subjective burden . Services appeared to delay nursing home placement among families with adult child caregivers , but encouraged placement by spouse caregivers This article summarizes the study results and presents an evaluative summary of the implementation of study methods design ed to provide guidance in the degree of confidence with which the results may be accepted and generalized to other situations . Patients who were offered VA-ADHC services in the first phase of this study had significantly higher VA health care costs on average than patients assigned to customary care , with no apparent incremental health benefit to themselves or their care givers . One can have a high level of confidence in these results . The ADHC clinical services were implemented as planned , the r and omized controlled trial was implemented successfully , and such threats to validity as insufficient numbers of patients and differential attrition were not present . Certain subgroups of patients assigned to VA-ADHC had VA costs of care that were not significantly higher than those assigned to customary care , although these results must be interpreted with caution . The findings of the second phase of the study evaluating contract ADHC provide no support for choosing to provide either contract ADHC or VA-ADHC over the other . The nonr and omized design and smaller sample size suggest that inferences from the contract ADHC evaluation should be drawn with more caution than those from the VA-ADHC evaluation OBJECTIVES This study reports the findings of an evaluation of the psychological benefits of use of adult day care by family caregivers assisting a relative with dementia . METHODS The study used a quasi-experimental design in which caregivers in the treatment group used substantial amounts of services , whereas caregivers in a control group did not use day care at any point during the evaluation and only small amounts of other respite services . The evaluation was guided by the stress process model of caregiving which distinguishes between appraisal s of primary stressors and well-being . RESULTS Results after 3 months of day care use showed that the treatment group had significantly lower scores than the control group on two of the three measures of primary appraisal s ( overload and strain ) and two of the three measures of well-being ( depression and anger ) . Findings at one year showed that the treatment group had significantly lower scores on overload and depression than the control group . DISCUSSION These results demonstrate that use of adult day care by caregivers of dementia patients results in lower levels of caregiving-related stress and better psychological well-being when compared to that of controls Collaborative working in care for older people is often seen as a desirable goal . However , there can be problems with this approach . This paper reports on a single blind r and omized controlled trial which was carried out to compare outcomes of rehabilitation in two setting s : a day hospital and social services day centres augmented by visiting therapists . The subjects were 105 older patients . Principal outcome measures were the Barthel Index , Philadelphia Geriatric Centre Morale Scale and the Caregiver Strain Index . Two aspects of the trial are examined here . Firstly , we investigated whether trial patients were more disabled than regular day centre attendees . Levels of health and well being amongst trial patients were compared with those of a r and om sample of 20 regular attendees from both of the participating day centres and an additional voluntary sector day centre . Secondly , key staff from the different setting s were interviewed to assess how well the day centre model had worked in practice . Trial patients were significantly more disabled than regular day centre attendees according to the Barthel Index ( P < 0.001 ) , but this difference was no longer significant after three months of treatment . The day centre model had several problems , principally discharge policy , acceptability , facilities and attitudes of staff and regular attendees . Positive aspects of the day centre model , as well as successful rehabilitation , included shared skills , knowledge and re sources . This paper suggests that collaborative working in day centres requires multi purpose facilities . If health staff maintain a permanent presence , benefits can include improved joint working , easier access to health care and the use of rehabilitative therapy as a preventative strategy . Day care setting s can be analyzed as representing different types of communities . Allowing older users a greater degree of choice in facilities may increase the acceptability of care Objectives : To assess outcomes and satisfaction among frail elderly day care clients and their informal caregivers and the impact of adult day care on the cost of health services . Methods : One-hundred eight elderly participants were r and omly assigned to the experimental group ( immediate admission to an adult day care center ) and 104 participants to the control group ( 3 months on a waiting list ) . Results : Participants ’ and caregivers ’ subjective perceptions of the day center ’s effects were positive . However , using st and ard research instruments , there was no evidence of an effect of day center attendance on the client ’s anxiety , depression , or functional status ; on caregiver burden ; or on the cost of health services . Discussion : It is difficult to demonstrate objective ly the benefits of programs and interventions that are perceived by clients , caregivers , and staff to have positive effects . In future studies , maintenance of high levels of participation should be incorporated as an explicit program goal After a baseline interview of 642 caregivers of aged Alzheimer 's disease victims , half were offered formal respite care . Over 12 months , families with respite care maintained their impaired relative significantly longer in the community ( 22 days ) . Although respite was ineffective for caregiver burden and mental health , satisfaction was very high . Although not a strong intervention , respite care can increase caregivers ' quality of life |
1,880 | 26,323,946 | CONCLUSIONS RTB is safe and has a high diagnostic yield in experienced centres .
Both CB and FNA have good accuracy for the diagnosis of malignancy and histologic subtype , with better performance for CB .
The accuracy for Fuhrman grade is fair .
The results suggest that RTB has good accuracy in diagnosing renal cancer and its subtypes , and it appears to be safe . | CONTEXT The role of percutaneous renal tumour biopsy ( RTB ) remains controversial due to uncertainties regarding its diagnostic accuracy and safety .
OBJECTIVE We performed a systematic review and meta- analysis to determine the safety and accuracy of percutaneous RTB for the diagnosis of malignancy , histologic tumour subtype , and grade .
PATIENT SUMMARY We systematic ally review ed the literature to assess the safety and diagnostic performance of renal tumour biopsy ( RTB ) . | BACKGROUND Most early stage kidney cancers are renal cell carcinomas ( RCCs ) , and most are diagnosed incidentally by imaging as small renal masses ( SRMs ) . Indirect evidence suggests that most small RCCs grow slowly and rarely metastasize . OBJECTIVE To determine the progression and growth rates for newly diagnosed SRMs stratified by needle core biopsy pathology . DESIGN , SETTING , AND PARTICIPANTS A multicenter prospect i ve phase 2 clinical trial of active surveillance of 209 SRMs in 178 elderly and /or infirm patients was conducted from 2004 until 2009 with treatment delayed until progression . INTERVENTION Patients underwent serial imaging and needle core biopsies . MEASUREMENTS We measured rates of change in tumor diameter ( growth measured by imaging ) and progression to ≥ 4 cm , doubling of tumor volume , or metastasis with histology on biopsy . RESULTS AND LIMITATIONS Local progression occurred in 25 patients ( 12 % ) , plus 2 progressed with metastases ( 1.1 % ) . Of the 178 subjects with 209 SRMs , 127 with 151 SRMs had>12 mo of follow-up with two or more images , with a mean follow-up of 28 mo . Their tumor diameters increased by an average of 0.13 cm/yr . Needle core biopsy in 101 SRMs demonstrated that the presence of RCC did not significantly change growth rate . Limitations included no central review of imaging and pathology and a short follow-up . CONCLUSIONS This is the first SRM active surveillance study to correlate growth with histology prospect ively . In the first 2 yr , the rate of local progression to higher stage is low , and metastases are rare . SRMs appear to grow very slowly , even if biopsy proven to be RCC . Many patients with SRMs can therefore be initially managed conservatively with serial imaging , avoiding the morbidity of surgical or ablative treatment PURPOSE To evaluate the feasibility and complications of ultrasound (US)-guided biopsy of small renal masses ( SRMs ) and to determine factors that contribute to nondiagnostic biopsy specimens . MATERIAL S AND METHODS Between June 2004 and May 2011 , 58 consecutive patients underwent US-guided core biopsy of a SRM ( > 1 cm and ≤4 cm ) using an 18-gauge core biopsy device . The diagnostic rate , histologic diagnosis , and complications of US-guided core biopsy were assessed . Mann-Whitney U and Fisher exact tests were used to compare diagnostic and nondiagnostic biopsy specimens . Univariate analysis was performed to determine the predictive factors for nondiagnostic biopsy specimens . RESULTS There were 59 biopsies of SRMs performed , and the diagnostic rate was 81 % ( 48 of 59 ) . The mass size of diagnostic and nondiagnostic biopsy specimens ranged from 1.2 - 3.9 cm ( 2.4 cm±0.7 ) for diagnostic specimens and from 1.1 - 3.5 cm ( 1.9 cm±0.7 ) for nondiagnostic specimens ( P = .024 ) . Of the diagnostic biopsy specimens , 77 % ( 37 of 48 ) were malignant , and 23 % ( 11 of 48 ) were benign . Minor complications developed in 20.3 % ( 12 of 59 ) of biopsies . The lesion size or core number threshold for decreasing diagnostic rate was 2 cm or three cores . A cystic mass , fewer cores ( three or fewer cores ) , an upper pole mass , and a small mass ( ≤2 cm ) significantly predicted a nondiagnostic biopsy specimen ( P = .007-.046 ) . CONCLUSIONS US-guided core biopsy is a feasible and safe procedure for histologic diagnosis of a SRM . However , nondiagnostic rates may increase when a cystic mass is biopsied , a mass is located in an upper pole mass , a mass is 2 cm or less , and three cores or fewer are sample OBJECTIVES To determine the accuracy and clinical utility of fine needle aspiration ( FNA ) of small , solid renal masses . METHODS A total of 25 patients with small ( less than 5.0 cm ) , solid , clinical ly localized renal masses were prospect ively identified and evaluated with computed tomography guided FNA with analysis for presence of malignant cells and determination of nuclear grade . The final pathologic findings were used for comparison in each case . All patients had renal cell carcinoma and were managed with radical or partial nephrectomy ; 3 had low- grade lesions ( Fuhrman 's grade 1/4 ) , 2 had high- grade lesions ( Fuhrman 's grade 4/4 ) , and all other patients had intermediate- grade lesions ( Fuhrman 's grade 2/4 or 3/4 ) on final histopathologic assessment . RESULTS Overall , 10 aspirations yielded diagnostic malignant cells , and 9 were read as rare as rare atypical cells suspicious for malignancy . The remainder were negative ( n = 6 ) . Correlation with final nuclear grade was observed in eight instances and discordance in two instances . Subcapsular hematomas were observed at the time of surgery in 10 patients , but in no instance was the operation adversely affected . CONCLUSIONS The diagnostic yield of FNA of small , solid renal masses appears to be too low to justify the potential morbidity of the procedure Purpose In some cases with uncertain renal tumour lesions , it would be helpful to perform biopsies for the preoperative differential diagnosis . In our study , we evaluated the benefit of multi-colour interphase fluorescence in situ hybridization ( M-FISH ) on fine-needle core biopsies in uncertain renal masses . Methods We prospect ively performed three ultrasound-guided percutaneous biopsies in 25 patients with indeterminate renal masses preoperatively . Histopathology was performed on two remaining cores sample s. M-FISH was performed on one core for chromosomes 1 , 2 , 6 , 9 , 7 , 17 , the loci 3p24pter , and 3p13p14 . After interphase FISH evaluation , we classified tumours and compared the results with histopathological findings . Results 16 were classified as renal malignancies : 14 ( 56 % ) clear cell renal cell carcinomas ( RCCs ) , 1 papillary RCCs ( 4 % ) , and 1 “ adenocarcinoma ” ( 4 % ) . Seven patients ( 28 % ) had a benign tumour , i.e. 6 ( 24 % ) were oncocytomas and 1 was classified as leiomyoma ( 4 % ) . In two cases ( 8 % ) , no renal neoplasms were found . In 19 out of 21 cases ( 90.5 % ) , the preoperative diagnostic fine-needle biopsy matched the final histological findings . The combination of histopathological examination and M-FISH leads to a higher ( 95.5 vs. 90.5 % ) diagnostic fidelity as histology alone . Conclusions Ultrasound-guided percutaneous renal tumour biopsy is an accurate and safety method for the histopathologic evaluation of uncertain renal masses . The M-FISH represents a new highly sensitive and specific method to confirm histopathological classification in less than 24 h which can be used in routine laboratory diagnosis OBJECTIVES We evaluated the reliability of sonographic criteria in selecting solid renal masses for percutaneous fine-needle biopsy . METHODS In study 1 ( intraoperative ultrasound study ) , we prospect ively examined 100 consecutive patients scheduled for partial/radical nephrectomy by using two different high-resolution probes ( Philips HDI 5000 , CT8 - 4 , L12 - 5 ; 4 - 12MHz ) . The main tumor was intraoperatively evaluated by B-mode and power Doppler sonography . Morphologic characteristics seen on ultrasound were categorized in (non-)homogenous and (non-)cystic renal masses and were related to findings of pathological examination . Study 1 provided the selection criteria for study 2 . In study 2 ( percutaneous biopsy study ) , under local anesthesia and with the use of an 18-G needle , we prospect ively performed two to three sonographically guided percutaneous biopsies in 30 consecutive patients whose tumors appeared to be homogenous and noncystic according to the sonograph ( convex array 3.5MHz , HDI 5000 , C5 - 2 and Falcon 2101 EXL , B+K Medical ) . RESULTS In the ultrasound study , only 16 ( 22.9 % ) of the 76 clear-cell carcinomas but all 9 ( 100 % ) oncocytoma appeared homogenous and noncystic on high-resolution intraoperative ultrasound . By applying these results to 30 patients of study 2 ( 18 men , 12 women ; aged 63+/-7.7 yr , tumor size 29+/-11.3 mm ) who met these sonographic criteria on preoperative transabdominal ultrasound , we bioptically diagnosed 8 ( 26.7 % ) benign tumors ; 25 of 30 ( 83.3 % ) patients were accurately diagnosed . Small tumors ( <3 cm ) , decreased breathing compliance , and medially located renal lesions seem to negatively influence biopsy results . CONCLUSIONS Kidney tumors that appear noncystic and homogenous on preoperative ultrasound are more likely to be of benign origin . Ultrasound-guided percutaneous biopsy of these solid renal masses could determine renal tumor patients for whom surveillance might be an option . However , experienced and dedicated histopathologic evaluation remains crucial to observe patients with clearly benign biopsy results . All even slightly question able biopsy findings require surgical exploration OBJECTIVE Modern imaging modalities increase the detection of small ( < or=4 cm ) renal tumors , of which about 20 % are benign . As a result , minimal invasive treatments , such as radiofrequency ablation and cryotherapy , and surveillance strategies are gaining popularity . Information that would be helpful when choosing the most appropriate management strategy for this patient group could be obtained from pretherapeutic image-guided biopsy . METHODS Under computed tomography (CT)-fluoroscopic guidance 78 patients with solid renal tumors prospect ively underwent 18-gauge core biopsy . In addition , using the same sheath , fine-needle aspiration was taken in 44 patients and analyzed cytologically . The renal masses were subsequently removed surgically and evaluated histologically . RESULTS Mean patient age was 63+/-13.5 yr ; mean tumor size was 4+/-1.8 cm . The sensitivity of core biopsy and fine-needle aspiration for the detection of renal cell carcinoma ( RCC ) was 93.5 % and 90.6 % , respectively ; Fuhrman grade was correctly predicted in 76 % and 28 % and the correct histologic subtype was identified 91 % and 86 % , respectively . Cytology from fine-needle aspiration revealed a sensitivity in detecting malignant and benign lesions of 100 % and 75 % , respectively . Two of the renal tumors diagnosed as oncocytomas on core biopsy were hybrid tumors with scattered areas of oncocytomas and chromophobe RCC . Complications of CT-guided biopsy included one marginal pneumothorax , which resolved under conservative management , and four small perirenal hematomas detected at follow-up ultrasonography not requiring further therapy . CONCLUSION CT-guided percutaneous preoperative renal tumor biopsy had a high diagnostic accuracy , particularly in predicting malignancy BACKGROUND Percutaneous needle core biopsy has become established in the management of small renal masses ≤ 4 cm ( SRMs ) . Recent series have reported success rates of ≥ 80 % . Nondiagnostic results continue to be problematic . OBJECTIVE To determine the results of SRM biopsy and the outcomes of nondiagnostic biopsy and repeat biopsy . DESIGN , SETTING , AND PARTICIPANTS Patients undergoing renal tumor biopsy ( RTB ) for suspected renal cell carcinoma ( RCC ) were included in a prospect ively maintained data base . MEASUREMENTS The data base was analyzed retrospectively to determine the pathology and outcomes of SRM biopsy . Outcomes of patients with nondiagnostic biopsy were determined . Patients undergoing repeat biopsy were identified and their outcomes analyzed . RESULTS AND LIMITATIONS Three hundred forty-five biopsies were performed ( mean diameter : 2.5 cm ) . Biopsy was diagnostic in 278 cases ( 80.6 % ) and nondiagnostic in 67 cases ( 19.4 % ) . Among diagnostic biopsies , 221 ( 79.4 % ) were malignant , 94.1 % of which were RCC . Histologic subtyping and grading of RCC was possible in 88.0 % and 63.5 % of cases , respectively . Repeat biopsy was performed in 12 of the 67 nondiagnostic cases , and a diagnosis was possible in 10 ( 83.3 % ) . Eight lesions were malignant and two were oncocytic neoplasms . Pathology was available for 15 masses after initial nondiagnostic biopsy ; 11 ( 73 % ) were malignant . Larger tumor size and a solid nature on imaging predicted a successful biopsy on multivariate analysis . Grade 1 complications were experienced in 10.1 % of cases , with no major bleeding and no seeding of the biopsy tract . There was one grade 3a complication ( 0.3 % ) . This is a retrospective study and some data are unavailable on factors that may affect biopsy success rates . Repeat biopsy was not st and ard practice prior to this analysis . CONCLUSIONS RTB can be performed safely and accurately in the investigation of renal masses ≤ 4 cm . A nondiagnostic biopsy should not be considered a surrogate for the absence of malignancy . Repeat biopsy can be performed with similar accuracy , providing a diagnosis for most patients |
1,881 | 27,000,385 | Moreover , percutaneous endovascular aneurysm repair did not increase the risk of haematoma , pseudoaneurysm , and arterial thrombosis or dissection .
Conclusion Percutaneous access demonstrates advantages over conventional surgical exposure for endovascular aneurysm repair , as indicated by access-related complications and hospital length of stay . | Purpose Our objective was to undertake a comprehensive review of the literature and conduct an analysis of the outcomes of percutaneous endovascular aneurysm repair . | OBJECTIVES The aim was to investigate whether the fascia suture technique ( FST ) can reduce access closure time and procedural costs compared with the Prostar technique ( Prostar ) in patients undergoing endovascular aortic repair and to evaluate the short- and mid-term outcomes of both techniques . METHODS In this two center trial , 100 patients were r and omized to access closure by either FST or Prostar between June 2006 and December 2009 . The primary endpoint was access closure time . Secondary outcome measures included access related costs and evaluation of the short- and mid-term complications . Evaluation was performed peri- and post-operatively , at discharge , at 30 days and at 6 months follow up . RESULTS The median access closure time was 12.4 minutes for FST and 19.9 minutes for Prostar ( p < .001 ) . Prostar required a 54 % greater procedure time than FST , mean ratio 1.54 ( 95 % CI 1.25 - 1.90 , p < .001 ) according to regression analysis . Adjusted for operator experience the mean ratio was 1.30 ( 95 % CI 1.09 - 1.55 , p = .005 ) and for patient body mass index 1.59 ( 95 % CI 1.28 - 1.96 , p < .001 ) . The technical failure rate for operators at proficiency level was 5 % ( 2/40 ) compared with 28 % ( 17/59 ) for those at the basic level ( p = .003 ) . The proficiency level group had a technical failure rate of 4 % ( 1/26 ) for FST and 7 % ( 1/14 ) for Prostar , p = 1.00 , while corresponding rates for the basic level group were 27 % ( 6/22 ) for FST and 30 % ( 11/37 ) for Prostar ( p = .84 ) . There was a significant difference in cost in favor of FST , with a median difference of € 800 ( 95 % CI 710 - 927 , p < .001 ) . CONCLUSIONS In aortic endovascular repair FST is a faster and cheaper technique than the Prostar technique OBJECTIVE The first multicenter r and omized controlled trial was design ed and conducted to assess the safety and effectiveness of totally percutaneous endovascular aortic aneurysm repair ( PEVAR ) with use of a 21F endovascular stent graft system and either an 8 F or 10 F suture-mediated closure system ( the PEVAR trial , NCT01070069 ) . A noninferiority trial design was chosen to compare percutaneous access with st and ard open femoral exposure . METHODS Between 2010 and 2012 , 20 U.S. institutions participated in a prospect i ve , Food and Drug Administration-approved r and omized trial to evaluate percutaneous femoral artery access and closure by a " preclose " technique in conjunction with endovascular abdominal aortic aneurysm repair . A total of 151 patients were allocated by a 2:1 design to percutaneous access/closure ( n = 101 ) or open femoral exposure ( n = 50 [ FE ] ) . PEVAR procedures were performed with either the 8 F Perclose ProGlide ( n = 50 [ PG ] ) or the 10 F Prostar XL ( n = 51 [ PS ] ) closure devices . All endovascular abdominal aortic aneurysm repair procedures were performed with the Endologix 21 F profile ( outer diameter ) sheath-based system . Patients were screened by computed tomography with three-dimensional reconstruction and independent physician review for anatomic suitability and adequate femoral artery anatomy for percutaneous access . The primary trial end point ( treatment success ) was defined as procedural technical success and absence of major adverse events and vascular complications at 30 days . An independent access closure sub study evaluated major access-related complications . Clinical utility and procedural outcomes , ankle-brachial index , blood laboratory analyses , and quality of life were also evaluated with continuing follow-up to 6 months . RESULTS Baseline characteristics were similar among groups . Procedural technical success was 94 % ( PG ) , 88 % ( PS ) , and 98 % ( FE ) . One-month primary treatment success was 88 % ( PG ) , 78 % ( PS ) , and 78 % ( FE ) , demonstrating noninferiority vs FE for PG ( P = .004 ) but not for PS ( P = .102 ) . Failure rates in the access closure sub study analyses demonstrated noninferiority of PG ( 6 % ; P = .005 ) , but not of PS ( 12 % ; P = .100 ) , vs FE ( 10 % ) . Compared with FE , PG and PS yielded significantly shorter times to hemostasis and procedure completion and favorable trends in blood loss , groin pain , and overall quality of life . Initial noninferiority test results persist to 6 months , and no aneurysm rupture , conversion to open repair , device migration , or stent graft occlusion occurred . CONCLUSIONS Among trained operators , PEVAR with an adjunctive preclose technique using the ProGlide closure device is safe and effective , with minimal access-related complications , and it is noninferior to st and ard open femoral exposure . Training , experience , and careful application of the preclose technique are of paramount importance in ensuring successful , sustainable outcomes Introduction While endovascular aortic aneurysm repair ( EVAR ) has significantly reduced the morbidity associated with open surgery , efforts continue to minimise the surgical insult to the patient . We report our experience of percutaneous EVAR . Patients and methods Since June 2005 , 17/20 EVARs ( 85 % ) have been attempted percutaneously by deployment of two Perclose © devices into each femoral artery prior to passage of the device sheath . The sutures are left untied until the sheath is removed at the end of the procedure , when haemostasis is obtained . Patients were entered onto a prospect ively maintained data base and followed up at regular intervals in a dedicated EVAR clinic . Results Access and subsequent graft deployment was successful in all the 17 cases . The range of defects closed ranged from 12–24 Fr . Five patients ( 29 % ) required open groin exploration at the end of the procedure to achieve haemostasis . There was a significantly lower incidence of wound complications in the percutaneous EVAR group ( 6 vs. 10 % open cutdown cases , P < 0.05 , Mann – Whitney U test ) . Conclusion Percutaneous EVAR is both a feasible and safe method of performing endovascular abdominal aortic aneurysm repair , which is associated with a reduction in wound complication rates PURPOSE To evaluate safety and cost benefits of the percutaneous technique for treatment of aortic aneurysm , a prospect i ve r and omized study was performed that compared the endovascular suture technique with conventional cutdown access and repair . MATERIAL S AND METHODS From January 2002 through July 2002 , 30 endografts , including 14 Talent stent-grafts ( Medtronic , Sunrise , Fla ) and 16 Zenith endografts ( Cook , Bloomington , Ind ) were implanted in 30 patients for endovascular aneurysm treatment . The patients were r and omized to either percutaneous technique ( group A ) or conventional cutdown ( group B ) . Fifty-five femoral arteries were cannulated with large-bore ( 14F-25F ) introducers and were included in the study . Safety and efficiency of both techniques were assessed by recording the complication rates , operation time , discharge , and time to ambulation . Comparison of selected estimated costs included both variable and fixed costs for femoral access and expenses for treatment of complications . RESULTS No operative deaths occurred . The complication rates were similar and included 1 arterial thrombosis in each group , 3 lymphoceles in group B , and 1 conversion to cutdown because of bleeding in group A. Mean surgery time ( 86.7 + /- 27 minutes vs 107.8 + /- 38.5 minutes ; P < .05 ) and time to ambulation ( 20.1 + /- 4.3 hours vs 33.1 + /- 18.4 hours ; P < .001 ) were significantly shorter in the group treated percutaneously . Because of the cost of the closure device , total cost of the percutaneous technique averaged 99.2 euro ; more than cutdown . CONCLUSIONS The percutaneous technique decreases the invasiveness of endovascular therapy of aortic aneurysm and reduces operative time and time to ambulation . Complications were roughly equivalent in severity . The additional cost for the device appears to justify its use for this form of aneurysm treatment PURPOSE This study was design ed to describe and evaluate our preliminary results with a percutaneous arterial closure device as compared to those obtained with conventional femoral surgical cut down during endovascular repair of abdominal aortic aneurysms ( AAA ) . MATERIAL AND METHODS Between January 2004 and December 2006 , 40 of 86 AAA patients selected for endovascular repair met the criteria for inclusion in this study . Nineteen of these patients ( Group A ) received a bifurcated endograft placed by direct puncture of the femoral arteries ( 38 femoral triangles ) with closure by a Prostar((R ) ) percutaneous arterial closure device ( Abbott ) . The other 21 patients ( control group B ) were managed with a bifurcated endograft placed by conventional open surgery ( 42 femoral triangles ) . Data concerning all 40 patients were collected prospect ively and analyzed . RESULTS The technical success rate was 92 % ( group A ) vs 90 % ( group B ) , P=0.79 . The incidence of perioperative complications was 16 % ( 3/19 ) in group A and 14 % ( 3/21 ) in group B ( P=0.89 ) . The mean hospital stay was 5.8 days in group A and 7.8 days in group B ( P=0.05 ) . The difference in the length of hospitalisation was associated with reduced cost for the percutaneous group ( 5579.60 euros vs. 7503.60 euros ; P=0.04 ) , that counterbalanced the cost induced by the Prostar XL((R ) ) suture mediated device . Mean follow-up in both groups was 12 months . The overall incidence of locoregional complications after one year of follow-up was 11 % ( 2/19 ) in group A and 19 % ( 4/21 ) in group B ( P=0.45 ) . CONCLUSION This study confirms the feasibility and safety of total percutaneous endovascular AAA repair . Our preliminary results suggest that the costs paid by healthcare providers for endovascular AAA repair might not be increased with the selective use of percutaneous closure devices Endovascular exclusion of abdominal aortic aneurysms ( AAAs ) was developed in an effort to treat patients who were at high risk for complications following st and ard surgical repair . Stent grafts used for endovascular repair of AAAs require the use of large‐bore sheaths and surgical exposure of the common femoral arteries ( CFAs ) . To decrease the invasiveness of AAA repair , we attempted to perform the procedure percutaneously utilizing the Prostar XL Percutaneous Vascular Surgery Device and the preclose technique . Thirty patients underwent an attempted percutaneous AAA repair . These patients were followed prospect ively to assess the success of the procedure . Twenty‐eight patients ( 93 % ) had successful percutaneous repair of both CFA access sites . One patient had inadequate hemostasis of the 22 Fr CFA entry site and one patient had inadequate hemostasis of the 16 Fr CFA entry site . Both of these CFA sites underwent open surgical repair . The rate of successful repair of the 22 Fr CFA access site was 29 of 30 ( 96 % ) ; for the 16 Fr CFA access site , 29 of 30 ( 96 % ) . No in‐hospital groin complications were seen . The procedure time was 105 ± 21 min . The estimated blood loss was 90.6 ± 50 cc . The hemoglobin loss was 1.54 ± 0.89 mg/dL and the hematocrit loss was 5.04 % ± 2.8 % . Complete percutaneous endoluminal AAA repair is feasible using the preclose technique . CFAs with sheaths up to 22 Fr can be safely and successfully accessed and repaired percutaneously using this technique . This method provides secure hemostasis and reduces the invasiveness of procedures requiring large‐bore sheaths . Cathet Cardiovasc Intervent 2002;55:281–287 . © 2002 Wiley‐Liss , PURPOSE To evaluate prospect ively the safety and efficacy of totally percutaneous placement of abdominal and thoracic aortic endografts using the Prostar XL suture-mediated closure system . METHODS From January 2002 to January 2005 , we attempted to insert percutaneously all bifurcated abdominal aortic and thoracic endografts . Consecutive patients ( 25 men , four women ) , with mean age 74.9 years ( range 44 - 84 ) , underwent endovascular repair for 20 abdominal aortic aneurysms ( AAA ) and nine thoracic aortic aneurysms ( repeat operation in one case ) . Endografts used included 21 Zenith ( Cook ) , eight Talent ( Medtronic ) , one AneuRx ( Medtronic ) . For the < < pre-close > > technique , two Prostar XL 8F were used to close 22 - 24F access sites and one Prostar XL 10F to close 16F access sites . RESULTS Procedural success was achieved in 21/29 ( 72.4 % ) patients and in 39/47 access sites ( 83 % ) . Closure of 22 - 24F access sites with t and em 8F Prostar devices was successful in 23/29 ( 79.3 % ) cases . Closure of 16F access sites with 10F Prostar device was successful in 16/18 ( 88.8 % ) cases . There were seven peri-procedural failures requiring surgery to repair the femoral artery in three cases . Four access complications healed without intervention . Overall 25/29 ( 86.2 % ) patients had complete percutaneous repair . No late complications were detected during follow-up ( median 17.5 months ) . CONCLUSIONS Percutaneous treatment of patients with AAA and thoracic aneurysms is feasible in most cases , with a very low risk of access-related complication , providing that the operator has sufficient practical experience of this technique In this prospect i ve , nonr and omized study , we compared outcome with percutaneous femoral artery closure to that with open femoral arteriotomy in 95 patients who underwent endovascular AAA repair . Devices were introduced using 22 Fr and /or 16 Fr sheaths . The 8 Fr/10 Fr Perclose devices ( Perclose Inc. , Redwood City , CA ) were used in an off-label " preclose technique . " Thirty-three patients had bilateral open femoral arteriotomies , 44 patients had bilateral attempted percutaneous closure , and 18 patients had open femoral arteriotomy on one side and attempted percutaneous closure on the other side . Percutaneous closure was successful in 85 % ( 47/55 ) of 16 Fr sheaths and 64 % ( 29/45 ) of 22 Fr sheaths ( p < 0.027 ) . BILATERAL PERCUTANEOUS CLOSURE WAS SUCCESSFUL IN 63 % ( 28/44 ) OF PATIENTS . CONVERSION TO OPEN FEMORAL ARTERIOTOMY DUE TO BLEEDING OCCURRED IN 24 OF 106 PERCUTANEOUS ATTEMPTS . THERE WERE NO DISSECTIONS , ARTERIAL THROMBOSES , OR PSEUDOANEURYSMS ASSOCIATED WITH PERCUTANEOUS ARTERIAL CLOSURE . WOUND COMPLICATIONS WERE SEEN IN 3.6 % ( 3/84 ) OF OPEN ARTERIOTOMIES AND 0.9 % ( 1/106 ) OF ALL PERCUTANEOUS ATTEMPTS AND ARTERIAL CLOSURES ( P > 0.05 ) . Gender , previous femoral access , obesity , and iliac occlusive disease were not predictive of percutaneous failure . Procedural success for percutaneous AAA repair is affected by sheath size . Devices delivered through 16 Fr or smaller sheaths will have successful femoral artery closure rates of at least 85 % BACKGROUND Endovascular grafting has markedly reduced the invasiveness of the treatment of abdominal aortic aneurysms . By using a modification of technique for available closure devices , we have been able to achieve percutaneous repair of aneurysms . This study review ed our initial experience with this technique . METHODS Demographics and background data from patients undergoing endovascular repair of abdominal aortic aneurysms were review ed from prospect ively collected registry data . Operative notes and angiographic and computed tomography scan data were retrospectively review ed to assess the success of the percutaneous approach . RESULTS Fourteen patients have undergone percutaneous placement of the AneuRx ( Medtronic , Sunnyvale , Calif ) endovascular graft , with a modification of the technique for the Prostar ( Perclose , Redwood City , Calif ) device for access site closure . Main graft body introduction with a 22F sheath proved successful in nine of 12 ( 75 % ) deployments . Contralateral limb deployment through a 16F sheath was successful in 10 of 14 deployments ( 71.4 % ) . Reasons for conversion to open groin incisions include inadequate percutaneous hemostasis ( six cases ) , iliofemoral dissection ( four cases ) , device failure ( one case ) , and compromised distal flow ( one case ) . Percutaneous deployment success appears to be improved with larger iliac artery dimensions , decreased calcification , and limited tortuosity , because of the limitation of complications related to delivering a larger diameter sheath . Of the 13 percutaneous endograft insertions that were attempted , six ( 46.2 % ) were completely successful . CONCLUSION Percutaneous deployment of available devices is technically feasible by using modifications of technique with percutaneous closure devices , despite large introducer sizes . Further experience with this technique offers the potential for identifying patients in whom this will prove successful and for even further reducing hospital stay and recovery times for aneurysm repair INTRODUCTION The effectiveness of percutaneous access with large vessel closure ( pEVR ) in non-selective groups of patients undergoing endovascular aneurysm repair ( EVR ) remains unclear . This study aims to identify factors that predict success in pEVR , performed using percutaneous access and the Prostar XL ( Abbott Vascular , Redwood City , Calif ) closure device . METHOD Consecutive patients who underwent pEVR between April 2010 and March 2011 were identified from a prospect ively maintained data base . Procedural and postoperative outcomes were compared with consecutive patients who underwent endovascular aneurysm repair using st and ard open femoral access between April 2008 and March 2009 . To determine the predictors of technical success of pEVR , the association between clinical , anatomical and procedural variables with technical success , were examined in a multiple logistic regression model . RESULTS pEVR was attempted in 186 common femoral arteries ( CFAs ) with a technical success rate of 95.2 % ( 177/186 ) . Conventional open femoral access in the historic control group was performed in 208 CFAs . pEVR was associated with a reduced operation length ( 131 min [ 105 - 152 ] versus 150 min [ 124 - 195 ] , p≤0.001 ) and length of stay ( 2 days [ 2 - 5 ] versus 4 days [ 2 - 7 ] , p = 0.01 ) in patients undergoing infrarenal EVR . In secondary analysis of outcomes following percutaneous access in 91 CFAs , pre-operative renal failure , CFA depth ( min and max ) , CFA diameter ( min and max ) and operator experience predicted success of percutaneous access in univariate analysis . Operator experience was the only independent predictor of technical success ( p = 0.05 ) after adjustment for all confounding variables . CONCLUSION pEVR using the Prostar XL device is effective in the majority of patients . In this study there were benefits in terms of reduced postoperative complications , shorter procedures and decreased lengths of stay . Operator experience is a predictor of technical success for pEVR , irrespective of clinical and morphological characteristics at baseline PURPOSE To determine the safety and efficacy of total percutaneous access closure for endovascular aortic aneurysm repair with a suture-mediated preclosing technique . MATERIAL S AND METHODS One hundred thirty-two femoral access sites in 70 patients who underwent endovascular aortic aneurysm repair were closed percutaneously with off-label use of two F-6 Perclose AT devices preapplied at a 90 degrees angle . Femoral access sizes ranged from 12 to 24 F. Technical success , complications , and procedure and access closure times were evaluated . Follow-up with computed tomography and /or magnetic resonance imaging was scheduled at 1 - 4 days and 3 , 6 , and 12 months and used to obtain groin hematoma and scar severity scores ( grade s 1 - 3 ) . Data were compared with those from a cohort of 67 patients who underwent endovascular aortic aneurysm repair with surgical femoral cutdown . RESULTS Technical success was achieved with the preclosing technique in 127 of the 132 arteries ( 96.2 % ) . Two to four closure devices were used per groin . Five technical failures were managed intraoperatively with surgical suture . There was no access-related mortality and no late groin complications . The mean procedure duration was 91 minutes + /- 32 , and the mean access closure time was 12 minutes + /- 9 . For surgical management , the mean procedure time was 153 minutes + /- 112 ( P < .05 ) , and the mean closure time was 12 minutes + /- 13 ( not statistically significant ) . Hematoma severity score at 1 - 4 days was 1.8 for total percutaneous endovascular aneurysm repair and 2.1 for surgical closure . Scar severity scores at 3 , 6 , and 12 months were 1.1 , 1.0 , and 1.0 for total percutaneous endovascular aneurysm repair and 2.4 , 2.4 , and 2.3 for surgical management , respectively . CONCLUSIONS Total percutaneous endovascular aneurysm repair with a dual 6-F-Perclose preclosing technique is safe and effective . Compared with femoral cutdown , there are fewer late groin complications and scar tissue formation is less severe Purpose : To assess if percutaneous insertion of large-bore sheaths is safe during endovascular repair ( EVR ) for abdominal aortic aneurysms ( AAA ) . Methods : Ninety-five AAA patients undergoing EVR had the endografts implanted percutaneously via 14-F to 20-F sheaths in a prospect i ve nonr and omized study . Vascular sutures were applied bilaterally to the common femoral arteries using a vascular closure device ; the sutures were tied after sheath withdrawal . Blood loss , operative time , and length of stay ( LOS ) were compared to 26 AAA patients undergoing EVR with bilateral femoral cutdowns before the percutaneous technique was available . Follow-up included duplex ultrasonography and clinical examination . Results : Bilateral percutaneous closure of the femoral arteries was successful in 78 ( 82 % ) patients . Fifteen patients required arteriorrhaphy intraoperatively and 2 others within 24 hours . The failure rate was 20 % , 0 % , 3 % , and 7 % for the 20-F , 18-F , 16-F , and 14-F introducers , respectively . Blood loss was 400 mL ( range 0–1800 ) in successful cases , 900 mL ( range 0–3000 ) in failures ( p<0.0001 ) . One deep infection at the puncture site required thrombectomy and patchplasty ; no other late complication occurred . There was no significant difference in operative time , blood loss , and LOS between patients treated with percutaneous EVR and those with primary femoral exposure . Conclusions : Percutaneous transfemoral EVR of AAA using large-bore introducer sheaths is safe . More than three quarters of the patients avoid femoral cutdown . Late complications are rare |
1,882 | 23,793,804 | Conclusions The use of mesh in the repair of large hiatal hernias is promising with respect to the reduction of anatomical recurrences . | Background The use of mesh is becoming more popular for large hiatal hernia ( type II – IV ) repair to reduce the recurrence rate .
The aim of this study was to outline the currently available literature on the use of mesh in laparoscopic large hiatal hernia repair , emphasizing objective outcome .
However , many different kinds and configurations of mesh are available . | Background / Aims : Primary repair of a large hiatal hernia is associated with a published recurrence rate of up to 10 % ; anecdotal rates even higher than this have been reported to the authors . The use of prosthetic material in the repair of other abdominal wall defects has often produced better results than primary repair . We wanted to compare laparoscopic primary repair of large hiatus hernias with laparoscopic primary repair reinforced with prosthetic . Methods : Thirty-one patients with symptomatic gastroesophageal reflux and a hiatal defect 8 cm or greater were r and omized to Nissen fundoplication with posterior cruroplasty ( n = 16 ) or Nissen cruroplasty , and onlay of polytetrafluoroethylene ( PTFE ) mesh ( n = 15 ) . All patients underwent preoperative esophagogastroduodenoscopy ( EGD ) and barium esophagography . After posterior cruroplasty with interrupted nonabsorbable suture , the mesh reinforcement group had an onlay of PTFE placed around the hiatus . A radial slit with 3 cm ‘ keyhole ’ ( to accommo date the esophagus ) was cut into the PTFE . The prosthetic was stapled to the diaphragm , and the two leaves of the slit were stapled to each other . All patients underwent EGD at 3 months and all had esophagrams every 6 months postoperatively . Follow-up ranged from 12 to 36 months . Results : Length of hospital stay was equal in both groups ( 2 days ) . The average cost to the patient with PTFE was USD 1,050 higher than to the patient with primary repair . There were 2 complications ( 1 pneumonia , 1 urinary retention ) in the PTFE group , and 1 complication ( pneumothorax ) in the primary repair group . There were 3 recurrences ( 18.8 % ) in the primary group ( p = 0.08 , χ2 test ) . Conclusion : The use of PFTE reinforcement for primary repair of large hiatal hernias may result in a lower rate of recurrent herniation compared to primary repair alone BACKGROUND Recent reports suggest that when laparoscopy is used to repair paraesophageal hernias recurrence rates reach 20 % to 40 % . Tension-free hernia closure with synthetic mesh reduces recurrence but occasionally results in esophageal injury . We hypothesized that reinforcement of the hiatal closure with small intestine submucosa ( SIS ) mesh , in some unusually large hernias , might reduce recurrence rates without causing injury to the esophagus . METHODS From January 2001 to March 2002 we treated 18 large paraesophageal hernias via a laparoscopic approach . In 9 of the largest hernias ( one type II and 8 type III , of which 1 was recurrent ) the repair was reinforced with SIS mesh ( Surgisis , Cook Surgical ) and represent the subjects of this study . Nissen fundoplication with gastropexy was performed in all patients . Clinical follow-up ranged from 3 to 16 months ( median 8) . Every patient was evaluated with barium esophagram or endoscopy or both 1 to 8 months ( median 2 ) postoperatively . RESULTS The presenting symptoms were postpr and ial pain/fullness ( 9 of 9 ) , heartburn ( 4 of 9 ) , anemia ( 4 of 9 ) , dysphagia ( 3 of 9 ) , regurgitation ( 3 of 9 ) , and chest pain ( 3 of 9 ) . One patient died of a hemorrhagic stroke within 30 days of the operation . Postoperatively , presenting symptoms resolved ( 83 % ) or improved ( 17 % ) in each of the remaining 8 patients . One patient required endoscopic dilation for mild dysphagia . Seven of 8 patients had a normal barium esophagram without evidence of hernia . One morbidly obese ( body mass index = 47 ) patient had a small ( 2 cm ) sliding hiatal hernia postoperatively . There were no other complications , and specifically no perforations or mesh erosions . CONCLUSIONS These observations suggest that the use of SIS in the repair of paraesophageal hernias is safe and may reduce recurrence . Longer follow-up and a r and omized study are needed to vali date these results HYPOTHESIS Large hiatal hernias are prone to disruption , result ing in reherniation , when repaired with simple cruroplasty . The use of mesh may decrease the rate of reherniation in the laparoscopic repair of large hiatal hernias . DESIGN Prospect i ve , r and omized controlled trial . SETTING University-affiliated private hospital . PATIENTS Seventy-two individuals undergoing laparoscopic Nissen fundoplication with a hernia defect greater or equal to 8 cm in diameter . INTERVENTION Nissen fundoplication with posterior cruroplasty ( n = 36 ) vs Nissen fundoplication with posterior cruroplasty and onlay of polytetrafluoroethylene ( PTFE ) mesh ( n = 36 ) . MAIN OUTCOME MEASURES Recurrences , complications , hospital stay , operative time , and cost . RESULTS Patients in both groups had similar hospital stays , but the PTFE group had a longer operative time . The cost of the repair was $ 960 + /- $ 70 more in the group with the prosthesis . Complications were minor and similar in both groups . There were 8 hernia recurrences ( 22 % ) in the primary repair group and none in the PTFE group ( P<.006 ) . CONCLUSION The use of prosthetic reinforcement of cruroplasty in large hiatal hernias may prevent hernia recurrences Abstract Background : Several studies have shown that large hiatal hernias are associated with a high recurrence rate . Despite the problem of recurrence , the technique of hiatal herniorrhaphy has not changed appreciably since its inception . In this 3-year study we have evaluated laparoscopic hiatal hernia repair in individuals with a hernia defect greater than 8 cm in diameter . Methods : A series of 35 patients with sliding or paraesophageal hiatal hernias was prospect ively r and omized to hiatal hernia repair with ( n= 17 ) or without ( n= 18 ) polytetrafluoroethylene ( PTFE ) . All patients had an endoscopic and radiographic diagnosis of large hiatal hernia . Both repairs were performed by using interrupted stitches to approximate the crurae . In the group r and omized to repair with prosthesis , PTFE mesh with a 3-cm ` ` keyhole ' ' was positioned around the gastroesophageal junction with the esophagus through the keyhole . The PTFE was stapled to the diaphragm and crura with a hernia stapler . Results : Patients were followed with EGD and esophagogram at 3 months postoperatively , and with esophagogram every 6 months thereafter . Individuals with PTFE had a longer operation time , but the 2-day hospital stay was the same in both groups . The cost of the repair was $ 1050 ± $ 135 more in the group with the prosthesis . There were two complications ( 1 pneumonia , 1 urinary retention ) in the group repaired with PTFE and one complication ( pneumothorax ) in the group without prosthesis . The group without PTFE was notable for three ( 16.7 % ) recurrences within the first 6 months of surgery . Conclusion : On the basis of these preliminary results it appears that repair with PTFE may confer an advantage , with lower rates of recurrence in patients with large hiatal hernia defects Background The use of mesh for laparoscopic repair of large hiatal hernias may reduce recurrence rates in comparison with primary suture repair . However , there is a potential risk of mesh-related oesophageal complications due to prosthesis erosion . The aim of this study was to evaluate a lightweight polypropylene mesh ( TiMesh ) repair of hiatal hernias with particular reference to intraluminal erosion . Methods Data were collected prospect ively on 18 consecutive patients undergoing elective laparoscopic repair of a large hiatal hernia with the use of TiMesh between November 2004 and December 2005 . Quality of life and symptom analysis was performed using QOLRAD question naires preoperatively and postoperatively after 6 weeks , 6 months , 1 year and 2 years . Barium studies were performed preoperatively and 2 years postoperatively to assess hernia recurrence . After 2 years , oesophagogastric endoscopy was performed to assess signs of mesh-related complications . Results All operations were completed laparoscopically . There was no 30-day mortality and median hospital stay was 2.8 days ( range 2–13 days ) . Complications occurred in two patients ( 11 % ) , both of whom were treated without residual disability . Two years after hiatal hernia repair , there was significant improvement in quality -of-life scores ( QOLRAD 5.79 , p < 0.001 ) . There was no difference between pre- and postoperative dysphagia scores . No signs of stricture formation or prosthetic erosion were identified during endoscopic follow-up . One patient had a small ( 2 cm ) sliding hiatal hernia demonstrated by barium studies , which was asymptomatic . Conclusions Laparoscopic reinforcement of primary hiatal closure with TiMesh leads to a durable repair in patients with large hiatal hernias . Endoscopic follow-up did not show any signs of mesh-related complications after prosthetic reinforcement of the crural repair . Our preliminary results suggest that it is safe to proceed with this lightweight polypropylene mesh for reinforcement of the hiatal repair Background The use of mesh for laparoscopic repair of large hiatal hernias may reduce recurrence rates in comparison to primary suture repair . However , there is a potential risk of mesh-related oesophageal complications due to prosthesis erosion . The aim of this study was to critically evaluate a novel mesh ( DualMesh ) repair of hiatal hernias with particular reference to intraluminal erosion . Method Medical records of 19 patients who underwent laparoscopic hiatal hernia repair with DualMesh reinforcement of the crural closure were review ed from a prospect ively collected data base . Quality of life and symptom analysis was performed using quality of life in reflux and dyspepsia ( QOLRAD ) question naires pre- and postoperatively after 6 weeks , 6 months , 1 year and 2 years . Barium studies were performed on patients pre-operatively and two years postoperatively to assess hernia recurrence . After 2 years , oesophagogastric endoscopy was performed to assess signs of erosion . Results Mean patient age was 70.5 years ( range 49–85 years ) . Two years after hiatal hernia repair , there was significant improvement in quality -of-life scores ( QOLRAD : p < 0.001 ) . Follow-up barium studies performed at 31.3 months ( range 29–40 months ) after surgery showed moderate recurrent hernias ( > 4 cm ) in 1/14 patients ( 7 % ) . Endoscopies performed at 34.4 months ( range 28–41 months ) after surgery did not show any signs of prosthetic erosion . Conclusion Laparoscopic reinforcement of primary hiatal closure with DualMesh leads to a durable repair in patients with large hiatal hernias . Long-term endoscopic follow-up did not show any signs of mesh erosion after prosthetic reinforcement of the crural repair HYPOTHESIS Laparoscopic repair of large hiatal hernia is an appropriate management strategy . DESIGN A prospect i ve patient series . SETTING A university teaching hospital . PATIENTS All patients with hiatal hernias 10 cm or greater in diameter repaired laparoscopically between February 1 , 1992 , and September 30 , 1998 . INTERVENTIONS Two operative strategies were used for laparoscopic repair : the first , which was used until early 1996 , entailed initial esophageal dissection while leaving the sac in the mediastinum . The second involved preliminary dissection of the hernial sac from the mediastinum before dissecting the esophagus . MAIN OUTCOME MEASURES Successful completion of the procedure using a laparoscopic technique , postoperative complication rate , reoperation rate , and clinical outcome . RESULTS Eighty-six patients with a large hiatal hernia underwent attempted repair using laparoscopic methods . The median age was 63 years ( range , 30 - 91 years ) , and 45 patients ( 52 % ) were women . There were 30 sliding , 10 rolling , and 46 mixed hiatal hernias . Operating times ranged from 48 to 240 minutes ( median , 90 minutes ) , and 20 procedures ( 23 % ) were converted to an open operation . Conversion was significantly more common in the first half of our experience ( 16 [ 40 % ] of 40 patients vs 4 [ 9 % ] of 46 patients ) before the operative strategy was changed . Esophageal-lengthening procedures were not carried out for any patient . At follow-up of a median of 2 years , 1 patient has moderate dysphagia , 4 patients have reflux symptoms , and 1 patient has undergone further surgery for a recurrent paraesophageal hernia . An overall satisfactory outcome was achieved in 81 patients ( 94 % ) . CONCLUSIONS Large hiatal hernias can be treated effectively laparoscopically . Dissecting the sac fully from the mediastinum before dissecting the esophagus helps to safely mobilize the esophagus , and we think changing to this strategy is the main reason for the improved laparoscopic success rate reported in the latter half of this series Background : Large paraesophageal hernias ( POHs ) predominantly occur in the elderly population . Early repair is recommended to avoid the risks associated with gastric volvulus . Methods : Data were collected prospect ively during an 8-year period . Laparoscopic repair of POHs initially included circumcision of the sac and mesh hiatal repair . Sac excision and suture hiatal repair were later adopted . A fundoplication was also included , initially as a selective procedure . Results : Fifty-three patients with large POHs were treated by one surgeon . All had attempted laparoscopic repair , with four conversions to an open procedure . Symptomatic hernia recurrence occurred in five patients ( 9 % ) . The 21 patients who had sac excision , hiatal repair , and fundoplication have remained free of symptomatic recurrence . The postoperative morbidity rate was 13 % , with one death . Conclusions : Laparoscopic repair of large POHs remains feasible . We advocate complete sac excision , hiatal repair , fundoplication , and gastropexy to prevent early recurrence Objective : Laparoscopic paraesophageal hernia repair ( LPEHR ) is associated with a high recurrence rate . Repair with synthetic mesh lowers recurrence but can cause dysphagia and visceral erosions . This trial was design ed to study the value of a biologic prosthesis , small intestinal submucosa ( SIS ) , in LPEHR . Methods : Patients undergoing LPEHR ( n = 108 ) at 4 institutions were r and omized to primary repair −1 ° ( n = 57 ) or primary repair buttressed with SIS ( n = 51 ) using a st and ardized technique . The primary outcome measure was evidence of recurrent hernia ( ≥2 cm ) on UGI , read by a study radiologist blinded to the r and omization status , 6 months after operation . Results : At 6 months , 99 ( 93 % ) patients completed clinical symptomatic follow-up and 95 ( 90 % ) patients had an UGI . The groups had similar clinical presentations ( symptom profile , quality of life , type and size of hernia , esophageal length , and BMI ) . Operative times ( SIS 202 minutes vs. 1 ° 183 minutes , P = 0.15 ) and perioperative complications did not differ . There were no operations for recurrent hernia nor mesh-related complications . At 6 months , 4 patients ( 9 % ) developed a recurrent hernia > 2 cm in the SIS group and 12 patients ( 24 % ) in the 1 ° group ( P = 0.04 ) . Both groups experienced a significant reduction in all measured symptoms ( heartburn , regurgitation , dysphagia , chest pain , early satiety , and postpr and ial pain ) and improved QOL ( SF-36 ) after operation . There was no difference between groups in either pre or postoperative symptom severity . Patients with a recurrent hernia had more chest pain ( 2.7 vs. 1.0 , P = 0.03 ) and early satiety ( 2.8 vs. 1.3 , P = 0.02 ) and worse physical functioning ( 63 vs. 72 , P = 0.03 per SF-36 ) . Conclusions : Adding a biologic prosthesis during LPEHR reduces the likelihood of recurrence at 6 months , without mesh-related complications or side effects The use of mesh for laparoscopic repair of large hiatal hernias may decrease recurrence rates in comparison with primary suture repair . The type of mesh material , as well as its size and shape , is still a matter of debate . The aim of this study was to evaluate a lightweight polypropylene mesh ( TiMesh ) repair of hiatal hernias , with particular reference to symptomatic relief , patient satisfaction and quality of life ( QOL ) . From a prospect ively maintained clinical data base , 40 consecutive patients were identified who underwent elective laparoscopic hiatal hernia repair with TiMesh between November 2004 and December 2006 . QOL and symptom analysis was carried out using Quality of Life in Reflux and Dyspepsia ( QOLRAD ) and dysphagia question naires preoperatively , and postoperatively after 6 weeks , 6 months , and 1 year . The mean age of the patient was 65.2 years ( range : 40–93 years ) . Total complication rate was 7.5 % ; all complications were treated without residual disability . There was no 30‐day mortality . Median hospital stay was 2.7 days ( range 2–13 days ) . Completed question naires were obtained from 37 ( 92.5 % ) of 40 patients . After 1 year , more than 90 % of patients were satisfied with their symptomatic outcome and regarded their surgery as successful . There was a significant improvement in QOL , measured with QOLRAD at all postoperative time‐points ( P < 0.001 ) . There was no difference between pre‐ and postoperative dysphagia scores . Laparoscopic repair of large hiatal hernias with TiMesh yields good symptomatic and clinical outcome . Further studies are needed to show whether the use of this lightweight polypropylene mesh is associated with a reduction in recurrence rates after hiatal hernia repair in the longer term BACKGROUND The laparoscopic repair of large hiatal hernia followed by an antireflux procedure is currently the gold st and ard therapy for gastroesophgeal reflux disease . However , it is recognized that recurrent hiatal herniation and wrap migration are major sources of operative failures in these patients . Some have described a reduction of such events with the placement of nonbiodegradable prosthetic patches over the primary cruroplasty . This prosthetic material may be associated with transesophageal and gastric erosions and a higher rate of postoperative dysphagia and chest pain when compared with simple suture cruroplasty alone . The aim of this study is to compare hiatal closure with a biodegradable patch ( acellular dermal matrix ) and simple suture curaplasty in patients undergoing laparoscopic antireflux surgery . METHODS A total of 44 patients were prospect ively enrolled in this study . Twenty-two consecutive patients undergoing large hiatal hernia repair ( > 5 cm ) and fundoplication with primary suture cruroplasty only ( group 1 ) were compared with 22 consecutive patients undergoing the same procedure with suture cruroplasty reinforced with an onlay acellular dermal matrix patch ( group 2 ) . The 2 groups were compared with regards to demographics , size of the hiatal hernia , pre- and postoperative symptom scores , pH studies , operative times , and hiatal hernia recurrence . RESULTS Patients in both groups were well matched by age , weight , height , and size of hiatal hernia . There were similar preoperative values in esophageal manometry , 24-hour pH monitoring , and symptom scoring in both groups . Average operative time was 108 minutes in group 1 and 121 minutes in group 2 . There were no major complications in either group . The median period of hospitalization was 1 day in both groups . Postoperative pH studies and symptoms score data were significantly improved in both groups . There was no significant difference in postoperative symptoms scores for dysphagia between the 2 groups . Two patients ( one in each group ) underwent esophageal dilatation for mild dysphagia postoperatively . In group 1 , 2 patients ( 9 % ) had Nissen failure with hiatal hernia recurrences 6 months after surgery . There were no recurrences for the follow-up period in group 2 . CONCLUSIONS Our early results suggest that hiatal hernia repair reinforced with an acellular dermal matrix patch may reduce the incidence of recurrent herniation and wrap migration . In addition , the increase in postoperative dysphagia , chest pain , and esophageal erosions associated with nondegradable mesh has not been observed in those with an acellular dermal matrix patch to this point in our follow up . However , future investigation of the material for this particular application as well as longer follow-up is necessary BACKGROUND The long-term durability of laparoscopic repair of paraesophageal hiatal herniation is uncertain . This study focuses on the long-term symptomatic and radiologic outcome of laparoscopic paraesophageal herniation repair . METHODS Between 2000 and 2007 , 70 patients ( 49 females , mean age + /- st and ard deviation 60.6 + /- 10.9 years ) undergoing laparoscopic repair of paraesophageal herniation were studied prospect ively . After a mean follow-up of 45.6 + /- 23.8 months , symptomatic ( 65 patients , 93 % ) and radiologic follow-up ( 60 patients , 86 % ) was performed by st and ardized question naires and esophagograms . RESULTS The symptomatic outcome was successful in 58 patients ( 89 % ) , and gastroesophageal anatomy was intact in 42 patients ( 70 % ) . The addition of a fundoplication was the only significant predictor of an unfavorable radiologic outcome in the univariate analysis ( odds ratio .413 ; 95 % confidence interval , .130 to 1.308 ; P = .125 ) . CONCLUSIONS The long-term symptomatic outcome of laparoscopic repair of paraesophageal hiatal herniation was favorable in 89 % of patients , and 70 % had successful anatomic repair . The addition of a fundoplication did not prevent anatomic herniation |
1,883 | 28,964,452 | In using adapted techniques , the primary challenge was identifying an appropriate intermediate " anchor " HS and the possibility of negative utilities .
CONCLUSIONS There is no agreement on the most method ologically robust approach to THS valuation . | BACKGROUND A broad literature on health state utility values exists , but compared with chronic health states ( HSs ) , issues surrounding the valuation of temporary health states ( THSs ) have been poorly explored .
OBJECTIVES To assess the methods used by previous studies to value HSs that are considered temporary so as to determine the strengths and limitations associated with various approaches and to inform future study design s. METHODS A systematic review was undertaken to explore the methods used , assess how the valuation was conducted for diseases that might lead to HSs deemed as temporary , and identify the challenges encountered in the valuation of THSs . | Background The aim of the study was to develop a menopause-specific , preference-based health-related quality -of-life ( HRQoL ) index reflecting both menopausal symptoms and potential side-effects of Hormone Replacement Therapy ( HRT ) . Methods The study had three phases : the development of a health state classification , a prospect i ve valuation survey and the estimation of a model to interpolate HRQoL indices for all remaining health states as defined by the classification . A menopausal health state classification was developed with seven dimensions : hot flushes , aching joints/muscles , anxious/frightened feelings , breast tenderness , bleeding , vaginal dryness and undesirable and rogenic signs . Each dimension contains between three and five levels and defines a total of 6,075 health states . A sample of 96 health states was selected for the valuation survey . These states were valued by a sample of 229 women aged 45 to 60 , r and omly selected from 6 general practice lists in Sheffield , UK . Respondents were asked to complete a time trade-off ( TTO ) task for nine health states , result ing in an average of 16.5 values for each health state . Results Mean health states valued range from 0.48 to 0.98 ( where 1.0 is full health and zero is for states regarded as equivalent to death ) . Symptoms , as described by the classification system , can be rank-ordered in terms of their impact ( from high to low ) on menopausal HRQoL as follows : aching joints and muscles , bleeding , breast tenderness , anxious or frightened feelings , vaginal dryness , and rogenic signs . Hot flushes did not significantly contribute to model fit . The preferred model produced a mean absolute error of 0.053 , but suffered from bias at both ends of the scale . Conclusion This article presents an attempt to directly value a condition specific health state classification . The overall fit was disappointing , but the results demonstrate that menopausal symptoms are perceived by patients to have a significant impact on utility . The overall effect is modest compared to the more generic health state descriptions such as the EQ-5D . The result ant algorithm generates a preference-based index that can be used economic evaluation and that reflects the impact of this condition To estimate patient preferences for gallstone-related treatments and outcomes , and assess how preferences vary by patient characteristics and scaling technique , the authors r and omly assigned 40 patients without gallstones to interviews based on a rating scale ( n = 22 ) and a st and ard gamble ( n = 18 ) . The patients assigned preference values ( possible values 0 to 1 ) to open cholecystectomy ( mean 0.45 by rating scale , 0.78 by st and ard gamble ) , laparoscopic cholecystectomy ( 0.71 , 0.91 ) , extracorporeal shock-wave lithotripsy ( 0.77 , 0.89 ) , acute cholecystitis ( 0.36 , 0.77 ) , lifetime biliary colic ( 0.41 , 0.71 ) , postcholecystectomy syn drome ( 0.43 , 0.79 ) , asymptomatic stone necessitating treatment with bile acids ( 0.76 , 0.96 ) , and surgical scar ( 0.79 , 0.998 ) . Preferences varied little by age , gender , or race . St and ard gamble values were highly correlated with , but significantly greater than , rating scale values . The authors conclude that patients ' preferences for gallstone-related conditions generally are significantly less than one , and differ markedly by the scaling technique used to derive them . These results should be considered when patient preferences are incorporated into analyses of gallstone treatments . Key words : patient preference values ; rating scale ; stan dard gamble ; gallstones ; cholecystectomy ; lithotripsy . ( Med Decis Making 1994;14:307- 314 Background . Health-related quality of life can be measured by patients ' health preferences ( utilities or values ) . No method for measuring health state preferences has been st and ardized for children with arthritis or other musculoskeletal disorders ( MSKDs ) . Such a method is needed for economic evaluations of current and new pediatric treatments . Objectives . 1 ) To assess the feasibility of utility measurements in children with MSKDs , 2 ) to test the validity of the Health Utility Index ( HUI ) for these children , 3 ) to assess whether rating scale values can be mathematically converted into meaningful st and ard gamble ( SG ) utilities , and 4 ) to study whether parents can act as proxies for their children with respect to health state preferences . Methods . Eighty parents of children with MSKDs were consecutively sample d. Their children , if 8 years of age or older ( n = 55 ) , were studied concurrently . Utilities of current health states were obtained by using the SG and the HUI in r and om order . In addition , health state preferences were assessed using categorical and analog rating scales . Traditional nonutility measures of health status ( the Childhood Health Assessment Question naire [ CHAQ ] and the Activities Scale for Kids [ ASK ] ) were also completed . Intraclass correlation coefficients ( ICCs ) were calculated to assess concordance between the different utility measures and also between the ratings of the parents and their children . Results . Children 8 years of age or older were able to express the strength of their health state preferences using the HUI and rating scales . Children older than 10 years of age were able to use the SG method . The health state utilities of the parents were higher than those of their children . The utilities varied widely depending on the elicitation method . The expected high agreement between the SG and the HUI was not found ( ICC = 0.028 for parents , ICC = 0.016 for patients ) . Unlike the SG , the global utilities derived from the HUI agreed better with preferences derived from rating scales ( ICC = 0.23 - 0.25 ) and correlated with traditional health status measures ( with CHAQ , r = -0.56 ; with ASK , r = 0.46 ) both for parents and children . It was not possible to mathematically convert rating scale preferences into SG utilities . The SG utilities were unrelated to results from the rating scales , the CHAQ , and the ASK . Especially for parents , the SG utilities were very high , even when ratings of the other measures indicated poor health . Conclusions . Although it is possible to measure health utilities for children with MSKDs , the results are highly method dependent . The properties of the HUI in this population are more like those of the traditional health status measures rather than those of the SG . Preferences derived from rating scales , although easily performed , can not readily be converted into SG utilities . Parents ' ratings for their children are impaired by risk aversion This article explores various method ological issues of patient utility measurement in two r and omized controlled clinical trials involving 85 patients with fibromyalgia and 144 with ankylosing spondylitis . In both trials one baseline and two follow-up measurements of the patients ' preferences for their own health state and several hypothetical states were performed using the rating scale and the st and ard gamble methods .It was confirmed that st and ard gamble scores are consistently higher than rating scale scores for both the experienced and the hypothetical states . The 3-month test-retest reliability for hypothetical states measured by intraclass correlation coefficients ranged from 0.24 to 0.33 for the rating scale and from 0.43 to 0.70 for the st and ard gamble . Although the reproducibility is not high , the group mean scores are fairly stable over time . Mean st and ard gamble scores tend to differ depending on the way the measurements are undertaken . Utilities elicited with chained gambles were significantly higher than utilities elicited with basic reference gambles . At the individual level some inconsistent responses occurred . However , more than 70 % of these fell within the bounds of the measurement error , which ranged from 0.11 to 0.13 on the st and ard gamble ( 0–1 scale ) and from 8 to 10 on the rating scale ( 0–100 scale ) . The large number of negative utilities for the severe hypothetical state , which was used as an anchor point in the chained gambles , and the magnitude of these negative utilities ( down to −19 ) calls for intensified research efforts to h and le these responses in utility calculations The techniques of cost utility analysis ( CUA ) were used to evaluate the treatment of gallstone disease by open and laparoscopic cholecystectomy and by extracorporeal shockwave lithotripsy ( ESWL ) . The application of the techniques in this context raised three method ological questions which are not satisfactorily resolved in the literature . The first is whether an ex ante or ex post perspective is best adopted for the measurement of quality of life ( QoL ) . The second is the method for converting a short term deterioration in QoL followed by full health into QALYs and the reliability of the methods available . The third is the issue of indirect costs which , in the context of a temporary disease state , can not be easily avoided . The economic evaluation found laparoscopic cholecystectomy to be generally superior than the competitor technologies ( entailing lower costs and better outcomes ) . However , the results were sensitive to assumptions about the perspective for measuring benefits and the inclusion of indirect costs Measuring preferences for schizophrenia outcomes facilitates meaningful integration of multiple outcome measures and multiple perspectives on treatment outcomes . The Time Tradeoff ( TTO ) technique , specifically developed for measuring health state preferences , is used widely in health research , but some evidence suggests that the TTO may work less well with schizophrenia than with other health conditions . This study tested the hypotheses that tailoring the time frame of the st and ard TTO to the course of schizophrenia and simplifying its presentation fromat would improve its feasibility and efficiency . Forty clinicians provided TTO ratings using 1 of 4 combinations of time frame and presentation format . Numeric ratings and quantitative and qualitative measures of feasibility showed that while participants preferred the simpler format , none of the alterations improved feasibility . Participants ' ratings were prone to logical inconsistencies and participants found all 4 versions of the TTO confusing and poorly suited to the context of schizophrenia treatment Objective To obtain quality -of-life ( QOL ) valuations associated with mammography screening and breast cancer treatment that are suitable for use in cost-effectiveness analyses . Methods Subjects comprised 131 women ( age range 50–79 years ) r and omly sample d from a breast cancer screening program . In an in-person or telephone interview , women rated the QOL impact of 14 clinical scenarios ( ranging from mammography to end-of-life care for breast cancer ) using a visual analogue scale anchored by death ( 0 ) and perfect health/ quality of life ( 100 ) . Results Women rated the scenarios describing true negative results , false positive results , and routine screening mammography at 80 or above on a scale of 0–100 , suggesting that they perceive these states as being close to perfect health . They rated adjuvant chemotherapy ( 39.7 ; range 10–90 ) , palliation/end-of-life care ( 35.8 ; range 0–100 ) , and recurrence at 1 year ( 33.0 ; range 0–95 ) the lowest , suggesting that these health states are perceived as compromised . Women rated receiving news of a breast cancer diagnosis ( true positive ) ( 45.7 ; range 5–100 ) and receiving delayed news of a breast cancer diagnosis ( false negative ) ( 48.5 ; range 5–100 ) as being comparable to undergoing mastectomy ( 48.3 ; range 10–100 ) and radiation therapy ( 46.2 ; range 5–100 ) for breast cancer . Conclusions These data can be used to up date cost analyses of mammography screening that wish to take into account the QOL impact of screening OBJECTIVE To examine preterm , near-term , and term mothers ' self-reported quality of life in the early postpartum period . DESIGN Prospect i ve , longitudinal repeated measures design . SETTING Four medical centers in the Midwest . PATIENTS / PARTICIPANTS A convenience sample of 184 mothers of either a preterm , near-term , or term infant . MAIN OUTCOME MEASURE Maternal Postpartum Quality of Life tool . RESULTS Mothers of preterm infants scored significantly lower on the subscale psychological/baby of the Maternal Postpartum Quality of Life tool compared to mothers of near-term and term infants . CONCLUSIONS Infant gestational age at birth has relevance for maternal quality of life during the postpartum period . Health care professionals need to be cognizant relative to infant gestational age and individualize nursing care |
1,884 | 24,817,558 | There is an indication from a single , large , unpublished study that inhaled mannitol increases time to first exacerbation in patients with bronchiectasis .
In patients with near normal lung function , spirometry does not change dramatically with mannitol and adverse events are not more frequent than placebo . | BACKGROUND Mucus retention in the lungs is a prominent feature of bronchiectasis .
The stagnant mucus becomes chronically colonised with bacteria , which elicit a host neutrophilic response .
This fails to eliminate the bacteria , and the large concentration of host-derived protease may contribute to the airway damage .
The sensation of retained mucus is itself a cause of suffering , and the failure to maintain airway sterility probably contributes to the frequent respiratory infections experienced by many patients .Hypertonic saline inhalation is known to accelerate tracheobronchial clearance in many conditions , probably by inducing a liquid flux into the airway surface , which alters mucus rheology in a way favourable to mucociliary clearance .
Inhaled dry powder mannitol has a similar effect .
Such agents are an attractive approach to the problem of mucostasis , and deserve further clinical evaluation .
OBJECTIVES To determine whether inhaled hyperosmolar substances are effective in the treatment of bronchiectasis . | BACKGROUND AND AIMS Inhalation of hypertonic saline ( HTS ) has short term positive effects on airways clearance in non-cystic fibrosis ( CF ) bronchiectasis , however its long term effects are unknown . The aim of this study was to determine the effect of HTS 6 % on exacerbations , quality of life ( QOL ) and respiratory function over 12 months in non-CF bronchiectasis . METHODS Forty patients were r and omised to inhale isotonic saline ( IS ) 0.9 % or HTS 6 % daily for 12 months . Participants recorded their symptoms in a daily diary . Quality of life and respiratory function were measured after three , six and 12 months . Number of exacerbations and changes in sputum colonisation were recorded at 12 months . Participants , assessors and clinicians were blinded to group allocation . RESULTS The exacerbation rate at 12 months was similar in the two groups and similar clinical ly significant improvements in QOL were seen in both groups . The FEV(1 ) increased in both groups after six months ( mean 90 ml , 95 % confidence interval 11 - 169 ml ) with no difference between groups ( p = 0.394 ) . The FEF(25 - 75 % ) significantly improved at all time points ( mean increase at 12 months 187 ml , 69 - 304 ml ) with no difference between groups ( p = 0.705 ) . There was a reduction in sputum colonisation in both groups ( p = 0.046 ) . CONCLUSIONS Inhalation of HTS or IS has similar effects on exacerbations , QOL , sputum colonisation and respiratory function over 12 months in non-CF bronchiectasis . The trial was registered with both Clinical Trials.gov - NCT00484263 and Australian New Zeal and Clinical Trials Registry - ACTRN12607000367448 BACKGROUND Inhaled dry powder mannitol enhanced mucus clearance and improved quality of life over 2 weeks in non-cystic fibrosis bronchiectasis . This study 's objective was to investigate the efficacy and safety of dry powder mannitol over 12 weeks . METHODS Patients with bronchiectasis confirmed by high-resolution CT ( H RCT ) scan , aged 15 to 80 years , with FEV1≥50 % predicted and ≥1 L participated in a r and omized , placebo-controlled , double-blind study . Patients with a negative mannitol provocation test were r and omized to inhale 320 mg mannitol ( n=231 ) or placebo ( n=112 ) bid for 12 weeks . To further assess safety , the same mannitol dose/frequency was administered to a patient subset in an open-label extension over 52 weeks . Primary end points were changes from baseline at 12 weeks in 24-h sputum weight and St. George 's Respiratory Question naire ( SGRQ ) score . RESULTS There was a significant difference of 4.3 g in terms of change in sputum weight over 12 weeks ( 95 % CI , 1.64 - 7.00 ; P=.002 ) between mannitol and placebo ; however , this was largely driven by a decrease in sputum weight in the placebo group . This was associated , in turn , with more antibiotic use in the placebo group ( 50 of 112 [ 45 % ] ) than in the inhaled mannitol group ( 85 of 231 [ 37 % ] ) . There was no statistical difference between the groups ( P=.304 ) in total SGRQ score ( mannitol , -3.4 points [ 95 % CI , -4.81 to -1.94 ] vs placebo , -2.1 points [ 95 % CI , -4.12 to -0.09 ] ) . In a subgroup study ( n=82 ) , patients receiving mannitol showed less small airway mucus plugging on H RCT scan at 12 weeks compared with patients receiving placebo ( P=.048 ) . Compliance rates were high , and mannitol was well tolerated with adverse events similar to those of placebo . CONCLUSION Because the difference in sputum weights appears to be associated with increased antibiotic use in the placebo group , a larger controlled study is now required to investigate the long-term mannitol effect on pulmonary exacerbations and antibiotic use . TRIAL REGISTRY Clinical Trials.gov ; No. : NCT0027753 ; URL : www . clinical trials.gov RATIONALE Bronchiectasis is a chronic debilitating disease with few evidence -based long-term treatments . OBJECTIVES A r and omized controlled trial assessing the efficacy of nebulized gentamicin therapy over 1 year in patients with non-cystic fibrosis bronchiectasis . METHODS Sixty-five patients were r and omized to either twice-daily nebulized gentamicin , 80 mg , or nebulized 0.9 % saline , for 12 months . All were review ed at three-monthly intervals during treatment and at 3 months ' follow-up . MEASUREMENTS AND MAIN RESULTS At each review the following were assessed : quantitative and qualitative sputum bacteriology ; sputum purulence and 24-hour volume ; FEV(1 ) , FVC , and forced expiratory flow , midexpiratory phase ; exercise capacity ; Leicester Cough Question naire and St. George 's Respiratory Question naire ; and exacerbation frequency . Fifty-seven patients completed the study . At the end of 12 months ' treatment , compared with the saline group , in the gentamicin group there was reduced sputum bacterial density with 30.8 % eradication in those infected with Pseudomonas aeruginosa and 92.8 % eradication in those infected with other pathogens ; less sputum purulence ( 8.7 % vs. 38.5 % ; P < 0.0001 ) ; greater exercise capacity ( 510 [ 350 - 690 ] m vs. 415 [ 267.5 - 530 ] m ; P = 0.03 ) ; and fewer exacerbations ( 0 [ 0 - 1 ] vs. 1.5 [ 1 - 2 ] ; P < 0.0001 ) with increased time to first exacerbation ( 120 [ 87 - 161.5 ] d vs. 61.5 [ 20.7 - 122.7 ] d ; P = 0.02 ) . The gentamicin group had greater improvements in Leicester Cough Question naire ( 81.4 % vs. 20 % ; P < 0.01 ) and St. George 's Respiratory Question naire ( 87.5 % vs. 19.2 % ; P < 0.004 ) score . No differences were seen in 24-hour sputum volume , FEV(1 ) , FVC , or forced expiratory flow , midexpiratory phase . No P. aeruginosa isolates developed resistance to gentamicin . At follow-up , all outcome measures were similar to baseline . CONCLUSIONS Regular , long-term nebulized gentamicin is of significant benefit in non-cystic fibrosis bronchiectasis but treatment needs to be continuous for its ongoing efficacy . Clinical trial registered with www . clinical trials.gov ( NCT 00749866 ) BACKGROUND Inhaled hypertonic saline acutely increases mucociliary clearance and , in short-term trials , improves lung function in people with cystic fibrosis . We tested the safety and efficacy of inhaled hypertonic saline in a long-term trial . METHODS In this double-blind , parallel-group trial , 164 patients with stable cystic fibrosis who were at least six years old were r and omly assigned to inhale 4 ml of either 7 percent hypertonic saline or 0.9 percent ( control ) saline twice daily for 48 weeks , with quinine sulfate ( 0.25 mg per milliliter ) added to each solution to mask the taste . A bronchodilator was given before each dose , and other st and ard therapies were continued during the trial . RESULTS The primary outcome measure , the rate of change ( slope ) in lung function ( reflected by the forced vital capacity [ FVC ] , forced expiratory volume in one second [ FEV1 ] , and forced expiratory flow at 25 to 75 percent of FVC [ FEF25 - 75 ] ) during the 48 weeks of treatment , did not differ significantly between groups ( P=0.79 ) . However , the absolute difference in lung function between groups was significant ( P=0.03 ) when averaged across all post-r and omization visits in the 48-week treatment period . As compared with the control group , the hypertonic-saline group had significantly higher FVC ( by 82 ml ; 95 percent confidence interval , 12 to 153 ) and FEV1 ( by 68 ml ; 95 percent confidence interval , 3 to 132 ) values , but similar FEF25 - 75 values . The hypertonic-saline group also had significantly fewer pulmonary exacerbations ( relative reduction , 56 percent ; P=0.02 ) and a significantly higher percentage of patients without exacerbations ( 76 percent , as compared with 62 percent in the control group ; P=0.03 ) . Hypertonic saline was not associated with worsening bacterial infection or inflammation . CONCLUSIONS Hypertonic saline preceded by a bronchodilator is an inexpensive , safe , and effective additional therapy for patients with cystic fibrosis . ( Clinical Trials.gov number , NCT00271310 . RATIONALE The prevalence of bronchiectasis is high in patients with moderate-to-severe chronic obstructive pulmonary disease ( COPD ) and it has been associated with exacerbations and bacterial colonization . These have demonstrated some degree of prognostic value in patients with COPD but no information about the relationship between bronchiectasis and mortality in patients with COPD is currently available . OBJECTIVES To assess the prognostic value of bronchiectasis in patients with moderate-to-severe COPD . METHODS Multicenter prospect i ve observational study in consecutive patients with moderate-to-severe COPD . Bronchiectasis was diagnosed by high-resolution computed tomography scan . A complete st and ardized protocol was used in all patients covering general , anthrophometric , functional , clinical , and microbiologic data . After follow-up , the vital status was recorded in all patients . Multivariate Cox analysis was used to determine the independent adjusted prognostic value of bronchiectasis . MEASUREMENTS AND MAIN RESULTS Ninety-nine patients in Global Initiative for Chronic Obstructive Lung Disease ( GOLD ) II , 85 in GOLD III , and 17 in GOLD IV stages were included . Bronchiectasis was present in 115 ( 57.2 % ) patients . During the follow-up ( median , 48 mo [ interquartile range , 35 - 53 ] ) there were 51 deaths ( 43 deaths in the bronchiectasic group ) . Bronchiectasis was associated with an increased risk of fully adjusted mortality ( hazard ratio , 2.54 ; 95 % confidence interval , 1.16 - 5.56 ; P = 0.02 ) . CONCLUSIONS Bronchiectasis was associated with an independent increased risk of all-cause mortality in patients with moderate-to-severe COPD Bronchiectasis is characterised by hypersecretion and impaired clearance of mucus . A 400-mg dose of inhaled mannitol improves mucus clearance however , the effect of other doses is unknown . A total of 14 patients , aged 63.3±5.7 yrs , were studied on five visits . Mucus clearance at baseline and with mannitol ( 160 , 320 and 480 mg ) was measured using technetium-99m-sulphur colloid and imaging with a gamma camera over 45 min , followed by a further 30 min involving 100 voluntary coughs . A control study assessed the effect of cough provoked by mannitol during the intervention . Whole right lung clearance over 45 min was 4.7±1.2 and 10.6±2.6 % on baseline and control days , respectively , and increased to 16.7±4.2 , 22.8±4.2 and 31±4.7 % with 160 , 320 and 480 mg mannitol , respectively . Clearance over 45 min with 480 mg mannitol was greater than clearance with 320 and 160 mg . Total clearance over 75 min , after mannitol administration and voluntary coughs , was 36.1±5.5 , 40.9±5.6 and 46.0±5.2 % with 160 , 320 and 480 mg mannitol , respectively , all significantly different from baseline ( 24.1±6.0 % ) and control ( 13.1±3.0 % ) . Total clearance over 75 min with 480 mg mannitol was greater compared with 160 mg . In conclusion , mucus clearance increases with increasing doses of mannitol and can be further increased by cough in patients with bronchiectasis The effects of broad-spectrum antibiotic and placebo therapy in patients with chronic obstructive pulmonary disease in exacerbation were compared in a r and omized , double-blinded , crossover trial . Exacerbations were defined in terms of increased dyspnea , sputum production , and sputum purulence . Exacerbations were followed at 3-day intervals by home visits , and those that resolved in 21 days were design ated treatment successes . Treatment failures included exacerbations in which symptoms did not resolve but no intervention was necessary , and those in which the patient 's condition deteriorated so that intervention was necessary . Over 3.5 years in 173 patients , 362 exacerbations were treated , 180 with placebo and 182 with antibiotic . The success rate with placebo was 55 % and with antibiotic 68 % . The rate of failure with deterioration was 19 % with placebo and 10 % with antibiotic . There was a significant benefit associated with antibiotic . Peak flow recovered more rapidly with antibiotic treatment than with placebo . Side effects were uncommon and did not differ between antibiotic and placebo Asthmatics with overproduction of mucus that is viscous and sticky have impaired mucociliary clearance ( MCC ) leading to mucus plugs , and airway obstruction . Inhaled mannitol improves mucus clearance in other hypersecretory diseases . This study investigated the effect of mannitol and cough in asthmatics with mucociliary dysfunction . Seven stable asthmatics , age 52 ± 20 yr , lifelong non-smokers , without the diagnosis of bronchiectasis , with chronic cough and sputum production , treated with inhaled corticosteroids participated in the study . MCC and cough clearance ( CC ) was measured on 4 visits : at baseline ( no cough or mannitol ) , with mannitol ( 240 and 480 mg ) and cough control ( no mannitol ) over total 90 min using a radioaerosol technique and imaging with a gamma camera . Cough clearance was assessed after MCC by asking subjects to cough 100 times over 30 min . Premedication with eformoterol ( 12 μg ) on all visits protected all subjects from bronchoconstriction ( fall in FEV(1 ) > 15 % ) in response to mannitol . Mean ( ±SD ) clearance over 60 min increased from 5.5 ± 5.6 % at baseline and 7.3 ± 6.6 % with cough control to 19.5 ± 14.6 % and 26.4 ± 11.5 % with 240 mg ( p < 0.003 ) and 480 mg ( p < 0.0001 ) of mannitol respectively . Total clearance ( MCC + CC ) over 90 min increased from 6.9 ± 6.5 % ( baseline ) and 12.6 ± 8.3 % without mannitol ( cough control ) to 34.6 ± 13.5 and 36.6 ± 10.4 % with 240 and 480 mg mannitol respectively ( p < 0.0001 ) . Clearance over 90 min at baseline was not significantly different to cough control ( p > 0.05 ) . Mannitol improved clearance in all lung regions ( p < 0.005 ) . In conclusion , mannitol improved both mucociliary and cough clearance in asthmatics with mucociliary dysfunction and ineffective cough clearance . Clinical Trial registered with www.anzctr.org.au ; Number ACTRN 12609001066279.aspx BACKGROUND Bronchiectasis is the outcome of a number of different airway insults . Very few studies have characterised the aetiology and utility of a dedicated screening proforma in adult patients attending a general bronchiectasis clinic . METHODS A prospect i ve observational study of 189 bronchiectasis patients attending two centres in the North East of Engl and over a two-year period was performed . RESULTS The aetiology of bronchiectasis was identified in 107/189(57 % ) patients . Idiopathic bronchiectasis ( IB ) represented the largest subgroup ( 43 % ) . Post-infection bronchiectasis ( PIB ) constituted the largest proportion ( 24 % ) of known causes . Mean age ( SD ) at diagnosis was 54(20 ) years with a mean age at symptom onset of 37(24 ) years , accounting for a diagnostic delay of 17 years . Age of symptom onset was significantly younger in patients with PIB compared to IB ( p < 0.0001 ) and in Pseudomonas sputum positive patients ( p = 0.007 ) . Screening for APBA and total immunoglobulin deficiency identified 9 ( 5 % ) patients who then had tailored treatment . Routine screening for other aetiologies was deemed unnecessary . CONCLUSION IB and PIB accounted for two thirds of cases of bronchiectasis in a general population . We recommend routine screening for ABPA and total immunoglobulin deficiency but not for other rarer aetiologies Sputum retention is a distressing feature of non-cystic fibrosis bronchiectasis and has been shown to contribute to the vicious cycle of infection seen in this disease . In a previous study we demonstrated that nebulised 7 % hypertonic saline was both safe and effective in this patient population . Patients with a clinical diagnosis of non-cystic fibrosis bronchiectasis , confirmed by H RCT , were entered into a r and omised single blind cross-over study to evaluate 0.9 % sodium chloride ( IS ) and 7 % hypertonic saline ( HS ) . Following a 4 week run in patients received a r and om order active HS or IS daily for 3 months . A 4 week wash-out phase was included between phases . We report lung function , quality of life , and health care utilisation responses . 32 patients mean age 56.6 years ( SD 14.6 ) , 16 male , were recruited of which 28 were r and omised and completed the study . Lung function ( % change from baseline ) improved in HS vs. IS ( FEV(1 ) : 15.1 , 1.8 p<0.01 ; FVC : 11.2 , 0.7 p<0.01 . SGRQ improved significantly from baseline ( HS 6.0 , IS 1.2 ; p<0.05 ) . There were reductions in annualised antibiotic usage ( HS 2.4 , IS 5.4 courses per patient per year ) , annualised emergency health care utilisation visits were reduced ( HS 2.1 , IS 4.9 events per patient per year ) . There were also improvements in sputum viscosity and ease of expectoration ( visual analogue scale ) . Regular use of 7 % hypertonic saline improves lung function , quality of life and health care utilisation in non-cystic fibrosis bronchiectasis patients Sputum clearance is of prime importance in the management of patients with bronchiectasis . While nebulised normal isotonic saline ( 0.9 % ) ( IS ) has been anecdotally used to treat patients with tenacious sputum , the use of hypertonic saline ( 7 % ) ( HS ) could have potential muco-protective and clearance properties . 24 patients with bronchiectasis were r and omised to receive four single treatment schedules in r and om order : ( 1 ) active cycle breathing technique ( ACBT ) alone , ( 2 ) nebulised terbutaline then ACBT , ( 3 ) nebulised terbutaline , nebulised IS then ACBT and ( 4 ) nebulised terbutaline , nebulised HS then ACBT . Sputum weights were significantly higher after HS than IS ( P = 0.002 ) . Ease of expectoration also differed overall ( P < 0.0001 ) and was significantly lower with HS than with IS ( P = 0.0005 ) . Sputum viscosity differed between treatment phases , with a significant linear trend to reduced sputum viscosity with HS ( P = 0.0002 ) . These changes were associated with small but statistically significant differences in FEV1 ( P = 0.043 ) and FVC ( P = 0.011 ) between treatment phases . Nebulised hypertonic saline can be used safely and effectively as an adjunct to physiotherapy in selected patients . A long-term prospect i ve trial is now indicated to determine its effectiveness on long-term infection rate , quality of life and lung function STUDY OBJECTIVE To investigate the acute effect of mannitol on the clearance of mucus , and ( 1 ) the 24-h mucus retention , and ( 2 ) the mucus clearance rate and lung function 24 h after inhalation of a single dose of mannitol . DESIGN Clearance of mucus was measured on 3 consecutive days using (99m)Tc-sulfur colloid radioaerosol and a gamma camera . INTERVENTIONS Mannitol , 330 + /- 68 mg ( mean+/- SD ) , was inhaled using a dry powder inhaler only on day 2 . PATIENTS Eight patients with bronchiectasis ( age range , 29 to 70 years ) . MEASUREMENTS AND RESULTS On each day , lung images were collected over 2 h and at 24 h. Key findings of the study are as follows : ( 1 ) the 24-h retention of mucus was reduced the day after mannitol had been inhaled , compared to the day without mannitol ( day 1 ) in the whole right lung ( 57.6 + /- 6.2 % vs 68.1 + /- 5.9 % ) , central ( 47.5 + /- 6.7 % vs 56.9 + /- 6.5 % ) , intermediate ( 61.7 + /- 5.6 % vs 73.8 + /- 5.5 % ) , and peripheral regions ( 70.9 + /- 4.3 % vs 86.6 + /- 4.6%)(p < 0.02 ) ; and ( 2 ) mannitol helped patients clear mucus within 2 h that might otherwise take up to 24 h , from the whole right lung and defined regions . However , clearance over 60 min measured 24 h after mannitol inhalation was not significantly different to baseline clearance without mannitol ( 8.7 + /- 1.9 % on day 1 vs 9.7 + /- 3.7 % 24 h after mannitol ; p > 0.8 ) . The patients maintained the same lung function the day before and after mannitol had been inhaled : FEV(1 ) ( percent predicted ) , 79 + /- 5 on day 1 vs 80 + /- 5 on day 3 ; and forced expiratory flow , midexpiratory phase ( percent predicted ) , 50 + /- 6 on day 1 vs 51 + /- 6 on day 3 ; p > 0.6 ) . CONCLUSIONS Mannitol inhalation acutely increases clearance of mucus , and this effect extends beyond the acute study period , result ing in decreased mucus retention at 24 BACKGROUND Patients with cystic fibrosis are known to have decreased mucociliary clearance . It has previously been shown that inhalation of a 7.0 % solution of hypertonic saline significantly improved mucociliary clearance in a group of adult patients with cystic fibrosis . The aim of this study was to measure the response to increasing concentrations of inhaled hypertonic saline . METHODS Ten patients ( seven men ) of mean ( SE ) age 22 ( 4 ) years and mean forced expiratory volume in one second ( FEV1 ) 52.0 (6.7)% predicted completed the study . Mucociliary clearance was measured using a radioaerosol technique for 90 minutes after the interventions which comprised 0.9 % NaCl + voluntary cough ( control ) , 3.0 % NaCl , 7.0 % NaCl , and 12 % NaCl . RESULTS There was a significant increase in the amount of activity cleared from the right lung with all concentrations of hypertonic saline ( HS ) compared with control . The amount cleared at 90 minutes on the control day was 12.7 % ( 95 % confidence interval ( CI ) 9.8 to 17.2 ) compared with 19.7 % ( 95 % CI 13.6 to 29.5 ) for 3 % HS , 23.8 % ( 95 % CI 15.9 to 36.7 ) for 7 % HS and 26.0 % ( 95 % CI 19.8 to 35.9 ) for 12 % HS . The improvement in mucociliary clearance was not solely due to coughing as the number of coughs recorded on the control day exceeded that recorded on any other day . The hypertonic saline did not induce a clinical ly significant change in FEV1 . CONCLUSIONS Within the range of concentrations examined in this study , the effect of hypertonic saline appears to be dose dependent . Inhalation of hypertonic saline remains a potentially useful treatment for patients with cystic fibrosis IMPORTANCE Macrolide antibiotics such as erythromycin may improve clinical outcomes in non-cystic fibrosis ( CF ) bronchiectasis , although associated risks of macrolide resistance are poorly defined . OBJECTIVE To evaluate the clinical efficacy and antimicrobial resistance cost of low-dose erythromycin given for 12 months to patients with non-CF bronchiectasis with a history of frequent pulmonary exacerbations . DESIGN , SETTING , AND PARTICIPANTS Twelve-month , r and omized ( 1:1 ) , double-blind , placebo-controlled trial of erythromycin in currently nonsmoking , adult patients with non-CF bronchiectasis with a history of 2 or more infective exacerbations in the preceding year . This Australian study was undertaken between October 2008 and December 2011 in a university teaching hospital , with participants also recruited via respiratory physicians at other centers and from public radio advertisements . INTERVENTIONS Twice-daily erythromycin ethylsuccinate ( 400 mg ) or matching placebo . MAIN OUTCOME MEASURES The primary outcome was the annualized mean rate of protocol -defined pulmonary exacerbations ( PDPEs ) per patient . Secondary outcomes included macrolide resistance in commensal oropharyngeal streptococci and lung function . RESULTS Six-hundred seventy-nine patients were screened , 117 were r and omized ( 58 placebo , 59 erythromycin ) , and 107 ( 91.5 % ) completed the study . Erythromycin significantly reduced PDPEs both overall ( mean , 1.29 [ 95 % CI , 0.93 - 1.65 ] vs 1.97 [ 95 % CI , 1.45 - 2.48 ] per patient per year ; incidence rate ratio [ IRR ] , 0.57 [ 95 % CI , 0.42 - 0.77 ] ; P = .003 ) , and in the prespecified subgroup with baseline Pseudomonas aeruginosa airway infection ( mean difference , 1.32 [ 95 % CI , 0.19 - 2.46 ] ; P = .02 ) . Erythromycin reduced 24-hour sputum production ( median difference , 4.3 g [ interquartile range [ IQR ] , 1 to 7.8 ] , P = .01 ) and attenuated lung function decline ( mean absolute difference for change in postbronchodilator forced expiratory volume in the first second of expiration , 2.2 percent predicted [ 95 % CI , 0.1 % to 4.3 % ] ; P = .04 ) compared with placebo . Erythromycin increased the proportion of macrolide-resistant oropharyngeal streptococci ( median change , 27.7 % [ IQR , 0.04 % to 41.1 % ] vs 0.04 % [ IQR , -1.6 % to 1.5 % ] ; difference , 25.5 % [ IQR,15.0 % to 33.7 % ] ; P < .001 ) . CONCLUSION AND RELEVANCE Among patients with non-CF bronchiectasis , the 12-month use of erythromycin compared with placebo result ed in a modest decrease in the rate of pulmonary exacerbations and an increased rate of macrolide resistance . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12609000578202 Bronchiectasis is a disease characterized by hypersecretion and retention of mucus requiring physical and pharmacologic treatment . Recently we reported that inhalation of dry powder mannitol markedly increases mucociliary clearance ( MCC ) in asthmatic and in healthy subjects ( Daviskas , E. , S. D. And erson , J. D. Brannan , H. K. Chan , S. Eberl , and G. Bautovich . 1997 . Inhalation of dry-powder mannitol increases mucociliary clearance . Eur . Respir . J. 10:2449 - 2454 ) . In this study we investigated the effect of mannitol on MCC in patients with bronchiectasis . Eleven patients 40 to 62 yr of age inhaled mannitol ( approximately 300 mg ) from a Dinkihaler . MCC was measured over 90 min , in the supine position , on three occasions involving : mannitol or control or baseline , using a radioaerosol technique . On the control day patients reproduced the breathing maneuvers and the number of coughs induced by the mannitol . Mannitol significantly increased MCC over the 75 min from the start of the intervention compared with control and baseline in the whole right lung , central , and intermediate region . Mean ( + /- SEM ) clearance with mannitol was 34.0 + /- 5.0 % versus 17.4 + /- 3.8 % with control and 11.7 + /- 4.4 % with baseline in the whole right lung ( p < 0.0001 ) . The mean number of coughs induced by mannitol was 49 + /- 11 . In conclusion , inhalation of dry powder mannitol increased clearance of mucus and thus has the potential to benefit patients with bronchiectasis BACKGROUND AND OBJECTIVE Dry powder mannitol has the potential to be used to enhance clearance of mucus in subjects with bronchiectasis . A reduction in FEV1 has been recorded in some subjects with bronchiectasis after inhaling mannitol . The aim of this study was to investigate if pre-medicating with either sodium cromoglycate ( SCG ) or eformoterol could inhibit this reduction in FEV1 . METHODS A double-blind , placebo-controlled , r and omized cross-over study was conducted . Lung function and airway response to mannitol was assessed on a control day and then re-assessed after pre-medication with placebo , SCG and eformoterol in nine subjects . Sensitivity to mannitol , expressed as the dose required to induce a 15 % fall in FEV1 ( PD15 ) , and reactivity to mannitol , expressed as the % fall in FEV1 per mg of mannitol ( response-dose ratio , RDR ) , are reported . RESULTS Subjects had an FEV1 of 68 ± 14 % predicted , FVC of 97 ± 15 % predicted and FEV1 /FVC of 71 ± 8 % . They were mildly hypoxemic and the SpO2 was 95 ± 2%.They had a PD15 to mannitol of 235 mg ( 95 % CI : 150 - 368 mg ) and a RDR of 0.057 % fall in FEV1 per mg ( 95 % CI : 0.038 - 0.085 ) . After pre-medication with SCG , PD15 increased ( 773 mg , P < 0.05 ) and RDR was reduced ( 0.013 , P < 0.05 ) . Pre-medication with eformoterol also result ed in an increased PD15 ( 1141 mg , P < 0.01 ) and a reduced RDR ( 0.009 , P < 0.01 ) . A small but significant decrease in SpO2 from baseline was noted after mannitol in the presence of SCG ( P < 0.05 ) . CONCLUSIONS Pre-medication with either SCG or eformoterol protects patients with bronchiectasis from developing a significant reduction in FEV1 after inhaling mannitol |
1,885 | 30,997,170 | Conclusion Structural interventions such as scale-up of antiretroviral treatment , prevention of medication stockouts , social empowerment and economic strengthening may help substantially reduce self-stigma among individuals . | Background Self-stigma , also known as internalised stigma , is a global public health threat because it keeps people from accessing HIV and other health services .
By hampering HIV testing , treatment and prevention , self-stigma can compromise the sustainability of health interventions and have serious epidemiological consequences .
This review synthesis ed existing evidence of interventions aim ing to reduce self-stigma experienced by people living with HIV and key population s affected by HIV in low-income and middle-income countries . | We developed a comprehensive and culturally applicable empowerment intervention social self-value package with an aim to assess its efficacy in order to improve the quality of life ( QoL ) of HIV infected people receiving antiretroviral treatment . Participants were r and omly allocated to receive either six weekly intervention sessions or st and ard care . Nonlinear mixed-effects models were performed to compare changes in empowerment scores over time . Between September and November 2014 , 1447 individuals were screened , of whom 132 were r and omly assigned to either the intervention or control group . The mean scores of empowerment , social support and quality of life increased and stigma scores were reduced in the intervention group at 3- and 6-months . An intervention effect on social support , stigma and QoL was significantly increased by time and group with low and high empowerment . No adverse events were reported . The empowerment intervention was efficacious in improving QoL of HIV infected people . ResumenHemos desarrollado un fortalecimiento completo y cultural applicable a la intervención social del paquete del valor propio con la intención de evaluar su eficacia para mejorar la calidad de vida de las personas infectadas por el VIH que están recibiendo ART . A los participantes se les adjudicó aleatoriamente la asignación de seis dosis semanales o los cuidados est and ar . El result ado de los efectos se presentó para comparar los cambios en los valores del fortalecimiento a lo largo del tiempo . Entre septiembre y noviembre de 2014 , 1447 individuos fueron moritonizados , de los cuales 132 fueron aleatoriamente asignados para cada intervención o grupo de control . La media del valor del fortalecimiento , apoyo social y calidad de vida incrementaron y los valores del estigma fueron reducidos en la intervención grupal entre 3 y 6 meses . Los efectos de una intervención al apoyo social , estigma y calidad de vida se incrementaron significativamente en ese periodo y el grupo con un bajo y alto fortalecimiento . No hubo efectos secundarios notificados . La intervención en el fortalecimiento fue satisfactoria en la mejora de la calidad de vida de la gente infectada por el VIH HIV-related stigma among persons living with HIV/AIDS ( PLHIV ) is prevalent throughout sub-Saharan Africa . There is limited evidence , however , on which interventions are effective in reducing it . We used data from a prospect i ve impact evaluation of a 12-month food assistance intervention among 904 antiretroviral therapy (ART)- naïve PLHIV in Ug and a to examine the program impact on stigma . Stigma was measured using the comprehensive HASI-P scale , which demonstrated good internal consistency ( Cronbach ’s alpha = 0.87 ) and was correlated with several related constructs including physical and mental health-related quality of life , disclosure , and physical health symptoms in the sample . Using quasi-experimental difference-in-difference matching methods to better infer causality , we tested whether the intervention improved the overall stigma scale and its subscales . The food assistance intervention had a significant effect on reported internalized ( but not external ) stigma of approximately 0.2 SD ( p < 0.01 ) . The HASI-P stigma scale is a useful tool for measuring and tracking stigma . Food assistance interventions , embedded in an HIV care program , can reduce internalized stigma This study sought to explore , describe and determine whether an HIV stigma-reduction community “ hub ” intervention would change the HIV stigma experiences of people living with HIV ( PLWH ) and the stigmatisation by the community in an urban area in South Africa . A convergent parallel mixed- method design with a single case pre-test post-test design and an interpretive description approach was utilised . The sample for this study included 62 PLWH recruited through accessibility sampling and 570 community members recruited through r and om voluntary sampling . A sub- sample of both groups , selected using purposive voluntary sampling , was utilised for the in-depth interviews about stigma experiences of PLWH , and for perceptions and attitudes of the community toward PLWH . Both quantitative and qualitative data showed that stigma is present . Although no statistically significant changes were found , small practically significant changes were demonstrated in the experiences of PLWH and in the perceptions and attitudes of the community . The extent of changes was much more obvious in the responses of the PLWH and the community during their post-intervention qualitative interviews than the changes found with the quantitative measures . This study thus concludes that the HIV stigma-reduction community hub intervention was successful in initiating the onset of changes in a community through the PLWH and people living close to PLWH ( PLC ) as community mobilisers active in the community hub to mobilise their own communities towards HIV stigma reduction through social change The authors of this study evaluated a structured 10-session psychosocial support group intervention for newly HIV-diagnosed pregnant South African women . Participants were expected to display increases in HIV disclosure , self-esteem , active coping and positive social support , and decreases in depression , avoidant coping , and negative social support . Three hundred sixty-one pregnant HIV-infected women were recruited from four antenatal clinics in Tshwane townships from April 2005 to September 2006 . Using a quasi-experimental design , assessment s were conducted at baseline and two and eight months post-intervention . A series of r and om effects regression analyses were conducted , with the three assessment points treated as a r and om effect of time . At both follow-ups , the rate of disclosure in the intervention group was significantly higher than that of the comparison group ( p < 0.001 ) . Compared to the comparison group at the first follow-up , the intervention group displayed higher levels of active coping ( t = 2.68 , p < 0.05 ) and lower levels of avoidant coping ( t = −2.02 , p < 0.05 ) , and those who attended at least half of the intervention sessions exhibited improved self-esteem ( t = 2.11 , p < 0.05 ) . Group interventions tailored for newly HIV positive pregnant women , implemented in re source -limited setting s , may accelerate the process of adjusting to one 's HIV status , but may not have sustainable benefits over time Abstract Background We evaluate the impact of clinic-based PMTCT community support by trained lay health workers in addition to st and ard clinical care on PMTCT infant outcomes . Methods In a cluster r and omized controlled trial , twelve community health centers ( CHCs ) in Mpumalanga Province , South Africa , were r and omized to have pregnant women living with HIV receive either : a st and ard care ( SC ) condition plus time-equivalent attention-control on disease prevention ( SC ; 6 CHCs ; n = 357 ) , or an enhanced intervention ( EI ) condition of SC PMTCT plus the “ Protect Your Family ” intervention ( EI ; 6 CHCs ; n = 342 ) . HIV-infected pregnant women in the SC attended four antenatal and two postnatal video sessions and those in the EI , four antenatal and two postnatal PMTCT plus “ Protect Your Family ” sessions led by trained lay health workers . Maternal PMTCT and HIV knowledge were assessed . Infant HIV status at 6 weeks postnatal was drawn from clinic PCR records ; at 12 months , HIV status was assessed by study administered DNA PCR . Maternal adherence was assessed by dried blood spot at 32 weeks , and infant adherence was assessed by maternal report at 6 weeks . The impact of the EI was ascertained on primary outcomes ( infant HIV status at 6 weeks and 12 months and ART adherence for mothers and infants ) , and secondary outcomes ( HIV and PMTCT knowledge and HIV transmission related behaviours ) . A series of logistic regression and latent growth curve models were developed to test the impact of the intervention on study outcomes . Results In all , 699 women living with HIV were recruited during pregnancy ( 8–24 weeks ) , and assessment s were completed at baseline , at 32 weeks pregnant ( 61.7 % ) , and at 6 weeks ( 47.6 % ) , 6 months ( 50.6 % ) and 12 months ( 59.5 % ) postnatally . Infants were tested for HIV at 6 weeks and 12 months , 73.5 % living infants were tested at 6 weeks and 56.7 % at 12 months . There were no significant differences between SC and EI on infant HIV status at 6 weeks and at 12 months , and no differences in maternal adherence at 32 weeks , reported infant adherence at 6 weeks , or PMTCT and HIV knowledge by study condition over time . Conclusion The enhanced intervention administered by trained lay health workers did not have any salutary impact on HIV infant status , ART adherence , HIV and PMTCT knowledge . Trial registration clinical trials.gov : number ABSTRACT The ANRS 12249 Treatment-as-Prevention ( TasP ) cluster-r and omized trial in rural South Africa uses a “ test and treat ” approach . Home-based testing services and antiretroviral treatment initiation satellite clinics were implemented in every cluster as part of the trial . A social science research agenda was nested within TasP with the aim of underst and ing the social , economic and context ual factors that affect individuals , households , communities and health systems with respect to TasP. Considering the rural nature of the trial setting , we sought to underst and community perceptions and experiences of the TasP Trial interventions as seen through the eyes of traditional health practitioners ( THPs ) . A qualitative study design was adopted using four repeat focus group discussion s conducted with nine THPs , combined with community walks and photo-voice techniques , over a period of 18 months . A descriptive , interpretive and explanatory approach to analysis was adopted . Findings indicate that THPs engaged with the home-based testing services and HIV clinics established for TasP. Specifically , home-based testing services were perceived as relatively successful in increasing access to HIV testing . A major gap observed by THPs was linkage to HIV clinics . Most of their clients , and some of the THPs themselves , found it difficult to use HIV clinics due to fear of labelling , stigma and discrimination , and the ensuing personal implication s of unsolicited disclosure . On the one h and , a growing number of patients diagnosed with HIV have found sanctuary with THPs as alternatives to clinics . On the other h and , THPs in turn have been struggling to channel patients suspected of HIV into clinics through referrals . Therefore , acceptability of the TasP test and treat approach by THPs is a major boost to the intervention , but further success can be achieved through strengthened ties with communities to combat stigma and effectively link patients into HIV care , including partnerships with THPs themselves Introduction Injecting drug use is a primary driver of HIV epidemics in many countries . People who inject drugs ( PWID ) and are HIV infected are often doubly stigmatized and many encounter difficulties reducing risk behaviors . Prevention interventions for HIV-infected PWID that provide enhanced support at the individual , family , and community level to facilitate risk-reduction are needed . Methods 455 HIV-infected PWID and 355 of their HIV negative injecting network members living in 32 sub-districts in Thai Nguyen Province were enrolled . We conducted a two-stage r and omization : First , sub-districts were r and omized to either a community video screening and house-to-house visits or st and ard of care educational pamphlets . Second , within each sub-district , participants were r and omized to receive either enhanced individual level post-test counseling and group support sessions or st and ard of care HIV testing and counseling . This result ed in four arms : 1 ) st and ard of care ; 2 ) community level intervention ; 3 ) individual level intervention ; and 4 ) community plus individual intervention . Follow-up was conducted at 6 , 12 , 18 , and 24 months . Primary outcomes were self-reported HIV injecting and sexual risk behaviors . Secondary outcomes included HIV incidence among HIV negative network members . Results Fewer participants reported sharing injecting equipment and unprotected sex from baseline to 24 months in all arms ( 77 % to 4 % and 24 % to 5 % respectively ) . There were no significant differences at the 24-month visit among the 4 arms ( Wald = 3.40 ( 3 df ) ; p = 0.33 ; Wald = 6.73 ( 3 df ) ; p = 0.08 ) . There were a total of 4 HIV seroconversions over 24 months with no significant difference between intervention and control arms . Discussion Underst and ing the mechanisms through which all arms , particularly the control arm , demonstrated both low risk behaviors and low HIV incidence has important implication s for policy and prevention programming . Trial Registration Clinical Trials.gov Background Among people living with HIV ( PLHIV ) on antiretroviral therapy ( ART ) , it is important to determine how quality of life ( QOL ) may be improved and HIV-related stigma can be lessened over time . This study assessed the effect of peer support on QOL and internal stigma during the first year after initiating ART among a cohort of PLHIV in north-eastern Vietnam . Methods A sub- sample study of a r and omised controlled trial was implemented between October 2008 and November 2010 in Quang Ninh , Vietnam . In the intervention group , participants ( n = 119 ) received adherence support from trained peer supporters who visited participants ’ houses biweekly during the first two months , thereafter weekly . In the control group , participants ( n = 109 ) were treated according to st and ard guidelines , including adherence counselling , monthly health check and drug refills . Basic demographics were measured at baseline . QOL and internal stigma were measured using a Vietnamese version of the WHOQOL-HIVBREF and Internal AIDS-related Stigma Scale instruments at baseline and 12 months . T-tests were used to detect the differences between mean values , multilevel linear regressions to determine factors influencing QOL . Results Overall , QOL improved significantly in the intervention group compared to the control group . Among participants initiating ART at clinical stages 3 and 4 , education at high school level or above and having experiences of a family member dying from HIV were also associated with higher reported QOL . Among participants at clinical stage 1 and 2 , there was no significant effect of peer support , whereas having children was associated with an increased QOL . Viral hepatitis was associated with a decreased QOL in both groups . Lower perceived stigma correlated significantly but weakly with improved QOL , however , there was no significant relation to peer support . Conclusion The peer support intervention improved QOL after 12 months among ART patients presenting at clinical stages 3 and 4 at baseline , but it had no impact on QOL among ART patients enrolled at clinical stages 1 and 2 . The intervention did not have an effect on Internal AIDS-related stigma . To improve QOL for PLHIV on ART , measures to support adherence should be context ualized in accordance with individual clinical and social needs Background While studies have suggested that depression and HIV-related stigma may impede access to care , a growing body of literature also suggests that access to HIV care itself may help to decrease internalized HIV-related stigma and symptoms of depression in the general population of persons living with HIV . However , this has not been investigated in postpartum women living with HIV . Furthermore , linkage to care itself may have additional impacts on postpartum depression beyond the effects of antiretroviral therapy . We examined associations between linkage to HIV care , postpartum depression , and internalized stigma in a population with a high risk of depression : newly diagnosed HIV-positive pregnant women . Methods In this prospect i ve observational study , data were obtained from 135 HIV-positive women from eight antenatal clinics in the rural Nyanza Province of Kenya at their first antenatal visit ( prior to testing HIV-positive for the first time ) and subsequently at 6 weeks after giving birth . Results At 6 weeks postpartum , women who had not linked to HIV care after testing positive at their first antenatal visit had higher levels of depression and internalized stigma , compared to women who had linked to care . Internalized stigma mediated the effect of linkage to care on depression . Furthermore , participants who had both linked to HIV care and initiated antiretroviral therapy reported the lowest levels of depressive symptoms . Conclusions These results provide further support for current efforts to ensure that women who are newly diagnosed with HIV during pregnancy become linked to HIV care as early as possible , with important benefits for both physical and mental health Motivational interviewing ( MI ) has been shown to reduce sexual risks among HIV-positive men who have sex with men ( HMSM ) in the US . We conducted a r and omized trial of Healthy Choices , a 4-session MI intervention , targeting sexual risks among 110 HIV-positive youth ages 16–25 years in Thail and . Risk assessment s were conducted at baseline , 1 month , and 6 months post-intervention . This report presents the analysis of 74 HMSM in the study . There were 37 HMSM in the Intervention group and 37 in the control group . The proportions of participants having anal sex and having sex with either HIV-uninfected or unknown partners in past 30 days were significantly lower in Intervention group than in Control group at 6 months post-intervention ( 38 vs. 65 % , p = .04 ; and 27 vs. 62 % , p < .01 , respectively ) . There were no significant differences in general mental health scores and HIV stigma scores between the two groups at any study visit . Thirty-five ( 95 % ) HMSM in the Intervention group vs. 31 ( 84 % ) in control group attended ≥ 3 sessions . Loss to follow-up was 8 and 30 % , respectively ( p = .04 ) . Healthy Choices for young Thai HMSM was associated with sexual risk reduction . Improvements in mental health were noted in Intervention group . Healthy Choices is a promising behavioral intervention and should be further developed to serve the needs of young HMSM in re source -limited countries Abstract The aim of this study is to examine whether internalized AIDS stigma among HIV patients one year after antiretroviral therapy ( ART ) initiation is associated with sociodemographic characteristics , health status , social support , quality of life ( QoL ) , and ARV adherence . This is a prospect i ve study of all treatment-naïve patients ( N=735 ) recruited from all three public hospitals in Uthukela health district in KwaZulu-Natal and followed up at 6 and 12 months being on ART . Results indicated that despite a decrease in stigma seen in this study ( may be due to ART ) the level of stigma and discrimination remains high , and stigma reduction interventions are urgently needed in this population . CD4 cell counts significantly increased and HIV symptoms reduced significantly but depression symptoms remained high and even increased after 12 months on treatment . In multivariate analysis lower CD4 cell counts ( odds ratio 0.5 , 0.3–0.9 ) , severe depression ( 5.6 , 2.5–12.5 ) and low QoL ( 0.6 , 0.5–0.8 ) were associated with internalized AIDS stigma . These findings may suggest that HIV care should include counseling and support that includes stigma concerns , depression , and QoL prior to and during the first year following diagnosis Social and structural factors including HIV stigma are theorized to drive global disparities in HIV prevalence . This study tests whether HIV self-stigma , or experiences of stigma at the individual level , is associated with engagement in unprotected sex among people living with HIV ( PLWH ) in KwaZulu-Natal , South Africa , where 37.4 % of adults are living with HIV compared with 0.8 % worldwide . It further explores whether depressive symptoms , HIV status disclosure to sex partners , and /or condom use attitudes mediate potential associations between HIV self-stigma and unprotected sex . Participants , including 924 PLWH , were recruited from primary care clinics and completed baseline , 6- , 12- , and 18-month survey assessment s between 2008 and 2011 . Hierarchical linear modeling analyses were used to examine longitudinal within-subjects associations between HIV self-stigma , mediators , and unprotected sex with both HIV-negative/unknown and HIV-positive partners . Results demonstrate that HIV self-stigma was prospect ively associated with greater likelihood of unprotected sex with HIV-negative/unknown partners . None of the variables explored significantly mediated this association . HIV self-stigma was also prospect ively associated with greater likelihood of unprotected sex with HIV-positive partners via the mediators of greater depressive symptoms and more negative condom use attitudes . The current study suggests that HIV self-stigma undermines HIV secondary prevention and care efforts among PLWH in KwaZulu-Natal . It is therefore critical to address HIV stigma at the social/structural level to reduce HIV self-stigma at the individual level and ultimately curb global disparities in HIV prevalence . In the absence of widespread social/structural change , interventions that treat depressive symptoms and encourage more positive condom use attitudes despite the existence of HIV stigma may buffer associations between HIV self-stigma and unprotected sex with HIV-positive partners among PLWH in KwaZulu-Natal ABSTRACT HIV stigma can inhibit uptake of HIV testing and antiretroviral therapy as well as negatively affect mental health . Efforts to reduce discrimination against people living with HIV ( LWH ) have contributed to greater acceptance of the infection . Female sex workers ( FSW ) LWH may experience overlapping stigma due to both their work and HIV status , although this is poorly understood . We examined HIV and sex-work stigma experienced by FSW LWH in Zimbabwe . Using the SAPPH-IRe cluster-r and omised trial baseline survey , we analysed the data from 1039 FSW self-reporting HIV . The women were recruited in 14 sites using respondent-driven sampling . We asked five questions to assess internalised and experienced stigma related to working as a sex worker , and the same questions were asked in reference to HIV . Among all FSW , 91 % reported some form of sex-work stigma . This was not associated with sociodemographic or sex-work characteristics . Rates of sex-work stigma were higher than those of HIV-related stigma . For example , 38 % reported being “ talked badly about ” for LWH compared with 77 % for their involvement in sex work . Those who reported any sex-work stigma also reported experiencing more HIV stigma compared to those who did not report sex-work stigma , suggesting a layering effect . FSW in Zimbabwe experience stigma for their role as “ immoral ” women and this appears more prevalent than HIV stigma . As HIV stigma attenuates , other forms of social stigma associated with the disease may persist and continue to pose barriers to effective care Abstract Introduction While biomedical HIV prevention offers promise for preventing new HIV infections , access to and uptake of these technologies remain unacceptably low in some setting s. New models for delivery of HIV prevention are clearly needed . This commentary highlights the potential of person‐centred programming and research for increasing the cultural relevance , applicability and use of efficacious HIV prevention strategies . It calls for a shift in perspective within HIV prevention programmes and research , whereby people are recognized for their agency rather than assumed to be passive beneficiaries or research participants . Discussion Person‐centred HIV prevention reorientates power dynamics so that individuals ( rather than interventions ) are at the centre of the response . Respecting personal choice and agency – and underst and ing how these are shaped by the context in which people exercise these choices – are critical dimensions of the person‐centred approach . Community‐based participatory research should be employed to inform and evaluate person‐centred HIV prevention . We argue that community‐based participatory research is an orientation rather than a method , meaning that it can be integrated within a range of research methods including r and omized controlled trials . But embracing community‐based participatory approaches in HIV prevention research requires a systemic shift in how this type of research is reported in high impact journals and in how research impact is conceived . Community‐based organizations have a critical role to play in both person‐centred HIV prevention and research . Conclusions HIV prevention is situated at the intersection of unprecedented opportunity and crisis . Person‐centred approaches to HIV prevention and research shift power dynamics , and have the potential to ensure a more sustainable response with each individual actively participating in their own care and meaningfully contributing to the production of knowledge on HIV prevention . This approach taps into the re source fulness , resilience and knowledge of the person and their communities , to strengthen research and programmes , making them more relevant , appropriate and effective Rural women living with HIV/AIDS ( WLA ) in India face multifarious challenges which affect access to antiretroviral regimens and management of HIV/AIDS . The purpose of this pilot study , using cluster r and omization , is to compare the effectiveness of the Asha-Life ( AL ) intervention , delivered by HIV-trained village women , Asha ( Accredited Social Health Activists ) , with a usual care group on reduction of internalized stigma and avoidant coping among 68 WLA in rural India over a 6-month period . The findings demonstrated that participation in the AL intervention was associated with significant reductions in internalized stigma and the use of avoidant coping strategies at follow-up . The findings of our study are promising in terms of the role rural village women ( Asha ) may play in reducing internalized stigma and avoidant coping in the lives of rural WLA in India |
1,886 | 23,597,688 | The strongest evidence supports using a problem-solving approach to improve leisure and social participation for older adults with low vision .
Evidence was moderate supporting the delivery of a combination of services , either by one professional or through an interdisciplinary approach . | This systematic review examined evidence regarding the effectiveness of interventions within the scope of occupational therapy practice to maintain , restore , and improve performance in leisure and social participation for older adults with low vision . | Abstract The purpose of this study was to conduct a r and omized clinical trial to assess whether a self-management group intervention can improve mood , self-efficacy , and activity in people with central vision loss due to age-related macular degeneration ( AMD ) . Ninety-two elderly patients with AMD ( average age=79 ) from a university ophthalmology clinic were r and omly assigned to the self-management intervention ( n=44 ) or to a wait-list ( n=48 ) . All patients were legally blind in at least one eye . The intervention consisted of 6 weekly 2-hour group sessions providing education about the disease , group discussion , and behavioral and cognitive skills training to address barriers to independence . All participants eventually completed the intervention allowing pre-post comparisons for all patients . The battery of measures included the Profile of Mood States ( POMS ) ; Quality of Well-Being Scale ; and assessment s of self-efficacy , participation in activities , and use of vision aids . Participants ' initial psychological distress was high ( mean total POMS=59.72 ) and similar to distress experienced by other serious chronic illness population s ( e.g. cancer , bone marrow transplant ) . Analysis of covariance testing the primary hypothesis revealed that intervention participants experienced significantly ( p=.04 ) reduced psychological distress ( pre $ $ \bar x = 61.45$$ ; post $ $ \bar x = 51.14$$ ) in comparison with wait-list controls ( pre $ $ \bar x = 57.72$$ ; post $ $ \bar x = 62.32$$ ) . Intervention participants also experienced improved ( p=.02 ) self-efficacy ( pre $ $ \bar x = 70.16$$ ; post $ $ \bar x = 77.27$$ ) in comparison with controls ( pre $ $ \bar x = 67.71$$ ; post $ $ \bar x = 69.07$$ ) . Further , intervention participants increased their use of vision aids ( p<.001 ; pre $ $ \bar x = 3.37$$ , post $ $ \bar x = 6.69$$ ) . This study demonstrates that a relatively brief behavioral intervention can substantially reduce psychological distress and increase self-efficacy in elderly adults experiencing vision loss due to macular degeneration . Self-management intervention appears to improve mood , self-efficacy , and use of vision aids , further enhancing the lives of poorly sighted individuals with AMD OBJECTIVE To determine whether problem-solving treatment ( PST ) can prevent depressive disorders in patients with age-related macular degeneration ( AMD ) . DESIGN Two hundred six patients with AMD were r and omly assigned to PST ( n = 105 ) or usual care ( n = 101 ) . PST therapists delivered six PST sessions over 8 weeks in subjects ' homes . MEASUREMENTS Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition Diagnoses of Depressive Disorders , Hamilton Depression Rating Scale scores , and rates of relinquishing valued activities were assessed at 2 months for short-term effects and 6 months for maintenance effects . RESULTS The 2-month incidence rate of depressive disorders in PST-treated subjects was significantly lower than controls ( 11.6 % versus 23.2 % , respectively ; OR = 0.43 ; 95 % CI [ 0.20 , 0.95 ] ) . PST also reduced the odds of relinquishing a valued activity ( OR = 0.48 ; 95 % CI [ 0.25 , 0.96 ] ) ; this effect mediated the relationship between treatment group and depression . By 6 months most earlier observed benefits had diminished . Secondary analyses showed that a minimal level of depressive symptoms were disabling and predicted incident depressive disorders . CONCLUSION PST prevented depressive disorders and loss of valued activities as a short-term treatment but these benefits were not maintained over time . To sustain PST 's effect , an intervention that uses a problem-solving framework to enhance rehabilitative skills may be necessary AIMS --A survey was undertaken to assess the effectiveness of an integrated approach to the provision of low visual aids ( LVAs ) in south Devon over a 2 year follow up period . This integrated approach includes the assessment of patient needs by low vision therapists , followed by the provision of suitable LVAs , with particular emphasis on training in their use . METHODS --A total of 125 patients were selected at r and om from the 445 patients seen in the low vision clinic at Torbay Hospital in the year 1991 . These patients were sent question naires relating to the service over a 2 year period . Question naires from 111 patients were analysed at 1 year and 75 question naires together with 46 clinical re assessment s , after 2 years . RESULTS --Using a similar question naire to one used in a previous study in the UK from a unit where LVA training was not provided , not only was a higher rate of satisfaction found with the services provided , but also the LVAs dispensed were used more frequently . The majority of the LVAs provided were of the simple , inexpensive variety and wastage was very low . CONCLUSIONS --It was concluded that this integrated approach to low vision rehabilitation with emphasis on training in the use of less complex LVAs exceeds the performance of other types of service that rely on the dispensing of more complex LVAs Aim : To compare the effectiveness of three models of low vision rehabilitation for people with age related macular degeneration ( AMD ) referred for low vision rehabilitation ( LVR ) : ( a ) an enhanced low vision rehabilitation model ( ELVR ) including supplementary home based low vision rehabilitation ; ( b ) conventional low vision rehabilitation ( CLVR ) based in a hospital clinic ; ( c ) CLVR with home visits that did not include rehabilitation ( CELVR ) , intended to act as a control for the additional contact time with ELVR . Method : A single centre parallel group r and omised controlled trial in participants ’ homes and the low vision clinic , Manchester Royal Eye Hospital . People referred for LVR with a primary diagnosis of AMD and visual acuity worse than 6/18 in both eyes and equal to or better than 1/60 in the better eye . The main outcome measures were vision specific quality of life ( QoL ) ( primary outcome , VCM1 ) and generic health related QoL ( SF-36 ) ; psychological adjustment to vision loss ; measured task performance ; restriction in everyday activities ; use of low vision aids ( LVAs ) . Results : 226 participants were recruited ( median age 82 years ) ; 194 completed the trial ( 86 % ) . Except for SF-36 physical and mental component summary scores , arms did not differ significantly for any of the outcomes . Differences for the VCM1 were ELVR v CLVR , 0.06 ( 95 % CI to 0.17 to 0.30 , p = 0.60 ) ; ELVR v CELVR , 0.12 ( 95 % CI to 0.11 to 0.34 , p = 0.31 ) ; CELVR v CLVR , –0.05 ( 95 % CI –0.29 to 0.18 , p = 0.64 ) . Differences for the SF-36 favoured CLVR compared to ELVR ( ELVR v CLVR : physical = –6.05 , 95 % CI –10.2 to –1.91 , p = 0.004 ; mental = –4.04 , 95 % CI –7.44 to –0.65 , p = 0.02 ) . At 12 months , 94 % of participants reported using at least one LVA . Conclusion : ELVR was no more effective than CLVR . Research ers should be wary of proposing new LVR interventions without preliminary evidence of effectiveness , given the manifest lack of effectiveness of the model of enhanced LVR evaluated in the trial PURPOSE : To test the hypothesis that vision rehabilitation using optometry , occupational therapy and social work services increases patients ' functional ability and to assess whether involving families in the intervention results in more successful outcomes . METHODS : We conducted an outcome study of 97 patients new to the Vision Rehabilitation Service . Subjects were between the ages of 19 and 91 years , with a median age of 76 . Their visual acuities were 20/100 or worse in the better eye , with 50 % of the subjects having acuities worse than 20/200 . Macular degeneration was the most prevalent diagnosis . Subjects were assigned to either an individually focused ( n=48 ) or a family focused ( n=49 ) intervention . The outcome measure was change in function , as assessed by speed and accuracy of performance ( objective measure ) and by the patients ' self-reports of difficulty and dependency in performing daily activities ( subjective measures ) . Data were collected before and after the intervention . RESULTS : Most patients had documented improvement after rehabilita-tion on both objective ( p=.0001 ) and subjective ( decreased dependency , p=.01 ) measures of function . The sample size did not provide adequate statistical power to show differences between family focused and individually focused interventions . CONCLUSIONS : This study documents significant improvement after vision rehabilitation for a predominately elderly population . Patients in both family and individually focused interventions improved comparably Purpose . ( 1 ) to document participation in daily activities and social roles of older adults seeking services for visual impairment ( VI ) and compare it with that of the older population without VI or other disabilities , and ( 2 ) to explore correlates of their participation . Methods . The 64 participants ( 46 women ) had an average age of 79.3 years ( SD = 5.9 years ) and presented various types of VI . Participants were interviewed at home to collect information regarding their visual function ( National Eye Institute Visual Function Question naire-25 ) , sociodemographic and clinical characteristics , including depressive symptoms ( Geriatric Depression Scale ) , and participation ( Assessment of Life Habits/LIFE-H ) . Each participant was matched with another person without disabilities r and omly recruited from the community . Results for the two population s on the Life-H participation domains were compared using t-tests . In the group with VI , general information ( independent variables ) was examined in relation to participation main scores ( dependent variables ) , followed by multiple linear regression analyses . Results . Participation in daily activities and social roles of participants with VI ( mean ± SD ( /9 ) = 6.8 ± 1.0 and 5.6 ± 1.6 , respectively ) was significantly lower than that of participants without VI ( 8.1 ± 0.4 and 8.3 ± 0.4 ) ( p < 0.0001 ) . Depressive symptoms and perceived quality of distance vision were the strongest correlates and together explained more than 65 % of the variance in the participation scores of the subjects with VI . Conclusions . This study demonstrates the participation restrictions associated with VI and underlines the importance of psychological aspects in participation PURPOSE The study has investigated the effect of lighting on the daily activities ( ADL ) of the visually impaired in their homes by comparison before and after light adjustments were made in the kitchen , hall and bathroom . It has also investigated the additional effects on the quality of life after providing task lighting in the living room . METHOD A total of 56 people were consecutively recruited from those receiving lighting adaptation help by the Low Vision Clinic in Göteborg . Ten persons did not complete the study . After medical examinations , lighting st and ards and psychosocial factors were charted . After lighting improvements were carried out in the kitchen , hall and bathroom , the subjects were r and omly divided into two groups , an intervention and a comparison group . The task lighting in the living room was also improved for those included in the intervention group . Follow-up interviews to determine ADL and quality of life were performed 6 months after lighting adaptation . RESULTS A marked effect on quality of life of the lighting in the living room was found for the intervention group . The effect on ADL of the basic lighting adaptation in kitchen , hall and bathroom for both groups was significant for tasks carried out on the working surface in the kitchen . Other activities in the kitchen and in the bathroom tended to improve but changes were not significant . CONCLUSION The results confirm that it is possible to increase quality of life by improving the lighting conditions OBJECTIVE The purpose of this r and omized , longitudinal study was to investigate the impact of a health education program on perceived security in the performance of daily occupations 4 months after the intervention period . METHOD Two groups of persons with age-related macular degeneration were compared : Those who had followed a newly developed health education program that was based on occupation and those who took part in a st and ard individual intervention program . RESULTS Significant differences in the level of perceived security between the groups were found for 13 of 28 occupations . Participants in the health education group maintained or improved their level of perceived security in 22 daily occupations , whereas those in the individual intervention group declined to a lower level in 17 daily occupations . CONCLUSION This study provides support for the effectiveness of the health education program to enhance security and hinder a progressive decline in perceived security in daily occupations |
1,887 | 23,593,053 | Home-based rehabilitation is unlikely to lead to cost-savings , but achieves better health outcomes .
Care in stroke units is more expensive than conventional care , but leads to improved health outcomes .
The cost-effectiveness studies on integrated stroke services suggest that they can reduce costs . | Introduction Given the high incidence of stroke worldwide and the large costs associated with the use of health care re sources , it is important to define cost-effective and evidence -based services for stroke rehabilitation .
The objective of this review was to assess the evidence on the relative cost or cost-effectiveness of all integrated care arrangements for stroke patients compared to usual care .
Integrated care was defined as a multidisciplinary tool to improve the quality and efficiency of evidence -based care and is used as a communication tool between professionals to manage and st and ardize the outcome -orientated care . | BACKGROUND AND PURPOSE The goal of the present study was to examine the re source and economic implication s of an early hospital discharge and home-based rehabilitation scheme for patients with acute stroke . METHODS A cost minimization analysis in conjunction with a r and omized controlled trial was carried out at 2 affiliated teaching hospitals in the southern metropolitan region of Adelaide , South Australia , between 1997 and 1998 . Eighty-six hospitalized patients with acute stroke who required rehabilitation were r and omized to receive both early hospital discharge and home-based rehabilitation , or conventional in-hospital rehabilitation and community care . Direct and indirect costs related to stroke rehabilitation were calculated , including hospital bed days , home-based intervention program , community services , and personal expenses during the 6 months after r and omization . RESULTS The mean cost per patient was lower for patients r and omized to the early hospital discharge and home-based rehabilitation ( $ 8040 ) compared with those who received conventional care ( $ 10 054 ) . This cost saving was not statistically significant ( P=0.14 ) . However , sensitivity analyses indicated that the cost of home-based rehabilitation was consistently lower than that of conventional care except when hospital costs were assumed to be 50 % less than those used in the main analysis . Multiple regression analysis demonstrated that the cost of the home-based program was significantly related to a patient 's level of disability after adjustment for age , comorbidity , and the presence or absence of a caregiver . CONCLUSIONS The early hospital discharge and home-based rehabilitation scheme was less costly than conventional hospital care for patients with stroke . Limitation of the provision of such services to patients with mild disability is likely to be most cost effective Background and Purpose — Early supported discharge ( ESD ) for stroke has been shown to yield outcomes similar to or better than those of conventional care , but there is less information on the impact on costs and on the caregiver . The purpose of this study is to estimate the costs associated with an ESD program compared with those of usual care . Methods — We conducted a r and omized controlled trial of stroke patients who required rehabilitation services and who had a caregiver at home . Results — Acute-care costs incurred before r and omization when patients were medically ready for discharge averaged $ 3251 per person . The costs for the balance of the acute-care stay , from r and omization to discharge , were $ 1383 for the home group and $ 2220 for the usual care group . The average cost of providing the 4-week home intervention service was $ 943 per person . The total cost generated by persons assigned to the home group averaged $ 7784 per person , significantly lower than the $ 11 065 per person for those assigned to usual care . A large proportion of the cost differential between the 2 groups arose from readmissions , for which the usual care group generated costs more than quadruple those of the home intervention group . Conclusions — Providing care at home was no more ( or less ) expensive for those with greater functional limitation than for those with less . Caregivers in the ESD group scored consistently lower on the Burden Index than caregivers with usual care , even caregivers of persons with major functional limitations . For persons recovering from stroke and their families , ESD provides a cost-effective alternative to usual care BACKGROUND AND PURPOSE In an inner-London teaching hospital , a r and omized trial of " conventional " care versus early discharge to community-based therapy found no significant differences in clinical outcomes between patient groups . This report examines the economic consequences of the alternative strategies . METHODS One hundred sixty-seven patients received the early discharge package , and 164 received conventional care . Patient utilization of health and social services was recorded over a 12-month period , and cost was determined using data from provider departments and other published sources . RESULTS Inpatient stay after r and omization was 12 days ( intervention group ) versus 18 days ( controls ) ( P=0.0001 ) . Average units of therapy per patient were as follows : physiotherapy , 22.4 ( early discharge ) versus 15.0 ( conventional ) ( P=0.0006 ) ; occupational therapy , 29.0 versus 23.8 ( P=0.002 ) ; speech therapy , 13 . 7 versus 5.8 ( P=0.0001 ) . The early discharge group had more annual hospital physician contacts ( P=0.015 ) and general practitioner clinic visits ( P=0.019 ) but fewer incidences of day hospital attendance ( P=0.04 ) . Other differences in utilization were nonsignificant . Average annual costs per patient were pound sterling 6800 ( early discharge ) and pound sterling 7432 ( conventional ) . The early discharge group had lower inpatient costs per patient ( pound sterling 4862 [ 71 % of total cost ] versus pound sterling 6343 [ 85 % ] for controls ) but higher non-inpatient costs ( pound sterling 1938 [ 29 % ] versus pound sterling 1089 [ 15 % ] ) . Further analysis demonstrated that early discharge is unlikely to lead to financial savings ; its main benefit is to release capacity for an expansion in stroke caseload . CONCLUSIONS Overall results of this trial indicate that early discharge to community rehabilitation for stroke is cost-effective . It may provide a means of addressing the predicted increase in need for stroke care within existing hospital capacity Background and Purpose The aim of the present study was to examine re source utilization during a 12-month period after acute stroke in elderly patients r and omized to care in an acute stroke unit integrated with a care continuum compared with conventional care in general medical wards . A secondary aim was to describe costs related to the severity of stroke . Methods Two hundred forty-nine consecutive patients aged ≥70 years with acute stroke within 7 days before admission , living in their own homes in Göteborg , Sweden , without recognized need of care were r and omized to 2 groups : 166 patients were assigned to nonintensive stroke unit care with a care continuum , and 83 patients were assigned to conventional care . There was no difference in mortality or the proportion of patients living at home after 1 year . Main outcomes were costs from inpatient care , outpatient care , and informal care . Results Mean annual cost per patient was 170 000 Swedish crowns ( SEK ) ( equivalent to $ 25 373 ) and 191 000 SEK ( $ 28 507 ) in the stroke unit and the general medical ward groups , respectively ( P = NS ) . Seventy percent of the total cost was for inpatient care , and 30 % was for outpatient and informal care . For patients with mild , moderate , and severe stroke , the mean annual costs per patient were 107 000 SEK ( $ 15 970 ) , 263 000 SEK ( $ 39 254 ) , and 220 000 SEK ( $ 32 836 ) , respectively ( P < 0.001 ) . There was no statistical difference in age or nonstroke diagnosis . Conclusions The total costs the first year did not differ significantly between the treatment groups in this prospect i ve study . The total annual cost per patient showed a very large variation , which was related to stroke severity at onset and not to age or nonstroke diagnoses . Costs other than those for hospital care constituted a substantial fraction of total costs and must be taken into account when organizing the management of stroke patients . The high variability in costs necessitates a larger study to assess long-term cost effectiveness Background and Purpose — Although stroke units reduce mortality and institutionalization , their comparative cost-effectiveness is unknown . Methods — Healthcare , social services , and informal care costs were compared for 447 acute stroke patients r and omly assigned to stroke unit , stroke team , or domiciliary stroke care . Prospect i ve and retrospective methods were used to identify re source use over 12 months after stroke onset . Cost-effectiveness and cost-utility analyses were undertaken . Results — Mean healthcare and social care costs over 12 months were £ 11 450 for stroke unit , £ 9527 for stroke team , and £ 6840 for domiciliary care . More than half the costs were for the initial episode of care . Institutionalization was a large proportion of follow-up costs . Inclusion of informal care increased costs considerably . When informal care was excluded , the incremental cost-effectiveness ratio per percentage point in deaths or institutionalizations avoided in the first year was £ 496 for the stroke unit over domiciliary care ; incremental cost per quality -adjusted life year quality -adjusted life year gained was £ 64 097 between these 2 groups . The stroke team was dominated by domiciliary care . Conclusions — Cost perspectives , especially those related to long-term and informal care , are important when stroke services are evaluated . Improved health outcomes in the stroke unit come at a higher cost Background and Purpose — Level I evidence from r and omized controlled trials demonstrates that the model of hospital care influences stroke outcomes ; however , the economic evaluation of such is limited . An economic appraisal of 3 acute stroke care models was facilitated through the Stroke Care Outcomes : Providing Effective Services ( SCOPES ) study in Melbourne , Australia . The aim was to describe re source use up to 28 weeks poststroke for each model and examine the cost-effectiveness of stroke care units ( SCUs ) . Methods — A prospect i ve , multicenter , cohort study design was used . Costs and outcomes of stroke patients receiving 100 % treatment in 1 of 3 inpatient care models ( SCUs , mobile service , conventional care ) were compared . Health-sector re source use up to 28 weeks was measured in 1999 . Outcomes were thorough adherence to a suite of important clinical processes and the number of severe inpatient complications . Results — The sample comprised 395 participants ( mean age 73 [ SD 14 ] , 77 % first-ever strokes , males 53 % ) . When compared with conventional care ( n=84 ) , costs for mobile service ( n=209 ) were significantly higher ( P=0.024 ) , but borderline for SCU ( n=102 , P=0.08 ; $ AUD12 251 ; $ AUD15 903 ; $ AUD15 383 respectively ) . This was primarily explained by the greater use of specialist medical services . The incremental cost-effectiveness of SCUs over conventional care was $ AUD9867 per patient achieving thorough adherence to clinical processes and $ AUD16 372 per patient with severe complications avoided , based on costs to 28 weeks . Conclusions — Although acute SCU costs are generally higher , they are more cost-effective than either mobile service or conventional care BACKGROUND AND PURPOSE Treatment of stroke patients in specialized stroke units has become more frequent , yet the effect of this treatment has not been determined . METHODS In a community-based , prospect i ve , and consecutive study of 1241 unselected acute stroke patients , we compared outcome of stroke treatment between two neighboring communities within Greater Copenhagen : the Bispebjerg community , where all acute stroke patients are treated and rehabilitated on a stroke unit , and Frederiksberg community , where all acute stroke patients are treated and rehabilitated on general neurological and medical wards . Except for the different organization of stroke treatment , the two communities and the two patient groups were comparable . Specifically , age , sex , marital status , prestroke residence , and stroke severity were not statistically different between patients treated on the stroke unit and those treated on the general neurological and medical wards . Multivariate regression analyses were used to estimate the independent influence of stroke unit treatment on outcome . RESULTS Stroke unit treatment significantly reduced in-hospital mortality ( odds ratio [ OR ] , 0.50 ; 95 % confidence interval [ CI ] , 0.34 to 0.74 ; P < .001 ) , case-fatality rate ( OR , 0.45 ; CI , 0.28 to 0.71 ; P < .001 ) , 6-month mortality ( OR , 0.57 ; CI , 0.39 to 0.82 ; P = .002 ) , 1-year mortality ( OR , 0.59 ; CI , 0.42 to 0.84 ; P = .003 ) , and discharge rate to a nursing home ( OR , 0.61 ; CI , 0.38 to 0.98 ; P = .04 ) . Discharge rate to the patient 's own home was significantly increased ( OR , 1.90 ; CI , 1.30 to 2.70 ; P < .001 ) . The length of hospital stay ( including rehabilitation ) was reduced significantly by 30 % in patients treated on the stroke unit despite their lower mortality ( P < .001 ) . The savings due to stroke unit treatment were estimated at 1313 bed-days and three places at a nursing home per 100 stroke patients . CONCLUSIONS Treatment of unselected acute stroke patients on a stroke care unit saved lives , reduced the length of hospital stay , reduced the frequency of discharge to a nursing home , and potentially reduced cost Background and Purpose Several trials have shown that stroke unit care improves outcome for stroke patients . The aim of the present trial was to evaluate the effects of an extended stroke unit service ( ESUS ) , with early supported discharge , cooperation with the primary healthcare system , and more emphasis on rehabilitation at home as essential elements . Methods In a r and omized , controlled trial , 160 patients with acute stroke were allocated to the ESUS and 160 to the ordinary stroke unit service ( OSUS ) . The primary outcome was the proportion of patients who were independent as assessed by the modified Rankin Scale ( RS ) ( RS ≤2=global independence ) and independent in activities of daily living ( ADL ) as assessed by Barthel Index ( BI ) ( BI ≥95=independent in ADL ) after 26 weeks . Secondary outcomes were RS and BI scores after 6 weeks ; the proportion of patients at home , in institutions , and deceased after 6 and 26 weeks ; and the length of stay in institutions . Results After 26 weeks , 65.0 % in the ESUS versus 51.9 % in the OSUS group showed global independence ( RS ≤2 ) ( P= 0.017 ) , while 60.0 % in the ESUS versus 49.4 % in the OSUS group were independent in ADL ( BI ≥95 ) ( P = 0.056 ) . The odds ratios for independence ( ESUS versus OSUS ) were as follows : RS , 1.72 ( 95 % CI , 1.10 to 2.70 ) ; BI , 1.54 ( 95 % CI , 0.99 to 2.39 ) . At 6 weeks , 54.4 % of the ESUS group and 45.6 % of the OSUS group were independent according to RS ( P = 0.118 ) , and 56.3 % versus 48.8 % were independent according to BI ( P = 0.179 ) . The proportion of patients at home after 6 weeks was 74.4 % for ESUS and 55.6 % for OSUS ( P = 0.0004 ) , and the proportion in institutions was 23.1 % versus 40.0 % , respectively ( P = 0.001 ) . After 26 weeks , 78.8 % in the ESUS group versus 73.1 % in the OSUS were at home ( P = 0.239 ) , while 13.1 % versus 17.5 % were in institutions ( P = 0.277 ) . The mortality in the 2 groups did not differ . Average lengths of stay in an institution were 18.6 days in the ESUS and 31.1 days in the OSUS group ( P = 0.0324 ) . Conclusions An ESUS with early supported discharge seems to improve functional outcome and to reduce the length of stay in institutions compared with traditional stroke unit care OBJECTIVES To compare the effectiveness and costs of a new domiciliary rehabilitation service for elderly stroke patients with geriatric day-hospital care . DESIGN R and omized controlled trial . PARTICIPANTS Stroke patients aged 55 + who required further rehabilitation after hospital discharge or after referral to geriatricians from the community . SETTING Poole area , East Dorset , a mixed urban/rural area on the south coast of Engl and . MAIN OUTCOMES Primary -changes between hospital discharge and 6-month follow-up in physical function as measured by Barthel index . Secondary -changes over this period in Rivermead Mobility Index and mental state ( Philadelphia Geriatric Centre Morale Scale ) and differences in social activity ( Frenchay Activities Index ) and generic health status ( SF-36 ) . Health service and social service cost per patient were compared for the two groups . RESULTS 180 patients were eligible and 140 ( 78 % ) were r and omized . The groups were well balanced for age , sex , social class and initial Barthel index . We achieved follow-up in 88 % of subjects who were alive at 6 months . We detected no significant differences in patient outcomes , although there was a non-significant improvement in measures of physical function and social activity in the domiciliary group . Domiciliary patients had more physiotherapy time per session and more district nurse time , and made greater use of social service day centres and home helps . Total cost per patient did not differ significantly between the two groups , with reduced health service costs in the domiciliary arm offset by higher social service costs . CONCLUSION No significant differences were detected in the effectiveness of the two services . Neither service influenced patients ' mental state , and their social activity remained low . Total costs were similar . A mixed model of day-hospital and domiciliary care may be most cost-effective for community stroke rehabilitation , but this requires further evaluation Objectives : The aim of the present trial was to compare the effects of an extended stroke unit service ( ESUS ) with the effects of an ordinary stroke unit service ( OSUS ) on long-term quality of life ( QoL ) . Design : One year follow-up of a r and omized controlled trial with 320 acute stroke patients allocated either to OSUS ( 160 patients ) or ESUS ( 160 patients ) with early supported discharge and follow-up by a mobile team . The intervention was a mobile team and close co-operation with the primary health care service . All assessment s were blinded . Main outcome measure : Primary outcome of QoL in this paper was measured by the Nottingham Health Profile ( NHP ) at 52 weeks . Secondary outcomes measured at 52 weeks were differences between the groups measured by the Frenchay Activity Index , Montgomery-A ° sberg Depression Scale , Mini-Mental State Score and the Caregivers Strain Index . Results : The ESUS group had a significantly better QoL ( mean score 78.9 ) assessed by global NHP after one year than the OSUS group ( mean score 75.2 ) ( p -0.048 ) . There were no significant differences between the groups in the secondary outcomes , but a trend in favour of ESUS . Caregivers Strain Index showed a mean score of 23.3 in the ESUS group and 22.6 in the OSUS group ( p -0.089 ) . Conclusion : It seems that stroke unit treatment combined with early supported discharge in addition to reducing the length of hospital stay can improve long-term QoL. However , similar trials are necessary to confirm the benefit of this type of service Background and Purpose : This study sought to evaluate early supported discharge and continued rehabilitation at home after stroke , at a minimum of 6 months after the intervention , in terms of patient outcome , re source use and health care cost . Methods : Eighty-three patients , moderately impaired 5–7 days after acute stroke , were included in a r and omized controlled trial , 42 being allocated to the intervention and 41 to routine rehabilitation . One-year follow-up of patient outcome included mortality , motor capacity , dysphasia , activities of daily living , social activities , perceived dysfunction , and self-reported falls . Re source use over 12 months included inpatient hospital care , outpatient health care , use of health-related services , informal care , and cost of health care . Results : On univariate analysis there was no difference in patient outcome . Multivariate regression analysis showed that intervention had a significant effect on independence in activities of daily living . A significant difference in inpatient hospital care , initial and recurrent , was observed , with a mean of 18 ( intervention ) versus 33 days ( control ) ( p = 0.002 ) . Further significant differences were that the control group registered more outpatient visits to hospital occupational therapists ( p = 0.02 ) , private physical therapists ( p = 0.03 ) and day-hospital attendance ( p = < 0.001 ) , while the intervention group registered more visits to nurses in primary care ( p = 0.03 ) and home rehabilitation ( p = < 0.001 ) . Other differences in outcomes or re source utilization were nonsignificant . Conclusion : In Sweden , early supported discharge with continued rehabilitation at home proved no less beneficial as a rehabilitation service , and provided care and rehabilitation for 5 moderately disabled stroke patients over 12 months after stroke onset for the cost of 4 in routine rehabilitation The DOMINO study ( DOMiciliary rehabilitation In NOttingham ) was a r and omized controlled trial comparing domiciliary and hospital-based rehabilitation for stroke patients after discharge from hospital , stratified according to the ward at hospital discharge . The outcomes of these patients have been reported previously . In this paper , we present estimates of health service costs of care . No difference in outcome had been found between the overall services , but we have found the hospital-based costs to be 27 % cheaper . However , different cost-effectiveness patterns are observable when the strata are analysed . Patients from geriatric wards had been shown to be 2.4 times less likely to die or become institutionalized by 6 months if allocated to a day hospital service , although the cost of this service was 25 % more than that of the domiciliary service . Patients from the Stroke Unit who had received domiciliary rehabilitation had been shown to have greater household and leisure abilities at 6 months than those treated in outpatient departments , but the domiciliary service was found to cost 2.6 times more . Patients from general medical wards had similar outcomes whether treated at home or in outpatient departments , but the cost of the latter service was 56 % of the former . Some patients may be best cared for in day hospitals and others may do better if treated at home , but for these groups the clinical advantages are achieved at an expense greater than that incurred by the alternative services . Other patients may do as well if treated in outpatient departments as at home , but the former approach is cheaper . A range of services is required for stroke patients leaving hospital Background Across the developed world , we are witnessing an increasing emphasis on the need for more closely coordinated forms of health and social care provision . Integrated care pathways ( ICPs ) have emerged as a response to this aspiration and are believed by many to address the factors which contribute to service integration . ICPs map out a patient 's journey , providing coordination of services for users . They aim to have : ' the right people , doing the right things , in the right order , at the right time , in the right place , with the right outcome ' . The value for ICPs in supporting the delivery of care across organisational boundaries , providing greater consistency in practice , improving service continuity and increasing collaboration has been advocated by many . However , there is little evidence to support their use , and the need for systematic evaluations in order to measure their effectiveness has been widely identified . A recent Cochrane review assessed the effects of ICPs on functional outcome , process of care , quality of life and hospitalisation costs of in patients with acute stroke , but did not specifically focus on service integration or its derivatives . To the best of our knowledge , no such systematic review of the literature exists . Objectives To systematic ally review all high‐ quality studies which have evaluated the impact of care pathway technologies on ' service integration ' and its derivatives in stroke care To examine how elements of service integration are defined in such studies To examine the type of evidence utilised to measure service integration To analyse the weight of evidence used to support cl aims about the effectiveness of ICPs on improving service integration To produce recommendations for ICP developers , users and evaluators . Inclusion criteria Types of participants The review focused on the care of adult patients who had suffered a stroke . It included the full spectrum of services ‐ acute care , rehabilitation and long‐term support ‐ in hospital and community setting s. Types of intervention(s)/phenomena of interest Integrated care pathways were the intervention of interest , defined for the purpose of this review as ' a multidisciplinary tool to improve the quality and efficiency of evidence based care and is used as a communication tool between professionals to manage and st and ardise the outcome orientated care ' . Here ' multidisciplinary ' is taken to refer to the involvement of two or more disciplines . Types of outcomes Service integration ' was the outcome of interest however , this was defined and measured in the selected studies . Types of studies This review was concerned with how ' service integration ' was defined in evaluations of ICPs ; the type of evidence utilised in measuring the impact of the intervention and the weight of evidence to support the effectiveness of care pathway technologies on ' service integration ' . Studies that made an explicit link between ICPs and service integration were included in the review . Evidence generated from r and omised controlled trials , quasi‐experimental , qualitative and health economics research was sought . The search was limited to publications after 1980 , coinciding with the emergence of ICPs in the healthcare context . Assessment for inclusion of foreign papers was based on the English‐ language abstract , where available . These were included only if an English translation was available . Exclusion criteria This review excluded studies that : focused only on a single aspect of stroke care ( e.g. dysphasia ) evaluated ICPs as part of a wider program of service development did not make an explicit link between ICPs and service integration did not meet the definition of ICP utilised for the purpose s of the review focused exclusively on the outcomes of variance analysis Search strategy In order to avoid replication , the Joanna Briggs Institute for Evidence Based Nursing and Midwifery Data base and the Cochrane Library were search ed to establish that no systematic review s existed and none were in progress . A three‐stage search strategy was then used to identify both published and unpublished studies ( see Appendix III ) . Data collection Our search strategy located 2123 papers , of which 39 were retrieved for further evaluation . We critically appraised seven papers , representing five studies . These were all evaluation studies and , as is typical in this field , comprised a range of study design s and data collection methods . Owing to the diversity of the study types included in the review , we developed a single‐ appraisal checklist and data ‐ extraction tool which could be applied to all research design s.32 The tool drew on the Joanna Briggs Institute ( JBI ) appraisal checklists for experimental studies and interpretive and critical research , and also incorporated specific information and issues which were relevant for our purpose s ( see Appendix VI ) . This extends the thinking outlined in Lyne et al.31 in which , drawing on Campbell and Stanley 's classic paper , the case is made for developing an appraisal tool which is applicable to all types of evaluation , irrespective of study design . In assessing the quality of the papers , we were sympathetic to the method ological challenges of evaluating complex interventions such as ICPs . We were also cognisant of the very real constraints in which service evaluations are frequently undertaken in healthcare context s. In accordance with the aims of this particular review , we have included studies , which are method ologically weaker than is typical of many systematic review s because , in our view , in the absence of stronger evidence , they yield useful information . Data synthesis Given the heterogeneity of the included studies , meta‐ analysis and /or qualitative synthesis was not possible . A narrative summary of the study findings is presented . Results ICPs can be effective in ensuring that patients receive relevant clinical interventions and /or assessment s in a timely manner , although these improvements may reflect better documentation rather than actual changes in practice . ICPs can be effective in improving the documentation of rehabilitation goals , documentation of communication with patients , carers ( diagnosis , prognosis and follow‐up arrangements ) and documentation of notification of primary care physicians of discharge . However , this can create additional burdens of work for staff . Early studies of ICP‐managed care in the acute stroke context have demonstrated reduced length of stay without any associated adverse effects on discharge destination , morbidity or mortality . These effects do not reach statistical significance , however , and may reflect wider changes in service provision and a general trend towards reduced length of hospital stay . While later studies in the acute and rehabilitation context s do not reveal any significant reduction in length of stay , they do report greater documented use of certain clinical interventions and assessment s , suggesting that ICPs can be effective in mobilising hospital re sources around the patient . ICPs implemented in the context of acute stroke care can be effective in reducing the occurrence of urinary tract infections , although we do not know whether this can be attributed to improved service integration . ICP management in stroke rehabilitation may not be flexible enough to meet diverse patient needs and can result in insufficient attention to higher‐level functioning and carer needs influencing perceptions of quality of life . ICP management may assist in clarifying role boundaries and a shared underst and ing of the work , but this can result in some members of the disciplinary team perceiving that their contribution is not appropriately reflected in the documentation . There is some evidence that ICPs may be effective in changing professional behaviours in the desired direction where there is scope for improvement , but in situations in which multidisciplinary working is effective , their positive effects may be limited . Furthermore , it is far from clear what the active ingredients of ICPs actually are . Kwan et al. suggest that it was the process of ICP development that had most impact on behaviours rather than the use of the artefact per se.20 None of the studies assessed the balance of costs and benefits of ICP use . Therefore , we do not know whether the costs of ICP development and implementation are justified by any of the reported benefits . Conclusions Implication s for practice There is some evidence that ICPs may support certain elements of service integration in the context of stroke care . This seems to be as a result of their ability to support the timely implementation of clinical interventions and the mobilisation of re sources around the patient without incurring additional increases in length of stay . ICPs appear to be most successful in improving service coordination in the acute stroke context where patient care trajectories are predictable . Their value in the context of rehabilitation setting s in which recovery pathways are more variable is less clear . There is some evidence that ICPs may be effective in bringing about behavioural changes in context s where deficiencies in service provision have been identified . Their value in context s where inter‐professional working is well established is less clear . While earlier before and after studies show a reduction in length of stay in ICP‐managed care , this may reflect wider healthcare trends , and the failure of later studies to demonstrate further reductions suggests that there may be limits as to how far this can continue to be reduced . There is some evidence to suggest that ICPs bring about improvements in documentation , but we do not know how far documented practice reflects actual practice . It is unclear how ICPs have their effects and the relative importance of the process of development and the artefact in use . As none of the studies review ed included an economic evaluation , moreover , it remains unclear whether the benefits of ICPs OBJECTIVE To compare a specialized interprofessional team approach to community-based stroke rehabilitation with usual home care for stroke survivors using home care services . METHODS R and omized controlled trial of 101 community-living stroke survivors ( < 18 months post-stroke ) using home care services . Subjects were r and omized to intervention ( n=52 ) or control ( n=49 ) groups . The intervention was a 12-month specialized , evidence -based rehabilitation strategy involving an interprofessional team . The primary outcome was change in health-related quality of life and functioning ( SF-36 ) from baseline to 12 months . Secondary outcomes were number of strokes during the 12-month follow-up , and changes in community reintegration ( RNLI ) , perceived social support ( PRQ85-Part 2 ) , anxiety and depressive symptoms ( Kessler-10 ) , cognitive function ( SPMSQ ) , and costs of use of health services from baseline to 12 months . RESULTS A total of 82 subjects completed the 12-month follow-up . Compared with the usual care group , stroke survivors in the intervention group showed clinical ly important ( although not statistically significant ) greater improvements from baseline in mean SF-36 physical functioning score ( 5.87 , 95 % CI -3.98 to 15.7 ; p=0.24 ) and social functioning score ( 9.03 , CI-7.50 to 25.6 ; p=0.28 ) . The groups did not differ for any of the secondary effectiveness outcomes . There was a higher total per-person costs of use of health services in the intervention group compared to usual home care although the difference was not statistically significant ( p=0.76 ) . CONCLUSIONS A 12-month specialized , interprofessional team is a feasible and acceptable approach to community-based stroke rehabilitation that produced greater improvements in quality of life compared to usual home care . Clinical trials.gov identifier : NCT00463229 Objective : To describe and compare six community services providing co-ordinated , multidisciplinary rehabilitation to people with stroke . Design : Prospect i ve , descriptive , quantitative study . Setting : Engl and and Northern Irel and . Subjects : Community rehabilitation teams and the patients treated by them . Main outcome measures : Annual numbers treated , Barthel Index , mortality , place of discharge , crude costs . Results : Between mid-1997 and mid-1999 , data were collected on 1076 patients who received community-based rehabilitation of whom 48.7 % were male . Mean age ( SD ) was 71 years ( 13.1 ) ; 115 ( 10.7 % ) were under 55 years of age and 278 ( 25.9 % ) under 65 years of age . Median time between stroke and intervention by the community service was six weeks ( 25th , 75th percentiles 2.6 , 14.4 weeks ) and 80.5 % had been admitted to hospital . The median Barthel score at the start of community rehabilitation was 15 ( 11.0 , 18.0 ) and at the end was 18.0 ( 14.0 , 20.0 ) . Median duration of intervention was 12 weeks ( 6.0 , 22.0 ) . At the end of community rehabilitation 912 patients ( 86.5 % ) were in the community , 52 ( 4.9 % ) had died , 10 ( 0.9 % ) were in hospital and 77 ( 7.3 % ) in long-term care . Comparative data given here are for one year , 1998 , when a total of 519 patients began community rehabilitation . Details of 1855 face-to-face interventions were also recorded from subsets of 10 consecutive patients . Conclusions : Community rehabilitation teams differed in their target population s , in the timing and duration of intervention . A taxonomy of four types of co-ordinated community-based rehabilitation for people with stroke is proposed : ( 1 ) Early-supported discharge rehabilitation aim ed to reduce length of hospital stay and offered an alternative to hospital rehabilitation . ( 2 ) Post-discharge rehabilitation provided additional rehabilitation and aim ed for a seamless transfer of patients from hospital to community . ( 3 ) General practitioner-oriented post-stroke rehabilitation provided an alternative to hospital admission and rehabilitation . ( 4 ) Late community rehabilitation provided patients with the opportunity of an autonomous service , unconnected with hospital or GP referral . Purchasers need to decide for what purpose a team is to be set up . Research ers need to be similarly aware of diversity in community rehabilitation before comparisons are made The diagnosis of stroke , which is diagnosis-related group ( DRG ) 014 , is the fourth most frequent discharge DRG at Macomb Hospital Center , Warren , Michigan . The length of stay for stroke was 7.52 days before intervention . Quality improvement techniques identified areas of delay that presented opportunities for improvement . After the initiation of a critical pathway that begins its interventions in the Emergency Department , the length of stay decreased to 6.33 days . Quality of care was also improved in delivery time of carotid artery ultrasound examinations , as well as in timeliness of obtaining head computed tomography scans and reports . This article describes the development , implementation , and results of a stroke critical pathway that was implemented to address excessive length of stay Background : An early supported discharge service ( ESD ) appears to be a promising alternative to conventional care . The aim of this trial was to compare the use of health services and costs with traditional stroke care during a one-year follow-up . Methods : Three hundred and twenty patients were r and omly allocated either to ordinary stroke unit care or stroke unit care combined with ESD which was coordinated by a mobile team . The use of all health services was recorded prospect ively ; its costs were measured as service costs and represent a combination of calculated average costs and tariffs . Hospital expenses were measured as costs per inpatient day and adjusted for the DRG . Results : There was a reduction in average number of inpatient days at 52 weeks in favour of the ESD group ( p = 0.012 ) , and a non-significant reduction in total mean service costs in the ESD group ( EUR 18,937/EUR 21,824 ) . ESD service seems to be most cost-effective for patients with a moderate stroke . Conclusion : Acute stroke unit care combined with an ESD programme may reduce the length of institutional stay without increasing the costs of outpatient rehabilitation compared with traditional stroke care This study tested the effects of a project network technique called the Critical Path Method ( CPM ) on the costs and outcomes of inpatient team stroke rehabilitation . On admission to a large , academic , inpatient rehabilitation hospital adults who had a recent ( < 120 days ) stroke were r and omly assigned to receive rehabilitation services from a team trained in CPM ( N = 53 ) or from usual care teams ( N = 68 ) . Results showed no significant difference between groups in length of stay , hospital charges , or functional status at discharge . CPM may be effective in patient care services that are less influenced by specialization , professional issues , and external regulation and in setting s where patient outcomes are relatively fixed and predictable , and medical care is integrated across institutions BACKGROUND R and omized trials have shown that integrating services for acute stroke care may lead to organizational improvements , higher efficiency and better patient outcomes in the acute phase . AIM To compare the costs and effects of stroke services in an experimental group of patients compared to a group of patients receiving conventional care . DESIGN Prospect i ve non-r and omized controlled trial . METHODS We compared all consecutively hospitalized stroke patients in three experimental stroke service setting s ( Delft , Haarlem and Nijmegen , n = 411 ) with concurrent patients receiving conventional stroke care ( n = 187 ) over 6 months follow-up . Main end-points were total costs per patient and total health-adjusted days per 100 patients as measured by the EuroQol-5D score during follow-up . RESULTS Mean total costs per patient were 16,000 Euro ( 95%CI 14,670 Euro-16,930 Euro ) : 13,160 Euro in Delft , 16,790 Euro in Haarlem , 20,230 Euro in Nijmegen , and 13,810 Euro in the control regions . Early discharge in Delft saved about 2500 Euro hospital costs per patient . General patient health in Delft was significantly better than in the control regions ; Haarlem and Nijmegen showed no difference in health . DISCUSSION Our study confirms the potential to improve stroke outcomes in a cost-effective way in Dutch setting s. This was seen in the group of patients in Delft , a complete and relatively simple stroke service , but not in two other regions with more complex stroke services . Important factors are reduction of hospital days and , most likely , adequate multidisciplinary rehabilitation BACKGROUND AND PURPOSE Because stroke management is aim ed at facilitating community reintegration , it would be logical that the sooner the patient can be discharged home , the sooner reintegration can commence . The purpose of this study was to determine the effectiveness of prompt discharge combined with home rehabilitation on function , community reintegration , and health-related quality of life during the first 3 months after stroke . METHODS A r and omized trial was carried out involving patients who required rehabilitation services and who had a caregiver at home . When medically ready for discharge , persons with stroke were r and omized to either the home intervention group ( n=58 ) or the usual care group ( n=56 ) . The home group received a 4-week , tailor-made home program of rehabilitation and nursing services ; persons r and omized to the usual care group received services provided through a variety of mechanisms , depending on institutional , care provider , and personal preference . The main outcome measure was the Physical Health component of the Measuring Outcomes Study Short-Form-36 ( SF-36 ) . Associated outcomes measures included the Timed Up & Go ( TUG ) , Barthel Index ( BI ) , the Older Americans Re source Scale for instrumental activities of daily living ( OARS-IADL ) , Reintegration to Normal Living ( RNL ) , and the SF-36 Mental Health component . RESULTS The total length of stay for the home group was , on average , 10 days , 6 days shorter than that for the usual care group . There were no differences between the 2 groups on the BI or on the TUG at either 1 or 3 months after stroke ; however , there was a significantly beneficial impact of the home intervention on IADL and reintegration ( RNL ) . By 3 months after stroke , the home intervention group showed a significantly higher score on the SF-36 Physical Health component than the usual care group . The total number of services received by the home group was actually lower than that received by the usual care group . CONCLUSIONS Prompt discharge combined with home rehabilitation appeared to translate motor and functional gains that occur through natural recovery and rehabilitation into a greater degree of higher-level function and satisfaction with community reintegration , and these in turn were translated into a better physical health BACKGROUND AND PURPOSE Much controversy exists over the value of geriatric day hospitals in the rehabilitation of elderly patients , and cerebrovascular accident is a particularly common diagnosis among patients referred to these day hospitals . We carried out a prospect i ve , r and omized study to compare the outcomes of elderly stroke patients managed by a geriatric team using a day hospital facility versus conventional medical management . METHODS One hundred twenty elderly patients with acute stroke were r and omized to inpatient care on a stroke ward under the care of either a neurologist or a geriatric team . Those under the care of neurologists were hospitalized until the attending physician felt that the patients had reached full rehabilitation potential . Patients under the care of the geriatric team were discharged home as soon as the team felt they were able to cope and given follow-up rehabilitation at the day hospital . Family or community support was arranged when necessary for both treatment groups . On recruitment , patient demographics , medical history , clinical features related to stroke , and functional ability as measured by the Barthel Index were noted . Subjects were review ed at 3 and 6 months to assess functional level , hospital and outpatient services received , general well-being , mood , and level of satisfaction . Costs of treatment of the two groups were also compared . RESULTS Functional improvement ( Barthel Index score ) was greater in the group managed by the geriatricians with a day hospital facility compared with the conventional group at 3 months ( P = .03 ) . There were also fewer outpatient visits among the day hospital patients at 6 months ( P = .03 ) . No significant difference was found in costs between the two treatment groups . CONCLUSIONS Compared with conventional medical management , care in the geriatric day hospital hastened functional recovery and reduced outpatient visits in elderly stroke patients without additional cost AIM To assess the validity of Barthel based poststroke triage , the effectiveness of a rehabilitation unit in minimising poststroke institutionalisation , and medical re source utilisation for stroke management . METHODS A prospect i ve study of stroke outcome for 115 consecutive patients admitted to Middlemore Hospital , Auckl and , between March and September 1993 , based on Barthel functional assessment s at 1 week and 3 months poststroke , postdischarge domicile and duration of inpatient stay in both acute medical and rehabilitation units . RESULTS For the 73 patients offered rehabilitation , 48 ( 76 % ) of the survivors were able to return home after a mean period of 6 weeks . Of 24 subjects with 1 week Barthel scores of five or less , 15 of 19 ( 84 % ) survivors returned to their original domicile . Of eight patients with 1 week Barthel scores of two or less , all survived and five returned home . The median delay between admission by the acute medical service and transfer to the rehabilitation unit was only four days for the 70 patients involved . CONCLUSION Our data provides local confirmation of internationally increasing acceptance of the effectiveness of rehabilitation units in reducing expensive long term institutionalisation and freeing up stressed acute medical re sources The financial cost of stroke rehabilitation is considerable but few cost-effectiveness studies are available to guide clinical practice . The Bradford community stroke trial was a r and omised trial comparing day hospital attendance with home physiotherapy for elderly stroke patients leaving hospital . The outcome measurements used indicated a consistent modest advantage in favour of home physiotherapy . This advantage is now re-examined in conjunction with the quantified costs of the rehabilitation services and community support received by the two patient groups . The results show that the median cost for the day hospital patients over the first eight weeks was 620.00 pounds ( interquartile range 555.00 - 730.00 pounds ) and 385.00 pounds for the home physiotherapy group ( interquartile range 240.00 - 510.00 pounds ) . These costs were significantly different ( median difference 265.00 pounds , 95 % confidence interval 190.00 - 340.00 pounds ; p < 0.01 ) . There were no significant differences between the two groups for the indirect costs . This cost-effectiveness study supports the clinical trial result that home physiotherapy should be the treatment of choice for stroke aftercare Objective : To determine the impact of a protocol on hospitalization costs for patients admitted with stroke . Design and setting : Nonr and omized control trial in an urban community hospital with 376 beds . Patients : All patients admitted with a diagnosis-related group code of 014 ( cerebrovascular disease ) were included ( N = 390 ) . Patients with subdural hematoma ( N = 2 ) or subarachnoid hemorrhage ( N = 2 ) were excluded . Intervention : A protocol for treatment of acute stroke was developed that included a critical path for nursing care , an algorithm for emergency department care , and suggested admission orders for physicians . Main outcome measures : The hospital information system computer data base was search ed for hospitalization charges , length of stay , tests performed , and treatments provided . Results : Patients treated with the protocol had lower charges compared with historical ( p = 0.026 ) and concurrent ( p = 0.02 ) control groups . Lower charges were accounted for by a decreased length of stay in the protocol group compared with historical ( p = 0.001 ) and concurrent ( p = 0.13 ) controls . Tests and treatments provided were similar except that carotid Doppler studies and deep venous thrombosis prophylaxis were more frequently done in those treated with the protocol ( p = 0.001 for carotid Doppler and p = 0.026 for deep venous thrombosis prophylaxis ) . There were no differences in outcome measures such as death or discharge disposition . Medical complications were similar in all groups . Conclusions : There were significant savings in hospitalization cost for patients with acute stroke after introduction of a treatment protocol . These savings were almost entirely related to decreased length of stay . The protocol led to modest differences in tests ordered and treatments provided |
1,888 | 22,651,380 | With only a few small studies available per supplement , evidence was insufficient for all predefined gradable clinical efficacy and harms outcomes , such as mortality and serious adverse events .
Incremental benefits were noted for triglyceridemia with omega-3 fatty acid added to statins ; and there was an improvement in levels of high-density lipoprotein cholesterol with garlic supplementation when people also consumed nitrates Conclusions Evidence of low-strength indicates benefits of omega-3 fatty acids ( plus statin , or calcium channel blockers and antiplatelets ) and garlic ( plus nitrates or warfarin ) on triglycerides and HDL-C , respectively . | Background The objective of this systematic review was to examine the benefits , harms and pharmacokinetic interactions arising from the co-administration of commonly used dietary supplements with cardiovascular drugs .
Many patients on cardiovascular drugs take dietary supplements for presumed benefits and may be at risk for adverse supplement-drug interactions . | Patients with combined hyperlipemia have lipid abnormalities associated with an increased tendency to develop atherosclerosis and thrombosis . This tendency may be accelerated during postpr and ial hyperlipemia . In the present double-blind parallel study , 41 patients with combined hyperlipemia and serum triacylglycerols between 2.0 and 15.0 mmol/L and serum total cholesterol > 5.3 mmol/L at the end of a 3-month dietary run-in period were treated with simvastatin at 20 mg/d for at least 10 weeks ; patients were then r and omized into 2 groups receiving simvastatin+omega-3 fatty acids at 3.36 g/d or placebo ( corn oil ) for an additional 5 weeks . Hemostatic variables that have been associated with increased thrombotic tendency were evaluated with subjects in the fasting state and during postpr and ial hyperlipemia before and after combined treatment . Supplementation of omega-3 fatty acid reduced tissue factor pathway inhibitor antigen ( P<0.05 ) in the fasting state , reduced the degree of postpr and ial hyperlipemia ( P<0.005 ) , and reduced activated factor VII concentration appearing during postpr and ial hyperlipemia . In conclusion , omega-3 fatty acids given in addition to simvastatin to patients with combined hyperlipemia reduced the free tissue factor pathway inhibitor fraction in the fasting state and inhibited the activation of factor VII occurring during postpr and ial lipemia , thus representing a potential beneficial effect on the hemostatic risk profile in this patient group Hypercholesterolemia is combined with enhanced lipid peroxidation , which can promote atherogenesis by inducing endothelial adhesion molecule expression . Statins may protect vascular endothelium in hypercholesterolemia by reducing enhanced plasma levels of low-density lipoprotein and decreasing oxidative stress . Herein , we describe increased circulating levels of soluble intercellular adhesion molecule-1 , vascular cell adhesion molecule-1 , and E-selectin and total 8-iso-prostagl and in F(2 alpha ) ( 8-iso-PGF(2 alpha ) ) concentrations , as indexes of endothelial activation and lipid peroxidation , respectively , in 67 hypercholesterolemic patients compared with 32 normocholesterolemic subjects . Significant cholesterol reductions were achieved in hypercholesterolemic patients after 6 months under either simvastatin ( 40 mg/d ) or bezafibrate ( 800 mg/d ) treatment , given according to a r and omized double-blind trial . Simvastatin but not bezafibrate simultaneously reduced soluble adhesin and total 8-iso-PGF(2 alpha ) concentrations also . Vitamin E supplementation ( 400 IU/d ) further reduced indexes of endothelial activation and lipid peroxidation in simvastatin-treated patients and significantly reduced the above indexes in bezafibrate-treated patients . Changes in circulating soluble adhesion molecule levels were directly correlated with changes in total 8-iso-PGF(2 alpha ) concentrations in simvastatin-treated patients also receiving vitamin E supplementation . All together , our data demonstrated that hypercholesterolemia was combined with endothelial activation and lipid peroxidation , which were efficaciously counteracted by simvastatin but not bezafibrate treatment . Thus , a different vascular protection can be achieved by different lipid-lowering treatments The objective of the study was to evaluate potential benefits of docosahexaenoic acid ( DHA ) rich fish oil supplementation as an adjunct to statin therapy for hyperlipidaemia . A total of 45 hyperlipidaemic patients on stable statin therapy with persistent elevation of plasma triglycerides ( averaging 2.2 mmol/L ) were r and omised to take 4 g/day ( n = 15 ) or 8 g/day ( n = 15 ) of tuna oil or olive oil ( placebo , n = 15 ) for 6 months . Plasma lipids , blood pressure and arterial compliance were assessed initially and after 3 and 6 months in 40 subjects who completed the trial . Plasma triglycerides were reduced 27 % by 8 g/day DHA-rich fish oil ( P < 0.05 ) but not by 4 g/day when compared with the placebo and this reduction was achieved by 3 months and was sustained at 6 months . Even though total cholesterol was already well controlled by the statin treatment ( mean initial level 4.5 mmol/L ) , there was a further dose-dependent reduction with fish oil supplementation ( r = −0.344 , P < 0.05 ) . The extent of total cholesterol reduction correlated ( r = −0.44 ) with the initial total cholesterol levels ( P < 0.005 ) . In the subset with initial plasma cholesterol above 3.8 mmol/L , plasma very low density lipoprotein ( VLDL ) , intermediate-density lipoprotein ( IDL ) and low-density lipoprotein ( LDL ) were isolated and assayed for cholesterol and apolipoprotein B ( apoB ) at the commencement of the trial and at 3 months of intervention . Fish oil tended to lower cholesterol and apoB in VLDL and raise both in LDL . There were no changes in IDL cholesterol , IDL apoB and high-density lipoprotein cholesterol . The results demonstrate that DHA-rich fish oil supplementation ( 2.16 g DHA/day ) can improve plasma lipids in a dose-dependent manner in patients taking statins and these changes were achieved by 3 months . Fish oil in addition to statin therapy may be preferable to drug combinations for the treatment of combined hyperlipidaemia Background The approximately 1100 medical journals now active in China are publishing a rapidly increasing number of research reports , including many studies identified by their authors as r and omized controlled trials . It has been noticed that these reports mostly present positive results , and their quality and authenticity have consequently been called into question . We investigated the adequacy of r and omization of clinical trials published in recent years in China to determine how many of them met acceptable st and ards for allocating participants to treatment groups . Methods The China National Knowledge Infrastructure electronic data base was search ed for reports of r and omized controlled trials on 20 common diseases published from January 1994 to June 2005 . From this sample , a subset of trials that appeared to have used r and omization methods was selected . Twenty-one investigators trained in the relevant knowledge , communication skills and quality control issues interviewed the original authors of these trials about the participant r and omization methods and related quality -control features of their trials . Results From an initial sample of 37,313 articles identified in the China National Knowledge Infrastructure data base , we found 3137 apparent r and omized controlled trials . Of these , 1452 were studies of conventional medicine ( published in 411 journals ) and 1685 were studies of traditional Chinese medicine ( published in 352 journals ) . Interviews with the authors of 2235 of these reports revealed that only 207 studies adhered to accepted methodology for r and omization and could on those grounds be deemed authentic r and omized controlled trials ( 6.8 % , 95 % confidence interval 5.9–7.7 ) . There was no statistically significant difference in the rate of authenticity between r and omized controlled trials of traditional interventions and those of conventional interventions . R and omized controlled trials conducted at hospitals affiliated to medical universities were more likely to be authentic than trials conducted at level 3 and level 2 hospitals ( relative risk 1.58 , 95 % confidence interval 1.18–2.13 , and relative risk 14.42 , 95 % confidence interval 9.40–22.10 , respectively ) . The likelihood of authenticity was higher in level 3 hospitals than in level 2 hospitals ( relative risk 9.32 , 95 % confidence interval 5.83–14.89 ) . All r and omized controlled trials of pre-market drug clinical trial were authentic by our criteria . Of the trials conducted at university-affiliated hospitals , 56.3 % were authentic ( 95 % confidence interval 32.0–81.0 ) . Conclusion Most reports of r and omized controlled trials published in some Chinese journals lacked an adequate description of r and omization . Similarly , most so called ' r and omized controlled trials ' were not real r and omized controlled trials owing toa lack of adequate underst and ing on the part of the authors of rigorous clinical trial design . All r and omized controlled trials of pre-market drug clinical trial included in this research were authentic . R and omized controlled trials conducted by authors in high level hospitals , especially in hospitals affiliated to medical universities had a higher rate of authenticity . That so many non-r and omized controlled trials were published as r and omized controlled trials reflected the fact that peer review needs to be improved and a good practice guide for peer review including how to identify the authenticity of the study urgently needs to be developed Thirty elderly ( mean + /- SEM : 73.8 + /- 2.1 y ) nondiabetic , moderately obese ( body mass index = 28.3 + /- 0.6 kg/m2 ) patients with stable effort angina underwent an oral-glucose-tolerance test and a euglycemic hyperinsulinemic glucose clamp before and after vitamin E supplementation ( 900 mg/d for 4 mo ) . The study was of a r and omized , placebo-controlled , double-blind , and crossover design . Anthropometric indexes were stable throughout the study . Despite similar fasting and 2-h plasma glucose concentrations , vitamin E administration ( compared with placebo ) lowered fasting ( 88 + /- 14 and 68 + /- 9 pmol/L , P < 0.02 ) and 2-h ( 348 + /- 43 and 263 + /- 28 pmol/L , P < 0.05 ) plasma insulin concentrations , plasma triglyceride concentrations ( 1.34 + /- 0.06 and 1.07 + /- 0.03 mmol/L , P < 0.05 ) , and the ratio of plasma LDL to HDL cholesterol ( 7.64 + /- 0.31 and 5.52 + /- 0.38 , P < 0.02 ) . Vitamin E administration was associated with higher nonoxidative glucose metabolism ( 18.1 + /- 0.5 and 10.6 + /- 0.7 mumol.kg lean body mass-1.min-1 , P < 0.03 ) than was placebo administration during the euglycemic glucose clamp . We conclude that chronic intake of pharmacological doses of vitamin E might be useful in the therapy of elderly insulin-resistant patients with coronary heart disease BACKGROUND Supplementation with vitamin E may antagonize vitamin K in healthy adults , but it is unclear whether intake of vitamin E decreases the risk of venous thromboembolism ( VTE ) . METHODS AND RESULTS The Women 's Health Study r and omized 39,876 women > or = 45 years of age to receive 600 IU of natural source vitamin E or placebo on alternate days . Before r and omization , 26,779 participants gave blood sample s , which were used to determine factor V Leiden , G20210A prothrombin , and 677C > T MTHFR polymorphisms . Documented VTE ( including deep vein thrombosis or pulmonary embolism ) and unprovoked VTE ( no recent surgery , trauma , or cancer diagnosis ) were prospect ively evaluated , secondary end points of the trial . During a median follow-up period of 10.2 years , VTE occurred in 482 women : 213 in the vitamin E group and 269 in the placebo group , a significant 21 % hazard reduction ( relative hazard , 0.79 ; 95 % CI , 0.66 to 0.94 ; P=0.010 ) . For unprovoked VTE , the hazard reduction was 27 % ( relative hazard , 0.73 ; 95 % CI , 0.57 to 0.94 ; P=0.016 ) . In subgroup analyses , the 3 % of participants who reported VTE before r and omization had a 44 % hazard reduction ( relative hazard , 0.56 ; 95 % CI , 0.31 to 1.00 ; P=0.048 ) , whereas women without prior VTE had an 18 % hazard reduction ( relative hazard 0.82 ; 95 % CI , 0.68 to 0.99 ; P=0.040 ) . Women with either factor V Leiden or the prothrombin mutation had a 49 % hazard reduction associated with vitamin E treatment ( relative hazard , 0.51 ; 95 % CI , 0.30 to 0.87 ; P=0.014 ) . CONCLUSIONS These data suggest that supplementation with vitamin E may reduce the risk of VTE in women , and those with a prior history or genetic predisposition may particularly benefit BACKGROUND Aged Garlic Extract ( AGE ) reduces multiple cardiovascular risk factors , including blood pressure , cholesterol , platelet aggregation and adhesion , while stimulating nitric oxide generation in endothelial cells . However , no study has evaluated the ability of AGE to inhibit vascular calcification , a marker of plaque formation in human coronary arteries . OBJECTIVE To assess the efficacy of Aged Garlic Extract ( AGE ) on changing the rate of atherosclerosis progression as compared to placebo . DESIGN A placebo-controlled , double-blind , r and omized pilot study to determine whether the atherosclerotic plaque burden detected by electron beam tomography ( EBT ) will change at a different rate under the influence of AGE as compared to placebo . Twenty-three patients were enrolled , and 19 patients completed the study protocol . AGE 4 ml or the equivalent amount of placebo was given to subjects . Duration of the study was 1 year . S-allylcysteine ( SAC ) , one of the active compound of AGE , was measured in the blood as a compliance marker . RESULTS The mean change of the calcium score ( volumetric method ) for the AGE group ( n = 9 ) was 7.5 + /- 9.4 % over 1 year . The placebo group ( n = 10 ) demonstrated an average increase in calcium scores of 22.2 + /- 18.5 % , significantly greater than the treated cohort ( P = 0.046 ) . There were no significant differences in individual cholesterol parameters or C reactive protein between the groups . In patients r and omized to AGE , there was a nonsignificant trend for improving cholesterol/high-density lipoprotein ratio ( P = 0.07 ) and homocysteine level ( P = 0.08 ) . CONCLUSIONS This small pilot study indicates the potential ability of AGE to inhibit the rate of progression of coronary calcification , as compared to placebo over 1 year . Should these findings be extended and confirmed in larger studies , garlic may prove useful for patients who are at high risk of future cardiovascular events Background —Both statins and vitamin E , by reducing the rate of lipid peroxidation , may interfere with oxidative stress , but the impact of their combination is unknown . Methods and Results —We r and omized 43 hypercholesterolemic patients ( 21 men , 22 women , age 63±11 years ) to either simvastatin , to achieve > 20 % reduction of total cholesterol , or simvastatin plus 600 mg/d vitamin E for 2 months . Patients were then crossed over to the alternative treatment . Lipid parameters documented patients ’ compliance to simvastatin , whereas plasma levels of vitamin E documented compliance and absorption of vitamin E. We assessed urinary excretion of the isoprostane 8-iso-prostagl and in F2&agr ; ( 8-iso-PGF2&agr ; ) as an in vivo index of oxidative stress at baseline and after each month of therapy . 8-Iso-PGF2&agr ; was significantly reduced by simvastatin , from 361±148 pg/mg creatinine ( mean±SD ) at baseline to 239±124 pg/mg creatinine after 1 month . The addition of vitamin E did not reduce such levels any further ( 256±125 after 1 month ) . Linear regression analysis showed a weak inverse relationship of 8-iso-PGF2&agr ; with vitamin E levels but a much stronger relationship with LDL cholesterol ( R2=0.162;P < 0.001 ) . Conclusions —In hypercholesterolemic patients , LDL cholesterol is a major correlate of oxidative stress . Concomitant with LDL cholesterol reduction , simvastatin causes a drastic reduction of oxidative stress to a level that is not further reduced by the addition of vitamin E. Results of clinical trials with vitamin E may have been hampered by inadequate knowledge of the background level of lipid peroxidation , which is a major determinant of vitamin E bioactivity The purpose of this placebo-controlled , r and omized , double-blinded , parallel study was to determine the existence and magnitude of effect of various doses of fish oil supplements on International Normalized Ratio ( INR ) determinations in patients receiving chronic warfarin therapy . Patients from anticoagulation clinics from both the Brady Green Community Health Center and Audie L. Murphy Veterans Administration in San Antonio , Texas were enrolled in the study . The enrolled subjects included 5 males and 11 females , all of whom were receiving chronic warfarin therapy for indications requiring oral anticoagulation . All enrolled patients underwent a 4-week placebo monitoring period in which INRs were determined on a weekly basis . If the INRs were found to be stable , patients were r and omized to receive a 4-week treatment period of either placebo capsules ( n = 6 ) , 3 grams of fish oil daily ( n = 5 ) , or 6 grams of fish oil daily ( n = 5 ) . Patients were followed on a twice-weekly basis for INR determinations and adverse reactions . Five patients were discontinued from the study due to noncompliance ( 2 ) and unstable INRs ( 3 ) . There was no statistically significant difference in INRs between the placebo lead-in and treatment period within each group ( P = 0.82 ) . There was also no difference in INRs found between groups ( P = 0.41 ) . One bruising episode was reported , yet no major bleeding episodes were observed during the study . Fish oil supplementation in doses of 3–6 grams per day does not seem to create a statistically significant effect on the anticoagulation status of patients receiving chronic warfarin therapy Fourteen patients suffering from familial hypercholesterolemia ( type IIa ) participated in a double-blind , placebo-controlled trial that evaluated the effects of fish oil ethyl ester ( K-85 , 5.7 g/day ) or a hydroxymethylglutaryl coenzyme A reductase inhibitor ( lovastatin , 40 mg/day ) alone or in combination on lipid metabolism and bleeding time at rest and after st and ardized exercise . Lovastatin treatment reduced total cholesterol ( -27 % ) , low density lipoprotein cholesterol ( -37 % ) , and triglycerides ( -18 % ) , whereas high density lipoprotein cholesterol increased significantly ( 14 % ) . K-85 affected total ( -4 % ) , low density lipoprotein ( -9 % ) , and high density lipoprotein ( + 7 % ) cholesterol insignificantly , whereas the triglyceride level decreased by 24 % ( p < 0.001 ) . The combined regimen caused an additive decrease in the triglyceride level ( 41 % ) , which differed significantly ( p < 0.01 ) from that gained by lovastatin alone . Under basal conditions the bleeding time was not influenced by the different interventions . St and ardized exercise shortened the bleeding time by 19 % ( p < 0.001 ) and 16 % ( p < 0.001 ) before intervention and after lovastatin treatment , respectively . After K-85 alone or in combination with lovastatin , the exercise-induced shortening of the bleeding time was totally inhibited , which may reflect a favorable influence of fish oil on the platelet-vessel wall interaction in these high-risk patients BACKGROUND Currently , several therapeutic protocol s exist for IgA nephropathy ( IgAN ) ; results in slowing the progression to end-stage renal disease ( ESRD ) are variable , but approximately 30 - 40 % of patients require replacement therapy ( dialysis or renal transplantation ) by 20 years from the onset . The adverse effects brought by the chronic assumption of drugs can be a potential limit . Actually , the most used therapies for IgAN are renin-angiotensin system blockers ( RASB ) , glucocorticoids and immunosuppressive agents . Trials with polyunsaturated fatty acids ( PUFA ) in IgAN have been done since the first successful attempt by Hamazaki in 1984 , result ing in alternate answers , but no trials have ever been done testing the efficacy of combined therapy with RASB and PUFA . METHODS We tested the effect of a 6-month course of PUFA ( 3 grams/day ) in a group of 30 patients with biopsy-proven IgAN and proteinuria already treated with RASB r and omized to receive PUFA supplementation or to continue their st and ard therapy . The primary end-point was the percent reduction of proteinuria from the baseline . Secondary end-points were modifications in glomerular filtration rate ( GFR ) , blood pressure , serum triglycerides and erythrocyturia . RESULTS At the end of the 6-month trial , the percent reduction of proteinuria was 72.9 % in the PUFA group and 11.3 % in the RASB group ( P < 0.001 ) . A reduction of > or=50 % of baseline proteinuria was achieved in 80.0 % of PUFA patients and 20.0 % of RASB patients ( P = 0.002 ) . Erythrocyturia was significantly lower in the PUFA group ( P = 0.031 ) . No significant changes in renal function , blood pressure and triglycerides were observed . CONCLUSIONS PUFA associated with RASB reduced proteinuria in patients with IgAN more than RASB alone Hawthorn , an herbal supplement , is currently being evaluated for the treatment of heart failure . The flavonoid components of hawthorn may be responsible for hawthorn 's beneficial effects in the treatment of heart failure . However , these components may also affect P-glycoprotein function and cause interactions with drugs that are P-glycoprotein substrates , such as digoxin , which is also used to treat heart failure . Therefore , the purpose of this study was to determine the effect of hawthorn on digoxin pharmacokinetic parameters . A r and omized , crossover trial with 8 healthy volunteers was performed evaluating digoxin 0.25 mg alone ( D ) for 10 days and digoxin 0.25 mg with Crataegus special extract WS 1442 ( hawthorn leaves with flowers ; Dr. Willmar Schwabe Pharmaceuticals ) 450 mg twice daily ( D + H ) for 21 days . Pharmacokinetic studies were performed for 72 hours . There were no statistically significant differences in any measured pharmacokinetic parameters . The AUC0-infinity , Cmax-Cmin , Cmin , and renal clearance for the D group were 79 + /- 26 mcg.h/L , 1.4 + /- 0.7 mcg/L , 0.84 + /- 0.2 mcg/L , and 74 + /- 10 mL/min versus 73 + /- 20 mcg.h/L , 1.1 + /- 0.1 mcg/L , 0.65 + /- 0.2 mcg/L , and 81 + /- 22 mL/min for the D + H group , respectively ( p > 0.05 ) . Following 3 weeks of concomitant therapy , hawthorn did not significantly alter the pharmacokinetic parameters for digoxin . This suggests that both hawthorn and digoxin , in the doses and dosage form studied , may be coadministered safely INTRODUCTION The fibrinolytic system has a major role as a defense mechanism against thrombus formation . Net fibrinolytic activity in plasma reflects the balance between tissue-type plasminogen activator and plasminogen activator inhibitor ( PAI ) . PAI is the main factor determining overall fibrinolytic activity . MATERIAL S AND METHODS We examined the effects of oral administration of vitamin E , an antioxidant , on fibrinolytic activity and oxidative stress in patients with coronary spastic angina . Forty patients with coronary spastic angina were r and omly assigned into two treatment groups , either vitamin E group ( alpha-tocopherol acetate , 400 mg/day ) or placebo group by means of computerized system . PAI activity and thioredoxin , a marker of oxidative stress , levels were measured before and at the end of 1 month treatment . RESULTS Before treatment , the levels of PAI activity and thioredoxin were increased in patients with coronary spastic angina as compared with control subjects ( n=17 ) ( PAI activity levels : 13.6+/-1.4 vs. 7.6+/-2.2 IU/ml , p<0.05 , thioredoxin levels : 22.8+/-1.7 vs. 16.0+/-1.4 ng/ml , p<0.05 ) . In patients with coronary spastic angina , administration of vitamin E decreased both PAI activity and thioredoxin levels ( PAI activity levels : 14.7+/-1.7 to 7.5+/-1.6 IU/ml , p<0.01 , thioredoxin levels : 23.3+/-2.4 to 15.1+/-2.5 ng/ml , p<0.01 ) , whereas placebo had no effect on these variables . CONCLUSIONS Oral administration of vitamin E improved fibrinolytic activity and the improvement was associated with a decrease in oxidative stress . Administration of vitamin E is possible to be an effective adjunct therapy of coronary spasm in the absence of coronary atherosclerosis Garlic has been known to have antiplatelet properties . Because of the lack of major clinical data regarding the safety of concomitant use of garlic supplements and anticoagulants , we decided to evaluate the safety of using garlic extract along with oral anticoagulation therapy . During this project we tested aged garlic extract ( AGE ) , a commercial garlic preparation , with warfarin ( Coumadin ) . Sixty-six ( 66 ) patients were screened for a double-blind , r and omized , placebo-controlled pilot study . Fifty-two ( 52 ) patients were r and omized for the project . Forty-eight patients ( 30 men and 18 women , with a mean age of 56+/-10 years ) completed the study . Eighteen patients ( 14 before r and omization , 4 after r and omization ) were dropped from the study . The study medication ( AGE or placebo ) was administered at a dose of 5 mL twice a day for 12 wk . Potential bleeding and thromboembolic episodes were monitored . There was no evidence of increased hemorrhage in either the placebo or the AGE group . Adverse events included headache , fatigue , colds , and dizziness . However , no significant difference was found in the incidence of these minor adverse events between the groups . Thus , the adverse events are unlikely to be attributable to AGE . The results suggest that AGE is relatively safe and poses no serious hemorrhagic risk for closely monitored patients on warfarin oral anticoagulation therapy . Although the risk-benefit ratio of AGE use needs to be considered carefully when warfarin therapy is necessary , its positive effects may be beneficial to people with a high-risk background or who are taking cardiovascular medications The coadministration of prescription omega-3-acid ethyl esters ( P-OM3 ) with a statin may present a treatment option for patients with mixed hyperlipidemia . This open-label , r and omized , 2-way crossover , drug-drug interaction study evaluated the impact of P-OM3 capsules on plasma simvastatin pharmacokinetics in 24 healthy volunteers . Under fasted conditions , 80 mg simvastatin was administered with or without 4 g P-OM3 for two 14-day periods . After 14 days of dosing to achieve steady state , no significant differences were found in either the extent ( AUC(tau ) ) or rate ( Cmax ) of exposure to simvastatin or its major beta-hydroxy metabolite after coadministration of P-OM3 with simvastatin compared with administration of simvastatin alone . At steady state , the coadministration of P-OM3 capsules did not appear to affect the pharmacokinetics of simvastatin tablets . The combination of P-OM3 capsules and simvastatin appeared to be well tolerated BACKGROUND There are few data on the prevalence and pattern of complementary and alternative medicine ( CAM ) supplement use among people with chronic heart failure ( CHF ) . The aim of this survey was to characterize the prevalence , pattern , and reasons for use of CAM supplements among those with CHF . METHODS AND RESULTS We conducted a cross-sectional survey in 2 groups : CHF patients who had participated in the Hawthorn Extract R and omized Blinded Chronic Heart Failure ( HERB CHF ) Trial , and CHF patients who attended the University of Michigan 's CHF Outpatient Clinic . We received 252 surveys . One third of respondents had used a CAM supplement in the last 6 months . There were 24 different supplements used . Reasons for use included heart problems , anxiety , weight loss , and arthritis . No demographic or behavioral characteristic identified CAM supplement users , although a 50 % lower use among HERB CHF participants approached statistical significance ( P = .08 ) . CONCLUSION One third of our CHF patients were taking CAM supplements , several of which may interact negatively with typical heart failure medications . CAM supplement use for weight loss may be underreported . Demographic and behavioral characteristics may not have identified people with CHF who were using CAM supplements BACKGROUND Today , the combined use of Oriental herbal medicines and Western biomedical medicines has been a prevalent yet controversial practice . Case reports and healthy volunteer trials have had conflicting results on the effect Panax ginseng has on warfarin 's pharmacologic action , some reporting a reductive and others a potentiating influence . OBJECTIVE This study investigated the interaction between warfarin and P. ginseng by observing the prothrombin time ( PT ) and the international normalized ratio ( INR ) in ischemic stroke patients who did not have a history of taking warfarin . DESIGN R and omized , open-label , controlled study . SUBJECTS Twenty-five ( 25 ) patients newly diagnosed with ischemic stroke by brain computed tomography or magnetic resonance imaging in the Korean Medical Hospital , Kyung Hee University ( Seoul , Republic of Korea ) . INTERVENTION Ischemic stroke patients were r and omized into 2 groups : the ginseng group ( n = 12 ) , given both P. ginseng and warfarin , and the control group ( n = 13 ) , given only warfarin , both for 2 weeks . The warfarin dose was restricted to 2 mg in the first week and 5 mg in the second week . RESULTS The peak values and the international normalized ratio ( INR ) and prothrombin time ( PT ) areas under the curve ( AUC ) in both groups significantly increased compared to those at baseline . However , there was no statistically significant difference in peak values and INR and PT AUC between groups in both the first and second weeks . CONCLUSIONS This study suggests that coadministration of P. ginseng and warfarin in ischemic stroke patients does not influence the pharmacologic action of warfarin Objective —Oxidative stress is believed to play a pivotal role in the initiation and progression of atherosclerosis . We analyzed whether vitamin E supplementation influences oxidative stress in plasma and atherosclerotic plaques of patients with severe atherosclerosis . Methods and Results —In 16 patients who were c and i date s for carotid endarterectomy and in 32 age- and sex-matched controls , plasma levels of 7&bgr;-hydroxycholesterol , 7-ketocholesterol , cholesterol , and vitamin E were measured . Patients were r and omly allocated to st and ard treatment with or without 900 mg/d vitamin E. After 6 weeks of treatment , the reported variables were measured in plasma and plaques . The plasma vitamin E/cholesterol ratio was significantly lower in patients than in controls ( 3.05±0.6 versus 6.3±1.7 & mgr;mol/mmol cholesterol , P < 0.001 ) . Plasma 7&bgr;-hydroxycholesterol was significantly higher in patients than in controls ( 5.0±1.04 versus 4.4±0.6 ng/mL , P < 0.05 ) . Patients who were given vitamin E supplementation showed a significant increase of plasma vitamin E with concomitant decrease of 7&bgr;-hydroxycholesterol . Conversely , no treatment dependence was observed in oxysterol or vitamin E content of plaques . Conclusions —An imbalance between oxidative stress and antioxidant status is present in patients with advanced atherosclerosis . Vitamin E supplementation improves this imbalance in plasma but not in plaques Treatment of hypercholesterolemia with statins ( 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ) is effective in the primary and secondary prevention of cardiovascular disease . However , statin use is often associated with a variety of muscle-related symptoms or myopathies . Myopathy may be related in part to statin inhibition of the endogenous synthesis of coenzyme Q10 , an essential cofactor for mitochondrial energy production . The aim of this study is to determine whether coenzyme Q10 supplementation would reduce the degree of muscle pain associated with statin treatment . Patients with myopathic symptoms were r and omly assigned in a double-blinded protocol to treatment with coenzyme Q10 ( 100 mg/day , n = 18 ) or vitamin E ( 400 IU/day , n = 14 ) for 30 days . Muscle pain and pain interference with daily activities were assessed before and after treatment . After a 30-day intervention , pain severity decreased by 40 % ( p < 0.001 ) and pain interference with daily activities decreased by 38 % ( p < 0.02 ) in the group treated with coenzyme Q10 . In contrast , no changes in pain severity ( + 9 % , p = NS ) or pain interference with daily activities ( -11 % , p = NS ) was observed in the group treated with vitamin E. In conclusion , results suggest that coenzyme Q10 supplementation may decrease muscle pain associated with statin treatment . Thus , coenzyme Q10 supplementation may offer an alternative to stopping treatment with these vital drugs OBJECTIVES We examined the effects of oral administration of vitamin E , an antioxidant , on endothelium-dependent vasodilation in patients with coronary spastic angina . BACKGROUND We have recently reported that endothelium-dependent vasodilation is impaired in patients with coronary spastic angina ( CSA ) . Furthermore , it is known that oxidative stress may play an important role in the impairment of endothelium-dependent vasodilation in cardiovascular diseases . METHODS With the ultrasound technique , flow-dependent vasodilation of the brachial arteries during reactive hyperemia was examined before and after treatment for a month with either oral administration of vitamin E ( alpha-tocopherol acetate , 300 mg/day ) or placebo , which is r and omly assigned , in patients with CSA ( n=60 ) . RESULTS Before treatment , patients with CSA had impaired flow-dependent vasodilation , lower plasma levels of alpha-tocopherol and higher plasma levels of thiobarbituric acid reactive substances ( TBARS ) , as compared with age- and sex-matched control subjects ( n=60 ) ( flow-dependent vasodilation : 3.1+/-1.8 vs. 7.1+/-2.5 % , p < 0.001 ; alpha-tocopherol levels : 8.9+/-1.8 vs. 10.8+/-1.8 microg/ml , p < 0.001 ) . In patients with CSA , treatment with vitamin E restored flow-dependent vasodilation ( 3.1+/-1.7 vs. 8.3+/-2.0 % , p < 0.001 ) , and this improvement was associated with the decreases in plasma TBARS levels and anginal attacks . CONCLUSIONS The results indicate that vitamin E treatment improved endothelium-dependent vasodilation and decreased plasma TBARS levels in patients with CSA . Thus , increased oxidative stress may contribute to endothelial dysfunction and anginal attacks in patients with CSA BACKGROUND Patients with persistent hypertriglyceridemia while on statin therapy may require adjunctive lipid-lowering therapy to meet treatment goals . OBJECTIVE To assess the effect of concomitant administration of prescription omega-3-acid ethyl esters ( P-OM3 ) , triglyceride-lowering agents , on the steady-state pharmacokinetics of rosuvastatin . METHODS A r and omized , open-label , repeated-dose , two-way crossover drug interaction study of two treatments - 4 g P-OM3 plus 40 mg rosuvastatin or 40 mg rosuvastatin alone administered daily for 14 days each under fasting conditions -- was conducted in 48 non-smoking healthy adults . MAIN OUTCOME MEASURES The primary determinants of drug interaction were the ln-transformed area under the plasma concentration versus time curve [ AUC(t(ss ) ) ] over the final ( day 14 ) 24 h dosing interval and maximum measured steady-state plasma rosuvastatin concentration [ C(max(ss ) ) ] on day 14 . Safety was assessed by clinical and laboratory testing and recording of adverse events . RESULTS AUC(t(ss ) ) and C(max(ss ) ) following daily administration of rosuvastatin with P-OM3 were similar to those following monotherapy with rosuvastatin . All adverse events recorded during the study were classified as mild and self-limited . CONCLUSIONS Administration of P-OM3 with rosuvastatin did not affect the pharmacokinetics of rosuvastatin under steady-state conditions in healthy individuals UNLABELLED M : The aim of this study was to investigate the effect of St John 's wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin . METHODS This was an open-label , three-way crossover r and omized study in 12 healthy male subjects , who received a single 25-mg dose of warfarin alone or after 14 days ' pretreatment with St John 's wort , or 7 days ' pretreatment with ginseng . Dosing with St John 's wort or ginseng was continued for 7 days after administration of the warfarin dose . Platelet aggregation , international normalized ratio ( INR ) of prothrombin time , warfarin enantiomer protein binding , warfarin enantiomer concentrations in plasma and S-7-hydroxywarfarin concentration in urine were measured . Statistical comparisons were made using anova and 90 % confidence intervals are reported . RESULTS INR and platelet aggregation were not affected by treatment with St John 's wort or ginseng . The apparent clearances of S-warfarin after warfarin alone or with St John 's wort or ginseng were , respectively , 198 + /- 38 ml h(-1 ) , 270 + /- 44 ml h(-1 ) and 220 + /- 29 ml h(-1 ) . The respective apparent clearances of R-warfarin were 110 + /- 25 ml h(-1 ) , 142 + /- 29 ml h(-1 ) and 119 + /- 20 ml h(-1 ) [ corrected ] . The mean ratio and 90 % confidence interval ( CI ) of apparent clearance for S-warfarin was 1.29 ( 1.16 , 1.46 ) and for R-warfarin it was 1.23 ( 1.11 , 1.37 ) when St John 's wort was coadministered . The mean ratio and 90 % CI of AUC(0 - 168 ) of INR was 0.79 ( 0.70 , 0.95 ) when St John 's wort was coadministered . St John 's wort and ginseng did not affect the apparent volumes of distribution or protein binding of warfarin enantiomers . CONCLUSIONS St John 's wort significantly induced the apparent clearance of both S-warfarin and R-warfarin , which in turn result ed in a significant reduction in the pharmacological effect of rac-warfarin . Coadministration of warfarin with ginseng did not affect the pharmacokinetics or pharmacodynamics of either S-warfarin or R-warfarin AIMS Ginkgo biloba is available as an over-the-counter drug and reported to cause haemorrhage when coadministered with other antiplatelet agents . We set out to study the interactions of G. biloba with cilostazol and clopidogrel . METHODS A r and omized , open-label , crossover study of 10 healthy male volunteers . The dosage schedules were 120 mg G. biloba , 240 mg G. biloba , 100 mg cilostazol , 200 mg cilostazol , 75 mg clopidogrel , 150 mg clopidogrel , 120 mg G. biloba+ 100 mg cilostazol and 120 mg G. biloba+ 75 mg clopidogrel . Platelet aggregation , platelet count , bleeding time and clotting time were measured 0 and 6 h after drug administration . Platelet aggregation was performed using a dual channel aggregometer , by the turbimetric technique using adenosine diphosphate 5 micromol and 10 micromol , and collagen 1 microg ml(-1 ) . RESULTS Platelet inhibition with the combination of G. biloba and clopidogrel or cilostazol was not statistically significant compared with individual doses of drugs , with all the three aggregants . There was significant ( P < 0.05 ) potentiation of prolongation of bleeding time with the combination of cilostazol and G. biloba compared with individual doses of both the drugs . There was no significant change in clotting time and platelet count . CONCLUSIONS Coadministration of G. biloba either with cilostazol or clopidogrel did not enhance antiplatelet activity compared with individual agents . Ginkgo biloba potentiated the bleeding time prolongation effect of cilostazol . There was no significant correlation between prolongation of bleeding time and inhibition of platelet aggregation Familial hypercholesterolemia is associated with premature coronary heart disease . In patients with familial hypercholesterolemia , monotherapy with hydroxymethylglutaril coenzyme . A reductase inhibitors rarely achieves the goal of desirable low-density lipoprotein levels . Epidemiological studies suggest that population s with a high dietary intake of marine n3 fatty acids are protected against coronary heart disease . Hepatic synthesis and secretion of very low density lipoproteins are reduced during fish oil supplementation while other effects on lipid and lipoprotein metabolism are controversial . Fourteen patients affected by familial heterozygous hypercholesterolemia on chronic treatment with simvastatin were enrolled in a double blind , placebo controlled , r and omized crossover trial that evaluated the effect of fish oil ethyl ester ( Esapent , 5.1 g/day ) on lipid and lipoprotein serum concentrations . Total cholesterol , low density lipoprotein cholesterol , high density lipoprotein cholesterol , triglycerides , apoprotein B , apoprotein AI , lipoprotein ( a ) did not show any significant variation during the four week treatment period with fish oil ethyl ester . The present data suggest that the possible favourable influence of fish oil on the progression of atherosclerosis in these high-risk patients might involve mechanisms which are different from lipid metabolism A study ( IS RCT N 77665712 ) was undertaken to test the effectiveness and the acceptability of vitamin E and low-dose aspirin , alone or in combination , as treatment for prolonged vaginal bleeding induced by Norplant . A total of 486 Norplant users who were requesting treatment for bleeding lasting longer than 7 days were enrolled in five centers : Beijing , China ; Jakarta , Indonesia ; Santiago , Chile ; Santo Domingo , Dominican Republic ; and Tunis , Tunisia . They were r and omized to one of four different 10-day oral treatments : 200 mg vitamin E daily , 80 mg aspirin daily , both or a placebo . Treatment packs were design ed to ensure blinding of both the subjects and the clinical staff . Neither vitamin E nor low-dose aspirin nor their combination was found to have any effect on reducing the length of the bleeding episode for which treatment was taken or on the vaginal bleeding patterns these women experienced during the year of follow-up AIMS This study investigated the pharmacokinetic and pharmacodynamic interactions of echinacea and policosanol with warfarin in healthy subjects . METHODS This was an open-label , r and omized , three-treatment , cross-over , clinical trial in healthy male subjects ( n= 12 ) of known CYP2C9 and VKORC1 genotype who received a single oral dose of warfarin alone or after 2 weeks of pre-treatment with each herbal medicine at recommended doses . Pharmacodynamic ( INR , platelet activity ) and pharmacokinetic ( warfarin enantiomer concentrations ) end points were evaluated . RESULTS The apparent clearance of (S)-warfarin ( 90 % CI of ratio ; 1.01 , 1.18 ) was significantly higher during concomitant treatment with echinacea but this did not lead to a clinical ly significant change in INR ( 90 % CI of AUC of INR ; 0.91 , 1.31 ) . Policosanol did not significantly affect warfarin enantiomer pharmacokinetics or warfarin response . Neither echinacea nor policosanol had a significant effect on platelet aggregation after 2 weeks of pre-treatment with the respective herbal medicines . CONCLUSION Echinacea significantly reduced plasma concentrations of S-warfarin . However , neither echinacea nor policosanol significantly affected warfarin pharmacodynamics , platelet aggregation or baseline clotting status in healthy subjects Impaired function of the endothelium may be a mechanism of the coronary vasospasm induced by acetylcholine . We examined whether purified eicosapentaenoic acid ( EPA ) , a major component of fish oil , improves the coronary vasomotion in response to acetylcholine , and the effect of purified EPA on acetylcholine (ACh)-induced coronary vasospasm in 22 patients with variant angina . ACh was infused into the coronary artery both before and after 4 months of EPA treatment ( EPA 1.8 g/day , n = 12 ) . In the control group ( n = 10 ) that did not receive EPA , the response of the coronary diameter to ACh did not change over time . In the EPA-treated group , the cholinergic response in non-spastic sites changed from vasoconstriction to vasodilation , while ACh-induced coronary vasospasm persisted at the spastic sites . Therefore , EPA treatment improved the coronary vasomotor responsiveness to ACh , but did not inhibit ACh-induced coronary vasospasm OBJECTIVE To evaluate the effects of prescription omega-3-acid ethyl esters on non-high-density lipoprotein cholesterol ( HDL-C ) levels in atorvastatin-treated patients with elevated non-HDL-C and triglyceride levels . PATIENTS AND METHODS This study , conducted between February 15 , 2007 , and October 22 , 2007 , r and omized patients with elevated non-HDL-C ( > 160 mg/dL ) and triglyceride ( > or=250 mg/dL and < or=599 mg/dL ) levels to double-blind treatment with prescription omega-3-acid ethyl esters , 4 g/d , or placebo for 16 weeks . Patients also received escalating dosages of open-label atorvastatin ( weeks 0 - 8 , 10 mg/d ; weeks 9 - 12 , 20 mg/d ; weeks 13 - 16 , 40 mg/d ) . RESULTS Prescription omega-3-acid ethyl esters plus atorvastatin , 10 , 20 , and 40 mg/d , reduced median non-HDL-C levels by 40.2 % vs 33.7 % ( P<.001 ) , 46.9 % vs 39.0 % ( P<.001 ) , and 50.4 % vs 46.3 % ( P<.001 ) compared with placebo plus the same doses of atorvastatin at the end of 8 , 12 , and 16 weeks , respectively . Prescription omega-3-acid ethyl esters plus atorvastatin also reduced median total cholesterol , triglyceride , and very low-density lipoprotein cholesterol levels and increased HDL-C levels to a significantly greater extent than placebo plus atorvastatin . Percent changes from baseline low-density lipoprotein-cholesterol , apolipoprotein A-I , and apolipoprotein B levels were not significantly different between groups at the end of the study . CONCLUSION Prescription omega-3-acid ethyl esters plus atorvastatin produced significant improvements in non-HDL-C and other lipid parameters in patients with elevated non-HDL-C and triglyceride levels OBJECTIVE To investigate the impact of Vitamin E on lipids and peroxidation during statin treatment . RESEARCH DESIGN AND METHODS T1DM patients with high cholesterol received Atorvastatin 20 mg with either placebo ( group AP , n = 11 ) or d-alpha-tocopherol 750 IU ( group AE , n = 11 ) daily . They were monitored for blood biochemistry , low-density lipoprotein ( LDL ) subfractions and lipid peroxidation at inclusion and after 3 and 6 months . RESULTS Serum cholesterol and triglycerides decreased to the same extent ( 29 and 21 % respectively ) in both groups . Serum tocopherol decreased by 18 % in AP and increased by 50 % in AE ( P < 0.0001 , between-group comparison by repeated measures ANOVA ) but relative to lipids it increased by 15 % in AP and by 100 % in AE . Copper-induced production of thiobarbituric reactive substances in the LDL + VLDL fraction increased by 18 % in AP and did not change in AE ( P = 0.02 ) . The lagtime for the production of fluorescent products was prolonged by 13 min only in group AE ( P = 0.028 ) . Plasma malondialdehyde decreased by 35 % in both groups ( P = 0.002 ) but not when adjusted for lipids . CONCLUSIONS In T1DM Vitamin E supplements do not affect the lowering of lipids and plasma malondialdehyde achieved by Atorvastatin . They reverse the increase of in vitro peroxidation caused by Atorvastatin but do not achieve the decreases observed in patients not receiving lipid-lowering drugs . These results indicate that the antioxidant effect of Vitamin E is attenuated when given in conjunction with this statin Context Consuming ginseng , a commonly used herbal dietary supplement , has been associated with a decrease in warfarin 's anticoagulant effect in at least 1 case report . Contribution Healthy volunteers took warfarin with and without concurrently taking ginseng . Ginseng consumption lowered the international normalized ratio and decreased plasma warfarin levels . Caution s Patients and physicians should be aware that ginseng is among many substances that can interfere with warfarin 's anticoagulant effect . The Editors The beneficial effects of several commonly used botanicals have been documented ( 1 ) , but data on the safety of these herbs are limited . At least 16 % of people using prescription medication concurrently take herbal supplements . An estimated 15 million Americans are at risk for herbdrug interactions ( 2 ) . Advocated for almost every purpose , including maintaining general health , combating fatigue , and improving immune function ( 3 ) , ginseng is one of the best-selling herbs in the United States ( 4 ) . Herbs such as ginseng may interact with medications that have a narrow therapeutic index , such as warfarin , a commonly used oral anticoagulant ( 5 , 6 ) . A widely cited case report showed a substantial decrease in the anticoagulant effect of warfarin after ginseng consumption in a patient who was previously maintained with stable warfarin therapy ( 7 ) . We conducted a r and omized , double-blind , placebo-controlled trial to evaluate the potential interactions between American ginseng and warfarin . Methods Patients Nine men and 11 nonpregnant women ( who were paid $ 250 after trial completion ) were enrolled in this study . Patients were screened with a medical history , physical examination , 12-lead resting electrocardiography , complete blood and platelet counts , international normalized ratio ( INR ) ( the prothrombin time testcontrol ratio ) ( 8) , blood chemistry tests , and urinalysis . Patients agreed to abstain from tobacco products for at least 2 weeks before and during the study , abstain from alcohol and other medications during the study , and limit caffeine-containing products for 48 hours before and during the study . Protocol The institutional review board approved this 4-week study conducted at the University of Chicago Medical Center , Chicago , Illinois . All patients provided written , informed consent . Patients received oral warfarin , 5 mg daily , for the first 3 consecutive days during week 1 . Beginning in week 2 , patients were r and omly assigned to receive either oral American ginseng , 1.0 g , or placebo , twice daily , for 3 consecutive weeks . During week 4 , all patients again received oral warfarin , 5 mg daily , for the first 3 consecutive days ( Appendix Figure ) . Ginseng or placebo assignment was determined by a table of r and om numbers with blocks of 8 ( 4 ginseng and 4 placebo assignments per block ) , from which sealed , opaque envelopes were prepared and opened sequentially as patients were enrolled in the study . A biostatistician who did not acquire data prepared the assignments . Patients and investigators were blinded to the treatment groups . Patients were instructed to eat a balanced diet to maintain a consistent amount of vitamin K and to avoid drastic changes in dietary habits . The daily intake of vitamin Kcontaining foods was recorded 1 week before the study to obtain the baseline value and to adjust the diet if vitamin K intake was high . Patients recorded their daily diet throughout the study period , completed a written weekly question naire , and were asked to report any adverse events . Blood sample s were obtained at the same time ( 0.5 hour ) on days 1 , 3 , 4 , 5 , and 7 of weeks 1 and 4 to measure INR and plasma warfarin levels ( detection limit , 0.1 g/mL ) . Study Drugs Warfarin ( 3-(-acetonylbenzyl)-4-hydroxycoumarin or Coumadin , DuPont Pharmaceuticals , Wilmington , Delaware ) is a racemic mixture composed of equal amounts of 2 optical isomers . In our laboratory , we ground the root of American ginseng ( Panax quinquefolius , Wisconsin Ginseng Board , Wausau , Wisconsin ) from 1 lot into a fine powder and placed 0.5 g in nontransparent capsules . Using a high-performance liquid chromatography method , we found that the total ginsenoside content was 5.19 % . The constituent split was as follows : ginsenoside Rb1 , 1.93 % ; Rb2 , 0.20 % ; Rc , 0.61 % ; Rd , 0.42 % ; Re , 1.68 % ; and Rg1 , 0.35 % . We prepared identical placebo capsules that contained cornstarch powder . Statistical Analysis The primary end point of this study was the change in peak INR ( week 4 week 1 ) . Additional analysis end points were change in INR area under the curve ( AUC ) ( week 4 week 1 ) , defined as the area under the INR versus time curve ; change in peak plasma warfarin level ; change in warfarin AUC ( week 4 week 1 ) , defined as the area under the plasma warfarin level versus time curve ; and weekly vitamin K intake . The AUC was calculated on the basis of the trapezoidal rule by using measurements for days 1 through 7 . We compared changes in peak INR , INR AUC , peak plasma warfarin level , and warfarin AUC between the ginseng and placebo groups by using the Wilcoxon rank-sum test . We calculated the difference in median changes between the 2 groups and corresponding 95 % CIs according to the method described by Holl and er and Wolfe ( 9 ) , which is based on consideration of all pairwise differences between the 2 sets of observations . We calculated the Spearman rank correlation coefficients to examine the correlation between the change in peak INR and change in peak plasma warfarin levels . Repeated- measures analysis of variance ( ANOVA ) models were used to test differences in vitamin K intake between the groups and over time . A P value less than 0.05 was considered statistically significant . Stata , version 8 ( Stata Corp. , College Station , Texas ) , and Minitab , version 13 ( Minitab , Inc. , State College , Pennsylvania ) , were used for statistical analysis . Role of the Funding Sources The funding sources had no role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results Data from all 20 patients ( 12 patients in the ginseng group and 8 patients in the placebo group ) were used in the analysis . For the 6 men and 6 women in the ginseng group ( 7 patients were white , 3 patients were black , 1 patient was Hispanic , and 1 patient was Asian ) , the mean age and body weight ( SD ) were 30.2 7.2 years and 69.220.6 kg , respectively . For the 3 men and 5 women in the placebo group ( 3 patients were white , 2 patients were black , 2 patients were Hispanic , and 1 patient was Asian ) , the mean age and body weight ( SD ) were 24.3 4.0 years and 62.09.1 kg , respectively ( Appendix Table ) . In both groups , INR generally reached peak levels on day 4 after 3 consecutive days of warfarin administration . The Figure shows changes in individual peak INR , INR AUC , peak plasma warfarin level , and warfarin AUC from weeks 1 to 4 . The modest reduction in INR magnitude in the ginseng group was statistically significant compared with the change in the placebo group ( P= 0.0012 ) . Changes in INR AUC , peak plasma warfarin level , and warfarin AUC were also statistically significantly greater in the ginseng group . The Table summarizes results for the primary and secondary end points . Figure . Changes in individual peak international normalized ratio ( INR ) , INR area under the curve ( AUC ) , peak plasma warfarin level , and warfarin AUC in weeks 1 and 4 in American ginseng or placebo groups . A. P B. P C. P D. P Appendix Figure . Study flow chart showing American ginseng and placebo dosing and blood sample collection . Table . Changes in Peak International Normalized Ratio , International Normalized Ratio Area under the Curve , Peak Plasma Warfarin Level , and Warfarin Area under the Curve between Weeks 1 and 4 in American Ginseng and Placebo Groups Appendix Table . Patient Information For both peak warfarin level and AUC , the changes in the placebo group were not statistically significant and therefore probably reflected r and om variation in the small sample size . The Spearman rank correlation coefficient between changes in peak INR values and changes in peak warfarin levels was 0.72 ( P < 0.001 ) . One patient ( patient 18 ) in the ginseng group had a high baseline INR ( 1.32 ) on day 1 compared with that in the other patients ( mean INR [ SD ] , 0.94 0.04 ) . For this patient , peak INR after warfarin administration on day 4 was 5.16 . After ginseng administration , the peak INR was 2.75 and the corresponding AUC decreased from 17.46 to 11.1 . The patient 's peak plasma warfarin level also decreased from 1.6 g/mL during week 1 to 0.9 g/mL in week 4 . If this patient is excluded from the analysis , the results remain statistically significant . No unusual medical or drug history or diet was noted for this patient . For weeks 1 , 2 , 3 , and 4 , average daily vitamin K intake ( SD ) for the ginseng group was 32.3 5.2 g/d , 42.6 7.6 g/d , 41.9 8.6 g/d , and 34.0 5.5 g/d , respectively . The average daily vitamin K intake ( SD ) for the placebo group for weeks 1 , 2 , 3 , and 4 was 36.4 11.2 g/d , 32.0 8.4 g/d , 39.5 8.7 g/d , and 38.6 11.4 g/d , respectively . Vitamin K intake did not statistically significantly differ between the 2 groups ( P > 0.2 ) or over time ( P > 0.2 ) . No adverse effects of clinical importance occurred in this study . Discussion Among the several different species of ginseng , the major active components are ginsenosides , which are a diverse group of steroidal saponins ( 3 ) . Ginseng may promote bleeding in surgical patients ( 6 ) . Ginsenosides prolonged both thrombin time and activated partial thromboplastin time in rats ( 10 ) and inhibited platelet aggregation in vitro in human platelets ( 11 ) . In our healthy patients , however , ginseng reduced the anticoagulant effect of warfarin . We selected the commonly consumed American ginseng and a dose at the high end of the recommended range ( 12 ) . Warfarin indirectly interferes with blood clotting by depressing the hepatic synthesis of vitamin Kdependent coagulation factors . The Several case reports have implicated Ginkgo biloba in clinical ly adverse bleeding disorders . Ginkgo biloba has been reported to increase pain-free walking distance among patients with peripheral artery disease ( PAD ) . St and ard PAD therapy includes 325 mg/day aspirin . The objective of this study was to examine potential adverse effects of concomitant aspirin and Ginkgo biloba on platelet function . Ginkgo biloba ( EGb 761 , 300 mg/day ) was compared with placebo for effects on measures of platelet aggregation among adults consuming 325 mg/day aspirin in a r and omized , double-blind , placebo-controlled , parallel design trial of 4-week duration . Participants were adults , age 69 ± 10 years , with PAD or risk factors for cardiovascular disease . Outcome measures included platelet function analysis ( PFA-100 analyzer ) using ADP as an agonist ( n = 26 placebo ; n = 29 ginkgo ) , and platelet aggregation using ADP , epinephrine , collagen and ristocetin as agonists ( n = 21 placebo ; n = 23 ginkgo ) . Participants kept daily logs of bleeding or bruising episodes . There were no clinical ly or statistically significant differences between treatment groups for any agonists , for either PFA-100 analysis or platelet aggregation . Reports of bleeding or bruising were infrequent and similar for both study groups . In conclusion , in older adults with PAD or cardiovascular disease risk , a relatively high dose of Ginkgo biloba combined with 325 mg/day daily aspirin did not have a clinical ly or statistically detectable impact on indices of coagulation examined over 4 weeks , compared with the effect of aspirin alone . No adverse bleeding events were observed , although the trial was limited to a small sample size Abstract Objective : The aim of this study was to determine whether Ginkgo biloba special extract EGb 761 ® amplifies the known effects of acetylsalicylic acid ( ASA ) on platelet aggregation , bleeding time or other coagulation parameters in healthy subjects . Methods : In a double-blind , double-dummy procedure , 50 healthy male subjects ( 20–44 years ) were r and omly allocated in equal numbers to one of two possible treatment sequences , i.e. ASA followed by ASA + EGb 761 ® or ASA + EGb 761 ® followed by ASA . Each treatment lasted 7 days ; the washout period between treatments was 3 weeks . Study medication was taken twice daily ( ASA group : ASA 500 mg tablet + placebo-coated tablet in the morning and placebo tablet + placebo-coated tablet in the evening ; ASA + EGb 761 ® group : ASA 500 mg tablet + EGb 761 ® 120mg-coated tablet in the morning and placebo tablet + EGb 761 ® 120mg-coated tablet in the evening ) , result ing in a daily dose of ASA 500 mg in the ASA group and 500 mg ASA + 240 mg EGb 761 ® in the ASA + EGb 761 ® group . Bleeding time , coagulation parameters and platelet activity in response to various agonists were determined . In addition , adverse events , laboratory variables and vital signs were measured . The primary variable bleeding time was assessed in confirmatory analysis , all other variables were evaluated descriptively . The coagulation variables were analysed by ANOVA under the crossover model . Results : ASA given alone clearly prolonged bleeding time . ASA and the combination of ASA + EGb 761 ® exerted quite similar effects on all coagulation parameters measured , including bleeding time ( ASA alone : 4.1 min before therapy , 6.2 min after therapy ; ASA + EGb 761 ® : 4.2 min before therapy , 6.3 min after therapy ; ratio of means : 1.01 , 90 % CI 0.86 , 1.19 ) and agonist-induced platelet aggregation ( collagen-induced platelet aggregation — ASA : 84.5 % before therapy , 81.0 % after therapy ; ASA + EGb 761 ® : 86.6 % before therapy , 81.0 % after therapy ; ratio of means : 1.00 , 90 % CI 0.95 , 1.05 ; adenosine diphosphate-induced platelet aggregation — ASA : 72.6 % before therapy , 47.2 % after therapy ; ASA + EGb 761 ® : 71.7 % before therapy , 44.8 % after therapy ; ratio of means : 0.95 , 90 % CI 0.85 , 1.06 ) . Both treatments were well tolerated , and both the number and nature of adverse events in the two groups were similar . Conclusions : Our findings suggest that co-administration of ASA and EGb 761 ® does not constitute a safety risk , including in an elderly patient population undergoing treatment with EGb 761 ® Myalgia is the most frequently reported adverse side effect associated with statin therapy and often necessitates reduction in dose , or the cessation of therapy , compromising cardiovascular risk management . One postulated mechanism for statin-related myalgia is mitochondrial dysfunction through the depletion of coenzyme Q(10 ) , a key component of the mitochondrial electron transport chain . This pilot study evaluated the effect of coenzyme Q(10 ) supplementation on statin tolerance and myalgia in patients with previous statin-related myalgia . Forty-four patients were r and omized to coenzyme Q(10 ) ( 200 mg/day ) or placebo for 12 weeks in combination with upward dose titration of simvastatin from 10 mg/day , doubling every 4 weeks if tolerated to a maximum of 40 mg/day . Patients experiencing significant myalgia reduced their statin dose or discontinued treatment . Myalgia was assessed using a visual analogue scale . There was no difference between combined therapy and statin alone in the myalgia score change ( median 6.0 [ interquartile range 2.1 to 8.8 ] vs 2.3 [ 0 to 12.8 ] , p = 0.63 ) , in the number of patients tolerating simvastatin 40 mg/day ( 16 of 22 [ 73 % ] with coenzyme Q(10 ) vs 13 of 22 [ 59 % ] with placebo , p = 0.34 ) , or in the number of patients remaining on therapy ( 16 of 22 [ 73 % ] with coenzyme Q(10 ) vs 18 of 22 [ 82 % ] with placebo , p = 0.47 ) . In conclusion , coenzyme Q(10 ) supplementation did not improve statin tolerance or myalgia , although further studies are warranted A double blind placebo controlled trial was conducted in 55 patients of acute ischaemic stroke . Twenty one and twenty six patients were r and omly allotted in group A and group B respectively . In group A , the patients received 40 mg Ginkgo biloba extract at 6 hourly intervals along with routine management . The placebo tablets were dispensed in the tablet form of same size , shape and colour and were given in the same way . After the patients were subjected to computerized tomographic ( CT ) scan to confirm acute ischaemic infa rct ion , they were assessed on Mathew 's scale and reassessed , at 2 weeks and 4 weeks of drug/placebo administration . Both groups showed significant improvement in Mathew 's scale score after 2 weeks and 4 weeks . The difference in degree of change was negligible ( p > 0.05 ) in either group . Estimation of relative changes of neurological deficit based on baseline values also showed negligible ( p > 0.05 ) difference . A trial of Ginkgo biloba extract within 6 hours of stroke in a larger dose and in larger sample could be beneficial clinical ly in patients of cerebral ischaemic infa rct , and needs further study . The usefulness of the plant extract has been demonstrated clinical ly and experimentally in more than 40 trials of chronic cerebral ischaemia , done elsewhere . This was not evident in our study as our study group was different ( more than 48 hours after stroke ) . There appears to be no contraindication or adverse effect of this medication ( Ginkgo biloba ) in acute ischaemic stroke Effects of dietary sodium restriction combined with fish oil supplementation on BP and related risk factors were assessed in hypertensives treated with angiotensin converting enzyme ( ACE ) inhibitors . After a four week run-in phase , a six week intervention trial was conducted in which four matched groups of 14 patients , taking either captopril or enalapril , were assigned to one of four dietary treatments : low sodium ( 80 mmol/day ) with fish oil ( 5 g of omega-3 fatty acids per day ) ; normal sodium ( 150 mmol/day ) with fish oil ; low sodium with olive oil ; normal sodium with olive oil . All subjects adopted a low sodium diet and adjustments of nutrient intake were made by double-blind administration of sodium and oils in supplementary tablets and capsules . BP fell in all treatment groups during intervention . However , the reduction of SBP was 4.2 mmHg greater in subjects on a low sodium intake than in those taking normal sodium . There were no differences in BP between those taking olive oil and those taking fish oil but plasma triglycerides and serum thromboxane production were reduced by 27 % and 51 % , respectively in the latter . Thus the antihypertensive effect of ACE inhibitors can be augmented by sodium restriction alone but supplementing the diet with fish oil may yield additional cardiovascular benefits Many medications are known to alter digoxin pharmacokinetics , including the herbal medication St. John 's wort . An open-labeled , r and omized , crossover trial was conducted in eight healthy human volunteers to determine if ginkgo biloba ( GB ) also alters the pharmacokinetics of digoxin . On two occasions separated by 2 weeks , subjects ingested digoxin , 0.5 mg . One week prior to each study phase , half of the volunteers were r and omly initiated on GB therapy , 80 mg three times daily , that continued until the end of the study phase . Immediately prior to and for 36 hours following digoxin ingestion , multiple blood sample s were collected for digoxin plasma concentration determination . No significant difference between treatments was observed with respect to AUC0−∞ ( digoxin alone : 21.0 ± 8.6 [ ng/mL ] × h ; digoxin + GB : 25.6 ± 13.2 [ ng/mL ] × h ) . Additionally , no significant difference between therapies was observed with respect to Cmax , Tmax , or Clo . In six subjects , ke and t1/2 were able to be determined . These parameters also did not differ significantly between treatments . In conclusion , within the context of the specific GB product used during this investigation , the concomitant use of GB and digoxin did not appear to have any significant effect on the pharmacokinetics of orally administered digoxin in healthy volunteers Activation of factor (F)VII by tissue factor may represent a critical event during plaque rupture in acute coronary syndromes . Patients with combined hyperlipemia are at high risk for developing coronary heart disease and their tendency to thrombosis may be accelerated during postpr and ial hyperlipemia . In the present double-blind , placebo-controlled parallel study , 42 patients with combined hyperlipemia and serum triglycerides between 2.0 and 15.0 mmol L(-1 ) and serum cholesterol > 5.3 mmol L-1 at the end of a 3-month dietary run-in period were treated with atorvastatin at 10 mg day-1 for at least 10 weeks . During the last 5 weeks the patients were r and omized into two groups receiving 1.68 g day(-1 ) omega-3 fatty acids ( omega-3 FA ) or placebo ( corn oil ) . The fasting levels of FVII antigen ( FVII-Ag ) and FVII coagulant activity ( FVII : C ) were high compared with healthy males . The fasting levels of activated FVII ( FVIIa ) and FVII-Ag correlated both to serum triglycerides and apolipoprotein A1 ( apoA1 ) . FVIIa and FVII : C increased during postpr and ial hyperlipemia . This increase of FVIIa correlated to the fasting triglyceride and apoA1 levels , but not to the degree of postpr and ial hypertriglyceridemia . The concentrations of fasting FVIIa in these patients were reduced in parallel with a reduction of fasting triglycerides by treatment with atorvastatin + placebo . This treatment also reduced the postpr and ial level of FVIIa . omega-3 FA in addition to atorvastatin further reduced FVIIa concentrations , fasting and postpr and ially , and also significantly reduced FVII : C and FVII-Ag during postpr and ial hyperlipemia . Prothrombin fragment 1 + 2 ( F1 + 2 ) increased during postpr and ial hyperlipemia . This increase was significantly reduced after treatment with atorvastatin plus omega-3 FA . The increase of F1 + 2 measured as incremental area under the curve ( iAUC ) during postpr and ial hyperlipemia correlated to the fasting levels of FVIIa , FVII : C and FVII-Ag and also to the levels of these factors during postpr and ial lipemia . In conclusion , patients with combined hyperlipemia are at risk for activation of the coagulation system , particularly during postpr and ial lipemia . This activation may be significantly reduced by statins and omega-3 FA Background / rationale : Treatment of severe hypertriglyceridemia is indicated to reduce the risk of pancreatitis in patients with triglyceride ( TG ) levels ≥500 mg/dL. Hypertriglyceridemia is also a risk factor for atherosclerotic coronary heart disease . Prescription omega-3 fatty acids ( P-OM3 ) and fenofibrate ( FENO ) are among the most effective lipid-altering agents that reduce TG levels . Given that some patients may not achieve optimal TG levels with a single agent , we hypothesized that concomitant use of P-OM3 or addition of P-OM3 to FENO would result in a TG reduction greater than that with FENO alone . Methods : This r and omized , 8-week , double-blind , placebo-controlled study was design ed to compare the safety and efficacy of P-OM3 4 g QD plus concomitant FENO 130 mg with FENO 130 mg QD plus placebo in subjects with very high TG levels ( ≥500 mg/dL ) . Subjects who completed the double-blind study were given the option to continue into an open-label , 8-week extension study , wherein they all received P-OM3 4 g plus FENO 130 mg QD . On completion of the first extension study , subjects were eligible to continue into an open-label 24-month extension of the treatment with P-OM3 4 g plus FENO 130 mg QD . Results : Concomitant P-OM3 + FENO ( n = 81 ) and FENO monotherapy ( n = 82 ) reduced median TG values from 649.5 to 267.5 mg/dL ( 60.8 % ) and from 669.3 to 310 mg/dL ( 53.8 % ) , respectively ( P = 0.059 ) . When subjects who had received 8 weeks of stable FENO monotherapy were given P-OM3 during the 8-week , open-label extension study ( n = 58 ) , TG levels were reduced 17.5 % ( P = 0.003 ) over the course of the extension . The second extension phase was terminated early ( n = 93)-not because of a safety signal but because of the lack of a substantial incremental change in the primary endpoint lipid values above that reached in either the original study or the first extension in subjects receiving the combination of fenofibrate and P-OM3 . Conclusions : Both FENO monotherapy and P-OM3 + FENO significantly reduced TGs in subjects with very high TGs , with a trend to greater reduction in the P-OM3 + FENO group . The addition of P-OM3 to stable FENO therapy in the same subjects in an open-label extension study result ed in a statistically significant reduction in TG levels . Subjects who received P-OM3 + FENO for 16 weeks and subjects in which P-OM3 was added to FENO monotherapy during the open-label phase of the study did not differ in their final lipid responses . In the second open-label extension , within the combined group taking P-OM3 and FENO , analysis of change from the second extension baseline to end of treatment revealed no clinical ly important change Arteriopathy is the principal complication of type 2 diabetes mellitus . It develops from endothelial dysfunction , which we have hypothesised occurs in diabetes primarily as a consequence of dyslipidaemia and oxidative stress . Fenofibrate and CoQ may improve endothelial function by regulating dyslipidaemia and oxidative stress , respectively . We therefore aim ed to assess the independent and combined effects of fenofibrate and coenzyme Q(10 ) ( CoQ ) on endothelium-dependent and endothelium-independent vasodilator function of the forearm microcirculation in type 2 diabetes . Eighty dyslipidaemic type 2 diabetics were r and omized to receive fenofibrate ( 200 mg/daily ) , CoQ ( 200 mg/daily ) , fenofibrate plus CoQ ( 200 + 200 mg daily ) , or placebo for 12 weeks . Forearm microcirculatory function was assessed with venous occlusion plethysmography during the infusion of acetylcholine ( ACh ) , bradykinin ( BK ) , sodium nitroprusside ( SNP ) and N(G)-monomethyl-L-arginine ( L-NMMA ) into the brachial artery . Blood flow responses were calculated as area under the curve ( AUC ) . Fenofibrate significantly lowered plasma cholesterol , triglyceride and fibrinogen ( P<0.001 ) , and elevated HDL-cholesterol and homocysteine ( P<0.001 ) . CoQ did not change plasma isoprostanes , but significantly lowered systolic blood pressure and HbA(1c ) ( P<0.05 ) . Fenofibrate plus CoQ significantly improved ( P<0.05 ) the AUC for ACh , BK and SNP without significantly altering basal responses to L-NMMA . Fenofibrate or CoQ alone did not significantly alter blood flow responses . Improvements in blood flow were independent of changes in plasma lipids , blood pressure , homocysteine and isoprostanes , but were correlated ( P=0.013 ) with HbA(1c ) . In conclusion , in this factorial trial we found that only the combination of fenofibrate and CoQ markedly improved endothelial and non-endothelial forearm vasodilator function in dyslipidemic type 2 diabetic patients . The favourable vascular effect of this therapeutic combination could be due to increase in the bioactivity of and /or responses to endothelium-derived relaxing factors , including nitric oxide , and this may entail synergistic stimulation of peroxisome proliferator-activated receptors BACKGROUND Ginkgo biloba extract is an herbal medicine used in the treatment of vascular disorders that may be coadministered with antiplatelet agents such as ticlopidine . Regulatory authorities requested evaluation of the pharmacodynamic and pharmacokinetic interactions between these entities , according to the drug-development guidance for fixed-dose combination formulations in Korea . OBJECTIVE This study was performed to evaluate the potential pharmacodynamic and pharmacokinetic interactions between ticlopidine and Ginkgo biloba extract . METHODS An open-label , r and omized , 2-period , 2-treatment , 2-sequence , single-dose crossover study was conducted in healthy Korean male volunteers . All volunteers were r and omly assigned to a sequence group for the 2 treatments , which consisted of ticlopidine 250 mg alone and ticlopidine 250 mg with Ginkgo biloba extract 80 mg , separated by a 1-week washout period between the treatments . Bleeding time was determined just before dosing and at 5 , 12 , and 48 hours after dosing . Platelet aggregation was evaluated before dosing and at 4 , 8 , 26 , and 48 hours after dosing . Blood sample s ( 8 mL ) from each of the volunteers were collected from an indwelling intravenous cannula inserted into a forearm vein before dosing and at 0.5 , 1 , 1.5 , 2 , 2.5 , 3 , 4 , 6 , 8 , 12 , 24 , and 48 hours after dosing . Ticlopidine concentrations were determined by a vali date d method using HPLC and ultraviolet detection . Adverse events were identified using general health-related questions , vital signs , physical examinations , ECGs , and laboratory tests . RESULTS A total of 24 healthy men participated in the study ( mean [ SD ] age , 24.1 [ 4.3 ] years ; weight , 66.6 [ 7.4 ] kg ; height , 174.7 [ 5.0 ] cm ) . The baseline corrected bleeding times were not significantly different between the ticlopidine-alone and ticlopidine/ Ginkgo biloba groups , and changes in platelet aggregation were not significantly different between the groups . Likewise , the pharmacokinetic parameters of ticlopidine were not significantly different between the groups ; the geometric mean ratios of the ticlopidine/ Ginkgo biloba group to the ticlopidine-alone group were 1.03 ( 90 % CI , 0.92 - 1.16 ) for C(max ) , 1.08 ( 90 % CI , 0.98 - 1.19 ) for AUC(0-last ) , and 1.10 ( 90 % CI , 1.00 - 1.20 ) for AUC(0-infinity ) . A total of 28 adverse events were reported : 11 in the ticlopidine-alone group and 17 in the ticlopidine/Ginkgo biloba group . The adverse events judged to be possibly related to ticlopidine in the ticlopidine-alone group were epigastric discomfort ( 2 cases ) , diarrhea ( 1 ) , skin eruption ( 1 ) , and a feeling of being cold ( 1 ) or hot ( 1 ) . The adverse events judged to be related to ticlopidine or Ginkgo biloba in the ticlopidine/Ginkgo biloba group were epigastric discomfort ( 2 ) , diarrhea ( 2 ) , nausea ( 2 ) , and headache ( 1 ) . CONCLUSIONS In this small group of healthy Korean men , the addition of a single dose of Ginkgo biloba extract did not prolong the bleeding time and was not associated with additional antiplatelet effects compared with the administration of ticlopidine alone . The coadministration of Ginkgo biloba extract with ticlopidine was not associated with any significant changes in the pharmacokinetic profile of ticlopidine compared with ticlopidine administered alone This study investigates the hypothesis that lipid soluble antioxidants may increase the resistance of low-density lipoprotein ( LDL ) to oxidation and also enhance vascular endothelial responses in humans . In a double-blind parallel group study , 24 hypercholesterolaemic patients already on treatment with simvastatin ( 20 mg day-1 ) , were r and omized to supplementary treatment with probucol ( 500 mg bd ) , vitamin E ( 400 IU daily ) or placebo for 8 weeks . Mean serum cholesterol before antioxidant treatment was 7.00 mmol l-1 . Resistance of LDL to oxidation by copper was increased by 830 % in the probucol group and by 30 % in the vitamin E group . However , thiobarbituric acid reacting substances in whole serum were not altered by either antioxidant . Probucol lowered HDL- and LDL-cholesterol levels and increased the QT interval . Forearm vascular responses , as measured by venous occlusion plethysmography , to acetylcholine , glyceryl trinitrate and NG-monomethyl-L-arginine , were not significantly changed by antioxidant treatment . Probucol has a major , and vitamin E a minor , effect on LDL resistance to oxidation but neither compound appears to alter forearm vascular responses in vivo BACKGROUND Dyslipidaemia may account for increased risk of cardiovascular disease in central obesity . Pharmacotherapy is often indicated in these patients , but the optimal approach remains unclear . We investigated the effects of atorvastatin and fish oil on plasma lipid and lipoprotein levels , including remnant-like particle-cholesterol and apolipoprotein C-III , in dyslipidaemic men with visceral obesity . METHODS We carried out a 6-week r and omized , placebo-controlled , 2 x 2 factorial intervention study of atorvastatin ( 40 mg day(-1 ) ) and fish oil ( 4 g day(-1 ) ) on plasma lipids and lipoproteins in 52 obese men ( age 53 + /- 1 years , BMI 33.7 + /- 0.55 kg m(-2 ) ) with dyslipidaemia and insulin resistance . Treatment effects were analysed by general linear modelling . RESULTS Atorvastatin had significant main effects in decreasing triglycerides ( -0.38 + /- 0.02 mmol L(-1 ) , P = 0.002 ) , total cholesterol ( -1.89 + /- 0.17 mmol L(-1 ) , P = 0.001 ) , LDL-cholesterol ( -1.78 + /- 0.14 mmol L(-1 ) , P = 0.001 ) , remnant-like particle-cholesterol ( -0.08 + /- 0.04 mmol L(-1 ) , P = 0.035 ) , apolipoprotein B ( -49 + /- 4 mg dL(-1 ) , P = 0.001 ) , apolipoprotein C-III ( -12.6 + /- 6.1 mg L(-1 ) , P = 0.044 ) and in increasing HDL-cholesterol ( + 0.10 + /0- 0.04 mmol L(-1 ) , P = 0.007 ) . Fish oil had significant main effects in decreasing triglycerides ( -0.38 + /- 0.11 mmol L(-1 ) , P = 0.002 ) and in increasing HDL-cholesterol ( + 0.07 + /- 0.04 mmol L(-1 ) , P = 0.041 ) . There were no significant changes in weight or insulin resistance during the study . CONCLUSIONS Atorvastatin and fish oil have independent and additive effects in correcting dyslipidaemia in viscerally obese men . Improvement in abnormalities in remnant lipoproteins may occur only with use of atorvastatin . Combination treatment with statin and fish oil may , however , offer an optimal therapeutic approach for globally correcting dyslipidaemia in obesity Thirty patients with coronary artery disease ( CAD ) were administered garlic ( study group ) while another 30 patients received the placebo ( control group ) . Various risk parameters were determined at 1.5 and 3 months of garlic administration . Garlic , administered in a daily dose of 2 x 2 capsules ( each capsule containing ethyl acetate extract from 1 g peeled and crushed raw garlic ) , reduced significantly total serum cholesterol and triglycerides , and increased significantly HDL-cholesterol and fibrinolytic activity . There was no effect on the fibrinogen and glucose levels . In vitro effects of the garlic oil on platelet aggregation ( PAg ) and eicosanoid metabolism were examined ; it inhibited PAg induced by several platelet agonists , and also platelet thromboxane formation . Two important paraffinic polysulphides - diallyl disulphide ( DADS ) and diallyl trisulphide ( DATS ) - derived from garlic and are usual constituents of garlic oil , showed antiplatelet activity , and also inhibited platelet thromboxane formation . In this respect DATS was more potent than DADS . The nature of inhibition of PAg by DATS was found to be reversible Marine oil plus simvastatin is an effective therapy for improving serum triglycerides , non-high-density lipoprotein cholesterol , and high-density lipoprotein cholesterol in patients with combined hyperlipidemia . Concurrent administration does not attenuate the individual effects of either marine oil or simvastatin on the serum lipid profile OBJECTIVE This study has dealt with the effects of gemfibrozil and vitamin E ( vit E ) therapies on lipoprotein levels , lipid peroxidation and antioxidant statuses of the elderly and young hyperlipidemic subjects . METHODS This study took place in the Internal Medicine Clinic , Faculty of Medicine , Osmangazi University , Turkey between 2004 - 2005 . This study was carried out on 99 hyperlipidemic and 40 control subjects . Subjects were divided into 2 groups ; elderly hyperlipidemic ( n=65 ) and young hyperlipidemic ( n=34 ) . In the young and elderly hyperlipidemic subjects of the first group treated only with vit E ( 600 mg/day ) for one month . In the young and elderly hyperlipidemic subjects of the second group were treated only with gemfibrozil ( 600 mg/twice daily ) for one month . The 2 therapies of vit E and gemfibrozil were then combined and applied to the third group of our study . Reduced glutathione ( GSH ) , glutathione peroxidase ( GPx ) , total cholesterol ( total chol ) , serum low density lipoprotein ( LDL ) , high density lipoprotein ( HDL ) , triglyceride ( TG ) , vit E , malondialdehyde ( MDA ) , superoxide dismutase ( SOD ) levels of the 3 groups were measured . RESULTS In elderly hyperlipidemic therapy group : vit E groups , the post-treatment vit E levels increased . In the gemfibrozil groups , post-treatment TG level decreased whereas HDL level increased . In the vit E plus gemfibrozil groups , post-treatment TG level decreased , HDL , and vit E levels increased . In young hyperlipidemic therapy group : vit E groups , the post-treatment HDL , vit E , GSH , GPX levels increased whereas LDL , MDA , levels decreased . In the gemfibrozil groups , post-treatment TG , LDL decreased , HDL level increased . In the vit E plus gemfibrozil groups , post-treatment TG , LDL , MDA levels decreased whereas HDL , vit E , GSH levels increased . CONCLUSION When combined , gemfibrozil and vit E are effective in preventing cardiovascular diseases We have evaluated the effect of fish oil supplementation in the prevention of restenosis after percutaneous transluminal coronary angioplasty by a r and omised trial conducted in 107 patients . The treatment group ( n = 58 , 96 significant coronary narrowings ) received 10 capsules of fish oil ( 1.8 g eicosapentaenoic acid , 1.2 g docosahexaenoic acid ) besides aspirin and calcium blockers , beginning 4.3 ( SD 2.9 ) days before coronary angioplasty . The conventional medical treatment group ( n = 49 , 81 significant coronary narrowings ) received only aspirin and calcium blockers . Enrollment required the presence of angina pectoris and successful dilatation of all significant coronary narrowings . All patients were followed-up for at least 6 months . Restenosis was identified by symptoms and exercise testing and confirmed by angiography . The incidence of angiographic restenosis was 32 % in the fish oil group and 27 % in the conventional treatment group . Biochemical investigations showed a greater decrease in serum triglyceride levels in fish oil group as compared to the conventional treatment group . There was no significant difference in the cholesterol levels over the treatment period . Administration of fish oil in a dose of 3 g per day did not reduce the incidence of early restenosis after coronary angioplasty To determine the safety and benefit of n-3 fatty acid therapy in the prevention of early restenosis after coronary angioplasty , we conducted a r and omized , unblinded study comparing a conventional antiplatelet regimen ( 325 mg of aspirin and 225 mg of dipyridamole per day ; control group ) with a similar regimen supplemented with 3.2 g of eicosapentaenoic acid per day ( treatment group ) . Treatment began seven days before angioplasty and continued for six months afterward . All angiographic analyses were blinded and performed by a method that was vali date d by comparison with quantitative coronary angiography . In 82 male patients , 103 coronary lesions were dilated . Both groups had similar base-line clinical and angiographic characteristics . The incidence of early vessel restenosis , as determined on a second angiogram three to four months after angioplasty , was 36 percent in the control group and 16 percent in the treatment group ( P = 0.026 ) . The incidence of restenosis per patient was also significantly lower in the treatment group ( 46 vs. 19 percent ) . Both multiple logistic regression and Mantel-Haenszel statistical analyses demonstrated a significant independent benefit of treatment with n-3 fatty acids . No important bleeding complications developed in the treated patients . These results , in a male population at relatively high risk for restenosis , suggest that a dietary supplement of n-3 fatty acids , administered for one week before and for six months after coronary angioplasty , is safe and reduces the occurrence of early restenosis after that procedure . Whether this beneficial effect also applies to other population s is unknown AIM The aim of this study was to investigate the effect of two common herbal medicines , ginkgo and ginger , on the pharmacokinetics and pharmacodynamics of warfarin and the independent effect of these herbs on clotting status . METHODS This was an open label , three-way crossover r and omized study in 12 healthy male subjects , who received a single 25 mg dose of warfarin alone or after 7 days pretreatment with recommended doses of ginkgo or ginger from herbal medicine products of known quality . Dosing with ginkgo or ginger was continued for 7 days after administration of the warfarin dose . Platelet aggregation , international normalized ratio ( INR ) of prothrombin time , warfarin enantiomer protein binding , warfarin enantiomer concentrations in plasma and S-7-hydroxywarfarin concentration in urine were measured . Statistical comparisons were made using anova and the 90 % confidence intervals ( CIs ) of the ratio of log transformed parameters are reported . RESULTS INR and platelet aggregation were not affected by administration of ginkgo or ginger alone . The mean ( 95 % CI ) apparent clearances of S-warfarin after warfarin alone , with ginkgo or ginger were 189 ( 167 - 210 ) ml h(-1 ) , 200 ( 173 - 227 ) ml h(-1 ) and 201 ( 171 - 231 ) ml h(-1 ) , respectively . The respective apparent clearances of R-warfarin were 127 ( 106 - 149 ) ml h(-1 ) , 126 ( 111 - 141 ) ml h(-1 ) and 131 ( 106 - 156 ) ml h(-1 ) . The mean ratio ( 90 % CI ) of apparent clearance for S-warfarin was 1.05 ( 0.98 - 1.21 ) and for R-warfarin was 1.00 ( 0.93 - 1.08 ) when coadministered with ginkgo . The mean ratio ( 90 % CI ) of AUC(0 - 168 ) of INR was 0.93 ( 0.81 - 1.05 ) when coadministered with ginkgo . The mean ratio ( 90 % CI ) of apparent clearance for S-warfarin was 1.05 ( 0.97 - 1.13 ) and for R-warfarin was 1.02 ( 0.95 - 1.10 ) when coadministered with ginger . The mean ratio ( 90 % CI ) of AUC(0 - 168 ) of INR was 1.01 ( 0.93 - 1.15 ) when coadministered with ginger . The mean ratio ( 90 % CI ) for S-7-hydroxywarfarin urinary excretion rate was 1.07 ( 0.85 - 1.32 ) for ginkgo treatment , and 1.00 ( 0.81 - 1.23 ) for ginger coadministration suggesting these herbs did not affect CYP2C9 activity . Ginkgo and ginger did not affect the apparent volumes of distribution or protein binding of either S-warfarin or R-warfarin . CONCLUSIONS Ginkgo and ginger at recommended doses do not significantly affect clotting status , the pharmacokinetics or pharmacodynamics of warfarin in healthy subjects Epidemiologic and experimental data suggest that a high dietary intake of long-chain polyunsaturated n-3 fatty acids may reduce the risk of atherothrombotic disease . In a r and omized , controlled study , 610 patients undergoing coronary artery bypass grafting were assigned either to a fish oil group , receiving 4 g/day of fish oil concentrate , or to a control group . All patients received antithrombotic treatment , either aspirin or warfarin . Their diet and serum phospholipid fatty acid profiles were monitored . The primary end point was 1-year graft patency , which was assessed by angiography in 95 % of patients . Vein graft occlusion rates per distal anastomoses were 27 % in the fish oil group and 33 % in the control group ( odds ratio 0.77 , 95 % confidence interval , 0.60 to 0.99 , p = 0.034 ) . In the fish oil group , 43 % of the patients had > or = 1 occluded vein graft(s ) compared with 51 % in the control group ( odds ratio 0.72 , 95 % confidence interval , 0.51 to 1.01 , p = 0.05 ) . Moreover , in the entire patient group , there was a significant trend to fewer patients with vein graft occlusions with increasing relative change in serum phospholipid n-3 fatty acids during the study period ( p for linear trend = 0.0037 ) . Thus , in patients undergoing coronary artery bypass grafting , dietary supplementation with n-3 fatty acids reduced the incidence of vein graft occlusion , and an inverse relation between relative change in serum phospholipid n-3 fatty acids and vein graft occlusions was observed Background The enzyme lecithin-cholesterol acyl transferase ( LCAT ) esterifies free cholesterol on highdensity lipoprotein ( HDL ) and the cholesteryl ester transfer protein ( CETP ) transfers cholesteryl esters to very-low-density lipoproteins ( VLDL ) and low-density lipoproteins ( LDL ) . Using statins , contradictory findings have been made regarding CETP activity in normolipidemic individuals and in those with familial dysbetatlipoproteinemia . In contrast , LCAT activity appears to be unaffected by simvastatin . Antioxidants have also been proposed for use in anti-atherosclerotic treatment , because the oxidation of LDL may have a key role in the pathophysiology of atherogenesis . Objective To investigate , in hypercholesterolemic patients , whether a combination of pravastatin with the antioxidant , vitamin E , has greater effects on the activity of CETP and of LCAT than does pravastatin alone . Methods This placebo-diet-controlled multicenter trial included 220 hypercholesterolemic patients who were assigned r and omly to groups to receive : diet and 20–40 mg pravastatin ( n = 52 ) , diet and pravastatin in combination with 100 mg/day vitamin E ( 100 IU ) as DL-α-tocopherol ( n = 56 ) , diet and α-tocopherol ( n = 60 ) , or diet associated with placebo ( n = 52 ) . Plasma LCAT activity was determined using excess exogenous substrate , containing [3H]cholesterol . Plasma CETP activity was measured in the supernatant fraction after precipitation of endogenous apo B-containing lipoproteins with phosphotungstate-Mg2 + . The exchange of cholesteryl esters between [14C]cholesteryl esterlabeled LDL and unlabeled HDL was measured during a 16-h incubation , while LCAT was inhibited . Results The addition of pravastatin to the diet induced a significant decrease in plasma CETP activity ( P < 0.05 ) ; this effect was less evident in the group cotreated with vitamin E. For the first time , it was shown that CETP concentrations increased significantly after vitamin E alone ( P < 0.05 ) . No significant differences in the plasma activity of LCAT were observed among the groups . Conclusions Pravastatin reduced CETP activity , but not that of LCAT . Addition of vitamin E prevented the decrease in CETP activity and had no effect on LCAT activity . The mechanism responsible for these effects is unknown , but could involve the prevention of radical-induced damage to CETP by vitamin E. Coronary Artery Dis Antiplatelet therapy with acetylsalicylic acid ( ASA ) is commonly used to reduce the risk of cardio- and cerebrovascular events . Fish consumption has been inversely related to coronary disease , which has been partly attributed to an inhibitory effect of n-3 polyunsaturated fatty acids ( n-3 PUFA ) on platelet production of tromboxane A2 . In this study , we investigated the acute and short-time effect of supplementation with n-3 PUFA and intravenous ASA on platelet function , platelet fatty acid composition and plasma lipids . Eighteen healthy men were r and omly allocated to a daily intake of 10 g n-3 PUFA or placebo . After this supplement ( 14 h and 14 days ) , blood was sample d before and after intravenous injection of 100 mg ASA . n-3 PUFA given for 14 days caused a minor inhibition of platelet reactivity but negligible compared to 100 mg ASA . No additive effect of n-3 PUFA and ASA could be demonstrated BACKGROUND Prescription omega-3-acid ethyl esters ( P-OM3 ) have been used as adjunctive therapy to statin drugs in patients with mixed hyperlipidemia . OBJECTIVE To assess the effect of concomitant administration of 4 g P-OM3 on the steady-state pharmacokinetics of the maximum recommended daily dose of atorvastatin ( 80 mg ) in healthy volunteers . METHODS This was a r and omized , open-label , repeated-dose , two-way crossover , drug interaction study of two treatments : 4 g of P-OM3 with 80 mg atorvastatin daily or 80 mg atorvastatin daily , each administered for 14 days under fasting conditions to 50 healthy adults . MAIN OUTCOME MEASURES The primary determinants of drug interaction were the ln-transformed area under the plasma concentration versus time curve ( AUCtau ) and maximum measured steady-state plasma concentration ( C(max , ss ) ) over the final 24 h dosing interval ( day 14 ) for atorvastatin and 2-hydroxyatorvastatin . Safety assessment included clinical laboratory evaluations and adverse event reporting . RESULTS The extent and rate of exposure ( AUCtau , C(max , ss ) ) to atorvastatin and its active metabolites following daily administration of P-OM3 with atorvastatin ( 80 mg ) were similar to those following the administration of atorvastatin ( 80 mg ) alone . Both treatments were well tolerated . CONCLUSIONS After 14 days of dosing , the rate and extent of exposure ( AUCtau , C(max , ss ) ) to atorvastatin and its active metabolites were similar with both treatments , indicating that administration of P-OM3 did not affect the steady-state bioavailability of orally administered atorvastatin 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 One hundred patients with transient ischemic attacks , minor strokes , or residual ischemic neurologic deficits were enrolled in a double-blind , r and omized study comparing the effects of aspirin plus vitamin E [ 0.4 g ( 400 IU)/d ; n = 52 ] with aspirin alone ( 325 mg ; n = 48 ) . The patients received study medication for 2 y or until they reached a termination point . Preliminary results show a significant reduction in the incidence of ischemic events in patients in the vitamin E plus aspirin group compared with patients taking only aspirin . There was no significant difference in the incidence of hemorrhagic stroke although both patients who developed it were taking vitamin E. Platelet adhesion was also measured in a r and omized subgroup of both study population s by using collagen III as the adhesive surface . There was a highly significant reduction in platelet adhesiveness in patients who were taking vitamin E plus aspirin compared with those taking aspirin only . Measurement of alpha-tocopherol concentrations confirmed compliance of the patients with the medication schedule , showing a near doubling of serum concentrations of alpha-tocopherol . We concluded that the combination of vitamin E and a platelet antiaggregating agent ( eg , aspirin ) significantly enhances the efficacy of the preventive treatment regimen in patients with transient ischemic attacks and other ischemic cerebrovascular problems Prescription omega-3 acid ethyl esters ( P-OM3 ) are commonly used for treatment of very high triglyceride levels , often in combination with a statin , to lower persistent hypertriglyceridemia . This r and omized , crossover trial evaluated 6 weeks of combination therapy with simvastatin 20 mg/day plus P-OM3 4 g/day or placebo in 39 men and women ( average age 58 years ) with a triglyceride concentration 200 to 600 mg/dl and non-high-density lipoprotein ( non-HDL ) cholesterol greater than their National Cholesterol Education Program treatment goals after a 5-week diet lead-in . Non-HDL cholesterol decreased from baseline ( 209 mg/dl ) by 40 % for P-OM3 + simvastatin compared with 34 % for placebo + simvastatin ( p < 0.001 ) . Favorable changes for P-OM3 + simvastatin versus placebo + simvastatin were also observed for very low-density lipoprotein ( VLDL ) cholesterol ( -42 % vs -22 % ) , triglyceride ( -44 % vs -29 % ) , total cholesterol ( -31 % vs -26 % ) , HDL cholesterol ( + 16 % vs + 11 % ) , apolipoprotein B ( -32 % vs -28 % ) , total cholesterol : HDL cholesterol ratio ( -39 % vs -33 % ) , triglyceride : HDL cholesterol ratio ( -51 % vs -37 % ) , and systolic ( -5.0 vs 0.3 mm Hg ) and diastolic ( -3.3 vs -1.8 mm Hg ) blood pressures ( p < 0.05 for all ) . VLDL particle concentration and size decreased and LDL particle size increased significantly more with P-OM3 + simvastatin than with placebo + simvastatin ( all p < 0.05 ) . Changes in LDL cholesterol , LDL particle concentration , HDL particle size and concentration , and apolipoprotein A-I did not differ significantly between treatments . In conclusion , P-OM3 + simvastatin appears to be a useful therapeutic option for the management of mixed dyslipidemia Dietary supplementation with omega-3 fatty acids reduces platelet aggregation in subjects who usually eat a diet low in these fatty acids . Aspirin also has an antiplatelet effect . The clinical effects of the concomitant administration of these agents were examined in this double-blind controlled crossover trial . Twelve healthy adults were r and omized to supplement their diet for 21 days with 8 g of omega-3 fatty acids or identical-looking olive oil capsules . At the end of each treatment period , bleeding times were obtained before and after the administration of one 325-mg aspirin tablet . Overall , percent change in bleeding time after omega-3 fatty acid supplementation was significantly prolonged compared with olive oil supplementation before aspirin administration but not after . Bleeding times were influenced significantly by the order of r and omization in the two treatment groups . Changes in post-aspirin bleeding time varied in subjects after they received olive oil . Post-aspirin bleeding times after omega-3 fatty acid supplementation were prolonged compared with baseline values but not significantly prolonged when compared with those after olive oil administration . The authors concluded that the concomitant administration of a single dose of aspirin does not prolong bleeding time in subjects who eat a diet enriched by omega-3 fatty acids versus a diet enriched by olive oil Ambulatory blood pressure ( ABP ) monitoring was undertaken in 25 hypertensives on beta-blocker monotherapy who completed a double-blind crossover trial to compare the effects of fish oil and corn oil supplements on BP . Clinic BP was measured with a Dinamap monitor on two consecutive days at the end of each treatment phase . ABP was recorded during the intervening 24-h period with a Spacelabs 90207 monitor . Averages of 24-h , daytime , and nighttime ABP readings correlated closely with Dinamap readings . Within-subject BP differences between fish oil and corn oil treatment were similar for Dinamap ( 3.2 + /- 1.8/2.5 + /- 1.0 mm Hg ) and for 24-h ABP ( 2.5 + /- 1.0/2.3 + /- 0.8 mm Hg ) , but were more significant with the latter . Thus detection of the antihypertensive effects of dietary intervention can be improved by the use of ABP |
1,889 | 29,552,976 | Conclusions : Although blood had a better specificity for detecting EGFR mutations , the absence of blood positivity should not necessarily be construed as confirmed negativity . | Background : Many studies have evaluated the accuracy of EGFR mutation status in blood against that in tumor tissues as the reference .
We conducted this systematic review and meta- analysis to assess whether blood can be used as a substitute for tumor tissue in detecting EGFR mutations . | Background Lung cancer patients with mutations in the epidermal growth factor receptor ( EGFR ) are primary c and i date s for EGFR-targeted therapy . Reliable analyses of such mutations have previously been possible only in tumour tissue . Here , we demonstrate that mutations can be detected in plasma sample s with allele-specific PCR assays . Methods Pairs of the diagnostic biopsy and plasma obtained just prior to start of erlotinib treatment were collected from 199 patients with adenocarcinoma of non-small-cell lung cancer . DNA from both sample types was isolated and examined for the presence of mutations in exons 18–21 of the EGFR gene , employing the cobas ® EGFR Tissue Test and cobas ® EGFR Blood Test ( in development , Roche Molecular Systems , Inc. , CA , USA ) . Results Test results were obtained in all 199 ( 100 % ) plasma sample s and 196/199 ( 98 % ) of the biopsies . EGFR-activating mutations were identified in 24/199 ( 12 % ) plasma sample s and 28/196 ( 14 % ) biopsy sample s , and 17/196 ( 9 % ) matched pairs contained the same mutation . Six EGFR mutations were present only in plasma sample s but not in the biopsy sample s. The overall concordance of the EGFR gene mutations detected in plasma and biopsy tissue was 179/196 ( 91 % ) ( kappa value : 0.621 ) . Conclusion Mutational analysis of the EGFR gene in plasma sample s is feasible with allele-specific PCR assays and represents a non-invasive supplement to biopsy analysis .Trial registration M-20080012 from March 10 , 2008 and reported to Clinical Trials.gov : NCT00815971 Cases of non – small-cell lung cancer ( NSCLC ) carrying the somatic mutation of epidermal growth factor receptor ( EGFR ) have been shown to be hyperresponsive to the EGFR tyrosine kinase inhibitor gefitinib ( IRESSA ) . If EGFR mutations can be observed in serum DNA , this could serve as a noninvasive source of information on the genotype of the original tumor cells that could influence treatment and the ability to predict patient response to gefitinib . Serum genomic DNA was obtained from Japanese patients with NSCLC before first-line gefitinib monotherapy . Scorpion Amplified Refractory Mutation System technology was used to detect EGFR mutations . Wild-type EGFR was detected in all of the 27 serum sample s. EGFR mutations were detected in 13 of 27 ( 48.1 % ) patients and two major EGFR mutations were identified ( E746_A750del and L858R ) . The EGFR mutations were seen significantly more frequently in patients with a partial response than in patients with stable disease or progressive disease ( P = 0.046 , Fisher 's exact test ) . The median progression-free survival was significantly longer in patients with EGFR mutations than in patients without EGFR mutations ( 200 versus 46 days ; P = 0.005 , log-rank test ) . The median survival was 611 days in patients with EGFR mutations and 232 days in patients without EGFR mutations ( P > 0.05 ) . In pairs of tumor and serum sample s obtained from 11 patients , the EGFR mutation status in the tumors was consistent with those in the serum of 8 of 11 ( 72.7 % ) of the paired sample s. Thus , EGFR mutations were detectable using Scorpion Amplified Refractory Mutation System technology in serum DNA from patients with NSCLC . These results suggest that patients with EGFR mutations seem to have better outcomes with gefitinib treatment , in terms of progression-free survival , overall survival , and response , than those patients without EGFR mutations Introduction : In IPASS ( IRESSA Pan-Asia Study ) , clinical ly selected patients with pulmonary adenocarcinoma received first-line gefitinib or carboplatin/paclitaxel . This preplanned , exploratory analysis was conducted to increase underst and ing of the use of surrogate sample s , such as serum , versus tumor biopsy sample s for determining EGFR mutation status in the Japanese cohort ( n = 233 ) . Methods : EGFR mutations were assessed using tumor tissue-derived DNA ( n = 91 ) and circulating free ( cf ) DNA from pretreatment serum sample s ( n = 194 ) . Results : Fewer patients were EGFR mutation positive when assessed using pretreatment cfDNA ( 23.7 % ) versus tumor tissue-derived DNA ( 61.5 % ) . cfDNA results identified no false positives but a high rate of false negatives ( 56.9 % ) . There was a significant interaction between cfDNA EGFR mutation status and treatment for progression-free survival ( PFS ) ( p = 0.045 ) . PFS was significantly longer and objective response rate ( ORR ) higher with gefitinib than carboplatin/paclitaxel in the cfDNA EGFR mutation-positive subgroup ( PFS : hazard ratio [ HR ] , 0.29 ; 95 % confidence interval [ CI ] , 0.14–0.60 ; p < 0.001 ; ORR : odds ratio [ OR ] , 1.71 ; 95 % CI , 0.48–6.09 ; 75.0 % versus 63.6 % ; p = 0.40 ) . There was a slight numerical advantage in PFS and ORR for gefitinib over carboplatin/paclitaxel in the cfDNA EGFR mutation-negative subgroup , likely due to the high rate of false negatives within this subgroup . Conclusions : These results merit further investigation to determine whether alternative sources of tumor DNA , such as cfDNA in serum , could be used for determining EGFR mutation status in future ; currently , where a sample is available , analysis of tumor material is recommended PURPOSE Mutations in the epidermal growth factor receptor ( EGFR ) kinase domain can predict tumor response to tyrosine kinase inhibitors ( TKIs ) in non-small-cell lung cancer ( NSCLC ) . However , obtaining tumor tissues for mutation analysis is challenging . We hypothesized that plasma-based EGFR mutation analysis is feasible and has value in predicting tumor response in patients with NSCLC . PATIENTS AND METHODS Plasma DNA sample s and matched tumors from 230 patients with stages IIIB to IV NSCLC were analyzed for EGFR mutations in exons 19 and 21 by using denaturing high-performance liquid chromatography . We compared the mutations in the plasma sample s and the matched tumors and determined an association between EGFR mutation status and the patients ' clinical outcomes prospect ively . RESULTS In 230 patients , we detected 81 EGFR mutations in 79 ( 34.3 % ) of the patients ' plasma sample s. We detected the same mutations in 63 ( 79.7 % ) of the matched tumors . Sixteen plasma ( 7.0 % ) and fourteen tumor ( 6.1 % ) sample s showed unique mutations . The mutation frequencies were significantly higher in never-smokers and in patients with adenocarcinomas ( P = .012 and P = .009 , respectively ) . In the 102 patients who failed platinum-based treatment and who were treated with gefitinib , 22 ( 59.5 % ) of the 37 with EGFR mutations in the plasma sample s , whereas only 15 ( 23.1 % ) of the 65 without EGFR mutations , achieved an objective response ( P = .002 ) . Patients with EGFR mutations had a significantly longer progression-free survival time than those without mutations ( P = .044 ) in plasma . CONCLUSION EGFR mutations can be reliably detected in plasma DNA of patients with stages IIIB to IV NSCLC and can be used as a biomarker to predict tumor response to TKIs Background : The authors evaluate the efficacy and safety of gefitinib monotherapy in chemotherapy-naive patients with advanced non – small-cell lung cancer ( NSCLC ) . A secondary endpoint is to evaluate the relationship between clinical manifestations and epidermal growth factor receptor ( EGFR ) mutation status . Methods : Japanese chemotherapy-naive NSCLC patients were enrolled . They had measurable lesions , Eastern Cooperative Oncology Group performance status of 0 to 2 , and adequate organ and bone marrow function . Patients received 250 mg of oral gefitinib daily . EGFR mutations in exon 18 , 19 , and 21 of DNA extracted from tumor and serum were analyzed by genomic polymerase chain reaction and direct sequence . Results : All 30 patients were eligible for the assessment of efficacy and safety . An objective response and stable disease were observed in 10 patients ( 33.3 % ) and nine patients ( 30.0 % ) , respectively . The median time to progression was 3.3 months and the median overall survival was 10.6 months . The 1-year survival rate was 43.3 % . Grade 3 toxicities were observed in seven patients . EGFR mutation was observed in four of 13 ( 30.8 % ) tumors , and two of them achieved partial response . In serum sample s , three of 10 patients with EGFR mutations in the serum before treatment had a response to gefitinib . EGFR mutation was observed in 10 of 27 and significantly more frequently observed in the posttreatment sample s from patients with a partial response or stable disease than in those from patients with progressive disease ( p = 0.006 ) . Conclusions : Gefitinib monotherapy in chemotherapy-naive NSCLC patients was active , with acceptable toxicities . These results warrant further evaluation of gefitinib monotherapy as a first-line therapy . The EGFR mutation in serum DNA may be a biomarker for monitoring the response to gefitinib during treatment |
1,890 | 23,152,261 | There was no evidence to indicate that clomiphene with gonadotropins ( with or without GnRH antagonist ) differed significantly from gonadotropins in GnRH agonist protocol s for women undergoing IVF treatment , in terms of live births or pregnancy rates .
Meanwhile , use of clomiphene led to a reduction in the incidence of OHSS .
Hence there was insufficient evidence to recommend use of clomiphene citrate in routine IVF practice . | BACKGROUND Gonadotropins are the most commonly used medication for controlled ovarian stimulation in in vitro fertilization ( IVF ) .
However , they are expensive , invasive and are associated with risk of ovarian hyperstimulation syndrome ( OHSS ) .
With recent calls for patient friendly IVF , there has been an interest in the use of clomiphene citrate with or without gonadotropins to reduce the burden of injections .
However , it is not known whether regimens using clomiphene are at least as effective as gonadotropins alone .
OBJECTIVES To determine whether clomiphene citrate with gonadotropins ( with or without mid-cycle antagonist ) is more effective than gonadotropins with gonadotropin-releasing hormone ( GnRH ) agonists for controlled ovarian stimulation in IVF or intracytoplasmic sperm injection ( ICSI ) treatment . | Twenty-four healthy adult female volunteers participated in a r and omized , three-phase double-blind crossover trial comparing the single-dose ( 50 mg ) pharmacokinetics of three formulations of clomiphene citrate ( CC ) . Plasma levels of both the Z(cis ) and E(trans ) isomers of CC , as well as principal metabolites , were determined at periodic intervals ; and no differences between formulations were observed . The active Z isomer attained peak blood levels later than the inactive E isomer and was eliminated much more slowly , significant plasma concentrations still being detected up to 1 month after treatment . The results of this study demonstrate that three commercially available formulations of CC are bioequivalent This study evaluates the efficacy of a stimulation protocol with clomiphene citrate (CC)/human menopausal gonadotropin (hMG)/cetrorelix and its effects on oocyte quality and endometrium . One hundred and twenty couples with male-factor infertility who were about to undergo their first intracytoplasmic sperm injection cycles were r and omized into two groups . Sixty women were stimulated with the CC/hMG/cetrorelix protocol ( cetrorelix group ) and 60 received the buserelin long protocol ( buserelin group ) . Fewer oocytes were recovered in the cetrorelix group than in the buserelin group ( mean ± st and ard deviation ( SD ) : 11.1 ± 4.0 vs. 17.3 ± 5.8 , p < 0.001 ) ; however , the percentages of metaphase II , metaphase I and germinal vesicle oocytes were similar between the two groups . Serum estradiol level was significantly lower in the cetrorelix than in the buserelin group ( mean ± SD : 2600.58 ± 1189.11 vs. 3293.46 ± 1221.49 pg/ml , p = 0.006 ) , but the endometrial thickness was similar . The implantation rates ( 19.2 % vs. 17.7 % ) and the pregnancy rates ( 41.7 % vs. 40.0 % ) were similar between groups . The ampoules ( mean ± SD : 18.9 ± 3.0 vs. 38.9 ± 12.2 , p < 0.001 ) and injections ( mean ± SD : 6.8 ± 1.1 vs. 15.7 ± 3.1 , p < 0.001 ) of gonadotropin used were significantly lower in the cetrorelix group than in the buserelin group . No patients in either group developed a premature luteinizing hormone surge . The present study found no statistically significant difference between the two treatment modalities with regard to pregnancy rates In an attempt to improve the pregnancy rate following in vitro fertilization and embryo transfer by increasing the numbers of embryos available for transfer to each patient , a prospect i ve , r and omized comparison of clomiphene citrate alone ( 50 mg/day , cycle days 5 to 9 ) with the combination of clomiphene as above plus human menopausal gonadotropin ( 2 ampules/day , cycle days 6 , 8 , and 10 ) was undertaken from January through April 1983 , with 17 patients in each group . The combination produced increased follicular development , compared with clomiphene alone , result ing in the retrieval of more fertilizable oocytes . Two clinical pregnancies result ed in each group . These results show that a fixed combination of clomiphene and human menopausal gonadotropin produces a greater degree of enhanced follicular recruitment , result ing in the recovery of an increased number of fertilizable oocytes . The lack of a statistically significant increase in the number of embryos transferred per patient in the combination group as well as the identical number of clinical pregnancies in both groups suggests that this particular combination of clomiphene and human menopausal gonadotropin offers no advantage over the use of clomiphene alone for enhanced follicular recruitment The efficiency of IVF in unstimulated cycles was compared with that following ovarian stimulation with clomiphene citrate in a simple protocol with ultrasound monitoring only . A total of 132 couples with no previous IVF attempts , selected by female age < 35 years , indication for intracytoplasmic sperm injection or infertility caused by tubal factor or unexplained infertility were r and omized to the two protocol s. R and omization yielded two comparable groups . The clomiphene group ( 68 couples ) performed significantly better than the unstimulated group ( 64 couples ) in terms of number of cycles with oocyte harvest ( 90/111 or 81 % versus 65/114 or 57 % ; chi(2 ) = 9.21 , P < 0.002 ) , embryo transfers per started cycle ( 59/111 or 53 % versus 29/114 or 25 % ; chi(2 ) = 18.14 , P < 0.0001 ) , live intrauterine pregnancy rate per started cycle ( 20/111 or 18 % versus 4/114 or 4 % ; chi(2 ) = 12.42 , P < 0.0001 ) , live intrauterine pregnancy rate per embryo transfer ( 20/59 or 34 % versus 4/29 or 14 % ; chi(2 ) = 3.96 , P = 0.047 ) , but not in terms of implantation rate ( 22/85 or 26 % versus 4/29 or 14 % ; chi(2 ) = 1.65 ) . Only two twin pregnancies occurred . Modest side-effects were recorded following clomiphene . Accordingly , a simple clomiphene citrate protocol , but not IVF in unstimulated cycles , seems compatible with the concept of ' friendly IVF ' , yielding a fair pregnancy rate both per cycle started and per embryo transfer in selected patients . The results do not substantiate any important negative anti-oestrogenic effects of clomiphene OBJECTIVE To determine the follicular and luteal phase impact of low-dose GnRH agonist ( GnRH-a ) treatment during follicular stimulation for IVF . DESIGN A r and omized prospect i ve study compared patients receiving low-dose GnRH-a and hMG therapy to clomiphene citrate ( CC ) and hMG cycles . SETTING Patients were treated through a university-based IVF-ET program . PATIENTS Thirty-six patients underwent follicular stimulation with low-dose GnRH-a and hMG and were compared with 34 patients undergoing ovulation induction with CC and hMG . RESULTS Significantly shorter luteal phase length occurred with GnRH-a and hMG therapy ; however , there was no statistically significant difference in luteal P levels . Follicular parameters were the same ( peak E2 , number of follicles , and number of oocytes ) , suggesting that folliculogenesis was not altered . There were no statistical differences in pregnancy rates . CONCLUSIONS Sustained low-dose GnRH-a therapy during follicular stimulation does not have a clinical effect on luteal function OBJECTIVE To compare 3 stimulation protocol s in poor ovulation responders undergoing in-vitro fertilization ( IVF ) . METHODS The study was a r and omized , prospect i ve clinical trial from June 2003 to July 2004 , in Royan Institute , Tehran , Iran . One hundred and fifty-four patients , who had poor responses to ovulation induction in at least one previous IVF attempt , were r and omly divided into 3 groups . In the first group , human menopausal gonadotropin ( HMG ) was administered from day 3 of the cycle at a dose rate of 150 IU/day . In the second group , gonadotropin-releasing hormone ( GnRH ) agonist was started at a dose rate of 800 microg/day by nasal spray or 500 microg/day subcutaneously in the mid-luteal phase , followed by a st and ard HMG dose after pituitary down regulation was confirmed . In the third group , clomiphene at a dose rate of 100 mg/day was given from day 3 and HMG from day 6 . Our main outcomes were number of mature oocytes , cancellation rate , number of HMG ampoules used and incidence premature luteinizing hormone ( LH ) surge . RESULTS There was a high incidence of premature LH surge in all groups except in the GnRH group ( p=0.0001 ) and there were significant differences between groups in HMG requirements ( p=0.004 ) . There were no significant differences between groups in number of mature oocytes recovered and cancellation rate . CONCLUSION Results showed no advantage in the use of GnRH agonist compared to the older regimens of clomiphene plus HMG and HMG alone . The cancellation rate was similar for 3 protocol s and HMG requirement was higher with the use of GnRH agonist . The treatment of poor responders in assisted reproductive technologies remains a challenge The quality of ovarian stimulation for in vitro fertilization with or without an LH-RH analogue was investigated in a r and omized trial involving 30 women divided into 3 groups . Group I women were treated with the conventional clomiphene citrate-human menopausal gonadotropin combination without LH-RH analogue . Group II women ( long regimen ) received a slow-release preparation of triptorelin ( DTRp6-LH-RH ) , an LH-RH analogue , and human menopausal gonadotropin . Group II women ( short regimen ) were given triptorelin with human menopausal gonadotropin . Inhibition of the endogenous luteinizing hormone using triptorelin improved the results of in vitro fertilization in group II and group III women , but the short regimen was distinctly less compelling and less expensive than the long regimen Purpose To compare the IVF outcome of clomiphene citrate/gonadotropin/antagonist ( mild protocol ) and microdose GnRH agonist flare protocol s for poor responders undergoing in vitro fertilization . Methods 159 poor responder patients were r and omized and ovarian stimulation was performed with clomiphene citrate , gonadotropin and antagonist ( group I ) or microdose GnRH agonist flare ( group II ) protocol s. Main outcome was clinical pregnancy rate and secondary outcomes were doses of gonadotropin administration and duration of stimulation . Results There were no significant differences in age , causes of infertility , basal FSH , BMI , duration of infertility , E2 level on the day of hCG injection in both groups . Although the cancellation , fertilization , and clinical pregnancy rates were similar in both groups , the endometrial thickness , number of retrieved oocytes , mature oocytes and implantation rate were significantly higher in mild protocol . The doses of gonadotropin administration and duration of stimulation were significantly lower in mild protocol . Conclusion We recommend mild protocol in assisted reproductive technology cycles for poor responders based on our results regarding less doses of used gonadotropin and a shorter duration of stimulation A prospect i ve , r and omized , double-blind , multicentre ( n = 6 ) study was conducted to compare the influence of either a 150 or 250 IU daily fixed-dose regimen of recombinant follicle stimulating hormone ( FSH , Puregon ) on the number of oocytes retrieved and the total dose used in down-regulated women between 30 and 39 years of age undergoing ovarian stimulation . In all , 138 women were treated with recombinant FSH , 67 with 150 IU and 71 with 250 IU . The number of oocytes retrieved in the low-dose group was 9.1 compared to 10.6 in the high-dose group ( not significant ) . In the 30 - 33 years of age class receiving the 250 IU dose , a surplus of 4.2 oocytes ( 14.8 versus 10.6 ) was found , whereas in the 37 - 39 age class nearly one oocyte more was retrieved in the 150 IU group ( 8.1 versus 7.4 ) . The total dose used to reach the criterion for human chorionic gonadotrophin ( HCG ) administration was 1727 IU for the women treated with 150 IU daily and 2701 IU for the 250 IU treated women ( P < 0 . 001 ) . No significant relationships were found between serum FSH concentrations as obtained in the early follicular phase and the number of oocytes collected , or the total dose . It is concluded that in women between 30 and 39 years of age , the decline in number of oocytes retrieved with increasing age can not be overcome by augmenting the daily dose of recombinant FSH from 150 to 250 IU OBJECTIVE To compare luteal phase leuprolide acetate ( LA ) initiated pituitary down regulation followed by human menopausal gonadotropins ( hMG ) versus clomiphene citrate ( CC ) and hMG for follicular recruitment and oocyte maturation before in vitro fertilization ( IVF ) . DESIGN R and omized , prospect i ve comparison in first cycles of IVF . SETTING University Hospital , a tertiary referral center offering assisted reproductive technologies . PARTICIPANTS Participants were couples undergoing their first ever cycle of IVF and consenting to participation in the trial . RESULTS Luteal phase initiated LA/hMG was associated with a lower probability of cycle cancellation , improved folliculogenesis , and a higher probability of embryo transfer ( ET ) compared with CC/hMG alone . Implantation rates were not different . CONCLUSION A higher rate of ET with LA/hMG suggests that gonadotropin-releasing hormone agonist for the induction of folliculogenesis before IVF may be appropriate In a prospect i ve study , we compared two protocol s of ovulation stimulation , the clomiphene citrate and human menopausal gonadotropin ( hMG ) versus D-triptorelin , a long-acting gonadotropin-releasing hormone ( GnRH ) agonist and hMG in 324 couples having their first in vitro fertilization or intracytoplasmic sperm injection ( IVF/ICSI ) program , in terms of pregnancy rates and cost-effectiveness of drugs used . The GnRH agonist/hMG group was characterized by a greater mean number of ampoules of hMG used ( 31.7 versus 10.2 ) , a larger number of oocytes collected ( 10.4 versus 4.2 ) , and a larger number of embryos obtained ( 5.8 versus 2.9 ) . With the policy of transferring only two of the best quality embryos , the mean number of embryos replaced were comparable ( 1.8 in clomiphene citrate/hMG and 1.9 in GnRH agonist/hMG group ) . The percentage of patients reaching embryo transfer was lower in the clomiphene citrate/hMG than in the GnRH agonist/hMG group ( 84.1 % versus 93.1 % , respectively ) . However , the combined results of the IVF and ICSI procedure in terms of pregnancy rate , both per patient and per embryo transfer were better , though not significantly in the clomiphene citrate/hMG than in GnRH agonist/hMG group ( 25.0 % and 29.7 % versus 23.7 % and 25.5 % , respectively ) . Similarly , the implantation rate was better ( 19.0 % versus 13.5 % , respectively ) . With the use of clomiphene citrate/hMG , a fivefold less costly drug regimen , we obtained pregnancy rates equivalent to those gained using GnRH agonist/hMG in our IVF/ICSI program OBJECTIVE To compare the efficacy of letrozole to recombinant FSH for ovarian stimulation combined with IUI in a group of patients that had failed to conceive after clomiphene citrate ( CC ) and IUI . DESIGN Prospect i ve r and omized trial with human subjects . SETTING University-based fertility center . PATIENT(S ) Fifty couples with unexplained infertility that failed to conceive after three cycles of CC combined to IUI . INTERVENTION(S ) Couples were r and omized to undergo superovulation either with letrozole or with recombinant FSH combined to IUI . MAIN OUTCOME MEASURE(S ) Clinical pregnancy per cycle of treatment and clinical pregnancy per couple . RESULT ( S ) Pregnancy rate ( PR ) per cycle was 8.9 % in the letrozole group as compared with 14 % in the gonadotropin IUI group . This result ed in a cumulative PR per couple of 24 % versus 36 % and a take home baby rate of 20 % versus 28 % . Endometrial thickness was significantly lower in the letrozole group ( 7.1 + /- 2.3 vs 8.6 + /- 1.8 ) . CONCLUSION ( S ) Ovarian stimulation with letrozole is associated with acceptable PRs compared with gonadotropin with significant less cost , risks , and patient inconvenience Over a period of 4 months , 262 infertile couples participated in a prospect i ve pseudor and om trial of a novel short-term luteinizing hormone-releasing hormone/human menopausal gonadotropin ( LH-RH/hMG ) treatment ; the short-Buserelin-gonadotropin ( Hoechst , Hounslow , United Kingdom ) regimen . Patients treated with the short-Buserelin-gonadotropin regimen had a significantly higher likelihood of achieving pregnancy than patients treated with the st and ard clomiphene citrate (CC)/hMG regimen ( respectively , 35.5 % and 18 % per treatment cycle ) . A significantly higher number of eggs were collected after short-Buserelin-gonadotropin treatment than CC/hMG , but the proportion of patients having a given number of embryos replaced was similar in the two groups . The short-Buserelin-gonadotropin-treated patients were distinguished from the CC/hMG-treated group by significantly lower levels of LH in the late follicular phase and a lower plasma level of estradiol . A detrimental relationship between elevated endogenous LH secretion and failure of implantation has been established . The nature of the short-Buserelin-gonadotropin regimen provokes high levels of endogenous gonadotropin secretion in the early follicular phase and induces a suppression of gonadotropin secretion in the late follicular phase . This may be the physiologic basis of the greater implantation rate after short-Buserelin-gonadotropin treatment than is seen with conventional CC/hMG treatment Summary . Sixty‐eight women with bilateral tubal disease and fertile male partners underwent ovarian stimulation in 187 cycles for IVF after r and omization to different ovulation induction regimens . All patients initially received 150 mg clomiphene citrate on days 5–9 , this regimen induced sufficient stimulation in a smaller proportion of patients than the two other regimens used subsequently which included clomiphene in combination with human menopausal gonadotrophins ( hMG ) . The fertilization rate was significantly reduced ( 52–4 % ) in oocytes collected from cycles stimulated with hMG alone ( in a small sub‐group of poor responders ) compared with a rate of 64·1–66·4 % in cycles stimulated with clomiphene alone or in combination with hMG . Embryonic development 44–48 h after insemination was significantly retarded when clomiphene alone was utilized but a higher proportion of fragmented or abnormal embryos was observed after stimulation with hMG alone . In 118 cycles embryo transfer was performed and 20 pregnancies were established , a pregnancy rate of 16·9 % . All but two pregnancies were established when two or more embryos were transferred and when the embryos were at the 4‐cell or later stage of development . The regimen of clomiphene in combination with 150 i.u . hMG result ed in significantly greater numbers of oocytes recovered and embryos available per patient for transfer than the other two regimens studied OBJECTIVE To compare IVF-ET outcome with a new stimulation protocol using clomiphene citrate ( CC ) with recombinant FSH and LH to stimulation with the st and ard long GnRH-a protocol . DESIGN Prospect i ve r and omized study . SETTING Outpatient infertility clinic in Vienna , Austria . PATIENT(S ) Two hundred ninety-four infertile women undergoing IVF-ET ; 154 IVF cycles stimulated with CC + recombinant FSH + recombinant LH ( group A ) and 140 cycles with long GnRH-a suppression + recombinant FSH ( group B ) . INTERVENTION(S ) Controlled ovarian hyperstimulation , egg retrieval , and ET . MAIN OUTCOME MEASURE(S ) Cycle parameters ( number of oocytes , fertilization , number of embryos ) and outcome ( pregnancy rate , cancellation rate , ovarian hyperstimulation syndrome [ OHSS ] ) . RESULT ( S ) Pregnancy rate per ET was 42.9 % ( implantation rate , 21.3 % ) in group A and 36.6 % ( 17.4 % ) in group B. Cancellation rates were similar . The OHSS occurred in four cases ( 3 % ) in group A and 12 cases ( 10 % ) in group B. CONCLUSION ( S ) Stimulation with CC + recombinant FSH + recombinant LH leads to comparable pregnancy rates vs. the long protocol . With this new stimulation , less gonadotropins are used and there is less need for monitoring ( lower cost for patient and clinic ) . The risk of OHSS is reduced as well . Therefore , this protocol should be regarded as the first-line treatment Objective — To determine the effect of a short course of the GnRH analogue buserelin and human menopausal gonadotrophin ( hMG ) , for ovarian stimulation in our IVF programme , on reproductive endocrinology and pregnancy rates compared with conventional clomiphene citrate and hMG treatment OBJECTIVE To compare the classic clomiphene citrate ( CC ) and hMG regime for ovarian stimulation before IVF in women who received hMG post-long protocol down-regulation with either 3 mg triptorelin [ INN ] IM or 150 mg buserelin acetate four times daily intranasally . Furthermore , if possible , to determine the preferred method of down-regulation . DESIGN A prospect i ve study of 150 women r and omized blind to the clinician to one of three alternative ovarian stimulation regimes when passing for the first time through an IVF program during 1992 . RESULTS Triptorelin [ INN ] down-regulated significantly more quickly than buserelin acetate . The non-down-regulated group CC and hMG used significantly less hMG in a shorter time . In these women LH levels at hCG administration were significantly higher . No other intergroup differences were found . Pregnancy and take-home baby rates for the overall study were , respectively , 32%:25 % ( per cycle ) and 42%:33 % ; ( per ET ) for the triptorelin [ INN ] group 28%:22 % and 39%:31 % ; the CC group 32%:24 % and 46%:34 % ; and the buserelin acetate group 34%:28 % and 42%:34 % . CONCLUSIONS Triptorelin [ INN ] and buserelin acetate were comparable in all parameters except down-regulation . The former was significantly quicker and more sure . In none of the clinical end points measured , however , was the classic CC and hMG non-down-regulation regime significantly less effective or troublesome than where down-regulation was used . These results therefore show that although indications for down-regulation before IVF exist , it should not be used on all patients We recently demonstrated , using transvaginal sonography , that conception cycles in in-vitro fertilization ( IVF ) are associated with a significantly thicker endometrium at midcycle than non-conception cycles , suggesting that endometrial growth may influence implantation . In the present study , to examine whether the type of stimulation protocol affects endometrial development , we compared the sonographic appearance of the endometrium in 22 patients r and omized to receive clomiphene citrate and human menopausal gonadotrophin ( CC/HMG ) and in 19 who received HMG alone . A significantly thicker endometrium was observed in the HMG patients compared to the CC/HMG group ( P less than 0.005 ) throughout the follicular phase of the cycle , although serum concentrations of oestradiol ( E2 ) did not differ in the two groups . Twenty-three patients ( 13 in the HMG group and 10 in the CC/HMG group ) had previous IVF cycles with CC/HMG stimulation in which endometrial thickness was measured . A thin endometrium recurred with subsequent CC/HMG cycles while increased growth occurred with HMG only compared to previous CC/HMG cycles . Therefore , ultrasound examination of the endometrium in this study demonstrated that CC results in a thinner endometrium than HMG alone . We believe these findings may be of importance in improving pregnancy rates in IVF and possibly in other infertility therapy which involves the use of clomiphene citrate We performed a prospect i ve r and omized study of goserelin , a long-acting gonadotrophin-releasing hormone agonist ( GnRHa ) and human menopausal gonadotrophin ( HMG ) versus clomiphene citrate and HMG for follicular stimulation in assisted reproduction to investigate whether the use of this GnRHa provides a clear advantage in terms of pregnancy per treatment cycle in unselected patients , who entered a first trial of assisted reproduction . From a retrospective analysis comparing the two stimulation protocol s , a relative increase of the pregnancy rate per cycle of 50 % was anticipated . To detect this difference with a power of 90 % , 300 patients had to be included . The main prognostic factors affecting the outcome of assisted reproduction were equally divided among the two groups by a minimization procedure . The pregnancy rates per cycle were significantly better in the goserelin/HMG group than in the clomiphene citrate/HMG group , both for all procedures of assisted reproduction combined ( 36.8 versus 24.5 % ; P < 0.02 ) and for the main procedure of in-vitro fertilization ( IVF ) ( 37.0 versus 23.5 % ; P < 0.02 ) . Differences in pregnancy rates per oocyte retrieval and per embryo transfer were less pronounced ( 37.8 versus 30.8 % ; P = 0.40 and 44.4 versus 36.8 % ; not significant ) . On the other h and , stimulation with goserelin/HMG was associated with a higher number of ampoules of HMG ( 44.9 versus 9.9 ; P < 0.0001 ) , a longer duration of stimulation ( 11.2 versus 8.7 days ; P < 0.0001 ) and an incidence of ovarian stimulation of 4.5 % ( 7/154 ) versus 0 % in the clomiphene citrate/HMG group . Goserelin was well tolerated and proved to be very reliable as an adjunct of follicular stimulation in assisted reproduction . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE To assess the deleterious effect of clomiphene citrate ( CC ) on the development of the endometrium and its improvement by the addition of ethinyl estradiol ( E2 ) . PARTICIPATING PATIENTS : Infertility-treated patients , monitored for induction of ovulation or timing of insemination ( control group ) . DESIGN We studied four groups of women during an ovulatory cycle with various treatment schedules . Group 1 : untreated patients ; group 2 : patients treated by CC ; group 3 : patients treated by CC + ethinyl E2 ; group 4 : patients treated by human menopausal gonadotropin . Follow-up of the patients was done by vaginal ultrasonography and measurements of blood E2 . RESULTS In the group treated by CC , both endometrial thickness and uterine volume growth during the follicular phase were lower as compared with untreated controls and menotropin-treated patients . The addition of ethinyl E2 to these patients reversed this deleterious effect of CC without interfering with ovulation . CONCLUSION Ethinyl E2 may reverse the deleterious effect of CC on endometrial development during the follicular phase Ovarian stimulation after pituitary suppression with gonadotropin-releasing hormone agonists ( GnRH-a ) has been effective in women who have exhibited a poor response to conventional superovulation strategies . Their effectiveness in unselected women undergoing their first cycle of in vitro fertilization or gamete intrafallopian transfer , however , remains to be established . To address this question , we r and omized 114 women to one of two treatment protocol s. Protocol 1 consisted of 100 mg of clomiphene citrate on days 5 to 9 , followed by 150 IU human menopausal gonadotropin ( hMG ) beginning on day 9 . Protocol 2 consisted of daily GnRH-a beginning in the midluteal phase . Stimulation with 150 IU hMG commenced after pituitary down regulation and ovarian suppression were achieved . Human menopausal gonadotropin was continued in both protocol s until adequate follicular development and serum estradiol concentrations were obtained . Protocol 2 patients reached egg retrieval significantly more often ( 87 % ) than Protocol 1 patients ( 61 % ) , but the mean number of mature eggs retrieved and the pregnancy rate per retrieval were not significantly different between the two groups A prospect i ve r and omized trial was conducted to compare the efficiency of two ovarian stimulation protocol s for in vitro fertilization-embryo transfer or gamete intrafallopian transfer . Protocol 1 consisted of clomiphene citrate and human menopausal gonadotropin ( hMG ) with 55 cycles of 42 patients being evaluated . Protocol 2 had 38 cycles of 34 patients receiving a gonadotropin-releasing hormone agonist ( GnRH-a ) and hMG . The incidence of a spontaneous luteinizing hormone surge was 38.2 % in protocol 1 and 0 % in protocol 2 . Both protocol s had a similar cancellation rate . The total clinical pregnancy rates per oocyte retrieval for patients receiving protocol 1 and protocol 2 were 19.5 % and 10.3 % , respectively . The difference was not statistically significant . Therefore , as first-line ovulation induction agents , it can not be concluded that either protocol demonstrates a clear superiority over the other and further trials of the GnRH-a/hMG combination are indicated BACKGROUND With the recently introduced GnRH antagonists , soft stimulation protocol s on the basis of clomiphene pretreatment should be possible as the pituitary remains fully sensitive at the beginning of the cycle . METHODS A prospect i ve trial was carried out on 107 patients undergoing IVF treatment using the multiple dose GnRH antagonist protocol ( cetrorelix ) , clomiphene citrate , and either HMG ( n = 54 ) or recombinant FSH ( rFSH ) ( n = 53 ) . Different stimulation protocol s were used to find the most appropriate one for clinical application . RESULTS Both treatment groups , HMG and rFSH , yielded comparable results concerning gonadotrophin dose , stimulation days and pregnancy rate . A mean number of 6.34 + /- 4.4 metaphase II oocytes was retrieved and a mean number of 2.45 + /- 0.65 embryos was transferred . However , the overall rate of premature LH surges was 21.5 % ( defined as measurement of LH > 10 IU/l and progesterone > 1 ng/ml ) which is unacceptable for clinical practice . CONCLUSIONS Increasing the daily cetrorelix dose from 0.25 to 0.5 mg might decrease the number of premature LH surges . Soft stimulation protocol s with clomiphene should be used cautiously To establish the usefulness of a new drug regimen in an assisted conception program , a trial was performed comparing clomiphene citrate ( CC ) plus human menopausal gonadotropins ( hMG ) with a new regimen of intranasal luteinizing hormone-releasing hormone ( LH-RH ) analog plus hMG . One hundred two patient cycles received treatment with CC and hMG and 118 patient cycles received treatment with LH-RH analog and hMG . Fifteen percent of cycles were canceled in the CC group and 8 % in the analog group . Four percent of cycles in the CC group were canceled due to premature ovulation . The number of oocytes collected in the analog group was significantly higher than in the CC group ( 8.5 versus 5.5 ) , as was the number of mature oocytes ( 3.5 versus 2.7 ) . However , the percentage of mature oocytes was higher in the CC group ( 54.2 % versus 42.3 % ) . The number of embryos result ing from in vitro fertilization as well as the number of cleaving embryos were significantly higher in the analog group ( 5.2 versus 2.8 and 4.6 versus 2.3 , respectively ) . The pregnancy rate in the analog group was significantly higher than in the CC group ( 30.6 % versus 16.1 % ) , as was the live birth rate ( 21 % versus 8 % ) . Early pregnancy loss was significantly higher in the CC group than in the analog group ( 35 % versus 9 % ) ; and the serum level of LH on the day of human chorionic gonadotropin ( hCG ) administration was also significantly elevated in the CC group when compared with the analog group ( 8.1 versus 4.1 ) . ( ABSTRACT TRUNCATED AT 250 WORDS |
1,891 | 12,492,603 | Collectively they failed to provide strong evidence in favour of homeopathy .
In particular , there was no condition which responds convincingly better to homeopathic treatment than to placebo or other control interventions .
Similarly , there was no homeopathic remedy that was demonstrated to yield clinical effects that are convincingly different from placebo .
It is concluded that the best clinical evidence for homeopathy available to date does not warrant positive recommendations for its use in clinical practice | Homeopathy remains one of the most controversial subjects in therapeutics . | Abstract Objective : To test the hypothesis that homoeopathy is a placebo by examining its effect in patients with allergic rhinitis and so contest the evidence from three previous trials in this series . Design : R and omised , double blind , placebo controlled , parallel group , multicentre study . Setting : Four general practice s and a hospital ear , nose , and throat outpatient department . Participants : 51 patients with perennial allergic rhinitis . Intervention : R and om assignment to an oral 30c homoeopathic preparation of principal inhalant allergen or to placebo . Main outcome measures : Changes from baseline in nasal inspiratory peak flow and symptom visual analogue scale score over third and fourth weeks after r and omisation . Results : Fifty patients completed the study . The homoeopathy group had a significant objective improvement in nasal airflow compared with the placebo group ( mean difference 19.8 l/min , 95 % confidence interval 10.4 to 29.1 , P=0.0001 ) . Both groups reported improvement in symptoms , with patients taking homoeopathy reporting more improvement in all but one of the centres , which had more patients with aggravations . On average no significant difference between the groups was seen on visual analogue scale scores . Initial aggravations of rhinitis symptoms were more common with homoeopathy than placebo ( 7 ( 30 % ) v 2 ( 7 % ) , P=0.04 ) . Addition of these results to those of three previous trials ( n=253 ) showed a mean symptom reduction on visual analogue scores of 28 % ( 10.9 mm ) for homoeopathy compared with 3 % ( 1.1 mm ) for placebo ( 95 % confidence interval 4.2 to 15.4 , P=0.0007 ) . Conclusion : The objective results reinforce earlier evidence that homoeopathic dilutions differ from placebo Little is known about long-term effects of homeopathic treatment . Following a double-blind , placebo controlled trial of classical homeopathy in chronic headaches , we conducted a 1-year observational study of 18 patients following the double-blind phase , and a complete follow-up study of all trial participants . Eighteen patients received free treatment for daily diary data ( frequency , intensity , duration of headaches ) over the course of 1 y. All patients enrolled in the double-blind study were sent a 6-week headache diary , a follow-up question naire , a personality inventory and a complaint list . Eighty-seven , of the original 98 patients enrolled returned question naires , 81 returned diaries . There was no additional change from the end of the trial to the one-year follow-up . The improvement seen at the end of the 12-week trial was stable after 1 y. No differential effects according to treatment after the trial could be seen . Patients with no treatment following the trial had the most improvement after 1 y. Five of 18 patients can be counted responders according to ARIMA analysis of single-case time-series . Patients with double diagnoses and longer treatment duration tended to have clearer improvements than the rest of the patients . Approximately 30 % of patients in homeopathic treatment will benefit after 1 y of treatment . There is no indication of a specific , or of a delayed effect of homeopathy Abstract Objective : To evaluate the efficacy of homoeopathic immunotherapy on lung function and respiratory symptoms in asthmatic people allergic to house dust mite . Design : Double blind r and omised controlled trial . Setting : 38 general practice s in Hampshire and Dorset . Participants : 242 people with asthma and positive results to skin prick test for house dust mite ; 202 completed clinic based assessment s , and 186 completed diary based assessment s. Intervention : After a four week baseline assessment , participants were r and omised to receive oral homoeopathic immunotherapy or placebo and then assessed over 16 weeks with three clinic visits and diary assessment s every other week . Outcome measure : Clinic based assessment s : forced expiratory volume in one second ( FEV1 ) , quality of life , and mood . Diary based assessment s : morning and evening peak expiratory flow , visual analogue scale of severity of asthma , quality of life , and daily mood . Results : There was no difference in most outcomes between placebo and homoeopathic immunotherapy . There was a different pattern of change over the trial for three of the diary assessment s : morning peak expiratory flow ( P=0.025 ) , visual analogue scale ( P=0.017 ) , and mood ( P=0.035 ) . At week three there was significant deterioration for visual analogue scale ( P=0.047 ) and mood ( P=0.013 ) in the homoeopathic immunotherapy group compared with the placebo group . Any improvement in participants ' asthma was independent of belief in complementary medicine . Conclusion : Homoeopathic immunotherapy is not effective in the treatment of patients with asthma . The different patterns of change between homoeopathic immunotherapy and placebo over the course of the study are unexplained BACKGROUND The use of antibiotics in the initial treatment of acute otitis media is currently being question ed . Homeopathy has been used historically to treat this illness , but there have been no method ologically rigorous trials to determine whether there is a positive treatment effect . METHODS A r and omized double blind placebo control pilot study was conducted in a private pediatric practice in Seattle , WA . Seventy-five children ages 18 months to 6 years with middle ear effusion and ear pain and /or fever for no more than 36 h were entered into the study . Children received either an individualized homeopathic medicine or a placebo administered orally three times daily for 5 days , or until symptoms subsided , whichever occurred first . Outcome measures included the number of treatment failures after 5 days , 2 weeks and 6 weeks . Diary symptom scores during the first 3 days and middle ear effusion at 2 and 6 weeks after treatment were also evaluated . RESULTS There were fewer treatment failures in the group receiving homeopathy after 5 days , 2 weeks and 6 weeks , with differences of 11.4 , 18.4 and 19.9 % , respectively , but these differences were not statistically significant . Diary scores showed a significant decrease in symptoms at 24 and 64 h after treatment in favor of homeopathy ( P < 0.05 ) . Sample size calculations indicate that 243 children in each of 2 groups would be needed for significant results , based on 5-day failure rates . CONCLUSIONS These results suggest that a positive treatment effect of homeopathy when compared with placebo in acute otitis media can not be excluded and that a larger study is justified Homeopathy is often advocated as a prophylaxis of migraine and headaches . The aim of this systematic review was to evaluate the clinical trials , testing the efficacy of homeopathy for these indications . Independent computerized literature search es were carried out in 4 data bases . Only r and omized , placebo-controlled trials were included . Four such studies were found . Their method ological quality was variable but , on average , satisfactory . One study suggested that homeopathic remedies were effective . The other , method ologically stronger trials did not support this notion . It is concluded that the trial data available to date do not suggest that homeopathy is effective in the prophylaxis of migraine or headache beyond a placebo effect BACKGROUND Stomatitis is a common consequence of chemotherapy and a condition for which there is little effective treatment . Although the management of patients with other chemotherapy-related toxicities has improved in recent years , the incidence of stomatitis is increasing because of more intensive treatment and is often a dose limiting factor in chemotherapy . The authors assessed the efficacy of a homeopathic remedy , TRAUMEEL S(R ) , in the management of chemotherapy-induced stomatitis in children undergoing bone marrow transplantation . METHODS A r and omized , placebo-controlled , double-blind clinical trial was conducted in 32 patients ages 3 - 25 years who had undergone allogeneic ( 16 patients ) or autologous ( 16 patients ) stem cell transplantation . Of the 30 evaluable patients , 15 were assigned placebo , and 15 were assigned TRAUMEEL S both as a mouth rinse , administered five times daily from 2 days after transplantation for a minimum of 14 days , or until at least 2 days after all signs of stomatitis were absent . Stomatitis scores were evaluated according to the World Health Organization grading system for mucositis . RESULTS A total of five patients ( 33 % ) in the TRAUMEEL S treatment group did not develop stomatitis compared with only one patient ( 7 % ) in the placebo group . Stomatitis worsened in only 7 patients ( 47 % ) in the TRAUMEEL S treatment group compared with 14 patients ( 93 % ) in the placebo group . The mean area under the curve stomatitis scores were 10.4 in the TRAUMEEL S treatment group and 24.3 in the placebo group . This difference was statistically significant ( P < 0.01 ) . CONCLUSIONS This study indicates that TRAUMEEL S may reduce significantly the severity and duration of chemotherapy-induced stomatitis in children undergoing bone marrow transplantation BACKGROUND Recent meta-analyses of r and omized controlled trials in homeopathy have suggested that homeopathy is more than a placebo response . OBJECTIVE Comparison of the effectiveness of homeopathy in primary care with conventional medicine in primary care for three commonly encountered clinical conditions . DESIGN An international multicenter , prospect i ve , observational study in a real world medical setting comparing the effectiveness of homeopathy with conventional medicine . PARTICIPANTS Thirty ( 30 ) investigators with conventional medical licenses at six clinical sites in four countries enrolled 500 consecutive patients with at least one of the following three complaints : ( 1 ) upper respiratory tract complaints including allergies ; ( 2 ) lower respiratory tract complaints including allergies ; or ( 3 ) ear complaints . MAIN OUTCOME MEASURES The primary outcomes criterion was the response to treatment , defined as cured or major improvement after 14 days of treatment . Secondary outcomes criteria were : ( 1 ) rate of recovery ; ( 2 ) occurrence of adverse events ; ( 3 ) patient satisfaction ; and ( 4 ) length of consultation . RESULTS Four hundred and fifty-six ( 456 ) patient visits were compared : 281 received homeopathy , 175 received conventional medicine . The response to treatment as measured by the primary outcomes criterion for patients receiving homeopathy was 82.6 % , for conventional medicine it was 68 % . Improvement in less than 1 day and in 1 to 3 days was noted in 67.3 % of the group receiving homeopathy and in 56.6 % of those receiving conventional medicine . The adverse events for those treated with conventional medicine was 22.3 % versus 7.8 % for those treated with homeopathy . Seventy-nine percent ( 79.0 % ) of patients treated with homeopathy were very satisfied and 65.1 % of patients treated with conventional , medicine were very satisfied . In both treatment groups 60 % of cases had consultations lasting between 5 and 15 minutes . CONCLUSIONS Homeopathy appeared to be at least as effective as conventional medical care in the treatment of patients with the three conditions studied |
1,892 | 27,076,950 | Our study presents the evidence that plaque with ultrasound signal attenuation would induce slow/no reflow phenomenon and distal embolization during PCI , but this appearance has no impact on MACE rates within three years | BACKGROUND Plaques with a large necrotic core or lipid pool and thin-cap fibroatheroma manifest as attenuated plaques on intravascular ultrasound ( IVUS ) .
Their impact on TIMI grade flow and clinical outcomes remains undefined .
We performed a systematic review and meta- analysis to summarize the association between attenuated plaque and distal embolization and clinical outcomes of coronary artery disease ( CAD ) from pooled data of published eligible cohort studies . | Background —The no-reflow phenomenon is associated with poor functional and clinical outcomes for patients with acute myocardial infa rct ion ( AMI ) . In the era of primary intervention , accurately identifying lesions at high risk of no reflow is of crucial importance . At present , no study into the relationship between lesion morphology and no reflow has been performed . The aim of this study was to investigate the relationship between preintervention intravascular ultrasound ( IVUS ) lesion morphology and the no-reflow phenomenon . Methods and Results —This study comprised 100 consecutive patients with AMI who underwent preintervention IVUS and were successfully recanalized with primary balloon angioplasty or stenting . IVUS was again performed to identify and exclude any mechanical vessel obstruction in cases of thrombolysis in myocardial infa rct ion flow grade 0 , 1 , or 2 after intervention in the absence of angiographic stenosis . Angiographic no reflow was seen in 13 patients ( 13 % ) . Univariate analysis indicated that hypercholesterolemia , fissure and dissection , lipid pool – like image , lesion , and reference external elastic membrane cross-sectional area correlate with the no-reflow phenomenon . Multivariate logistic regression analysis showed that lipid pool – like image ( P < 0.05 ; odds ratio 118 ; 95 % CI , 1.28 to 11 008 ) and lesion elastic membrane cross-sectional area ( P < 0.05 ; odds ratio 1.55 ; 95 % CI 1.01 to 2.38 ) are independent predictive factors of no-reflow phenomenon after reperfusion for AMI . Conclusions —Large vessels with lipid pool – like image are at high risk for no reflow after primary intervention for AMI . Also , plaque content may play a role in damage to the microcirculation after primary intervention for AMI OBJECTIVES The aim of this study was to underst and the impact of attenuated plaque on distal embolization during stent implantation in patients with acute myocardial infa rct ion ( AMI ) . BACKGROUND Attenuated plaques identified by grayscale intravascular ultrasound ( IVUS ) might predict transient deterioration in coronary flow and /or no-reflow during percutaneous coronary intervention ( PCI ) . METHODS We analyzed clinical , angiographic , and IVUS data from 364 patients ( n = 364 infa rct -related arteries ) enrolled in the r and omized HORIZONS-AMI ( Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infa rct ion ) trial . No-reflow was final Thrombolysis In Myocardial Infa rct ion ( TIMI ) flow grade ≤2 in the absence of mechanical obstruction . Attenuated plaque was hypoechoic or mixed atheroma with ultrasound attenuation without calcification . A mean attenuation score was created by measuring the angle of attenuation each 1 mm , scoring the angle as 1 to 4 ( corresponding to < 90 ° , 90 ° to 180 ° , 180 ° to 270 ° , or 270 ° to 360 ° , respectively ) , summing the scores , and normalizing for analysis length . RESULTS Overall , 284 ( 78.0 % ) patients had attenuated plaques ; no-reflow occurred in 37 ( 10.2 % ) . Patients with no-reflow had a higher mean attenuation score ( median [ interquartile range ] 2.2 [ 0.0 to 2.8 ] vs. 1.3 [ 0.7 to 1.8 ] , p < 0.001 ) , lower baseline left ventricular ejection fraction ( 52.8 % [ 43.2 % to 61.5 % ] vs. 61.4 % [ 52.2 % to 68.1 % ] , p = 0.002 ) , and more baseline angiographic thrombus ( 89.2 % vs. 74.1 % , p = 0.043 ) with no differences in post-PCI stent expansion versus patients without no-reflow . Multivariate analysis indicated that mean attenuation score was the strongest predictor of no-reflow . The mean attenuation score that best predicted no-reflow was ≥2 points ( 90 ° to 180 ° , sensitivity of 81.5 % , and specificity of 80.5 % ) . CONCLUSIONS Attenuated plaque was present in three-quarters of patients with AMI . The amount of attenuated plaque strongly correlated with no-reflow ; the larger the attenuated plaque , the greater the likelihood of no-reflow . ( Dual Arm Factorial R and omized Trial in Patients w/ST Segment Elevation AMI to Compare the Results of Using Anticoagulation With Either Unfractionated Heparin + Routine GP IIb/IIIa Inhibition or Bivalirudin + Bail-out GP IIb/IIIa Inhibition ; and Primary Angioplasty with stent implantation with Either a Slow Rate-release Paclitaxel-eluting Stent [ TAXUS ™ ] or Uncoated Bare Metal Stent [ EXPRESS2 ™ ] ; NCT00433966 ) OBJECTIVES We aim ed to predict the high-risk plaque of distal embolization after stent deployment in patients with acute ST-segment elevation myocardial infa rct ion ( STEMI ) with Virtual Histology intravascular ultrasound ( VH-IVUS ) ( Volcano Therapeutics , Inc. , Rancho Cordova , California ) . BACKGROUND Distal embolization during primary percutaneous coronary intervention ( PCI ) carries a poor prognosis in patients with STEMI . However , it is unclear which plaque characteristics cause distal embolization after stent deployment . METHODS A total of 71 patients with STEMI were included prospect ively . All patients underwent primary PCI within 12 h of symptom onset . After crossing the lesion with a guidewire and performing thrombectomy with an aspiration catheter , VH-IVUS of the infa rct -related vessel was performed . Stent deployment was then undertaken without embolic protection . ST-segment re-elevation ( STR ) was used to evaluate distal embolization . Correlations among plaque characteristics , morphology , and distal embolization were analyzed . RESULTS The STR after stent deployment was observed in 11 patients ( STR group , 15.5 % ) . Necrotic core volume was significantly higher in the STR group than in the non-STR group ( 32.9 + /- 14.1 mm3 vs. 20.4 + /- 19.1 mm3 , p < 0.05 ) . Total plaque volume was similar in both groups . On receiver-operating characteristic analysis , necrotic core volume clearly predicted STR after stent deployment as compared with fibrous , fibro-lipid , dense calcium , and total plaque volumes . The necrotic core volume that was best predictive for STR was 33.4 mm3 , with a sensitivity of 81.7 % and a specificity of 63.6 % . CONCLUSIONS Virtual Histology IVUS is a useful means of predicting the risk of distal embolization after primary stent deployment in patients with STEMI OBJECTIVES We evaluated the clinical significance of attenuated plaque ( hypoechoic plaque with deep ultrasound attenuation ) . BACKGROUND Attenuated plaques are unusual intravascular ultrasound ( IVUS ) findings in patients with acute coronary syndrome ( ACS ) . METHODS We review ed clinical presentations and angiographic and pre-intervention IVUS findings in 293 ACS patients undergoing percutaneous coronary intervention ( PCI ) without a distal protection device : 187 with non-ST-segment elevation myocardial infa rct ion ( NSTEMI ) and 106 with ST-segment elevation myocardial infa rct ion ( STEMI ) . RESULTS Attenuated plaque was observed in 75 patients ( 25.6 % ) : 39.6 % of STEMI versus 17.6 % of NSTEMI ( p < 0.001 ) . ( We also review ed 100 r and omly selected patients with stable angina and pre-intervention IVUS ; none had attenuated plaque . ) Overall , in ACS patients with attenuated plaques : 1 ) the level of C-reactive protein was higher ; 2 ) angiographic thrombus and initial coronary flow Thrombolysis In Myocardial Infa rct ion flow grade < 2 were more common ; and 3 ) IVUS lesion site plaque burden and remodeling index were significantly greater , lesion site luminal dimensions significantly smaller , and thrombus , positive remodeling , and plaque rupture were more common . No-reflow ( 26.7 % vs. 4.6 % , p < 0.001 ) and deteriorated post-PCI coronary blood flow ( 8.0 % vs. 2.8 % , p = 0.001 ) were higher . In ACS patients with normal coronary blood flow at baseline , deterioration in the coronary blood flow post-PCI was more common in lesions with attenuated plaque . CONCLUSIONS Attenuated plaque was more common in ACS patients with STEMI than NSTEMI . Attenuated plaque in ACS patients was associated with a higher C-reactive protein level , more severe and complex lesion morphology , reduced coronary blood flow before PCI , and especially no-reflow after PCI BACKGROUND Atherosclerotic plaques that lead to acute coronary syndromes often occur at sites of angiographically mild coronary-artery stenosis . Lesion-related risk factors for such events are poorly understood . METHODS In a prospect i ve study , 697 patients with acute coronary syndromes underwent three-vessel coronary angiography and gray-scale and radiofrequency intravascular ultrasonographic imaging after percutaneous coronary intervention . Subsequent major adverse cardiovascular events ( death from cardiac causes , cardiac arrest , myocardial infa rct ion , or rehospitalization due to unstable or progressive angina ) were adjudicated to be related to either originally treated ( culprit ) lesions or untreated ( nonculprit ) lesions . The median follow-up period was 3.4 years . RESULTS The 3-year cumulative rate of major adverse cardiovascular events was 20.4 % . Events were adjudicated to be related to culprit lesions in 12.9 % of patients and to nonculprit lesions in 11.6 % . Most nonculprit lesions responsible for follow-up events were angiographically mild at baseline ( mean [ ±SD ] diameter stenosis , 32.3±20.6 % ) . However , on multivariate analysis , nonculprit lesions associated with recurrent events were more likely than those not associated with recurrent events to be characterized by a plaque burden of 70 % or greater ( hazard ratio , 5.03 ; 95 % confidence interval [ CI ] , 2.51 to 10.11 ; P<0.001 ) or a minimal luminal area of 4.0 mm(2 ) or less ( hazard ratio , 3.21 ; 95 % CI , 1.61 to 6.42 ; P=0.001 ) or to be classified on the basis of radiofrequency intravascular ultrasonography as thin-cap fibroatheromas ( hazard ratio , 3.35 ; 95 % CI , 1.77 to 6.36 ; P<0.001 ) . CONCLUSIONS In patients who presented with an acute coronary syndrome and underwent percutaneous coronary intervention , major adverse cardiovascular events occurring during follow-up were equally attributable to recurrence at the site of culprit lesions and to nonculprit lesions . Although nonculprit lesions that were responsible for unanticipated events were frequently angiographically mild , most were thin-cap fibroatheromas or were characterized by a large plaque burden , a small luminal area , or some combination of these characteristics , as determined by gray-scale and radiofrequency intravascular ultrasonography . ( Funded by Abbott Vascular and Volcano ; Clinical Trials.gov number , NCT00180466 . ) OBJECTIVES We investigated attenuated plaque ( hypoechoic plaque with deep ultrasonic attenuation despite absence of bright calcium ) in nonculprit lesions . BACKGROUND Recent intravascular ultrasound ( IVUS ) studies describe acoustic shadowing behind large , echolucent , acute culprit lesion sites in the absence of bright calcium . Such " attenuated plaque " is considered a characteristic of high-risk lesions , but its prevalence in stable nonculprit lesions is incompletely known . METHODS We review ed IVUS pullback data from nonculprit vessels in 159 patients from the ASTEROID ( A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden ) trial . We identified attenuated plaque and compared volumetric IVUS data in the segments with and without attenuation . In addition , we described plaque morphology in segments with attenuation at baseline and follow-up . RESULTS Attenuated plaque was found in 17 of 159 patients ( 10.7 % , 95 % confidence interval : 6 % to 17 % ) . At baseline , there were no significant differences in clinical presentation and cardiovascular risk factors between patients with and without attenuation . Other than a greater plaque eccentricity index ( p = 0.008 ) , there were no significant differences between segments with and without attenuation . In segments with attenuated plaque , expansive remodeling was observed in 53 % , and calcified plaque adjacent to the attenuation site in 70 % of patients . During follow-up , attenuation remained stable , and no events occurred in the patients with attenuation . CONCLUSIONS Attenuated plaque is present in a significant number of nonculprit segments in patients enrolled in IVUS progression trials and remains stable during follow-up . There is a relationship with mixed calcified lesions . These findings challenge the prior assumption that attenuated plaque is a finding limited to culprit lesions associated with acute clinical presentation |
1,893 | 23,881,731 | The median SMDs indicate that mass media interventions may have a small to medium effect in decreasing prejudice , and are equivalent to reducing the level of prejudice from that associated with schizophrenia to that associated with major depression .
AUTHORS ' CONCLUSIONS Mass media interventions may reduce prejudice , but there is insufficient evidence to determine their effects on discrimination . | BACKGROUND Mental health-related stigma is widespread and has major adverse effects on the lives of people with mental health problems .
Its two major components are discrimination ( being treated unfairly ) and prejudice ( stigmatising attitudes ) .
Anti-stigma initiatives often include mass media interventions , and such interventions can be expensive .
It is important to know if mass media interventions are effective .
OBJECTIVES To assess the effects of mass media interventions on reducing stigma ( discrimination and prejudice ) related to mental ill health compared to inactive controls , and to make comparisons of effectiveness based on the nature of the intervention ( e.g. number of mass media components ) , the content of the intervention ( e.g. type of primary message ) , and the type of media ( e.g. print , internet ) . | This study examined how two types of public education programs influenced how the public perceived persons with mental illness , their potential for violence , and the stigma of mental illness . A total of 161 participants were r and omly assigned to one of three programs : one that aim ed to combat stigma , one that highlighted the association between violence and psychiatric disorders , and a control group . Participants who completed the education-about-violence program were significantly more likely to report attitudes related to fear and dangerousness , to endorse services that coerced persons into treatment and treated them in segregated areas , to avoid persons with mental illness in social situations , and to be reluctant to help persons with mental illness Background : Studies regarding the effectiveness of CME programmes on physicians ’ behaviour and communication skills showed inconsistent results . Few r and omized controlled trials have been conducted in Asia . Methods : To evaluate the effectiveness of a 4 2-hour education programme to improve GP interviewing behaviours , 16 general practitioners were r and omized to the intervention and control groups , respectively . Physicians assigned to the intervention group received 8 hours of training emphasizing interviewing behaviours in the diagnosis and treatment of depression and generalized anxiety disorders ( GDS ) . Those assigned to the control group did not receive any training until the completion of study . St and ardized patients were used to evaluate the performance of physicians . Two consultations before and after enrolling in the education programme were videotaped . Independent evaluations of consultations were made by a trained clinical psychologist and a social worker blinded to the study status of physicians . The rating schedule for the videotapes was based on the tasks listed on the Calgary Cambridge Observation Guide . Results : The change of score between the intervention and control physicians was significantly different in ‘ active listening and facilitating patients ’ response ’ ( p = 0.011 ) with the intervention physicians having improvement of score . For ‘ non-verbals ’ , ‘ underst and ing patient 's perspective ’ and ‘ negotiating mutual plan of action ’ , positive change of score in the intervention physicians were seen when compared to that of the control , although the difference did not reach statistical significance ( p = 0.06 , p = 0.05 , p = 0.06 , respectively ) . However , for ‘ opening ’ , ‘ structuring the consultation ’ , ‘ explanation and planning ’ and ‘ closure ’ , there were no statistical significant differences between control and intervention group . Conclusions : Our results showed that only certain communication skills , such as active listening and facilitating patient 's response , can be taught in the management of depression and generalized anxiety disorder ( GAD ) in Chinese primary care physicians This study examines the personal and attitudinal variables that are associated with helping behavior in a hypothetical general practice setting . We explored the effect of an antistigma seminar during a psychiatric clerkship on medical students ’ attitudes toward the mentally ill . We r and omly assigned three rotations of students ( 81 students ) to receive the seminar and three rotations ( 85 students ) as controls . The students expressed views about patients with schizophrenia or depressive disorder portrayed in video vignettes . How dangerous the students perceived target individuals to be was the major determinant of helping behavior . The students ’ gender , religious affiliation , affective reaction , skill assessment , and controllability attribution were less consistent in predicting behavior . Exposure to the seminar and clerkship experience significantly improved attitudes , but attributes of responsibility and readiness to provide medical care for psychiatric patients were the most resistant to change . We identified certain issues that should be highlighted in future antistigma programs Stigmatizing , or discriminatory , perspectives and behaviour , which target individuals on the basis of their mental health , are observed in even the youngest school children . We conducted a systematic review of the published and unpublished , scientific literature concerning the benefits and harms of school-based interventions , which were directed at students 18 years of age or younger to prevent or eliminate such stigmatization . Forty relevant studies were identified , yet only a qualitative synthesis was deemed appropriate . Five limitations within the evidence base constituted barriers to drawing conclusive inferences about the effectiveness and harms of school-based interventions : poor reporting quality , a dearth of r and omized controlled trial evidence , poor methods quality for all research design s , considerable clinical heterogeneity , and inconsistent or null results . Nevertheless , certain suggestive evidence derived both from within and beyond our evidence base has allowed us to recommend the development , implementation and evaluation of a curriculum , which fosters the development of empathy and , in turn , an orientation toward social inclusion and inclusiveness . These effects may be achieved largely by bringing especially but not exclusively the youngest children into direct , structured contact with an infant , and likely only the oldest children and youth into direct contact with individuals experiencing mental health difficulties . The possible value of using educational activities , material s and contents to enhance hypothesized benefits accruing to direct contact also requires investigation . Overall , the curriculum might serve as primary prevention for some students and as secondary prevention for others Background A Mental Health First Aid course has been developed which trains members of the public in how to give initial help in mental health crisis situations and to support people developing mental health problems . This course has previously been evaluated in a r and omized controlled trial in a workplace setting and found to produce a number of positive effects . However , this was an efficacy trial under relatively ideal conditions . Here we report the results of an effectiveness trial in which the course is given under more typical conditions . Methods The course was taught to members of the public in a large rural area in Australia by staff of an area health service . The 16 Local Government Areas that made up the area were grouped into pairs matched for size , geography and socio-economic level . One of each Local Government Area pair was r and omised to receive immediate training while one served as a wait-list control . There were 753 participants in the trial : 416 in the 8 trained areas and 337 in the 8 control areas . Outcomes measured before the course started and 4 months after it ended were knowledge of mental disorders , confidence in providing help , actual help provided , and social distance towards people with mental disorders . The data were analysed taking account of the clustered design and using an intention-to-treat approach . Results Training was found to produce significantly greater recognition of the disorders , increased agreement with health professionals about which interventions are likely to be helpful , decreased social distance , increased confidence in providing help to others , and an increase in help actually provided . There was no change in the number of people with mental health problems that trainees had contact with nor in the percentage advising someone to seek professional help . Conclusions Mental Health First Aid training produces positive changes in knowledge , attitudes and behaviour when the course is given to members of the public by instructors from the local health service BACKGROUND AND OBJECTIVES Although many studies have investigated the impact of causal models on public attitudes toward people with psychosis , the effect of causal models on patients with psychosis is unclear . Clinicians must therefore decide about providing causal information without knowing how it will impact on patient and treatment . This study investigates the effect of causal models on different aspects of treatment motivation . METHODS In an experimental online study healthy individuals ( n = 461 ) were instructed to imagine experiencing psychotic symptoms and seeking professional help . The imagination was supported by an audio play cover story . Subsequently , participants were r and omized to four conditions differing in the content of the causal model given for the occurring symptoms ( biological , psychological , combined and no causal explanation ) . RESULTS Different causal models impacted on different aspects of treatment motivation : Participants who had received a biological causal model showed high willingness to take medication , whereas participants who had received a psychological model reported high perceived personal control over symptoms . Participants who had received a causal model that combined biological and psychological aspects reported high acceptance of medication and high motivation to undergo treatment by this clinician . CONCLUSIONS The results underline the impact the content of a causal model may have on patients ' treatment motivation and - as a consequence - on treatment success . Overall , the integration of psychological and biological aspects within a causal model seems most promising in terms of adherence to various types of treatment This study attempted to determine the effects of a direct-mail campaign on the attitudes of managers and presidents of industries toward the mentally retarded . The participants in the study were 99 managers and presidents selected from a total population of 4290 within the State of Alabama , USA . R and om sampling techniques were utilized to select and assign managers and presidents into an experimental group ( n = 50 ) and a control group ( n = 49 ) , giving a total usable sample size of 99 . The size of this sample was adequate to insure that , in 19 out of 20 cases , the sample mean was within 0.50 points of the population mean on the response scale according to Elliot ( 1980 ) . The pre-test of the attitude scale was administered to the experimental and control groups by mail . A post-test was administered to the control and experimental groups one week after the mailing of the final pamphlet . The major finding of this study revealed positive attitude gains from pre-test to post-test for the experimental group following the direct-mail campaign . No significant difference was noted for the control group from pre-test and post-test . Pre-test scores of the experimental and control groups were not significantly different ; however , post-test scores between these groups were significantly different . The results of this research contribute further information on a direct-mail approach for changing attitudes of managers and presidents of industries toward mentally retarded persons OBJECTIVES The authors used nationwide survey data to characterize current public conceptions related to recognition of mental illness and perceived causes , dangerousness , and desired social distance . METHODS Data were derived from a vignette experiment included in the 1996 General Social Survey . Respondents ( n = 1444 ) were r and omly assigned to 1 of 5 vignette conditions . Four vignettes described psychiatric disorders meeting diagnostic criteria , and the fifth depicted a " troubled person " with sub clinical problems and worries . RESULTS Results indicate that the majority of the public identifies schizophrenia ( 88 % ) and major depression ( 69 % ) as mental illnesses and that most report multicausal explanations combining stressful circumstances with biologic and genetic factors . Results also show , however , that smaller proportions associate alcohol ( 49 % ) or drug ( 44 % ) abuse with mental illness and that symptoms of mental illness remain strongly connected with public fears about potential violence and with a desire for limited social interaction . CONCLUSIONS While there is reason for optimism in the public 's recognition of mental illness and causal attributions , a strong stereotype of dangerousness and desire for social distance persist . These latter conceptions are likely to negatively affect people with mental illness Authors examined the combined effects of descriptive and explanatory information on peers ' perceptions and behavioral intentions toward an unfamiliar child with autism . Children ( N = 576 ; M age = 10.06 ) were r and omly assigned to view two videotapes of a boy engaging in typical and autistic behaviors receiving either descriptive ( AUT-D ) or descriptive and explanatory information ( AUT-D + E ) . Children responded to measures of attitudes ( Adjective Checklist ) and behavioral intentions ( Shared Activities Question naire ) . Children rated the typical boy more favorably than the boy showing autistic symptoms . When compared to descriptive information alone , the combination of descriptive and explanatory information result ed in improved third- and fourth- grade rs ' but not fifth- grade rs ' attitudes toward the child with autism . Combined information improved behavioral intentions across grade s ; however , girls ( vs. boys ) were more responsive to information as evidence d by differences in academic intentions . The combination of descriptive and explanatory information about autism appears to have a positive effect on children 's attitudes and behavioral intentions . Implication s of the findings are briefly discussed as well as study limitations and recommendations for future research BACKGROUND Direct social contact interventions are known to reduce mental health stigma . Filmed social contact may be equally effective and have practical and cost advantages . AIMS To compare the effectiveness of a DVD , a live intervention and a lecture control , in reducing stigma , testing the hypotheses that : ( a ) DVD and live interventions will be equally effective ; and ( b ) the interventions with social contact ( DVD/live ) will be more effective than the lecture . Cost-effectiveness , process and acceptability are also assessed . METHOD Student nurses were r and omised to : ( a ) watch a DVD of service users/informal carers talking about their experiences , ( b ) watch a similar live presentation , or ( c ) attend a lecture . Primary outcomes were changes in attitudes ( using the Mental Illness : Clinicians Attitudes Scale , MICA ) , emotional reactions ( using the Emotional Reactions to Mental Illness Scale , ERMIS ) , intended proximity ( using the Reported and Intended Behaviour Scale , RIBS ) , and knowledge ( using the Social Contact Intended Learning Outcomes , SCILO ) , immediately after the intervention and at 4-month follow-up . RESULTS For the 216 participants , there were no differences between the DVD and live groups on MICA , ERMIS or RIBS scores . The DVD group had higher SCILO ( knowledge ) scores . The combined social contact group ( DVD/live ) had better MICA and RIBS scores than the lecture group , the latter difference maintained at 4 months . The DVD was the most cost-effective of the interventions , and the live session the most popular . CONCLUSIONS Our hypotheses were confirmed . This study supports the wider use of filmed social contact interventions to reduce stigma about mental illness The issue of suicide warning signs on the Internet is considered . In addition to review ing some of the relevant conceptual issues about warning signs , a r and om sample of Internet sites was selected and review ed . Warning signs were grouped and agreement across sites was examined , with results confirming broad disparity in what is presented to the public . The implication s of a lack of consensus on warning signs for suicide are discussed Acceptance and commitment therapy ( ACT ) has previously been shown to alter stigmatizing attitudes and to be relatively useful for psychologically inflexible participants . The present study is the first to bring those two findings together by comparing ACT to an education intervention for reducing stigma toward people with psychological disorders , and examining whether results differ for psychologically inflexible versus flexible individuals . A sample of college students ( N = 95 ) was r and omly assigned to a 2(1)2h ACT or educational workshop . Measures were taken before and after the workshop and at a 1-month follow-up . ACT reduced mental health stigma significantly regardless of participants ' pre-treatment levels of psychological flexibility , but education reduced stigma only among participants who were relatively flexible and non-avoidant to begin with . Acceptance could be an important avenue of exploration for stigma research ers Existing literature shows that the level of biological attribution and stigma of depression influences willingness to seek help . However , no study has used experimental methods to explore the question whether increasing biological attribution and decreasing blameworthy attitude towards depression will enhance willingness to seek help . In so doing , 299 college students were r and omly assigned to biological , destigmatization , combined , and control groups . The measures included the Biological Attribution Scale , Psychological Blame Scale , and Help-Seeking Willingness Scale . The data were analyzed by a 2 x 2 ancova ( with or without biological attribution education x with or without destigmatization education ) on willingness to seek professional help which was assessed 2 weeks later , with adjusting for help-seeking willingness at baseline . Results showed that biological education had a significant main effect to elevate help-seeking willingness , but destigmatization education did not . In addition , no interaction effect existed between the two independent variables . The authors suggested that biological education makes people legitimize depression as a disease entity , so that it would be a practical approach to increase people 's motivation to solve their emotional afflictions , especially in societies that emphasize emotional constraints . In contrast , although destigmatization information reduces people 's negative appraisal s to the depressed individuals , it does not go a step further to increase people 's motivation to seek professional help . Further studies are needed to clarify the mechanisms of educational effects Systematic review s provide the best evidence on the effectiveness of healthcare interventions including quality improvement strategies . The methods of systematic review of individual patient r and omised trials of healthcare interventions are well developed . We discuss method ological and practice issues that need to be considered when undertaking systematic review s of quality improvement strategies including developing a review protocol , identifying and screening evidence sources , quality assessment and data abstract ion , analytical methods , reporting systematic review s , and appraising systematic review s. This paper builds on our experiences within the Cochrane Effective Practice and Organisation of Care ( EPOC ) review group Objective : To evaluate the effectiveness of a web-based multimedia health promotion program for the workplace , design ed to help reduce stress and to prevent depression , anxiety , and substance abuse . Methods : Using a r and omized controlled trial design , 309 working adults were r and omly assigned to the web-based condition or to a wait-list control condition . All participants were assessed on multiple self-reported outcomes at pretest and posttest . Results : Relative to controls , the web-based group reduced their stress , increased their knowledge of depression and anxiety , developed more positive attitudes toward treatment , and adopted a more healthy approach to alcohol consumption . Conclusions : We found that a brief and easily adaptable web-based stress management program can simultaneously reduce worker stress and address stigmatized behavioral health problems by embedding this prevention material into a more positive stress management framework This study examined children 's ratings of attitudes and behavioral intentions toward a peer presented with or without autistic behaviors . The impact of information about autism on these ratings was investigated as well as age and gender effects . Third- and sixth- grade children ( N = 233 ) were r and omly assigned to view a video of the same boy in one of three conditions : No Autism , Autism , or Autism/Information . Children at both grade levels showed less positive attitudes toward the child in the two autism conditions . In rating their own behavioral intentions , children showed no differences between conditions . However , in attributing intentions to their classmates , older children and girls gave lower ratings to the child in the autism conditions . Information about autism did not affect ratings of either attitudes or behavioral intentions as ascribed to self or others AIM To describe the development of the Mental Health First Aid ( MHFA ) programme in Australia , its roll-out in other countries and evaluation studies which have been carried out . METHODS A description of the programme 's development and evaluation , its cultural adaptations and its dissemination in seven countries . RESULTS The programme was developed in Australia in 2001 . By the end of 2007 , there were 600 instructors and 55,000 people trained as mental health first aiders . A number of evaluations have been carried out , including two r and omized controlled trials that showed changes in knowledge , attitudes and first aid behaviours . Special adaptations of the course have been rolled out for Aboriginal and Torres Strait Isl and er peoples and some non-English speaking immigrant groups . The course has spread to seven other countries with varying degrees of penetration . In all countries , the programme has been initially supported by government funding . Independent evaluations have been carried out in Scotl and and Irel and . CONCLUSIONS The concept of first aid by the public for physical health crises is familiar in many countries . This has made it relatively easy to extend this approach to early intervention by members of the public for mental disorders and crises . Through MHFA training , the whole of a community can assist formal mental health services in early intervention for mental disorders In this study , the authors evaluated the effectiveness of a video , developed for this study and using principles of cognitive learning theory , to produce positive attitudinal change toward mental health treatment . The participants were 35 men and 45 women who were r and omly assigned to watch either an experimental video , which included 3 positive 1st-person accounts of psychotherapy or a control video that focused on the psychological construct of self . Pre-intervention , post-intervention , and 2-week follow-up levels of attitude toward mental health treatment were measured using the Attitude Toward Seeking Professional Help Scale ( E. H. Fischer and J. L. Turner , 1970 ) . The experimental video group showed a significantly greater increase in positive attitude than did the control group . These results support the effectiveness of using the vicarious reinforcement elements of cognitive learning theory as a basis for changing attitudes toward mental health treatment PURPOSE To evaluate the acceptability , feasibility , and effectiveness of a population -based intervention to promote health of youth ( age : 16 - 24 years ) in Goa . METHODS Two pairs of urban and rural communities were selected ; one of each was r and omly assigned to receive a multi-component intervention and the other wait-listed . The intervention comprised educational institution-based peer education and teacher training ( in the urban community ) , community peer education , and health information material s. Effectiveness was assessed through before-after population surveys at baseline and at 18 months . Outcomes were measured using a structured interview schedule with all eligible youth . Logistic regression compared each pair , adjusted for baseline differences , on prevalence of outcomes in the domains of reproductive and sexual health ( RSH ) , violence , mental health , substance use , and help seeking for health concerns . RESULTS In both intervention communities , prevalence of violence perpetrated and probable depression was significantly lower and knowledge and attitudes about RSH significantly higher ( p < .05 ) . The rural sample also reported fewer menstrual complaints and higher levels of help-seeking for RSH complaints by women , and knowledge and attitudes about emotional health and substance use ; and , the urban sample reported significantly lower levels of substance use , suicidal behavior , sexual abuse , and RSH complaints . Although information material s were acceptable and feasible in both communities , community peer education was feasible only in the rural community . The institution-based interventions were generally acceptable and feasible . CONCLUSIONS Multicomponent interventions comprising information material s , educational-institution interventions and , in rural context s , community peer interventions are acceptable and feasible and likely to be effective for youth health promotion Background The Mental Health First Aid training course was favorably evaluated in an uncontrolled trial in 2002 showing improvements in participants ' mental health literacy , including knowledge , stigmatizing attitudes , confidence and help provided to others . This article reports the first r and omized controlled trial of this course . Methods Data are reported on 301 participants r and omized to either participate immediately in a course or to be wait-listed for 5 months before undertaking the training . The participants were employees in two large government departments in Canberra , Australia , where the courses were conducted during participants ' work time . Data were analyzed according to an intention-to-treat approach . Results The trial found a number of benefits from this training course , including greater confidence in providing help to others , greater likelihood of advising people to seek professional help , improved concordance with health professionals about treatments , and decreased stigmatizing attitudes . An additional unexpected but exciting finding was an improvement in the mental health of the participants themselves . Conclusions The Mental Health First Aid training has shown itself to be not only an effective way to improve participants ' mental health literacy but also to improve their own mental health . It is a course that has high applicability across the community Background Mental disorders often have their first onset during adolescence . For this reason , high school teachers are in a good position to provide initial assistance to students who are developing mental health problems . To improve the skills of teachers in this area , a Mental Health First Aid training course was modified to be suitable for high school teachers and evaluated in a cluster r and omized trial . Methods The trial was carried out with teachers in South Australian high schools . Teachers at 7 schools received training and those at another 7 were wait-listed for future training . The effects of the training on teachers were evaluated using question naires pre- and post-training and at 6 months follow-up . The question naires assessed mental health knowledge , stigmatizing attitudes , confidence in providing help to others , help actually provided , school policy and procedures , and teacher mental health . The indirect effects on students were evaluated using question naires at pre-training and at follow-up which assessed any mental health help and information received from school staff , and also the mental health of the student . Results The training increased teachers ' knowledge , changed beliefs about treatment to be more like those of mental health professionals , reduced some aspects of stigma , and increased confidence in providing help to students and colleagues . There was an indirect effect on students , who reported receiving more mental health information from school staff . Most of the changes found were sustained 6 months after training . However , no effects were found on teachers ' individual support towards students with mental health problems or on student mental health . Conclusions Mental Health First Aid training has positive effects on teachers ' mental health knowledge , attitudes , confidence and some aspects of their behaviour . Trial registration This study examined whether viewing a documentary that depicts individuals with schizophrenia can reduce psychiatric stigma . One hundred and sixty-three individuals were r and omly assigned to one of four conditions : no documentary film , documentary about polar bears , documentary about fears of being overweight , and documentary about schizophrenia . Participants also completed a battery of tasks assessing attitudes toward persons with schizophrenia , attributions about the disorder , and intentions to interact with individuals with schizophrenia . The findings showed that compared to the other experimental conditions , the documentary about schizophrenia result ed in more benign attributions about schizophrenia ( e.g. , less likely to blame individuals with schizophrenia for the disorder ) but did not change general attitudes about schizophrenia ( e.g. , perceived dangerousness ) . The film also did not increase participants ' intentions to interact with persons with schizophrenia . These findings could not be attributed to mood changes associated with the film or how much participants liked the film . The findings provide partial support for the hypothesis that a media depiction of persons with schizophrenia can reduce stigma Examined children 's ratings of attitudes and behavioral intentions toward a boy presented , on videotape , with or without symptoms of Tourette syndrome ( TS ) . Effects of information about TS on these ratings were investigated as well as the influence of gender and grade . Children in Grade s 3 and 5 were r and omly assigned to one of three conditions : No TS , TS , or TS/information . On the attitude measure , children rated the peer presented with TS less positively than they did the peer presented without TS . On behavioral intention measures , no significant differences were found between conditions . Information about TS did not affect ratings . Implication s of these findings as well as limitations of the study are discussed Background Early detection and treatment of mental disorders in adolescents and young adults can lead to better health outcomes . Mental health literacy is a key to early recognition and help seeking . Whilst a number of population health initiatives have attempted to improve mental health literacy , none to date have specifically targeted young people nor have they applied the rigorous st and ards of population health models now accepted as best practice in other health areas . This paper describes the outcomes from the application of a health promotion model to the development , implementation and evaluation of a community awareness campaign design ed to improve mental health literacy and early help seeking amongst young people . Method The Compass Strategy was implemented in the western metropolitan Melbourne and Barwon regions of Victoria , Australia . The Precede-Proceed Model guided the population assessment , campaign strategy development and evaluation . The campaign included the use of multimedia , a website , and an information telephone service . Multiple levels of evaluation were conducted . This included a cross-sectional telephone survey of mental health literacy undertaken before and after 14 months of the campaign using a quasi-experimental design . R and omly selected independent sample s of 600 young people aged 12–25 years from the experimental region and another 600 from a comparison region were interviewed at each time point . A series of binary logistic regression analyses were used to measure the association between a range of campaign outcome variables and the predictor variables of region and time . Results The program was judged to have an impact on the following variables , as indicated by significant region-by-time interaction effects ( p < 0.05 ) : awareness of mental health campaigns , self-identified depression , help for depression sought in the previous year , correct estimate of prevalence of mental health problems , increased awareness of suicide risk , and a reduction in perceived barriers to help seeking . These effects may be underestimated because media distribution error result ed in a small amount of print material " leaking " into the comparison region . Conclusion We believe this is the first study to apply the rigorous st and ards of a health promotion model including the use of a control region to a mental health population intervention . The program achieved many of its aims despite the relatively short duration and moderate intensity of the campaign ABSTRACT This study examines the impact of two versions of anti-stigma programs — education and contact — presented on videotape . A total of 244 people were r and omly assigned to education or contact conditions and completed pre-test , post-test , and follow-up measures of stereotypes . Results suggest that the education videotape had limited effects , mostly showing improvement in responsibility ( people with mental illness are not to blame for their symptoms and disabilities ) . Watching the contact videotaped showed significant improvement in pity , empowerment , coercion , and segregation . Contact effects were evident at post-test and 1 week follow-up . Implication s of these findings for future research are discussed A r and omized , blinded , multicenter , controlled study was undertaken to assess the impact of a multiyear continuing medical education ( CME ) initiative on physician knowledge and behavior in the treatment of erectile dysfunction ( ED ) . The objective of this study was to assess the efficacy of CME and compare applied knowledge and attitude scores of participants in the Consortium for Improvement in Erectile Function ( CIEF ) , to non-CIEF participants . Subjects were selected r and omly and contacted anonymously , by mail , email and fax and requested to enroll in this study . A blinded , vali date d question naire and series of st and ardized patient ( SP ) case studies and attitude questions were given to CIEF participants , defined as those who showed an interest in learning more about ED and who took at least one CME-certified program on ED from the CIEF website and non-CIEF participants , defined as those who showed interest in learning more about ED and who took at least one CME-certified program on ED from any organization other than CIEF . The primary outcome was a comparison of subjects ' scores who participated in at least one CIEF program to non- participants in CIEF programs . Subjects were also compared based on SP case scores , attitude scores , specialty , years in practice , age and gender . Answers were ranked from best to worst and assigned a corresponding value of 10 … 3 , 2 , 1 and 0 ( 10 being the best ) , assuming that there may be more than one correct answer to each question in clinical practice . SAS version 9.1 analysis of variance model was used by an independent consultant . A total of 120 physicians completed the question naire : 87 urologists ( UROs ) and 33 primary care physicians ( PCPs ) . UROs scored higher on SP cases compared with PCPs ( P=0.0039 ) ; however , as a result of participating in CIEF programs , PCPs trended toward more comparable scores to UROs ; P=0.23 for SP case 2 that was clinical ly less complex and P=0.19 for SP case 3 that was more complex . In the other two cases , the gap was reduced ; however , UROs scored better than PCPs . PCPs in CIEF ( n=23 ) had significantly higher SP case scores compared with non-CIEF PCPs ( n=10 ) ; 216.6 vs 191.0 , respectively ( P=0.0437 ) . PCPs in CIEF also showed a significantly greater level in mean attitude scores compared with UROs , 10.82 vs 8.15 , respectively ( P<0.0001 ) . Both PCPs and UROs scored higher after participating in CIEF ED educational programs than those clinicians who participated in non-CIEF ED educational programs . In addition , clinicians participating in more CIEF programs scored higher than those participating in fewer CIEF programs . As expected , UROs consistently scored better than PCPs , indicating a higher baseline level of knowledge base about ED . However , this educational gap was significantly reduced in PCPs who participated in CIEF programs . The study demonstrated that PCPs who took more CIEF courses were almost as knowledgeable as UROs on the subject of ED . Longitudinal , disease-specific CME initiatives are valuable in that they positively impact the knowledge and thus the behavior of participating physicians , potentially conferring clinical benefits toward patient outcomes BACKGROUND Mental Health Nurses working in secure environments with patients suffering from serious mental illness have been shown to be at risk of clinical burnout syndrome , this can have adverse effects both on the nurses ' health and the st and ards of care that they deliver . AIM To evaluate the effect of Psychosocial Intervention Training ( PSI ) on the knowledge , attitudes and levels of clinical burnout in a group of forensic mental health nurses . DESIGN Baseline assessment s of knowledge , attitude and burnout were completed by asking a group of 33 nurses working in a medium secure psychiatric unit to complete question naires . Twenty of the nurses volunteered to be included in a PSI training course and were r and omly allocated either to receive the training or to a waiting list control group . The duration of the training was 6 months and on completion subjects in the experimental and control group completed the question naires again . RESULTS Staff in the experimental group showed significant improvements in their knowledge and attitudes about serious mental illness and a significant decrease in burnout rates , whilst staff in the control group showed a small but nonsignificant improvement in knowledge and attitudes , and increase in burnout . CONCLUSION The findings suggest that providing forensic mental health nurses with a better underst and ing of serious mental illness and training them in a broader range of interventions , helps them to be more positive in their attitudes towards the clients that they work with and experience less negative effects of stress result ing from their caring role . The implication s of this study for clinical practice and future research will be discussed OBJECTIVE We design ed our study to assess if computer-assisted anti-stigma interventions can be effective in reducing the level of psychiatric stigma in a sample of special education university students . METHODS We enrolled 193 graduate students . They had two study visits with an interval of 6 months . The participants were r and omly distributed into three study groups : 76 students read anti-stigma printed material s ( reading group , RG ) , and 69 studied an anti-stigma computer program ( program group , PG ) , and 48 students were in a control group ( CG ) and received no intervention . We used the Bogardus scale of social distance ( BSSD ) , the community attitudes toward the mentally ill ( CAMI ) question naire , and the psychiatric knowledge survey ( PKS ) as the main outcome measures . RESULTS After the intervention BSSD , CAMI and PKS scores significantly improved both in RG and PG . After 6 months in RG two out of three CAMI subscales and PKS scores were not different from the baseline . In PG all stigma and knowledge changes remained significant . CONCLUSIONS This study demonstrated that computers can be an effective mean in changing attitudes of students toward psychiatric patients . PRACTICE IMPLICATION S A computer-mediated intervention has the potential for educating graduate students about mental disease and for reducing psychiatric stigma BACKGROUND Little is known about the efficacy of educational interventions for reducing the stigma associated with depression . AIMS To investigate the effects on stigma of two internet depression sites . METHOD A sample of 525 individuals with elevated scores on a depression assessment scale were r and omly allocated to a depression information website ( BluePages ) , a cognitive-behavioural skills training website ( MoodGYM ) or an attention control condition . Personal stigma ( personal stigmatising attitudes to depression ) and perceived stigma ( perception of what most other people believe ) were assessed before and after the intervention . RESULTS Relative to the control , the internet sites significantly reduced personal stigma , although the effects were small . BluePages had no effect on perceived stigma and MoodGYM was associated with an increase in perceived stigma relative to the control . Changes in stigma were not mediated by changes in depression , depression literacy or cognitive-behavioural therapy literacy . CONCLUSIONS The internet warrants further investigation as a means of delivering stigma reduction programmes for depression This study examines the effects of Entertainment-Education strategy on knowledge acquisition about schizophrenia and stigma reduction , using pretest posttest control group and 2 X 3 ( advocate 's perspective X message style ) between-subjects factorial design . Participants watched an accurate and empathetic movie portrayal of schizophrenia , followed by an educational trailer . Participants ( N= 165 ) were r and omly assigned to one of eight conditions ( six manipulated conditions , control , a group who watched a trailer prior to the movie ) . Results showed that viewing an accurate and empathetic movie portrayal increased knowledge . The educational trailer increased not only knowledge acquisition but influenced stigma reduction . Structural equation modeling analysis revealed that entertainment and educational value of the movie mediated stigma reduction . Implication s of this study to the mental health research and the design of Entertainment-Education contents are discussed The purpose of this school-based cluster-r and omized trial was to determine the initial acceptability , feasibility , and efficacy of an existing community-based intervention , In Our Own Voice , in a sample of US adolescent girls aged 13 - 17 years ( n = 156 ) . In Our Own Voice is a knowledge-contact intervention that provides knowledge about mental illness to improve mental health literacy and facilitates intergroup contact with persons with mental illness as a means to reduce mental illness stigma . This longitudinal study was set in two public high schools located in a southern urban community of the U.S. Outcomes included measures of mental illness stigma and mental health literacy . Findings support the acceptability and feasibility of the intervention for adolescents who enrolled in the study . Findings to support the efficacy of In Our Own Voice to reduce stigma and improve mental health literacy are mixed . The intervention did not reduce mental illness stigma or improve mental health literacy at one week follow up . The intervention did not reduce mental illness stigma at 4 and 8 weeks follow up . The intervention did improve mental health literacy at 4 and 8 weeks follow up . Previous studies have assessed the preliminary efficacy In Our Own Voice among young adults ; rarely has In Our Own Voice been investigated longitudinally and with adolescents in the United States . This study provides initial data on the effects of In Our Own Voice for this population and can be used to further adapt the intervention for adolescents BACKGROUND A school mental-health programme has been developed as a component of the community mental-health programme in Rawalpindi , Pakistan . It has the objective of improving the underst and ing of disorders of mental health in the rural community . We aim ed to assess the impact of a school mental-health programme on the awareness of schoolchildren , their parents , friends who were not attending school , and neighbours . METHODS We chose two secondary schools for boys and two for girls that were similar in terms of size , staff-pupil ratio , and drop-out rates . 100 children aged 12 - 16 years ( 25 girls and 25 boys in each of the study and control groups ) , 100 parents ( one for each child ) , 100 friends who did not attend school ( one for each child ) , and 100 neighbours ( one for each child ) were given a 19-item question naire before and after the study group had had a 4-month programme of mental-health education . The maximum score for the question naire was 16 points . FINDINGS Before the school mental-health programme the awareness of mental-health issues was poor ( mean score 5.7 - 7.6 ) in the four groups of participants . In the study group there was a significant improvement in the mean scores after the school programme in the schoolchildren ( mean improvement 7.6 [ 95 % CI 6.7 - 8.5 ] , p<0.01 ) , their parents ( 5.3 [ 4.5 - 6.1 ] , p<0.01 ) , friends ( 5.1 [ 4.1 - 6.1 ] , p<0.01 ) , and neighbours ( 3.4 [ 2.6 - 4.2 ] , p<0.01 ) . In the control group the difference in awareness was significant only in schoolchildren ( 1.5 [ 0.5 - 2.3 ] , p=0.01 ) and their friends ( 0.8 [ 0.3 - 1.3 ] , p<0.01 ) . INTERPRETATION The school programme succeeded in improving awareness of mental health in schoolchildren and the community . The schoolchildren were receptive to the programme , and shared their new underst and ing with family , friends , and neighbours . Mental-health planners who wish to improve community awareness of mental health , particularly in areas with low literacy rates , should consider setting up school mental-health programmes This study evaluated the effectiveness of a cognitive behaviour therapy Internet program ( MoodGYM ) for depressive symptoms , attributional style , self‐esteem and beliefs about depression , and on depression and depression‐vulnerable status in male youth . A total of 78 boys age 15 and 16 years were allocated to either undertake MoodGYM or to st and ard personal development activities . Outcomes were measured before commencement , post‐program and 16 weeks post‐program . There were no significant between‐group differences in change scores pre‐ to post‐ or pre‐ to follow‐up using the intention to treat sample or for participants with post‐ and /or follow‐up data . For boys completing 3 or more modules there were small relative benefits of MoodGYM for depressive symptoms ( Effect Size , ES = 0.34 ) , attributional style ( ES = 0.17 ) and self‐esteem ( ES = 0.16 ) at post‐program , although only the effect for self‐esteem was sustained at follow‐up . Both groups showed improvement in their beliefs about depression at follow‐up , with the control group showing a moderate relative benefit ( ES = 0.40 ) . While the numbers are small , there was a reduction in the risk of being depressed in the MoodGYM group of 9 % at post‐treatment compared with a slightly increased risk for the control group . The risk of being classified as vulnerable to depression reduced by 17 % in the MoodGYM group at post‐treatment compared with no change in risk for the control group . These reductions in risk for the MoodGYM group were not sustained at follow‐up . The limitations of the study highlight several important challenges for MoodGYM and other self‐directed Internet cognitive behaviour therapy programs . These include how to ensure enough of the program is received and that people who could potentially benefit access the program and continue to remain engaged with it , and how to enhance the sustainability of any benefits Abstract The media are often identified as partially responsible for increasing the stigma of mental illness through their negatively focused representations . For many years , training programs have educated journalists on how to report on mental illness to reduce stigma . This purpose of this study was to evaluate the benefits of reading a positive , neutral or a negative journalism article that discusses mental illness . Consenting adult participants were r and omly assigned to read one of three published articles about recovery from mental illness , a dysfunctional public mental health system , or dental hygiene . The participants completed measures immediately before and after the intervention ; the measures administered evaluated stigmatizing and affirming attitudes toward people with mental illness . Public stigma was assessed using the nine-item Attribution Question naire and the Stigma Through Knowledge Test ( STKT ) . The STKT is a measure of mental illness stigma less susceptible to the impact of social desirability . Affirming attitudes represent public perceptions about recovery , empowerment , and self-determination , indicated as important to accepting and including people with psychiatric disabilities into society . Significant differences were observed between the articles on recovery and dysfunctional public mental health system , as well as the control condition , on the measures of stigma and affirming attitudes . The recovery article reduced stigma and increased affirming attitudes , whereas the dysfunctional public mental health system article increased stigma and decreased affirming attitudes . Not all journalistic stories have positive effects on attitudes about mental illness Two stigmatizing attitudes related to dangerousness and personal responsibility may undermine the opportunities of persons with serious mental illness . This study set out to examine path models that explain how these attitudes lead to discriminatory behavior and to assess the impact of antistigma programs on components of personal responsibility and dangerousness models . Two hundred thirteen persons were r and omly assigned to one of five antistigma conditions : education on personal responsibility , education on dangerousness , contact with a person with serious mental illness where personal responsibility is discussed , contact where dangerousness is discussed , or no change . Persons completed an attribution question naire ( AQ ) representing personal responsibility and dangerousness path models at pretest , posttest , and 1-week followup . They also completed tasks that represented helping behavior . Goodness of fit indexes from linear structural modeling were mixed for both models but suggested that fear of dangerousness was a key attitude leading to discriminatory behavior . Results also showed that subjects who had contact with persons with serious mental illness experienced greater changes than subjects in the education or control groups did on measures of attribution and helping behavior BACKGROUND Depression is an important cause of disability worldwide , with many people experiencing their first depressive episode before the age of 18 . University students are particularly vulnerable to depression . Depression can be treated successfully in most patients . However , for treatment to be successful , depressed people need to recognize their symptoms as illness , present to medical care , and be aware that effective treatment is available . A thoughtful health campaign might therefore increase the likelihood of successful treatment . METHOD A cluster r and omized controlled trial was conducted to determine the effectiveness of an educational intervention . A total of 3313 undergraduate students participated in the study . The intervention consisted of postcards and posters on depression and its treatment . The primary outcome was student awareness that depression can be treated effectively . Secondary outcomes included the proportion of students reading the postcards , recognition of symptoms and knowledge of treatments . RESULTS The postcards were read by 69 % of students . Less than half of participants reported that depression could be treated effectively , and there was no evidence of a difference between the intervention and control groups [ 341 ( 49.1 % ) v. 379 ( 49.7 % ) , difference -0.7 , p=0.8 , 95 % confidence interval ( CI ) -5.1 to 3.7 ] . However , intervention group participants were more likely than control group participants to recognize depressive symptoms and to report that antidepressants are not addictive . CONCLUSIONS Many university students lack knowledge about depression and its treatment . Simple and cheap media , such as postcards and posters , might help to improve awareness in areas where current knowledge is low BACKGROUND This study evaluates the benefits of a self-directed Internet intervention for depression ( MoodGYM ) delivered as a part of the high school curriculum . METHOD One hundred and fifty-seven girls , aged 15 and 16 years , were allocated to undertake either MoodGYM or their usual curriculum . MoodGYM 's impact on depressive symptoms , risk of depression , attributional style , depression literacy and attitudes toward depression was examined using r and om effect regression . RESULTS MoodGYM produced a significantly faster rate of decline in depressive symptoms over the trial period than the control condition . The effect size for MoodGYM was not significant immediately after the intervention ( Cohen 's d=.19 , 95 % CI -.18-.56 ) but was moderate and significant 20 weeks after the intervention ( d=.46 , 95 % CI .10-.82 ) . Girls with high depression scores before intervention showed the strongest benefits on self-reported depression at follow-up ( d=.92 , 95 % CI .10 - 1.38 ) . There were no significant intervention effects on depression status , attributional style , depression literacy , and attitudes . Approximately 70 % of girls in the MoodGYM group completed less than three of its modules and completion of fewer modules was related to high depression score before intervention . CONCLUSIONS The findings suggest that there are benefits from MoodGYM on self-reported depressive symptoms but has low rates of completion highlight problems in ensuring adherence to Internet programs for depression AIM although inclusive education of disabled children is now an accepted practice , it is often challenged by negative peer attitudes . We undertook an interventional study aim ed at improving students ' attitudes towards their disabled peers . METHOD the participants were students from the 7th grade of twelve paired schools ( 1509 students from 62 classes ; age 12 - 13y ) , r and omly allocated to an intervention group ( 205 males , 285 females ) or a control group ( 132 males , 165 females ) . The intervention consisted of a m and atory comprehensive educational project on disability . The Chedoke-McMaster Attitudes Towards Children with H and icaps Scale ( CATCH ) was used to assess children 's attitudes before ( T0 ) and after ( T1 ) intervention . The hierarchical structure of the data was taken into account by adjusting st and ard deviations and using linear multilevel models . RESULTS seven hundred and eighty-four students had at least one score on the three domains ( cognitive , affective , behavioural ) of the CATCH at T0 and T1 . The final scores were higher than baseline scores ( total scores , intervention group : baseline score 25.6 ( SD=5.4 ) , final score 26.8 ( 5.9 ) , p<0.001 ; CONTROL GROUP baseline 25.2 ( 5.4 ) , final 26.0 ( 5.7 ) , p<0.009 ) with no significant difference between the intervention and control groups . Individual score changes over time were associated with baseline score ( p<0.001 for total and all sub-scores ) . Lower improvement in attitudes was found in students from schools with special units for their peers with cognitive impairment for total ( p=0.013 ) , affective ( p<0.001 ) , and behavioural ( p=0.001 ) scores , while higher improvement existed for the cognitive domain ( p=0.029 ) . INTERPRETATION although we found no effect of our intervention , we found an improvement in attitudes in the intervention and control groups that could be a result of the nature of the scales and question naires the students had to complete before the intervention BACKGROUND Suicide is a significant public health problem worldwide that requires evidence -based prevention efforts . One approach to prevention is gatekeeper training . Gatekeeper training programs for community members have demonstrated positive changes in knowledge and attitudes about suicide . Changes in gatekeeper skills have not been well established . AIMS To assess and to predict the impact of a brief , gatekeeper training on community members ' observed skills . METHODS Participants in a community gatekeeper training were employees at US universities . 50 participants were r and omly selected for skills assessment and videotaped interacting with a st and ardized actor prior to and following training . Tapes were reliably rated for general and suicide-specific skills . RESULTS Gatekeeper skills increased from pre- to posttest : 10 % of participants met criteria for acceptable gatekeeper skills before training , while 54 % met criteria after training . Pretraining variables did not predict increased skills . LIMITATIONS Results do not provide conclusions about the relationship between observed gatekeeper skills and actual use of those skills in the future . CONCLUSIONS Gatekeeper training enhances suicide-specific skills for the majority of participants . Other strategies , such as behavioral rehearsal , may be necessary to enhance skills in the remaining participants AIM To investigate whether employers who have experience of hiring people with mental health problems differ significantly from those without such experience in terms of knowledge , attitudes and behaviours regarding mental health in the workplace , and the concerns which they report about employing people with mental health problems . We also examine whether non-workplace social contact is associated with the above variables . METHODS A telephone survey was conducted with a r and omly selected sample of British employers . The sample included a similar number of human re source managers and managers/executive employees in other roles . RESULTS 502 employers took part . Having employed someone with a mental health problem was associated with closer non-workplace social contact . Those with experience of employing applicants with mental health problems had significant differences in knowledge ( regarding the law ) , and behaviour ( having a policy on hiring applicants with disabilities ) but not in attitudes . CONCLUSIONS Non-workplace social contact may be useful to consider in underst and ing hiring practice s. The nature of social contact at work and possible lack of impact of this contact on employer attitudes and concerns warrants further study . Greater support is needed for employers to underst and the law regarding mental health problems in the workplace BACKGROUND Many people who are depressed do not receive any professional help and their beliefs about the helpfulness of treatment do not always correspond with those of health professionals . To facilitate choices about treatment , the present study examined the effects of providing depressed people in the community with evidence on whether various treatment options work . METHOD A r and omized controlled trial was carried out with 1094 persons selected at r and om from the community who screened positive for depressive symptoms and agreed to participate . Participants were mailed either an evidence -based consumer guide to treatments for depression or , as a control , a general brochure on depression . Outcomes were the rated usefulness of the information provided , changes in attitudes to depression treatments , actions taken to reduce depression , and changes in depressive symptoms , anxiety symptoms and disability . RESULTS Participants rated the evidence -based consumer guide as more useful than the control brochure . Attitudes to some treatments changed . Improvements in symptoms and disability did not differ significantly between interventions . CONCLUSION Providing people who are depressed with evidence on which treatments work produces some changes in attitudes and behaviour . However , this intervention may need to be enhanced if it is to produce symptom change Employees fail to seek help for alcohol or drug ( AOD ) abuse because of unhealthy work climates , stigma , and distrust in Employee Assistance Programs ( EAPs ) . To address such problems , the authors r and omly assigned groups of municipal employees ( N = 260 ) to 2 types of training : a 4-hr informational review of EAPs and policy and an 8-hr training that embedded messages about AOD reduction in the context of team building and stress management . Pre- and posttraining and 6-month follow-up surveys assessed change . Group privacy regulation , EAP trust , help seeking , and peer encouragement increased for team training . Stigma of substance users decreased for information training . EAP/policy knowledge increased for both groups . A control group showed little change . Help seeking and peer encouragement also predicted EAP utilization . Integrating both team and informational training may be the most effective for improving help seeking and EAP utilization Background Numerous studies have established proof of selective media reporting about the mentally ill , with the majority of the reports focusing almost exclusively on violence and dangerousness . A h and ful of studies found that there is an association between negative media portrayals and negative attitudes toward people with mental illness . However , empirical evidence of the impact of newspaper reports about mentally ill people on readers ’ attitudes is very scarce . Aims To examine the impact of a newspaper article linking mentally ill persons with violent crime and the impact of an article providing factual information about schizophrenia on students ’ attitudes toward people with mental illness . Method A total of 167 students aged 13–18 years were r and omly assigned one of two articles . A period of 1 week before and 3 weeks after reading the newspaper article , they were asked to complete a self-administered question naire for the assessment of their attitudes toward mentally ill people . Results Respondents who read the article linking mentally ill persons with violent crime displayed an increased likelihood to describe a mentally ill person as dangerous and violent . Conversely , respondents who read the informative article used terms like ‘ violent ’ or ‘ dangerous ’ less frequently . The desire for social distance remained virtually unchanged at follow-up in both groups . Conclusion Two potential approaches to break the unwanted link between negative media reporting and negative attitudes are suggested . First , an appeal to media professionals to report accurate representations of mental illness . And second , an appeal to the adults living and working with adolescents to provide opportunities to discuss and reflect on media contents Mental illness stigma is quite prevalent with dire consequences . A number of interventions to decrease stigma have been formulated , but have variable effectiveness and limited dissemination . This research examined the impact of two brief interventions : a film depicting individuals with schizophrenia ( filmed contact ) and a simulation of auditory hallucinations . Participants ( N = 143 ) were r and omly assigned to one of three interventions : ( 1 ) filmed contact , ( 2 ) simulation , or ( 3 ) no intervention , and completed two stigma measures prior to , immediately after , and 1 week after the intervention . The filmed contact intervention led to decreases in stigma which persisted across 1 week . However , the simulation led to increases in stigma . The results suggest that a filmed contact intervention may decrease two aspects of mental illness stigma ( social distance and negative emotions ) , which has implication s for wide dissemination . The efficacy of a hallucination simulations intervention remains dubious OBJECTIVE This study was design ed to investigate the efficacy of a web-based mental disorder stigma education program for mental health professionals . METHODS The sample consisted of 205 individuals who were either residents or specialists in psychiatry . Participants were contacted through a national web-based e-mail group that consisted of professionals in psychiatry , who were r and omly assigned to experimental and control groups . The experimental group received an informative e-mail which contained a general account of " stigma " before they were asked to respond to an Internet-based question naire which was design ed to predict their stigmatizing attitudes towards individuals with mental disorders . Control subjects , on the other h and , were asked to respond to the same Internet-based question naire without having been given the aforementioned informative e-mail . RESULTS The experimental group , compared to the control group , demonstrated a lesser stigmatizing attitude towards individuals with mental illness , as measured by the Internet-based survey which utilized the " social distance " concepts of stigma . CONCLUSIONS These data suggest that such " anti-stigma " campaigns using the potential of the Internet might be an effective tool in the fight against the stigmatization of persons with mental illness Objective The authors address the issue of cultivating medical students ’ empathy for the mentally ill by examining medical student empathy pre- and postsimulated auditory hallucination experience . Methods At the University of Utah , 150 medical students participated in this study during their 6-week psychiatry rotation . The Jefferson Scale of Physician Empathy , Student Version , was used before and after the experience . The auditory hallucinations were provided as part of the “ Hearing Voices That Are Distressing ” curriculum created by the National Empowerment Center , which attempted to simulate the experience of hearing auditory hallucinations . While the students were listening to the auditory hallucinations , they underwent a psychiatric interview and simplified cognitive testing and were asked to socially interact in the community . We conducted a paired sample t-test of significance to identify pre- and postsimulated auditory hallucination changes in medical student empathy . Fifty students were r and omly selected to serve as a comparison group . Results The paired sample t-test revealed that after listening to the simulated auditory hallucinations and participating in the simplified neurocognitive testing , the students ’ empathy score increased . Students in the comparison group had no significant difference in their empathy scores . Conclusion These results suggest that empathy may increase when students are given a brief glimpse into the mind of a mentally ill patient by listening to simulated auditory hallucinations . Specific interventions to increase empathy for the mentally ill can lead to a better underst and ing of how empathy can improve patient care , enhance the doctor-patient relationship , and direct future educational strategies Individuals who exhibit motor and vocal tics are viewed as less socially acceptable than persons who do not exhibit tics . Efforts have been made to alter the negative perceptions through the use of education . However , the effectiveness of peer education and whether it need be Tourette syndrome ( TS ) specific remains unclear . One hundred and seventy college students were r and omly assigned to view either an educational video about TS , a video about depression , or no educational video , before providing attitudinal and behavioral data on social acceptance of either an actor or actress engaging in motor and vocal tics . Those viewing the TS-specific educational video held more positive attitudes toward persons with tics than those receiving the other two interventions ; however , the effect on social behavior intentions and actual social behavior was unclear . Implication s of these findings and directions for future research are discussed The effects of three strategies for changing stigmatizing attitudes -- education ( which replaces myths about mental illness with accurate conceptions ) , contact ( which challenges public attitudes about mental illness through direct interactions with persons who have these disorders ) , and protest ( which seeks to suppress stigmatizing attitudes about mental illness)--were examined on attributions about schizophrenia and other severe mental illnesses . One hundred and fifty-two students at a community college were r and omly assigned to one of the three strategies or a control condition . They completed a question naire about attributions toward six groups -- depression , psychosis , cocaine addiction , mental retardation , cancer , and AIDS -- prior to and after completing the assigned condition . As expected , results showed that education had no effect on attributions about physical disabilities but led to improved attributions in all four psychiatric groups . Contact produced positive changes that exceeded education effects in attributions about targeted psychiatric disabilities : depression and psychosis . Protest yielded no significant changes in attributions about any group . This study also examined the effects of these strategies on processing information about mental illness AIM This study was design ed to investigate the learning outcomes of a suicide education programme for second-year student nurses in Taiwan . BACKGROUND Research demonstrates that nurses ' attitudes impact on the care provided to suicidal patients . However , evidence is sparse on promoting positive caring attitudes in nurses towards suicidal patients . DESIGN A quasi-experiment . METHOD The total sample group ( n = 174 ) comprised second-year student nurses . Some ( n = 95 ) were r and omly allocated to an experimental group who attended a four-hour suicidal education programme and others ( n = 79 ) comprised a control group who did not attend the programme . All participants were given a question naire before and after the programme in 2008 . The question naire contained 30 items and was divided into five categories . They were ( 1 ) the acceptability of suicidal behaviours , ( 2 ) morality and mental illness , ( 3 ) professional role and care , ( 4 ) communication and attention and ( 5 ) beliefs . RESULTS Results demonstrated that the experimental group had higher scores on all five categories of the question naire than the control group did . Participants in the experimental group held more positive attitudes towards the acceptance of suicidal behaviours and were non-judgmental in their morality . Further , they showed more positive attitudes towards the provision of professional care and believed that people who attempt suicide are communicating their psychic pain . Moreover , participants in the experimental group held more positive beliefs about people who attempt suicide than the control group did . CONCLUSION This suicide education programme raised student nurses ' awareness about the phenomenon of suicide and promoted positive caring attitudes towards people who attempt suicide and hence their nursing care . RELEVANCE TO CLINICAL PRACTICE A four-hour suicide education programme can promote positive caring attitudes towards people who attempt suicide and may have an affirmative influence on the nursing care provided to suicidal patients Supervisor tolerance-responsiveness , referring to the attitudes and behaviors associated with either ignoring or taking proactive steps with troubled employees , was investigated in two studies . The studies were conducted to help examine , underst and and improve supervisor responsiveness to employee substance abuse . Study 1 examined supervisor response to and tolerance of coworker substance use and ways of interfacing with the Employee Assistance Program ( EAP ) in two workplaces ( n = 244 and 107 ) . These surveys suggested that engaging supervisors in a dialogue about tolerance might improve their willingness to use the EAP . Study 2 was a r and omized control field experiment that assessed a team-oriented training . This training adopted a cognitive mapping technique to help improve supervisor responsiveness . Supervisors receiving this training ( n = 29 ) were more likely to improve on several dimensions of responsiveness ( e.g. likely to contact the EAP ) than were supervisors who received a more didactic , informational training ( n = 23 ) or a no-training control group ( n = 17 ) . Trained supervisors also showed increases in their own help-seeking behavior . Procedures and maps from the mapping activity ( two-stage conversational mapping ) are described . Overall , results indicate that while supervisor tolerance of coworker substance use inhibits EAP utilization , it may be possible to address this tolerance using team-oriented prevention training in the work-site Objective : Mental Health First Aid training is a course for the public that teaches how to give initial help to a person developing a mental health problem or in a mental health crisis . The present study evaluated the effects of Mental Health First Aid training delivered by e-learning on knowledge about mental disorders , stigmatizing attitudes and helping behaviour . Method : A r and omized controlled trial was carried out with 262 members of the Australian public . Participants were r and omly assigned to complete an e-learning CD , read a Mental Health First Aid manual or be in a waiting list control group . The effects of the interventions were evaluated using online question naires pre- and post-training and at 6-months follow up . The question naires covered mental health knowledge , stigmatizing attitudes , confidence in providing help to others , actions taken to implement mental health first aid and participant mental health . Results : Both e-learning and the printed manual increased aspects of knowledge , reduced stigma and increased confidence compared to waiting list . E-learning also improved first aid actions taken more than waiting list , and was superior to the printed manual in reducing stigma and disability due to mental ill health . Conclusions : Mental Health First Aid information received by either e-learning or printed manual had positive effects , but e-learning was better at reducing stigma Mental health literacy is the knowledge and beliefs about mental disorders that aid in their recognition , management , or prevention ; it is also a determinant of help seeking . As such , it is presumed to be important in community suicide prevention programs . In Australia there have been a number of government , professional , and charitable organizations as well as pharmaceutical company suicide prevention initiatives which have been design ed to enhance public and professional knowledge about mental disorders , particularly depression . This naturalistic study conducted between 1998 and 2004 in a r and om and representative population sample examined the changes in mental health literacy and treatment seeking of those with major depression , both with and without suicidal ideation , and those who were neither depressed nor suicidal . Results indicated that there was marked improvement in mental health literacy for all three groups , although there was less change for those most in need of intervention ( i.e. , those with major depression and suicidal ideation ) . Furthermore , there were fewer changes in appropriate treatment seeking in those with major depression and suicidal ideation . These findings are consistent with literature reporting limited problem solving and decision making in those who are suicidal , and indicate that there are limits to broadbased community education programs . More focused suicide prevention initiatives are required , specifically for those who are depressed and suicidal |
1,894 | 29,126,708 | INTERPRETATION The risk of residual or recurrent CIN2 + is significantly greater with involved margins on excisional treatment ; however , high-risk HPV post-treatment predicts treatment failure more accurately than margin status . | BACKGROUND Incomplete excision of cervical precancer is associated with therapeutic failure and is therefore considered as a quality indicator of clinical practice .
Conversely , the risk of preterm birth is reported to correlate with size of cervical excision and therefore balancing the risk of adequate treatment with iatrogenic harm is challenging .
We review ed the literature with an aim to reveal whether incomplete excision , reflected by presence of precancerous tissue at the section margins , or post-treatment HPV testing are accurate predictors of treatment failure .
METHODS We did a systematic review and meta- analysis to assess the risk of therapeutic failure associated with the histological status of the margins of the tissue excised to treat cervical precancer .
We estimated the accuracy of the margin status to predict occurrence of residual or recurrent high- grade cervical intraepithelial neoplasia of grade two or worse ( CIN2 + ) and compared it with post-treatment high-risk human papillomavirus ( HPV ) testing . | BACKGROUND In this study , our prospect i ve experience with a multimodal follow-up protocol is summarized , with special emphasis on predicting the treatment outcome of cervical diseases . MATERIAL S AND METHODS Liquid-based cytology sample s ( ThinPrep ) from 209 women exhibiting the whole spectrum of human papilloma virus (HPV)-related cervical diseases were investigated by cytology , PCR-based HPV genotyping and DNA cytometry pre-surgery . The first control cytology and type-specific HPV tests were performed at 3 months post-surgery . RESULTS The success rate of surgery was 95 % in eradicating high- grade cervical disease and 90 % in eliminating the baseline HPV genotype . Treatment failure was significantly correlated with baseline cytology ( p=0.011 ) , resection margin status ( p=0.016 ) and HPV positivity at 3 months post-surgery ( p=0.04 ) . Multivariate logistic regression analysis showed that type-specific persistent HPV infection ( p=0.028 ) , baseline cytology ( p=0.039 ) and histology ( p=0.065 ) were independent predictors of residual cervical neoplasias . CONCLUSION Our results showed that our multimodal surveillance protocol may help to individually assess the anticipated clinical outcome of cervical diseases post-surgery Cervical intraepithelial neoplasia 3 ( CIN3 ) is the precursor of mostsquamous carcinomas and serves as a surrogate end point . However , small CIN3 lesions are rarely associated with concurrent invasion . We hypothesized that aggressive follow-up for cytology of atypical squamous cells of undetermined significance ( ASCUS ) or low- grade squamous intraepithelial lesion ( LSIL ) leads predominantly to detection of smaller CIN3 lesions than those usually associated with cancer . We assessed this hypothesis in a masked histopathologic review of 330 CIN3 lesions in the ASCUS LSILTriage Study , focusing on ASCUS referrals . ASCUS referrals underwent r and omized management [ colposcopy for repeat cytology of high- grade squamous intraepithelial lesion ( HSIL ) , colposcopy for oncogenic human papillomavirus ( HPV ) detection or repeat HSIL , or immediate colposcopy ] ; then all were followed with repeat cytology for 2 years , followed by colposcopy and aggressive treatment . We assessed all CIN3 lesions qualitatively and measured 39 of them . CIN3 lesions were overwhelmingly small . Compared with enrollment , lesions found at follow-up or exit involved fewer tissue fragments ( P < 0.01 ) and showed less diffuse gl and involvement ( P = 0.03 ) . CIN3 lesions found postenrollment after HPV testing involved the fewest tissue fragments [ versus immediate colposcopy ( P = 0.04 ) or repeat cytology of HSIL ( P = 0.02 ) ] , and none showed diffuse gl and involvement . The median distal-proximal length was 6.5 mm ( median replacement of total epithelium = 5 % ) in the 39 measured cases . We conclude that CIN3 lesions underlying ASCUS or LSIL generally lack features associated with invasion , particularly if managed using HPV testing , suggesting that aggressive management leads to early detection of CIN3 but probably prevents relatively few cancers in screened population OBJECTIVE To evaluate testing for high-risk human papillomavirus ( HR HPV ) E6/E7 mRNA transcripts 6 months after conisation for cervical intraepithelial neoplasia grade 2 or worse ( CIN2 + ) to determine the risk of residual CIN2 + . METHODS We prospect ively followed 344 women treated for CIN2 + by conisation . HR HPV mRNA testing ( PreTect HPV-Proofer , NorChip ® ) , HR HPV DNA testing ( AMPLICOR HPV Test , Roche Diagnostics ® ) and cytology was performed at 6 and 12 months after conisation . Biopsies were taken within 18 months of conisation if indicated by abnormal cytology , abnormal colposcopy , or positive HPV test . The LINEAR ARRAY HPV Genotyping Test ( Roche Diagnostics ® ) was used to genotype cases with histologically confirmed residual disease diagnosed within 18 months after conisation . RESULTS 6.4 % ( 22/344 ) of study women had detected residual CIN2 + . They were significantly older than those without residual CIN2 + ( 43.2 and 37.2 years respectively , p<0.001 ) . Among women with detected residual CIN2 + , 54.5 % ( 12/22 ) had positive resection margins , 63.6 % ( 14/22 ) had abnormal cytology , and 95.5 % ( 21/22 ) had a positive HR HPV DNA test at 6 months . Sensitivity of HR HPV mRNA testing was 45.5 % ( 95 % confidence interval : 26.8 - 65.5 % ) at 6 months to predict detected residual CIN2 + . Eight of 12 women who were HR HPV mRNA-negative at 6 months were HR HPV DNA-positive for one of the HPV types included in the mRNA test . CONCLUSION Detection of E6/E7 mRNA transcripts by PreTect HPV Proofer does not seem suitable for short-term follow-up to detect residual CIN2 + after conisation OBJECTIVE : To estimate the effectiveness of the human papillomavirus ( HPV ) test performed after conization in predicting residual disease in patients who subsequently underwent hysterectomy . METHODS : A total of 115 patients who underwent hysterectomy after conization caused by cervical intraepithelial neoplasia grade 3 ( CIN 3 ) and microinvasive cervical cancer ( IA1 cancer ) were included in this prospect i ve study . All patients underwent HPV testing with a liquid hybridization assay immediately before hysterectomy . Differences in sensitivity , specificity , and accuracy between resection margin and the HPV test in predicting residual disease in subsequent hysterectomy sample s were estimated using the McNemar exact test . RESULTS : Univariable analysis showed that age , parity , menopausal status , gl and ular extension , and severity of disease were not predictive for residual disease , but positive resection margin and positive HPV tests were significant factors for predicting residual disease . These factors were also significant in a multivariable analysis ( positive resection margin 45.5 % , odds ratio [ OR ] 3.09 , 95 % confidence interval [ CI ] 1.19–8.03 , P=.021 ; positive HPV test 57.6 % , OR 11.05 , 95 % CI 4.01–30.49 , P<.001 ) . With resection margin , the sensitivity , specificity , and accuracy in predicting residual disease were 75 % , 53 % , and 61 % , respectively , whereas , with the HPV test , these values were 85 % , 67 % , and 73 % , respectively ( P=.454 , .080 , and .044 , respectively ) . Of patients with positive resection margins , 79 % of HPV-negative patients had no residual disease . Of patients with negative resection margins , no HPV-negative patient had residual disease . CONCLUSION : The HPV test after conization was significantly more accurate than resection margin for predicting residual disease . The predictive value of resection margin for predicting residual disease was much improved when used in combination with the HPV test . Use of the HPV test is recommended for identifying patients for subsequent hysterectomy after conization for CIN 3 and IA1 cancer . LEVEL OF EVIDENCE : AIM To investigate the therapeutic efficacy of cylindrical or cone-shaped excision performed by laser CO2 in the conservative management of persistent-recurrent high- grade cervical intraepithelial neoplasia ( HG-CIN ) in women of fertile age . PATIENTS AND METHODS Ninety-four premenopausal patients with persistent-recurrent HG-CIN had undergone re-conization or cylindrical excision according to the time of reappearance of the disease . The length of the procedures , intra- and postoperative complications , height of the excised specimens , final histological findings and follow-up data were retrospectively evaluated . RESULTS Fifty-five ( 58.5 % ) persistent and 39 ( 41.5 % ) recurrent cases had undergone cylindrical excision and st and ard re-conization respectively . All the treatments were successfully performed in an out-patient setting under local anesthesia with no differences in term of operative time , height of removed specimens , intra- and postoperative complications between the two groups . Definitive histology confirmed HG-CIN in 95.7 % of the cases and FIGO Stage Ia1 cervical cancer ( negative lymph vascular space involvement , LVSI ) in 4.3 % of the cases . The endocervical margins were involved in 3.6 % of the cylindrical ( persistent ) and in 17.9 % of the cone-shaped ( recurrent ) specimens ( p = 0.03 ) . The overall cure rate after a median follow-up time of 54 months ( range 10 - 196 ) was 91.5 % . A third excisional procedure was performed in 8 cases of persistent-recurrent HG-CIN with a disease-free subsequent follow-up of 38 months ( range 6 - 108 ) . CONCLUSION Cylindrical or conical re-excision performed by CO2 laser according to the time of reappearance of the disease seems to be a promising conservative approach for persistent-recurrent HG-CIN even though further r and omised prospect i ve studies are needed to confirm the long-term efficacy and reproductive outcomes OBJECTIVES Loop electrosurgical excision of the transformation zone ( LEETZ ) was recently associated with relatively high failure rates . We evaluated whether the combination of LEETZ with laser vaporization is superior to LEETZ alone in reducing the rates of recurrent abnormal cytology and residual disease . METHODS The study population included 426 women with histologic diagnosis of cervical intraepithelial neoplasia ( CIN ) 2 - 3 , of whom 289 ( study group ) were treated by LEETZ followed by laser vaporization of the crater base and walls and 137 ( control group ) were treated by LEETZ alone . All women were followed scrupulously at regular intervals for recurrent abnormal cytology and residual disease . The mean follow-up periods were 43 and 59 months for the study and control groups , respectively . RESULTS Both groups were derived from the same community and were similar in epidemiologic characteristics and disease severity . Although the incidence of positive surgical margins was similar in both groups ( 10.4 and 9.5 % for the study and control groups , respectively ) , recurrent abnormal cytology ( 10.2 % vs 5.5 % , P = 0.07 ) and histologic residual disease ( 21.4 % vs 0 % , P = 0.05 ) were more frequent among women in the control group . This applied to women with both negative and positive surgical margins . Both study and control women with positive surgical margins , especially at the endocervix , were at higher risk for recurrence . CONCLUSION The addition of laser vaporization to LEETZ may improve outcome of both women with positive margins and women with negative margins . Our results support conservative management for all treated women , regardless of cone margin status OBJECTIVE The goal of this study was to determine/evaluate the negative predictive value of human papillomavirus ( HPV ) testing following conization of cervix uteri . METHODS A prospect i ve analysis was undertaken on 79 cone biopsies of women with high- grade lesions ( cervical intraepithelial neoplasia ( CIN ) III ) . HPV testing was performed on cervical smears before and after conization . We correlated the margin status ( defined as positive cone margin or endocervical curettage status ) and positive conization HPV status with the residual disease in a hysterectomy specimen . A Digene II kit was used to perform HPV testing . HPV detection was done by Hybrid Capture assay . RESULTS Of the 79 patients , 47(59.5 % ) had positive margins after conization . HPV testing was positive in 37 cases ( 78.7 % ) and negative in 10 cases ( 21.3 % ) . Residual disease was found in 31 of 47 ( 66 % ) postconization hysterectomy specimens . No residual lesions were found in HPV-negative cases . Of the 32 cases with negative margins following conization , HPV testing was negative in 25 cases ( 78 % ) and was positive in 7 cases ( 22 % ) . Among these 25 cases with negative HPV tests , no residual lesion was detected , and in 7 HPV-positive cases , only one residual lesion was found . CONCLUSION HPV testing is potentially an effective tool in predicting residual dysplasia after conization and could potentially assist in the decision between hysterectomy and conservative follow-up in women with CIN III Objective To evaluate whether microcolposcopic topographic endocervical assessment reduces the failures of excisional treatment of cervical intraepithelial neoplasia ( CIN ) . Methods Three hundred fifty patients with colposcopic and histopatologic findings of endocervical CIN were recruited for excisional treatment . Three hundred forty-eight of these were r and omized to have or not have microcolposcopy before excisional treatment . Measurement of endocervical lesion was the only aim of microcolposcopic evaluation . When an endocervical extension was available , the cone biopsy was cut according to microcolposcopic measurement . Excision status was evaluated and related to presurgical management on operative specimens . After excision , patients were followed-up for at least 5 years after treatment . Three hundred thirty ( 171 and 159 with and without preoperative microcolposcopy , respectively ) patients completed the study . Disease persistences were defined by cytologic , colposcopic , and histologic results . Microcolposcopic value was defined as completeness of excision and /or lack of persistent disease . Results On surgical specimens , involved margins were detected in 19 ( 5.4 % ) cases . Presurgical microcolposcopy was performed in only one of these cases . The difference of incomplete excision between cases with or without microcolposcopy was statistically significant ( P < .001 ) . In patients who were followed-up , persistent disease was detected in one ( 0.6 % ) woman in the microcolposcopy group and in 16 ( 10 % ) women in the control group . Comparison between the two groups showed a significantly lower risk of persistent disease when presurgical microcolposcopy was performed ( P < .001 ) . Conclusion By measuring endocervical extension of the lesion , preoperative microcolposcopy allows individualized cones , thus improving the prognosis after excisional treatment of CIN OBJECTIVE The purpose of this study was to evaluate a conservative cold-knife section technique for treatment of cervical intraepithelial neoplasia ( CIN ) . This procedure can be adapted to patient age , preservation of childbearing potential and extent of dysplasia . DESIGN Prospect i ve study . SETTING Gynecological Oncology Department in French Public Hospital . POPULATION A total of 460 women treated for CIN between 1985 and 1999 were included . METHODS A conservative cold-knife cervical section followed by blanket suture reconstruction was used in all cases . MAIN OUTCOME MEASURES Immediate operative results , recurrence and reproductive function were assessed . RESULTS The mean length of the cervical specimen was 11.4 mm ( range , 4 - 22 mm ) . Mean specimen thickness was strongly correlated with age : 10.6 + /- 4.1 mm in women < 40 years versus 12.1 in women > 40 years ; p < 0.001 . Complete excision was achieved in 395 cases ( 85.8 % ) . Post-operative bleeding was observed in 5 cases ( 1.1 % ) . The mean duration of follow-up was 62 months ( range , 12.3 - 156.5 months ) . Recurrences developed in 26 patients ( 6.6 % ) including CIN 1 in 9 cases , CIN 2 in 9 and CIN 3 in 8 . No patient developed carcinoma . The actuarial risk of recurrence was 2.4 % ( + /- S.D. , 0.9 ) at 24 months and 7.8 % ( + /-S.D. , 1.9 ) at 60 months . A total of 52 pregnancies were observed in 39 patients . No case of de novo infertility was reported post-operatively . Amenorrhea was noted in 1 patient ( 0.1 % ) and dysmenorrhea in 1 patient ( 0.1 % ) . CONCLUSIONS This conservative cold-knife section technique is effective for treatment of CIN with low morbidity and little adverse effect on childbearing potential . Exposure of the squamocolumnar junction ( SCJ ) greatly facilitates follow-up UNLABELLED PRÉCIS : Positive endocervical margins are an important predictor of recurrence in high- grade cervical lesions , and though they do not always warrant retreatment , closer surveillance is recommended . OBJECTIVE To identify predictors of recurrence and persistence of high- grade cervical dysplasia and to determine appropriate follow-up . DESIGN prospect i ve pilot study . SETTING Gynaecological surgical center . POPULATION Three hundred fifty-two patients were treated between 1999 and 2002 for high- grade lesions . METHODS According to the accessibility of the transformation zone and the degree of dysplasia , patients were treated either by conization or by loop electrosurgical excision procedure ( LEEP ) . Follow-up comprised colposcopy and Pap-smear screening 4 - 6 months after treatment as well as high-risk human papillomavirus ( HR-HPV ) testing before and after treatment . MAIN OUTCOME MEASURES underscore predictors of recurrence and propose a treatment flowchart for both management and follow-up . RESULTS Of the 352 patients , 37 ( 10.5 % ) had true recurrence 6 months after initial surgical treatment and 6 patients ( 1.7 % ) had persistent lesions . Overall , 43 patients ( 12.2 % ) were considered as having recurrent disease . Patients were followed up for 5 years with a mean of 73 months . The most important predictor of recurrence was a positive HR-HPV test at 6 months postoperatively ( odds ratio 38.8 , 95 % confidence interval 14.09 , 107.05 ) . The second significant predictor was positive endocervical margins and the third was positive pre-treatment HPV typing . A positive post-treatment HPV test had a more significant influence on risk than a positive test before treatment . CONCLUSION In agreement with recent findings , our study supports the usefulness of the HR-HPV test in the follow-up of treated high- grade lesions , especially when excision margins were positive OBJECTIVE To assess the use of human papillomavirus genotyping in cervical intraepithelial neoplasia posttreatment follow-up . STUDY DESIGN Prospect i ve observational study . Ninety women underwent cytologic testing and human papillomavirus genotyping at the follow-up visit after conization . Cones were retrospectively genotyped . A second cytologic follow-up was performed . RESULTS Margin status and presence of cervical intraepithelial neoplasia 3 + in the cone were poor predictors of treatment outcome ( sensitivity , < 50 % ; diagnostic odds ratio , < or= 2.5 ) . Presence of high-/intermediate-risk human papillomavirus types predicted 100 % of residual high- grade squamous intraepithelial lesion/cervical intraepithelial 2 + at a specificity of 73 % . Testing only 13 high-risk types showed equal sensitivity but higher specificity ( 86 % ; P < .01 ) . Persistent high-risk human papillomavirus infection ( 13 types ) detected high- grade residual disease with a sensitivity of 60 % at a very high specificity ( 95 % ) , result ing in a positive predictive value of 43 % , which exceeded the positive predictive values of all other criteria . CONCLUSION Testing for high-risk human papillomavirus identified all recurrent/residual high- grade cervical intraepithelial neoplasia . Focusing on women with persistent human papillomavirus types through genotyping substantially increased positive predictive value but at a loss in sensitivity Six hundred thirty-nine patients with CIN on referral Pap were evaluated cytocolposcopically at the first visit and decided whether to be treated the same day or not . One hundred ninety-two patients ( 30 % ) were considered negative . Follow-up evidence d later appearance of CIN in five of them . One hundred fifty-three ( 24 % ) were c and i date s for delayed treatment due to conditions contraindicating same-day treatment . Two hundred ninety-four patients ( 46 % ) were r and omly allocated in LEEP ( 149 ) or excisional laser ( 145 ) arms , and treated the same day under local anesthesia . Both arms were comparable . There were three microinvasive carcinomas diagnosed in the surgical specimen . LEEP was faster and produced less bleeding than laser , although required a mean of four slices to remove the lesion . Arterial hypertension after anesthetic infiltration was detected in 26 % of cases . Two intraoperative and two delayed bleeders required surgery . The size of lesion and surgical defect were larger than those reported in the literature . Margins were involved in 8 patients ( 2.7 % ) . Only 4.7 % ( 7/149 ) of patients r and omized to LEEP and 3.4 % ( 5/145 ) with excisional laser had persistent or recurrent CIN on follow-up . Factors predisposing to failure included depth of surgical defect , grade of lesion , and operator 's expertise . With this approach , 69 % of patients referred for cytology of CIN were adequately managed in the first visit , which contrasts to classical management that reaches the state of treatment in 30 % of patients . LEEP appears to be faster , less costly , and requires less expertise . Its use in conjunction with adequate screening is recommended for developing countries Women with abnormal smears have an increased risk of developing cervical cancer . During the 8 years following conservative treatment of cervical intraepithelial neoplasia ( CIN ) , their risk of invasive cervical cancer is about 5 times greater than that of the general population . Human papillomavirus ( HPV ) has been associated with the natural history of both CIN and cervical cancer . To date , there have been no published reports on the predictive value of HPV testing in the treatment outcome of CIN . A prospect i ve , multi-center , cohort study was conducted on women in the Northwest of Engl and who were attending for treatment of CIN . They were asked to complete a question naire , which included a detailed smoking history . Pre- and post-treatment HPV testing was performed on cervical biopsies and cervical swab , being taken with the first follow-up smear at 6 months . A nested case-control analysis was performed , cases being defined as women who developed CIN within the 2 years of treatment and controls being sample d from those who did not experience treatment failure within 2 years . Multiple conditional logistic regression is used to study the factors associated with treatment failure of CIN . The cohort included 958 women of whom 77 ( 8 % ) experienced treatment failure ( cases ) . Two controls were matched to each case ( 154 ) . Smoking status was significantly associated with CIN treatment failure(p= 0.0013 ) . Current smokers had a 3-fold increased risk of treatment failure of CIN as compared to non-smokers ( 95 % CI 1.65 to 5.91 ) . Five hundred twenty-five women underwent HPV sampling following treatment , of whom 47 ( 8.9 % ) developed further CIN . Post-treatment positive HPV testing was found to be strongly associated with treatment failure of CIN ( OR 23.3 ; 95 % CI 3.15 - 172.1 ) . In 11/45 cases with negative smear at first follow-up , the HPV test was positive . The combination of both HPV and cytology in the first follow-up visit predicted treatment failure in 72 % of the cases . Cigarette smoking is a factor , which , independently of HPV infection , influences the treatment outcome of CIN . Smokers and those who are HPV positive during follow-up appear to require longer , more intensive follow-up . HPV testing requires careful consideration as part of routine follow-up protocol following treatment of CIN OBJECTIVES To evaluate the therapeutic and diagnostic potential of large loop excision of the transformation zone ( LLETZ ) in the management of cervical dysplasia ( CD ) when colposcopy is satisfactory ; to determine if there is a relationship between completeness of excision and outcome . STUDY DESIGN Ninety loop diathermies performed in the management of CD were studied prospect ively . RESULTS Eighty ( 88.89 % ) were indicated due to a high grade CD , 7 ( 7.78 % ) due to a low grade CD and 3 LLETZ ( 3.35 % ) due to a cytology-biopsy discordance . The margins were free of disease on 69 occasions ( 76.67 % ) ; on 15 ( 16.67 % ) the margins were affected by the disease and on 6 ( 6.67 % ) they were not evaluable . Using the Kaplan-Meier approach to survival analysis , the cumulative probability of continuing free of disease at the end of our study ( 36 months ) was 0.89 . In the margins free of disease group , patients stayed free of disease for an average of 32.98 months , and the cumulative probability of continuing free of disease at 36 months was 0.97 . In the affected-margins group , patients stayed free of disease for an average of 20.91 months and the cumulative probability of continuing free of disease at 36 months dropped to 0.70 . In the unevaluable-margins group , patients stayed free of disease for an average of 19.50 months and the cumulative probability of continuing free of disease at 36 months dropped still further to 0.67 . Applying the Mantel-Cox Log-Rank Test we obtained differences among these three groups that are statistically significant ( P<0.005 ) . CONCLUSIONS LLETZ could be considered the treatment of choice for CD when colposcopy is satisfactory , as it is effective , simple , fast , inexpensive , unaggressive , and of low morbidity . It also permits adequate pathology reporting . When a pathology report states that the margins of the specimen are not free of disease or are not evaluable , special caution in follow-up may be warranted The aims of the study were to investigate the relationship between human papillomavirus ( HPV ) DNA status and recurrence of cervical intraepithelial neoplasia ( CIN ) after loop excision ( LEEP/LLETZ ) . Women ( n=161 ) who underwent loop excision for CIN III and who were followed up prospect ively for at least 4 years were the study cohort . Cervical smear cytology and testing for HPV DNA was performed at 3 , 6 and 12 months prospect ively and thereafter at intervals of 6 - 12 months , using the PCR method with a consensus primer targeting the L1 region . There has been no recurrence in 141 ( 81.6 % ) out of 161 subjects , while squamous intra-epithelial lesions ( SIL ) of low or high grade on cytology and CIN grade I-III on histology have been detected in 20 subjects . Prior to loop excision , HPV DNA was detected in 17 subjects who developed recurrence ( 9 had type 16 , 2 each had types 18 and 52 , and 1 each had types 31 , 51 , 58 , and unknown ) . Within 3 months postoperatively , 12 ( 70.7 % ) subjects became negative for HPV , but 2 remained positive for the same type ( 1 each had types 16 , 18 ) , along with high- grade SIL on cytology , and CIN III on histology within 6 months , so repeat loop excision was performed . On the other h and , cytological findings were normalized in all transiently infected subjects within 18 - 36 months . Our results suggest that loop excision has improved HPV infection in many cases of CIN III and the persistent infection with a high-risk type of HPV is a predictor of the recurrence of CIN grade III BACKGROUND AND OBJECTIVE Publication bias and other sample size effects are issues for meta-analyses of test accuracy , as for r and omized trials . We investigate limitations of st and ard funnel plots and tests when applied to meta-analyses of test accuracy and look for improved methods . METHODS Type I and type II error rates for existing and alternative tests of sample size effects were estimated and compared in simulated meta-analyses of test accuracy . RESULTS Type I error rates for the Begg , Egger , and Macaskill tests are inflated for typical diagnostic odds ratios ( DOR ) , when disease prevalence differs from 50 % and when thresholds favor sensitivity over specificity or vice versa . Regression and correlation tests based on functions of effective sample size are valid , if occasionally conservative , tests for sample size effects . Empirical evidence suggests that they have adequate power to be useful tests . When DORs are heterogeneous , however , all tests of funnel plot asymmetry have low power . CONCLUSION Existing tests that use st and ard errors of odds ratios are likely to be seriously misleading if applied to meta-analyses of test accuracy . The effective sample size funnel plot and associated regression test of asymmetry should be used to detect publication bias and other sample size related effects BACKGROUND High-risk human papillomavirus infection plays a predominant role in the pathogenesis of preinvasive and invasive cervical cancer . One of the recognized treatments of cervical intraepithelial neoplasia is conization . The aim of this study was to evaluate if cold-knife conization is sufficient to eliminate cervical intraepithelial neoplasia and the associated high-risk HPV infection . PATIENTS AND METHODS Thirty-seven high-risk HPV-positive women who underwent cold-knife conization entered this study . The cervical sampling for HPV DNA was performed using the Digene cervical sample r. Smears were taken immediately before and 3 months after conization and the patients were followed-up for 2 years . RESULTS High-risk HPV was identified in all 37 patients before conization . In 4 out of 37 patients a coincidence of low/intermediate and high-risk HPV types was present . A CIN II was detected in 5 out of 37 , a CIN III in 25 out of 37 and a carcinoma in situ in 7 out of 37 cases . Follow-up at three months revealed that HPV was eradicated by conization in 73 % . Patients with persistent HPV infection tended to be older compared to patients with eliminated HPV infection ( mean : 34 vs. 36 years ; p = 0.25 ) and showed a higher rate of severe dysplasia ( p = 0.07 ) . A high HPV prevalence among patients with positive resection margins and /or recurrence disease was detected ( 83 % and 100 % , respectively ) . A statistically significant higher rate of positive margins and recurrences was observed in patients with persistent compared to patients with eliminated HPV infection ( 50 % vs. 4 % . p = 0.001 and 30 % vs. 0 % , p = 0.003 ) . CONCLUSION The data of the present study demonstrated that a high-risk HPV infection is successfully eliminated by conization in most cases . A high HPV prevalence in patients who had positive cone margins and /or disease recurrence was observed . Patients with persisting HPV infection after conization show statistically significant higher rates of positive resection margins and are at increased risk of disease recurrence . HPV testing seems to be , therefore , a valuable tool to monitor the therapeutic results of conization and to discriminate patients who have a higher risk of disease recurrence Adequate follow‐up of women who have undergone conization for high‐ grade cervical lesions is crucial in cervical cancer screening programs . We evaluated the performance of testing for high‐risk human papillomavirus ( HPV ) types , cytology alone , and combined testing in predicting cervical intraepithelial neoplasia grade 2 or worse ( CIN2 + ) after conization OBJECTIVE To investigate whether high-risk HPV infection associated with cervical intraepithelial neoplasia ( CIN ) was successfully eliminated after electrosurgical conization by large-loop excision of the transformation zone ( LLETZ ) . STUDY DESIGN 142 women , who were admitted for conization of CIN 1 - 3 were recruited into a prospect i ve follow-up study of HPV infection , including cervical sampling for HPV DNA before , and then 3 , 6 and 12 months after surgery . We examined whether there were any differences in the rate of HPV DNA positivity after LLETZ between specific risk groups , such as patients with primary ( i.e. before surgical treatment ) high-risk HPV infection , CIN of different grade s , and positive margins . RESULTS We did not detect statistically significant differences between specific risk groups . According to the assay used ( hybrid capture II ) at the last follow-up visit 94 % of primarily infected patients were completely free from infection with high-risk HPV types , while 6 % had persisting HPV infection . CONCLUSIONS With a detection limit of 5000 genomes/ml HPV DNA the hybrid capture II results revealed , that after electrosurgical removal of CIN in 94 % of patients testing positive for high-risk HPV DNA prior to surgery were negative 12 months post-surgery Objective To determine whether frozen section in conisation improves the management of cervical intraepithelial neoplasia Objectives The aim of this study was to examine the accuracy of the presence of high‐risk human papillomavirus ( HR‐HPV ) DNA ( HR‐HPV DNA test ) postconisation as prediction of recurrent or residual cervical intraepithelial neoplasia ( CIN ) after treatment of high‐ grade cervical intraepithelial lesions ( CIN2 + ) in a prospect i ve study and to compare this with follow‐up cytology and the marginal status of the excised tissue The aim of this case-control study was to examine if type-specific human papillomavirus ( HPV ) DNA geno-typing before and after treatment of high- grade cervical intra-epithelial neoplasia ( CIN ) improves prediction of recurring or persisting CIN 2 or 3 compared with follow-up cytology or high-risk (hr)HPV testing . Women with biopsy-proven recurrence of CIN 2 or 3 ( cases ) in a follow-up period of at least 24 months after treatment of high- grade CIN were compared with women without recurrence ( controls ) . These cohorts were identified by a data base search of the Riatol Laboratoria ( Antwerp , Belgium ) . In a cohort of 823 women treated with conisation for high- grade CIN between January 2001 and December 2007 , 21 patients with a histologically proven recurrence of CIN2 + were identified . A group of women ( n=42 ) from the same cohort without recurrence was r and omly chosen . We found that hrHPV testing at 6 months post-treatment is significantly more sensitive compared with follow-up cytology ( ratio : 1.31 , 95 % confidence interval ( CI ) : 1.10 - 1.54 ) , but less specific ( ratio : 0.85 , 95 % CI : 0.81 - 0.90 ) to predict failure of treatment . When compared with hrHPV testing , HPV geno-typing is more efficient ( equal sensitivity , but higher specificity , ratio : 1.43 , 95 % CI : 1.280 - 1.62 ) . When compared with follow-up cytology , HPV geno-typing is more sensitive ( ratio : 1.31 , 95 % CI : 1.10 - 1.54 ) and more specific ( ratio : 1.22 , 95 % CI : 1.14 - 1.36 ) . All women who developed a recurrence tested positive for hrHPV . The negative predictive value in the absence of hrHPV DNA was 100 % . Six months after treatment HPV geno-typing is the most sensitive and specific method to predict recurrent or persistent CIN 2 - 3 in the next 24 months OBJECTIVE To evaluate the role of human papillomavirus ( HPV ) testing in post-treatment follow-up of patients after therapeutic excision of the cervix due to positive screening tests . STUDY DESIGN A hospital-based retrospective analysis was performed with prospect i ve collection of patient data of women screened for cervical cancer at a Gynecologic Outpatient Clinic . Patients after therapeutic excision due to positive screening results were identified and followed up with HPV testing and serial cytology . RESULTS After 61 treatment for cervicalis intraepithelialis neoplasia ( CIN ) , high-risk HPV infection was detected during the post-treatment follow-up at 18 cases ( 29.5 % ) , 10 of them had persisting cytological atypia ( positive predictive value ( PPV ) : 56 % ) , 5 developed CIN ( PPV : 28 % ) . When the HPV test was negative ( 43 patients ) in the post-treatment period , neither CIN nor persisting cytological atypia developed ( negative predictive value ( NPV ) : 100 % ) during 1201 patient months ( median 26 months ) . CONCLUSIONS A negative HPV test eliminates the risk of recurrent disease after treatment for CIN OBJECTIVE The aim of the study was to evaluate human papillomavirus ( HPV ) testing during the follow-up of patients after conization by loop electrosurgical excision for high- grade squamous intraepithelial lesion . METHODS A prospect i ve study was conducted on 205 patients who underwent conization for high- grade squamous intraepithelial lesion ( CIN 2 or 3 ) . Loop electrosurgical excision procedure ( LEEP ) was used in all cases . High-risk HPV testing was realized by the Hybrid Capture II system before and 3 months after conization . RESULTS Of the 205 patients , 193 ( 94.1 % ) were positive for the HPV test before conization . Seventy-one were HPV positive after conization ( 34.6 % ) . The margins were positive in 36.1 % . Residual disease was observed in 27 cases ( 13.2 % ) . Four patients ( 2 % ) developed a recurrence after a mean follow-up of 18.1 months ( + /-12 ) . There was no correlation between pretreatment HPV testing and the residual disease or recurrence . Patients with positive margins were significantly more likely to have residual disease than those with negative margins ( P < 0.0001 ) . Residual disease was more likely to occur when the posttreatment HPV test was positive ( P < 10(-7 ) ) . All recurrences were observed in patients with a positive posttreatment HPV test ( P < 0.05 ) . Residual disease and recurrence were correctly predicted with a sensitivity of 81 and 100 % , respectively , and a negative predictive value of 96 and 100 % . CONCLUSION Posttreatment HPV testing could be useful in the follow-up of patients after conization . In case of negative posttreatment HPV testing , the frequency of follow-up could be reduced , particularly in those patients with free margins |
1,895 | 31,537,570 | Review findings identified a diverse and disaggregated body of ACP literature describing barriers and enablers to ACP in general practice , and interventions testing single or multiple mechanisms to improve ACP generally without explicit consideration for level of influence . | OBJECTIVES How advance care planning ( ACP ) is conceptualised in Australia including when , where and how ACP is best initiated , is unclear .
It has been suggested that healthcare delivered in general practice provides an optimal setting for initiation of ACP discussion s but uptake remains low .
This systematic review and critical interpretive synthesis sought to answer two questions : ( 1 ) What are the barriers and enablers to uptake of ACP in general practice ? (
2 ) What initiatives have been used to increase uptake of ACP in general practice ? | CONTEXT Primary care physicians are well placed to identify patients in need of advance care planning ( ACP ) and initiate ACP in advance of an acute situation . OBJECTIVES This study aim ed to underst and Australian general practitioner ( GP ) clinical decision making relating to a patient 's " need for ACP " and the likelihood of initiating ACP . METHODS An experimental vignette study pseudor and omly manipulated factors thought to influence decision making regarding ACP . Patient-level factors included gender , age , type of disease , medical severity , openness to ACP , doctor-patient relationship , and family support . An accompanying demographic survey assessed health professional-level factors , including gender , years of experience , place of training , place of practice , caseload of patients with ACP , direct personal experience in ACP , and self-reported attitudes toward ACP . Seventy GPs were recruited , and each completed six unique vignettes , providing ratings of patient need for ACP , importance of initiating ACP in the coming months , and likelihood of initiating ACP at the next consultation . RESULTS Older patients , with malignant or cardiovascular disease , severe clinical presentations , good doctor-patient relationship , female gender , and poor family support were more likely to receive prompt ACP . Positive GP attitudes toward ACP were associated with greater likelihood of initiating ACP promptly . CONCLUSION Patients with presentations suggesting higher mortality risk were identified as being in need of ACP ; however , the likelihood of initiating ACP was sensitive to GP attitudes and psychosocial aspects of the doctor-patient interaction . Training material s aim ed at encouraging GP involvement in ACP should target attitudes toward ACP and communication skills , rather than focusing solely on prognostic risk This summary reflects on this monograph regarding multilevel intervention ( MLI ) research to 1 ) assess its added value ; 2 ) discuss what has been learned to date about its challenges in cancer care delivery ; and 3 ) identify specific ways to improve its scientific soundness , feasibility , policy relevance , and research agenda . The 12 su bmi tted chapters , and discussion of them at the March 2011 multilevel meeting , were review ed and discussed among the authors to elicit key findings and results addressing the questions raised at the outset of this effort . MLI research is underrepresented as an explicit focus in the cancer literature but may improve implementation of studies of cancer care delivery if they assess context ual , organizational , and environmental factors important to underst and ing behavioral and /or system-level interventions . The field lacks a single unifying theory , although several psychological or biological theories are useful , and an ecological model helps conceptualize and communicate interventions . MLI research design s are often complex , involving nonlinear and nonhierarchical relationships that may not be optimally studied in r and omized design s. Simulation modeling and pilot studies may be necessary to evaluate MLI interventions . Measurement and evaluation of team and organizational interventions are especially needed in cancer care , as are attention to the context of health-care reform , eHealth technology , and genomics-based medicine . Future progress in MLI research requires greater attention to developing and supporting relevant metrics of level effects and interactions and evaluating MLI interventions . MLI research holds an unrealized promise for underst and ing how to improve cancer care delivery Advance directives name a surrogate decision maker or provide written instructions with the intent of extending patient autonomy with respect to end-of-life decisions [ 1 - 3 ] . Supported on various grounds by the public [ 1 ] , physicians [ 4 ] , ethicists [ 5 ] , and legislators [ 6 ] , advance directives have also been promoted as a way to control the high costs of health care at the end of life [ 7 , 8 ] . Most patients are interested in establishing advance directives , but few actually complete them [ 1 , 9 , 10 ] . In 1990 , the U.S. Congress passed the Patient Self-Determination Act , which requires hospitals to inform admitted patients about their right to record advance directives [ 6 , 11 ] . The Act does not dictate who should initiate these discussion s ( patients , physicians , or an admissions officer , for example ) [ 12 , 13 ] . It is therefore not surprising that the Act has had little effect on the rate of completion of advance directives [ 11 , 13 - 15 ] . Because hospitalized patients are often acutely ill and lose their ability to make decisions [ 3 ] , it may be more appropriate to discuss such issues before hospitalization [ 12 , 16 , 17 ] . Other interventions aim ed at increasing the establishment of advance directives have met with mixed success [ 18 ] . With one exception [ 19 ] , patient education has had little or no effect [ 20 - 24 ] . More effective interventions have trained physicians , social workers , or counselors to discuss advance directives [ 18 , 22 , 25 - 27 ] ; this has led to the conclusion that counseling by a clinician is the best catalyst for the completion of advance directives [ 28 ] . However , little is known about how to educate and motivate clinicians to solicit advance directives [ 28 ] . We [ 29 - 31 ] and others [ 32 ] have previously shown that computer reminders increase physician compliance with practice guidelines . In this study , we tested the hypothesis that reminding primary care physicians to discuss advance directives would stimulate such discussion s and lead to the establishment of more advance directives . Methods Setting and Patients This study was approved by the institutional review board of Indiana University as expedited research with waiver of informed consent from both patients and physicians . It was conducted in the General Medicine Practice [ 31 ] , an academic primary care practice affiliated with an urban public teaching hospital . This practice is staffed by general internal medicine faculty , fellows , and residents . Each resident and fellow attends the General Medicine Practice one half-day per week ; faculty attend one to four half-days per week . Residents always practice with the same attending faculty physicians . All physicians , except for study investigators , were eligible to participate . At the time of this study , the General Medicine Practice comprised four separate practice s with separate waiting areas , clerks , and nurses . Each practice held eight half-day sessions per week . Each session was attended by two faculty members and two or three residents , each of whom provided primary care to assigned panels of patients . Residents were required to briefly discuss each patient with the attending faculty . Fellows served as faculty and were treated as such . Since 1981 , a computerized program has r and omly assigned new physicians to the practice sessions [ 31 ] . New patients have been sequentially assigned to open appointment slots ; this result ed in no important differences in patients or clinical practice among the sessions [ 29 , 33 ] . We included patients who were at risk for acute deterioration ( and therefore might benefit from advance directives ) because of advanced age ( 75 years , the typical threshold for the oldest old ) or because they were 50 years of age or older and had one of the following chronic conditions : cardiac ischemia , heart failure , chronic lung disease , cancer other than nonmelanomatous skin cancer , cerebrovascular disease , renal insufficiency , or cirrhosis . We chose 50 years of age as a cut-off to yield sufficient numbers of patients . A computer program identified eligible patients among those with scheduled appointments at the General Medicine Practice by using problem lists and test results stored in the Regenstrief Medical Record System [ 34 ] . Eligible patients who kept appointments at the General Medicine Practice were approached by research assistants in the waiting room . The research assistants , who were blinded at all times to the patients ' study groups , explained the study to the patients , invited them to participate , and interviewed those who agreed to participate ; patients from nursing homes and prisons and patients who were deaf or did not speak English were excluded . The assistants then administered the Pfeiffer Mental Status Question naire [ 35 ] ; patients whose scores indicated cognitive dysfunction were excluded . The remaining patients provided sociodemographic information and stated whether they had previously discussed or completed advance directives ; patients who had completed advance directives were excluded . Patients also stated their preferences with regard to six treatments in the event of a terminal illness [ 36 ] . Advance Directives Before the study , we created two separate forms for instruction directives and proxy directives ; these forms became the official advance directive documents of the hospital and its outpatient services . The instruction directive allowed patients to indicate whether , in the event of terminal illness and mental incapacity , they wanted or did not want eight types of care : cardiopulmonary resuscitation , mechanical ventilation , surgery , invasive procedures , nutrition and hydration , transfusion of blood or blood products , antibiotics , or noninvasive diagnostic tests . The primary care physician had to sign each completed instruction directive form to indicate that he or she was aware of its contents . The proxy directive design ated both primary and secondary health care representatives . We placed both advance directive forms in a drawer of the desk of each physician in the General Medicine Practice . We also placed the forms in a bin near the door of the staff room along with other forms and requisitions and business reply envelopes for patients who wanted to complete the forms at home . Research assistants entered the data from completed forms into the Regenstrief Medical Record System , where the forms were available for viewing through computer terminals and workstations in all inpatient and outpatient venues [ 34 ] . Before the study , the three physician-investigators presented the basic concepts of advance directives at gr and rounds . They also had face-to-face meetings with each physician in the General Medicine Practice and explained how to complete and process the forms . We encouraged physicians to discuss advance directives with their elderly and debilitated patients and posted flyers in each practice staffing room suggesting that physicians discuss advance directives with patients who had the target study conditions . Study Methods The intent of the r and omization scheme was to expose physicians to the same type of reminder or reminders , or no reminders , during all of their scheduled primary care visits with enrolled patients . At the time of this study , 32 weekly half-day sessions took place on the four General Medicine Practice practice s. Two sessions attended by study investigators were excluded . We r and omly assigned all of the physicians who worked in a particular half-day session to the same reminder category . At the time of r and omization , 16 physicians ( all of whom were faculty members ) practice d in more than 1 session per week ( 14 practice d in 2 sessions and 2 practice d in 3 sessions ) . Therefore , we r and omly assigned the sessions in a stepped manner by first allocating the 16 physicians and all of their associated sessions to four categories : control ( no reminders ) , computer-generated reminders for instruction directives , computer-generated reminders for proxy directives , and computer-generated reminders for both types of directives . We then r and omly assigned the remaining 8 sessions and their physicians to the four categories ( Table 1 ) . Each practice contained sessions in all four categories , which were equally distributed between mornings and afternoons . Table 1 . Results of R and omization All physicians routinely received computer-generated reminders for patients with scheduled visits . They were reminded to give preventive care , note abnormal test results , and avoid drug interactions [ 29 , 34 ] . These reminders appeared at the bottom of computer-generated printed encounter forms [ 34 ] ( Figure 1 ) . Physicians routinely review ed the encounter forms and the practice chart immediately before visiting the patient . As recommended by Litzelman and coworkers [ 37 ] , the advance directive reminders were followed by a choice list ( discussed today , next visit , not applicable , patient too ill , patient refuses to discuss , I disagree with advance directives ) . Instruction directives were called advance directives , and proxies were called health care representatives ( Figure 1 ) . Figure 1 . General Medicine Practice encounter form showing reminders for both types of advance directive . After patients were enrolled , research assistants attempted to interview them in the waiting room after each scheduled appointment to assess whether they had discussed advance directives with their physicians that day . Patients who answered yes were defined as having had an advance directive discussion . During the first scheduled General Medicine Practice visit in the 5-month period between 11 and 16 months after enrollment , a close-out interview was attempted . If no scheduled visit had occurred by 15 months after enrollment , the close-out interview was attempted by telephone . Form completion was defined as having occurred if either completed form was received between study enrollment and 30 days after the final interview ( this made it possible to receive by mail forms that were completed after the close-out OBJECTIVE : To determine efficient ways of promoting advance directives among heterogeneous population s of elderly ambulatory patients . DESIGN : One-year quasi-experimental trial . SETTING : Five suburban and urban health centers in one region of a large managed care organization . One additional suburban center served as a control site . PARTICIPANTS : Individuals ages 65 and older ( N=2,120 ) who were continuously enrolled and had a health maintenance visit with their primary care provider during the study year . INTERVENTION : Physician education ( oral and written ) and physician and patient prompts to discuss advance directives . MAIN RESULTS : Sixty-six ( 7.8 % ) of patients at the intervention centers completed new advance directives , versus 9 of 1,277 ( < 1 % ) at the comparison center ( P<.001 ) . Patients 75 and older were twice as likely ( odds ratio [ OR ] , 2.0 ; 95 % confidence limits [ CL ] , 1.2 to 3.3 ) as those 65 to 74 to file a new advance directive , and the odds were twice as great ( OR , 2.6 ; 95 % CL , 1.4 to 4.6 ) at centers serving communities with median household income over the state median . Gender , recent hospitalization , emergency room visits , and number of chronic conditions were not related to making new directives nor was predominant ethnicity of the center community ( African-American versus white ) . Adjusted for these factors , the intervention result ed in a 20-fold increase ( 95 % CL , 10.4 to 47.8 ) in the odds of creating a new advance directive . Doctors reported barriers of time and unwillingness to press discussion s with patients . CONCLUSIONS : A replicable intervention largely targeting doctors achieved a modest increase in advance directives among elderly ambulatory patients . Future interventions may need to target lower-income patients , “ younger ” elderly , and more specifically address doctors ’ attitudes and comfort discussing advance directives BACKGROUND Since 1991 , hospitals have asked patients whether they have advance directives , but few patients complete these documents . We assessed two simple interventions to improve completion of advance directives among elderly or chronically ill out patients . METHODS We conducted a cluster r and omized controlled trial involving 1079 patients from five general medicine clinics that were affiliated with an academic medical center . Patients were either > or = 70 years of age or > or = 50 years old with a chronic illness . The study comprised three arms : physician reminders recommending documentation of advance directives , physician reminders plus mailing advance directives to patients together with educational literature , or neither intervention ( control ) . The main outcome measure was completion of an advance directive . RESULTS After 28 weeks , 1.5 % ( 5/332 ) of patients in the physician reminder group , 14 % ( 38/277 ) in the physician reminder plus patient mailing group , and 1.8 % ( 5/286 ) in the control group had completed advance directives . In multivariate analyses , patients in the physician reminder plus patient mailing group were much more likely than controls to have completed advance directives ( odds ratio [ OR ] = 5.9 ; 95 % confidence interval [ CI ] : 1.5 to 22 ) , whereas patients in the physician reminder-only group were no more likely than controls to have completed advance directives ( OR = 0.88 ; 95 % CI : 0.21 to 3.7 ) . CONCLUSION Mailing health care proxy and living will forms and literature to patients before an appointment at which their physicians received a reminder about advance directives yielded a small but significant improvement in completion of these documents . A physician reminder alone did not have an effect OBJECTIVE To determine whether an advance directive re design ed to meet most adults ' literacy needs ( fifth grade reading level with graphics ) was more useful for advance care planning than a st and ard form ( > 12th grade level ) . METHODS We enrolled 205 English and Spanish-speaking patients , aged > /=50 years from an urban , general medicine clinic . We r and omized participants to review either form . Main outcomes included acceptability and usefulness in advance care planning . Participants then review ed the alternate form ; we assessed form preference and six-month completion rates . RESULTS Forty percent of enrolled participants had limited literacy . Compared to the st and ard form , the re design ed form was rated higher for acceptability and usefulness in care planning , P</=0.03 , particularly for limited literacy participants ( P for interaction < /=0.07 ) . The re design ed form was preferred by 73 % of participants . More participants r and omized to the re design ed form completed an advance directive at six months ( 19 % vs. 8 % , P=0.03 ) ; of these , 95 % completed the re design ed form . CONCLUSIONS The re design ed advance directive was rated more acceptable and useful for advance care planning and was preferred over a st and ard form . It also result ed in higher six-month completion rates . PRACTICE IMPLICATION S An advance directive re design ed to meet most adults ' literacy needs may better enable patients to engage in advance care planning OBJECTIVES To estimate the proportion of seniors in a large health maintenance organization ( HMO ) who had been asked about their end-of-life care preferences ( EOLCPs ) by a clinician and who had completed an advance directive ( AD ) . To examine the association of having had an EOLCP discussion and AD completion . SUBJECTS AND METHODS A r and om sample of HMO members aged 65 years or older were asked to complete a mailed survey about health and health-related issues in 1996 . Data provided by 5117 seniors ( 80 % response rate ) were used to estimate the prevalence of EOLCP and AD among seniors overall and in specific risk groups . Bivariate and multiple logistic regression models were used to identify predictors of AD completion , especially having been asked about EOLCP . RESULTS One third of seniors reported having an AD on file with the HMO , but only 15 % had talked with a clinician about EOLCP . Both having been asked about EOLCP and having an AD were positively associated with age , but not significantly associated with sex , race/ethnicity , marital status , or self-rated health status . Having been asked by a clinician about EOLCP was significantly associated with completion of an AD . CONCLUSION Clinicians can play an important role in increasing AD completion rates among seniors by bringing up the subject of EOLCPs Autonomous decision making by patients can be enhanced by a variety of advance directives . These directives , the living will and the durable power of attorney , have an ethical and legal basis on which the patient can prospect ively make decisions about life-sustaining therapies . The strength of these directives can be enhanced by the use of the Values History , serving as an adjunct to them . The Values History can also be used as a clinical tool to elicit the values of the patient as they pertain to chronic as well as critical medical care . Documentation of the patient 's values will give the health care team a fuller underst and ing of the patient 's preferences and directions OBJECTIVE : To compare the effectiveness of two means for increasing the use of advance medical directives : written material s only versus written material s and an educational videotape . DESIGN : Population -based , r and omized controlled trial with 3-month follow up . SETTING : Kaiser Permanente Colorado Region , a not-for-profit group-model health maintenance organization . PARTICIPANTS : A population -based sample of all 1,302 members aged 75 years and older who used the Franklin Medical Office , excluding 55 persons who died or disenrolled during the study period or were identified by their physicians as blind or cognitively impaired . INTERVENTIONS : All subjects were mailed a 10-page cartoon-illustrated educational pamphlet on patient choices , a selection of Colorado advance medical directive forms , and a guide to their completion ; 619 subjects also were mailed a 20-minute videotape on advance directives . Both groups had access to a study nurse for assistance in completing and placing advance medical directives . MEASUREMENTS AND MAIN RESULTS : The main outcome measure is the proportion of subjects who placed a directive in their medical record for the first time . Placement rates increased almost identically , from 21.2 % to 35.0 % in the written material s-only group and from 18.9 % to 32.6 % in the group receiving the videotape ( 95 % confidence interval for difference −0.04 , 0.04 , p=.952 ) . CONCLUSIONS : In an elderly population with a substantial baseline placement rate , mailing of written material s substantially increased placement of an advance directive in the medical record , but the addition of a videotape did not . Mailing the video did increase the use of treatment trials and made patients more aware of reasons not to use advance directives Background : Advance care planning ( ACP ) is an instrumental mechanism aim ed at preserving patient autonomy . Numerous interventions have been proposed to facilitate the implementation of ACP ; however , rates of completed advance directives ( ADs ) are universally low . Patient electronic portal messaging is a newer tool in patient – provider communication which has not been studied as a method to promote ACP . In this study , we hypothesized that the use of ACP-specific patient electronic messages would increase rates of AD completion in patients aged 65 years and older in an academic primary care practice . Methods : All primary care patients , aged 65 + , who had previously enrolled in a patient electronic messaging system , within an academic primary care practice , were included for r and omization . Two hundred patients were r and omized to receive an electronic message . The primary outcome was the proportion of patients in each group who completed an AD , 3 months after intervention . Secondary outcomes included clinical utility of the completed ADs and proportion of patients who viewed their electronic messages . Results : The intervention group completed an AD 5.5 % of the time when compared to 2 % in the control group ( odds ratio 3.2 [ 1.6 - 6.3 ] ) . Up to 74.5 % of patients opened their electronic messages . Conclusion : Among primary care patients aged 65 years and older , use of AD-specific electronic messaging statistically significantly increased the rate of AD completion , but the absolute number of completed AD remained relatively low . These data suggest that this valuable communication tool holds opportunities for further improvement . Older , frailer adults were more likely to complete an AD , and prompted directives were more likely to include a written expression of the individual ’s health-care values and preference BACKGROUND : Discussion s of end-of-life care should be held prior to acute , disabling events . Many barriers to having such discussion s during primary care exist . These barriers include time constraints , communication difficulties , and perhaps physicians ’ anxiety that patients might react negatively to such discussion s. OBJECTIVE : To assess the impact of discussion s of advance directives on patients ’ satisfaction with their primary care physicians and outpatient visits . DESIGN : Prospect i ve cohort study of patients enrolled in a r and omized , controlled trial of the use of computers to remind primary care physicians to discuss advance directives with their elderly , chronically ill patients . SETTING : Academic primary care general internal medicine practice affiliated with an urban teaching hospital . PARTICIPANTS : Six hundred eighty-six patients who were at least 75 years old , or at least 50 years old with serious underlying disease , and their 87 primary care physicians ( 57 residents , 30 faculty general internists ) participated in the study . MEASUREMENTS AND MAIN RESULTS : We assessed patients ’ satisfaction with their primary care physicians and visits via interviews held in the waiting room after completed visits . Controlling for satisfaction at enrollment and physician , patient , and visit factors , discussing advance directives was associated with greater satisfaction with the physician ( P=.052 ) . At follow-up , the strongest predictor of satisfaction with the primary care visit was having previously discussed advance directives with that physician ( P=.004 ) , with a trend toward greater visit satisfaction when discussion s were held during that visit ( P=.069 ) . The percentage of patients scoring a visit as “ excellent ” increased from 34 % for visits prior without advance directive discussion s to 51 % for visits with such discussion s ( P=.003 ) . CONCLUSIONS : Elderly patients with chronic illnesses were more satisfied with their primary care physicians and outpatient visits when advanced directives were discussed . The improvement in visit satisfaction was substantial and persistent . This should encourage physicians to initiate such discussion s to overcome communication barriers that might result in reduced patient satisfaction levels BACKGROUND Advance care planning ( ACP ) aims to guide health care in the event of decisional incapacity . Interventions to promote ACP have had limited effectiveness . We conducted an educational and motivational intervention in Department of Veterans Affairs outpatient clinics to increase ACP use and proxy and health care provider underst and ing of patients ' preferences and values . METHODS We recruited 23 providers and up to 14 of each of their patients ; the patients were r and omized to the control or intervention group . Eligibility criteria included a preexisting relationship with the provider , age 55 years or older , chronic health condition(s ) , and no recorded advance directive . The intervention group ( n = 119 ) received an ACP workbook , motivational counseling by social workers , and cues to providers to discuss ACP . The control group ( n = 129 ) received an advance directive booklet . RESULTS The intervention patients reported more ACP discussion s with their providers ( 64 % vs 38 % ; P<.001 ) . Living wills were filed in the medical record twice as often in the intervention group ( 48 % vs 23 % ; P<.001 ) . Provider-patient dyads in the intervention group had higher agreement scores than the control group for treatment preferences , values , and personal beliefs ( 58 % vs 48 % , 57 % vs 46 % , and 61 % vs 47 % , respectively ; P<.01 for all comparisons ) . The agreement scores for the proxy-patient dyads did not differ between groups for treatment preferences and values , but were higher in the intervention than the control group for personal beliefs ( 67 % vs 56 % ) . CONCLUSION This intervention demonstrates mixed results and highlights the ongoing challenges of helping health care providers and potential proxy decision makers represent patient preferences and values BACKGROUND Advance care planning ( ACP ) provides patients with the ability to make their decisions known about how they would like to be treated if they lose capacity . Medical practitioners have a key role to play in providing information on ACP to their patients . This research explores their knowledge and attitudes to advance care planning and how this affects their practice . AIM The objective of this study is to assess the NSW medical practitioners ' knowledge and self-reported practice of ACP . METHODS A postal survey of a r and om sample of 650 general practitioners plus 350 medical specialists from specialties most often involved in end-of-life decisions was conducted . Respondents ' work location post codes were subsequently used to assign respondents to one of the eight NSW Area Health Services . The main outcome measures were medical practitioners ' knowledge of and practice pertaining to ACP . RESULTS Thirty-four per cent of specialists ( n = 110 ) and 24 % of general practitioners ( n = 150 ) responded ; the majority of respondents had heard of all ACP options . However , respondents ' underst and ing of the uses and legal requirements of the relevant ACP options vary widely . CONCLUSIONS Respect for patient wishes expressed in advance directives is reassuringly high . The findings suggest significant misunderst and ing by medical practitioners of terminologies and systems around substitute decision-making for incompetent persons . Further education and st and ardisation of terminologies and systems across different jurisdictions would assist in addressing these issues . Low response rate , relating to only one legal jurisdiction , means results may not be generalisable OBJECTIVE To examine the attitudes toward , the experience with and the knowledge of advance directives of family physicians in Ontario . DESIGN Cross-sectional survey . PARTICIPANTS A question naire was mailed to 1000 family physicians , representing a r and om sample of one-third of the active members of the Ontario College of Family Physicians ; 643 ( 64 % ) responded . RESULTS In all , 86 % of the physicians favoured the use of advance directives , but only 19 % had ever discussed them with more than 10 patients . Most of the physicians agreed with statements supporting the use of advance directives and disagreed with statements opposing their use . Of the respondents 80 % reported that they had never used a directive in managing an incompetent patient . Of the physicians who responded that they had such experience , over half said that they had not always followed the directions contained in the directive . The proportions of physicians who responded that certain patient groups should be offered the opportunity to complete an advance directive were 96 % for terminally ill patients , 95 % for chronically ill patients , 85 % for people with human immunodeficiency virus infection , 77 % for people over 65 years of age , 43 % for all adults , 40 % for people admitted to hospital on an elective basis and 33 % for people admitted on an emergency basis . The proportions of physicians who felt that the following strategies would encourage them to offer advance directives to their patients were 92 % for public education , 90 % for professional education , 89 % for legislation protecting physicians against liability when following a directive , 80 % for legislation supporting the use of directives , 79 % for hospital policy supporting the use of directives , 73 % for reimbursement for time spent discussing directives with patients and 64 % for hospital policy requiring that all patients be routinely offered the opportunity to complete a directive at the time of admission . CONCLUSIONS Family physicians favour advance directives but use them infrequently . Most physicians support offering them to terminally or chronically ill patients but not to all patients at the time of admission to hospital . Although governments emphasize legislation , most physicians believe that public and professional education programs would be at least as likely as legislation to encourage them to offer advance directives to their patients Objectives It is important that the outcomes of advance care planning ( ACP ) conversations are documented and available at the point of care . Advance care directives ( ACDs ) are a subset of ACP documentation and refer to structured documents that are completed and signed by competent adults . Other ACP documentation includes informal documentation by the person or on behalf of the person by someone else ( eg , clinician , family ) . The primary objectives were to describe the prevalence and correlates of ACDs among Australians aged 65 and over accessing health and residential aged care services . The secondary aim was to describe the prevalence of other ACP documentation . Design and setting A prospect i ve multicentre health record audit in general practice s ( n=13 ) , hospitals ( n=12 ) and residential aged care facilities ( RACFs ; n=26 ) . Participants 503 people attending general practice , 574 people admitted to hospitals and 1208 people in RACFs . Primary and secondary outcome measures Prevalence of one or more ACDs ; prevalence of other ACP documentation . Results 29.8 % of people had at least one ACD on file . The majority were non-statutory documents ( 20.9 % ) . ACD prevalence was significantly higher in RACFs ( 47.7 % ) than hospitals ( 15.7 % ) and general practice s ( 3.2 % ) ( p<0.001 ) , and varied across jurisdictions . Multivariate logistic regression showed that the odds of having an ACD were positively associated with greater functional impairment and being in an RACF or hospital compared with general practice . 21.6 % of people had other ACP documentation . Conclusions In this study , 30 % of people had ACDs accessible and a further 20 % had other ACP documentation , suggesting that approximately half of participants had some form of ACP . Correlates of ACD completion were greater impairment and being in an RACF or hospital . Greater efforts to promote and st and ardise ACDs across jurisdictions may help to assist older people to navigate and complete ACDs and to receive care consistent with their preferences . Trial registration number ACTRN12617000743369 Background : Oklahoma 's Advance Directive completion rate is less than 10 % . We compared the implementation performance of 2 advance directive forms to determine which form could be more successfully disseminated . Methods : The implementation of the Oklahoma Advance Directive ( OKAD ) and the Five Wishes form were compared in an 8-month pair-matched cluster r and omized study in 6 primary care practice s. The outcomes measured during the 22-week implementation included form offering rate , acceptance/completion rate by patients , and documentation in the chart . Twenty semistructured interviews with patients and clinicians were conducted to assess intervention experience . Results : A total of 2748 patient encounters were evaluated . OKAD was offered in 33 % of eligible patient visits ( 493/1494 ) and accepted 54 % of the time ( 266/493 ) . Five Wishes was offered in 36 % of eligible patient visits ( 450/1254 ) and accepted 82 % of the time ( 369/450 ) . Unadjusted analyses found no significant difference in offering of advance directive forms between groups . However , the odds of accepting Five Wishes were 3.89 times that of OKAD ( 95 % CI , 2.88 to 5.24 ; P < .0001 ) . Logistic regression models controlling for several confounders indicated that the acceptance of Five Wishes was favored significantly over OKAD ( OR = 1.52 ; 95 % CI , 1.27 to 1.81 ; P < .0001 ) . Qualitative analyses indicated a clear clinician and patient preference for Five Wishes . Conclusions : Results suggest that Five Wishes was more readable , underst and able , appealing , and usable . It seemed to capture patient preferences for end-of-life care more effectively and it more readily facilitated patient-clinician conversations |
1,896 | 16,856,057 | AUTHORS ' CONCLUSIONS Given that only two r and omised controlled trials were included , and the high risk of bias of both trials , there is insufficient evidence to either support or refute the routine use of mass , selective or opportunistic screening compared to no screening for reducing prostate cancer mortality . | BACKGROUND Any form of screening aims to reduce mortality and increase a person 's quality of life .
Screening for prostate cancer has generated considerable debate within the medical community , as demonstrated by the varying recommendations made by medical organizations and governed by national policies .
Much of this debate is due to the limited availability of high quality research and the influence of false-positive or false-negative results generated by use of the diagnostic techniques such as the digital rectal examination ( DRE ) and prostate specific antigen ( PSA ) blood test .
OBJECTIVES To determine whether screening for prostate cancer reduces prostate cancer mortality and has an impact on quality of life . | PURPOSE Screening with serum prostate specific antigen testing leads to the detection of many prostate cancers early in their natural history . Statistical models have been proposed to predict indolent cancer . We vali date d and up date d model predictions for a screening setting . MATERIAL S AND METHODS We selected 247 patients with clinical stage T1C or T2A from the European R and omized Study on Screening for Prostate Cancer who were treated with radical prostatectomy . We vali date d a nomogram that had previously been developed in a clinical setting . Predictive characteristics were serum prostate specific antigen , ultrasound prostate volume , clinical stage , prostate biopsy Gleason grade , and total length of cancer and noncancer tissue in biopsy cores . Indolent cancer was defined as pathologically organ confined cancer 0.5 cc or less in volume without poorly differentiated elements . Logistic regression was used to up date the previous model and examine the contribution of other potential predictors . RESULTS Overall 121 of 247 patients ( 49 % ) had indolent cancer , while the average predicted probability was around 20 % ( p < 0.001 ) . Effects of individual variables were similar to those found before and discriminative ability was adequate ( AUC 0.76 ) . An up date d model was constructed , which merely recalibrated the nomogram and did not apply additional predictors . CONCLUSIONS Prostate cancers identified in a screening setting have a substantially higher likelihood of being indolent than those predicted by a previously proposed nomogram . However , an up date d model can support patients and clinicians when the various treatment options for prostate cancer are considered BACKGROUND There is no conclusive evidence that screening based on serum prostate-specific antigen ( PSA ) tests decreases prostate-cancer mortality . Since its introduction in the USA around 1990 , uptake of PSA testing has been rapid in the USA , but much less common in the UK . Our aim was to study trends over time in prostate-cancer mortality and incidence in the USA and UK in 1975 - 2004 , and compare these patterns with trends in screening and treatment . METHODS Joinpoint regression analysis of cancer-mortality statistics from Cancer Research UK ( London , UK ) and from the US National Cancer Institute Surveillance , Epidemiology and End Results ( SEER ) programme from 1975 to 2004 was used to estimate the annual percentage change in prostate-cancer mortality in both countries and the points in time when trends changed . The ratio of USA to UK age-adjusted prostate-cancer incidence was also assessed . FINDINGS Age-specific and age-adjusted prostate-cancer mortality peaked in the early 1990s at almost identical rates in both countries , but age-adjusted mortality in the USA subsequently declined after 1994 by -4.17 % ( 95 % CI -4.34 to -3.99 ) each year , four-times the rate of decline in the UK after 1992 ( -1.14 % [ -1.44 to -0.84 ] ) . The mortality decline in the USA was greatest and most sustained in patients aged 75 years or older ( -5.32 % [ -8.23 to -2.32 ] ) , whereas death rates had plateaued in this age group in the UK by 2000 . The mean ratio of USA to UK age-adjusted prostate-cancer incidence rates in 1975 - 2003 was 2.5 , with a pronounced peak around the time that PSA testing was introduced in the USA . Numbers needed to treat to prevent one death from prostate cancer were 33 000 in the 55 - 64-year age group . INTERPRETATION The striking decline in prostate-cancer mortality in the USA compared with the UK in 1994 - 2004 coincided with much higher uptake of PSA screening in the USA . Explanations for the different trends in mortality include the possibility of an early effect of initial screening rounds on men with more aggressive asymptomatic disease in the USA , different approaches to treatment in the two countries , and bias related to the misattribution of cause of death . Speculation over the role of screening will continue until evidence from r and omised controlled trials is published A consensus meeting on screening and global strategy for prostate carcinoma , held in Antwerp in 1994 , determined the willingness among European cancer prevention centers to pursue vigorously the collaborative formation of a multinational r and omized screening trial . This trial was to be named the European R and omized Study of Screening for Prostate Cancer ( ERSPC ) PURPOSE Despite the tremendous stage migration associated with prostate cancer screening to our knowledge it remains unproven whether prostate specific antigen based screening decreases prostate cancer specific mortality . Recent studies have shown that prostate specific antigen velocity more than 2 ng/ml per year in the year before diagnosis is associated with a significantly greater risk of prostate cancer specific mortality after treatment . This may serve as a surrogate marker for prostate cancer outcomes . We compared the prostate specific antigen velocity profile between patients with prostate cancer in whom the tumor was detected in a formal screening study and those who were referred for treatment . MATERIAL S AND METHODS We evaluated prostate specific antigen velocity in 1,101 men from a prostate cancer screening study and in 368 not enrolled in a screening study who were referred for treatment . All patients underwent radical prostatectomy for clinical ly localized disease and had multiple preoperative prostate specific antigen measurements to calculate prostate specific antigen velocity . RESULTS Median prostate specific antigen velocity before diagnosis was significantly higher in referred vs screened men ( 1.35 vs 0.68 ng/ml per year , p < 0.0001 ) . In addition , a significantly greater proportion of referred patients had prostate specific antigen velocity more than 2 ng/ml per year ( 38 % vs 17 % , p < 0.0001 ) . On multivariate analysis using prostate specific antigen , clinical stage and biopsy Gleason score screened vs referred status was a significant independent predictor of prostate specific antigen velocity more than 2 ng/ml per year ( p < 0.0004 ) . CONCLUSIONS Prostate specific antigen velocity more than 2 ng/ml per year has been linked to a significantly greater risk of prostate cancer specific mortality . Patients who underwent serial screening had a more favorable prostate specific antigen velocity profile at diagnosis , suggesting that screen detected prostate cancer may be more likely to be cured with definitive therapy OBJECTIVES To determine the prostate-specific antigen ( PSA ) velocity , PSA slope , and PSA doubling time ( PSADT ) in men with positive biopsies , negative biopsies , and no biopsy indications 4 years after an initial screening ; and to use this information to improve the test characteristics in the early detection of prostate cancer and provide normal values for these parameters in screened men with and without evidence of prostate cancer . METHODS Within the European R and omized Study of Screening for Prostate Cancer , section Rotterdam , we identified 9575 men with a second determination of PSA 4 years after the initial screening . These men were divided into three groups : men with positive biopsies , negative biopsies , and no biopsy indications in the second round ( PSA less than 3.0 ng/mL ) . The predictive values of PSA dynamics for detection of prostate cancer were calculated . RESULTS The mean PSA velocity of men with prostate cancer was 0.62 ng/mL/yr versus 0.46 ng/mL/yr for men with a negative biopsy ( P = 0.001 ) . The mean PSADT for men with prostate cancer was 5.1 years and for those with a negative biopsy it was 6.1 years ( P = 0.002 ) . The PSADT for men with no indication for biopsy was 25.1 years . However , receiver operating characteristic analyses revealed only a moderate value for these test parameters in predicting biopsy outcome . CONCLUSIONS The mean values of PSA velocity , PSA slope , and PSADT in a rescreened population differed significantly between men with and without prostate cancer . However , in predicting the biopsy outcome , the PSA dynamics were of limited value In a study of 2,400 r and omly selected men ( age 55 - 70 years ) for early detection of prostate cancer the authors have compared the diagnostic value of digital rectal examination ( DRE ) , transrectal ultrasound ( TRUS ) and prostate specific antigen ( PSA ) . Altogether 62 prostate cancers were detected , corresponding to a detection rate of 3.5 % but by use of DRE the detection rate was only 2.3 % . The study showed that TRUS added significantly to the detection rate . If radical surgery is restricted to stages T1 and T2A , the combined use of DRE and TRUS detected twice as many cases fit for this treatment than DRE alone . The authors advocate r and omized studies for evaluation of early radical treatment of prostate cancer . Before results of such studies have appeared they recommend method ological studies aim ed at development and enhancement of the accuracy of the diagnostic tools PURPOSE Early detection of prostate cancer has been recommended for men with affected first-degree relatives despite the lack of evidence for mortality reduction . We therefore evaluated the impact of family history in the Finnish prostate cancer screening trial . PATIENTS AND METHODS Approximately 80,000 men were identified from the population register for the first screening round . Of the 32,000 men r and omized to the screening arm , 30,403 were eligible at the time of invitation . A blood sample was drawn from the participants ( n = 20,716 ) , and serum prostate-specific antigen ( PSA ) was determined . Men with a PSA level > or = 4.0 ng/mL were referred for prostate biopsy . Information on family history was obtained through a self-administered question naire at baseline . RESULTS A total of 964 ( 5 % ) of the 20,716 screening participants had a positive family history , and 105 ( 11 % ) were screening-positive . Twenty-nine tumors were diagnosed , corresponding to a detection rate of 3.0 % ( 29 of 964 ) and a positive predictive value of 28 % ( 29 of 105 ) . Of the 19,347 men without a family history , 1,487 ( 8 % ) had a PSA level > or = 4.0 ng/mL. The detection rate was 2.4 % ( 462 of 19,347 ) and the positive predictive value was 31 % ( 462 of 1,487 ) . The risk associated with a positive family history was not substantially increased ( rate ratio , 1.3 ; 95 % confidence interval , 0.9 to 1.8 ) . The results were not affected by the age of the screenee or age at diagnosis of the affected relative . The program sensitivity was 6 % ( 29 of 491 ) ( ie , selective screening policy would have missed 94 % of cancers in the population ) . No differences were seen in the characteristics of screen-detected cancers by family history . CONCLUSION Our findings provide no support for selective screening among men with affected relatives The Prostate , Lung , Colorectal and Ovarian ( PLCO ) Cancer Screening Trial is enrolling 148,000 men and women ages 55 - 74 at ten screening centers nationwide with balanced r and omization to intervention and control arms . For prostate cancer , men receive a digital rectal examination and a blood test for prostate-specific antigen . For lung cancer , men and women receive a posteroanterior view chest X-ray . For colorectal cancer , men and women undergo a 60-cm flexible sigmoidoscopy . For ovarian cancer , women receive a blood test for the CA125 tumor marker and transvaginal ultrasound . Members of the control arm continue with their usual care . Follow-up in both groups will continue for at least 13 years from r and omization to assess health status and cause of death . The primary endpoint is mortality from the four PLCO cancers , which accounts for about 53 % of all cancer deaths in men and 41 % of cancer deaths in women in the United States each year . Blood specimens are collected from screened participants , buccal cell DNA from controls , and histology slides from cases ; these are maintained in a biorepository . Participants complete a baseline question naire ( covering health status and risk factors ) and a dietary question naire . More than 12,000 participants were enrolled in the pilot phase ( concluded in September 1994 ) . Changes in the eligibility criteria followed . As of April 2000 , enrollment exceeded 144,500 . Data are scanned into design ated on-site computers for uploading by participant identification number to the coordinating center for quality checks , archival storage , and preparation of analysis data sets for use by the National Cancer Institute ( NCI ) . Scientific direction is provided by NCI scientists , trial investigators , external consultants , and an independent data safety and monitoring board . Performance and data quality are monitored via data edits , site visits , r and om record audits , and teleconferences . The PLCO trial is formally endorsed by the American Cancer Society and has been ranked by the American Urological Association as one of the most important prostate cancer studies being conducted . Special efforts to enroll black participants are cosponsored by the U.S. Centers for Disease Control and Prevention BACKGROUND Residents are required to demonstrate competency in communication skills . Prostate cancer screening discussion s are examples of complex physician-patient communication processes , requiring an objective presentation of the known risks , potential benefits , and scientific uncertainties surrounding screening . National organizations recommend shared decision making ( SDM ) in these discussion s. METHODS A stratified analysis to contrast resident and faculty outcomes was planned as part of a r and omized controlled trial comparing decision aids for prostate cancer screening in a suburban Washington , DC , residency practice . All eligible men between the ages of 50 and 70 years scheduled for a wellness examination with either a resident or a faculty physician were r and omly assigned to one of two intervention arms ( Web- or paper-based decision aid ) or to the control group ( no pre-visit education ) . Patients were asked to complete exit surveys that evaluated their perceptions of key elements of SDM for prostate cancer screening ( PCS ) . RESULTS Patients seen by resident physicians were younger than patients seen by faculty , and a smaller proportion had undergone previous prostate-specific antigen ( PSA ) testing . Patients seen by residents and faculty reported similar levels of the elements of SDM ( eg , knowledge about PCS , achieving their desired locus of control for the decision ) and similar time spent discussing screening . Both groups also had nearly identical decisional conflict scores and PSA testing rates . Residents discussed more PCS topics ( 6.3 versus 5.3 topics ) , including more topics that might influence a patient to decide against screening , than did faculty physicians . CONCLUSIONS According to patient perceptions , residents appeared to perform as well as faculty in SDM and other aspects of PCS discussion s , although the topics that they covered with patients might have differed The objectives of the Prostate , Lung , Colorectal and Ovarian Cancer Screening Trial are to determine in screenees ages 55 - 74 at entry whether screening with flexible sigmoidoscopy ( 60-cm sigmoidoscope ) can reduce mortality from colorectal cancer , whether screening with chest X-ray can reduce mortality from lung cancer , whether screening men with digital rectal examination ( DRE ) plus serum prostate-specific antigen ( PSA ) can reduce mortality from prostate cancer , and whether screening women with CA125 and transvaginal ultrasound ( TVU ) can reduce mortality from ovarian cancer . Secondary objectives are to assess screening variables other than mortality for each of the interventions including sensitivity , specificity , and positive predictive value ; to assess incidence , stage , and survival of cancer cases ; and to investigate biologic and /or prognostic characterizations of tumor tissue and biochemical products as intermediate endpoints . The design is a multicenter , two-armed , r and omized trial with 37,000 females and 37,000 males in each of the two arms . In the intervention arm , the PSA and CA125 tests are performed at entry , then annually for 5 years . The DRE , TVU , and chest X-ray exams are performed at entry and then annually for 3 years . Sigmoidoscopy is performed at entry and then at the 5-year point . Participants in the control arm follow their usual medical care practice s. Participants will be followed for at least 13 years from r and omization to ascertain all cancers of the prostate , lung , colorectum , and ovary , as well as deaths from all causes . A pilot phase was undertaken to assess the r and omization , screening , and data collection procedures of the trial and to estimate design parameters such as compliance and contamination levels . This paper describes eligibility , consent , and other design features of the trial , r and omization and screening procedures , and an outline of the follow-up procedures . Sample -size calculations are reported , and a data analysis plan is presented OBJECTIVE To examine the impact of a decision aid ( DA ) design ed to promote informed decision making for screening with the prostate-specific antigen ( PSA ) test and to test a theoretical model of factors influencing decisional conflict . DESIGN Structural equation modeling examined pathways between DA exposure , knowledge , schema , prostate cancer risk perceptions , decisional anxiety , and decisional conflict . Sample participants included 200 men from the general population ( exclusive of African Americans ) and 200 African American men . Half of the men in each sub sample were r and omly assigned to receive the DA . MAIN OUTCOME MEASURES Decisional conflict regarding prostate cancer screening . RESULTS The DA influences level of decisional conflict by increasing patient knowledge . This effect of knowledge on decisional conflict is indirect , however , through an association with greater perceived risk and lower decisional anxiety . Also , positive PSA schema was associated with lower decisional anxiety and decisional conflict . It is important that exposure to the DA had no impact on PSA schema . CONCLUSION Schemas about testing must be considered in developing messages about the risks and benefits of testing . If schemas are counter to message content , mechanisms for modifying schemas must be incorporated into interventions CONTEXT The European R and omized Study of Screening for Prostate Cancer ( ERSPC ) section Rotterdam was initiated in 1993 . Men who initially presented with prostate-specific antigen ( PSA ) values < 3.0 ng/ml were not biopsied ( with few exceptions ) . In the Prostate Cancer Prevention Trial ( PCPT ) eligible men who initially presented with PSA values < 3.0 ng/ml were all biopsied during or at the end of a 7-yr study period . OBJECTIVE To compare biopsy rates in PCPT and cancer detection rates , interval cancers , and prostate cancer deaths in ERSPC . Report the number of additional biopsies needed to detect these cases using PCPT policy . EVIDENCE ACQUISITION 21,210 men , aged 55 - 74 yr , were r and omised to screening ; 19,970 were actually screened between November 1993 and December 1999 . A total of 15,852 initially presented with PSA values of < 3.0 ng/ml ; after excluding 79 detected at first screens , 15,773 remained as the study population . A second and third screening round followed after 4- and 8-yr intervals . All cancers found in three rounds of screening or as interval cancers during the 12-yr interval were identified and characterised . EVIDENCE SYNTHESIS Screening for prostate cancer and routine clinical management , comparison of detection rates and outcome data . During the 12-yr observation period , which may be too short , 700 cancers were found , 620 through screening and 80 as interval cancers . None of the screen-detected cases but 6 of the 80 men with interval cancers died of prostate cancer . Applying the positive predictive value of 21.7 % of the PCPT trial 3472 cancers would have been detected in ERSPC Rotterdam had all men with PSA values < 3.0 ng/ml been biopsied . Assuming 80 interval cancers and 6 deaths from prostate cancer might have been prevented if all 15,773 eligible men had undergone biopsy . CONCLUSIONS The present data suggest a very much unfavourable " number needed to be biopsied " to find one missed cancer or to detect the deadly interval cancers OBJECTIVE With increased incidence of prostate cancer and an increased number of patients undergoing radical prostatectomy in China , it will be necessary to elaborate the diagnosis , clinical significance and treatment of patients whose tumors have positive surgical margins following radical prostatectomy . DATA SOURCES Positive surgical margin , prostate cancer and radical prostatectomy were used as subject words and the medical literature in recent decades was search ed using the PubMed data base and the results are summarized . STUDY SELECTION Using positive surgical margin , prostate cancer and radical prostatectomy as subject words the PubMed medical data base produced 275 papers of pertinent literature . By further screening 28 papers were selected and they represent relatively large-scale clinical r and omized and controlled clinical trials . RESULTS A pertinent literature of 275 papers was identified and 28 papers on large clinical studies were obtained . Analysis of results indicated that the positive rate of surgical margin after radical prostatectomy is 20%-40 % , and although most patients with positive surgical margins are stable for a considerable period , the data available now suggested that the presence of a positive surgical margin will have an impact on the patient 's prognosis . The risk factors of positive surgical margin include preoperative prostate specific antigen level , Gleason 's score and pelvic lymph node metastasis . The most common site with positive surgical margin is in apical areas of the prostate ; therefore surgical technique is also a factor result ing in positive surgical margins . From data available now it appears that as long as the surgical technique is skilled , different surgical modes do not affect the rate of surgical margin . Adjuvant radiotherapy is mainly used to treat patients with positive surgical margin after radical prostatectomy , but combination with and rogen deprivation therapy may increase the curative effect . CONCLUSION The current data indicated that the presence of positive surgical margins can markedly affect the patient 's prognosis . Therefore we should be aware how we reduce the positive surgical margin , how to diagnose positive surgical margin and how to treat when there are positive surgical margins OBJECTIVES To evaluate the features , rates , and characteristics of prostate cancer detected during two subsequent screening rounds . METHODS Data were retrieved from the data base of European R and omized Study of Screening for Prostate Cancer ( ERSPC ) , section Rotterdam . Men , ages 55 - 74 yr were screened with a 4-yr interval . Different biopsy indications were used in the first and second screens in the PSA range < 4.0 ng/ml . Clinical features and a total of 1548 sextant biopsies were recorded for Gleason score and tumour extent , and 550 radical prostatectomy specimens were evaluated for Gleason score , pathologic T category , and tumour volume . RESULTS Clinical stage , Gleason score , involvement of biopsy by tumour , and PSA levels were more favourable in patients of the second round compared with those of the first round . The number of men chosen for watchful waiting increased from 98 ( 10 % ) to 123 ( 22 % ) in the second round ( p<0.0001 ) . In patients undergoing radical prostatectomy , median tumour volume in the first and second screening round was 0.65 and 0.45 ml ( p=0.001 ) . Minimal cancer ( cancer < 0.5 ml , organ-confined , no Gleason pattern 4 or 5 ) was found in 122 ( 31.6 % ) in the first and 60 ( 42.6 % ) in the second screening round ( p=0.03 ) . The 5-yr PSA progression-free survival after radical prostatectomy was 87 % . CONCLUSIONS Despite the 4-yr interval an important shift of all prognostic factors occurred in favour of round 2 . In those men who underwent radical prostatectomy , 42.6 % fulfilled the criteria of minimal cancer . These data suggest that overdiagnosis increases with repeat screening The early detection of prostate cancer is feasible ; the use of PSA-driven screening techniques produces a ` lead time ' and advances the diagnosis of the disease by 5±10 years [ 1±3 ] . While early detection regimens dramatically shift the stage at the time of detection toward locally con ® ned disease , and while there is no debate that early aggressive treatment is the only way of curing prostate cancer , the application of screening in practice and healthcare policy remains controversial . This is because there are uncertainties about the degree of ` over-diagnosis ' which most probably results from screening , and from uncertainties about the risk-bene ® t balance . This paper exp and s on the SocieÂte Internationale d'Urologie lecture given at the Annual Meeting of the European Association of Urology in 2001 . In it we address four practice -related issues of screening for prostate cancer by review ing recent literature and using recent data obtained within the ` European R and omised Study of Screening for Prostate Cancer ' ( ERSPC ) Section , Rotterdam [ 4 ] OBJECTIVE To address detection rates and clinical features of the cancers detected with low prostate specific antigen ( PSA ) levels . METHODS In the context of a prostate cancer ( PCa ) screening program 1097 men attended to a new rescreen round . Sextant prostate biopsy was recommended when PSA > or =3 ng/ml . We also recommended to undergo biopsy in the range 1.0 - 2.99 ng/ml when free to total ( f/t ) PSA ratio < or = 20 % . Detection rate was calculated and clinical features of the cancers detected were studied . RESULTS Mean age was 61.1 years . A total of 497 ( 45.3 % ) had total PSA < 1.0 ng/ml , 439 ( 40 % ) between 1.0 and 2.99 ng/ml , and 161 ( 14.7 % ) > or = 3.0 ng/ml . In the group with PSA between 1.0 and 2.99 ng/ml and f/t PSA ratio < or = 20 % a total of 249 biopsies were indicated ( 159 performed , acceptance 63.9 % ) , and 15 cancers detected ( detection rate 9.4 % ) . Biopsy was recommended to 72 men with PSA between 3.0 and 3.99 ng/ml , performed in 56 ( 77.8 % ) , and 12 tumors detected ( detection rate 21.4 % ) . All cancers in the study were clinical ly localized . Only 4 out of 15 cancers with PSA in the range 1.0 - 2.99 ng/ml ( 26.7 % ) fulfilled clinical criteria of insignificant cancer . Two were poorly differentiated and found to have patologically extracapsular disease . None of the 12 patients with PCa and PSA between 3.0 and 3.99 ng/ml had poorly differentiated features and only one complied with criteria of insignificant cancer . One out of seven who underwent RRP was found to have extracapsular disease . CONCLUSIONS Cancer detection in low PSA ranges is lower but still relevant . The detection of potentially aggresive cancers is still of concern Background There is no available evidence from r and omized trials that early detection of prostate cancer improves health outcomes , but the prostate-specific antigen ( PSA ) test is commonly used to screen men for prostate cancer . Objective The objective of the study is to see if screening with PSA decreases mortality from prostate cancer . Design , setting , and participants This is a case-control study using one-to-one matching on race , age , and time of availability of exposure to PSA screening . Decedents , 380 , from New Jersey Vital Statistics 1997 to 2000 inclusive , 55–79 years of age at diagnosis were matched to living controls without metastatic prostate cancer . Medical records were obtained from all providers , and we abstract ed information about PSA tests from 1989 to the time of diagnosis in each index case . Measurements Measurements consist of a comparison of screening ( yes , no ) between cases and controls . Measure of association was the odds ratio . Results Eligible cases were diagnosed each year from 1989 to 1999 with the median year being 1993 . PSA screening was evident in 23.2–29.2 % of cases and 21.8–26.1 % of controls depending on the screening criteria . The unadjusted , matched odds ratio for dying of prostate cancer if ever screened was 1.09 ( 95 % CI 0.76 to 1.60 ) for the most restrictive criteria and 1.19 ( 95 % CI , 0.85 to 1.66 ) for the least restrictive . Adjustment for comorbidity and education level made no significant differences in these values . There were no significant interactions by age or race . Conclusions PSA screening using an ever/never tabulation for tests from 1989 until 2000 did not protect New Jersey men from prostate cancer mortality PURPOSE Little is known about the incidence rate and clinical relevance of prostate cancer in a low prostate specific antigen ( PSA ) level . In a prospect i ve PSA based screening study we investigated the incidence and clinicopathological features of prostate cancer that occurred within PSA range 1 to 3 ng./ml . when the free-to-total ratio was 0.20 or less . MATERIAL S AND METHODS Men participating in the Aarau , Switzerl and , section of the European R and omized Study of Screening for Prostate Cancer between October 1998 and July 2000 were included in the study . As a side study , all men with PSA between 1 and 3 ng./ml . and free-to-total ratio 0.20 or less were invited to undergo further evaluation with ultrasound guided sextant prostate biopsy . RESULTS Overall , 168 ( 7.8 % ) participants fulfilled inclusion criteria . A total of 158 ( 94 % ) patients underwent prostate biopsy , and prostate cancer was detected in 17 ( 10.8 % ) . There were no statistically significant differences between prostate cancer and benign prostatic hyperplasia in regard to patient age ( 60.7 versus 59.8 years ) , prostate volume ( 23.9 versus 23.0 cc ) , PSA ( 1.98 versus 1.86 ng./ml . ) , free-to-total ratio ( 0.161 versus 0.160 ) , PSA density ( 0.089 versus 0.076 ng./ml . ) or PSA transition zone density ( 0.33 versus 0.24 ng./ml . , respectively ) . Median Gleason score was 5 on prostate biopsy versus 6 on retropubic prostatectomy specimen . Of the 14 patients who underwent surgery there were positive lymph nodes in 1 , stage pT3b Gleason 7 disease in 1 , and pathologically organ confined Gleason 5 in 2 , Gleason 6 in 5 and Gleason 7 in 5 . Mean tumor volume was 1.01 cc ( range 0.02 to 5.17 ) . There were 2 ( 14.3 % ) insignificant ( less than 0.2 cc , Gleason grade 3 or less ) , 1 ( 7.1 % ) minimal ( less than 0.5cc , Gleason grade 3 or less ) and 11 ( 78.6 % ) clinical ly relevant and potentially harmful cancers . CONCLUSIONS There is a significant number of prostate cancer cases diagnosed at PSA as low as 1 to 3 ng./ml . A majority of these tumors are clinical ly significant . This free-to-total ratio range may be helpful for identifying prostate cancer . The " window of opportunity " for detection of curable cancer may change in population s with higher life expectancy towards lower PSA . Lack of specificity and characterization of tumor aggressiveness remains an unsolved issue for PSA PURPOSE This study is an assessment of the acceptability and short-term educational efficacy of interactive spaced education compared to web based teaching cases within the compact time frame of a clinical clerkship . MATERIAL S AND METHODS All 237 third-year students completing their 3-month surgery clerkships at 2 medical schools were asked to complete a urology online-education program covering 4 core topics of benign prostatic hyperplasia , erectile dysfunction , prostate cancer and screening with prostate specific antigen . Students were stratified by clinical site and r and omized to 1 of 2 cohorts . Students in cohort A received interactive spaced education on prostate cancer/prostate specific antigen and web based teaching on benign prostatic hyperplasia/erectile dysfunction . Students in cohort B received interactive spaced education on benign prostatic hyperplasia/erectile dysfunction and web based teaching on prostate cancer/prostate specific antigen . A vali date d 28-item test on all 4 topics was administered at the end of the 10-week program . RESULTS No statistically significant differences in end-of-program test scores were observed between cohorts in the topics of prostate cancer/prostate specific antigen with 87.6 % ( SD 12.9 ) for cohort A ( interactive spaced education ) and 82.4 % ( SD 19.6 ) for cohort B ( web based teaching ) ( p = 0.25 ) . Similarly there was also no statistically significant difference in test scores in the topics of benign prostatic hyperplasia/erectile dysfunction with 79.5 % ( SD 15.9 ) for cohort A ( web based teaching ) and 82.1 % ( SD 14.7 ) for cohort B ( interactive spaced education , p = 0.28 ) . When students were asked which format they would prefer if they were to receive all their urology online education in a single format , 55 % of students ( 109 of 198 respondents ) preferred interactive spaced education while 45 % ( 89 of 109 ) preferred web based teaching ( p = 0.16 ) . CONCLUSIONS Within the compact time frame of a clinical clerkship interactive spaced education is equivalent to web based teaching in short-term learning gains and in acceptability by medical students BACKGROUND Population -based screening for prostate cancer is currently being evaluated in r and omized clinical trials in the United States and in Europe . Side effects arising from the process of screening and from the earlier treatment of screen-detected prostate cancer may be important factors in the evaluation . To examine health-related quality of life ( or health status ) among men screened for prostate cancer , we conducted a longitudinal study of 626 attenders to the Rotterdam ( The Netherl and s ) prostate cancer screening program and of 500 non participants . METHODS Attenders of the screening program and non participants completed self- assessment question naires ( SF-36 [ i.e. , Medical Outcomes Study 36-Item Short-Form Health Survey ] and EQ-5D [ i.e. , EuroQol measure for health-related quality of life ] health surveys ) to measure generic health status , as well as an additional question naire for anxiety and items relating to prostate cancer screening . RESULTS Physical discomfort during digital rectal examination and during transrectal ultrasound was reported by 181 ( 37 % ) of 491 men and by 139 ( 29 % ) of 487 men , respectively ; discomfort during prostate biopsy was reported by 64 ( 55 % ) of 116 men . Mean scores for health status and anxiety indicated that the participants did not experience relevant changes in physical , psychological , and social functioning during the screening procedure . However , high levels of anxiety were observed throughout the screening process among men with a high predisposition to anxiety . Similar scores for anxiety predisposition were observed among attenders and non participants . CONCLUSIONS At the group level , we did not find evidence that prostate cancer screening induced important short-term health-status effects , despite the short-lasting side effects related to the biopsy procedure . However , subgroups may experience high levels of anxiety . The implication is that unfavorable health-status effects of prostate cancer screening occur mainly in the treatment phase OBJECTIVES To study active surveillance as a management option for the important number of prostate cancer patients who would not have been diagnosed in the absence of screening . PATIENTS AND METHODS We analyzed baseline characteristics and outcome parameters of all men on active surveillance who were screen-detected in the Rotterdam section of the European R and omized Study of Screening for Prostate Cancer ( ERSPC ) . Recruitment and surveillance of men were not guided by a protocol but depended on individual decisions of patients and their physicians . RESULTS Active surveillance was applied in 278 men detected by screening from 1993 to 2006 . At diagnosis , their median age was 69.8 yr ( 25 - 75p ; 66.1 - 72.8 ) ; median PSA 3.6 ng/ml ( 25 - 75p ; 3.1 - 4.8 ) , and the clinical stage was T1c in 220 ( 79.1 % ) and T2 in 58 ( 20.9 % ) . During the follow-up of median 3.4 yr , 103 men ( 44.2 % ) had a PSA doubling time that was negative ( ie , half-life ) or longer than 10 yr . Men detected at rescreening were significantly more likely to be on active surveillance , and they had more beneficial characteristics . Deferred treatment was elected in 82 cases ( 29.0 % ) . Overall survival was 89 % after 8 yr ; the cause-specific survival was 100 % . CONCLUSIONS This report shows a beneficial , although preliminary , outcome of screen-detected men managed on active surveillance . Men were more likely to be on active surveillance if the disease was detected at repeated screening . The report also shows that an important proportion of men have prolonged PSA doubling times , although the value of this parameter has not been established in untreated men At the Rotterdam site of the ERSPC approximately 9600 men between 54 and 76 years old have been r and omized at the time of writing , of which 50 % for screening by PSA ( Hybritech T and em E ) , DRE , and TRUS until March 1996 . The cancer detection rate is 4.3 % , and the overall biopsy-to-carcinoma rate is 5.1 . By clinical staging 91 % of cancers are organ-confined ( T2c or less ) , by pathologic staging after radical prostatectomy 64 % of tumors are specimen-confined . The best sole predictor of a positive biopsy is total serum PSA , followed by DRE . The specificity of PSA in the intermediate PSA range between 4 and 10 ng/mL can be improved significantly by application of the f-PSA/t-PSA ratio , PSA density and age-specific reference ranges . The f-PSA/t-PSA ratio with a cut-off value of 0.20 appears to be the most effective parameter and reduces in combination with DRE the number of biopsies in the intermediate PSA range by 38 % with 12 % of carcinomas undetected . This leads to an overall biopsy-to-carcinoma ratio of 4.6 . The evaluation of TRUS- , DRE- , and PSA-driven biopsies will lead to a change of the screening procedure within the study The possibility of screening the general population for prostate cancer using serum prostate-specific antigen ( PSA ) level ( alone or in combination with other tests ) as screening test has recently been discussed . A number of studies are on the way , but the published reports have almost exclusively been based on men volunteering for screening . We assessed the feasibility of a screening study based on men identified from a central population registry . A r and om sample of 600 men in the age groups 55 , 60 and 65 years was identified from the Finnish Population Registry as the study population . Half of them were r and omised to the intervention group and an invitation to participate was sent to them . The participation rate was 77 % ( 230 out of 300 ) . Twenty-five men had a serum PSA concentration of 4.0 micrograms l-1 or above and were invited for further examination including digital rectal examination , transrectal ultrasound and transrectal Tru-cut biopsies ( directed and /or r and om ) . Six cases of cancer were detected among the 230 participating men , which corresponds to a detection rate of 2.6 % and a positive predictive value of 24 % . The number of cases detected is equivalent to the expected number of prostate cancer cases during a 10 year follow-up in this population . The ratio of free to total PSA was also measured and a cut-off level of 0.20 was chosen . Its use as an additional criterion of the screening test would have decreased the prevalence of false-positive screening tests from 8 % ( 19 of 230 ) to 3 % ( 7 of 230 ) at a cost of missing one of the six cancers compared with serum total PSA concentration alone . Of the six cancers , five were clinical ly regarded as localised and locally confined disease was confirmed pathologically in four of them . In conclusion , a population -based study in Finl and seems feasible and the properties of the PSA test can be regarded as suitable for a r and omised screening study . Thus , all prerequisites for a multicentre study , which is planned , seem to exist Prostate cancer is the second most common cancer in men , with a lifetime prevalence of 17 percent . Prostate cancer symptoms generally occur in advanced stages , making early detection desirable . Digital rectal examination and prostate-specific antigen testing are the most commonly used screening tools . The goal of screening is to detect clinical ly significant prostate cancers at a stage when intervention reduces morbidity and mortality ; however , the merits and methods of screening continue to be debated . Prostate-specific antigen levels may be less than 4 ng per mL in 15 to 38 percent of men with cancer , indicating a high false-negative rate . The positive predictive value of the prostate-specific antigen test is approximately 30 percent ; therefore , less than one in three men with an abnormal finding will have cancer on biopsy . These limitations of the prostate-specific antigen test have led to variations design ed to improve its accuracy ( e.g. , age- and race-specific cutoffs , free prostate-specific antigen tests ) ; however , none of these modifications have been widely adopted because of unclear benefits . Although treatments have improved in the past two decades , therapy for prostate cancer is not benign and may lead to urinary incontinence , sexual dysfunction , or bowel dysfunction . New evidence affecting screening recommendations continues to accumulate , and two large r and omized controlled trials of screening will be completed in the next few years . Current guidelines recommend an individualized , targeted , patient-centered discussion to facilitate a shared decision about screening plans PURPOSE Worldwide 2 large-scale r and omized screening trials for prostate cancer have been initiated . Determining prostate specific antigen ( PSA ) involves a simple test that may influence the outcome of these trials if frequently done in the control arm or before study enrollment . We quantified PSA and digital rectal examination before and during the screening trial in Rotterdam , The Netherl and s and in the general population . MATERIAL S AND METHODS Trial participants were administered study intake question naires on tests done before study participation . Data on PSA from the regional general practice laboratory were correlated with participant data . Various sources were used to quantify PSA tests and digital rectal examinations in the general population . RESULTS Of men 55 to 74 years old 45 % underwent digital rectal examination at 1 time and 13 % reported that PSA was tested before trial participation . Each rate increased with age . No statistically significant effect of former PSA testing or digital rectal examination on the cancer detection rate was identified . The rate of PSA determination after initial screening and /or r and omization in the control arm was 2-fold that in the screening arm ( 76 versus 33/1,000 person-years ) . PSA determination initially decreased in the screening arm but increased rapidly after some time . The number of PSA determinations in the general population was estimated to be 45/1,000 person-years at ages 55 to 69 years . CONCLUSIONS PSA testing was moderate in the control arm but if different men undergo this test each year , the contamination rate may become rather high . In the final analysis of mortality PSA testing should be considered A r and omized screening trial was started in Europe to show the effect of early detection and treatment of prostate cancer on mortality ( European Study on Screening of Prostate Cancer ) . In one centre ( Rotterdam ) , the screening protocol initially consisted of 3 screening tests for all men : prostate‐specific antigen ( PSA ) , digital rectal examination ( DRE ) and transrectal ultrasonography ( TRUS ) . A PSA value of ≥4 ng/ml and /or an abnormality on DRE and /or TRUS were taken to indicate that biopsy was required . In this study , we examined the possibilities for a more efficient screening protocol . A logistic‐regression model was used to predict the number of cancers for PSA < 4 ng/ml if all men were biopsied ( predictive index , PI ) . Effects of a change in PSA cut‐off on the screening results were explored . Weights were applied to procedures and cancers to explore the possibility of expressing differences between protocol s in one overall figure . Biopsies in men with PSA < 1 ng/ml and a positive DRE or TRUS were very inefficient . Applying DRE and TRUS only in the PSA ranges 1.5 to 3.9 and 2 to 3.9 ng/ml to determine whether a biopsy was required would result in a decrease of 29 to 36 % in biopsies and a decrease of 5 to 8 % in cancers . However , the results of DRE and TRUS could not be duplicated entirely . A protocol with only PSA ≥ 3 ng/ml as a direct biopsy indicator result ed in a decrease of detected cancers by 7.6 % and of biopsies by 12 % , also a much simpler screening procedure . Use of the PI would give more efficient protocol s , but this should be viewed as a preliminary finding , with the disadvantage of necessitating many additional screening visits . Since the results of DRE and TRUS could not be duplicated , a change in protocol towards PSA ≥ 3 ng/ml appears acceptable . If this proves effective , a final judgement about the optimal combination of screening tests may be made . Int . J. Cancer ( Pred . Oncol . ) 84:437–441 , 1999 . © 1999 Wiley‐Liss , PURPOSE We evaluated the positive predictive value and cancer detection rate in the prostate specific antigen ( PSA ) range of 2.0 to 3.9 ng/ml and assessed the value of percent free ( F ) PSA ( FPSA ) on tumor detection and tumor aggressiveness in this low PSA range . MATERIAL S AND METHODS Of 3623 men who were attending the second round of screening within the European R and omized Study of Screening for Prostate Cancer , section Rotterdam 883 had PSA values of 2.0 to 3.9 ng/ml . These men were offered laterally directed sextant biopsy . FPSA was prospect ively determined from pretreatment serum . Cancers were classified as prognostically favorable and unfavorable using biopsy results and other pretreatment diagnostic features . RESULTS Using the PSA range of 2.0 to 3.9 ng/ml as a biopsy indication 126 cancers were detected , result ing in a positive predictive value of 17.1 % and a cancer detection rate of 14.3 % . By using percent FPSA and setting relative sensitivity at 95 % 9 % of biopsies could have been avoided . Unfavorable tumor characteristics were found in 46.9 % of the men with T1C tumors . Mean percent FPSA was significantly lower in such men compared to men with favorable tumor characteristics . Of the men with percent FPSA lower than 10 % 90 % had unfavorable tumor characteristics . CONCLUSIONS The PSA range 2.0 to 3.9 ng/ml is accessible for prostate cancer screening . Percent FPSA is of moderate value in avoiding unnecessary biopsies in the PSA range of 2.0 to 3.9 ng/ml . However , when assessing tumor aggressiveness in biopsy results , percent FPSA is predictive and can be used to select treatment options , such as watchful waiting OBJECTIVES The ratio between free and total prostate-specific antigen ( PSA ) in serum ( F/T ratio ) was shown to improve the differentiation between prostate carcinoma and benign conditions in selected series of patients . In this study the F/T ratio was analyzed for its ability to improve the specificity of total serum PSA , digital rectal examination ( DRE ) , and transrectal ultrasonography ( TRUS ) for the detection of prostate cancer in an unselected screening population of men identified in the Rotterdam population . METHODS In 1726 men between 55 and 76 years old , 67 prostate carcinomas were detected by DRE , TRUS , and total serum PSA ( Abbott IMx , Hybritech T and em E ) . The DELFIA ProStatus PSA EQM and ProStatus PSA Free/Total assays ( Wallac ) were applied in retrospect to determine total and free serum PSA . Age , total prostate and inner zone volumes were taken into consideration . RESULTS Sixty-seven carcinomas were detected , two by TRUS and three by DRE alone . Total serum PSA was the most important single predictor of prostate cancer , followed by DRE . The F/T ratio increased the specificity of total serum PSA in the PSA range between 4.0 and 10.0 ng/mL. However , this improved specificity was not significant , nor for gl and volumes restricted to 50 mL or less . CONCLUSIONS The combination of total serum PSA and DRE remains the st and ard for detection of prostate carcinoma in a screening population . Their specificity may be improved minimally by the F/T ratio , but not significantly in a sample of 1726 screened men . The threshold of the F/T ratio , and the optimal PSA range for its application , remains to be assessed prospect ively It is common belief that in families with hereditary prostate cancer ( HPC ) , unaffected men should be screened periodically with PSA , but little is known about the effects of such screening . We studied test and tumor characteristics in unaffected 50–75‐year‐old screenees from HPC families . In the Netherl and s , 153 verified HPC families are registered ; 132 unaffected men in these families were not under surveillance for prostate cancer and gave informed consent for PSA testing by their GP and referral to a urologist in the case of a PSA level ≥ 3.0 ng/ml . Results were compared to published data from the Rotterdam and Göteborg sections of the European R and omized Study of Screening for Prostate Cancer ( ERSPC ) . A PSA ≥ 3.0 ng/ml was found in 20 men : referral rate , 15.1 % ( ERSPC Rotterdam : 20.1 % ; ERSPC Göteborg : 12.0 % ) . Only 3 cases of prostate cancer were diagnosed in these men : detection rate in the first screening round 2.3 % ( ERSPC Rotterdam : 5.3 % ; ERSPC Göteborg : 2.3 % ) . Frequent opportunistic PSA testing made it impossible to estimate the detection rates in subsequent screening rounds . In the first and subsequent PSA screening rounds , 11 cases of cancer were detected . All but 1 had favorable tumor characteristics ( cT1c/pT2 ; Gleason < 7 ) . These results raise the question as to whether men from all HPC families should be considered at high‐risk . We suggest that the same PSA testing guidelines should apply to HPC families and the general population . A more aggressive screening policy in HPC families does not seem to be justified . © 2007 Wiley‐Liss , Purpose : Large r and omized trials provide the only valid means of quantifying the benefits and drawbacks of prostate-specific antigen ( PSA ) screening , but the follow-up of ongoing studies is still too short to allow evaluation of mortality . We report here the intermediate indicators of screening efficacy from the second round of the Finnish trial . Experimental Design : The Finnish trial , with ∼80,000 men in the target population , is the largest component in the European R and omized Study of Screening for Prostate Cancer . The first round was completed in 1996–1999 . Each year 8,000 men 55–67 years of age were r and omly assigned to the screening arm , and the rest formed the control arm . Men r and omized to the screening arm in 1996 were reinvited 4 years later , in 2000 , and PSA was determined . Results : Of the eligible 6415 men , 4407 ( 69 % ) eventually participated in the second round of screening . Of the first-round participants , up to 84 % ( 3833 of 4556 ) attended rescreening . A total of 461 screenees ( 10.5 % ) had PSA levels of ≥4 μg/liter . Altogether , 97 cancers were found , yielding an overall detection rate of 2.2 % ( 97 of 4407 ) . Seventy-nine cases were found among the 3833 second-time screenees ( detection rate 2.1 % ) and 18 in those 574 men ( 3.1 % ) who had not participated previously . A PSA of ≥4 μg/liter , but negative biopsy in the first screening round was associated with an up to 9-fold risk of cancer in rescreening relative to those with lower PSA levels at baseline . Ninety-one ( 94 % ) of all of the detected cancers were clinical ly localized . Conclusions : As surrogate measures of an effective screening program , both compliance as well as the overall and advanced prostate cancer detection rates remained acceptable . Men defined as screen-positive but with a negative confirmation of cancer at prevalence screen formed a high-risk group at rescreening OBJECTIVES To describe the self-reported use of prostate specific antigen ( PSA ) tests , faecal occult blood tests ( FOBTs ) , and whole-body skin examinations among Queensl and men , reasons for use , and the personal characteristics of men undergoing the tests for cancer screening . SETTING AND DESIGN Data were obtained from the Queensl and Cancer Risk Study ( QCRS ) , a population -based telephone survey conducted in 2004 , which used r and om sampling stratified by age , sex , and geographic location . PARTICIPANTS All men aged 50 - 75 years who participated in the QCRS ( n = 2336 ) . MAIN OUTCOME MEASURES Use of PSA test , FOBT , or whole-body skin examination , specifically as a screening procedure ; the probability of being screened ; and associations with sociodemographic factors , risk behaviour , and cancer experience . RESULTS More than a third of men reported never having been screened for prostate , colorectal , or skin cancer . Of those who had been screened , the odds of PSA testing being reported were more than two times greater than the odds of whole-body skin examination ( adjusted odds ratio [ OR ] , 2.54 ; 95 % CI , 1.49 - 4.32 ) , and the odds of reporting an FOBT were less ( adjusted OR , 0.48 ; 95 % CI , 0.22 - 1.04 ) . Men who participated in cancer screening tended to be older , white , living with a partner , and to have private health insurance . Smokers were less likely to be screened with any of the three screening tests . CONCLUSIONS Of these three cancer screening tests , the FOBT has the best evidence for reducing mortality and yet is the least frequently used by Queensl and men . There are disparities in reported screening prevalence between the specific tests and across certain population subgroups Background Prostate-specific antigen ( PSA ) is widely used to detect prostate cancer . The low positive predictive value of elevated PSA results in large numbers of unnecessary prostate biopsies . We set out to determine whether a multivariable model including four kallikrein forms ( total , free , and intact PSA , and human kallikrein 2 ( hK2 ) ) could predict prostate biopsy outcome in previously unscreened men with elevated total PSA . Methods The study cohort comprised 740 men in Göteborg , Sweden , undergoing biopsy during the first round of the European R and omized study of Screening for Prostate Cancer . We calculated the area-under-the-curve ( AUC ) for predicting prostate cancer at biopsy . AUCs for a model including age and PSA ( the ' laboratory ' model ) and age , PSA and digital rectal exam ( the ' clinical ' model ) were compared with those for models that also included additional kallikreins . Results Addition of free and intact PSA and hK2 improved AUC from 0.68 to 0.83 and from 0.72 to 0.84 , for the laboratory and clinical models respectively . Using a 20 % risk of prostate cancer as the threshold for biopsy would have reduced the number of biopsies by 424 ( 57 % ) and missed only 31 out of 152 low- grade and 3 out of 40 high- grade cancers . Conclusion Multiple kallikrein forms measured in blood can predict the result of biopsy in previously unscreened men with elevated PSA . A multivariable model can determine which men should be advised to undergo biopsy and which might be advised to continue screening , but defer biopsy until there was stronger evidence of malignancy Summary Approximately 20 000 men 55–67 years of age from two areas in Finl and were identified from the Population Registry and r and omized either to the screening arm ( 1/3 ) or the control arm ( 2/3 ) of a prostate cancer screening trial . In the first round , the participation rate in the screening arm was 69 % . Of the 5053 screened participants , 428 ( 8.5 % ) had a serum prostate-specific antigen ( PSA ) concentration of 4.0 ng/ml or higher , and diagnostic examinations were performed on 399 of them . A total of 106 cancers were detected among them corresponding to a positive predictive value of 27 % , which is comparable with mammography screening for breast cancer . The prostate cancer detection rate based on a serum PSA concentration of 4.0 ng ml–1 or higher was 2.1 % . Approximately nine out of ten screen-detected prostate cancers were localized ( 85 % clinical stage T1–T2 ) and well or moderately differentiated ( 42 % World Health Organization ( WHO ) grade I and 50 % grade II ) , which suggests a higher proportion of curable cancers compared with cases detected by other means BACKGROUND Screening for prostate cancer advances the time of diagnosis ( lead time ) and detects cancers that would not have been diagnosed in the absence of screening ( overdetection ) . Both consequences have considerable impact on the net benefits of screening . METHODS We developed simulation models based on results of the Rotterdam section of the European R and omized Study of Screening for Prostate Cancer ( ERSPC ) , which enrolled 42,376 men and in which 1498 cases of prostate cancer were identified , and on baseline prostate cancer incidence and stage distribution data . The models were used to predict mean lead times , overdetection rates , and ranges ( corresponding to approximate 95 % confidence intervals ) associated with different screening programs . RESULTS Mean lead times and rates of overdetection depended on a man 's age at screening . For a single screening test at age 55 , the estimated mean lead time was 12.3 years ( range = 11.6 - 14.1 years ) and the overdetection rate was 27 % ( range = 24%-37 % ) ; at age 75 , the estimates were 6.0 years ( range = 5.8 - 6.3 years ) and 56 % ( range = 53%-61 % ) , respectively . For a screening program with a 4-year screening interval from age 55 to 67 , the estimated mean lead time was 11.2 years ( range = 10.8 - 12.1 years ) , and the overdetection rate was 48 % ( range = 44%-55 % ) . This screening program raised the lifetime risk of a prostate cancer diagnosis from 6.4 % to 10.6 % , a relative increase of 65 % ( range = 56%-87 % ) . In annual screening from age 55 to 67 , the estimated overdetection rate was 50 % ( range = 46%-57 % ) and the lifetime prostate cancer risk was increased by 80 % ( range = 69%-116 % ) . Extending annual or quadrennial screening to the age of 75 would result in at least two cases of overdetection for every clinical ly relevant cancer detected . CONCLUSIONS These model-based lead-time estimates support a prostate cancer screening interval of more than 1 year Specificity constitutes a component of validity for a screening test . The number of false-positive ( FP ) results has been regarded as one of major shortcomings in prostate cancer screening . We estimated the specificity of serum prostate-specific antigen ( PSA ) determination in prostate cancer screening using data from a r and omised , controlled screening trial conducted in Finl and with 32 000 men in the screening arm . We calculated the specificity as the proportion of men with negative findings ( screen negatives , SN ) relative to those with negative and FP results ( SN/(SN+FP ) ) . A SN finding was defined as either PSA⩽4 ng ml−1 or PSA 3.0–3.9 ng ml−1 combined with a negative ancillary test ( digital rectal examination , DRE or free/total , F/T PSA ratio ) . False positives were those with positive screening test followed by a negative diagnostic examination . Of the 30 194 eligible men , 20 794 ( 69 % ) attended the first screening round and 1968 ( 9.5 % ) had a screen-positive finding . A total of 508 prostate cancers were detected at screening ( 2.4 % ) . Hence , the number of SN findings was 18 825 and the number of FP results 1358 . Specificity was estimated as 0.933 ( 18 825 out of 20 183 ) with 95 % confidence interval ( CI ) 0.929–0.936 . Specificity decreased with age . Digital rectal examination as ancillary examination had similar or higher specificity than F/T PSA . In the second screening round , specificity was slightly lower ( 0.912 , 95 % CI 0.908–0.916 ) . The specificity of PSA screening in the Finnish screening trial is acceptable . Further improvement in specificity could , however , improve acceptability of screening and decrease screening costs Background : Previous studies suggest a positive association between markers of trans-fatty acid intake and prostate cancer . We therefore prospect ively evaluated the association between blood trans-fatty acid levels and risk of prostate cancer . Methods : We conducted a nested case-control study among 14,916 apparently healthy men who provided blood sample s in 1982 . Blood fatty acid levels were determined for 476 men diagnosed with prostate cancer during a 13-year follow-up and their matched controls . Controls were individually matched to cases according to age and smoking status at baseline . Conditional logistic regression was used to estimate the relative risk and 95 % confidence interval of total , nonaggressive ( stage A/B and low grade ) , and aggressive ( stage C/D , high grade , subsequent distant metastasis or death ) prostate cancer associated with blood levels of specific trans-fatty acids . Results : Blood levels of all the trans-fatty acids examined were unrelated to total prostate cancer risk . When results were divided according to tumor aggressiveness , blood levels of 18:1n-9 t , all the 18:2 t examined , and total trans-fatty acids were positively associated to nonaggressive tumors . The relative risks ( 95 % confidence intervals ; P trend ) comparing top with bottom quintile trans-fatty acid levels were 2.16 ( 1.12 - 4.17 ; 0.11 ) for 18:1n-9 t , 1.97 ( 1.03 - 3.75 ; 0.01 ) for total 18:2 t , and 2.21 ( 1.14 - 4.29 ; 0.06 ) for total trans-fatty acids . None of the trans fats examined was associated with aggressive prostate tumors . Conclusion : Blood levels of trans isomers of oleic and linoleic acids are associated with an increased risk of nonaggressive prostate tumors . As this type of tumors represents a large proportion of prostate cancer detected using prostate-specific antigen screening , these findings may have implication s for the prevention of prostate cancer . ( Cancer Epidemiol Biomarkers Prev 2008;17(1):95–101 BACKGROUND Professional organizations recommend that physicians discuss prostate cancer with patients to make individual screening decisions . However , few studies have tested strategies to encourage such discussion s , particularly among high-risk population s. We examined the effects of two low-literacy interventions on the frequency of prostate cancer discussion and screening . DESIGN R and omized , blinded , controlled trial with concealed allocation . SETTING / PARTICIPANTS Inner-city primary care clinic , serving a predominately African-American population . Participants were men aged 45 - 70 with no history of prostate cancer , presenting for a regular appointment . INTERVENTIONS While waiting to see their physician , patients received a patient education h and out on prostate cancer screening ( PtEd ) , a h and out simply encouraging patients to talk to their doctor about prostate cancer ( Cue ) , or a control h and out . The interventions did not advocate for or against screening . MEASURES Patient-reported discussion of prostate cancer with the physician and chart review s determine prostate-specific antigen ( PSA ) test orders and performance of digital rectal examination ( DRE ) . Adjusted odds ratios ( aOR ) and 95 % confidence intervals ( CI ) were computed . Data were collected in 2003 , and analyses were completed in 2006 . RESULTS Most of the 250 subjects ( 90.4 % ) were African American and 78.8 % read below the ninth grade level . Overall , 48.4 % reported discussing prostate cancer during the appointment . Compared to the control group ( 37.3 % ) , discussion s were significantly more common in the Cue group ( 58.0 % , aOR=2.39 [ 1.26 - 4.52 ] ) , as well as in the PtEd group ( 50.0 % , aOR=1.92 [ 1.01 - 3.65 ] ) . When prostate cancer was discussed , patients in the intervention groups more commonly initiated the conversation ( 47.6 % PtEd and 40.0 % Cue , vs 9.7 % control , p<0.01 for each comparison to control ) . Compared to the control group ( 2.4 % ) , PSA test orders increased in the PtEd group ( 14.1 % , aOR=7.62 [ 1.62 - 35.83 ] ) and in the Cue group ( 12.3 % , aOR=5.86 [ 1.24 - 27.81 ] ) . Documentation of DRE did not change significantly ( 4.7 % PtEd , 6.2 % Cue , and 6.0 % control ) . CONCLUSIONS Two simple low-literacy interventions significantly increased discussion of prostate cancer and PSA test orders but not performance of DRE . Both interventions were effective in empowering low-literacy patients to initiate conversations about prostate cancer with their physician Introduction for screening for prostate cancer as a healthcare policy is desirable provided its effectiveness can be shown in terms of decreasing prostate cancer mortality at an acceptable price in terms of quality of life and costs . The European R and omized Study of Screening for Prostate Cancer ( ERSPC ) was initiated in 1993 and should in 2008 have the power to produce the required information . The structure and status of ERSPC . ERSPC is a r and omized controlled trial running in eight European countries ( Belgium , Finl and , France , Italy , The Netherl and s , Spain , Sweden , and Switzerl and ) . A total of 267,994 have been r and omized to screening vs. control . An interim look at the data has taken place in 2006 ; the advice of the Data Monitoring Committee was to continue the study . This was based on a total of 23,794 deaths in both study groups , 6,033 cases of prostate cancer detected in both groups of which about 1 , 200 had died . Contributions to a better underst and ing of the screening methodology . ERSPC has contributed with a large number of publications , either coming from individual centers or combining data of several centers . A complete listing can be found at www.erspc.org . Lead-time and overdiagnosis with the screening regimen utilized in ERSPC Rotterdam were established to amount to 10.3 years and 54 % . This information is of great importance for the development of further screening strategies . During the process of ERSPC , digital rectal examination was omitted and replaced by the inclusion of PSA 3 - 4 as a biopsy indication . The data on which this decision has been based were published and vali date d. Overdiagnosis and overtreatment have an adverse influence on quality of life , as it will be included in the evaluation of ERSPC . The recent development of a nomogram for the identification of indolent disease is a major step to improve on this outcome parameter . The application of this nomogram to screen detected cases allows the the advice " active observation " to about 30 % of such patients . ERSPC is set to show or exclude at least a 25 % reduction in prostate cancer mortality through screening . Many pending problems still have to be resolved prior to the introduction of population s based screening as a worldwide healthcare policy PURPOSE This clinical trial is aim ed at evaluating the impact of prostate cancer screening on cancer-specific mortality . SUBJECTS AND METHODS Forty-six thous and four hundred and eighty-six ( 46,486 ) men aged 45 - 80 years registered in the electoral roll of the Quebec city area were r and omized in 1988 between screening and no screening . Screening included measurement of serum prostatic specific antigen ( PSA ) using 3.0 ng/ml as upper limit of normal and digital rectal examination ( DRE ) at first visit . At follow-up visits , serum PSA only was used . RESULTS Seventy-four ( 74 ) deaths from prostate cancer occurred in the 14,231 unscreened controls while 10 deaths were observed in the screened group of 7,348 men during the first 11 years following r and omization . Median follow-up of screened men was 7.93 years . A Cox proportional hazards model of the age at death from prostate cancer shows a 62 % reduction ( P < 0.002 , Fisher 's exact test ) of cause-specific mortality in the screened men ( P = 0.005 ) . These results are in agreement with the continuous decrease of prostate cancer mortality observed in North America PURPOSE We defined the yield and nature of prostate cancer in the setting of population based , r and omized prostate specific antigen ( PSA ) guided screening in men with PSA levels between 3 and 4 ng./ml . who were 50 to 65 years old at the time of r and omization . MATERIAL S AND METHODS Sextant biopsies were performed in 243 men with PSA of 3 to 4 ng./ml . Therapy decisions were based on core cancer length , histological grade and life expectancy . RESULTS Of the men 32 ( 13.2 % ) had prostate cancer constituting 23 % of all of the 137 prostate cancers to data detected in the first round of our screening study . Age and PSA were similar in men with and without prostate cancer . Men with prostate cancer had significantly lower free PSA and free-to-total PSA ratio , and higher PSA density . Cancer was clinical stage T1c in 27 cases and stage T2 in 5 . Hypoechoic areas were noted at transrectal ultrasound in 10 cases . Digital rectal examination and transrectal ultrasound were normal in 21 cases ( 66 % ) . To date 14 patients have undergone prostatectomy . Surgical specimens showed a mean tumor volume of 1.8 cc ( range 0.6 to 4.4 ) and significant amounts of high grade tumor were present in only 3 cases . Margins were positive in 5 cases , and pathological stage was pT2 in 8 cases and pT3 in 6 . CONCLUSIONS By lowering the PSA cutoff from 4 to 3 ng./ml . an increase in cancer detection by 30 % was achieved . While the addition of free-to-total ratio and PSA density may reduce the number of biopsies by about 15 % with sensitivity maintained at 90 % , systematic sextant biopsies were necessary in most of these mean as 66 % of the tumors were negative on transrectal ultrasound and digital rectal examination . The majority of these cancers were clinical ly significant and suitable for curative treatment . If therapy decisions are based on the pathological findings of the biopsies , the risk of treating insignificant cancers seems low Screening for prostate cancer is controversial . While in some parts of the world screening is practised as a healthcare policy , it is strongly rejected in other areas , because solid evidence of effectiveness of screening combined with early treatment with respect to lowering the mortality of prostate cancer has not been shown . It is for this reason that a large European study is installed to establish or rule out the value of screening for this frequent disease . The present paper presents the goal of the study and elaborates on the value of presently available screening tests . Preliminary results with respect to the first round of screening in the Rotterdam area relating to 32,000 r and omized men are presented . Evidence of effectiveness of screening through other studies and mechanisms is discussed PURPOSE Many clinicians lack re sources to engage patients in shared decision making for prostate cancer screening . We sought to evaluate whether previsit educational decision aids facilitate shared decision making . METHODS This r and omized controlled study compared a Web-based and a paper-based decision aid with no previsit education . Men aged 50 to 70 years undergoing a health maintenance examination at a large family practice were enrolled . The primary outcome was patient-reported level of control over the decision to be screened . Secondary outcomes included frequency of screening , patient knowledge , decisional conflict , and time spent discussing screening . RESULTS A total of 497 men participated ( 75 control , 196 brochure , 226 Web site ) . Patients exposed to either aid were no more likely than control patients to report a collaborative decision : 36 % of patients in each group reported equally sharing decision responsibility . Exposure to either decision aid increased patients ’ involvement in decision making compared with the control condition ( Web site , P = .03 ; brochure , P = .03 ) . Only 46 % of control patients reported an active decision-making role , compared with 56 % of Web site and 54 % of brochure patients . Patients exposed to a decision aid answered a greater percentage of knowledge questions correctly ( 54 % control vs 69 % Web site , P < .001 , and vs 69 % brochure , P < .001 ) and were less likely to be screened ( 94 % control vs 86 % Web site , P = .06 , and vs 85 % brochure , P = .04 ) . CONCLUSIONS Patients in the decision aid groups were more informed and more engaged in the screening decision than their control counterparts . Exposure did not promote shared decision-making control , however . Whether shared decision making is the ideal model and how to measure its occurrence are subjects for further research Objective A history of diabetes has been fairly consistently related to a reduced prostate cancer risk , but previous investigations have not always addressed whether the relation with diabetes varies by prostate cancer aggressiveness or the association between diabetes and prostate cancer is modified by physical activity level and body mass , variables closely related to glucose metabolism . Methods We prospect ively examined the diabetes – prostate cancer risk relationship among 33,088 men in the screening arm of the Prostate , Lung , Colorectal and Ovarian ( PLCO ) Cancer Screening Trial . Results During 8.9 years follow-up , we ascertained 2,058 incident prostate cancer cases . Diabetes history was related to decreased risk of total prostate cancer ( RR = 0.80 , 95 % CI = 0.68–0.95 ) . The apparent protection afforded by diabetes was primarily due to the inverse relation with non-aggressive disease ( i.e. , the combination of low grade ( Gleason sum < 8) and low stage ( clinical stages I or II ) ; RR = 0.75 ; 95 % CI = 0.62–0.91 ) . In contrast , no association was noted between diabetes and aggressive disease ( i.e. , high grade or high stage ( Gleason sum ≥8 or clinical stages III or IV ) ; RR = 1.04 , 95 % CI = 0.74–1.45 ) . In further analyses , the association between diabetes and aggressive prostate cancer was suggestively positive for men who were lean ( RR = 1.64 , 95 % CI = 0.87–3.07 ; BMI < 25 kg/m2 ) and it was positive for men who were the most physically active ( RR = 1.63 ; 95 % CI = 1.07–2.62 ; 3 + hours vigorous activity/week ) . By comparison , no relations of diabetes to aggressive prostate cancer were noted for their heavier or physically less active counterparts ( p-value for tests of interaction = 0.10 and 0.03 BMI and physical activity , respectively ) . Conclusion In this study , diabetes showed divergent relations with prostate cancer by tumor aggressiveness . Specifically , diabetes was inversely associated with early stage prostate cancer but it showed no relation with aggressive prostate cancer . Exploratory analyses suggested a positive association between diabetes and aggressive prostate cancer in the subgroup of men with a low BMI The finding of isolated high grade prostatic intraepithelial neoplasia ( PIN ) or borderline lesions ( lesions suspicious for malignancy ) in prostate needle biopsies warrants repeat biopsies . The reported frequency of these lesions in prostate needle biopsies varies considerably . The authors evaluated the frequency and clinical impact of high grade PIN and borderline lesions in sextant prostate needle biopsies obtained from screened participants in the European R and omized study of Screening for Prostate Cancer ( ERSPC ) Levels of anxiety were assessed through question naires completed by 1781 screen-positive ( PSA > or = 3 ng/mL ) men attending the European R and omised Study of Screening for Prostate Cancer in Gothenburg , Sweden . During the first visit ( clinical examination , including biopsies ) , no anxiety whilst awaiting the PSA test results was reported by 66 % and 2 % reported high levels of anxiety . A multinomial logistics model for repeated measurements , adjusted for age , PSA level , heredity , biopsy finding and urinary symptoms , revealed that anxiety awaiting the PSA was only influenced ( increased ) by the existence of previously elevated PSA tests ( p<.0001 ) . No anxiety associated with biopsy was reported by 45 % , while 6 % experienced high levels of anxiety . Levels of anxiety decreased significantly with subsequent rounds of examinations ( p<0.0001 ) and with increasing age ( p=0.0016 ) . Anxiety associated with prostate cancer screening in general is low to moderate , even in men with elevated PSA , and severe anxiety affects a smaller group of susceptible men BACKGROUND The incidence of prostate cancer has increased substantially since it became common practice to screen asymptomatic men for the disease . The European R and omized Study of Screening for Prostate Cancer ( ERSPC ) was initiated in 1993 to determine how prostate-specific antigen ( PSA ) screening affects prostate cancer mortality . Variations in the screening algorithm , such as the interval between screening rounds , likely influence the morbidity , mortality , and quality of life of the screened population . METHODS We compared the number and characteristics of interval cancers , defined as those diagnosed during the screening interval but not detected by screening , in men in the screening arm of the ERSPC who were aged 55 - 65 years at the time of the first screening and were participating through two centers of the ERSPC : Gothenburg ( 2-year screening interval , n = 4202 ) and Rotterdam ( 4-year screening interval , n = 13301 ) . All participants who were diagnosed with prostate cancer through December 31 , 2005 , but at most 10 years after the initial screening were ascertained by linkage with the national cancer registries . A potentially life-threatening ( aggressive ) interval cancer was defined as one with at least one of the following characteristics at diagnosis : stage M1 or N1 , plasma PSA concentration greater than 20.0 ng/mL , or Gleason score greater than 7 . We used Mantel Cox regression to assess differences between rates of interval cancers and aggressive interval cancers at the two centers . All statistical tests were two-sided . RESULTS The 10-year cumulative incidence of all prostate cancers in Rotterdam versus Gothenburg was 1118 ( 8.41 % ) versus 552 ( 13.14 % ) ( P<.001 ) , the cumulative incidence of interval cancer was 57 ( 0.43 % ) versus 31 ( 0.74 % ) ( P = .51 ) , and the cumulative incidence of aggressive interval cancer was 15 ( 0.11 % ) versus 5 ( 0.12 % ) ( P = .72 ) . CONCLUSION The rate of interval cancer , especially aggressive interval cancer , was low in this study . The 2-year screening interval had higher detection rates than the 4-year interval but did not lead to lower rates of interval and aggressive interval prostate cancers BACKGROUND The use of PSA as a screening test has become increasingly prevalent in the general population and therefore also in the control arm of the European R and omized study of Screening for Prostate Cancer ( ERSPC ) . We present a feasibility study and impact simulation of a secondary analysis , which imitates a situation where all participants in the study are managed according to their r and om assignment . METHODS The results of the Rotterdam section of the ERSPC were adjusted for contamination and non-compliance according to Cuzick et al. [ Stat Med 1997 ; 16:1017 - 1029 ] . Endpoints of this analysis were simulated reductions in prostate cancer mortality . RESULTS Of the men allocated to the screen arm , 27.1 % were non-compliant . In the control arm 30.7 % had their PSA-level measured by a general practitioner ( GP ) ( i.e. , contamination ) . For a scenario in which the intention-to-screen analysis was assumed to give a decrease in the mortality in the men r and omized to screening of 6.7 % , the secondary analysis result ed in a decrease of 16.1 % for those actually screened . CONCLUSION Although the definition of contamination as " PSA ever tested " gives an indication of the proportion of contamination , it will be important to differentiate the screening use of PSA from its diagnostic use . For the rest , adjustment for non-compliance and contamination was shown to be feasible in this prostate cancer screening trial . It can therefore be used to carry out a secondary analysis on the definitive outcome of the ERSPC and will provide accurate information for those men who are in fact screened There continues to be controversy regarding serum Prostate-Specific Antigen ( PSA ) and prostate cancer screening . We anxiously await the results of two large prospect i ve r and omized clinical trials ( Prostate , Lung , Colon , and Ovary-PCLO screening trial in the US and European R and omized Study of Screening for Prostate Cancer-ERSPC in Europe ) assessing the benefits of prostate cancer screening . However the true question to answer may be which cancer to treat and when should we treat it OBJECTIVES To evaluate the complication rates and possible risk factors of biopsy of the prostate , with the aim of improving patient counseling and the safety of the procedure . Biopsy of the prostate has to be a relatively safe procedure and the participants have to be well informed about the possible complications . METHODS Within the biopsy protocol of the Rotterdam section of the European R and omized Study of Screening for Prostate Cancer , we evaluated 5802 transrectal ultrasound-guided systematic sextant biopsies . All participants received prophylactic antibiotic therapy . RESULTS We performed 5802 biopsies . Hematuria lasting longer than 3 days and hematospermia were present after 22.6 % and 50.4 % of the procedures , respectively . More severe complications were far less frequent . Two hundred participants ( 3.5 % ) developed fever after biopsy . Urinary retention was seen 20 times ( 0.4 % ) , and hospitalization was needed in 27 cases ( 0.5 % ) . Twenty-five of these men were admitted because of signs of prostatitis and /or urosepsis . Risk factor analyses revealed that an earlier episode of prostatitis was significantly associated with hospital admission and pain after biopsy . Characteristics of prostatic hyperplasia , such as prostate volume , transition zone volume/total prostate volume ratio , and a higher International Prostate Symptom Score , were all predictors of urinary retention . CONCLUSIONS Minor complications are frequently seen but major complications are rare after prostate biopsy . Assessment of the risk factors before biopsy can help to improve the adequacy of counseling , and pre caution ary measures can be taken to minimize the risk of complications after the procedure . Transrectal ultrasound-guided sextant biopsy remains a safe procedure for the diagnosis of prostate cancer within the general population To assess the potential problem that different tools for predicting a positive outcome of prostate biopsy can produce divergent outcomes in the same man , by comparing the risk calculators based on the Prostate Cancer Prevention Trial ( PCPT ) and the European R and omized Study of Screening for Prostate Cancer ( ERSPC ) We recently reported on the willingness to pay ( WTP ) for prostate cancer screening with prostate specific antigen ( PSA ) using the contingent valuation method ( CVM ) . This study , a continuation of the work outlined in the previous report , comprises a more precise and detailed survey . In an Internet question naire survey , 400 men aged 50 - 59 in Japan were r and omly split into two groups : the ill-informed group ( n = 207 ) , which was provided with information about the detection rate , and the well-informed group ( n = 193 ) , which was given additional information about false positive/negative results , latent cancer , and the yet-to-be-demonstrated mortality-reducing effect of the test . The mean WTP was yen1670 ( $ 15.2 ) . Giving sufficient information would not decrease WTP for PSA screening . Men place a high value on ' peace of mind ' through the ascertaining of no sign of cancer at the present rather than on the future-oriented life-saving effects that may be gained through such screening BACKGROUND The 11,811 first visits and 46,751 annual follow-up visits performed since 1988 were analyzed in order to assess the efficacy of serum prostatic specific antigen ( PSA ) and digital rectal examination ( DRE ) for diagnosis of prostate cancer . METHODS At first visit , screening included DRE and measurement of PSA using 3.0 ng/ml as upper limit of normal , demonstrated as optimal value in the course of the study . Transrectal echography of the prostate ( TRUS ) was performed only if PSA and /or DRE was abnormal . For elevated PSA , biopsy was performed only if PSA was above the value predicted from prostatic volume measured by TRUS . At follow-up visits , it was decided during the course of the study to use PSA alone . RESULTS PSA was above 3.0 ng/ml in 16.6 % and 15.6 % of men at first and follow-up visits , respectively . Prostate cancer was found in 2.9 % of men invited for screening at first visit and in only 0.4 % of men at follow-up visits for a 7.1-fold decrease at follow-up visits done up to 11 years . PSA alone allowed to find 90.5 % and 90 . 0 % of cancers at first and follow-up visits , respectively , compared to 41.1 % and 25.0 % by DRE alone . In the presence of normal PSA , 344 and 1,919 DREs are needed to find one prostate cancer at first and follow-up visits , respectively . A significant improvement in stage of the disease is found at follow-up ( 215 cancers ) compared to first visits ( 337 cancers ) . Comparison made between men invited for screening and those who were not invited but screened showed no significant difference in terms of incidence and prevalence of prostate cancer as well as diagnosis of cancer as a function of age or as a function of PSA , DRE , and TRUS data . The cost for finding one case of prostate cancer is estimated at Can $ 2,420 and Can $ 7 , 105 ( first and follow-up visits , respectively , when PSA is used as prescreening ) . CONCLUSIONS PSA used as prescreening and followed by DRE and TRUS when PSA is abnormal is highly efficient in detecting prostate cancer at a localized ( potentially curable ) stage since 99 % of the cancers diagnosed were at such a localized stage , thus practically eliminating the diagnosis of metastatic and noncurable prostate cancer . The approach used is highly reliable , sensitive , efficient , and acceptable by the general population . The detection of clinical ly nonsignificant cancer is an exception The study purpose was to assess PSA velocity ( PSAV ) in healthy subjects in order to establish a reliable cutoff for the differential diagnosis of prostate cancer in a screening setting . We studied a series of 1666 healthy men aged 55 to 74 years undergoing two total PSA determinations at a four-year interval within a population -based r and omized screening trial at the Centro per lo Studio e la Prevenzione Oncologica of Florence . First and second screening round PSA assays ( PSA1 and PSA2 ) were carried out with the same method and by the same laboratory . PSAV ( PSA1-PSA2/year ) was determined in non-cancer subjects in the overall series or in specific age and PSA subgroups , and in subjects with cancer detected at the second screening round . Average PSAV in 1648 non-cancer subjects was 0.07 ng/mL/year ( range -2.18 + 5.99 , 95 % CI 0.05 - 0.09 ) ; at least one third of subjects showed a decrease in PSA ( negative PSAV ) , mostly of limited magnitude and in the low PSA range . Average PSAV in the 18 cancer patients was 1.16 ng/mL/year ( range 0.10 - 5.6 , 95 % CI 0.56 - 1.77 ) , which is significantly higher ( p<0.01 ) than in non-cancer subjects . None of the cancer patients showed a PSA decrease over time . Whatever cutoff was taken for PSAV , its power to discriminate cancer was limited : in particular the previously used PSAV cutoff of 0.75 ng/mL/year would have included only 42 of the 1648 non-cancer subjects ( specificity 97.5 % ) but excluded eight of the 18 cancer patients ( sensitivity 55.5 % ) . At best , with the adopted screening protocol PSAV ( cutoff 0.10 ng/mL/year ) could have spared 27.9 % of non-cancer subjects with PSA > or = 2.5 ng/mL further diagnostic assessment and 22.7 % of non-cancer subjects with PSA > or = 4 ng/mL r and om sextant biopsy , while missing no cancers . This study provides a reliable estimate of PSAV based on a large unbiased population sample . PSAV is widely variable over time , particularly at low PSA values . PSAV might be of value as an indicator for diagnostic assessment and r and om sextant biopsy in a screening setting Objective . The measurement of prostate-specific antigen ( PSA ) is a useful tool in the screening and follow-up of prostate cancer , but its diagnostic validity is uncertain in hemodialysis patients . The aim of this study was to evaluate the effects of hemodialysis on serum complexed PSA ( cPSA ) levels . Material and methods . A total of 36 men ( mean age 62.54±8.20 years ) with end-stage renal disease were enrolled in a prospect i ve study . Serum total PSA ( tPSA ) , free PSA ( fPSA ) and cPSA , and hematocrit levels were measured before and immediately after dialysis using low-flux membranes in the serum and in the dialysis ultrafiltrate . Results . After hemodialysis , cPSA , fPSA and the fPSA : tPSA ratio increased significantly ( p<0.05 ) . However , there was no significant increase in tPSA . fPSA , cPSA and tPSA were not detected in ultrafiltrate . Hematocrit levels increased significantly ( p<0.0001 ) due to hemoconcentration . Of patients with initial serum tPSA and cPSA values and fPSA : tPSA ratios below the cut-off values , none had a post-hemodialysis value greater than the cut-off point . There were weak correlation between the difference in values after and before hemodialysis of hematocrit and cPSA ( p=0.035 ) , and between the percentage change in levels before and after hemodialysis of hematocrit and cPSA ( p=0.041 ) . Conclusions . Hemodialysis induced elevations in all forms of PSA , but tPSA was the least affected form . cPSA did not show any diagnostic superiority over other forms of PSA . Thus , serum tPSA remains a reliable parameter for follow-up of prostate cancer in uremic patients receiving long-term dialysis . However , further research is needed to explain the pathophysiology of alterations in the concentrations of different forms of PSA In Hungary , prostate cancer is a major public health problem , therefore screening should be considered to reduce the number of deaths . Screening tests are available , i.e. prostate-specific antigen ( PSA ) and digital-rectal examination , nevertheless their sensitivity , specificity and positive predictive value are far from being perfect . Evidence s from non-r and omized screening trials suggest possible benefit but r and omized controlled trials are still needed for conclusive evidence . The screening might cause more harm than good due to overdiagnosis and overtreatment as a result of limited specificity of the test . According to authors ' point of view , opportunistic screening as part of diagnostics of patients having symptoms indicative of prostatic disorder is fully justified but mass screening of population of average risk should not be introduced until supportive evidence is available from the ongoing r and omized-controlled screening trials OBJECTIVE Implementation of a pilot screening program for prostate cancer among Saudi patients that would serve as a nucleus for a Kingdom-wide screening program . METHODS A prospect i ve study on 1,213 Saudi males between 50 - 80 years of age who attended the Outpatient Department at King Fahd Hospital of King Faisal University , Al-Khobar , Kingdom of Saudi Arabia during a period of 18 months ( April 2001-October 2002 ) . They were included at r and om from different clinics including the urology clinic . Free and total prostate specific antigen ( PSA ) , and digital rectal examination ( DRE ) of the prostate were performed in all patients . Patients with abnormal DRE or PSA were scheduled for transrectal ultrasound ( TRUS ) and ultrasound guided biopsy of the prostate . RESULTS Abnormal DRE or PSA were present in 84 out of 1,213 patients . Only 63 patients agreed to have TRUS and ultrasound guided biopsies . Prostate cancer was confirmed in 14 out of 1,192 patients who completed the study ( 1.17 % ) . CONCLUSION The incidence of prostate cancer among Saudi men in this hospital based study is low . A population based screening for prostate cancer may reveal the incidence of this disease BACKGROUND The aim of the present study was to evaluate the future cumulative risk of prostate cancer in relation to levels of prostate-specific antigen ( PSA ) in blood and to determine whether this information could be used to individualize the PSA testing interval . METHODS The study included 5855 of 9972 men ( aged 50 - 66 years ) who accepted an invitation to participate in a prospect i ve , r and omized study of early detection for prostate cancer . We used a protocol based on biennial PSA measurements starting from 1995 and 1996 . Men with serum PSA levels of 3.0 ng/mL or more were offered prostate biopsies . RESULTS Among the 5855 men , 539 cases of prostate cancer ( 9.2 % ) were detected after a median follow-up of 7.6 years ( up to July 1 , 2003 ) . Cancer detection rates during the follow-up period in relation to PSA levels were as follows : 0 to 0.49 ng/mL , 0 % ( 0/958 ) ; 0.50 to 0.99 ng/mL , 0.9 % ( 17/1992 ) ; 1.00 to 1.49 ng/mL , 4.7 % ( 54/1138 ) ; 1.50 to 1.99 ng/mL , 12.3 % ( 70/571 ) ; 2.00 to 2.49 ng/mL , 21.4 % ( 67/313 ) ; 2.50 to 2.99 ng/mL , 25.2 % ( 56/222 ) ; 3.00 to 3.99 ng/mL , 33.3 % ( 89/267 ) ; 4.00 to 6.99 ng/mL , 38.9 % ( 103/265 ) ; 7.00 to 9.99 ng/mL , 50.0 % ( 30/60 ) ; and for men with an initial PSA of 10.00 ng/mL or higher , 76.8 % ( 53/69 ) . Not a single case of prostate cancer was detected within 3 years in 2950 men ( 50.4 % of the screened population ) with an initial PSA level less than 1 ng/mL. CONCLUSIONS Retesting intervals should be individualized on the basis of the PSA level , and the large group of men with PSA levels of less than 1 ng/mL can safely be scheduled for a 3-year testing interval BACKGROUND The 46,193 men aged 45 to 80 years registered in the electoral roll of Quebec City and its Metropolitan area were r and omized in November 1988 between screening and no screening in a study aim ed of assessing the impact of prostate cancer screening on cause-specific death . METHODS At first visit , screening included measurement of serum prostatic specific antigen ( PSA ) using 3.0 ng/ml as upper limit of normal and a digital rectal examination ( DRE ) . Transrectal echography of the prostate ( TRUS ) was performed only if PSA and /or DRE was abnormal and biopsy was then done , only if PSA was above the predicted PSA value . At follow-up visits , PSA alone was used as prescreening . RESULTS 137 deaths due to prostate cancer occurred between 1989 and 1996 , inclusively , in the 38,056 unscreened men while only 5 deaths were observed among the 8,137 screened individuals . The prostate cancer death rates during the eight-year period were 48.7 and 15 per 100,000 man-years in the unscreened and screened groups , respectively , for a 3.25 odds ratio in favor of screening and early treatment ( P < 0.01 ) . CONCLUSIONS If PSA screening is started at the age of 50 years ( or 45 years in the higher risk population ) , annual or biannual PSA alone is highly efficient to identify the men who are at high risk of having prostate cancer . Coupled with treatment of localized disease , this approach demonstrates , for the first time , that early diagnosis and treatment permits a dramatic decrease in deaths from prostate cancer PURPOSE At low prostate specific antigen ( PSA ) the indication for prostate biopsy is usually an abnormal digital rectal examination . We evaluate the diagnostic value of PSA , digital rectal examination , transrectal ultrasonography and tumor characteristics at low PSA ( 0 to 4.0 ng./ml . ) . We confirm and add to recent evidence that digital rectal examination has a low predictive value and that many significant cancers at this PSA range may be missed . MATERIAL S AND METHODS From 1994 to 1997 a total of 10,523 participants 54 to 74 years old were r and omized to screening in the Rotterdam section of the European R and omized Study of Screening for Prostate Cancer . Of the participants 9,211 ( 87.5 % ) had PSA less than 4.0 ng./ml . , and underwent digital rectal examination and transrectal ultrasonography . Expected rates of prostate cancer detection were calculated using logistic regression analysis . Radical prostatectomy was performed in about half of the 478 men diagnosed with prostate cancer . Tumors were characterized by pT category , Gleason score and cancer volume in 166 processed radical prostatectomy specimens . In 50 of these cases PSA was 0 to 4.0 ng./ml . RESULTS The positive predictive value of digital rectal examination and transrectal ultrasonography at PSA 0 to 4.0 ng./ml . was only 9.7 % . Positive predictive value strongly depended on PSA . Sensitivity was calculated by using estimates of the prevalence of sextant biopsy detectable prostate cancers . Of 760 detectable cancers 478 ( 67 % ) were diagnosed irrespective of PSA in men screened with digital rectal examination , transrectal ultrasonography and PSA . Only 127 of 348 detectable prostate cancers ( 36.5 % ) were actually diagnosed in men with PSA 2 to 4 mg./ml . The importance of these missed cancers was evaluated with parameters of tumor aggressiveness within PSA ranges . CONCLUSIONS Approximately half of the tumors missed with PSA 0 to 4 ng./ml . had aggressive characteristics ( Gleason score 7 or greater , Gleason 4 - 5 components ) and were organ confined . These tumors should be diagnosed and treated according to the present underst and ing of their natural history . More sensitive and selective screening strategies are needed . Presently a wrong " window of opportunity " is used for early detection of prostate cancer PURPOSE This article describes the demographic characteristics of participants in a r and omized trial ( the AAMEN Project ) design ed to recruit older ( aged 55 + years ) African American men to a cancer screening trial . DESIGN AND METHODS The AAMEN Project is a recruitment trial developed for African American men aged 55 + years living in southeastern Michigan . RESULTS Of the 34,376 African American men in the study , 37.6 % had low incomes and 62.4 % had moderate-to-high incomes . The average age of the men was 63.3 years ( SD = 5.9 years ) . Among men who were eligible and interested in participating , the proportion of men with low incomes was significantly greater than the proportion of men with moderate-to-high incomes ( p < .001 ) . IMPLICATION S The AAMEN Project demonstrated success in recruiting a substantial proportion of men with low incomes as well as men with moderate-to-high incomes . These findings may facilitate the development of future recruitment efforts involving older African American men Abstract : This unblinded , r and omized , Phase I clinical trial was conducted to determine whether lycopene supplementation lowered serum prostate specific antigen ( PSA ) , surrogate endpoint for prostate cancer initiation or progression , in men with elevated prostate cancer risk . Afro-Caribbean men ( n = 81 ) with high- grade prostatic intraepithelial neoplasia , atypical foci or repeated non-cancerous biopsies , ascertained in a population -based screening program , were r and omized to four months intervention with 30 mg/day lycopene ( Lyc-O-Mato ® ) plus a multivitamin , or to multivitamin , only . Serum PSA and lycopene were compared at r and omization , 1 , and 4 mo using two-sided χ 2 and t-tests for independent sample s. Treatment groups were similar at baseline . Serum lycopene levels approximately doubled in the lycopene intervention group . Serum PSA declined during the first month of treatment , but returned to r and omization level by month 4 . The PSA response was nearly identical in both treatment groups . No adverse effects attributed to lycopene supplementation were documented . We conclude that the PSA lowering response to antioxidant supplementation observed in previous 3-wk studies in men awaiting prostatectomy may have been a transient response , perhaps not specific to lycopene . Lowering of serum PSA may not be an appropriate endpoint for the long-term studies needed to evaluate lycopene supplementation for reducing prostate cancer initiation or progression Of 9,026 males aged 50 - 69 years , 1,494 were r and omly selected and invited to participate in a programme including two screenings for carcinoma of the prostate by digital rectal examination performed in 1987 and 1990 . The remaining 7,532 served as a control group . Of the selected persons , 78 % accepted the invitation to the first screening round and 70 % to the second one . Carcinoma of the prostate was suspected in 45 of 1,163 men examined at the first screening round and in 42 of 953 at the second round . Carcinoma was confirmed by fine-needle aspiration biopsy in 13 cases from the first and in 7 from the second round . In the study group , 17.4 carcinomas were diagnosed per 1,000 men and in the control group 8.6 per 1,000 men . The screening cost was 1,640 pounds per detected cancer and 2,343 pounds per detected and potentially cured cancer . Screening for carcinoma of the prostate by digital rectal examination can be organised with a high population acceptance , and at a reasonable cost . The impact of screening on mortality in prostatic cancer remains uncertain PURPOSE Differences in prostate specific antigen awareness may contribute to differences in the frequency of prostate specific antigen testing . We investigated the association of health risk behaviors , including smoking , physical inactivity , obesity and excessive alcohol consumption , with awareness of the prostate specific antigen test in men in California at risk for prostate cancer . MATERIAL S AND METHODS Using 2003 data from the California Health Interview Survey , a population based , r and om digit dial telephone survey , the records of 7,297 men 50 years or older without a history of prostate cancer were identified . The outcome was self-reported awareness of the prostate specific antigen test . The main independent variables were smoking status , physical activity level , body mass index and alcohol consumption . The prevalence , OR and 95 % CI for prostate specific antigen awareness were calculated using SUDAAN to account for the complex sampling design . RESULTS The overall prevalence of prostate specific antigen awareness was 73.0 % . After controlling for potential confounders the odds of being aware of the prostate specific antigen test was lower in current smokers ( vs never smoked OR 0.53 , 95 % CI 0.41 - 0.68 ) , physically inactive men ( vs physically active OR 0.77 , 95 % CI 0.63 - 0.93 ) and obese men ( vs normal weight OR 0.77 , 95 % CI 0.62 - 0.95 ) . CONCLUSIONS Health risk behaviors are associated with lower prostate specific antigen awareness . Our findings suggest opportunities for focused health education interventions and quality improvement programs tailored to men who engage in unhealthy behaviors to improve their prostate specific antigen test awareness Background : The purpose of this study was to examine the effects of baseline comorbidities on screening adherence in a sample of older African American men ( ages ≥55 years ) enrolled in a case management intervention in a cancer screening trial . Methods : Baseline comorbidity data were obtained from 683 African American men who were r and omly assigned to a case management intervention group ( n = 344 ) or to a case management control group ( n = 339 ) . The effects of comorbidities on the screening adherence rates of each group were then assessed . Results : No statistically significant interactions were found between each health history characteristic and the intervention . Therefore , analyses were not stratified by intervention status . In general , participants with comorbidities were no less likely to adhere to trial screening than participants without comorbidities . Exceptions were current smokers and participants with chronic bronchitis . Current smokers were less likely than others to adhere to the prostate-specific antigen test ( P = 0.02 ) and the digital rectal examination for prostate cancer screening ( P = 0.01 ) , to the chest X-ray for lung cancer screening ( P < 0.01 ) , and to the flexible sigmoidoscopy for colorectal cancer screening ( P = 0.04 ) . Participants with chronic bronchitis had lower rates of adherence to the chest X-ray ( P = 0.06 ) . Having a relative with cancer positively influenced adherence to the digital rectal examination ( P = 0.05 ) . Conclusions : Overall , older African American men with comorbidities appear to be very good c and i date s for participation in longitudinal cancer screening trials . However , smoking had a statistically significant and deleterious effect on adherence to all types of screening . ( Cancer Epidemiol Biomarkers Prev 2008;17(5):1234–9 OBJECTIVES The purpose of screening for prostate cancer is to decrease the disease-specific mortality . However not every screen-detected prostate cancer is a threat to the patient 's life . The risk of overdetection and subsequent overtreatment in prostate cancer has been recognised . The purpose of this investigation was to evaluate the role of tumour markers total PSA , free PSA , and hK2 , and their combinations in predicting minimal prostate cancer . METHODS Within the European R and omized Study of Screening for Prostate Cancer ( ERSPC ) , section Rotterdam , The Netherl and s , prebiopsy serum sample s were analysed for 100 selected men who underwent a radical prostatectomy for their screen-detected prostate cancer . All had a PSA value between 4 and 10 ng/ml prior to diagnosis . Minimal prostate cancer is defined as organ confined , Gleason score < /=6 ( no Gleason grade 4 or 5 ) , and tumour volume < 0.5 ml . RESULTS Sera and tumour volumes from 91 men were available for analysis . Minimal prostate cancer was diagnosed in 16.5 % of the selected cases . Mean tumour volume was 1.2 ml ( range : 0.04 - 13.5 ) ; hK2 , the algorithms hK2/fPSA , and hK2/%fPSA have significant correlations with tumour volume . Both algorithms also yielded the best test results in predicting minimal disease with an area under the receiver operator characteristics curve of 82 % . CONCLUSIONS hK2 and percent free PSA have added prognostic value for the detection of minimal prostate cancer in screen-detected cases within PSA range 4 - 10 ng/ml . These biomarkers can possibly be used to select less invasive treatment options like active surveillance and to prevent overtreatment The extent of effective prostate‐specific antigen ( PSA ) contamination in the Rotterdam section of the ongoing European R and omized Study of Screening for Prostate Cancer ( ERSPC ) trial was evaluated and defined as when opportunistic PSA testing of ≥ 3.0 ng/ml was followed by biopsy , similar to the regular procedure within the trial . Records of participants aged 55–74 years at entry were linked to the regional data base of the general practitioner ( GP ) laboratory to obtain PSA tests requested by GPs in the period 1 July 1997 to 31 May 2000 ( 2.9 years ) , and to the national pathology data base to quantify the number of biopsies . All men r and omized were included , only those with prostate cancer screen‐detected or clinical ly diagnosed before July 1997 were omitted from the analyses . 2,895 out of the 14,349 men ( 20.2 % ) in the control arm and 1,981 out of the 14,052 men ( 14.1 % ) in the screening arm were PSA‐tested , at an average annual rate of 73 and 52 per 1,000 person‐years , respectively . These rates were higher than those recorded at the national and regional levels , 33 and 38 per 1,000 person‐years , respectively . Opportunistic PSA testing in the control arm reached a peak within the first months of r and omization , after which it decreased to around 70 per 1,000 person‐years . An opposite pattern was observed in the screening arm , where participants already had received the scheduled screening within the trial . The proportion of men in the control arm with PSA ≥ 3.0 ng/ml followed by biopsy and prostate cancer was 7–8 % and 3 % , respectively ( 3 % and 0.4–0.6 % in the screening arm ) , over the whole study period . Over a 4‐year rescreening interval , the average PSA and effective contamination amount were approximately 28 % and 10 % , respectively . PSA testing in the control arm in the Rotterdam ERSPC section is high , but was not followed by a substantial increase in prostate biopsies . Although the reasons for ordering PSA test or indicating biopsy are unknown , effective PSA contamination in the Rotterdam ERSPC section is low and not likely to jeopardize the power of the trial . © 2003 Wiley‐Liss , The preliminary results of a feasibility study of a r and omized trial for the early detection of prostate carcinoma are reported . 4,229 healthy men aged 60 - 75 years were invited to undergo digital rectal examination ( DRE ) and transrectal ultrasonography ( TRUS ) ; 1,284 of them responded and were thus examined . Subjects with suspicious findings at DRE and /or TRUS underwent transperineal US-guided biopsy and prostate-specific antigen ( PSA ) determination . Subjects with equivocal findings were controlled after 6 months with DRE , TRUS and PSA . The screening program was rather simple ( examination time < 10 ' ) and cost was limited ( cost x subject = US $ 25 ) . So far , 27 biopsies ( 2.1 % ) have been performed . Eighteen cancers have been detected ( 1.41 % ) , the prevalence/expected incidence ratio being 10.6:1 . Stage at diagnosis was B1 in 12 , B2 in 3 , C in 2 and D in one case , respectively . Cancer had been suspected at DRE in 12 , at TRUS in 17 and at PSA ( cutoff = 4 micrograms/ml ) in 15 of 18 cases , respectively . This study provides evidence that screening for prostate cancer is feasible at a moderate cost and diagnostic anticipation is relevant . A prospect i ve r and omized trial is needed to assess whether early detection has any impact at all on mortality . When design ing such a study , the effect of compliance , which was low in our experience , on the statistical power should be carefully evaluated . The possibility of pre-screening with PSA , which is much more accepted and might improve attendance rates , should also be evaluated by specific studies BACKGROUND We performed a prospect i ve r and omized trial comparing 5 contrast-enhanced color Doppler ( CECD ) ultrasound ( US ) targeted biopsy cores to 10 gray-scale US guided systematic biopsy ( SB ) cores to determine the impact on the cancer detection rate . METHODS We prospect ively r and omized 100 prostate specific antigen ( PSA ) screening volunteers with an elevated PSA ( > or = 1.25 ng/ml and free-to-total PSA < 18 % ) to undergo contrast-enhanced targeted or SB . Contrast-enhanced targeted biopsies with a limited number of five cores were performed into hypervascular areas of the peripheral zone ( PZ ) during administration of the US contrast agent SonoVue ( Bracco , Italy ) . A subjective grading of the vascularity from 0 to 3 was used : grade 0 , no color signal ; 1 , low density ; 2 , medium density ; and 3 , high density of color signals . Ten SBs were obtained in a st and ard spatial distribution . Cancer detection rates were compared in the groups . RESULTS Cancer was detected in 16/50 subjects ( 32 % ) by targeted biopsy , and in 13/50 patients ( 26 % ) with SB . The cancer detection rate was significantly better for the targeted approach ( P < 0.04 , McNemar ) . The detection rate for targeted biopsy cores ( 15.6 % or 39/250 cores ) was significantly better than for SB cores ( 6.8 % or 34/500 cores , P < 0.001 , McNemar ) . CONCLUSIONS CECD targeted biopsy detected more cancers than SB with a reduced number of biopsy cores The aim of the present study was to identify the effects of physical exercise on PSA serum levels and the diagnostic validity of PSA in the screening of prostate cancer in subjects undergoing physical exercise during chronic hypoxia . The study was performed during trekking between 3,200 and 5,600 meters of altitude on K2 mountain for 26 days . Mean serum PSA values before and after exposure did not show significant difference due to physical exercise . These data indicate that physical exercise or mountain hypoxia do not affect the diagnostic validity of PSA OBJECTIVE To evaluate patients ' perception of pain and discomfort during DRE , the impact of discomfort on potential future screening compliance , and if emptying the bladder immediately before DRE reduces patient discomfort . METHODS One-hundred patients undergoing DRE for prostate cancer screening answered an anonymous question naire regarding pain , urinary urgency and bowel urgency during DRE and its potential impact on future examination . Another group with 100 patients was r and omized in two subgroups to analyze if urinating immediately before DRE reduces patient discomfort . RESULTS Seventy-three ( 73 % ) patients reported moderate or higher discomfort for at least one of the domains evaluated : 61 % complained of pain ; 22 % of urinary urgency ; and 22 % of bowel urgency . Emptying the bladder immediately before examination did not reduce pain ( 58 % vs. 50 % , p = 0.115 ) , urinary urgency ( 22 % vs. 16 % , p = 0.151 ) , or bowel urgency intensity ( 16 % vs. 14 % , p = 0.264 ) . There was no difference in the number of patients that answered they will repeat the prostate exam next year ( 96 % vs. 90 % , p = 0.211 ) or in those that would encourage a friend that needs the prostate exam to do it ( 96 % vs. 98 % , p = 0.378 ) . CONCLUSIONS Pain and discomfort during DRE are not negligible but they do not affect intention to have a prostate exam in the future . Urinating immediately before examination does not significantly reduce the incidence of pain , urinary urgency , or bowel urgency during DRE OBJECTIVES Few decision aids are tailored for African-American men . We sought to determine if web-based decision aids increased knowledge of prostate cancer screening among African men . METHODS This postintervention , quasiexperimental research measured knowledge of prostate cancer screening among African-American men following receipt of 1 of 2 web-based decision aids : enhanced or usual care . Men ages 40 - 65 were recruited at the annual convention of the Prince Hall Masons in the summer of 2007 , which was attended by 1170 masons . The primary outcome was knowledge of prostate cancer screening . RESULTS There were 87 participants in the sample with a mean age of 52 years ( st and ard deviation = 6.9 ) . Forty-six masons were r and omized to the enhanced decision aid , and 41 masons were r and omized to the usual care decision aid . Knowledge scores were statistically significantly higher among the men receiving the enhanced decision aid compared to the usual care decision aid after simultaneously adjusting for age , educational level , marital status , family history , previous prostate specific antigen test and digital rectal exam ( p = 0.01 ) . CONCLUSION We found evidence that the enhanced web decision aid was significantly more effective than the usual care decision aid in promoting knowledge of the benefits , limitations and risks of prostate cancer screening . Web-based sites may be effective in facilitating discussion s about screening between patients and health care providers Background Although prostate cancer screening by measurement of serum prostate-specific antigen ( PSA ) and digital rectal examination ( DRE ) is common in clinical practice , the impact of such screening on prostate cancer-specific mortality remains uncertain . Methods Data from a population -based case – control study in King County , Washington , among men aged 50–64 years ( 706 cases , 645 controls ) were used to examine the relationships between PSA and DRE screening and fatal prostate cancer and other-cause mortality . Incident cases were diagnosed in 1993–1996 , identified via the Seattle-Puget Sound SEER cancer registry and followed for vital status through 1 June 2007 . Controls were ascertained by r and om digit dialing and frequency age-matched to cases . The screening variable used in this analysis was self-reported receipt of one or more PSA and /or DRE tests performed as part of a routine checkup in the five-year period before diagnosis or reference date . Results A smaller proportion of men with fatal prostate cancer had one or more PSA and /or DRE screening tests compared to controls , result ing in an adjusted odds ratios ( OR ) of 0.38 ( 95 % CI 0.19–0.77 ) . There was no association , however , between PSA and /or DRE screening and other-cause mortality ( OR = 1.02 ; 95 % CI 0.51–2.02 ) . Conclusions Results of this study suggest a reduction in prostate cancer-specific mortality associated with PSA and /or DRE screening in middle-aged men . Findings should be interpreted cautiously , however , as results are based on observational data . Further , the study was not able to separate the relative efficacy of PSA versus DRE screening BACKGROUND Because neither continuous nor intermittent hormonal therapy is curative , we design ed a clinical model to screen new drugs for additive or synergistic effects with hormonal therapy and used IM862 , a naturally occurring dipeptide with antiangiogenic and immunomodulatory properties , to test it . METHODS Patients with prostate cancer who had rising PSA levels after radical prostatectomy and /or radiation therapy were given combined and rogen ablation for 3 months . After 2 months ' treatment , patients were r and omly assigned in a double-blind fashion to receive intranasal IM862 or placebo daily . Treatment continued for 6 months or until disease progression , which was defined by a rising serum PSA level , the appearance of new skeletal or extraskeletal metastatic disease , or new symptoms requiring intervention . RESULTS Seventy-one patients were evaluable for response . Median time to PSA progression was not reached in either group . At 6 months , disease had progressed in 14 ( 41 % ) of the 34 patients receiving treatment and 18 ( 49 % ) of the 37 receiving placebo ( P = 0.39 ) . No significant toxicities emerged . CONCLUSIONS The model was demonstrated to be an efficient platform for new drug screening ; however , IM862 , though well tolerated , failed to demonstrate superiority over placebo in prolonging time to PSA progression BACKGROUND We conducted a r and omized controlled trial to evaluate the effects of patient decision support Web sites on decision quality for men considering prostate cancer screening . METHODS Men older than 50 years ( N = 611 ) were r and omly assigned to 1 of 4 Internet conditions : traditional didactic decision aid providing information about prostate-specific antigen ( PSA ) screening options and outcomes ; chronic disease trajectory model for prostate cancer followed by a time-trade-off exercise ; both the didactic decision aid and the chronic disease trajectory model ; or links to public prostate cancer-specific Web sites from credible sources ( control condition ) . Participants completed question naires at baseline and after their physical examination . Primary outcome measures were PSA test choice , prostate cancer treatment preferences , knowledge and concern about prostate cancer , and decisional conflict . RESULTS Participants assigned to view public Web sites were less likely to review information ( 116 participants [ 76.8 % ] review ed ) than those assigned to experimental groups ( 399 [ 86.7 % ] review ed ; P = .004 ) . Greater reductions in PSA screening from pretest to posttest were observed among participants assigned to the traditional decision aid ( -9.1 % ) or chronic disease trajectory model ( -8.7 % ) , compared with participants assigned to the combination ( -5.3 % ) or control ( -3.3 % ) groups ( P = .047 ) . Preferences for watchful waiting increased significantly in all 4 groups ( baseline , 219 [ 35.8 % ] ; follow-up , 303 [ 66.2 % ] ; P < .001 ) . Knowledge scores were lowest for those assigned to public Web sites ( mean [ SD ] score , 7.49 [ 0.19 ] of questions correct ) and highest for the traditional decision aid ( 8.65 [ 0.18 ] of questions correct ; P = .005 ) . CONCLUSION Public Web sites about prostate cancer provide less effective decision support than a specially design ed Internet decision aid Background . The feasibility of screening and early detection of prostate cancer are controversial issues at this time . To conduct a r and omized screening study with prostate cancer mortality as the major endpoint is one possible solution to the present controversy OBJECTIVES Numerous commercial assays are available for measuring total and free prostate-specific antigen ( PSA ) levels in serum . These assays can be referenced to different laboratory st and ards , and interassay variability occurs . Patients and physicians might be affected by the variability between PSA assays that results from the use of different PSA st and ards . METHODS We prospect ively compared the free and total PSA measurements obtained using two commercially available PSA assays in 103 participants from a prostate cancer screening program in Caracas , Venezuela . We recommended biopsy to men with a total PSA level of 3 to 10 ng/mL and a free/total PSA ratio of 20 % or less with either assay . We compared the sensitivity , specificity , and concordance index between the two assays to assess the effects of interassay variability on the cancer detection rate and clinical outcomes . RESULTS Although the total PSA results were similar between the assays , the free PSA level was significantly greater with one assay . Therefore , the free/total PSA ratio was discordant between the two assays , result ing in different biopsy recommendations and cancer detection rates . CONCLUSIONS Using a free/total PSA ratio of 20 % or less as the threshold for biopsy , the differences in assay sensitivity and specificity for detecting prostate cancer are significant . Commercially available assays for PSA and its derivatives are not necessarily interchangeable , and these differences might lead to different clinical outcomes . When using free and total PSA measurements to make clinical decisions , patients and physicians should be aware of the potential st and ardization bias and which assay is being used OBJECTIVE To study the follow-up of men with elevated prostate-specific antigen ( PSA ) ( > 3 ng/ml ) after one benign set of sextant biopsies . From the Göteborg branch of the European R and omised Study of Screening for Prostate Cancer ( ERSPC ) . METHOD 456 men with one set of benign sextant biopsies were followed every second year for 4 years with PSA determinations . In cases of elevated PSA , transrectal ultrasound ( TRUS ) guided sextant biopsies were suggested . Digital rectal examination ( DRE ) , prostate volume , PSA , PSA density ( PSAD ) and the ratio between free and total PSA ( PSA F/T ) were recorded . RESULTS Complete data were available for 322 men . 3 groups were identified . In 84/322 ( 26 % ) men cancer was found ( " cancer " group ) . 182/322 ( 56 % ) had benign biopsies ( " benign " group ) and 56/322 ( 17 % ) had normalised PSA ( " normalised PSA " group ) . Median prostate volumes were 36 , 46 , and 33 cc respectively in the three groups . DRE and /or TRUS were abnormal in only 30 % of the men in all groups . Cancer was not found in any prostate > 70 cc volume . In prostates of < 20 cc either cancer was found or PSA was normalised . The " normalised PSA " group had initial PSA , PSAD and PSA F/T similar to cancer , normalising during follow-up . CONCLUSIONS Patients with one negative sextant biopsy still have a high likelihood of cancer , especially men with persistently elevated PSA and small prostates ( < 20 cc ) while the majority of men with large prostates ( > 70 cc ) have PSA elevation due to benign prostate hyperplasia ( BPH ) and not to cancer PURPOSE The European R and omized Study of Screening for Prostate Cancer investigates the impact of screening on prostate cancer mortality and contributes to a better underst and ing of available screening tests . The present study evaluates the predictive value of a prostate specific antigen ( PSA ) increase to PSA 3.0 ng/ml or greater in a 4-year period in men who present with low PSA values ( less than 3.0 ng/ml ) at first screen . MATERIAL S AND METHODS A total of 42,376 men were r and omized to screening vs control in Rotterdam . Of 6,467 men 5,771 had PSA values of less than 3.0 ng/ml , did not undergo biopsy at baseline and were rescreened after 4 years with PSA 3.0 ng/ml or greater as biopsy indication . PSA progression in a 4-year interscreening interval is evaluated by determining the positive predictive values , detection rates and parameters of aggressiveness of round 2 cancers . RESULTS PSA progression to more than 3.0 ng/ml occurred in 0.9 % , 9.3 % and 48.6 % of men who presented with PSA values less than 1.0 , 1 to 1.9 and 2 to 2.9 ng/ml , respectively , in round 1 . Their respective positive predictive values amounted to 19.0 % , 23.8 % and 27.9 % . Cancer detection rates increased with increasing PSA values in round 1 . The distribution of low , moderate and high risk cancers depends on round 2 but not on round 1 PSA ranges . CONCLUSIONS PSA progression to the ( arbitrary ) cutoff value of 3.0 ng/ml and the diagnosis of prostate cancer in round 2 screening with a 4-year interval depends strongly on PSA values at the time of the 1st screen . These observations will be helpful to design future screening procedures . With levels less than 2.0 ng/ml PSA progression to levels of 3.0 ng/ml or greater is rare as it was seen only in 4.8 % of all men OBJECTIVES The evaluation of the screening procedures for prostate cancer ( PCa ) was a part of the protocol of the European R and omized Study of Screening for Prostate Cancer ( ERSPC ) , section Rotterdam , The Netherl and s. We sought to establish an improved strategy for the early detection of PCa using a prostate-specific antigen ( PSA ) cutoff of 3.0 ng/mL or greater as the only indication for prostate biopsy with omission of the digital rectal examination ( DRE ) . METHODS In June 1996 , 8612 men , 55 to 74 years old , were r and omized to screening and were screened within the ERSPC Rotterdam by a PSA level of 4.0 ng/mL or greater or positive DRE or transrectal ultrasound findings as the indication for biopsy . Four hundred thirty men had PCa . Those treated by radical prostatectomy provided the tumor characteristics considered essential for a change in the screening strategies . Various options were evaluated and predictions made by logistic regression analyses . The protocol change was implemented in February 1997 . Another 7943 men were screened according to the new protocol ( PSA 3.0 ng/mL or greater ) . The result ing data were used to compare the two protocol s. RESULTS The detection rate ( proportion of PCa in those screened ) turned out to be very similar , with rates of 5.0 and 4.7 at a PSA cutoff of 4.0 ng/mL or greater and 3.0 ng/mL or greater , respectively . This was due to a much larger number of cases of PCa per biopsy in the PSA range of 3 to 3.9 ng/mL than expected . The positive predictive value of the PSA range 3.0 to 3.9 ng/mL in the two protocol s was 18.0 % and 6.4 % , respectively . Tumor characteristics were studied on radical prostatectomy specimens from the original protocol . PCa detected with the new screening regimen had a similar distribution of Gleason scores but a larger proportion of confined disease . Tumor volumes were smaller in patients with PSA levels of less than 2.9 ng/mL ; the proportion of " minimal disease " in that group was 50 % compared with 28 % in the group with a PSA level between 3.0 and 3.9 ng/mL. CONCLUSIONS Lowering the biopsy indication to a PSA cutoff of 3.0 ng/mL or greater without a DRE improved the positive predictive value from 18.2 % to 24.3 % . The number of biopsies necessary to detect 1 case of PCa accordingly changed from 5.2 to 3.4 . The overall characteristics of the cases detected at that PSA cutoff differed very little from those detected with the regimen based on PSA , DRE , and transrectal ultrasound OBJECTIVES To compare the discriminatory potential between prostate cancer and benign conditions of the prostate in a population -based screening study , of serum prostate-specific antigen levels ( PSA ) and PSA corrected for both the total prostate volume ( PSA-D ) and the transition zone volume ( PSA-T ) . METHODS In a r and omized population -based screening study ( Rotterdam section of the European R and omized Study of Screening for Prostate Cancer ) , in which 10,865 men have been screened , the biopsy results of 1202 men with PSA levels of 4 ng/mL or more were evaluated . Planimetric and prolate ellipsoid volumes of the total prostate as well as of the transition zone were measured . The measured volumes were compared with the volumes of 57 radical prostatectomy specimens through Spearman 's rank correlation coefficient and agreement tests . A receiver operating characteristic ( ROC ) curve analysis was done of sensitivity and specificity of biopsy indications through PSA and PSA corrected for the volumes measured with transrectal ultrasound . RESULTS In the 1202 men studied , 361 cases of prostate cancer were diagnosed . Both PSA-D and PSA-T showed a significantly higher area under the ROC curve ( 0.77 and 0.79 , respectively ) than PSA alone ( area 0.65 ) . There was no significant difference between PSA-D and PSA-T. The use of a PSA-D threshold value of 0 . 10 ng/mL/cc would have avoided 28 % of biopsies at the cost of 10 % of detectable cancers . A PSA-D threshold of 0.15 ng/mL/cc would have avoided 73.8 % of biopsies at the cost of not diagnosing 43.8 % of detectable cancers . CONCLUSIONS The planimetrically obtained prostate volume showed a more favorable agreement with the radical prostatectomy volume than the prolate ellipsoid volume . The discriminatory potential of the corrected PSA value is better at predicting the results of needle biopsy of the prostate when compared with PSA alone . The use of the transition zone volume for this correction results in a higher discriminatory potential when compared to the use of the total prostate volume ; however , the observed difference was not statistically significant OBJECTIVE To report the results from an Iranian large population -based r and omized study of screening using prostate-specific antigen ( PSA ) to detect prostate cancer . MATERIAL S AND METHODS A total of 3758 Iranian men older than 40 years were mass checked by PSA-based screening . Men with an abnormal digital rectal examination ( DRE ) and serum total PSA level of greater than 4 ng/mL , underwent transrectal ultrasonography (TRUS)-guided extended prostate biopsy . RESULTS The PSA value ( mean + /- st and ard deviation , SD ) in all men without prostate cancer was 1.6 + /- 1.1 ng/mL and in those with cancer 18 + /- 44.8 ng/mL ( P = 0.001 ) . PSA values increased with age . In those aged 40 - 49 , 50 - 59 , 60 - 69 and > or = 70 years , the mean + /- SD PSA values were 1.3 + /- 0.7 , 1.4 + /- 0.8 , 1.8 + /- 1 and 2.2 + /- 1.6 ng/mL , respectively . Among the screened men , 323 ( 8.6 % ) had a serum PSA concentration greater than 4 ng/mL. Of patients who underwent prostate biopsy ( 230 , 71.2 % ) , 129 ( positive predictive value , 56.1 % ) had prostate cancer . Additionally , nine cancers were detected among 16 patients with PSA of less than 4 ng/mL who had a doubtful DRE finding . The overall cancer detection rate was 3.6 % ; 1.4 % at 40 - 49 , 1.6 % at 50 - 59 , 4.2 % at 60 - 69 and 12.9 % at > /=70 years . Conventional systematic sextant biopsies , which accounted for six of the 10 cores in our biopsy scheme , detected 98 ( 71 % ) of the cancers . CONCLUSIONS The Iranian male population develops prostate cancer quite commonly if their serum PSA levels are greater than 4.0 ng/mL. In this study , 65.9 % of the detected cancers were clinical ly significant . The conventional systematic sextant technique may be inappropriate for detection of all prostate cancers . The results need to be confirmed in other r and omized trials OBJECTIVES To determine the percentage of localized and potentially curable prostate cancers diagnosed at follow-up screening visits compared with the first screening visit . METHODS Within the context of a prospect i ve screening study performed in r and omly chosen men aged between 45 and 80 years , up to 6-year follow-up screening visits have been performed with serum prostate-specific antigen ( PSA ) measurement and digital rectal examination ( DRE ) followed by transrectal ultrasonography of the prostate when PSA or DRE is abnormal . RESULTS Of the 117 prostate cancers diagnosed at 14,554 annual follow-up visits , only 1 cancer ( 0.9 % ) was metastatic compared with 8 % ( 26/322 ) at 8029 first visits . Moreover , 97 % of the cancers detected at follow-up visits could be identified by PSA alone compared with 86 % at first visit . The incidence of 0.8 % per year during 15 years of screening between the ages of 55 and 70 years would diagnose localized prostate cancer in 12 % of the population , a value not too different from the 10 % diagnosed with prostate cancer during life-time in the absence of screening . CONCLUSIONS The present data show that annual screening with PSA diagnoses clinical ly localized prostate cancer in more than 95 % of cases , thus almost completely eliminating the diagnosis of metastatic prostate cancer . Moreover , the number of prostate cancers diagnosed is not significantly increased by screening OBJECTIVES The stage and grade shift of currently diagnosed prostate cancer has led to a diminished prognostic power of the Gleason score system . We investigated the predictive value of the amount of high- grade cancer ( Gleason growth patterns 4/5 ) in the biopsy for prostate-specific antigen ( PSA ) and clinical relapse after radical prostatectomy . METHODS PSA-tested participants ( N=281 ) of the European R and omized Study of Screening for Prostate Cancer ( ERSPC ) who underwent radical prostatectomy were analyzed . Besides clinical features , and serum-PSA , histopathologic features as determined in the diagnostic biopsy and matching radical prostatectomy specimen were related to patient outcome . RESULTS At a median follow-up of 7 yr , 39 ( 13.9 % ) , 24 ( 8.5 % ) , and 12 ( 4.3 % ) patients had PSA > /=0.1 ng/ml , PSA > /=1.0 ng/ml , and clinical relapse after radical prostatectomy , respectively . Using Cox proportional hazards , PSA level ( p=0.002 ) , length of tumour ( p=0.040 ) , and length of high- grade cancer ( p=0.006 ) in the biopsy , but not Gleason score , were independent prognostic factors for biochemical relapse ( PSA > /=0.1 ng/ml ) when assessed as continuous variables . In radical prostatectomies , the proportion of high- grade cancer ( p<0.001 ) was most predictive of relapse ( PSA > /=0.1 ng/ml ) . For PSA > /=1.0 ng/ml and clinical relapse , the amount of high- grade cancer , both in the biopsy specimen ( p=0.016 and p=0.004 , respectively ) and radical prostatectomy specimen ( p=0.002 and p=0.005 , respectively ) , but not Gleason score , was an independent predictor . CONCLUSIONS In biopsy and radical prostatectomy specimens of surgically treated prostate cancer , the amount of high- grade cancer is superior to the Gleason grading system in predicting patient outcome . We propose that , in addition to the Gleason score , the amount of Gleason growth patterns 4/5 in the biopsy ( whether absolute length or proportion ) should be mentioned in the pathology report Sex steroid hormones influence prostate development and maintenance through their roles in prostate cellular proliferation , differentiation and apoptosis . Although suspected to be involved in prostate carcinogenesis , an association between circulating and rogens and prostate cancer has not been clearly established in epidemiologic studies . We conducted a nested case‐control study with prospect ively collected sample s in the Prostate , Lung , Colorectal and Ovarian ( PLCO ) Cancer Screening Trial , to examine associations of prostate cancer with and rostenedione ( Δ4‐A ) , testosterone ( T ) , sex hormone‐binding globulin ( SHBG ) and 3α‐ and rostanediol glucuronide ( 3α‐diolG ) . A total of 727 incident Caucasian prostate cancer cases ( age ≥ 65 years , N = 396 ) and 889 matched controls were selected for this analysis . Overall , prostate cancer risks were unrelated to serum T , estimated free and bioavailable T , and SHBG ; however , risks increased with increasing T : SHBG ratio ( ptrend = 0.01 ) , mostly related to risk in older men ( ≥65 years , ptrend = 0.001 ) , particularly for aggressive disease [ highest versus lowest quartile : odds ratio ( OR ) 2.76 , 95 % confidence interval ( CI ) 1.50–5.09 ] . No clear patterns were noted for Δ4‐A and 3α‐diolG. In summary , our large prospect i ve study did not show convincing evidence of a relationship between serum sex hormones and prostate cancer . T : SHBG ratio was related to risk in this older population of men , but the significance of this ratio in steroidal biology is unclear . © 2008 Wiley‐Liss , BACKGROUND Although serum PSA testing is widely used as a screening test for prostate cancer ( PC ) , it is known that it is not specific for PC . The study described here focuses on the value of screening tests next to PSA in identifying men with an elevated risk of having PC and the differences between three centers of the European R and omised study of Screening for Prostate Cancer ( ERSPC ) . METHODS The study population consists of 2,483 men with a PSA > or = 4.0 ng/ml , all biopsied . We assessed data on age , serum PSA level at initial and repeat screening , prostate volume , number of positive DRE and TRUS findings , number of previous negative biopsies , and PPV of the three centers and overall . Using logistic regression analysis , predictors for biopsy outcome at repeat screening in men with a PSA value > or = 4.0 ng/ml were determined on the complete data set and per center . RESULTS In 2,483 men biopsied , 665 cancers were detected ( PPV = 26.8 % ) . Data show that all predictors except prostate volume loose their predictive value in men previously biopsied . In men not previously biopsied , the predictive value of DRE and TRUS vary considerably among the three centers . CONCLUSIONS Looking at the differences in the predictive value of screening tests in three " comparable " centers , generasibility is not as straightforward as it seems . Using a nomogram for predictive purpose s developed elsewhere will require a thorough knowledge of the patient population of which it is derived , and one should interpret its results with a critical mind OBJECTIVE to estimate the st and ard performance measures of prostate-specific antigen ( PSA ) screening as implemented in the existing health care system and to compare the observed results with those fom the European R and omized Screening for Prostate Cancer ( ERSPC ) trial . DESIGN in a consecutive series of men living in two Italian health districts , aged > or = 30 years , with at least one total PSA test between 2000 and 2003 , those subjects putatively tested for screening purpose s were identified using record linkage with multiple local health data bases . This was also used to determine the outcomes of follow-up of subjects with positive test result ( PSA > or = 4 ng/ml ) at 12 and 24 months of observation . SETTING clinical chemistry laboratories , outpatient urology clinics , pathology departments , and mortality registries of the health districts of Ravenna and Forlì , and the Romagna Cancer Registry . PARTICIPANTS 52,513 total subjects , 42,398 of whom putatively tested for screening purpose s. MAIN OUTCOME MEASURES the most common performance measures of cancer screening . RESULTS the 2-year screening rate increased until 80 years of age . In the age range 55 - 69 years , i.e. the target age of the ERSPC trial , the screening rate was 38.1 % , and the rate of positive test results ( 9.1 % ) was within the expected range . The PSA level , but not the subjects age , was strongly associated with follow-up procedures . After 24 months of observation , 24.4 % PSA-positive patients received no further evaluation , 54.8 % underwent repeat testing as the initial follow-up action , and 44.0 % were referred for urologic assessment . The biopsy rate was 25.3 % , the positive predictive value of PSA testing 10.1 % , the detection rate of prostate cancer 9.4 per thous and , and the detected/expected ratio 8.4 . CONCLUSION compared with methods and results of the ERSPC trial , the management of PSA-positive subjects was much more conservative , and the yield of disease much smaller Prostate cancer is the second leading cause of cancer deaths among U.S. men . Early detection is associated with drastically improved 5-year survival rates . It is unclear , however , what psychosocial factors motivate or discourage men from taking advantage of both prostate-specific antigen ( PSA ) testing and digital rectal examination ( DRE ) . The goal of the current study was to identify psychosocial factors that influence screening behavior for prostate cancer in a cohort of 2,447 men . In 1990 , a r and omly selected cohort of Caucasian men , ages 40 to 79 years , from Olmsted County , Minnesota , were enrolled in the study . These men completed a question naire containing queries on family history of prostate cancer , concern about getting prostate cancer , and marital status . Medical and laboratory records were review ed to determine the number DREs ( 1989 - 1996 ) and PSA tests ( 1989 - 1998 ) . Frequent screening was defined as the upper 25th percentile for number of DREs ( > 4 ) or PSAs ( > 3 ) . Men who have a family history and men who worry or have concern about prostate cancer were more likely [ odds ratio ( OR ) , 1.5 ; 95 % confidence interval ( 95 % CI ) , 1.2 - 2.0 and OR , 1.9 ; 95 % CI , 1.4 - 2.5 ] to seek screening compared with those without a family history or worry . The association between family history and frequent screening was similar in men who were married or living with someone ( OR , 1.7 ; 95 % CI , 1.2 - 2.2 ) ; however , it was reduced among men who live alone ( OR , 0.6 ; 95 % CI , 0.2 - 1.8 ) . These data suggest that psychosocial factors such as family history , worry , or concern about prostate cancer and marital status may play an important role in men 's decisions about prostate cancer screening . ( Cancer Epidemiol Biomarkers Prev 2008;17(12):3588–92 Of 9,026 males , aged 50 - 69 years , 1,494 were r and omly selected and invited to participate in a screening programme for carcinoma of the prostate . Of these 1,163 ( 78 % ) accepted . Rectal examination was performed independently by a general practitioner ( GP ) and by a urologist at the GP 's surgery . Carcinoma of the prostate was suspected by one or both physicians in 45 cases , and subsequently confirmed by cytological investigation in 13 cases . Ten patients underwent radical prostatectomy , one received radiation treatment , one case was too advanced for curative treatment , and one was scheduled for subsequent re assessment . Screening , as a means of early diagnosis of carcinoma of the prostate by either a urologist or a GP , using digital rectal examination , thus appears to be a cost-effective procedure , though the question still remains whether this will lead to prolongation of survival or not We report the results of two pilot studies for the early detection of prostatic carcinoma in resident men aged 60 - 75 years , using combined digital rectal examination ( DRE ) and transrectal ultrasonography ( TRUS ) versus prostate-specific antigen ( PSA ; cutoff : 4 ng/ml ) as screening tests . Both screening protocol s exhibited high cancer detection rates ( DRE + TRUS = 1.82 % , PSA = 1.67 % ) , with a high prevalence/incidence ratio ( observed/expected ratio : DRE-TRUS = 13.8:1 , PSA = 11.3:1 ) and a diagnostic anticipation of about 6 - 7 years . Stage ( DRE + TRUS : A = 0 % , B = 69 % , C-D = 31 % ; PSA : A = 14 % , B = 77 % , C-D = 9 % ) and grading distribution ( no case with Gleason score < 5 ) suggests that most screen-detected cancers were clinical ly assessable but the extent of overdiagnosis of latent carcinomas can not be estimated . Both screening protocol s proved to be cost-effective ( biopsy rate : DRE + TRUS = 2.7 % , PSA = 2.8 % ; cost per screened subject : DRE + TRUS = L. 33,750 , PSA = L. 30,400 ; cost per cancer detected : DRE + TRUS = L. 1,854,000 , PSA = L. 1,817,500 ) but screening by PSA was much better accepted ( attendance rate : DRE + TRUS = 33.7 % , PSA = 66.9 % ) , which makes it the screening test of choice for controlled studies on screening efficacy . This study allows no definitive conclusions to be drawn on screening efficacy but confirms only that screening is feasible at a reasonable cost and yields high diagnostic anticipation . Whether this benefits the screened population is currently debated and needs to be confirmed by controlled studies . Screening may have up setting negative outcomes such as overdiagnosis , overtreatment , increased treatment-related mortality rates and worsened quality of life , and there is no evidence supporting the recommendation of screening as a routine practice Background / aim The effects of printed educational material on cancer screening in women ( Pap test and mammography ) are well documented and confirmed by several studies . The aim of our study was to evaluate the impact of similar printed educational material on prostate cancer screening by PSA and DRE . Material and methods Thous and five hundred men aged between 50 and 86 years of age , who attended our institutions for various medical conditions except prostate-related conditions , were r and omly assigned to two study groups . Men in the informed group , received an educational leaflet with simple , general information on prostate cancer screening methods given by their physician along with treatment and other regular recommendations , while men in the non-informed group , were only informed by their physician in the examination room during an interview . Results After 24 months , there was no statistically significant difference between the two groups in terms of DRE screening . The percentages of men who were actually screened by DRE were 4 and 5 % in the informed and non-informed groups , respectively , while the difference in the percentages of PSA screening was of statistical significance , with 31 % of men screened in the non-informed group as compared to 93 % of men screened in the informational leaflet group . Conclusions A single , one-shift distribution of printed educational material on prostate cancer screening , changed their attitude regarding prostate cancer screening only in favour of PSA testing , while did not manage to change the DRE acceptance behavior . However , since the combination of the two tests is more sensitive for diagnosis than either one alone , there is a need of introducing intervention strategies , in the efforts of ameliorating the prostate cancer screening behavior BACKGROUND Use of 5 mg/day finasteride ( Proscar ) for benign prostatic hyperplasia is known to affect serum concentrations of prostate-specific antigen ( PSA ) . When men taking this treatment undergo screening for prostate cancer , a compensatory adjustment of the PSA concentration ( to multiply the value by two ) is recommended . Whether this recommendation should apply to men taking 1 mg/day finasteride ( Propecia ) for the treatment of and rogenic alopecia is unknown . We aim ed to assess the effect of 1 mg/day finasteride on serum PSA in men aged 40 - 60 years with male-pattern hair loss . METHODS Between March 13 , 1998 , and Jan 12 , 2000 , 355 men aged 40 - 60 years with male-pattern hair loss were stratified by age decade ( 40 - 49 years and 50 - 60 years ) , and r and omised in a ratio of four to one to 1 mg/day finasteride or placebo . The primary endpoint was the effect of this treatment for 48 weeks on serum PSA concentration compared with placebo . This trial is in the process of being registered on the US National Institutes of Health website . Analyses were according to protocol . FINDINGS Within 48 weeks of r and omisation , men aged 40 - 49 years and 50 - 60 years who were assigned 1 mg/day finasteride had a median decrease in serum PSA concentration of 40 % ( 95 % CI 34 - 46 ) and 50 % ( 44 - 57 ) , respectively . In men assigned placebo , the median changes were 0 % [ -14 to 14 ] and a median increase of 13 % [ 2 to 24 ] , respectively . INTERPRETATION In men aged 40 - 60 years , 1 mg/day finasteride for 48 weeks lowers serum PSA concentration . Therefore , the existing recommendation for the adjustment of serum PSA concentration in prostate-cancer screening in men taking 5 mg/day finasteride should also apply to men taking the 1 mg/day preparation for male-pattern hair loss . Research is needed to assess the effect of 1 mg/day finasteride preparation beyond 48 weeks of treatment PURPOSE We evaluated the significance of focal prostate cancer found in sextant biopsies in men participating in a biennial prostate specific antigen ( PSA ) based screening program . MATERIAL S AND METHODS In 1995 , 10000 men 50 to 65 years old were r and omized to biennial screening with PSA testing . Sextant biopsies were recommended when total PSA was 3 ng/ml or greater at screening rounds 1 and 2 , and 2.54 ng/ml or greater at subsequent screening rounds . Focal cancer was defined as total a core cancer length of less than 3 mm in the biopsy specimen . Low volume cancer was defined as a total tumor volume of less than 0.5 cm in the radical retropubic prostatectomy specimen . RESULTS The number of men who underwent biopsy and the number of cancers detected in the 5 possible sets of biopsies were 1725 and 402 , 706 and 124 , 307 and 36 , 103 and 9 , and 13 and 0 , respectively . The risk of detecting focal cancer was 7.9 % , 10.2 % , 7.5 % , 5.8 % and 0 % , respectively , but the relative ratio ( focal-to-all cancers ) increased 34 % , 58 % , 64 % , 67 % and , not applicable , respectively . In men with a total core cancer length of less than 10 mm there was no correlation between core cancer length and total tumor volume , as measured in the prostatectomy specimen . Two-thirds of men with a total core cancer length of less than 3 mm had a tumor volume of greater than 0.5 cm , while the risk of low volume cancer was less than 5 % only in men with a total core cancer length of greater than 10 mm . CONCLUSIONS In a repeat PSA based screening program sextant biopsies are of little or no value for predicting tumor volume BACKGROUND Most medical associations recommend that patients make informed decisions about whether to be screened for prostate cancer with the prostate-specific antigen ( PSA ) test . Studies assessing how to promote PSA informed decision-making ( IDM ) have been conducted almost exclusively in healthcare setting s ; there is a need for similar research in community setting s. METHODS This paper describes the results of a 5-year study ( 2002 - -2007 ) in which two community-level interventions were developed , implemented , and evaluated in matched upper- and lower-SES comparison communities in Greensboro and Wilmington , North Carolina . Both interventions promoted PSA informed decision-making . One intervention ( PSA-Only ) consisted of educational information about prostate cancer and the PSA test , and the other ( Men 's Health ) included additional information about recognizing and preventing heart attack , stroke , and colon cancer . Structured survey , semistructured interview , and structured observational data were combined to compare participating community residents ' pre/post changes in knowledge , intentions , and behaviors related to PSA IDM . RESULTS The community-level interventions successfully engaged community participants in discussion s , educated individuals , encouraged deliberation of information , and facilitated PSA test discussion s with physicians . Men who participated in the PSA-Only educational sessions were more likely than those who attended the Men 's Health educational sessions to discuss the PSA test with their physician ( p=0.037 ) . CONCLUSIONS When prospect i ve SES-related confounding factors are matched across comparison communities , PSA IDM interventions can be shown to promote IDM . Framing the PSA test decision relative to less-ambiguous screening decisions does not appear to increase the likelihood of PSA IDM We investigated the value of digital rectal examination , transrectal ultrasonography and prostatic specific antigen ( PSA ) analysis as aids in general clinical practice and in the early detection of prostate cancer . Of a r and omly selected population of 2,400 men 55 to 70 years old who were offered examination with digital rectal examination , transrectal ultrasound and PSA analysis , 1,782 ( 74 % ) accepted and prostate cancer was detected in 65 ( 3.6 % ) . When the transrectal ultrasound results were also considered the detection rate of digital rectal examination ( 2.3 % ) was increased by 50 % and the number of stage T2A or less tumors was doubled . At reexamination due to markedly high PSA values ( 7 micrograms/l . or more ) only a few additional cancers ( 5 % ) were detected . However , it is noteworthy that 80 % of the detected cancers were found among the subgroup with abnormal PSA values ( 4 micrograms/l . or more ) and comprising 17 % of the study population , which suggests the possibility of selecting a risk group at mass screening . Moreover , the positive predictive value increased from 4 % ( when only digital rectal examination was positive ) to 71 % for the combination of positive digital rectal examination , positive transrectal ultrasound and an increased PSA concentration ( that is 7 micrograms/l . or greater ) Objective To assess the magnitude of prostate cancer detection by serendipity ( the coincidental detection of prostate cancer during the evaluation of an abnormal screening test result ) when a digital rectal examination ( DRE ) and transrectal ultrasonography ( TRUS ) are used as initial screening tests for prostate cancer in men with low levels of prostate‐specific antigen ( PSA ; 0.0–3.9 ng/mL ) At the Rotterdam branch of the European R and omized Study of Screening for Prostate Cancer , a cohort of 19,970 men ages 55–75 years is screened at an interval of 4 years . Screening includes systematic sextant needle biopsy for men with elevated prostate‐specific antigen ( PSA ) levels and /or positive findings on digital rectal examination or transrectal ultrasound . Detection during the second screening round of a large number of high‐ grade ( Gleason Grade 4 or 5 ) malignancies and /or a large number of malignancies in general could be considered the result of a failure to identify these malignancies at an early stage , during prevalence screening From 1992 - 2001 , 7 countries in Europe gradually recruited men for the European R and omised Screening for Prostate Cancer ( ERSPC ) trial . Centres recruit different age groups and have different design s for recruiting and countries have different underlying risks for prostate cancer . Recruitment has reached 163,126 men aged 55 - 69 at entry now . Our purpose was to calculate the power of the trial and at what point in time can statistically significant differences in prostate cancer mortality be expected . Recruitment data were collected from the screening centres . We calculated the expected number of prostate cancer deaths in each follow-up year , based on national statistics and expected rate in trial entrants . The power was calculated using different assumptions on intervention effect and contamination rate and also if the ERSPC trial would cooperate with other trials . With an assumed 25 % intervention effect in men actually screened and a 20 % contamination rate , the trial will reach a power of 0.86 in 2008 . With an assumed intervention effect of 40 % , the power reaches 0.90 in 2003 - 2004 . Pooling data with those of the Prostate , Lung , Colorectal and Ovary ( PLCO ) trial early is expected to improve the power to 79 % ( 20 % intervention effect ) to 92 % ( 40 % intervention effect PLCO ) . Adding more centres with compliance rates lower than 45 % decreases the power of the trial . The ERSPC trial has sufficient power to detect a significant difference in prostate cancer mortality between the 2 arms if the true reduction in mortality by screening is 25 % or more or if contamination remains limited to 10 % if the true effect is 20 % or more . If early detection and treatment turns out to have a stronger effect as may be suggested by observational data , the ERSPC trial is likely to conclusively show that within the next 5 years Two large‐scale r and omized screening trials , the Prostate , Lung , Colorectal and Ovary ( PLCO ) cancer trial in the USA and the European R and omized Screening for Prostate Cancer ( ERSPC ) trial in Europe are currently under way , aim ed at assessing whether screening reduces prostate cancer mortality . Up to the end of 1998 , 102,691 men have been r and omized to the intervention arm and 115,322 to the control arm ( which represents 83 % of the target sample size ) from 7 European countries and 10 screening centers in the USA . The principal screening method at all centers is determination of serum prostate‐specific antigen ( PSA ) . The PLCO trial and some European centers use also digital rectal examination ( DRE ) as an ancillary screening test . In the core age group ( 55–69 years ) , 3,362 of 32,486 men screened ( 10 % ) had a serum PSA concentration of 4 ng/ml or greater , which is 1 cut‐off for biopsy ( performed in 84 % ) . An additional 6 % was referred for further assessment based on other criteria , with much less efficiency . Differences in PSA by country are largely attributable to the age structure of the study population . The mean age‐specific PSA levels are lower in the PLCO trial ( 1.64 ng/ml [ in the age group 55–59 years ] , 1.80 [ 60–64 years ] and 2.18 [ 65–69 years ) than in the ERSPC trial ( 1.28–1.71 [ 55–59 ] , 1.75–2.87 [ 60–64 ] and 2.48–3.06 [ 65–69 years ] ) . Detection rates at the first screen in the ERSPC trial range from 11 to 42/1,000 men screened and reflect underlying differences in incidence rates and screening procedures . In centers with consent to r and omization design , adherence in the screening arm is 91 % , but less than half of the men in the target population are enrolled in the trial . In population ‐based centers in which men were r and omized prior to consent , all eligible subjects are enrolled , but only about two‐thirds of the men in the intervention arm undergo screening . Considerable progress has been made in both trials . Enrollment will be completed in 2001 . A substantial number of early prostate cancers have been detected . The differences between countries seem to reflect both underlying prostate cancer incidence and screening policy . The trials have the power to show definitive results in 2005–2008 . © 2002 Wiley‐Liss , Background / Aims : The diagnostic validity of prostate-specific antigen ( PSA ) among men receiving hemodialysis ( HD ) has not been well defined . The aim of this study was to evaluate PSA levels in HD men and to compare them with those of non-uremic controls . Methods : PSA levels were measured in 620 HD men ( 40–89 years old , mean age 62.4 years ) . In patients with PSA > 4.1 ng/ml , prostate biopsies were performed . Cancer-free men were defined as having PSA ranging between 0 and 4.0 ng/ml , or PSA > 4.1 ng/ml but with a pathologically negative biopsy . The result ing data was compared with that for 3,636 non-uremic controls ( 55–59- ( n = 468 ) , 60–69- ( n = 2,220 ) , and 70–79-year-old men ( n = 948 ) ) . Results : Of 45 HD men with PSA > 4.1 ng/ml , 22 consented to undergo a biopsy . Ten were positive and 12 were negative . The mean PSA of cancer-free HD men of 50–59 ( n = 159 ) , 60–69 ( n = 214 ) , 70–79 ( n = 116 ) , and 80–89 ( n = 30 ) were 1.0 , 1.0 , 1.3 , and 2.1 ng/ml , respectively . Cancer-free HD men demonstrated significantly lower PSA compared to controls . Conclusions : HD men had lower PSA levels than those of controls Prostate cancer screening with DRE , TRUS , and PSA testing was offered to 2,400 r and omly selected men 55 - 70 years old . Among 1,782 examined , 65 ( 3.6 % ) men with prostate cancer were diagnosed . The PSA results were correlated to the diagnosis , the men 's age , and the prostate volume . Least square regression analysis was used to calculate the 95 % upper confidence intervals for PSA in each year of age in men without prostate cancer . The PPV was calculated for : ( i ) PSA > 4 ng/ml , ( ii ) PSAD > 0.15 , ( iii ) PSAD > 0.20 and ( iv ) age-adjusted PSA reference values . A significant correlation was found between PSA and prostate volume , between PSA and age , and between the prostate volume and age . The calculated annual growth of the prostate was 1.6 % and the annual increase in PSA was 2.4 % . The age-adjusted upper PSA reference values for the three age categories studied ( 55 - 59 , 60 - 64 and 65 - 70 years ) were 5.2 , 5.8 , and 6.7 ng/ml , respectively . The PPVs for PSA > 4 ng/ml , PSAD > 0.15 , PSAD > 0.20 , and the age-adjusted PSA reference values were 17 % , 14 % , 22 % , and 27 % , respectively . Age-adjusted PSA or PSAD may increase the PPV compared to PSA > 4 ng/ml . The detection rate is , however , inadequate . A PSA cut-off at 4 ng/ml could therefore be maintained in men 55 - 70 years old . The median PSA values and median prostate volumes calculated for men with benign findings may serve as a reference in future studies There is a paucity of research on the effects of pretest measurement with prostate cancer screening . What effect does a pretest measurement have on posttest outcomes ? This research reports knowledge of prostate cancer screening among men r and omized to an Enhanced decision aid versus an Usual Care decision aid . Using a Solomon Four research design , there were a total of 198 men in 4 groups . Most of the sample was African American ( 78 % ) , with a mean age of 52 years . The greatest posttest knowledge occurred with the Enhanced decision aid in contrast to the Usual Care . The Enhanced/Usual Care groups that had both a pretest and posttest and had received a previous digital rectal examination had the highest means ( P = .015 ) , with means of 9.1 and 7.0 , respectively . Among men who had a previous digital rectal examination , the greatest increase in score occurred among men r and omized to the Enhanced decision aid in contrast to the Usual Care decision aid , 2.9 versus 0.4 ( P = .008 ) . The outcome varied based on the status of ( 1 ) r and om group assignment of the Solomon Four design and ( 2 ) status of previous digital rectal examination . Implication s for nurses include consideration 1 of a pretest to increase posttest knowledge scores BACKGROUND The benefit of radical prostatectomy in patients with early prostate cancer has been assessed in only one r and omized trial . In 2005 , we reported that radical prostatectomy improved prostate cancer survival compared with watchful waiting after a median of 8.2 years of follow-up . We now report results after 3 more years of follow-up . METHODS From October 1 , 1989 , through February 28 , 1999 , 695 men with clinical ly localized prostate cancer were r and omly assigned to radical prostatectomy ( n = 347 ) or watchful waiting ( n = 348 ) . Follow-up was complete through December 31 , 2006 , with histopathologic review and blinded evaluation of causes of death . Relative risks ( RRs ) were estimated using the Cox proportional hazards model . Statistical tests were two-sided . RESULTS During a median of 10.8 years of follow-up ( range = 3 weeks to 17.2 years ) , 137 men in the surgery group and 156 in the watchful waiting group died ( P = .09 ) . For 47 of the 347 men ( 13.5 % ) who were r and omly assigned to surgery and 68 of the 348 men ( 19.5 % ) who were not , death was due to prostate cancer . The difference in cumulative incidence of death due to prostate cancer remained stable after about 10 years of follow-up . At 12 years , 12.5 % of the surgery group and 17.9 % of the watchful waiting group had died of prostate cancer ( difference = 5.4 % , 95 % confidence interval [ CI ] = 0.2 to 11.1 % ) , for a relative risk of 0.65 ( 95 % CI = 0.45 to 0.94 ; P = .03 ) . The difference in cumulative incidence of distant metastases did not increase beyond 10 years of follow-up . At 12 years , 19.3 % of men in the surgery group and 26 % of men in the watchful waiting group had been diagnosed with distant metastases ( difference = 6.7 % , 95 % CI = 0.2 to 13.2 % ) , for a relative risk of 0.65 ( 95 % CI = 0.47 to 0.88 ; P = .006 ) . Among men who underwent radical prostatectomy , those with extracapsular tumor growth had 14 times the risk of prostate cancer death as those without it ( RR = 14.2 , 95 % CI = 3.3 to 61.8 ; P < .001 ) . CONCLUSION Radical prostatectomy reduces prostate cancer mortality and risk of metastases with little or no further increase in benefit 10 or more years after surgery BACKGROUND The value of rectal examination as initial screening test for prostate cancer at low PSA values ( 0.0 - 3.9 ng/ml ) was determined by evaluating the number and tumor characteristics of the cancers detected . METHODS Two study population s were subjected to screening with ( n = 10,226 ) and without ( n = 10,753 ) rectal examination as initial screening test . The number of cancers detected at low PSA values for both screening regimens , the corresponding biopsy and radical prostatectomy tumor characteristics were assessed . Possibly harmless cancers were defined as small ( < 0.5 ml ) organ-confined tumors without Gleason growth-patterns 4/5 . RESULTS At low PSA , 26.6 % ( 117/440 ) of screen-detected cancers were detected after the evaluation of a suspicious rectal examination . The number of cancers and tumor aggressiveness features were highly associated with serum-PSA level . The proportion of possibly harmless disease steadily declined from 100 % ( PSA 0.0 - 0.9 ng/ml ) to 15.4 % ( PSA 3.0 - 3.9 ng/ml ) . Rectal examinations were performed unnecessarily in 94.7 - 100 % of cases , when detection of clinical ly significant disease was aim ed at . Using PSA ( and a cut-off of 3.0 ng/ml ) as the only screening tool , 24.3 % ( 121/498 ) of screen-detected cancers were in the PSA range 3.0 - 3.9 ng/ml , and 60.0 % were assessed as clinical ly significant . CONCLUSIONS Rectal examination as initial screening test for prostate cancer at low PSA values may be replaced by screening using serum-PSA only . At PSA levels below 3.0 ng/ml , 289 rectal examinations are required to find one case of clinical ly significant disease , and 96 rectal examinations are needed to diagnose prostate cancer of any size , grade , or stage AIM The disc assay system for prostate-specific antigen ( PSA ) is a novel technique using a small amount of whole blood on filter paper . The accuracy of this assay system and its feasibility for use in prostate cancer mass screening were evaluated . METHODS In the first arm of the study , to evaluate the accuracy of the disc assay system , PSA values were determined by both a disc assay system and a st and ard serum assay system using the same blood sample s obtained from 420 out patients . In the second arm of the study , the feasibility and reliability of the disc assay system were examined in prostate cancer mass screening . A total of 2475 men were screened by the disc assay ( disc group ) and 3348 men were screened by the st and ard serum assay ( serum group ) in the first step of mass screening . In the second step of the screening in the disc group , 101 men underwent PSA tests by a st and ard serum assay , then the first PSA values determined by the disc assay were compared with the second PSA values determined by the st and ard serum assay . In the second step of the screening in the serum group , 94 men underwent additional PSA tests by a serum assay , and then the first PSA values were compared with the second PSA values . Two men in each group were excluded from analysis because the true PSA values of the first step were not available ( more than 50 ng/mL ) . RESULTS The PSA values determined by the disc assay closely correlated with those obtained by the st and ard assay ( r = 0.987 ) in 295 out patients with PSA levels between 1.0 and 20 ng/mL. In the PSA mass screening , the PSA values determined in the first step closely correlated with those in the second step both in the disc group ( r = 0.916 ) and in the serum group ( r = 0.845 ) . A significant dissociation of the two PSA values was observed in seven of 99 men in the disc group and in three of 92 men in the serum group . However , there was no statistical significance in the incidence of dissociation in the two PSA values between the disc group and the serum group . CONCLUSIONS The disc assay system seems to be a sensitive and accurate assay system . The feasibility and reliability of the disc assay system were well demonstrated in the field during prostate cancer mass screening OBJECTIVE To evaluate the cumulative risk of having a prostate cancer diagnosis in a repeated screening situation in relation to the free-to-total prostate specific antigen ratio ( F/T-PSA ) . PATIENTS AND METHODS The present study includes 1385 men ( aged 50 - 70 years ) who underwent prostate biopsy for the first time in the screening program that started in 1995 . In case of a benign finding , the men have been followed biennially and new biopsies performed in case of persistently elevated PSA . The cumulative risk to be diagnosed with prostate cancer until July 1 , 2002 was calculated by the Kaplan-Meier method and comparison was made between different levels of T-PSA and F/T-PSA ratios . RESULTS Of 2129 biopsies 469 showed cancer . The cumulative 5-year risk to be diagnosed with prostate cancer was significantly dependent of the F/T-ratio . The risk for men with a T-PSA of 3 - 5.99 g/ml was 16 % [ 6 - 25 % ] for those who had a ratio of > 30 % and 44 % [ 34 - 60 % ] for those with a ratio of < 10 % . The corresponding difference for patients with a T-PSA of 6 - 9.99 g/ml was even more pronounced : 21 % [ 0 - 42 % ] vs. 80 % [ 64 - 96 % ] . CONCLUSION By completing the T-PSA measurement with the F/T-PSA ratio it is possible to significantly better assess the cumulative prostate cancer risk within the next five years ( without the aid of further urological work-up ) Context : Although having a usual source of care has been associated with cancer screening , whether there is additional benefit from continuity with a specific physician is uncertain . In addition , little is known about the relationship between continuity of care and receipt of colorectal and prostate cancer screening . Methods : Subjects were enrolled in a Washington State health plan that operates an integrated delivery system that emphasizes access to primary care . Among patients age 50–78 years old with 2 or more primary care visits in 2002–2003 ( N = 67,633 ) , we determined whether higher continuity ( ≥50 % of visits with the most visited primary care provider ) was associated with colorectal , breast , and prostate cancer screening . R and om-effects logistic regression estimated adjusted percentages of patients who received fecal occult blood testing , lower endoscopy ( sigmoidoscopy or colonoscopy ) , screening mammography , and prostate specific antigen ( PSA ) testing . Results : Patients with higher continuity were more likely to receive fecal occult blood testing than patients with lower continuity ( 28.9 % vs. 26.8 % ; P < 0.001 ) but less likely to receive lower endoscopy ( 12.9 % vs. 14.3 % ; P < 0.001 ) . Although higher continuity was not significantly associated with screening mammography ( P = 0.38 ) , men with higher continuity were more likely to receive PSA testing than men with lower continuity ( 39.4 % vs. 37.4 % ; P = 0.008 ) . Conclusions : In an insured population with a high degree of primary care access , continuity with a specific primary care physician was associated with the selection of less invasive colorectal cancer screening tests by patients and physicians and greater likelihood of PSA testing BACKGROUND Subdividing cancers according to the natural course of disease , both at the time of diagnosis and after radical prostatectomy , may influence management decisions of patients with prostate cancer . We investigated whether categorization of prostate cancers into different prognostic subgroups is feasible . METHODS In 218 screened participants of a r and omized study , conventional post-operative tumor features were assessed for their accuracy in predicting PSA relapse after radical prostatectomy using Cox regression analysis . Independent prognostic tumor features were combined to identify subsets of cancers with similar biological potential . A cancer was defined that may be curable after its detection by screening tests , though is destined to progress to clinical ly manifest disease and cancer-related mortality in the absence of screening . RESULTS After a median follow-up of 33.0 months , pathological stage ( P = 0.03 ) , tumor volume ( P = 0.04 ) , and margin status ( P = 0.01 ) each independently predicted PSA relapse after surgery . The proportion of poorly differentiated cancer proved highly superior to the Gleason score and most strongly predicted PSA relapse ( P < 0.0001 ) . Based on combined independent prognostic tumor features , a tumor classification model powerfully predicted PSA relapse . CONCLUSIONS Based on tumor characteristics , possibly harmless , and conversely , possibly non-curable disease , may be distinguished from cancers that are likely to show clinical progression in the absence of screening and treatment . Prediction of these subclasses prior to treatment may eventually lead to proper patient management OBJECTIVE To test the feasibility of a population -based prostate cancer screening programme in general practice and explore the outcome after a 15-year follow-up period . METHODS From the total population of men aged 50 - 69 years in Norrköping ( n = 9026 ) every sixth man ( n = 1494 ) was r and omly selected to be screened for prostate cancer every third year over a 12-year period . The remaining 7532 men were treated as controls . In 1987 and 1990 only digital rectal examination ( DRE ) was performed , in 1993 and 1996 DRE was combined with a test for Prostate-Specific Antigen ( PSA ) . TNM categories , grade of malignancy , management and cause of death were recorded in the South-East Region Prostate Cancer Register . RESULTS There were 85 ( 5.7 % ) cancers detected in the screened group ( SG ) , 42 of these in the interval between screenings , and 292 ( 3.8 % ) in the unscreened group ( UG ) . In the SG 48 ( 56.5 % ) of the tumours and in the UG 78 ( 26.7 % ) were localised at diagnosis ( p < 0.001 ) . In the SG 21 ( 25 % ) and in the UG 41 ( 14 % ) received curative treatment . There was no significant difference in total or prostate cancer-specific survival between the groups . CONCLUSIONS Although PSA had not been introduced in the clinical practice at the start of the study , we were still able to show that it is possible to perform a long-term population -based r and omised controlled study with st and ardised management and that screening in general practice is an efficient way of detecting prostate cancer whilst it is localised . Complete data on stage , treatment and mortality for both groups was obtained from a vali date d cancer register , which is a fundamental prerequisite when assessing screening programmes BACKGROUND The aim of our study was to determine the association between hormone treatment of prostate cancer and survival for those affected . MATERIAL AND METHODS Data were retrieved from several official Norwegian registries on hormone treatment , cancer in various stages , and the use of radical prostatectomies and external beam radiation therapy with curative intent . RESULTS The number of patients treated with hormones has risen 10-fold during the last decade . GnRH analogues and /or bicalutamide are used to treat more than 90 % of patients . The counties that use radical prostatectomy most frequently also have the most pronounced increase in hormone treatment and the increases in parallel over time . A cohort of Norwegian men will have a net loss of 1025 patient-years over a 10-year period if the number of patient-years gained and lost is calculated with current treatment practice and based on the number of radical treated and hormone-treated patients and expected survival with prostate cancer in Norway and expectations according to r and omised , controlled studies on radical treatment and hormone treatment in general . INTERPRETATION There are reasons to discuss whether the extent of hormone-treatment and radical treatment should be reduced . A reduction would be most easily achieved by reducing wild-screening of PSA in serum Screening for prostate cancer and subsequent treatment is of unknown benefit but carries known treatment related morbidity and mortality risks . The recent enthusiasm for screening in the United States contrasts sharply with the more cautious attitudes of the European and Canadian medical communities . Current data from screening series without r and omization and controls are inadequate to determine screening benefit . The prostate , lung , colorectal and ovarian cancer ( r and omized , controlled ) screening trial of the National Cancer Institute , to include 74,000 men ( and 74,000 women ) 60 to 74 years old , has a design power of 90 % to determine a 20 % reduction of prostate cancer mortality from a baseline and 3 subsequent annual screens using prostate specific antigen and digital rectal examination . R and omization of participants into this trial began on November 16 , 1993 . Ten screening centers nationwide , a coordinating center , a laboratory and a biorepository are participating under contract BACKGROUND AND OBJECTIVE Approximately 70 % of the men with an elevated serum prostate-specific antigen ( PSA ) identified in prostate cancer screening do not have prostate cancer . Other available diagnostic variables may be utilized to reduce the number of false positive PSA results , but few algorithms for calculation of the combined impact of multiple variables are available . The objective of this study was to establish nomograms showing the probability of detecting prostate cancer at biopsy on the basis of total PSA , and the percentage of free PSA in serum , prostate volume and digital rectal examination ( DRE ) findings . METHODS In a r and omized , population -based prostate cancer screening trial 10284 men aged 55 - 67 years were screened during 1996 and 1997 in two metropolitan areas in Finl and . Results for men ( n=758 ) with a serum PSA of 4 - 20 microg/l were used to establish the risk nomograms . Of these 200 ( 26 % ) had prostate cancer at biopsy . RESULTS Prostate cancer probability depended most strongly on the percentage of free PSA . Total PSA , prostate volume , and DRE also contributed to prostate cancer probability , whereas age and family history of prostate cancer did not . More false positive PSA results could be eliminated by using the multivariate risk model rather than the percentage of free PSA ( p<0.001 ) or PSA density ( p=0.003 ) alone . CONCLUSIONS Wide variation in probability of detecting prostate cancer among screened men with a serum PSA of 4 - 20 microg/l was observed . The nomograms established can be used to avoid or defer biopsy in men with a low prostate cancer probability in spite of a serum PSA level exceeding 4 microg/l Screening serum levels of prostate-specific antigen ( PSA ) is now a major strategy for early detection of prostate cancer ( PC ) . Quantification of the lead time thus obtained is important both for underst and ing the development of PC and for evaluating the advantages and disadvantages of widespread screening . In our study , 1,233 r and omly selected men living in Stockholm in 1988 were invited to participate in an early detection ( ED ) program , in which suspicious findings provided by digital rectal examination ( DRE ) , transrectal ultrasonography ( TRUS ) and /or a PSA value > /=10.0 ng/mL were followed up by biopsy . The cumulative incidence ( Kaplan-Meier ) of PC in the 946 participants ( ED ) during 12 years of follow-up was compared to that of an age-matched , r and omly selected reference population ( RP ) of 657 men for whom PSA values ( from frozen serum sample s ) could also be obtained . The PC incidence in men in the RP with PSA values > /=3.0 ng/mL reached the corresponding level for the ED group after 10.6 years ( the " catch-up " point ) . After 12 years of follow-up , the estimated median lead time for men with PSA values in this interval was 4.5 years in the ED population , compared to 7.8 years in the RP . With 20 years of follow-up , the estimated median lead time of the RP was enhanced to 10.7 years . The lead time in connection with PC was influenced by the initial PSA level ( although with large variations ) , length of follow-up and sensitivity of the ED procedure employed . The ED program described here was not associated with major overdetection Prostate cancer has become the most common cancer and the second cause of death due to cancer in men in North America . Since curative therapies are limited to early stages of the disease , the availability of an efficient , easy to perform , widely acceptable and cost-effective method of early detection of prostate cancer is particularly important . Thus , digital rectal examination , transrectal ultrasonography of the prostate as well as measurements of serum prostate specific antigen ( PSA ) were performed independently in a series of 1,002 men between 45 and 80 years old r and omly selected from the electoral rolls of Quebec City and its vicinity as part of a screening program for prostate cancer . Using this population of r and omly chosen men , various cutoff serum PSA values were selected in an attempt to find the optimal decision threshold that would indicate a much greater risk of having prostatic cancer . At a threshold value of 3.0 micrograms./l . the sensitivity and specificity of the test are 80.7 and 89.6 % , respectively , while the area under the receiver operating characteristic curve reflecting the accuracy of the test is 87.8 + /- 3.3 % ( plus or minus st and ard deviation ) . Moreover , the negative predictive value was estimated at 98.6 % , thus leaving only a 1.4 % chance of missing cancer when the serum PSA value was 3.0 micrograms./l . or less . Most importantly , such a threshold level of serum PSA retains only 19 % of the whole cohort as c and i date s for transrectal ultrasonography and expensive diagnostic procedures , thus leading to the finding of 1 prostate cancer of 4 such examinations . The present data indicate that simple measurement of serum PSA can be used efficiently as a pre-screening test for prostate cancer in the general population to identify , at a low cost , the sub population of men at a much greater risk of having prostate cancer , and who should then be su bmi tted to the more elaborate and expensive diagnostic procedures BACKGROUND To analyze to what extent the percentage of suspicious digital rectal examination ( DRE ) findings vary between examiners and to what extent the percentage of prostate cancers ( PCs ) detected in men with these suspicious findings varies between examiners . METHODS In the first screening round of the European R and omized study of Screening for PC ( ERSPC ) Rotterdam , 7,280 men underwent a PSA-determination and DRE of whom 2,102 underwent prostate biopsy ( biopsy indication PSA > or = 4.0 ng/ml and /or suspicious DRE and /or TRUS ) . Descriptive statistics of DRE- outcome per PSA-range were used to determine the observer variability of six examiners . Because this analysis did not correct properly for other predictors of a suspicious DRE ( PSA-level , biopsy indication , TRUS- outcome , prostate volume and age ) , a logistic regression analysis controlling for these explanatory variables was performed as well . RESULTS In 2,102 men biopsied , 443 PCs were detected ( PPV = 21 % ) . For all PSA levels the percentage suspicious DRE varied between examiners from 4 % to 28 % and percentage PC detected in men with a suspicious DRE varied from 18 % to 36 % . Logistic regression analysis showed that three of six examiners considered DRE significantly more often abnormal than others ( ORs 3.48 , 2.80 , 2.47 , P < 0.001 ) . For all examiners the odds to have PC was statistically significantly higher in case of a suspicious DRE ( ORs 2.21 - 5.96 , P < 0.05 ) . This increased chance to find PC was not significantly observer-dependent . CONCLUSIONS Three of six examiners considered DRE significantly more often suspicious than the others . However , under equal circumstances a suspicious DRE executed by each examiner increased the chance of the presence of PC similarly OBJECTIVES The efficacy of screening for prostate cancer ( PCa ) with digital rectal examination ( DRE ) and prostate-specific antigen ( PSA ) measurement has not been proved in r and omized clinical trials . In an earlier case-control study , we found that DRE might reduce PCa mortality . The present case-control study assessed the association between PSA and DRE testing and PCa mortality . METHODS The case subjects included 74 Olmsted County residents who had died from 1992 to 2005 with PCa as the underlying cause of death . From 1 to 3 community control subjects ( alive at time of case subject 's death ) were matched to each case subject . The medical records were review ed to identify DREs and PSA determinations performed 0 to 5 years before the date the case was diagnosed ( index date ) . Tests performed in the absence of symptoms were considered to be " screening tests . " Conditional logistic regression analysis was used to estimate the odds ratios and 95 % confidence intervals for the association of screening ( defined in multiple ways ) and PCa mortality . RESULTS From 1 to 5 years before the index date , control subjects were more likely than case subjects to have undergone a previous screening PSA test or DRE ( 81.3 % versus 60.8 % , P = 0.0005 ) . The unadjusted odds ratio associated with a previous screening PSA test or DRE was 0.34 ( 95 % confidence interval 0.18 to 0.63 ) , and the odds ratio adjusted for potential confounders was 0.35 ( 95 % confidence interval 0.17 to 0.71 ) . PSA testing was frequently done in conjunction with DRE , making evaluation of the individual effects difficult . CONCLUSIONS The results of this case-control study suggest a potential benefit of screening by PSA testing and /or DRE on PCa mortality BACKGROUND In 2002 , we reported the initial results of a trial comparing radical prostatectomy with watchful waiting in the management of early prostate cancer . After three more years of follow-up , we report estimated 10-year results . METHODS From October 1989 through February 1999 , 695 men with early prostate cancer ( mean age , 64.7 years ) were r and omly assigned to radical prostatectomy ( 347 men ) or watchful waiting ( 348 men ) . The follow-up was complete through 2003 , with blinded evaluation of the causes of death . The primary end point was death due to prostate cancer ; the secondary end points were death from any cause , metastasis , and local progression . RESULTS During a median of 8.2 years of follow-up , 83 men in the surgery group and 106 men in the watchful-waiting group died ( P=0.04 ) . In 30 of the 347 men assigned to surgery ( 8.6 percent ) and 50 of the 348 men assigned to watchful waiting ( 14.4 percent ) , death was due to prostate cancer . The difference in the cumulative incidence of death due to prostate cancer increased from 2.0 percentage points after 5 years to 5.3 percentage points after 10 years , for a relative risk of 0.56 ( 95 percent confidence interval , 0.36 to 0.88 ; P=0.01 by Gray 's test ) . For distant metastasis , the corresponding increase was from 1.7 to 10.2 percentage points , for a relative risk in the surgery group of 0.60 ( 95 percent confidence interval , 0.42 to 0.86 ; P=0.004 by Gray 's test ) , and for local progression , the increase was from 19.1 to 25.1 percentage points , for a relative risk of 0.33 ( 95 percent confidence interval , 0.25 to 0.44 ; P<0.001 by Gray 's test ) . CONCLUSIONS Radical prostatectomy reduces disease-specific mortality , overall mortality , and the risks of metastasis and local progression . The absolute reduction in the risk of death after 10 years is small , but the reductions in the risks of metastasis and local tumor progression are substantial Five r and omized pilot studies of screening for prostate cancer ( PC ) have been conducted in the area of Rotterdam from 1991 to 1994 . The purpose of these studies was to establish the feasibility of a r and omized screening protocol with PC mortality as the major end point in The Netherl and s and at a European level . All procedures related to recruitment of participants , to application of the screening tests and to data collection were evaluated . Men ( 7,200 ) aged 55 - 74 years were invited through the Rotterdam Population Registry . The recruitment rate over the 5 pilot studies averaged 38.2 % ( 2,747 men ) . Recruitment procedures proved to be relevant for establishing higher participation rates ( invitation and consent by mail ) . The screening tests were well accepted and tolerated . The general population -based character of the sample was confirmed by study ing symptoms of prostatic disease in participants and in men who refused participation . Data based on one PSA serum determination , rectal examination and transrectal ultrasonography are presented ; 204/1,403 men ( 14.5 % ) had a positive screening result by either test combination and underwent biopsy . Forty-nine cancers were found in 1,403 men ( 3.5 % ) ; 65 % of prostate cancers ( 17/26 ) identified in men who eventually underwent radical prostatectomy proved to be locally confined . From the pilot studies , we conclude that a large contribution to a European R and omized Study of Screening for Prostate Cancer ( ERSPC ) can be made by recruiting about 40,000 men in the area of Rotterdam . The preliminary data suggest that after confirmation of the present data during the first years in the European study , DRE and TRUS can be withheld depending on the PSA result in a large proportion of the screening population OBJECTIVES R and omized controlled trials are currently conducted to assess whether the mortality from prostate cancer is reduced by early detection with the use of prostate-specific antigen ( PSA ) measurements in serum . To be effective , such a program should be able to reduce the absolute number of men diagnosed with metastatic prostate cancer ( for which no cure is available ) . The aim of the present report is to evaluate whether PSA-based screening reduces the risk of being diagnosed with metastatic prostate cancer . METHODS A population -based , prospect i ve , r and omized , controlled screening trial for prostate cancer started in 1995 ( the Göteborg branch of the European R and omized Study of Screening for Prostate Cancer [ ERSPC ] ) . Ten thous and , r and omly selected men aged 50 - 66 yr were invited for biennial PSA testing , with 10,000 men serving as passive controls for whom diagnosis of metastatic prostate cancer was monitored by using the Swedish Cancer Registry . RESULTS After a follow-up of 10 yr , the risk of being diagnosed with metastatic prostate cancer was reduced by 48.9%-that is , decreasing from 47 cases in the control group to 24 cases in the group r and omized to PSA-based screening ( p=0.0084 ) . However , the risk of being diagnosed with prostate cancer increased 1.8-fold with PSA-based screening . CONCLUSIONS Biennial PSA screening reduces the risk of being diagnosed with metastatic prostate cancer , the first prerequisite for achieving decreased cancer mortality in younger men . This putative benefit is balanced by a 1.8-fold increased risk for diagnosis of prostate cancer Of 9,008 males , aged 50 - 69 years , 1,494 were r and omly selected and invited to participate in a screening programme for carcinoma of the prostate ; 1,163 ( 78 per cent ) accepted . Rectal examination was performed independently by a GP and by a urologist at the GP 's surgery . Carcinoma of the prostate was suspected by one or both physicians in 45 cases , and subsequently confirmed by cytological investigation in 13 cases . Ten patients underwent radical prostatectomy , one received radiation treatment , one case was too advanced for curative treatment , and one was scheduled for subsequent re assessment . Screening for early diagnosis of carcinoma of the prostate either by a urologist or by a GP , using digital rectal examination , would thus appear to be a cost-effective procedure , though the question remains whether it will promote prolongation of survival OBJECTIVE --To study the acceptability , costs , psychosocial consequences , and organisation of screening for carcinoma of the prostate . DESIGN --A r and omly selected population was personally invited for digital rectal examination by a urologist and a general practitioner . Further examinations were performed if in duration was felt . Each man completed a question naire on his response to the examination . SETTING --General practice s in the area of Norrköping . PATIENTS --1494 Men aged 50 - 69 r and omly selected from a population of 9026 . MAIN OUTCOME MEASURE -- Prostates having a firm nodular consistency . RESULTS --Carcinoma of the prostate was suspected in 45 of 1163 patients examined ; in 10 by the general practitioners , in 10 by the urologists , and in 25 by both . Forty four men had a fine needle aspiration biopsy , and carcinomas were found in 13 cases . Of these , one had been suspected by the general practitioner , four by urologists , and eight by both . The cost for each man was 11.60 pounds , and the cost for each case of carcinoma detected and treated by potentially curative methods was 2477 pounds . Of the 13 men with carcinoma , 10 underwent radical prostatectomy and one radiotherapy . One man had advanced disease and was given endocrine treatment , another was not treated . Only 193 men felt distress during the initial examination . Of the 44 men who had an aspiration biopsy , 25 experienced anxiety . CONCLUSIONS --Screening for carcinoma of the prostate by a urologist or a general practitioner using digital rectal examination is a cost effective method of early diagnosis . Whether such screening leads to prolonged survival , however , remains doubtful PURPOSE We describe the yield of a repeat examination and biopsy procedure 1 year after initial biopsy was negative . We also assessed the parameters responsible for the failure to diagnose these cancers at the primary screening . MATERIAL S AND METHODS We screened 8,103 men r and omized to the screening arm of the Rotterdam section of the European R and omized Study of Screening for Prostate Cancer using prostate specific antigen measurement , digital rectal examination and transrectal ultrasound . At the primary screening biopsy of 1,875 men was positive for prostate cancer in 374 . Of the remaining 1,501 men 984 underwent repeat screening . RESULTS Biopsy at repeat screening diagnosed prostate cancer in 49 of 442 men ( 11 % ) , a rate significantly lower than the 19.9 % true positive biopsy rate at the primary screening . Pathological characteristics of the tumors diagnosed were not significantly different in the 2 groups . However , prostate volume in men diagnosed with prostate cancer was significantly greater at repeat versus primary screening ( mean 42.6 versus 34.9 cc , p = 0.003 ) . The clinical characteristics were more favorable because of an increased proportion of stage T1C tumors . Prostate volume in men with stage T1C cancer was significantly greater than in those with palpable or visible tumors in whom prostate specific antigen values were in the same range . CONCLUSIONS The most important factor responsible for the failure to diagnose these cancers at the primary screening was significantly greater prostate volume . Tumor characteristics were not significantly different in the groups . If prostate cancer screening were to become a routine health care policy , efforts would have to be made to improve the chances of diagnosing prostate cancer in larger prostates by repeat biopsy or by increasing the number of cores obtained OBJECTIVES To study retrospectively whether the prostate-specific antigen ( PSA ) velocity , that is , the change in PSA level over time , might serve as a screening tool in this PSA range . It is estimated that 40 % of detectable prostate cancers are present in men with a PSA level of 4.0 ng/mL or less . Digital rectal examination and /or transrectal ultrasonography have been used as screening tools at these low PSA levels , but this approach is not very efficient . METHODS The possible predictors ( including PSA velocity ) for biopsy outcome were studied using univariate and multivariate logistic regression analysis in 774 men who underwent biopsy between November 1997 and January 2002 in the second screening round of the European R and omised Study of Screening for Prostate Cancer ( ERSPC ) . The clinical stage of the tumors was determined , and the Gleason scores of the biopsies were studied . RESULTS A total of 149 cancers were found ( positive predictive value 19.2 % ) . The odds ratio for the PSA velocity determined by univariate logistic regression analysis was 2.2 ( 95 % confidence interval 0.7 to 6.9 , P = 0.19 ) and was 0.73 ( 95 % confidence interval 0.20 to 2.6 , P = 0.64 ) by multivariate analysis . The distribution of the clinical stage of the detected tumors was 64.4 % T1c , 32.2 % T2 , and 3.4 % T3 . The biopsy Gleason score was 6 in 84.5 % , 7 in 14.2 % , and 8 in 1.3 % . CONCLUSIONS The number of cancers detected in this study and the distribution of clinical stage and biopsy Gleason score confirmed that a relatively large proportion of potentially curable cancers can be found in the low PSA ranges . The PSA velocity did not appear to be a useful screening tool for the identification of these cancers OBJECTIVES Although several nomograms for prostate cancer detection have been developed for Western population s , the models constructed on Japanese data would be more useful for the Japanese population because of various differences between Western and Asian population s. We previously developed a model for predicting the probability of a positive initial prostate biopsy using clinical and laboratory data from Japanese males . In the present study , a predictive model for Japanese males with a prostate-specific antigen ( PSA ) < 10 ng/mL was developed to guide decision-making for prostate biopsies . METHODS The age , total PSA level , free to total PSA ratio , prostate volume , and the digital rectal examination findings of 1037 Japanese males with a PSA < 10 ng/mL undergoing initial prostate biopsy as part of individual screening were analyzed . For study validation , 20 % of these data was r and omly reserved . Logistic regression analysis estimated relative risk , 95 % confidence intervals , and P-values . RESULTS Age and the independent predictors of a positive biopsy result ( elevated PSA , decreased free to total PSA ratio , small prostate volume , and abnormal digital rectal examination findings ) were used to develop a predictive nomogram . The area under the receiver operating characteristic curve was significantly higher for the model ( 73.0 % ) than for PSA alone ( 55.0 % ) . If externally vali date d , the use of this nomogram could reduce unnecessary biopsies by 26 % and overall prostate biopsies by 7.8 % . CONCLUSIONS This predictive nomogram could provide more precise risk- analysis information for individual Japanese patients with PSA levels less than 10 ng/mL and may help to identify patients who need a prostate biopsy |
1,897 | 29,459,980 | However , the studies did not show consistent beneficial effects of osteoporosis medications on BMD .
In conclusion , DXA BMD assessment is reasonable if low or decreasing BMD will lead to additional interventions to reduce falls or recommendations for use of osteoporosis medications .
The analysis underscored the importance of potential interactions among components of CKDMBD in terms of risk prediction for death or cardiovascular events .
High- quality evidence now links high phosphate concentrations with mortality among patients with CKD stage G3a to G5 and transplant recipients ( 1928 ) .
However , there is still a lack of data from clinical trials showing that therapeutic approaches to decreasing serum phosphate levels improve patient-centered outcomes .
The 2009 guideline suggested maintenance of normal serum phosphate levels for patients with CKD stages G3a to G4 .
Most studies found phosphate to be consistently associated with excess mortality at levels above and below the limits of normal but not in the normal range . | As kidney function decreases , marked changes in bone mineral metabolism occur , result ing in increased risk for fractures , cardiovascular disease , and overall mortality .
In 2009 , Kidney Disease : Improving Global Outcomes ( KDIGO ) published the Clinical Practice Guideline for the Diagnosis , Evaluation , Prevention , and Treatment of Chronic Kidney DiseaseMineral and Bone Disorder ( CKDMBD ) ( 1 ) .
Prognosis of CKD , by categories of GFR and albuminuria .
This synopsis focuses on diagnosis of CKDMBD and management of serum phosphate , calcium , and PTH levels in adults areas in which controversy and knowledge gaps exist .
Grade 2B recommendation ) When the 2009 KDIGO CKDMBD guideline was published , cross-sectional studies of dual-energy x-ray absorptiometry ( DXA ) that compared bone mineral density ( BMD ) in patients with CKD with and without a prevalent fracture were limited .
Consequently , the 2009 guideline recommended that BMD testing not be routinely performed in patients with CKD stage G3a to G5D and CKDMBD ( 1 ) .
Not grade d ) Bone biopsy is the gold st and ard for diagnosis and classification of renal osteodystrophy ( 12 ) .
The 2009 guideline noted that DXA BMD testing does not distinguish among types of renal osteodystrophy , and the diagnostic utility of biochemical markers was limited by their poor sensitivity and specificity ( 1 ) .
Grade 2C recommendation ) In patients with CKD , clinical decisions are routinely based on serum phosphate , calcium , and PTH concentrations .
However , these are influenced by several factors , including diurnal changes ( 15 , 16 ) .
A recent post hoc analysis of large dialysis cohorts suggested that the prognostic implication s of individual biochemical components of CKDMBD largely depend on their context within the full array of MBD biomarkers ( 17 ) . | Background Heart and coronary calcifications in hemodialysis patients are of very common occurrence and linked to cardiovascular events and mortality . Several studies have been published with similar results . Most of them were mainly cross-sectional and some of the prospect i ve protocol s were aim ed to evaluate the results of the control of altered biochemical parameters of mineral disturbances with special regard to serum calcium , phosphate and CaxP with the use of calcium containing and calcium free phosphate chelating agents . The aim of the present study was to evaluate in hemodialysis patients classic and some non classic risk factors as predictors of calcification changes after one year and to evaluate the impact of progression on survival . Methods 81 patients on hemodialysis were studied , with a wide age range and HD vintage . Several classic parameters and some less classic risk factors were studied like fetuin-A , CRP , 25-OHD and leptin . Calcifications , as Agatston scores , were evaluated with Multislice CT basally and after 12 - 18 months . Results Coronary artery calcifications were observed in 71 of 81 patients . Non parametric correlations between Agatston scores and Age , HD Age , PTH and CRP were significant . Delta increments of Agatston scores correlated also with serum calcium , CaxP , Fetuin-A , triglycerides and serum albumin . Logistic regression analysis showed Age , PTH and serum calcium as important predictors of Delta Agatston scores . LN transformation of the not normally distributed variables restricted the significant correlations to Age , BMI and CRP . Considering the Delta Agatston scores as dependent , significant predictors were Age , PTH and HDL . A strong association was found between basal calcification scores and Delta increment at one year . By logistic analysis , the one year increments in Agatston scores were found to be predictors of mortality . Diabetic and hypertensive patients have significantly higher Delta scores . Conclusions Progression of calcification is of common occurrence , with special regard to elevated basal scores , and is predictive of survival . Higher predictive value of survival is linked to the one year increment of calcification scores . Some classic and non classic risk factors play an important role in progression . Some of them could be controlled with appropriate management with possible improvement of mortality BACKGROUND AND OBJECTIVES Hyperphosphatemia , vitamin D deficiency , hyperparathyroidism , and high serum fibroblast growth factor 23 ( FGF23 ) levels , when studied separately , were found to predict the progression of CKD . However , studies with simultaneous measurement of mineral bone disorder (MBD)-related factors were scarce . This study aim ed to identify factors predicting renal outcome independent of other factors . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS This was a prospect i ve cohort study of 738 Japanese predialysis out patients in the nephrology departments of two hospitals . The outcome was defined as a doubling of serum creatinine or initiation of dialysis . RESULTS Mean estimated GFR ( eGFR ) was 35 ml/min per 1.73 m(2 ) . At enrollment , the increase in intact FGF23 with decreasing eGFR was the earliest among changes in MBD-related factors , followed by 1,25-dihydroxyvitamin D decrease , parathyroid hormone increase , and phosphate increase . During a median duration of 4.4 years , 213 patients reached the endpoint . In a multivariable Cox model , high FGF23 and low 25-hydroxyvitamin D ( 25D ) levels were the only MBD-related factors associated with a higher risk of renal endpoint ( adjusted hazard ratio [ 95 % confidence interval ] per unit change of log FGF23 and 10 ng/ml of 25D : 1.83 [ 1.28 - 2.61 ] and 0.61 [ 0.41 - 0.90 ] , respectively ) . There was no significant interaction between 25D and FGF23 ( P=0.11 ) . Active vitamin D therapy , serum phosphate , 1,25-dihydroxyvitamin D , and parathyroid hormone levels were not related to the renal endpoint . Treating death as a competing risk or multiple imputation for missing values yielded similar results . CONCLUSIONS Combined use of two markers is useful for the risk stratification of renal outcome Background — Patients with kidney disease have disordered bone and mineral metabolism , including elevated serum concentrations of fibroblast growth factor-23 ( FGF23 ) . These elevated concentrations are associated with cardiovascular and all-cause mortality . The objective was to determine the effects of the calcimimetic cinacalcet ( versus placebo ) on reducing serum FGF23 and whether changes in FGF23 are associated with death and cardiovascular events . Methods and Results — This was a secondary analysis of a r and omized clinical trial comparing cinacalcet to placebo in addition to conventional therapy ( phosphate binders/vitamin D ) in patients receiving hemodialysis with secondary hyperparathyroidism ( intact parathyroid hormone ≥300 pg/mL ) . The primary study end point was time to death or a first nonfatal cardiovascular event ( myocardial infa rct ion , hospitalization for angina , heart failure , or a peripheral vascular event ) . This analysis included 2985 patients ( 77 % of r and omized ) with serum sample s at baseline and 2602 patients ( 67 % ) with sample s at both baseline and week 20 . The results demonstrated that a significantly larger proportion of patients r and omized to cinacalcet had ≥30 % ( 68 % versus 28 % ) reductions in FGF23 . Among patients r and omized to cinacalcet , a ≥30 % reduction in FGF23 between baseline and week 20 was associated with a nominally significant reduction in the primary composite end point ( relative hazard , 0.82 ; 95 % confidence interval , 0.69–0.98 ) , cardiovascular mortality ( relative hazard , 0.66 ; 95 % confidence interval , 0.50–0.87 ) , sudden cardiac death ( relative hazard , 0.57 ; 95 % confidence interval , 0.37–0.86 ) , and heart failure ( relative hazard , 0.69 ; 95 % confidence interval , 0.48–0.99 ) . Conclusions — Treatment with cinacalcet significantly lowers serum FGF23 . Treatment-induced reductions in serum FGF23 are associated with lower rates of cardiovascular death and major cardiovascular events . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00345839 BACKGROUND In chronic kidney disease stage 5D , diagnostic usefulness of bone mineral density ( BMD ) in predicting fracture has not been established because of variable results in previous studies . The reason for this may be the heterogeneity of underlying pathogenesis of the fracture . METHODS BMD was measured annually and serum biochemistry monthly for 485 hemodialyzed patients from April 2003 to March 2008 , and all fractures were recorded . RESULTS Forty-six new episodes of any type of fracture and 29 cases of prevalent spine fracture were recorded . Serum bone-specific alkaline phosphatase ( b-AP ) was a very useful surrogate marker for any type of incident fracture risk [ area under curve ( AUC ) = 0.766 , P < 0.0001 ] . A significantly greater risk of any type of incident fracture was associated with parathyroid hormone ( PTH ) levels either < 150 pg/mL [ hazard ratio ( HR ) = 3.47 , P < 0.01 ] or > 300 pg/mL ( HR = 5.88 , P < 0.0001 ) compared with 150 - 300 pg/mL. Receiver-operating characteristic analysis demonstrated a significant predictive power for incident of any type of fracture by BMD at the total hip ( AUC = 0.760 , P < 0.0001 ) and other hip regions in females in the lower PTH group ( PTH < 204 pg/mL ) . BMDs at every site but whole body or lumbar spine had significant power to discriminate prevalent spine fracture regardless of gender or PTH . CONCLUSIONS Hemodialyzed patients with low or high PTH or increased b-AP had a high fracture risk . BMD by Dual Energy X-ray Absorptiometry ( DEXA ) , especially at the total hip region , was useful to predict any type of incident of fracture for females with low PTH or to discriminate prevalent spine fracture for every patient BACKGROUND AND OBJECTIVES Higher phosphate is associated with mortality in dialysis patients but few prospect i ve studies assess this in nondialysis patients managed in an outpatient nephrology clinic . This prospect i ve longitudinal study examined whether phosphate level was associated with death in a referred population . DESIGN , SETTING , PARTICIPANTS & MEASUREMENTS Patients ( 1203 ) of nondialysis chronic kidney disease ( CKD ) in the Chronic Renal Insufficiency St and ards Implementation Study were assessed . Survival analyses were performed for quartiles of baseline phosphate relative to GFR , 12-month time-averaged phosphate , and baseline phosphate according to published phosphate targets . RESULTS Mean ( SD ) eGFR was 32 ( 15 ) ml/min per 1.73 m(2 ) , age 64 ( 14 ) years , and phosphate 1.2 ( 0.30 ) mmol/L. Cox multivariate adjusted regression in CKD stages 3 to 4 patients showed an increased risk of all-cause and cardiovascular mortality in the highest quartile compared with that in the lowest quartile of phosphate . No association was found in CKD stage 5 patients . Patients who had values above recommended targets for phosphate control had increased risk of all-cause and cardiovascular death compared with patients below target . The highest quartile compared with the lowest quartile of 12-month time-averaged phosphate was associated with an increased risk of mortality . CONCLUSIONS In CKD stages 3 to 4 patients , higher phosphate was associated with a stepwise increase in mortality . As phosphate levels below published targets ( as opposed to within them ) are associated with better survival , guidelines for phosphate in nondialysis CKD patients should be re-examined . Intervention trials are required to determine whether lowering phosphate will improve survival Background Serum phosphate is a known risk factor for cardiovascular events and mortality in people with chronic kidney disease ( CKD ) , however data on the association of these outcomes with serum phosphate in the general population are scarce . We investigate this relationship in people with and without CKD in a large community-based population . Methods Three groups from an adult cohort of the Quality Improvement in Chronic Kidney Disease ( QICKD ) cluster r and omised trial ( IS RCT N56023731 ) were followed over a period of 2.5 years : people with normal renal function ( N = 24,184 ) , people with CKD stages 1–2 ( N = 20,356 ) , and people with CKD stages 3–5 ( N = 13,292 ) . We used a multilevel logistic regression model to determine the association between serum phosphate , in these groups , and a composite outcome of all-cause mortality , cardiovascular events , and advanced coronary artery disease . We adjusted for known cardiovascular risk factors . Findings Higher phosphate levels were found to correlate with increased cardiovascular risk . In people with normal renal function and CKD stages 1–2 , Phosphate levels between 1.25 and 1.50 mmol/l were associated with increased cardiovascular events ; odds ratio ( OR ) 1.36 ( 95 % CI 1.06–1.74 ; p = 0.016 ) in people with normal renal function and OR 1.40 ( 95 % CI 1.09–1.81 ; p = 0.010 ) in people with CKD stages 1–2 . Hypophosphatemia ( < 0.75 mmol/l ) was associated with fewer cardiovascular events in people with normal renal function ; OR 0.59 ( 95 % CI 0.36–0.97 ; p = 0.049 ) . In people with CKD stages 3–5 , hyperphosphatemia ( > 1.50 mmol/l ) was associated with increased cardiovascular risk ; OR 2.34 ( 95 % CI 1.64–3.32 ; p<0.001 ) . Other phosphate ranges were not found to have a significant impact on cardiovascular events in people with CKD stages 3–5 . Conclusions Serum phosphate is associated with cardiovascular events in people with and without CKD . Further research is required to determine the mechanisms underlying these associations BACKGROUND The management of chronic kidney disease-mineral and bone disorder requires the assessment of bone turnover , which most often is based on parathyroid hormone ( PTH ) concentration , the utility of which remains controversial . STUDY DESIGN Cross-sectional retrospective diagnostic test study . SETTING & PARTICIPANTS 492 dialysis patients from Brazil , Portugal , Turkey , and Venezuela with prior bone biopsy and stored ( -20 ° C ) serum . INDEX TESTS Sample s were analyzed for PTH ( intact [ iPTH ] and whole PTH ) , bone-specific alkaline phosphatase ( bALP ) , and amino-terminal propeptide of type 1 procollagen ( P1NP ) . REFERENCE TEST Bone histomorphometric assessment of turnover ( bone formation rate/bone surface [ BFR/BS ] ) and receiver operating characteristic curves for discriminating diagnostic ability . RESULTS The biomarkers iPTH and bALP or combinations thereof allowed discrimination of low from nonlow and high from nonhigh BFR/BS , with an area under the receiver operating characteristic curve > 0.70 but < 0.80 . Using iPTH level , the best cutoff to discriminate low from nonlow BFR/BS was < 103.8 pg/mL , and to discriminate high from nonhigh BFR/BS was > 323.0 pg/mL. The best cutoff for bALP to discriminate low from nonlow BFR/BS was < 33.1 U/L , and for high from nonhigh BFR/BS , 42.1U/L. Using the KDIGO practice guideline PTH values of greater than 2 but less than 9 times the upper limit of normal , sensitivity and specificity of iPTH level to discriminate low from nonlow turnover bone disease were 65.7 % and 65.3 % , and to discriminate high from nonhigh were 37.0 % and 85.8 % , respectively . LIMITATIONS Cross-sectional design without consideration of therapy . Potential limited generalizability with sample s from 4 countries . CONCLUSIONS The serum biomarkers iPTH , whole PTH , and bALP were able to discriminate low from nonlow BFR/BS , whereas iPTH and bALP were able to discriminate high from nonhigh BFR/BS . Prospect i ve studies are required to determine whether evaluating trends in biomarker concentrations could guide therapeutic decisions BACKGROUND Secondary hyperparathyroidism is observed in patients with early chronic kidney disease ( CKD ) . This study investigated the safety and efficacy of cinacalcet for secondary hyperparathyroidism in participants with CKD not receiving dialysis . STUDY DESIGN Double-blind , r and omized , 32-week , phase 3 study . SETTING & PARTICIPANTS 404 participants with stage 3 or 4 CKD from 73 centers in 9 countries . INTERVENTIONS Cinacalcet : placebo ( 3:1 ratio ) . OUTCOMES & MEASUREMENTS Proportion of participants with a mean decrease of 30 % or greater in intact parathyroid hormone ( iPTH ) level , proportion with iPTH level of 70 or less or 110 or less pg/mL ( stage 3 and 4 CKD , respectively ) , and mean percentage of iPTH change from baseline , all during the efficacy- assessment phase . RESULTS A greater proportion of cinacalcet than placebo participants achieved a 30 % or greater decrease in iPTH level ( 74 % versus 28 % ; P < 0.001 ) , corresponding to a 43.1 % decrease in iPTH level from baseline ( cinacalcet ) compared with a 1.1 % increase ( placebo ) . At week 32 , serum calcium levels were 8.9 + /- 0.8 mg/dL ( -8.9 % ; cinacalcet ) and 9.9 + /- 0.6 mg/dL ( + 0.8 % ; placebo ) , phosphorus levels were 4.5 + /- 1.0 mg/dL ( + 21.4 % ) and 4.0 + /- 0.7 mg/dL ( + 6.8 % ) , and calcium-phosphorus product values were 40.1 + /- 8.3 mg(2)/dL(2 ) ( + 18.9 % ) and 38.9 + /- 6.9 mg(2)/dL(2 ) ( + 17.1 % ) , respectively . During the study course , 62 % ( cinacalcet ) and 1 % ( placebo ) of participants experienced 2 consecutive serum calcium concentrations less than 8.4 mg/dL. They generally were asymptomatic and without significant clinical consequences . Treatment generally was well tolerated , and most adverse events were mild to moderate in severity . LIMITATIONS The study was not design ed to assess the effects of cinacalcet on vascular calcification , bone histomorphometric parameters , or other clinical outcomes . It is not known whether the observed differences in changes in iPTH levels are clinical ly more important than observed differences in changes in serum calcium or phosphorus levels or dosages of vitamin D sterols and phosphate binders . CONCLUSIONS These data show that cinacalcet treatment in patients with CKD not receiving dialysis can decrease plasma iPTH levels , but with frequent ( albeit generally asymptomatic ) serum calcium levels less than 8.4 mg/dL and increases in serum phosphorus levels Chronic kidney disease ( CKD ) patients are given calcium carbonate to bind dietary phosphorus and reduce phosphorus retention , and to prevent negative calcium balance . Data are limited on calcium and phosphorus balance in CKD to support this . The aim of this study was to determine calcium and phosphorus balance and calcium kinetics with and without calcium carbonate in CKD patients . Eight stage 3/4 CKD patients , eGFR 36 mL/min , participated in two 3-week balances in a r and omized placebo-controlled cross-over study of calcium carbonate ( 1500 mg/d calcium ) . Calcium and phosphorus balance were determined on a controlled diet . Oral and intravenous 45calcium with blood sampling and urine and fecal collection s were used for calcium kinetics . Fasting blood and urine were collected at baseline and end of each week of each balance period for biochemical analyses . Results showed that patients were in neutral calcium and phosphorus balance while on placebo . Calcium carbonate produced positive calcium balance , did not affect phosphorus balance , and produced only a modest reduction in urine phosphorus excretion compared with placebo . Calcium kinetics demonstrated positive net bone balance but less than overall calcium balance suggesting tissue deposition . Fasting biochemistries of calcium and phosphate homeostasis were unaffected by calcium carbonate . If they can be extrapolated to effects of chronic therapy , these data caution against the use of calcium carbonate as a phosphate binder Vitamin D seems to protect against cardiovascular disease , but the reported effects of vitamin D on patient outcomes in CKD are controversial . We conducted a prospect i ve , double blind , r and omized , placebo-controlled trial to determine whether oral activated vitamin D reduces left ventricular ( LV ) mass in patients with stages 3 - 5 CKD with LV hypertrophy . Subjects with echocardiographic criteria of LV hypertrophy were r and omly assigned to receive either oral paricalcitol ( 1 μg ) one time daily ( n=30 ) or matching placebo ( n=30 ) for 52 weeks . The primary end point was change in LV mass index over 52 weeks , which was measured by cardiac magnetic resonance imaging . Secondary end points included changes in LV volume , echocardiographic measures of systolic and diastolic function , biochemical parameters of mineral bone disease , and measures of renal function . Change in LV mass index did not differ significantly between groups ( median [ interquartile range ] , -2.59 [ -6.13 to 0.32 ] g/m(2 ) with paricalcitol versus -4.85 [ -9.89 to 1.10 ] g/m(2 ) with placebo ) . Changes in LV volume , ejection fraction , tissue Doppler-derived measures of early diastolic and systolic mitral annular velocities , and ratio of early mitral inflow velocity to early diastolic mitral annular velocity did not differ between the groups . However , paricalcitol treatment significantly reduced intact parathyroid hormone ( P<0.001 ) and alkaline phosphatase ( P=0.001 ) levels as well as the number of cardiovascular-related hospitalizations compared with placebo . In conclusion , 52 weeks of treatment with oral paricalcitol ( 1 μg one time daily ) significantly improved secondary hyperparathyroidism but did not alter measures of LV structure and function in patients with severe CKD Exposure to high Ca concentrations may influence the development of low-turnover bone disease and coronary artery calcification ( CAC ) in patients on hemodialysis ( HD ) . In this r and omized , controlled study , we investigated the effects of lowering dialysate Ca level on progression of CAC and histologic bone abnormalities in patients on HD . Patients on HD with intact parathyroid hormone levels ≤300 pg/ml receiving dialysate containing 1.75 or 1.50 mmol/L Ca ( n=425 ) were r and omized to the 1.25-mmol/L Ca ( 1.25 Ca ; n=212 ) or the 1.75-mmol/L Ca ( 1.75 Ca ; n=213 ) dialysate arm . Primary outcome was a change in CAC score measured by multislice computerized tomography ; main secondary outcome was a change in bone histomorphometric parameters determined by analysis of bone biopsy specimens . CAC scores increased from 452±869 ( mean±SD ) in the 1.25 Ca group and 500±909 in the 1.75 Ca group ( P=0.68 ) at baseline to 616±1086 and 803±1412 , respectively , at 24 months ( P=0.25 ) . Progression rate was significantly lower in the 1.25 Ca group than in the 1.75 Ca group ( P=0.03 ) . The prevalence of histologically diagnosed low bone turnover decreased from 85.0 % to 41.8 % in the 1.25 Ca group ( P=0.001 ) and did not change in the 1.75 Ca group . At 24 months , bone formation rate , trabecular thickness , and bone volume were higher in the 1.25 Ca group than in the 1.75 Ca group . Thus , lowering dialysate Ca levels slowed the progression of CAC and improved bone turnover in patients on HD with baseline intact parathyroid hormone levels ≤300 pg/ml BACKGROUND AND OBJECTIVES Kidney Disease Improving Global Outcomes guidelines recommend against bone mineral density ( BMD ) screening in CKD patients with mineral bone disease , due to a lack of association of BMD with fractures in cross-sectional studies in CKD . We assessed whether BMD is associated with fractures in participants with and without CKD in the Health , Aging , and Body Composition study , a prospect i ve study of well functioning older individuals . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Hip BMD was measured by dual-energy x-ray absorptiometry . Osteoporosis was defined as a femoral neck BMD ( FNBMD ) T score below -2.5 and CKD as an estimated GFR < 60 ml/min per 1.73 m(2 ) . The association of BMD with incident nonspine , fragility fractures to study year 11 was analyzed using Cox proportional hazards analyses , adjusting for age , race , sex , body mass index , hyperparathyroidism , low vitamin D level , and CKD . Interaction terms were used to assess whether the association of BMD with fracture differed in those with and without CKD . RESULTS There were 384 incident fractures in 2754 individuals ( mean age 73.6 years ) . Lower FNBMD was associated with greater fracture , regardless of CKD status . After adjustment , the hazard ratios ( 95 % confidence intervals ) were 2.74 ( 1.99 , 3.77 ) and 2.15 ( 1.80 , 2.57 ) per lower SD FNBMD for those with and without CKD , respectively ( interaction P=0.68 ) , and 2.10 ( 1.23 , 3.59 ) and 1.63 ( 1.18 , 2.23 ) among those with osteoporosis in patients with and without CKD , respectively ( interaction P=0.75 ) . CONCLUSIONS BMD provides information on risk for fracture in older individuals with or without moderate CKD BACKGROUND AND AIM OF THE STUDY Valvular calcification is common in patients with end-stage renal disease , and is associated with an unfavorable prognosis . It was hypothesized that sevelamer , a non-calcium-based phosphorus binder , might attenuate the progression of valvular calcification . METHODS Two hundred subjects on maintenance hemodialysis received either sevelamer or calcium-based phosphorus binders . To assess the extent of calcification , 186 subjects underwent baseline electron beam tomography ( EBT ) of the coronary arteries , aorta and mitral and aortic valves , and 132 had follow up EBT scans at week 52 . Changes in valvular calcification and combined valvular/vascular calcification were monitored and compared . RESULTS At baseline , mitral valve calcification was seen in 46 % of subjects , aortic valve calcification in 33 % . Most subjects with zero values at baseline failed to progress over one year . Aortic valve calcification was significantly increased in calcium-treated subjects . Changes in mitral valve calcification , and combined mitral + aortic valve calcification were less in sevelamer-treated than in calcium-treated subjects , but not significantly so . When combining valvular and vascular calcification , the median ( 10 % , 90 % ) change in sevelamer-treated subjects was significantly lower than in calcium-treated subjects ( 6 , -5084 to 1180 versus 81 , -1150 to 2944 , p = 0.04 ) . The effect of sevelamer remained significant after adjustment for baseline calcification and the time-averaged calcium-phosphorus product , and was independent of the calcium preparation ( acetate versus carbonate ) , geographic region ( US versus Europe ) , LDL- or HDL-cholesterol , C-reactive protein and statin use . Significantly more sevelamer-treated subjects experienced an arrest ( 45 versus 28 % , p = 0.047 ) or regression ( 26 versus 10 % , p = 0.02 ) in total valvular and vascular calcification . CONCLUSION Sevelamer arrested the progression of valvular and vascular calcification in almost 50 % of hemodialysis subjects . Sevelamer treatment , plus intensive control of calcium and phosphorus levels , may attenuate progression of , or achieve regression in , cardiac valvular calcification INTRODUCTION This study was aim ed to investigate the effects of raloxifene on intact parathyroid hormone ( PTH ) level and bone mineral density ( BMD ) for 8 months in women on hemodialysis and women with chronic kidney disease stage 5 not dependent on dialysis to determine its effect on secondary hyperparathyroidism and osteoporosis . MATERIAL S AND METHODS Fifty-one women on hemodialysis and 9 with chronic kidney disease stage 5 were r and omly assigned to receive oral raloxifene , 60 mg/d , or placebo for 8 months . Baseline blood determinations and BMD were done and repeated after 8 months . Serum levels of total calcium , phosphorus , alkaline phosphatase , and intact PTH were measured . RESULTS Serum levels of intact PTH significantly decreased in both groups , and there was no difference between the two groups after 8 months ( P = .37 ) . Serum phosphorus levels also decreased by 1.8 % in the two groups . After 8 months of treatment , the BMD of the lumbar spine and femural neck decreased by 1.9 % in the control group , while an increase in BMD was observed in the raloxifene group , with an average increase in both BMDs of the lumbar spine and the femural neck by 2 % ( significant in the lumbar spine ; P = .01 ) . CONCLUSIONS Raloxifene has proven to be an effective medication in terms of improving BMD , with no adverse effects . However , it had no effect on controlling hyperparathyroidism in our patients . Long-term studies should be done to investigate the effects of raloxifene in chronic kidney disease and dialysis patients Background . High serum phosphate has been identified as an important contributor to the vascular calcification seen in patients with chronic kidney disease ( Block et al. , Am J Kidney Dis 1998 ; 31 : 607 ) . In patients on hemodialysis , elevated serum phosphate levels are an independent predictor of mortality ( Block et al. , Am J Kidney Dis 1998 ; 31 : 607 ; Block , Curr Opin Nephrol Hypertens 2001 ; 10 : 741 ) . The aim of this study was to investigate whether an elevated serum phosphate level was an independent predictor of mortality in patients with a renal transplant . Methods . Three hundred seventy-nine asymptomatic renal transplant recipients were recruited between June 2000 and December 2002 . Serum phosphate was measured at baseline and prospect i ve follow-up data were collected at a median of 2441 days after enrolment . Results . Serum phosphate was significantly higher in those renal transplant recipients who died at follow-up when compared with those who were still alive at follow-up ( P<0.001 ) . In Kaplan-Meier analysis , serum phosphate concentration was a significant predictor of mortality ( P=0.0001 ) . In multivariate Cox regression analysis , serum phosphate concentration remained a statistically significant predictor of all-cause mortality after adjustment for traditional cardiovascular risk factors , estimated glomerular filtration rate , and high sensitivity C reactive protein ( P=0.036 ) and after adjustment for renal graft failure ( P=0.001 ) . Conclusions . The results of this prospect i ve study are the first to show that a higher serum phosphate is a predictor of mortality in patients with a renal transplant and suggest that serum phosphate provides additional , independent , prognostic information to that provided by traditional risk factors in the risk assessment of patients with a renal transplant CONTEXT Vitamin D is associated with decreased cardiovascular-related morbidity and mortality , possibly by modifying cardiac structure and function , yet firm evidence for either remains lacking . OBJECTIVE To determine the effects of an active vitamin D compound , paricalcitol , on left ventricular mass over 48 weeks in patients with an estimated glomerular filtration rate of 15 to 60 mL/min/1.73 m(2 ) . DESIGN , SETTING , AND PARTICIPANTS Multinational , double-blind , r and omized placebo-controlled trial among 227 patients with chronic kidney disease , mild to moderate left ventricular hypertrophy , and preserved left ventricular ejection fraction , conducted in 11 countries from July 2008 through September 2010 . INTERVENTION Participants were r and omly assigned to receive oral paricalcitol , 2 μg/d ( n = 115 ) , or matching placebo ( n = 112 ) . MAIN OUTCOME MEASURES Change in left ventricular mass index over 48 weeks by cardiovascular magnetic resonance imaging . Secondary end points included echocardiographic changes in left ventricular diastolic function . RESULTS Treatment with paricalcitol reduced parathyroid hormone levels within 4 weeks and maintained levels within the normal range throughout the study duration . At 48 weeks , the change in left ventricular mass index did not differ between treatment groups ( paricalcitol group , 0.34 g/m(2.7 ) [ 95 % CI , -0.14 to 0.83 g/m(2.7 ) ] vs placebo group , -0.07 g/m(2.7 ) [ 95 % CI , -0.55 to 0.42 g/m(2.7 ) ] ) . Doppler measures of diastolic function including peak early diastolic lateral mitral annular tissue velocity ( paricalcitol group , -0.01 cm/s [ 95 % CI , -0.63 to 0.60 cm/s ] vs placebo group , -0.30 cm/s [ 95 % CI , -0.93 to 0.34 cm/s ] ) also did not differ . Episodes of hypercalcemia were more frequent in the paricalcitol group compared with the placebo group . CONCLUSION Forty-eight week therapy with paricalcitol did not alter left ventricular mass index or improve certain measures of diastolic dysfunction in patients with chronic kidney disease . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00497146 BACKGROUND Abnormalities in serum calcium , phosphorus , and parathyroid hormone ( PTH ) concentrations are common in patients with chronic kidney disease and have been associated with increased morbidity and mortality . No clinical trials have been conducted to clearly identify categories of calcium , phosphorus , and PTH levels associated with the lowest mortality risk . Current clinical practice guidelines are based largely on expert opinions , and clinical ly relevant differences exist among guidelines across countries . We sought to describe international trends in calcium , phosphorus , and PTH levels during 10 years and identify mortality risk categories in the Dialysis Outcomes and Practice Patterns Study ( DOPPS ) , an international study of hemodialysis practice s and associated outcomes . STUDY DESIGN Prospect i ve cohort study . PARTICIPANTS 25,588 patients with end-stage renal disease on hemodialysis therapy for longer than 180 days at 925 facilities in DOPPS I ( 1996 - 2001 ) , DOPPS II ( 2002 - 2004 ) , or DOPPS III ( 2005 - 2007 ) . PREDICTORS Serum calcium , albumin-corrected calcium ( Ca(Alb ) ) , phosphorus , and PTH levels . OUTCOMES Adjusted hazard ratios for all-cause and cardiovascular mortality calculated using Cox models . RESULTS Distributions of mineral metabolism markers differed across DOPPS countries and phases , with lower calcium and phosphorus levels observed in the most recent phase of DOPPS . Survival models identified categories with the lowest mortality risk for calcium ( 8.6 to 10.0 mg/dL ) , Ca(Alb ) ( 7.6 to 9.5 mg/dL ) , phosphorus ( 3.6 to 5.0 mg/dL ) , and PTH ( 101 to 300 pg/mL ) . The greatest risk of mortality was found for calcium or Ca(Alb ) levels greater than 10.0 mg/dL , phosphorus levels greater than 7.0 mg/dL , and PTH levels greater than 600 pg/mL and in patients with combinations of high-risk categories of calcium , phosphorus , and PTH . LIMITATIONS Because of the observational nature of DOPPS , this study can only indicate an association between mineral metabolism categories and mortality . CONCLUSIONS Our results provide important information about mineral metabolism trends in hemodialysis patients in 12 countries during a decade . The risk categories identified in the DOPPS cohort may be relevant to efforts at international harmonization of existing clinical guidelines for mineral metabolism Some propose using phosphate binders in the CKD population given the association between higher levels of phosphorus and mortality , but their safety and efficacy in this population are not well understood . Here , we aim ed to determine the effects of phosphate binders on parameters of mineral metabolism and vascular calcification among patients with moderate to advanced CKD . We r and omly assigned 148 patients with estimated GFR=20 - 45 ml/min per 1.73 m(2 ) to calcium acetate , lanthanum carbonate , sevelamer carbonate , or placebo . The primary endpoint was change in mean serum phosphorus from baseline to the average of months 3 , 6 , and 9 . Serum phosphorus decreased from a baseline mean of 4.2 mg/dl in both active and placebo arms to 3.9 mg/dl with active therapy and 4.1 mg/dl with placebo ( P=0.03 ) . Phosphate binders , but not placebo , decreased mean 24-hour urine phosphorus by 22 % . Median serum intact parathyroid hormone remained stable with active therapy and increased with placebo ( P=0.002 ) . Active therapy did not significantly affect plasma C-terminal fibroblast growth factor 23 levels . Active therapy did , however , significantly increase calcification of the coronary arteries and abdominal aorta ( coronary : median increases of 18.1 % versus 0.6 % , P=0.05 ; abdominal aorta : median increases of 15.4 % versus 3.4 % , P=0.03 ) . In conclusion , phosphate binders significantly lower serum and urinary phosphorus and attenuate progression of secondary hyperparathyroidism among patients with CKD who have normal or near-normal levels of serum phosphorus ; however , they also promote the progression of vascular calcification . The safety and efficacy of phosphate binders in CKD remain uncertain Elevated levels of serum alkaline phosphatase ( AlkPhos ) have been reported to be associated with increased mortality risk in hemodialysis ( HD ) patients . We examined the association of serum AlkPhos with all-cause mortality in our PD patients . The study enrolled 90 PD patients beginning in 1995 . On enrollment , demographics and clinical and biochemical data were recorded . Patients were followed to September 2011 . Mean age of the enrollees was 52 years , with 61 % being women , and most ( 81 % ) being of African descent . Mean and median AlkPhos were 135 U/L and 113 U/L respectively . Mean and maximum follow-up were 2.61 and 16 years respectively . As expected , AlkPhos correlated directly with serum intact parathyroid hormone ( r = 0.36 , p = 0.003 ) . In a Cox multivariate regression analysis with adjustment for confounding variables , AlkPhos as a continuous ( relative risk : 1.016 ; p = 0.004 ) and a categorical variable [ > 120 U/L and < or = 120 U/L ( relative risk : 6.0 ; p = 0.03 ) ] remained a significant independent predictor of mortality . For each unit increase in enrollment AlkPhos , there was a 1.6 % increase in the relative risk of death . Elevated serum AlkPhos is significantly and independently associated with increased mortality risk in our PD patients followed for up to 16 years . AlkPhos should be evaluated prospect ively as a potential therapeutic target in clinical practice BACKGROUND AND OBJECTIVES Dietary phosphorous overload and excessive calcium intake from calcium-containing phosphate binders promote coronary artery calcification ( CAC ) that may contribute to high mortality of dialysis patients . CAC has been found in patients in early stages of nondialysis-dependent CKD . In this population , no study has evaluated the potential role of phosphorus binders on mortality . This study aim ed to evaluate all-cause mortality as the primary end point in nondialysis-dependent CKD patients r and omized to different phosphate binders ; secondary end points were dialysis inception and the composite end point of all-cause mortality and dialysis inception . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS This is a r and omized , multicenter , nonblinded pilot study . Consecutive out patients ( n=212 ; stage 3 - 4 CKD ) were r and omized to either sevelamer ( n=107 ) or calcium carbonate ( n=105 ) . Phosphorus concentration was maintained between 2.7 and 4.6 mg/dl for patients with stage 3 - 4 CKD and between 3.5 and 5.5 mg/dl for patients with stage 5 CKD . The CAC score was assessed by computed tomography at study entry and after 6 , 12 , 18 , and 24 months . All-cause mortality , dialysis inception , and the composite end point were recorded for up to 36 months . RESULTS In patients r and omized to sevelamer , all-cause mortality and the composite end point were lower ; a nonsignificant trend was noted for dialysis inception . CONCLUSIONS Sevelamer provided benefits in all-cause mortality and in the composite end point of death or dialysis inception but not advantages in dialysis inception . Larger studies are needed to confirm these results Fractures are common in chronic kidney disease ( CKD ) . The optimal methods by which to assess fracture risk are unknown , in part , due to a lack of prospect i ve studies . We determined if bone mineral density ( BMD ) by dual-energy X-ray absorptiometry ( DXA ) , and /or high-resolution peripheral quantitative computed tomography ( HRpQCT ) could predict fractures in men and women ≥18 years old with stages 3 to 5 CKD . BMD was measured by DXA ( at the total hip , lumbar spine , ultradistal , and 1/3 radius ) and by HRpQCT ( at the radius ) , and subjects were followed for 2 years for incident morphometric spine fractures and low-trauma clinical fractures . The mean age of the subjects was 62 years with equal numbers having stages 3 , 4 , and 5 CKD . Over 2 years there were 51 fractures in 35 subjects . BMD by DXA at baseline was significantly lower at all sites among those with incident fractures versus those without . For example , the mean BMD at the total hip in those with incident fractures was 0.77 g/cm2 ( 95 % confidence interval [ CI ] , 0.73 to 0.80 ) and in those without fracture was 0.95 g/cm2 ( 95 % CI , 0.92 to 0.98 ) . Almost all baseline HRpQCT measures were lower in those with incident fracture versus those without . For example , volumetric BMD in those with incident fractures was 232 mg HA/cm3 ( 95 % CI , 213 to 251 ) and in those without fracture was 317.6 mg HA/cm3 ( 95 % CI , 306 to 329.1 ) . Bone loss occurred in all subjects , but was significantly greater among those with incident fractures . Our data demonstrate that low BMD ( by DXA and HRpQCT ) and a greater annualized percent decrease in BMD are risk factors for subsequent fracture in men and women with predialysis CKD BACKGROUND Vascular calcification contributes to cardiovascular disease in patients with chronic kidney disease ( CKD ) . Few studies have addressed interventions to decrease vascular calcification ; however , experimental studies report benefits of bisphosphonates . Recent studies of hemodialysis patients also suggest benefits of bisphosphonates on vascular calcification ; however , no study exists in nondialysis patients with CKD . STUDY DESIGN We conducted a r and omized controlled trial to determine the effect of bisphosphonates on vascular calcification in patients with CKD . SETTING & PARTICIPANTS 51 patients with CKD stages 3 - 4 were recruited from a hospital outpatient setting ; 50 were treated with study medication . INTERVENTIONS Patients were r and omly assigned to either alendronate , 70 mg ( n = 25 ) , or matching placebo ( n = 25 ) , administered weekly . OUTCOMES The primary outcome was change in aortic vascular calcification after 18 months . Secondary outcomes included superficial femoral artery vascular calcification , arterial compliance , bone mineral density ( BMD ) , renal function , and serum markers of mineral metabolism . MEASUREMENTS At baseline and 12 and 18 months , computed tomography , pulse wave velocity using SphygmoCor ( AtCor Medical , PWV Inc , www.atcormedical.com ) , and dual-energy x-ray absorptiometry were performed to measure vascular calcification , arterial compliance , and BMD , respectively . Analysis was by intention to treat , with a r and om-effect linear regression model to assess differences . RESULTS 46 patients completed the study ( 24 alendronate , 22 placebo ) ; baseline mean age was 63.1 + /- 1.8 years , estimated glomerular filtration rate was 34.5 + /- 1.4 mL/min/1.73 m(2 ) , 59 % had diabetes , and 65 % were men . 91 % had aortic vascular calcification at the start and 78 % showed progression . At 18 months , there was no difference in vascular calcification progression with alendronate compared with placebo ( adjusted difference , -24.2 Hounsfield units [ 95 % CI , -77.0 to 28.6 ] ; P = 0.4 ) . There was an increase in lumbar spine BMD ( T score difference , + 0.3 [ 95 % CI , 0.03 - 0.6 ] ; P = 0.04 ) and a trend toward better pulse wave velocity ( -1 m/s [ 95 % CI , -2.1 to 0.1 ] ; P = 0.07 ) with alendronate . Femoral BMD was similar between groups . There was a nonsignificant decrease in kidney function in patients on alendronate therapy compared with placebo ( -1.2 mL/min/1.73 m(2 ) [ 95 % CI , -4.0 to 1.7 ] ) . LIMITATIONS Small sample size and baseline differences , especially with aortic vascular calcification , may have diminished any potential difference between groups . CONCLUSIONS Unlike previous studies of hemodialysis patients , alendronate did not decrease the progression of vascular calcification compared with placebo in patients with CKD during 18 months BACKGROUND The existence of adynamic bone disease ( ABD ) as most prevalent form of renal osteodystrophy in recent years and its reduced ability to h and le an exogenous calcium load has implied a higher risk for vascular and soft-tissue calcifications . The effect of low dialysate calcium ( LCD ) on parathyroid hormone ( PTH ) secretion in ABD patients has not yet sufficiently been clarified . This r and omized , prospect i ve study aim ed to compare the effects of LCD and high calcium dialysate ( HCD ) on the evolution of bone and mineral parameters related to ABD in dialysis patients . METHODS 52 out of 60 patients with predialysis intact PTH<100 pg/ml completed this study and were equally distributed over LCD ( 1.25 mmol/l ) or HCD ( 1.75 mmol/l ) treatment . The duration of the study was 6 months and the only peroral phosphate binder administered was calcium carbonate . Total and ionised calcium were measured monthly in serum before and after dialysis while serum parameters relevant to bone were measured at the enrollment and at 3-month intervals . RESULTS There were no differences in predialysis mean phosphate or calcium x phosphorus product ( Ca x P ) . The most common side effects of both treatments were comparable . Hypotension occurred in 16 % and 17 % and cramps in 6 % and 8 % of the dialysis sessions , in the HCD and LCD group , respectively . The groups did not differ in the mean tCa before dialysis , but this parameter was significantly higher in the HCD group vs. LCD at the end of dialysis ( 2.59+/-0.18 vs. 2.44+/-0.19 mmol/l ; p<0.01 ) . The patients of the HCD group also had a significantly higher mean iCa both before ( 1.08+/-0.05 vs. 1.04+/-0.06 mmol/l ; p=0.02 ) and at the end of dialysis ( 1.18+/-0.04 vs. 1.48+/-0.04 mmol/l ; p<0.01 ) . There were no differences within the LCD group between baseline and end of dialysis treatment values of tCa and iCa . However , the mean tCa and iCa were markedly increased at the end of dialysis in the HDC group [ 2.40+/-0.21 vs. 2.59+/-0.18 mmol/l ( p<0.01 ) ; 1.08+/-0.05 vs. 1.18+/-0.04 mmol/l ( p<0.01 ) ] . Mean serum levels of iPTH and total alkaline phosphatase in the LCD group were increased at 3 months and at the end of the study compared with the baseline levels [ ( 38.6+/-22.9 vs. 63.3+/-46.0 vs. 78.6+/-44.7 pg/ml ) ; ( 59.5+/-18.7 vs. 75.9+/-26.7 vs. 84.0+/-35.4 U/l ) ] , respectively , and bone alkaline phosphatase increased also only after 6 months of treatment ( 23.4+/-7.3 U/l vs. 35.6+/-22.3 ) . The bone markers in the HCD group did not change . At the end of the study all bone parameters in the LCD group were significantly higher than in the HCD group . CONCLUSION There was an evolution towards parameters reflecting higher bone turnover in patients treated with dialysate calcium of 1.25 mmol/l , probably by prevention of a positive calcium balance and enabling sustained stimulation of PTH secretion . Hence , LCD might be considered a valuable therapeutic option for ABD patients |
1,898 | 26,792,993 | Antipsychotic treatment in patients with FEP produced high rates of remission in the year following treatment initiation , and untreated FEP reduced the odds of later achieving remission .
Maintenance therapy was more effective than treatment discontinuation or intermittent/guided discontinuation in preventing relapse .
Initiating antipsychotic treatment in patients with FEP also produced sustained cognitive improvement for up to 2 years .
CONCLUSION Treatment of patients with FEP is associated with benefits in the long-term outcomes of remission , relapse , and cognition . | BACKGROUND Treatment during first-episode psychosis ( FEP ) or early schizophrenia may affect the rates of relapse and remission , as well as cognitive functioning , over time .
Prolonged duration of psychosis is associated with a poor prognosis , but the effects of treatment in patients with FEP or early schizophrenia on the long-term outcomes are not well defined .
OBJECTIVE To underst and the long-term effects of treatment with antipsychotic agents on remission , relapse , and cognition in patients with FEP or early schizophrenia . | Genetic risk prediction has several potential applications in medical research and clinical practice and could be used , for example , to stratify a heterogeneous population of patients by their predicted genetic risk . However , for polygenic traits , such as psychiatric disorders , the accuracy of risk prediction is low . Here we use a multivariate linear mixed model and apply multi-trait genomic best linear unbiased prediction for genetic risk prediction . This method exploits correlations between disorders and simultaneously evaluates individual risk for each disorder . We show that the multivariate approach significantly increases the prediction accuracy for schizophrenia , bipolar disorder , and major depressive disorder in the discovery as well as in independent validation data sets . By grouping SNPs based on genome annotation and fitting multiple r and om effects , we show that the prediction accuracy could be further improved . The gain in prediction accuracy of the multivariate approach is equivalent to an increase in sample size of 34 % for schizophrenia , 68 % for bipolar disorder , and 76 % for major depressive disorders using single trait models . Because our approach can be readily applied to any number of GWAS data sets of correlated traits , it is a flexible and powerful tool to maximize prediction accuracy . With current sample size , risk predictors are not useful in a clinical setting but already are a valuable research tool , for example in experimental design s comparing cases with high and low polygenic risk BACKGROUND Cognitive impairment in schizophrenia-spectrum disorders is highly prevalent and notably influences functional outcomes . AIMS To characterise the cognitive effectiveness of second-generation antipsychotic drugs . METHOD One hundred consecutive and previously unmedicated patients with first-episode schizophrenia-spectrum disorders were admitted . Seventy-seven completed baseline , 1-month and 6-month psychopathological and neuropsychological assessment s. Patients were r and omised to risperidone or olanzapine treatment . Four final treatment allocation groups were defined since patients continued treatment in their normal setting : risperidone , olanzapine , mixed and no-antipsychotic groups . RESULTS There were no differences in cognitive effectiveness between the four treatment groups . Reliable change index methods demonstrated that nearly a half of patients showed an improvement in Global Cognitive Score at the 6-month assessment . Improvement on the neuropsychological tests ranged from 17 to 54 % . A strong predictor of cognitive response was poor performance on baseline neuropsychological tests ; response was moderately influenced by a low premorbid scholastic performance and IQ . CONCLUSIONS Cognitive improvement related to second-generation antipsychotic drugs appeared within the first 4 weeks of treatment and persisted at 6 months irrespective of treatment group . Greater cognitive dysfunction at baseline and lower premorbid cognitive background predicted cognitive improvement in our sample BACKGROUND The purpose of this investigation was to test the efficacy of novel antipsychotic medications in the treatment of cognitive impairment in early phase schizophrenia . METHODS Sixty-five patients in this multicenter double-blind study were r and omly assigned to olanzapine ( 5 - 20 mg ) , risperidone ( 4 - 10 mg ) , or haloperidol ( 5 - 20 mg ) . St and ard measures of clinical and motor syndromes were administered , as well as a comprehensive battery of tests to assess ( 1 ) motor skills , ( 2 ) attention span , ( 3 ) verbal fluency and reasoning , ( 4 ) nonverbal fluency and construction , ( 5 ) executive skills , and ( 6 ) immediate recall at baseline and after 6 , 30 , and 54 weeks of treatment . RESULTS The general cognitive index derived from the 6 domain scores revealed a significantly greater benefit from treatment with olanzapine relative to haloperidol and olanzapine relative to risperidone , but no significant difference was shown between risperidone and haloperidol . The improvement related to olanzapine was apparent after 6 weeks and enhanced after 30 and 54 weeks of treatment . Exploratory within-group analyses of the 6 cognitive domains after a conservative Bonferroni adjustment revealed a significant improvement with olanzapine only on the immediate recall domain , and similar analyses of the 17 individual tests revealed a significant improvement with olanzapine only on the Hooper Visual Organization Test . CONCLUSIONS These data suggest that olanzapine has some superior cognitive benefits relative to haloperidol and risperidone . A larger sample replication study is necessary to confirm and generalize the observations of this study and begin evaluation of the implication s of this change to cerebral function and quality of life for people with schizophrenia The study investigated the non-inferiority of flupentixol compared to risperidone in the treatment of negative symptoms . In addition , the effects of flupentixol on mood and cognitive symptoms were explored . In a r and omized , double-blind multicenter study , 144 non-acute schizophrenia patients with predominant negative symptoms were treated with a flexible dose of either flupentixol ( 4 - 12 mg/d ) or risperidone ( 2 - 6 mg/d ) for up to 25 weeks . In addition to a non-inferiority analysis , a principal component analysis ( PCA ) of the PANSS was performed post hoc . Regarding negative symptoms , flupentixol proved to be non-inferior to risperidone . Both drugs improved depressed mood with effect sizes favoring flupentixol . PCA suggested a five-factor structure . Effect sizes for the cognitive factor were up to 0.74 for flupentixol and up to 0.80 for risperidone . EPS scores were rather low and Parkinsonism improved in both groups , but anticholinergic drugs were prescribed significantly more frequently in the flupentixol group , which generally showed significantly more adverse events . Results indicate that the 1st generation antipsychotic flupentixol improves negative , affective and cognitive symptoms in chronic schizophrenia comparable to risperidone . Further studies should confirm the latter using neuropsychological performance tests and should investigate whether tolerability improves with a markedly lower dose range OBJECTIVE Newer antipsychotic drugs have shown promise in ameliorating neurocognitive deficits in patients with schizophrenia , but few studies have compared newer antipsychotic drugs with both clozapine and conventional agents , particularly in patients who have had suboptimal response to prior treatments . METHOD The authors examined the effects of clozapine , olanzapine , risperidone , and haloperidol on 16 measures of neurocognitive functioning in a double-blind , 14-week trial involving 101 patients . A global score was computed along with scores in four neurocognitive domains : memory , attention , motor function , and general executive and perceptual organization . RESULTS Global neurocognitive function improved with olanzapine and risperidone treatment , and these improvements were superior to those seen with haloperidol . Patients treated with olanzapine exhibited improvement in the general and attention domains but not more than that observed with other treatments . Patients treated with risperidone exhibited improvement in memory that was superior to that of both clozapine and haloperidol . Clozapine yielded improvement in motor function but not more than in other groups . Average effect sizes for change were in the small to medium range . More than half of the patients treated with olanzapine and risperidone experienced " clinical ly significant " improvement ( changes in score of at least one-half st and ard deviation relative to baseline ) . These findings did not appear to be mediated by changes in symptoms , side effects , or blood levels of medications . CONCLUSIONS Patients with a history of suboptimal response to conventional treatments may show cognitive benefits from newer antipsychotic drugs , and there may be differences between atypical antipsychotic drugs in their patterns of cognitive effects OBJECTIVE To investigate the neurocognitive effectiveness of haloperidol , risperidone , and olanzapine in first-episode schizophrenia-spectrum disorders . METHOD This prospect i ve , r and omized , open-label study was conducted from February 2001 to February 2005 . Data for the present investigation were obtained from a large epidemiologic and 3-year longitudinal intervention program of first-episode psychosis ( DSM-IV criteria ) conducted at the outpatient clinic and the inpatient unit at the University Hospital Marques de Valdecilla , Sant and er , Spain . One hundred four patients r and omly assigned to haloperidol ( N = 35 ) , olanzapine ( N = 30 ) , or risperidone ( N = 39 ) who completed clinical and cognitive evaluations at baseline , 6 months , and 1 year were included in the final analysis . Thirty-seven healthy individuals were also longitudinally assessed . A neuropsychological battery that comprised 9 cognitive domains was used . The contribution of clinical changes , concomitant medications , and the severity of motor side effects to cognitive changes was controlled . The main outcome measure was cognitive changes at 1-year follow-up . RESULTS The 3 treatment groups showed a significant improvement in cognitive scores after 1 year . The differential cognitive effectiveness between antipsychotics was insignificant . The magnitude of cognitive changes was similar in the 3 treatment groups and controls , although a greater improvement on the Finger Tapping Test , Trail Making Test B , and Rey Complex Figure Test was found in the treatment groups . Clinical changes , use of concomitant medications , and the emergence of motor side effects did not significantly account for cognitive changes over time . CONCLUSION Haloperidol , olanzapine , and risperidone were equally effective in treating cognitive deficits of psychosis . The effect of practice clearly contributes to cognitive score improvements after treatment with antipsychotics . Our results provide important information regarding the practical utility of antipsychotic treatments to improve cognition and could have implication s for developing novel approaches for cognitive pharmacotherapy in schizophrenia OBJECTIVE The authors sought to compare the effects of olanzapine , quetiapine , and risperidone on neurocognitive function in patients with early psychosis . METHOD In a 52-week double-blind , multicenter study , 400 patients early in the course of psychotic illness ( < 5 years ) were r and omly assigned to treatment with olanzapine ( 2.5 - 20 mg/day ) , quetiapine ( 100 - 800 mg/day ) , or risperidone ( 0.5 - 4 mg/day ) . The mean modal daily dose was 11.7 mg ( SD=5.3 ) for olanzapine , 506 mg ( SD=215 ) for quetiapine , and 2.4 mg ( SD=1.0 ) for risperidone . A total of 224 patients completed neurocognitive assessment s at baseline and at 12 weeks , and 81 patients also completed them at 52 weeks . Neurocognitive composite scores were calculated from the neurocognitive battery used in the Clinical Antipsychotic Trials of Intervention Effectiveness ( CATIE ) and from the Brief Assessment of Cognition in Schizophrenia . RESULTS At week 12 , there was significant improvement in neurocognition for each treatment ( p<0.01 ) , but no significant overall difference between treatments . Composite z score improvements on the CATIE neurocognitive battery were 0.17 for olanzapine , 0.33 for quetiapine , and 0.32 for risperidone . Composite z score improvements on the Brief Assessment of Cognition in Schizophrenia were 0.19 for olanzapine , 0.34 for quetiapine , and 0.22 for risperidone . Statistically significant relationships between improvements in neurocognition and functional outcome were observed at weeks 12 and 52 . CONCLUSIONS Olanzapine , quetiapine , and risperidone all produced significant improvements in neurocognition in early-psychosis patients . Although cognitive improvements were modest , their clinical importance was suggested by relationships with improvements in functional outcome OBJECTIVE To compare the consequences of a guided discontinuation strategy and maintenance treatment in remitted first-episode psychosis in terms of relapse rates and functional outcome . METHOD The study was conducted in 7 mental health care organizations and the Department of Psychiatry of the University Medical Center Groningen in The Netherl and s , covering a catchment area of 3.1 million inhabitants . A sample of 131 remitted first-episode patients , aged 18 to 45 years , with a DSM-IV diagnosis of schizophrenia or related psychotic disorder was included ( i.e. , all patients with a first psychotic episode from October 2001 through December 2002 who were willing to participate ) . After 6 months of positive symptom remission , they were r and omly and openly assigned to the discontinuation strategy or maintenance treatment . Maintenance treatment was carried out according to American Psychiatric Association guidelines , preferably using low-dose atypical antipsychotics . The discontinuation strategy was carried out by gradual symptom-guided tapering of dosage and discontinuation if feasible . Follow-up was 18 months . Main outcome measures were relapse rates and social and vocational functioning . RESULTS Twice as many relapses occurred with the discontinuation strategy ( 43 % vs. 21 % , p = .011 ) . Of patients who received the strategy , approximately 20 % were successfully discontinued . Recurrent symptoms caused another approximately 30 % to restart antipsychotic treatment , while in the remaining patients discontinuation was not feasible at all . There were no advantages of the discontinuation strategy regarding functional outcome . CONCLUSIONS Only a limited number of patients can be successfully discontinued . High relapse rates do not allow a discontinuation strategy to be universal practice . However , if relapse risk can be carefully managed by close monitoring , in some remitted first-episode patients a guided discontinuation strategy may offer a feasible alternative to maintenance treatment . Further research is needed to find predictors of successful discontinuation Impact of dose reduction of atypical antipsychotics on cognitive function has not been investigated in stable patients with schizophrenia . In this open-label , 28-week , r and omized controlled trial , stable patients with schizophrenia treated with risperidone or olanzapine were r and omly assigned to the reduction group ( dose reduced by 50 % in 4 weeks and then maintained ) or maintenance group ( dose kept constant ) . Assessment s at baseline and week 28 included the Repeatable Battery for the Assessment of Neuropsychological Status ( RBANS ) , Positive and Negative Syndrome Scale ( PANSS ) , and Drug-Induced Extrapyramidal Symptoms Scale ( DIEPSS ) . Sixty-one patients were enrolled ; 2 of 31 ( 6.5 % ) and 5 of 30 ( 16.7 % ) patients prematurely withdrew from the study in the reduction and maintenance groups , respectively . While no significant differences in change in the PANSS total score were observed between the 2 groups , the reduction group showed significantly greater improvements in the RBANS and DIEPSS total scores compared with the maintenance group ( mean ± SD , + 7.0±7.1 vs -0.1±8.0 , P < .001 ; -0.9±1.7 vs + 0.1±1.2 , P = .010 , respectively ) . This 6-month pilot study suggests that risperidone or olanzapine dose reduction of 50 % can improve cognitive function for stable patients with schizophrenia . Due to the open-label design , small sample size , and short study duration , however , there is a need to confirm the finding through double-blind , larger scale trials with longer follow-up periods . Moreover , potential risks of relapse following antipsychotic dose reduction should be thoroughly investigated in longer term studies Social cognition has received increased attention in schizophrenia research because it is associated with functional outcomes . Psychosocial interventions are being developed to enhance social cognition , however less attention has been paid to the association between antipsychotic medication use and social cognition . This study evaluated whether individuals treated with olanzapine ( n=117 ) or quetiapine ( n=106 ) achieved improvements in social cognition . Participants were drawn from a larger 6-month , multi-site , r and omized , double-blind clinical trial . Social cognition was assessed using signal detection analysis of performance on the Social Cue Recognition Test . Social functioning was measured with an interpersonal functioning index and a broader quality of life measure . Results revealed that participants in both medication groups improved significantly but modestly on three out of four social cognition subscales . The small observed effect in this trial is generally consistent with previous studies , and supports the need for ongoing research into the biological mechanisms of social cognitive dysfunction in schizophrenia BACKGROUND Aripiprazole is a novel antipsychotic for the management of schizophrenia . This study investigated the efficacy , safety , and tolerability of aripiprazole in preventing relapse in adult chronic schizophrenia patients experiencing ongoing stable symptomatology . METHOD In this 26-week , r and omized , double-blind , placebo-controlled , parallel-group , multi-center study , 310 patients with DSM-IV schizophrenia ( mean Positive and Negative Syndrome Scale [ PANSS ] total score = 82 ) were r and omly assigned to receive a once-daily fixed dose of aripiprazole , 15 mg , or placebo . The primary outcome measure was time to relapse following r and omization . Secondary objectives were to assess the efficacy , safety , and tolerability of aripiprazole , 15 mg , compared with placebo , in the study population . The study was conducted between Dec. 21 , 2000 , and Aug. 20 , 2001 . RESULTS The time to relapse following r and omization was significantly ( p < .001 ) longer for aripiprazole compared with placebo . More patients relapsed with placebo ( N = 85 ; 57 % ) than aripiprazole ( N = 50 ; 34 % ) ; the relative risk of relapse for the aripiprazole group was 0.59 ( p < .001 ) . Aripiprazole was significantly superior to placebo from baseline to endpoint in PANSS total , PANSS positive , PANSS-derived Brief Psychiatric Rating Scale , and Clinical Global Impressions-Severity of Illness scale ( CGI-S ) scores and demonstrated significantly better mean Clinical Global Impressions-Global Improvement scale scores ( p < or = .01 for all comparisons except CGI-S : .01 < p < or = .05 ) . Aripiprazole was well tolerated , with no evidence of marked sedation and no evidence of hyperprolactinemia or prolonged heart rate-corrected QT interval ( QTc ) . Extrapyramidal symptoms were comparable in the aripiprazole and placebo groups . Modest mean weight loss at endpoint was evident in both groups . CONCLUSION Aripiprazole , 15 mg once daily , is an effective , well-tolerated treatment for prevention of relapse in patients with chronic , stable schizophrenia The purported advantages of second-generation or ‘ atypical ’ antipsychotics relative to first-generation antipsychotics have not been examined in patients with a first episode of schizophrenia . This flexible-dose study examined efficacy and safety in a r and omized , double-blind , 52-week trial , comparing chlorpromazine ( CPZ ) and clozapine ( CLZ ) in treatment naive patients experiencing their first episode of schizophrenia . In all , 160 in patients with first-episode schizophrenia or schizophreniform disorder were r and omized to CPZ or CLZ and followed them for 52 weeks or until dropout . The primary efficacy measure was time to first remission and proportion of time remaining in remission . The analysis was supplemented by comparisons on a profile of clinical symptoms and side effects . Of these first-episode patients , 80 % achieved remission within 1 year ( 79 % CPZ , 81 % CLZ ) . The Kaplan – Meier estimated median time to first remission was 8 weeks for CLZ vs 12 weeks for CPZ ( χ2(1)=5.56 , p=0.02 ) . Both the rate of first achieving remission and the odds for being in remission during the trial were almost doubled for the CLZ group in comparison with the CPZ group . At 12 weeks , CLZ was superior on many rating scale measures of symptom severity while CPZ was not superior on any . These symptom differences remained significant when controlling for EPS differences . By 52 weeks many of the symptom differences between groups were no longer significantly different . Generally , CLZ produced fewer side effects than CPZ , particularly extrapyramidal side effects . There was no significant difference between treatments in weight change or glucose metabolism . For each prior year of untreated psychosis , there was a 15 % decrease in the odds of achieving remission ( OR=0.85 ; CI 0.75–0.95 ) . A high proportion of first-episode patients remitted within 1 year . We detected no difference in the proportion of first-episode patients receiving CLZ or CPZ that achieved remission . However , first-episode patients receiving CLZ remitted significantly faster and remained in remission longer than subjects receiving CPZ . While the CLZ group showed significantly less symptomatology on some measures and fewer side effects at 12 weeks , the two treatment groups seemed to converge by 1 year . Longer duration of untreated psychosis was associated with lower odds of achieving remission OBJECTIVE Data on the effectiveness of antipsychotics in the early phase of schizophrenia are limited . The authors examined the risk of rehospitalization and drug discontinuation in a nationwide cohort of 2,588 consecutive patients hospitalized for the first time with a diagnosis of schizophrenia between 2000 and 2007 in Finl and . METHOD The authors linked national data bases of hospitalization , mortality , and antipsychotic prescriptions and computed hazard ratios , adjusting for the effects of sociodemographic and clinical variables , the temporal sequence of the antipsychotics used , and the choice of the initial antipsychotic for each patient . RESULTS Of 2,588 patients , 1,507 ( 58.2 % ) collected a prescription for an antipsychotic during the first 30 days after hospital discharge , and 1,182 ( 45.7 % , 95 % confidence interval [CI]=43.7 - 47.6 ) continued their initial treatment for 30 days or longer . In a pairwise comparison between depot injections and their equivalent oral formulations , the risk of rehospitalization for patients receiving depot medications was about one-third of that for patients receiving oral medications ( adjusted hazard ratio=0.36 , 95 % CI=0.17 - 0.75 ) . Compared with oral risperidone , clozapine ( adjusted hazard ratio=0.48 , 95 % CI=0.31 - 0.76 ) and olanzapine ( adjusted hazard ratio=0.54 , 95 % CI=0.40 - 0.73 ) were each associated with a significantly lower rehospitalization risk . Use of any antipsychotic compared with no antipsychotic was associated with lower mortality ( adjusted hazard ratio=0.45 , 95 % CI=0.31 - 0.67 ) . CONCLUSIONS In Finl and , only a minority of patients adhere to their initial antipsychotic during the first 60 days after discharge from their first hospitalization for schizophrenia . Use of depot antipsychotics was associated with a significantly lower risk of rehospitalization than use of oral formulations of the same compounds . Among oral antipsychotics , clozapine and olanzapine were associated with more favorable outcomes . Use of any antipsychotic was associated with lower mortality Aripiprazole is a novel atypical antipsychotic for the treatment of schizophrenia . It is a D2 receptor partial agonist with partial agonist activity at 5-HT1A receptors and antagonist activity at 5-HT2A receptors . The long-term efficacy and safety of aripiprazole ( 30 mg/d ) relative to haloperidol ( 10 mg/d ) were investigated in two 52-wk , r and omized , double-blind , multicentre studies ( using similar protocol s which were prospect ively identified to be pooled for analysis ) in 1294 patients in acute relapse with a diagnosis of chronic schizophrenia and who had previously responded to antipsychotic medications . Aripiprazole demonstrated long-term efficacy that was comparable or superior to haloperidol across all symptoms measures , including significantly greater improvements for PANSS negative subscale scores and MADRS total score ( p<0.05 ) . The time to discontinuation for any reason was significantly greater with aripiprazole than with haloperidol ( p=0.0001 ) . Time to discontinuation due to adverse events or lack of efficacy was significantly greater with aripiprazole than with haloperidol ( p=0.0001 ) . Aripiprazole was associated with significantly lower scores on all extrapyramidal symptoms assessment s than haloperidol ( p<0.001 ) . In summary , aripiprazole demonstrated efficacy equivalent or superior to haloperidol with associated benefits for safety and tolerability . Aripiprazole represents a promising new option for the long-term treatment of schizophrenia OBJECTIVE The goal of this report was to examine the clinical course following neuroleptic discontinuation of patients with recent-onset schizophrenia who had been receiving maintenance antipsychotic treatment for at least 1 year . METHOD Fifty-three volunteer patients with recent-onset schizophrenia who had been clinical ly stabilized on a maintenance regimen of fluphenazine decanoate for a mean of 16.7 months had their antipsychotic medications withdrawn under clinical supervision . Participants initially entered a 24-week , double-blind crossover trial in which fluphenazine and placebo were administered for 12 weeks each . For those who did not experience symptom exacerbation or relapse during this period , fluphenazine was openly withdrawn ; participants were then followed for up to 18 additional months . RESULTS When a low threshold for defining symptom reemergence was used , 78 % ( N=39 of 50 ) of the patients experienced an exacerbation or relapse within 1 year ; 96 % ( N=48 of 50 ) did so within 2 years . Mean time to exacerbation or relapse was 235 days . When hospitalization was used as a relapse criterion , only six of 45 of individuals ( 13 % ) experiencing an exacerbation or relapse who continued in treatment in the clinic were hospitalized , demonstrating the sensitivity of the psychotic exacerbation criterion . CONCLUSIONS The vast majority of clinical ly stable individuals with recent-onset schizophrenia will experience an exacerbation or relapse after antipsychotic discontinuation , even after more than a year of maintenance medication . However , clinical monitoring and a low threshold for reinstating medications can prevent hospitalization for the majority of these patients BACKGROUND Neurocognitive deficits are severe in first-episode psychosis . METHODS Patients ( N = 263 ) with first-episode psychosis ( schizophrenia , schizoaffective , or schizophreniform disorders ) were r and omly assigned to double-blind treatment with olanzapine ( mean 11.30 mg/day ) or haloperidol ( mean 4.87 mg/day ) for 104 weeks . A neurocognitive battery was administered at baseline ( n = 246 ) and 12 ( n = 167 ) , 24 ( n = 126 ) , 52 ( n = 89 ) , and 104 ( n = 46 ) weeks during treatment . Weighted principal component and unweighted composite scores were derived from individual tests . RESULTS Both treatment groups demonstrated significant improvement on both composite scores . On the basis of the weighted composite score , olanzapine had greater improvement than haloperidol only at 12 ( p = .014 ) and 24 ( p = .029 ) weeks . For the unweighted composite , olanzapine had significantly better improvement compared with haloperidol only at week 12 ( p = .044 ) . At week 12 only , olanzapine improved performance on the Digit Symbol and Continuous Performance Test significantly more than haloperidol . CONCLUSIONS Both antipsychotic agents appeared to improve neurocognitive functioning among first-episode psychosis patients with schizophrenia . A significantly greater benefit in terms of neurocognitive improvement was found with olanzapine than with haloperidol at weeks 12 and 24 OBJECTIVE Cognitive impairment , manifested as mild to moderate deviations from psychometric norms , is present in many but not all schizophrenia patients . The purpose of the present study was to compare the effect of haloperidol with that of second-generation antipsychotic drugs on the cognitive performance of patients with schizophreniform disorder or first-episode schizophrenia . METHODS Subjects were 498 patients with schizophreniform disorder or first-episode schizophrenia who were r and omly assigned to open-label haloperidol ( 1 to 4 mg/day [ N=103 ] ) , amisulpride ( 200 to 800 mg/day [ N=104 ] ) , olanzapine ( 5 to 20 mg/day [ N=105 ] ) , quetiapine ( 200 to 750 mg/day [ N=104 ] ) , or ziprasidone ( 40 to 160 mg/day [ N=82 ] ) . The Rey Auditory Verbal Learning Test , Trail Making Test Part A and Part B , WAIS Digit Symbol Test , and Purdue Pegboard Test were administered at baseline and the 6-month follow-up evaluation . RESULTS Compared with scores at baseline , composite cognitive test scores improved for all five treatment groups at the 6-month follow-up evaluation . However , there were no overall differences among the treatment groups . In addition , there was a weak correlation between the degree of cognitive improvement and changes in Positive and Negative Syndrome Scale scores . CONCLUSION Treatment with antipsychotic medication is associated with moderate improvement in the cognitive test performance of patients who have schizophreniform disorder or who are in their first episode of schizophrenia . The magnitude of improvement does not differ between treatment with haloperidol and treatment with second-generation antipsychotics . Moreover , cognitive improvement is weakly related to symptom change Recently proposed criteria for remission by a ‘ Remission in Schizophrenia Working Group ’ have generated considerable interest . We assessed rates , predictors , and correlates of remission in a sample of patients with first-episode schizophrenia treated with injectable , long-acting risperidone . This allowed us to examine remission among patients known to be receiving medication . This was a single-site open-label study in which 50 newly diagnosed cases of schizophreniform disorder or schizophrenia aged 16 to 43 years were treated with injectable , long-acting risperidone 25–50 mg every 2 weeks for 2 years . Remission , according to Remission in Schizophrenia Working Group criteria , was achieved in 64 % of the patients . Of those achieving remission , 97 % maintained this status until study completion . Remission was associated with greater improvements in other symptom domains , insight , and social and occupational functioning . Patients in remission received lower doses of antipsychotic medication , had fewer extrapyramidal symptoms , and a more favorable attitude toward medication . The results of this open-label study suggest that a majority of first-episode patients who receive long-acting injectable antipsychotic medication may achieve sustained remission . Double-blind-controlled studies using long-acting injectable antipsychotics in early psychosis are warranted to further test this OBJECTIVE The first episode of psychotic illness is a key intervention point . The initial experience with medication can affect willingness to accept treatment . Further , relapse prevention is a treatment cornerstone during the first years of illness because active psychotic illness may affect lifetime outcomes . Thus , initial treatment of active symptoms and subsequent relapse prevention are central goals of pharmacotherapy . This study compared long-term effectiveness of risperidone versus haloperidol in first-episode psychosis patients . METHOD First-episode psychosis patients ( N=555 , mean age=25.4 years ) participated in a double-blind , r and omized , controlled flexible-dose trial that compared risperidone ( mean modal dose=3.3 mg ) and haloperidol ( mean modal dose=2.9 mg ) . The median treatment length was 206 days ( maximum=1,514 ) . RESULTS Positive and Negative Syndrome Scale scores and Clinical Global Impression ratings improved significantly relative to baseline , with no significant differences between groups . Three-quarters of the patients achieved initial clinical improvement , defined as > 20 % reduction in total Positive and Negative Syndrome Scale score . However , among those who achieved clinical improvement , 42 % of the risperidone group experienced a relapse compared with 55 % of the haloperidol group . The median time to relapse was 466 days for risperidone-treated subjects and 205 days for those given haloperidol . These differences were statistically significant based on Kaplan-Meier survival analysis . Adverse effects distinguished the treatments : there were significantly more extrapyramidal signs and symptoms and adjunctive medication use in the haloperidol group and greater prolactin elevation in the risperidone group . There was less weight gain with haloperidol initially but no significant differences between groups at endpoint . CONCLUSIONS Relatively low doses of antipsychotic drugs lead to significant symptom amelioration in the majority of first-episode psychosis patients . In the long term , risperidone prevents relapse in more patients and for a longer time and also induces less abnormal movements than haloperidol Objective To study rates of relapse in remitted patients with first episode psychosis who either continued or discontinued antipsychotic drugs after at least one year of maintenance treatment . Design 12 month r and omised , double blind , placebo controlled trial . Setting Early psychosis outpatient clinics in Hong Kong . Participants 178 patients with first episode psychosis who had received at least one year of antipsychotic drug treatment between September 2003 and July 2006 and had no positive symptoms of psychosis . Interventions Patients received either maintenance treatment with quetiapine ( 400 mg/day ) or placebo and were followed up for the next 12 months or until a relapse occurred . Main outcome measure Relapse assessed monthly and defined as re-emergence of psychotic symptoms ( delusions , conceptual disorganisation , hallucinations , suspiciousness , and unusual thought content ) according to predefined thresholds . Results 178 patients were r and omised ( 89 to quetiapine and 89 to placebo ) . The Kaplan-Meier estimate of the risk of relapse at 12 months was 41 % ( 95 % confidence interval 29 % to 53 % ) for the quetiapine group and 79 % ( 68 % to 90 % ) for the placebo group ( P<0.001 ) . Although quetiapine was generally well tolerated , the rate of discontinuation due to adverse or serious adverse events was greater in the quetiapine group ( 18 % ; 16/89 ) than in the placebo group ( 8 % ; 7/89 ) ( relative risk 2.29 , 95 % confidence interval 0.99 to 5.28 ; χ2=3.20 , df=1 ; P=0.07 ) . Conclusion In a group of asymptomatic patients with first episode psychosis and at least one year of previous antipsychotic drug treatment , maintenance treatment with quetiapine compared with placebo result ed in a substantially lower rate of relapse during the following year . Trial registration Clinical trials NCT00334035 |
1,899 | 27,301,957 | Discussion This systematic review will identify the available evidence on the effectiveness of cell therapies in patients with CLD and in ACLF subgroup . | Background Chronic liver disease ( CLD ) is a major health burden worldwide .
Liver cirrhosis , a form of CLD is the fifth most common cause of death in the UK .
Acute-on-chronic liver failure ( ACLF ) is the result of an acute insult superimposed on patients with liver cirrhosis as a result of precipitating events such as infection or bleeding .
ACLF has a high associated mortality as a result of multi-organ failure .
The only effective treatment for CLD is liver transplantation , but the treatment is limited by shortage of donor organs .
As a result , alternative treatments such as cell therapies have been studied in patients with liver diseases .
This study will systematic ally review the evidence on clinical effectiveness of cell therapies in patients . | We here report nine liver cirrhosis ( LC ) patients that underwent autologous bone marrow cell infusion ( A BMI ) from the peripheral vein . Subjects were patients with LC with total bilirubin of less than 3.0 mg/dl , platelet count of more than 5 ( 10(10)/l ) , and no viable hepatocellular carcinoma on diagnostic imaging . Autologous bone marrow ( BM ; 400 ml ) was isolated from the ilium under general anesthesia . Mononuclear cells ( MNCs ) were separated by cell washing and were infused via the peripheral vein . MNC characteristics were confirmed by fluorescence-activated cell sorting analysis ( CD34 , CD45 , and c-kit ) . After A BMI therapy , liver function was monitored by blood examination for 24 weeks . From 400 ml of BM , we obtained 7.81 + /- 0.98 x 10(9 ) MNCs . After washing , 5.20 + /- 0.63 x 10(9 ) MNCs were infused into patients with LC . Significant improvements in serum albumin levels and total protein were observed at 24 weeks after A BMI therapy ( p < .05 ) . Significantly improved Child-Pugh scores were seen at 4 and 24 weeks ( p < .05 ) . alpha-Fetoprotein and proliferating cell nuclear antigen ( PCNA ) expression in liver biopsy tissue was significantly elevated after A BMI therapy ( p < .05 ) . No major adverse effects were noted . In conclusion , A BMI therapy should be considered as a novel treatment for patients with decompensated LC OBJECTIVES : Severe alcoholic hepatitis has high short-term mortality . The aim of this study was to test the hypothesis that treatment of patients with alcoholic hepatitis with granulocyte colony-stimulating factor ( G-CSF ) might mobilize bone marrow – derived stem cells and promote hepatic regeneration and thus improve survival . METHODS : Forty-six patients with severe alcoholic hepatitis were prospect ively r and omized in an open study to st and ard medical therapy ( SMT ) plus G-CSF ( group A ; n=23 ) at a dose of 5 μg/kg subcutaneously every 12 h for 5 consecutive days or to SMT alone ( group B ; n=23 ) at a tertiary care center . We assessed the mobilization of CD34 + cells on day 6 , Child-Turcotte-Pugh ( CTP ) , model for end-stage liver disease ( MELD ) , and modified Maddrey ’s discriminant function ( mDF ) scores , and survival until day 90 . RESULTS : There was a statistically significant increase in the number of CD34 + cells in peripheral blood in group A as compared with group B ( P=0.019 ) after 5 days of G-GSF therapy . There was a significant reduction in median Δ change% in CTP , MELD , and mDF at 1 , 2 , and 3 months in group A as compared with group B ( P<0.05 ) . There was marked improvement in survival in group A as compared with group B ( 78.3 % vs. 30.4 % ; P=0.001 ) at 90 days . CONCLUSIONS : G-CSF is safe and effective in the mobilization of hematopoietic stem cells and improves liver function as well as survival in patients with severe alcoholic hepatitis BACKGROUND Cirrhosis , the end stage of progressive hepatic fibrosis , is characterized by distortion of the hepatic architecture and the formation of regenerative nodules . Liver transplantation is one of the few available therapies for such patients . However , due to a severe shortage of organ donors , surgical complications , transplant rejection and the high cost of this procedure much interest has focused on research to find new treatment modalities for this disease . There is accumulating evidence for the contribution of bone marrow stem cells to participate in liver regeneration . METHODS Here we report on six patients with end stage liver disease who were subjected to intraportal administration of autologous bone marrow-derived CD133(+ ) in comparison to mononuclear cells in short-term ( 6 months ) and long-term ( 24 months ) follow up . RESULTS There were no adverse effects in any of the patients during the short- and long-term follow up period . Moreover , there were no significant alterations of liver function parameters , liver enzymes , serum albumin , creatinine , serum bilirubin and /or liver volume after transplantation of both types of autologous cells in these patients . CONCLUSION Our study has shown both the safety and feasibility of this type of liver cell therapy and may be a bridge to liver transplantation . The trial was registered with NIH clinical trials ( www . clinical trials.gov ) as identifier : NCT00713934 OBJECTIVES : Recent advances in regenerative medicine , including hematopoietic stem cell ( HSC ) transplantation , have brought hope for patients with severe alcoholic liver cirrhosis ( ALC ) . The aim of this study was to assess the safety and efficacy of administering autologous exp and ed mobilized adult progenitor CD34 + cells into the hepatic artery of ALC patients and the potential improvement in the liver function . METHODS : Nine patients with biopsy-proven ALC , who had abstained from alcohol for at least 6 months , were recruited into the study . Following granulocyte colony-stimulating factor ( G-CSF ) mobilization and leukapheresis , the autologous CD34 + cells were exp and ed in vitro and injected into the hepatic artery . All patients were monitored for side effects , toxicities , and changes in the clinical , hematological , and biochemical parameters . RESULTS : On average , a five-fold expansion in cell number was achieved in vitro , with a mean total nucleated cell count ( TNCC ) of 2.3 × 108 pre infusion . All patients tolerated the procedure well , and there were no treatment-related side effects or toxicities observed . There were significant decreases in serum bilirubin ( P < 0.05 ) 4 , 8 , and 12 wk post infusion . The levels of alanine transaminase ( ALT ) and aspartate transaminase ( AST ) showed improvement through the study period and were significant ( P < 0.05 ) 1 wk post infusion . The Child-Pugh score improved in 7 out of 9 patients , while 5 patients had improvement in ascites on imaging . CONCLUSION : It is safe to mobilize , exp and , and reinfuse autologous CD34 + cells in patients with ALC . The clinical and biochemical improvement in the study group is encouraging and warrants further clinical trials AIM To assess the utility of an autologous CD34(+ ) and CD133(+ ) stem cells infusion as a possible therapeutic modality in patients with end-stage liver diseases . METHODS One hundred and forty patients with end-stage liver diseases were r and omized into two groups . Group 1 , comprising 90 patients , received granulocyte colony stimulating factor for five days followed by autologous CD34(+ ) and CD133(+ ) stem cell infusion in the portal vein . Group 2 , comprising 50 patients , received regular liver treatment only and served as a control group . RESULTS Near normalization of liver enzymes and improvement in synthetic function were observed in 54.5 % of the group 1 patients ; 13.6 % of the patients showed stable states in the infused group . None of the patients in the control group showed improvement . No adverse effects were noted . CONCLUSION Our data showed that a CD34(+ ) and CD133(+ ) stem cells infusion can be used as supportive treatment for end-stage liver disease with satisfactory tolerability BACKGROUND / AIMS To evaluate feasibility , safety and pattern of bone marrow-derived cells ( BMC ) mobilization in patients with end stage liver cirrhosis following granulocyte-colony stimulating factor ( G-CSF ) administration . METHODS Eight patients with severe liver cirrhosis ( Child-Pugh score B-C , spleen diameter less than 170 mm ) were included . They were treated with G-CSF ( 5 microg/kg b.i.d for three consecutive days ) to mobilize BMC , evaluated as circulating CD34+ve cells ( flow cytometry ) and myeloid CFU-GM progenitors ( in vitro colony growth assay ) . Co-expression in CD34+ve cells markers of differentiation ( Thy1 , CD133 , CXCR4 , c1qRp ) were investigated on CD34+ve cells by double direct immunofluorescence . Data from 40 healthy haematopoietic stem cell donors were used as controls . RESULTS Mobilization of CD34+ve cells occurred in all patients . It was paralleled by expansion of circulating CFU-GM progenitors . Circulating CD34+ve cells co-expressed epithelial and stem cell markers in both cirrhotics and volunteer stem cell donors . G-CSF was well tolerated , no adverse event occurred , a significant reversible increase of splenic longitudinal diameter was observed . CONCLUSIONS ( i ) G-CSF mobilization of BMC co-expressing epithelial and stem markers occurred in all cirrhotic patients ; ( ii ) splenomegaly up to 170 mm does not prevent safe BMC mobilization following G-CSF in patients with end stage liver disease ; ( iii ) mobilized BMC may represent an easy immature cell source potentially useful for novel approaches for liver regeneration BACKGROUND & AIMS A consensus has been reached that liver donor allocation should be based primarily on liver disease severity and that waiting time should not be a major determining factor . Our aim was to assess the capability of the Model for End-Stage Liver Disease ( MELD ) score to correctly rank potential liver recipients according to their severity of liver disease and mortality risk on the OPTN liver waiting list . METHODS The MELD model predicts liver disease severity based on serum creatinine , serum total bilirubin , and INR and has been shown to be useful in predicting mortality in patients with compensated and decompensated cirrhosis . In this study , we prospect ively applied the MELD score to estimate 3-month mortality to 3437 adult liver transplant c and i date s with chronic liver disease who were added to the OPTN waiting list at 2A or 2B status between November , 1999 , and December , 2001 . RESULTS In this study cohort with chronic liver disease , 412 ( 12 % ) died during the 3-month follow-up period . Waiting list mortality increased directly in proportion to the listing MELD score . Patients having a MELD score < 9 experienced a 1.9 % mortality , whereas patients having a MELD score > or = 40 had a mortality rate of 71.3 % . Using the c-statistic with 3-month mortality as the end point , the area under the receiver operating characteristic ( ROC ) curve for the MELD score was 0.83 compared with 0.76 for the Child-Turcotte-Pugh ( CTP ) score ( P < 0.001 ) . CONCLUSIONS These data suggest that the MELD score is able to accurately predict 3-month mortality among patients with chronic liver disease on the liver waiting list and can be applied for allocation of donor livers AIM To evaluate safety and feasibility of autologous bone marrow-enriched CD34 + hematopoietic stem cell Tx through the hepatic artery in patients with decompensated cirrhosis . METHODS Four patients with decompensated cirrhosis were included . Approximately 200 mL of the bone marrow of the patients was aspirated , and CD34 + stem cells were selected . Between 3 to 10 million CD34 + cells were isolated . The cells were slowly infused through the hepatic artery of the patients . RESULTS Patient 1 showed marginal improvement in serum albumin and no significant changes in other test results . In patient 2 prothrombin time was decreased ; however , her total bilirubin , serum creatinine , and Model of End-Stage Liver Disease ( MELD ) score worsened at the end of follow up . In patient 3 there was improvement in serum albumin , porthrombin time ( PT ) , and MELD score . Patient 4 developed radiocontrast nephropathy after the procedure , and progressed to type 1 hepatorenal syndrome and died of liver failure a few days later . Because of the major side effects seen in the last patient , the trial was prematurely stopped . CONCLUSION Infusion of CD34 + stem cells through the hepatic artery is not safe in decompensated cirrhosis . Radiocontrast nephropathy and hepatorenal syndrome could be major side effects . However , this study does not preclude infusion of CD34 + stem cells through other routes |
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